Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors.

Abstract: Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C1 -O-octyloxy glycans, α/β-glucoside (α/β-Glc), α/β-mannoside (α/β-Man), and β-galactoside (β-Gal), was studied by mass spectrometry, 1 H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to β-Glc. SCR019 (3-indole) binds only to β-Man. SCR020 (2-pyridine) binds β-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and β-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center-perpendicular, and off-center. Many host-guest combinations formed higher stoichiometry complexes, 2:1 glycan⋅SCR or 1:2 glycan⋅SCR, where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts.

D002241:Carbohydrates
D037181:Lectins, C-Type
D009682:Magnetic Resonance Spectroscopy
D008358:Mannose
D000090323:Mannose Receptor
D037241:Mannose-Binding Lectins
D008958:Models, Molecular
D015394:Molecular Structure
D011134:Polysaccharides
D062165:Receptors, Artificial
D011956:Receptors, Cell Surface

carbohydrates
computational chemistry
host-guest systems
molecular recognition
supramolecular chemistry


A simple and ultra-low cost homemade seamless ligation cloning extract (SLiCE) as an alternative to a commercially available seamless DNA cloning kit.

Abstract: The seamless ligation cloning extract (SLiCE) method is a novel seamless DNA cloning tool that utilizes homologous recombination activities in Escherichia coli cell lysates to assemble DNA fragments into a vector. Several laboratory E. coli strains can be used as a source for the SLiCE extract; therefore, the SLiCE-method is highly cost-effective.The SLiCE has sufficient cloning ability to support conventional DNA cloning, and can simultaneously incorporate two unpurified DNA fragments into vector. Recently, many seamless DNA cloning kits have become commercially available; these are generally very convenient, but expensive. In this study, we evaluated the cloning efficiencies between a simple and highly cost-effective SLiCE-method and a commercial kit under various molar ratios of insert DNA fragments to vector DNA. This assessment identified that the SLiCE from a laboratory E. coli strain yielded 30-85% of the colony formation rate of a commercially available seamless DNA cloning kit. The cloning efficiencies of both methods were highly effective, exhibiting over 80% success rate under all conditions examined. These results suggest that SLiCE from a laboratory E. coli strain can efficiently function as an effective alternative to commercially available seamless DNA cloning kits.

G6PDH1, glucose-6-phosphate dehydrogenase 1

SLiCE, seamless ligation cloning extract


Effects of Preoxygenation with Tidal Volume Breathing Followed by Apneic Oxygenation with and without Continuous Positive Airway Pressure on Duration of Safe Apnea Time and Arterial Blood Gases.

Abstract:
Background
Application of continuous positive airway pressure (CPAP) helps to recruit collapsed areas of the lung, which improves the oxygen reserve.

Aim of the Study
To compare the time to desaturate to 90% during apnea following preoxygenation and apneic ventilation with tidal volume breathing for 3 min with and without the application of CPAP.

Settings and Design
This prospective randomized study was conducted in a tertiary care institution.

Subjects and Methods
Twenty adult surgical patients were allocated into two groups. Group C patients were preoxygenated with 100% oxygen with CPAP of 20 cm H2O for 3 min. Group P patients were preoxygenated for 3 min without CPAP. In Group C, apneic oxygenation was initiated following induction and neuromuscular blockade with CPAP of 20 cm H2O. In Group P, no CPAP was applied. The study was terminated when the patient desaturated to 90%.

Statistical Analysis Used
Chi-square test and Mann-Whitney test.

Results
Group C had a significantly longer apnea time as compared to Group P (816.00 ± 30.98 vs. 348.00 ± 122.64 s). Three patients in Group P desaturated to <90% by 3 min and the remaining soon after 6 min. No patient in Group C desaturated till 12 min of apnea. PaO2 was significantly higher in Group C at 3 and 6 min of apnea. At 3 and 6 min, Group P had significantly lower saturation as compared to Group C.

Conclusion
Preoxygenation with CPAP significantly delayed desaturation during apnea with significantly higher arterial partial pressure of oxygen as compared to preoxygenation without CPAP.

Rajan|Sunil|S| Joseph|Nandhini|N| Tosh|Pulak|P| Paul|Jerry|J| Kumar|Lakshmi|L|

tidal volume breathing
oxygenation
continuous positive airway pressure
Apneic ventilation
PaO2


Risk of multi-drug resistant Campylobacter spp. and residual antimicrobials at poultry farms and live bird markets in Bangladesh.

Abstract:
BACKGROUND
Understanding potential risks of multi-drug resistant (MDR) pathogens from the booming poultry sector is a crucial public health concern. Campylobacter spp. are among the most important zoonotic pathogens associated with MDR infections in poultry and human. This study systematically examined potential risks and associated socio-environmental factors of MDR Campylobacter spp. in poultry farms and live bird markets (LBMs) of Bangladesh.

METHODS
Microbial culture and PCR-based methods were applied to examine the occurrence and MDR patterns of Campylobacter spp. in potential sources (n = 224) at 7 hatcheries, 9 broiler farms and 4 LBMs in three sub-districts. Antimicrobial residues in broiler meat and liver samples (n = 50) were detected by advanced chromatographic techniques. A questionnaire based cross-sectional survey was conducted on socio-environmental factors.

RESULTS
Overall, 32% (71/ 224) samples were found contaminated with Campylobacter spp. In poultry farms, Campylobacter spp. was primarily found in cloacal swab (21/49, 43%), followed by drinking water (8/24, 33%), and meat (8/28, 29%) samples of broilers. Remarkably, at LBMs, Campylobacter spp. was detected in higher prevalence (p < 0.05) in broiler meat (14/26, 54%), which could be related (p < 0.01) to bacterial contamination of drinking water (11/21, 52%) and floor (9/21, 43%). Campylobacter isolates, one from each of 71 positive samples, were differentiated into Campylobacter jejuni (66%) and Campylobacter coli (34%). Alarmingly, 49 and 42% strains of C. jejuni and C. coli, respectively, were observed as MDR, i.e., resistant to three or more antimicrobials, including, tetracycline, amoxicillin, streptomycin, fluoroquinolones, and macrolides. Residual antimicrobials (oxytetracycline, ciprofloxacin and enrofloxacin) were detected in majority of broiler liver (79%) and meat (62%) samples, among which 33 and 19%, respectively, had concentration above acceptable limit. Inadequate personal and environmental hygiene, unscrupulously use of antimicrobials, improper waste disposal, and lack of health surveillance were distinguishable risk factors, with local diversity and compound influences on MDR pathogens.

CONCLUSION
Potential contamination sources and anthropogenic factors associated with the alarming occurrence of MDR Campylobacter, noted in this study, would aid in developing interventions to minimize the increasing risks of poultry-associated MDR pathogens under 'One Health' banner that includes poultry, human and environment perspectives.

Neogi|Sucharit Basu|SB|
Islam|Md Mehedul|MM|
Islam|S K Shaheenur|SKS|
Akhter|A H M Taslima|AHMT|
Sikder|Md Mahmudul Hasan|MMH|
Yamasaki|Shinji|S|
Kabir|S M Lutful|SML|

D024901:Drug Resistance, Multiple, Bacterial

Multi-drug resistance
Campylobacter
Residual antimicrobial
Poultry farm
Live bird market
Risk factors


Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension.

Abstract:
OBJECTIVE
Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion.

METHODS
From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed.

RESULTS
Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015).

CONCLUSION
The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.

Baroreflex activation therapy
Resistant hypertension
Sympathetic nervous system
Urinary sodium excretion
Kawasaki formula


Non-clinical studies of progesterone.

Abstract: Progesterone is a steroid hormone that is essential for the regulation of reproductive function. Progesterone has been approved for several indications including the treatment of anovulatory menstrual cycles, assisted reproductive technology, contraception during lactation and, when combined with estrogen, for the prevention of endometrial hyperplasia in postmenopausal hormonal therapy. In addition to its role in reproduction, progesterone regulates a number of biologically distinct processes in other tissues, particularly in the nervous system. This physiological hormone is poorly absorbed when administered in a crystalline form and is not active when given orally, unless in micronized form, or from different non-oral delivery systems that allow a more constant delivery rate. A limited number of preclinical studies have been conducted to document the toxicity, carcinogenicity and overall animal safety of progesterone delivered from different formulations, and these rather old studies showed no safety concern. More recently, it has been shown in animal experiments that progesterone, its metabolite allopregnanolone and structurally related progestins have positive effects on neuroregeneration and repair of brain damage, as well as myelin repair. These recent preclinical findings have the potential to accelerate therapeutic translation for multiple unmet neurological needs.

Progesterone
carcinogenicity
neuroregeneration
pharmacodynamics
toxicology studies


Quality assessment and potential health risk of heavy metals in leafy and non-leafy vegetables irrigated with groundwater and municipal-waste-dominated stream in the Western Region, Ghana.

Abstract: Vegetables cultivated in soil irrigated with untreated groundwater and municipal-waste-dominated (MWD) stream can elevate the concentration of heavy metals (Cd, Fe, Zn, Hg, Cr, and Ni) in edible parts of the crop, affecting food safety and public health worldwide. This study assessed the quality, sources, and distribution of heavy metals in surface soils, MWD stream and groundwater, and edible tissues of leafy and non-leafy vegetables from a major urban farm in the Sekondi-Takoradi metropolis, Ghana. Human health risk due to exposure to the metals in frequently consumed vegetables were investigated. Indigenous leafy vegetables (Corchorus olitorious and Amaranthus spinosus), exotic leafy vegetables (Lactuca sativa, Brassica oleracea, and Brassica rapa), and non-leafy vegetables (Capsicum annum, Raphanus sativus, Daucus carota, and Allium cepa) were collected from the urban farm. The mean concentration of Cd, Hg, and Fe ranged from 0.008 - 0.027, 0.001-0.013, and 4.517-36.178 mg/kg fw in edible parts of non-leafy vegetables, respectively and 0.011-0.035, 0.002-0.011, and 3.617-13.695 mg/kg fw in exotic or indigenous leafy vegetables. The vegetables were less impacted with the metals if compared to similar vegetables produced from other urban farms, locally and in some countries in Africa, Asia, and Europe. Water resource on the farm were not suitable for vegetable crop irrigation since mean concentration of E. coli (200 cfu/mL), Hg (0.009 mg/L), and Cd (0.019 mg/L) in the MWD stream and 80 % of the groundwater sources exceeded the safe limits recommended by the Food and Agriculture Organization. Geo-accumulation index for each metal in soil was ≤0, however, enrichment factor indicated a high anthropic enriched soil for Cr and Ni. Principal component analysis-multiple linear regression of the metals in soil identified mixed household waste/fertilizer, fertilizer, and crustal material as main sources for the heavy metal load in soil for which geogenic sources accounted for 74.3 %. Preferentially, Cd and Hg accumulated in Amaranthus spinosus, Daucus carota, and Corchorus olitorious. The estimated daily intake of each metal in the vegetables were below local and international daily dietary intake levels. At the 95th percentile concentration of each metal, target hazard quotient and the hazard index was <1 for adult male or female who consume the vegetables. Finally, appropriate agri-horticultural practices must be enforced to mitigate Cd, Ni, Cr, and Hg accumulation in the soil-vegetable system since the metals have profound adverse effect on human health.

Affum|Andrews Obeng|AO|
Osae|Shiloh Dede|SD|
Kwaansa-Ansah|Edward Ebow|EE|
Miyittah|Michael K|MK|

Heavy metals
Vegetables
Soil
Irrigation water
Risk assessment
Source apportionment


Redox Modulation Matters: Emerging Functions for Glutaredoxins in Plant Development and Stress Responses.

Abstract: Glutaredoxins (GRXs) are small ubiquitous glutathione (GSH)-dependent oxidoreductases that catalyze the reversible reduction of protein disulfide bridges or protein-GSH mixed disulfide bonds via a dithiol or monothiol mechanism, respectively. Three major classes of GRXs, with the CPYC-type, the CGFS-type or the CC-type active site, have been identified in many plant species. In spite of the well-characterized roles for GRXs in Escherichia coli, yeast and humans, the biological functions of plant GRXs have been largely enigmatic. The CPYC-type and CGFS-type GRXs exist in all organisms, from prokaryotes to eukaryotes, whereas the CC-type class has thus far been solely identified in land plants. Only the number of the CC-type GRXs has enlarged dramatically during the evolution of land plants, suggesting their participation in the formation of more complex plants adapted to life on land. A growing body of evidence indicates that plant GRXs are involved in numerous cellular pathways. In this review, emphasis is placed on the recently emerging functions for GRXs in floral organ development and disease resistance. Notably, CC-type GRXs have been recruited to participate in these two seemingly unrelated processes. Besides, the current knowledge of plant GRXs in the assembly and delivery of iron-sulfur clusters, oxidative stress responses and arsenic resistance is also presented. As GRXs require GSH as an electron donor to reduce their target proteins, GSH-related developmental processes, including the control of flowering time and the development of postembryonic roots and shoots, are further discussed. Profiling the thiol redox proteome using high-throughput proteomic approaches and measuring cellular redox changes with fluorescent redox biosensors will help to further unravel the redox-regulated physiological processes in plants.

development
glutaredoxins (GRXs)
iron-sulfur clusters
biotic and abiotic stresses
glutathione (GSH)
redox regulation
thioredoxins (TRXs)


Selfish genetic elements and male fertility.

Abstract: Selfish genetic elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here, we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex ratios and in particular reducing sperm-competitive success of SGE-carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely. This article is part of the theme issue 'Fifty years of sperm competition'.

Verspoor|Rudi L|RL|
Price|Tom A R|TAR|
Wedell|Nina|N|

D012091:Repetitive Sequences, Nucleic Acid

sperm competition
Wolbachia
meiotic drive
polyandry


RAGE-dependent NF-kB inflammation processes in the capsule of frozen shoulders.

Abstract:
BACKGROUND
The etiology of frozen shoulder (FS) remains uncertain. Advanced glycation end-products (AGEs) cause the cross-linking and stabilization of collagen and are increased in FS. The purpose of this study was to elucidate the pathogenesis of FS by evaluating the receptor of AGE (RAGE)-dependent pathways.

METHODS
Tissue samples of the coracohumeral ligament (CHL) and anterior inferior glenohumeral ligament (IGHL) were collected from 33 patients with FS, with severe stiffness, and 25 with rotator cuff tears (RCTs) as controls. Gene expression levels of RAGE, high-mobility group box 1 (HMGB1), Toll-like receptor 2 (TLR2), TLR4, nuclear factor-kappa B (NF-kB), and cytokines were evaluated using a quantitative real-time polymerase chain reaction. The immunoreactivities of carboxymethyllysine (CML), pentosidine, and RAGE were also evaluated. CML and pentosidine were further evaluated using high-performance liquid chromatography.

RESULTS
Gene expression levels of RAGE, HMGB1, TLR2, TLR4, and NF-kB were significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group. Immunoreactivities of RAGE and CML were stronger in the CHLs and IGHLs from the FS group than in those from the RCT group. Pentosidine was weakly immunostained in the CHLs and IGHLs from the FS group. CML using high-performance liquid chromatography was significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group.

CONCLUSIONS
AGEs and HMGB1 might play important roles in the pathogenesis of FS by binding to RAGE and activating NF-kB signaling pathways. Suppression of these pathways could be a treatment option for FS.

Yano|Toshihisa|T| Hagiwara|Yoshihiro|Y| Ando|Akira|A| Kanazawa|Kenji|K| Koide|Masashi|M| Sekiguchi|Takuya|T| Itaya|Nobuyuki|N| Onoki|Takahiro|T| Suzuki|Kazuaki|K| Tsuchiya|Masahiro|M| Sogi|Yasuhito|Y| Yabe|Yutaka|Y| Itoi|Eiji|E|

D060888:Real-Time Polymerase Chain Reaction

D000067759:Receptor for Advanced Glycation End Products

receptor of advanced glycation end-products


Metal Distribution and Contamination Assessment in Drainage Ditch Water in the Main Rice/Vegetable Area of Sichuan Hilly Basin.

Abstract: In order to assess the impact of four land use changes on metal concentrations in the hilly Sichuan Basin of China, 71 surface water samples were collected in July and November 2014. Samples from residential ditch water were found to have higher metal concentrations than those in other types of ditches, while the lowest occurred in barren land ditch water. However, the selected metals were below the Chinese surface water quality standards and WHO (2011). The pollution index of four determined land use types was also below the critical pollution index, suggesting there were low levels of pollution in Sichuan Basin. Arsenic was the most important pollutant of concern. Results indicate steps should be taken to control and reduce the risk of metals released from residential ditch water.

Kumwimba|Mathieu Nsenga|MN|
Zhu|Bo|B|
Wang|Tao|T|
Yuan|Zhao|Z|
Muyembe|Diana Kavidia|DK|

Land use
Channel
Pollution evaluation indices
Spatial distribution


Fluorescence quenching investigation on the interaction of glutathione-CdTe/CdS quantum dots with sanguinarine and its analytical application.

Abstract: Water-soluble glutathione (GSH)-capped core/shell CdTe/CdS quantum dots (QDs) were synthesized. In pH5.4 sodium phosphate buffer medium, the interaction between GSH-CdTe/CdS QDs and sanguinarine (SA) was investigated by spectroscopic methods, including fluorescence spectroscopy and ultraviolet-visible absorption spectroscopy. Addition of SA to GSH-CdTe/CdS QDs results in fluorescence quenching of GSH-CdTe/CdS QDs. Quenching intensity was in proportion to the concentration of SA in a certain range. Investigation of the quenching mechanism, proved that the fluorescence quenching of GSH-CdTe/CdS QDs by SA is a result of electron transfer. Based on the quenching of the fluorescence of GSH-CdTe/CdS QDs by SA, a novel, simple, rapid and specific method for SA determination was proposed. The detection limit for SA was 3.4 ng/mL and the quantitative determination range was 0.2-40.0 µg/mL with a correlation coefficient of 0.9988. The method has been applied to the determination of SA in synthetic samples and fresh urine samples of healthy human with satisfactory results.

fluorescence
GSH-CdTe/CdS QDs
quenching, sanguinarine


Dissociated large-scale functional connectivity networks of the precuneus in medication-naïve first-episode depression.

Abstract: An imbalance in neural activity within large-scale networks appears to be an important pathophysiological aspect of depression. Yet, there is little consensus regarding the abnormality within the default mode network (DMN) in major depressive disorder (MDD). In the present study, 16 first-episode, medication-naïve patients with MDD and 16 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest. With the precuneus (a central node of the DMN) as a seed region, functional connectivity (FC) was measured across the entire brain. The association between the FC of the precuneus and overall symptom severity was assessed using the Hamilton Depression Rating Scale. Patients with MDD exhibited a more negative relationship between the precuneus and the non-DMN regions, including the sensory processing regions (fusiform gyrus, postcentral gyrus) and the secondary motor cortex (supplementary motor area and precentral gyrus). Moreover, greater severity of depression was associated with greater anti-correlation between the precuneus and the temporo-parietal junction as well as stronger positive connectivity between the precuneus and the dorsomedial prefrontal cortex. These results indicate that dissociated large-scale networks of the precuneus may contribute to the clinical expression of depression in MDD.

Peng|Daihui|D|
Liddle|Elizabeth B|EB|
Iwabuchi|Sarina J|SJ|
Zhang|Chen|C|
Wu|Zhiguo|Z|
Liu|Jun|J|
Jiang|Kaida|K|
Xu|Lin|L|
Liddle|Peter F|PF|
Palaniyappan|Lena|L|
Fang|Yiru|Y|

Functional connectivity network
Precuneus
Depression
Functional magnetic resonance imaging
Resting state


Giant coronary artery aneurysm in infantile Kawasaki disease: When to use cardiac computed tomography angiography.

Abstract: Transthoracic echocardiography is the imaging modality of choice for the detection of coronary artery aneurysms (CAAs) in Kawasaki disease. However, cardiac computed tomography angiography is useful in the diagnosis of distal CAAs.

coronary artery aneurysm
Kawasaki disease
cardiac computed tomography angiography
infant
ultrasound


Examining healthcare inequities relative to United States safety net hospitals.

Abstract:
INTRODUCTION
The impact of safety net (SN) hospitals relative to racial and healthcare disparities remains largely unknown.

METHODS
Using the Nationwide Inpatient Sample, adults undergoing coronary artery bypass grafting, colectomy, or total hip arthroplasty were identified. Multivariable regression analysis was performed to determine association between SN burden and outcomes. Within each SN burden tier, the association between race/ethnic group and outcomes was defined.

RESULTS
Overall 865,648 patients were identified. After adjustment for potential confounders, patients operated at the highest SN burden hospitals had increased odds of complications (OR 1.14, 95%CI 1.10-1.18), death (OR 1.41, 95%CI 1.31-1.52), FTR (OR 1.36, 95%CI 1.25-1.47) and a never event (OR 1.57, 95%CI 1.47-1.68). Irrespective of hospital SN burden, racial minorities had greater odds of a complication, and prolonged LOS compared to whites (p < 0.05).

CONCLUSION
While overall degree of safety net burden was associated with worse overall outcomes, SN hospitals did not mitigate racial disparities experienced by minority patients.

Paredes|Anghela Z|AZ|
Hyer|J Madison|JM|
Diaz|Adrian|A|
Tsilimigras|Diamantis I|DI|
Pawlik|Timothy M|TM|


Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells.

Abstract:
BACKGROUND/AIMS
Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells.

METHODS
HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues.

RESULTS
We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer.

CONCLUSIONS
Our results suggest the potential use of cobimetinib in colorectal cancer therapy.

Gong|Shu|S| Xu|Dongsheng|D| Zhu|Jialin|J| Zou|Fangdong|F| Peng|Rui|R|

D050759:Cyclin-Dependent Kinase Inhibitor p21

Cobimetinib
Colorectal Cancer
Cancer therapy
Thymidylate synthetase


GITR differentially affects lung effector T cell subpopulations during influenza virus infection.

Abstract: Tissue resident memory T cells (Trm) are critical for local protection against reinfection. The accumulation of T cells in the tissues requires a post-priming signal from TNFR superfamily members, referred to as signal 4. Glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18) signaling is important for this post-priming signal and for Trm formation during respiratory infection with influenza virus. As GITR signaling impacts both effector T cell accumulation and Trm formation, we asked if GITR differentially affects subsets of effector cells with different memory potential. Effector CD4+ T cells can be subdivided into 2 populations based on expression of lymphocyte antigen 6C (Ly6C), whereas effector CD8+ cells can be divided into 3 populations based on Ly6C and CX3CR1. The Ly6Chi and CX3CR1hi T cell populations represent the most differentiated effector T cells. Upon transfer, the Ly6Clo CD4+ effector T cells preferentially enter the lung parenchyma, compared to the Ly6Chi CD4+ T cells. We show that GITR had a similar effect on the accumulation of both the Ly6Chi and Ly6Clo CD4+ T cell subsets. In contrast, whereas GITR increased the accumulation of all three CD8+ T cell subsets defined by CX3CR1 and Ly6C expression, it had a more substantial effect on the least differentiated Ly6Clo CX3CR1lo subset. Moreover, GITR selectively up-regulated CXCR6 on the less differentiated CX3CR1lo CD8+ T cell subsets and induced a small but significant increase in CD127 selectively on the Ly6Clo CD4+ T cell subset. Thus, GITR contributes to accumulation of both differentiated effector cells as well as memory precursors, but with some differences between subsets.

Chu|Kuan-Lun|KL|
Batista|Nathalia V|NV|
Girard|Mélanie|M|
Law|Jaclyn C|JC|
Watts|Tania H|TH|0000-0001-7897-4890

D053699:Interleukin-7 Receptor alpha Subunit

lung
influenza
tissue resident memory T cells
TNFR superfamily
TNFRSF18


Crystal structure and mutational analyses of ribokinase from Arabidopsis thaliana.

Abstract: Nitrogen remobilization is a key issue in plants. Recent studies in Arabidopsis thaliana have revealed that nucleoside catabolism supplies xanthine, a nitrogen-rich compound, to the purine ring catabolic pathway, which liberates ammonia from xanthine for reassimilation into amino acids. Similarly, pyrimidine nuclosides are degraded and the pyrimidine bases are fully catabolized. During nucleoside hydrolysis, ribose is released, and ATP-dependent ribokinase (RBSK) phosphorylates ribose to ribose-5'-phosphate to allow its entry into central metabolism recycling the sugar carbons from nucleosides. In this study, we report the crystal structure of RBSK from Arapidopsis thaliana (AtRBSK) in three different ligation states: an unliganded state, a ternary complex with ribose and ATP, and a binary complex with ATP in the presence of Mg2+. In the monomeric conformation, AtRBSK is highly homologous to bacterial RBSKs, including the binding sites for a monovalent cation, ribose, and ATP. Its dimeric conformation, however, does not exhibit the noticeable ligand-induced changes that were observed in bacterial orthologs. Only in the presence of Mg2+, ATP in the binary complex adopts a catalytically competent conformation, providing a mode of action for Mg2+ in AtRBSK activity. The structural data combined with activity analyses of mutants allowed assignment of functional roles for the active site residues. Overall, this study provides the first structural characterization of plant RBSK, and experimentally validates a previous hypothetical model concerning the general reaction mechanism of RBSK.

Kang|Pyeoung-Ann|PA| Oh|Juntaek|J| Lee|Haehee|H| Witte|Claus-Peter|CP| Rhee|Sangkee|S|

D017853:Phosphotransferases (Alcohol Group Acceptor)

Ribokinase
Arabidopsis
Enzyme catalysis
Nucleoside metabolism
Protein structure


PPARβ/δ Is Required for Mesenchymal Stem Cell Cardioprotective Effects Independently of Their Anti-inflammatory Properties in Myocardial Ischemia-Reperfusion Injury.

Abstract: Myocardial infarction ranks first for the mortality worldwide. Because the adult heart is unable to regenerate, fibrosis develops to compensate for the loss of contractile tissue after infarction, leading to cardiac remodeling and heart failure. Adult mesenchymal stem cells (MSC) regenerative properties, as well as their safety and efficacy, have been demonstrated in preclinical models. However, in clinical trials, their beneficial effects are controversial. In an experimental model of arthritis, we have previously shown that PPARβ/δ deficiency enhanced the therapeutic effect of MSC. The aim of the present study was to compare the therapeutic effects of wild-type MSC (MSC) and MSC deficient for PPARβ/δ (KO MSC) perfused in an ex vivo mouse model of ischemia-reperfusion (IR) injury. For this purpose, hearts from C57BL/6J mice were subjected ex vivo to 30 min ischemia followed by 1-h reperfusion. MSC and KO MSC were injected into the Langendorff system during reperfusion. After 1 h of reperfusion, the TTC method was used to assess infarct size. Coronary effluents collected in basal condition (before ischemia) and after ischemia at 1 h of reperfusion were analyzed for their cytokine profiles. The dose-response curve for the cardioprotection was established ex vivo using different doses of MSC (3.105, 6.105, and 24.105 cells/heart) and the dose of 6.105 MSC was found to be the optimal concentration. We showed that the cardioprotective effect of MSC was PPARβ/δ-dependent since it was lost using KO MSC. Moreover, cytokine profiling of the coronary effluents collected in the eluates after 60 min of reperfusion revealed that MSC treatment decreases CXCL1 chemokine and interleukin-6 release compared with untreated hearts. This anti-inflammatory effect of MSC was also observed when hearts were treated with PPARβ/δ-deficient MSC. In conclusion, our study revealed that the acute cardioprotective properties of MSC in an ex vivo model of IR injury, assessed by a decreased infarct size at 1 h of reperfusion, are PPARβ/δ-dependent but not related to their anti-inflammatory effects.

Nernpermpisooth|Nitirut|N| Sarre|Charlotte|C| Barrere|Christian|C| Contreras|Rafaël|R| Luz-Crawford|Patricia|P| Tejedor|Gautier|G| Vincent|Anne|A| Piot|Christophe|C| Kumphune|Sarawut|S| Nargeot|Joel|J| Jorgensen|Christian|C| Barrère-Lemaire|Stéphanie|S| Djouad|Farida|F|

mesenchymal stem cells
cardioprotection
myocardial infarction
PPAR
inflammation
reperfusion injury


Sauti Za Wananchi "voice of the people": patient satisfaction on the medical wards at a Kenyan Referral Hospital.

Abstract:
INTRODUCTION
Patient satisfaction is one indicator of healthcare quality. Few studies have examined the inpatient experiences in resource-scarce environments in sub-Saharan Africa.

METHODS
To examine patient satisfaction on the public medical wards at a Kenyan referral hospital, we performed a cross-sectional survey focused on patients' satisfaction with medical information and their relationship with staffing and hospital routine. Ratings of communication with providers, efforts to protect privacy, information about costs, food, and hospital environment were also elicited.

RESULTS
Overall, the average patient satisfaction rating was 64.7, nearly midway between "average" and "good" Higher rated satisfaction was associated with higher self-rated general health scores and self-rated health gains during the hospitalization (p=0.023 and p=0.001). Women who shared a hospital bed found privacy to be "below average" to "poor" Most men (72.7%) felt information about costs was insufficient. Patients rated food and environmental quality favorably while also frequently suggesting these areas could be improved.

CONCLUSION
Overall, patients expressed satisfaction with the care provided. These ratings may reflect modest patients' expectations as well as acceptable circumstances and performance. Women expressed concern about privacy while men expressed a desire for more information on costs. Inconsistencies were noted between patient ratings and free response answers.

Stone|Geren Starr|GS|
Jerotich|Tecla Sum|TS|
Cheriro|Betsy Rono|BR|
Kiptoo|Robert Sitienei|RS|
Crowe|Susie Joanne|SJ|
Koros|Elijah Kipkorir|EK|
Muthoni|Doreen Mutegi|DM|
Onalo|Paul Theodore|PT|

Patient satisfaction
sub-Saharan Africa
global health
underserved population


'I was broken in so many different ways': The intersection of complex factors impacting homeless and at-risk African American women's mental health and well-being.

Abstract: African American women are at higher risk of poor mental ill health compared with other racial and ethnic groups in the United States. For low-income and homeless African American populations, the risk of poor mental ill health is even higher. The purpose of our study was to learn what programmes at a long-term transitional living centre helped at-risk and homeless African American mothers to succeed on their own, in accordance with self-identified goals. We conducted ten focus group interviews with 39 graduates of a long-term transitional living centre located in a Midwestern city, and an individual interview with the founder of that centre (N = 40). Our study was informed by Black Feminist Thought, Life Course Theory, and an instrumental case study design. Thematic analysis was used to identify patterns in the qualitative data collected. Findings pertaining to mental health included impacts of adverse childhood experiences, lack of social networks, child placement in foster care, and implications on self-esteem and self-worth. Our findings demonstrate the need for healthcare providers to take into account the intersecting factors facing African American women experiencing homelessness undergirded by systemic racism, which impacts their mental health and well-being.

African Americans
mental health
adverse childhood experiences
racism
homeless persons


Diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life over time in Chinese youth with type 1 diabetes.

Abstract:
AIMS AND OBJECTIVES
To describe the patterns of diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life over time in a cohort of Chinese youth with type 1 diabetes and to determine the relationships between these variables over time.

BACKGROUND
Nurses have an important role in facilitating optimal self-management and health outcomes in youth with type 1 diabetes. Only a few studies have focused on patterns of diabetes adaptation over time in youth with type 1 diabetes, especially in China. Understanding changes in diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life can facilitate assessment and intervention.

DESIGN
This is a multi-site longitudinal descriptive study. Data for this report were collected at baseline with 136 eligible Chinese youth and 86 of them were followed up for the second time, 6-12 months after baseline data collection.

METHODS
Instruments to measure diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life were collected at two time points. The data were collected from July 2009-October 2010. Linear mixed model analysis was used to analyse the longitudinal data.

RESULTS
Self-management decreased over time; however, depressive symptoms, metabolic control and satisfaction with quality of life did not change from baseline to 6-12 months in this sample of Chinese youth with type 1 diabetes. A decrease in diabetes self-management over time was associated with worse metabolic control, while an increase in depressive symptoms over time was associated with poorer quality of life satisfaction in this sample.

CONCLUSIONS
Chinese youth faced difficulties with diabetes adaptation, especially with the deterioration of diabetes self-management. Improving self-management and decreasing depressive symptoms may enhance diabetes adaptation with respect to metabolic control and quality of life.

RELEVANCE TO CLINICAL PRACTICE
The deterioration of diabetes self-management over time in youth with type 1 diabetes in China deserves nurses' careful surveillance. Clinical interventions appropriate to the Chinese culture and health care system are needed to improve self-management and depressive symptoms in Chinese youth with type 1 diabetes.

Guo|Jia|J| Whittemore|Robin|R| Jeon|Sangchoon|S| Grey|Margaret|M| Zhou|Zhi-Guang|ZG| He|Guo-Ping|GP| Luo|Zi-Qiang|ZQ|

diabetes self-management
depressive symptoms
metabolic control
quality of life
youth
type 1 diabetes
nursing
longitudinal survey


Neurologic Complications in Treated HIV-1 Infection.

Abstract: Effective combination antiretroviral therapy has transformed HIV infection into a chronic disease, with HIV-infected individuals living longer and reaching older age. Neurological disease remains common in treated HIV, however, due in part to ongoing inflammation and immune activation that persist in chronic infection. In this review, we highlight recent developments in our understanding of several clinically relevant neurologic complications that can occur in HIV infection despite treatment, including HIV-associated neurocognitive disorders, symptomatic CSF escape, cerebrovascular disease, and peripheral neuropathy.

Neurological complications
HIV infection
Viral suppression


Who runs the fastest? Anthropometric and physiological correlates of 20 m sprint performance in male soccer players.

Abstract: The aim of the present study was to examine the relationship of 20 m sprint performance with anthropometrical and physiological parameters in male soccer players. A hundred and 81 soccer players from the region of Athens (age 23.4 ± 5.0 yrs, body mass 73.4 ± 7.7 kg, height 180.0 ± 5.9 cm, body fat (BF) 14.4 ± 3.6%), classified into quartiles according to 20 m sprint time (group A, 2.84-3.03 s; group B, 3.04-3.09 s; group C, 3.10-3.18 s; group D, 3.19-3.61 s), participated. Soccer players in group A were younger and had better performance in vertical jumps and in the Wingate anaerobic test (WAnT, p < 0.05). Sprint time correlated to age (r = 0.27), body mass (r = 0.23), body height (r = 0.20), BF (r = 0.23), vertical jumps (-0.58 ≤ r ≤ -0.50) and the WAnT (-0.45 ≤ r ≤ -0.30, p < 0.05). In summary, the magnitude of correlations of sprint time with measures of lower limbs muscle strength and power (WAnT and jumps) was larger than with anthropometric measures (body mass and BF).

Nikolaidis|P T|PT|
Ruano|M A G|MA|
de Oliveira|N C|NC|
Portes|L A|LA|
Freiwald|J|J|
Leprêtre|P M|PM|
Knechtle|B|B|

muscle strength
Acceleration
body composition
football
speed


In search of a caring relationship - Nursing students' notions of interactions in the nurse-patient relationship.

Abstract: The aim of the study is to explore how nursing students talks about their notions on interactions in the relationship between nurse and patient. Empirical data has been obtained from 22 students in their first semester of the Swedish undergraduate nursing programme, applying thematic, individual interviews and using qualitative content analyses. The most significant finding is that although the students had none or limited pre-understanding of caring and the interaction between nurse and patient they were aware of the pre-supposes for establishing such an interplay, articulated in a desire to find out how to build an authentic and trustful caring relationship. Empirical data also show that the students, in the stage of beginners, were trying to identify and relate to basic concepts within caring science. The restricted understanding could then be understood as a matter of the students not being able to express more than they had words for. The results provide new insights into the interactions in the nurse-patient relationship, seen from the perspective of beginner students. These insights could be useful, for lecturers and clinical supervisors, who play a paramount role in the development of each student's acquisition of theoretical and practical knowledge.

caring relationship
caring actions
hermeneutic interpretation
nurse education
nurse-patient interaction


Loss of the tRNALys CUU encoding gene, Chr-11 tRNA-Lys-CUU, is not associated with Type 2 diabetes mellitus.

Abstract:
AIM
To investigate the presence/absence of the Chr-11 tRNA-Lys-CUU gene as a marker for genetic predisposition to Type 2 diabetes mellitus (T2DM).

METHODS
We enrolled 122 patients diagnosed with T2DM and 77 non-diabetic individuals. We evaluated clinical and biochemical parameters (body mass index, hypertension, cholesterol levels, glycosylated hemoglobin, triglycerides, etc.), and performed a genotypic profiling of Chr-11 tRNA-Lys-CUU by polymerase chain reaction analyses.

RESULTS
Approximately one third of the population lacked Chr-11 tRNA-Lys-CUU. We did not observe a statistically significant association between the presence/absence of Chr-11 tRNA-Lys-CUU and T2DM.

CONCLUSION
The genotypic distribution of Chr-11 tRNA-Lys-CUU in our population was consistent to that reported by others. This gene failed as a marker for T2DM predisposition.

Yang|Pablo|P|
Beltramo|Dante Miguel|DM|
de Pouplana|Lluís Ribas|LR|
Soria|Néstor Walter|NW|
Torres|Adrian Gabriel|AG|

D020022:Genetic Predisposition to Disease

tRNA-Lys-CUU
Type 2 diabetes mellitus
T2DM
genotypic profiling
PCR
biomarker
gene translation
insulin
tRNA
tRNA gene


Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish.

Abstract: The progestin receptor membrane components (Pgrmcs) contain two paralogs, Pgrmc1 and Pgrmc2. Our previous research into single knockout of Pgrmc1 or Pgrmc2 suggests that Pgrmc1 and Pgrmc2 regulate membrane progestin receptor or steroid synthesis and therefore female fertility in zebrafish. Additional roles of Pgrmcs may not be determined in using single Pgrmc knockouts due to compensatory roles between Pgrmc1 and Pgrmc2. To address this question, we crossed single knockout pgrmc1 (pgrmc1-/-) with pgrmc2 (pgrmc2-/-), and generated double knockouts for both pgrmc1 and pgrmc2 (pgrmc1/2-/-) in a vertebrate model, zebrafish. In addition to the delayed oocyte maturation and reduced female fertility, significant reduced ovulation was found in double knockout (pgrmc1/2-/-) in vivo, though not detected in either single knockout of Pgrmc (pgrmc1-/- or pgrmc2-/-). We also found significant down regulation of nuclear progestin receptor (Pgr) protein expression only in pgrmc1/2-/-, which was most likely the cause of reduced ovulation. Lower protein expression of Pgr also resulted in reduced expression of metalloproteinase in pgrmc1/2-/-. With this study, we have provided new evidence for the physiological functions of Pgrmcs in the regulation of female fertility by regulation of ovulation, likely via regulation of Pgr, which affects regulation of metalloproteinase expression and oocyte ovulation.

Progestins Pgr Pgrmc1 Pgrmc2 Ovulation Metalloproteinase


Effect of NiO/SiO2 on thermo-chemical conversion of waste cooking oil to hydrocarbons.

Abstract: Increase in organic waste generation, dwindling nature of global oil reserves coupled with environmental challenges caused by waste oil disposal and burning of fossil fuels necessitated the need for alternative energy resources. Waste cooking oil obtained from the frying fish outlet was analyzed for its physicochemical properties using ASTM D-975 methods. Acid and Iodine values of the oil were 30.43 ± 0.32 mgKOH/g and 57.08 ± 0.43 mgI2/100 g respectively. Thermo-chemical conversion of the oil using NiO/SiO2 at different reaction conditions (pressure, temperature, and catalyst concentration) at a residence time of 3 h yielded 33.63% hydrocarbons. Hydro-catalytic pyrolysis of waste cooking oil at 400 °C, H2 pressure of 15 bars, and catalyst to oil ratio of 0.25 g/100 cm3 resulted in highest hydrocarbon yield (41.98%). The fuel properties of the product were: cetane number (71.16), high heating value (41.43 MJ/kg), kinematic viscosity (2.01 mm2/s), density (0.94 g/ml), saponification value (185.1 ± 3.96 mgKOH/g), and iodine value (20.57 ± 0.20 I2/100 g) respectively. These results show that the NiO/SiO2 could be a suitable catalyst for conversion of waste vegetable oil to hydrocarbons.

Sani|J|J|
Sokoto|A M|AM|
Tambuwal|A D|AD|
Garba|N A|NA|


In vitro clonal propagation of Achyranthes aspera L. and Achyranthes bidentata Blume using nodal explants.

Abstract:
OBJECTIVE
To develop the reproducible in vitro propagation protocols for the medicinally important plants viz., Achyranthes aspera (A. aspera) L. and Achyranthes bidentata (A. bidentata) Blume using nodal segments as explants.

METHODS
Young shoots of A. aspera and A. bidentata were harvested and washed with running tap water and treated with 0.1% bavistin and rinsed twice with distilled water. Then the explants were surface sterilized with 0.1% (w/v) HgCl2 solutions for 1 min. After rinsing with sterile distilled water for 3-4 times, nodal segments were cut into smaller segments (1 cm) and used as the explants. The explants were placed horizontally as well as vertically on solid basal Murashige and Skoog (MS) medium supplemented with 3% sucrose, 0.6% (w/v) agar (Hi-Media, Mumbai) and different concentration and combination of 6-benzyl amino purine (BAP), kinetin (Kin), naphthalene acetic acid (NAA) and indole acetic acid (IAA) for direct regeneration.

RESULTS
Adventitious proliferation was obtained from A. aspera and A. bidentata nodal segments inoculated on MS basal medium with 3% sucrose and augmented with BAP and Kin with varied frequency. MS medium augmented with 3.0 mg/L of BAP showed the highest percentage (93.60±0.71) of shootlets formation for A. aspera and (94.70±0.53) percentages for A. bidentata. Maximum number of shoots/explants (10.60±0.36) for A. aspera and (9.50±0.56) for A. bidentata was observed in MS medium fortified with 5.0 mg/L of BAP. For A. aspera, maximum mean length (5.50±0.34) of shootlets was obtained in MS medium augmented with 3.0 mg/L of Kin and for A. bidentata (5.40±0.61) was observed in the very same concentration. The highest percentage, maximum number of rootlets/shootlet and mean length of rootlets were observed in 1/2 MS medium supplemented with 1.0 mg/L of IBA. Seventy percentages of plants were successfully established in polycups. Sixty eight percentages of plants were well established in the green house condition. Sixty five percentages of plants were established in the field.

CONCLUSIONS
The results have shown that use of nodal buds is an alternative reproducible and dependable method for clonal propagation of A. aspera and A. bidentata. The high rate of direct shoot-root multiplication and their high rate of post-hardening survival indicate that this protocol can be easily adopted for commercial large scale cultivation.

Gnanaraj|Wesely Edward|WE|
Antonisamy|Johnson Marimuthu|JM|
R B|Mohanamathi|M|
Subramanian|Kavitha Marappampalyam|KM|

D029044:Achyranthes
D003470:Culture Media
D018517:Plant Roots
D018520:Plant Shoots
D010946:Plants, Medicinal
D016019:Survival Analysis

In vitro
Clonal propagation
Achyranthes aspera
Achyranthes bidentata
Nodal explant
Reproducible
Nodal segment
Shoots
BAP
Kinetin
NAA
IAA
MS medium
Shootlet
Rootlet
Nodal culture
Plant regeneration
Tissue culture


Surface models of the male urogenital organs built from the Visible Korean using popular software.

Abstract: Unlike volume models, surface models, which are empty three-dimensional images, have a small file size, so they can be displayed, rotated, and modified in real time. Thus, surface models of male urogenital organs can be effectively applied to an interactive computer simulation and contribute to the clinical practice of urologists. To create high-quality surface models, the urogenital organs and other neighboring structures were outlined in 464 sectioned images of the Visible Korean male using Adobe Photoshop; the outlines were interpolated on Discreet Combustion; then an almost automatic volume reconstruction followed by surface reconstruction was performed on 3D-DOCTOR. The surface models were refined and assembled in their proper positions on Maya, and a surface model was coated with actual surface texture acquired from the volume model of the structure on specially programmed software. In total, 95 surface models were prepared, particularly complete models of the urinary and genital tracts. These surface models will be distributed to encourage other investigators to develop various kinds of medical training simulations. Increasingly automated surface reconstruction technology using commercial software will enable other researchers to produce their own surface models more effectively.

Shin|Dong Sun|DS|
Park|Jin Seo|JS|
Shin|Byeong-Seok|BS|
Chung|Min Suk|MS|

Three-dimensional imaging
Computer-assisted image processing
Urogenital system
Visible Human Projects


In vitro function of random donor platelets stored for 7 days in composol platelet additive solution.

Abstract:
BACKGROUND AND AIM
Platelets are routinely isolated from whole blood and stored in plasma for 5 days. The present study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C.

MATERIALS AND METHODS
The study sample included 30 blood donors of both sex in State Blood Bank, CSM Medical University, Lucknow. Random donor platelets were prepared by platelet rich plasma method. Whole blood (350 ml) was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators, with and without additive solution.

RESULTS
Platelet swirling was present in all the units at 22°C on day 7, with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution, whereas platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001) on day 7 without additive solution at 22°C.

CONCLUSION
Our study infers that platelet viability and aggregation were best maintained within normal levels on day 7of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

in vitro
random donor platelets
Additive solution
storage


Uterine Leiomyomas: An ENIGMA.

Abstract:
INTRODUCTION
Leiomyomas are benign tumors composed of smooth muscle cells and varying amounts of fibrous connective tissue commonly encountered in women of reproductive age group. Leiomyomas need hormonal milieu for their growth and maintenance. Unopposed estrogenic stimulation manifests as leiomyomas undergoing secondary changes, endometrial proliferation or hyperplasia, and other associated pathological findings.

OBJECTIVE
To study and analyze various histopathological changes within uterine leiomyomas in hysterectomy specimens. And also, to analyze the associated endometrial and adnexal structures pathology.

MATERIALS AND METHODS
A 4 years retrospective study from June 2010 to June 2014 conducted in the Department of Pathology and Obstetrics and Gynecology, ESIC Medical College and PGIMSR, wherein 820 hysterectomy specimens clinically diagnosed as uterine leiomyomas were subjected to histopathological examination and relevant clinical data were analyzed.

RESULTS
Leiomyomas occurred mostly in women aged 31-50 years (90.23%). Menorrhagia (49.36%) and pain abdomen (30.6%) were the chief clinical manifestations. Endometrial patterns commonly seen were proliferative and hyperplastic endometrium together accounting for 73.4% and dual pathology with adenomyosis was 29.1%. Four cases of tubercular etiology and a single case of granulosa cell tumor of ovary was noted.

CONCLUSION
Though hysterectomy is a routine procedure in the management of uterine leiomyomas, occasional cases of tumor or infective pathology may be missed. Therefore, histopathology is mandatory and conscientious quest must be done for confirmed diagnosis and ensuring optimal management.

Geethamala|Kempula|K|
Murthy|Venkataramappa Srinivasa|VS|
Vani|Bangalore Ramalingiah|BR|
Rao|Sudha|S|

leiomyomas
hysterectomy
Endometrial changes


Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose.

Abstract:
PURPOSE
During development, various life stages of Drosophila melanogaster (D. melanogaster) show different levels of resistance to gamma irradiation, with the early pupal stage being the most radiation sensitive. This provides us an opportunity to explore the biochemical basis of such variations. The present study was carried out to understand the mechanisms underlying radiation resistance during life stages of D. melanogaster.

MATERIALS AND METHODS
Homogenates from all the life stages of D. melanogaster were prepared at stipulated age. These homogenates were used for the determination of (1) enzymatic antioxidants: superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx), and glutathione S-transferase (GST); (2) reducing non-enzymatic antioxidants: total antioxidant capacity (TAC), reduced glutathione (GSH) and non-reducing non-enzymatic antioxidant trehalose; and (3) levels of protein carbonyl (PC) content. Age-dependent changes in radiation resistance and associated biochemical changes were also studied in young (2 d) and old (20 and 30 d) flies.

RESULTS
TAC and GSH were found high in the early pupal stage, whereas catalase and DmGPx were found to increase in the early pupal stage. The non-feeding third instar (NFTI) larvae were found to have high levels of SOD and GST, besides NFTI larvae showed high levels of trehalose. A remarkable decrease was observed in radiation resistance and trehalose levels during the early pupal stage. The PC level was the highest during early pupal stage and was the lowest in NFTI larvae. Older flies showed high level of PC compared with young flies.

CONCLUSION
In vitro increments in trehalose concentration correspond to reduced formation of PCs, suggesting a protective role of trehalose against free radicals. A strong correlation between levels of trehalose and PC formation suggests amelioration of proteome damage due to ionizing radiation (IR). Stages with high trehalose levels showed protected proteome and high radiation resistance, suggesting a significant role for this disaccharide in radiation resistance.

radiation resistance
trehalose
Drosophila melanogaster
antioxidants
protein carbonylation
gamma radiation


Creatine Kinase Is a Marker of Metabolic Syndrome in Qatari Women With and Without Polycystic Ovarian Syndrome.

Abstract: Objective: To correlate features of metabolic syndrome with creatine kinase (CK) in women with and without polycystic ovary syndrome (PCOS). Design: Comparative cross-sectional analysis. Methods: Demographic and metabolic data from Qatari women aged 18-40 years from the Qatar Biobank (97 diagnosed with PCOS, 563 controls). The primary outcome was the association between plasma CK and features of metabolic syndrome. Results: CK increased when the waist circumference was >80 cm (p < 0.015) and when associated with 2 or more features of the metabolic syndrome (p < 0.01). CK correlated with BMI (p < 0.003) but not with waist/hip ratio. Overall, CK did not differ between PCOS and controls, rising equally in both as body mass index (BMI) increased. C reactive protein (CRP) was higher in obese PCOS (P < 0.05) compared to controls, but did not correlate with CK (p > 0.05). Conclusion: CK was associated with an increase in BMI, waist circumference >80 cm and 2 or more features of the metabolic syndrome, in accord with the central role of type II skeletal muscle fibers in energy metabolism and obesity. CK was, however, independent of the PCOS phenotype.

Al-Hail|Noora|N|
Butler|Alexandra E|AE|
Dargham|Soha R|SR|
Abou Seif|Ahmed|A|
Atkin|Stephen L|SL|

creatine kinase
metabolic syndrome
polycystic ovarian syndrome
obesity
inflammation


Time-course of plasma inflammatory mediators in a rat model of brain death.

Abstract:
BACKGROUND
Brain death (BD) is a donor-associated risk factor that negatively affects transplantation outcome. The inflammation associated with BD appears to have a negative effect on organ quality. Complement activation, apoptosis, and pro-inflammatory cytokine and chemokine expression are significantly increased after BD. To better understand this process, we investigated plasma chemokine and cytokine levels for 8h after BD in a rodent model.

METHODS
Thirteen healthy adult male Sprague Dawley rats were intubated and mechanically ventilated. After induction of BD, animals were kept hemodynamically stable for 8h. A panel of immune response factors, including cytokines and chemokines, were measured immediately prior to the induction of BD and at 1, 4, and 8h after BD by multiplex analyses in 10 rats.

RESULTS
In the early phase of BD, we observed an increase in heart rate and a decrease in mean arterial pressure. Only limited fluctuations were noted in the partial pressure of O2, O2 saturation, and HCO3. Monocyte-/macrophage- and lymphocyte-derived mediators (IL-2, IL-4, and IFN-γ) increased steadily during the 8-hour monitoring period.

CONCLUSIONS
The increase in immune responses, particularly pro-inflammatory responses, after BD is time-dependent. Cytokines and chemokines from donors and recipients require further investigation to determine the optimal time frames for organ transplantation in rodent models and humans.

Esmaeilzadeh|Majid|M|
Sadeghi|Mahmoud|M|
Galmbacher|Roland|R|
Daniel|Volker|V|
Knapp|Jürgen|J|
Heissler|Hans E|HE|
Krauss|Joachim K|JK|
Mehrabi|Arianeb|A|

Inflammatory mediators
Rat model
Brain death
Cytokine
Chemokine


Competition for nutrients and light: testing advances in resource competition with a natural phytoplankton community.

Abstract: A key challenge in ecology is to understand how nutrients and light affect the biodiversity and community structure of phytoplankton and plant communities. According to resource competition models, ratios of limiting nutrients are major determinants of species composition. At high nutrient levels, however, species interactions may shift to competition for light, which might make nutrient ratios less relevant. The "nutrient-load hypothesis" merges these two perspectives, by extending the classic model of competition for two nutrients to include competition for light. Here, we test five key predictions of the nutrient-load hypothesis using multispecies competition experiments. A marine phytoplankton community sampled from the North Sea was inoculated in laboratory chemostats provided with different nitrogen (N) and phosphorus (P) loads to induce either single resource limitation or co-limitation of N, P, and light. Four of the five predictions were validated by the experiments. In particular, different resource limitations favored the dominance of different species. Increasing nutrient loads caused changes in phytoplankton species composition, even if the N:P ratio of the nutrient loads remained constant, by shifting the species interactions from competition for nutrients to competition for light. In all treatments, small species became dominant whereas larger species were competitively excluded, supporting the common view that small cell size provides a competitive advantage under resource-limited conditions. Contrary to expectation, all treatments led to coexistence of diatoms, cyanobacteria and green algae, resulting in a higher diversity of species than predicted by theory. Because the coexisting species comprised three phyla with different photosynthetic pigments, we speculate that niche differentiation in the light spectrum might play a role. Our results show that mechanistic resource competition models that integrate nutrient-based and light-based approaches provide an important step forward to understand and predict how changing nutrient loads affect community composition.

Burson|Amanda|A| Stomp|Maayke|M| Greenwell|Emma|E| Grosse|Julia|J| Huisman|Jef|J|

light
resource competition
phytoplankton
biodiversity
North Sea
nitrogen
phosphorus
nutrient load


Affect, work-goal schemas, and work-goal striving among adults with chronic pain: a multilevel structural equation analysis.

Abstract: For individuals with chronic pain, the within-person influence of affect and goal cognition on daily work-related goal striving is not yet well understood. The present study tested the hypothesis that anticipatory goal cognition in the form of a morning work goal schema mediates the relations between morning affect and later (afternoon and evening) work goal striving. Working adults with chronic pain (N = 131) completed a 21-day diary with morning, afternoon, and evening assessments analyzed via multi-level structural equation modeling. At the within-person level, morning positive and negative affect were positively associated with morning work goal schemas; and morning work goal schemas, in turn, positively predicted both afternoon and evening work goal striving. Our findings underscore the complex dynamics over time of the relationship between affect and self-regulatory processes and have implications for future studies and for interventions to assist working adults with chronic pain.

Mun|Chung Jung|CJ|
Karoly|Paul|P|
Okun|Morris A|MA|
Kim|Hanjoe|H|
Tennen|Howard|H|

Affect
Chronic pain
Work goals
Goal schemas
Mediation
Daily diary
Self-regulation


First Reports, Morphological, and Molecular Characterization of Longidorus caespiticola and Longidorus poessneckensis (Nematoda: Longidoridae) from Ukraine.

Abstract: Seven needle nematode species of the genus Longidorus have been reported in Ukraine. Nematological surveys for needle nematodes were carried out in Ukraine between 2016 and 2017 and two nematode species of Longidorus (L. caespiticola and L. poessneckensis) were collected from natural and anthropogenically altered habitats on the territory of Opillia and Zakarpattia in Ukraine. Nematodes were extracted from 500 cm3 of soil by modified sieving and decanting method. Extracted specimens were processed to glycerol and mounted on permanent slides and subsequently identified morphologically and molecularly. Nematode DNA was extracted from single individuals and PCR assays were conducted as previously described for D2-D3 expansion segments of 28S rRNA. Sequence alignments for D2-D3 from L. caespiticola showed 97%-99% similarity to other sequences of L. caespiticola deposited in GenBank from Belgium, Bulgaria, Czech Republic, Russia, Slovenia, and Scotland. Similarly, D2-D3 sequence alignments from L. poessneckensis, showed 99% to other sequences of L. poessneckensis deposited in GenBank from Slovakia and Czech Republic. Morphology, morphometry, and molecular data obtained from these samples were consistent with L. caespiticola and L. poessneckensis identification. To our knowledge, these are the first reports of L. caespiticola and L. poessneckensis in Ukraine, extending the geographical distribution of these species.

needle nematodes
28S rDNA
D2–D3 segments
detection
taxonomy


Inhibition of DNA Methyltransferase by RG108 Promotes Pluripotency-Related Character of Porcine Bone Marrow Mesenchymal Stem Cells.

Abstract: Mesenchymal stem/stromal cells (MSCs) have been identified in almost all adult human tissues and been used in numerous clinical trials for a variety of diseases. Studies have shown that MSCs would undergo cellular senescence when cultured over a long term, which is brought on by increased epigenetic modifications, including DNA methylation. However, the mechanism of MSCs senescence is not well studied. In this study, the effects of RG108, a DNA methyltransferase inhibitor (DNMTi), on senescence, apoptosis, and pluripotency gene expressions in porcine bone marrow (pBM)-MSCs were investigated. First, we determined the optimized dose and time of RG108 treatment in pBM-MSCs to be 10 μM for 48 hours, respectively. Under these conditions, the pluripotency genes (NANOG, POU5F1), the anti-senescence genes (TERT, bFGF), and the anti-apoptosis gene (BCL2) were increased, whereas the apoptotic gene (BAX) was decreased. RG108 protected against apoptosis when pBM-MSC induces apoptosis with H2O2 for 1.5 hours. We also found that RG108 significantly induced the expression of NANOG and POU5F1 by decreasing DNA methylation in gene promoter regions. These results indicate that an optimized dose of RG108 may promote the pluripotency-related character of pBM-MSCs through improving cellular anti-senescence, anti-apoptosis, and pluripotency, which provide a better cell origin for stem cell therapy.

Li|Qi|Q| Zhai|Yanhui|Y| Man|Xiaxia|X| Zhang|Sheng|S| An|Xinglan|X|

porcine bone marrow mesenchymal stem cells


Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.

Abstract: ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.

ATG4D
Apoptosis
Hepatocellular carcinoma
Chemotherapy


Tetracycline, an Appropriate Reagent for Measuring Bone-Formation Activity in the Murine Model of the Streptococcus mutans-Induced Bone Loss.

Abstract: Tetracycline is used as a fluorescent reagent to measure bone formation activity in bone histomorphometric analyses. However, there is a possibility to lead a different conclusion when it is used in a bacteria-infected murine model since the tetracycline is considered to work as an antibiotic reagent. There are non-antibiotic fluorescent reagents such as alizarin and calcein for measuring bone formation activity. The purpose of this study was to clarify whether tetracycline could be an appropriate reagent to measure bone formation activity in a murine bacterial model in the same way as a non-antibiotic fluorescent reagent. We used Streptococcus mutans (S. mutans), a normal inhabitant in the oral cavity and tetracycline-sensitive bacteria, for inducing the bacterial model. The murine bacterial model was generated by intravenously inoculating S. mutans to the tail vein, followed immediately by the injection of the first fluorescent reagent, and the second one was injected 2 days prior to euthanization. After one day of inoculation with S. mutans, the subcutaneously injected alizarin had a similar colony count derived from the liver and the bone marrow tissue compared to the phosphate buffered saline (PBS)-injected control group. On the other hand, subcutaneous injection of tetracycline led to a significantly lower colony count from the liver compared to alizarin- or calcein-injected group. However, on day seven, after S. mutans intravenous injections, bone mineral density of distal femurs was significantly reduced by the bacteria inoculation regardless of which fluorescent reagents were injected subcutaneously. Finally, S. mutans inoculation reduced bone-formation-activity indices in both the tetracycline-alizarin double-injected mice and the calcein-alizarin double-injected mice. These results suggested that a one-time injection of tetracycline did not affect bone formation indices in the S. mutans-induced bone loss model. Tetracycline could be used for measuring bone formation activity in the same way as non-antibiotic fluorescent reagent such as calcein and alizarin, even in a tetracycline-sensitive bacterium-infected model.

Hirohashi|Yuna|Y| Kamijo|Shingo|S| Khan|Masud|M| Ikeda|Masaomi|M| Oki|Meiko|M| Matin|Khairul|K| Rashed|Fatma|F| Aoki|Kazuhiro|K|

tetracycline
bone loss
bone formation indices
Streptococcus. mutans
fluorescent labeling


Lower antibody functionality in middle-aged adults compared to adolescents after primary meningococcal vaccination: Role of IgM.

Abstract:
INTRODUCTION
Successful vaccination of elderly persons is often hampered by immunological ageing, leaving part of the elderly population vulnerable for infectious diseases. As an alternative, timely vaccinations might be administered at middle-age, before reaching old age. Studies evaluating the immunological fitness of middle-aged adults are warranted. In this study we compared the immunogenicity of a primary meningococcal vaccination in Dutch middle-aged adults with that in adolescents, in order to gain knowledge on the early signs of immune ageing.

METHODS
In this study, we compared the antibody responses after a primary meningococcal vaccination between middle-aged adults (50-65years of age, N=204) and adolescents (10-15years of age, N=225). Blood samples were taken pre-, as well as 28days and 1year post-vaccination. Functional antibody titers were measured with the serum bactericidal killing assay using baby rabbit complement (rSBA). Meningococcal polysaccharide (PS) specific IgG and IgM concentrations were determined with a fluorescent bead-based multiplex immunoassay.

RESULTS
Lower post-vaccination functional antibody titers against meningococcal group W and Y were observed in the middle-aged adults compared to the adolescents. One year post-vaccination, also a significantly higher proportion of the middle-aged adults possessed an rSBA titer below protection level. A large reduction in post-vaccination IgM concentrations was observed in the middle-aged adults, whereas IgG concentrations were only marginally different between the two age groups. Strong correlations between the post-vaccination rSBA titers and IgM concentrations were found both in the middle-aged adults and the adolescents.

CONCLUSION
Although protective antibody titers were initiated after primary meningococcal vaccination in middle-aged adults, antibody functionality was significantly lower as compared to that in adolescents. This difference was mainly caused by lower IgM responses. Our results indicate early signs of immune ageing in middle-aged adults, which is important knowledge for the development of future vaccine strategies to better protect elderly persons against infectious diseases.

van der Heiden|Marieke|M|
van Ravenhorst|Mariette B|MB|
Bogaard|Marjan|M|
Boots|Annemieke M H|AMH|
Berbers|Guy A M|GAM|
Buisman|Anne-Marie|AM|

Middle-aged adults
Adolescents
IgM
MenACWY
Primary vaccination


Synthesis and Investigation of Cryogenic Mechanical Properties of Chopped-Glass-Fiber-Reinforced Polyisocyanurate Foam.

Abstract: Polyisocyanurate foam (PIF) has been adopted as a liquefied natural gas (LNG) insulating material owing to its various mechanical merits such as high structural stability and mechanical strength, and excellent insulating ability. In an attempt to increase the mechanical strength of PIF, chopped-glass-fiber-reinforced polyisocyanurate foam (CGR-PIF) was synthesized by adding chopped glass fibers to polyol and isocyanate, which are the raw materials used in the polymerization process for producing PIF. The main objective is to closely observe the compression material characteristics of PIF and CGR-PIF in terms of the cryogenic temperature. Therefore, compressive tests were conducted at cryogenic temperature including low temperatures, and microscopic images were obtained to analyze the cell size and distribution that affects the mechanical and thermal properties of the foam. Furthermore, recovery ratio and weight loss which are important factors of brittle fracture were evaluated, and the applicability of the foams to a cryogenic environment was evaluated. Finally, thermal conductivity, an important parameter of insulation, was evaluated. The obtained results confirm that the compressive strength of CGR-PIF significantly increases at cryogenic temperatures; moreover, a relatively higher thermal conductivity was observed in the case of CGR-PIF as compared to that of PIF owing to the chopped glass fibers.

Kim|Jeong-Dae|JD| Kim|Jeong-Hyeon|JH| Lee|Dong-Ha|DH| Yeom|Dong-Ju|DJ| Lee|Jae-Myung|JM|

synthesis
mechanical properties
compression
thermal properties
reinforcement


The thermal-mechanical properties of functionally graded membrane electrode assembly of PEMFC.

Abstract: Proton exchange membrane fuel cell (PEMFC) is one of the most promising clean energy technologies in the future because of its advantages of having zero pollution and high-power generation efficiency. However, the commercialization of PEMFC is difficult because of the constraints of operational lifetime and cost. Membrane electrode assembly (MEA) is the core component, and its durability determines the performance and life of PEMFC. Owing to the different expansion properties of each layer in MEA, stress concentration and uneven distribution are easily occurred in the process of dynamic cycling of PEMFC, causing the electrode crack and delamination and highly dropping the cell performance. We established the sandwich molecular model of functionally graded membrane electrode assembly (FG-MEA) and investigated the coefficient of thermal expansion and elastic modulus by molecular dynamics simulation. The relationship between gradient structure of FG-MEA and thermomechanical properties was discussed. Three FG-MEA models were established by adding different volume fraction of platinum (Pt) particles along the thickness direction of the membrane. It was found that with the decrease of gradient value, the coefficient of volumetric thermal expansion decreases and elastic modulus along gradient direction slightly increases. The results were in agreement with the estimation of empirical formula of exponential function. The research provides an idea and theoretical reference for the design of FG-MEA materials.

Membrane electrode assembly
Coefficient of thermal expansion
Elastic modulus
Molecular dynamics simulation
Functionally graded material


Selective prey avoidance learning in the predatory sea slug Pleurobranchaea californica.

Abstract: Predator-prey interactions involving aposematic signaling, where predators learn the warning cues of well-defended prey, are clear examples of cost-benefit decisions in foraging animals. However, knowledge of the selectivity of predator learning and the natural conditions where it occurs is lacking for those foragers simpler in brain and body plan. We pursued the question in the sea slug Pleurobranchaea californica, a generalist forager of marked simplicity of body form, nervous system and behavior. This predator exploits many different types of prey, some of which are costly to attack. When offered Flabellina iodinea, an aeolid nudibranch with a stinging defense, biting attack was followed by rapid rejection and aversive turns. The predatory sea slug rapidly learned avoidance. Notable exceptions were animals with extremely high or low feeding thresholds that either ignored F. iodinea or completely consumed it, respectively. Experienced slugs showed strong avoidance of F. iodinea for days after exposure. Aposematic odor learning was selective: avoidance was not linked to change in feeding thresholds, and trained animals readily attacked and consumed a related aeolid, Hermissenda crassicornis. For P. californica, aposematic learning is a cognitive adaptation in which sensation, motivation and memory are integrated to direct cost-benefit choice, and thereby lend flexibility to the generalist's foraging strategy.

aposematism
decision
odor learning
choice
discrimination


The Role of PET Imaging in Gynecologic Radiation Oncology.

Abstract: The goal of this review is to discuss the current utility of fluorine-18-fluorodeoxyglucose (FDG)-PET for radiation oncologists who treat gynecologic malignancies. FDG-PET/computed tomography (CT) is recommended for baseline assessment in cervical cancer and for staging in vulvar and vaginal cancer. The authors use FDG-PET/CT in definitive radiation treatment planning for cervical, vulvar, and vaginal cancer. PET may be helpful for salvage radiation treatment planning for any recurrent gynecologic malignancy. There are published data to support the use of PET in posttreatment evaluation of cervical and vulvar cancer.

D000072078:Positron Emission Tomography Computed Tomography

PET
Cervical cancer
Vulvar cancer
Gynecologic oncology
Ovarian cancer
Radiation therapy
Uterine cancer


Pseudomonas fluorescens Transportome Is Linked to Strain-Specific Plant Growth Promotion in Aspen Seedlings under Nutrient Stress.

Abstract: Diverse communities of bacteria colonize plant roots and the rhizosphere. Many of these rhizobacteria are symbionts and provide plant growth promotion (PGP) services, protecting the plant from biotic and abiotic stresses and increasing plant productivity by providing access to nutrients that would otherwise be unavailable to roots. In return, these symbiotic bacteria receive photosynthetically-derived carbon (C), in the form of sugars and organic acids, from plant root exudates. PGP activities have been characterized for a variety of forest tree species and are important in C cycling and sequestration in terrestrial ecosystems. The molecular mechanisms of these PGP activities, however, are less well-known. In a previous analysis of Pseudomonas genomes, we found that the bacterial transportome, the aggregate activity of a bacteria's transmembrane transporters, was most predictive for the ecological niche of Pseudomonads in the rhizosphere. Here, we used Populus tremuloides Michx. (trembling aspen) seedlings inoculated with one of three Pseudomonas fluorescens strains (Pf0-1, SBW25, and WH6) and one Pseudomonas protegens (Pf-5) as a laboratory model to further investigate the relationships between the predicted transportomic capacity of a bacterial strain and its observed PGP effects in laboratory cultures. Conditions of low nitrogen (N) or low phosphorus (P) availability and the corresponding replete media conditions were investigated. We measured phenotypic and biochemical parameters of P. tremuloides seedlings and correlated P. fluorescens strain-specific transportomic capacities with P. tremuloides seedling phenotype to predict the strain and nutrient environment-specific transporter functions that lead to experimentally observed, strain, and media-specific PGP activities and the capacity to protect plants against nutrient stress. These predicted transportomic functions fall in three groups: (i) transport of compounds that modulate aspen seedling root architecture, (ii) transport of compounds that help to mobilize nutrients for aspen roots, and (iii) transporters that enable bacterial acquisition of C sources from seedling root exudates. These predictions point to specific molecular mechanisms of PGP activities that can be directly tested through future, hypothesis-driven biological experiments.

Shinde|Shalaka|S|
Cumming|Jonathan R|JR|
Collart|Frank R|FR|
Noirot|Philippe H|PH|
Larsen|Peter E|PE|

Pseudomonas
transportomics
plant growth promotion
aspen
nitrogen
phosphorus
computational modeling


Antifungal activity of deferiprone and EDTA against Sporothrix spp.: Effect on planktonic growth and biofilm formation.

Abstract:
The present study evaluated the antifungal activity of the chelators deferiprone (DFP) and ethylenediaminetetraacetic acid (EDTA) and their effect on biofilm formation of the S. schenckii complex. Eighteen strains of Sporothrix spp. (seven S. brasiliensis, three S. globosa, three S. mexicana and five Sporothrix schenckii sensu stricto) were used. Minimum inhibitory concentration (MIC) values for EDTA and DFP against filamentous forms of Sporothrix spp. ranged from 32 to 128 μg/ml. For antifungal drugs, MIC values ranged from 0.25 to 4 μg/ml for amphotericin B, from 0.25 to 4 μg/ml for itraconazole, and from 0.03 to 0.25 μg/ml for terbinafine. The chelators caused inhibition of Sporothrix spp. in yeast form at concentrations ranging from 16 to 64 μg/ml (for EDTA) and 8 to 32 μg/ml (for DFP). For antifungal drugs, MIC values observed against the yeast varied from 0.03 to 0.5 μg/ml for AMB, 0.03 to 1 μg/ml for ITC, and 0.03 to 0.13 μg/ml for TRB. Both DFP and EDTA presented synergistic interaction with antifungals against Sporothrix spp. in both filamentous and yeast form. Biofilms formed in the presence of the chelators (512 μg/ml) showed a reduction of 47% in biomass and 45% in metabolic activity. Our data reveal that DFP and EDTA reduced the growth of planktonic cells of Sporothrix spp., had synergistic interaction with antifungal drugs against this pathogen, and reduced biofilm formation of Sporothrix spp.

LAY SUMMARY
Our data reveal that iron chelators deferiprone and ethylenediaminetetraacetic acid reduced the growth of planktonic cells of Sporothrix spp. as well as had synergistic interaction with antifungal drugs against this pathogen and reduced biofilm formation of Sporothrix spp.

Brilhante|Raimunda Sâmia Nogueira|RSN|
Costa|Anderson da Cunha|ADC|
Pereira|Vandbergue Santos|VS|
Fernandes|Mirele Rodrigues|MR|
de Oliveira|Jonathas Sales|JS|
Rodrigues|Anderson Messias|AM|
Camargo|Zoilo Pires|ZP|
Pereira-Neto|Waldemiro de Aquino|WA|
Sidrim|José Júlio Costa|JJC|
Rocha|Marcos Fábio Gadelha|MFG|

antifungal activity
deferiprone
EDTA
Sporothrix, biofilm


Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

Abstract:
RATIONALE
Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking.

OBJECTIVE
To assess the role of macrophage cholesterol efflux pathways in atherogenesis.

METHODS AND RESULTS
We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production.

CONCLUSIONS
These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Westerterp|Marit|M|
Murphy|Andrew J|AJ|
Wang|Mi|M|
Pagler|Tamara A|TA|
Vengrenyuk|Yuliya|Y|
Kappus|Mojdeh S|MS|
Gorman|Darren J|DJ|
Nagareddy|Prabhakara R|PR|
Zhu|Xuewei|X|
Abramowicz|Sandra|S|
Parks|John S|JS|
Welch|Carrie|C|
Fisher|Edward A|EA|
Wang|Nan|N|
Yvan-Charvet|Laurent|L|
Tall|Alan R|AR|

D064286:ATP Binding Cassette Transporter 1

D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1

macrophages
inflammation
atherosclerosis
high-density lipoprotein
monocytes


Emerging role of chemokine CC motif ligand 4 related mechanisms in diabetes mellitus and cardiovascular disease: friends or foes?

Abstract: Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases.

D000818:Animals
D002317:Cardiovascular Agents
D002318:Cardiovascular Diseases
D054407:Chemokine CCL4
D048909:Diabetes Complications
D003922:Diabetes Mellitus, Type 1
D003924:Diabetes Mellitus, Type 2
D006801:Humans
D007004:Hypoglycemic Agents
D008024:Ligands
D019713:Receptors, CCR5
D015398:Signal Transduction

Chemokine
Chemokine CC motif ligand 4
Diabetes mellitus
Cardiovascular disease
Fifth CC chemokine receptor


Down-regulation of nerve growth factor expression in the bladder by antisense oligonucleotides as new treatment for overactive bladder.

Abstract:
PURPOSE
Nerve growth factor over expression in the bladder has a role in overactive bladder symptoms via the mediation of functional changes in bladder afferent pathways. We studied whether blocking nerve growth factor over expression in bladder urothelium by a sequence specific gene silencing mechanism would suppress bladder overactivity and chemokine expression induced by acetic acid.

MATERIALS AND METHODS
Female Sprague-Dawley® rats anesthetized with isoflurane were instilled with 0.5 ml saline, scrambled or TYE™ 563 labeled antisense oligonucleotide targeting nerve growth factor (12 μM) alone or complexed with cationic liposomes for 30 minutes. The efficacy of nerve growth factor antisense treatments for acetic acid induced bladder overactivity was assessed by cystometry. Bladder nerve growth factor expression levels and cellular distribution were quantified by immunofluorescence staining and enzyme-linked immunosorbent assay. Effects on bladder chemokine expression were measured by Luminex® xMAP® analysis.

RESULTS
Liposomes were needed for bladder uptake of oligonucleotide, as seen by the absence of bright red TYE 563 fluorescence in rats instilled with oligonucleotide alone. At 24 hours after liposome-oligonucleotide treatment baseline bladder activity during saline infusion was indistinct in the sham and antisense treated groups with a mean ± SEM intercontraction interval of 348 ± 55 and 390 ± 120 seconds, respectively. Acetic acid induced bladder overactivity was shown by a decrease in the intercontraction interval to a mean of 33.2% ± 4.0% of baseline in sham treated rats. However, the reduction was blunted to a mean of 75.8% ± 3.4% of baseline in rats treated with liposomal antisense oligonucleotide (p <0.05). Acetic acid induced increased nerve growth factor in the urothelium of sham treated rats, which was decreased by antisense treatment, as shown by enzyme-linked immunosorbent assay and reduced nerve growth factor immunoreactivity in the urothelium. Increased nerve growth factor in bladder tissue was associated with sICAM-1, sE-selectin, CXCL-10 and 1, leptin, MCP-1 and vascular endothelial growth factor over expression, which was significantly decreased by nerve growth factor antisense treatment (p <0.01).

CONCLUSIONS
Acetic acid induced bladder overactivity is associated with nerve growth factor over expression in the urothelium and with chemokine up-regulation. Treatment with liposomal antisense suppresses bladder overactivity, and nerve growth factor and chemokine expression. Local suppression of nerve growth factor in the bladder could be an attractive approach for overactive bladder. It would avoid the systemic side effects that may be associated with nonspecific blockade of nerve growth factor expression.

Kashyap|Mahendra|M| Kawamorita|Naoki|N| Tyagi|Vikas|V| Sugino|Yoshio|Y| Chancellor|Michael|M| Yoshimura|Naoki|N| Tyagi|Pradeep|P|

nerve growth factor
oligonucleotide
overactive bladder
urothelium
bladder overactivity
chemokines
acetic acid
liposomes
intercontraction interval
sICAM-1
sE-selectin
MCP-1
vascular endothelial growth factor
AA
BO
CMG
ICI
NGF
OAB
OND
PBS
VEGF
cystometrogram
monocyte chemoattractant protein-1
phosphate buffered saline
soluble endothelial adhesion molecule
soluble intracellular adhesion molecule
urinary bladder, overactive

P P P P P P P P P P P P P U U U U U U U U U U U M M U M


Ascitic fluid with ammonia odor as a symptom of bladder rupture.

Abstract:
Case
An 88-year-old woman presented with abdominal pain, massive ascites, and acute kidney injury. She was clinically hypervolemic and the computed tomography attenuation value of the ascites was near that of water. Subsequent abdominocentesis revealed ammonia-smelling ascites fluid, leading to a suspicion of urinary tract injury, and a conclusive diagnosis of spontaneous bladder rupture was achieved using cystography.

Outcome
The patient was managed conservatively with antibiotics, percutaneous drainage, and bladder catheter. As a result, she was discharged with normal renal function.

Conclusion
The diagnosis of bladder rupture is difficult, and is rarely confirmed in the absence of a diagnostic suspicion. This case indicates that ascitic fluid odor, patient volume status, and the computed tomography attenuation value of ascites are potential indicators of bladder rupture.

Mizumura|Naoto|N| Imagawa|Atsuo|A| Kawasaki|Masayasu|M| Okumura|Satoshi|S| Toyoda|Sho|S| Ogawa|Masao|M|

ammonia odor
bladder rupture
computed tomography attenuation values
Abdominocentesis
volume status


Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation.

Abstract:
OBJECTIVES
The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8 hours of non-ischemic heart preservation.

DESIGN
Porcine hearts were perfused for 8 hours at 8 °C, either in cycles of 15 minutes perfusion and 60 minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20 mmHg. In organ baths, coronary artery segments from the preserved hearts were studied and compared to fresh controls.

RESULTS
Endothelium-dependent relaxation and contractility were fully preserved after both intermittent and continuous perfusion, as compared to fresh controls. No myocardial edema was seen; water content of the myocardium was 79.5 ± 0.2%, 79.0 ± 0.4% and 79.0 ± 0.3% (ns) for fresh controls, intermittently perfused, and continuously perfused hearts, respectively.

CONCLUSION
Intact endothelial and contractile function of coronary artery may be obtained after 8 hours of non-ischemic heart preservation.

Qin|Guangqi|G| Sjöberg|Trygve|T| Liao|Qiuming|Q| Sun|Xiaoke|X| Steen|Stig|S|

D000818:Animals
D002314:Cardioplegic Solutions
D003331:Coronary Vessels
D004730:Endothelium, Vascular
D066298:In Vitro Techniques
D000067268:Isolated Heart Preparation
D009926:Organ Preservation
D019188:Organ Preservation Solutions
D010477:Perfusion
D034421:Sus scrofa
D013997:Time Factors
D020858:Tissue and Organ Harvesting
D014661:Vasoconstriction
D014664:Vasodilation

Heart preservation
coronary contractility
coronary endothelial function