bluuebunny/crossref_metadata_2025 huggingface dataset:
The nitrogen window for arctic herbivores: plant phenology and protein gain of migratory caribou (Rangifer tarandus)
Authors: Barboza Perry S. , Van Someren Lindsay L. , Gustine David D. , Bret‐Harte M. Syndonia
Published: January 2018

Terrestrial plants are often limited by nitrogen (N) in arctic systems, but constraints of N supply on herbivores are typically considered secondary to those of energy. We tested the hypothesis that forage N is more limiting than energy for arctic caribou by collecting key forages (three species of graminoids, three species of woody browse, and one genus of forb) over three summers in the migratory range of the Central Arctic Herd in Alaska from the Brooks Range to the Coastal Plain on the Arctic Ocean. We combined in vitro digestion and detergent extraction to measure fiber, digestible energy, and usable fractions of N in forages (n = 771). Digestible energy content fell below the minimum threshold value of 9 kJ/g for one single forage group: graminoids, and only beyond 64–75 d from parturition (6 June), whereas all forages fell below the minimum threshold value for digestible N (1% of dry matter) before female caribou would have weaned their calves at 100 d from parturition. The window for digestible N was shortest for browse, which fell below 1% at 30–41 d from parturition, whereas digestible N contents of graminoids were adequate until 46–57 d from parturition. The low quality of browse as a source of N was also apparent from concentrations of available N (i.e., the N not bound to fiber) that were <1% at 72–80 d from parturition. The Coastal Plain may be favored by female caribou because available and digestible concentrations of N are not only greater than those on the Brooks Range, the window of usable N on the Coastal Plain extends the period of protein gain for females and their calves by 17 d. Conversely, inland areas with greater biomass and densities of digestible N than the Coastal Plain may be more favorable for large male caribou that begin gaining protein from spring to breed in autumn. Our study provides evidence that phenological windows for protein gain in caribou are both spatially and temporally dynamic and likely to affect the distribution and growth of the population.
Bacterial diversity is positively correlated with soil heterogeneity
Authors: Curd Emily E. , Martiny Jennifer B. H. , Li Huiying , Smith Thomas B.
Published: January 2018

Plant and animal diversity generally increases with increasing environmental heterogeneity. Here, we test whether this relationship also holds for bacterial communities in soil. Specifically, we investigate whether invasive annual grasslands have reduced soil heterogeneity and, thereby, decreased bacterial alpha‐ and beta‐diversity. Soils were sampled at nine sites within a 5‐km stretch of Southern California, at five depths in three habitats, including non‐native invasive annual grassland, native oak woodland, and native coastal sage scrub. We characterized soil heterogeneity as well as bacterial alpha‐ and beta‐diversity by 16S ribosomalRNAsequencing. We found that invasive annual grasslands harbored less soil heterogeneity and reduced bacterial alpha‐diversity relative to the two native woody habitats. Further, across all habitats and depths, bacterial alpha‐ and beta‐diversity was positively related to soil heterogeneity. These results suggest that plant invasions associated with soil homogenization may lead to reduced microbial diversity.
Development of Corrosion‐Resistant Pressure Sensor with Semiconductor Strain Sensor
Authors: SUZUKI KENGO , OOTA HIROYUKI , UMEYAMA TAKAHIRO
Published: January 2018

In automotive and industrial fields, pressure sensors are a key component for precisely controlling the mechanical systems. Conventional micro electro mechanical system (MEMS)‐based pressure sensors have an advantage in noise resistance, because both strain gauges and control circuits are integrated in one chip. However, the MEMS‐based pressure sensors are generally fabricated on an Si substrate, and have a low stability against various active gases. Thus, we have newly proposed a pressure sensor which consists of an Si‐based strain sensor set on a stainless steel diaphragm with a high stability against the active gases. The key technology is that a Koval plate is inserted between the strain sensor and the stainless steel diaphragm, for preventing the breakage or the delamination of the strain sensor at the bonding interface due to a difference in thermal expansion. Structure of the sensor including the shape and the size of Koval plate and the assembly position of the strain sensor were designed using structural simulation and experiments.

Eventually, the 2.8 mm wide and 0.17 mm thick Koval beam was bridged on the stainless steel diaphragm for efficiently transmitting the diaphragm deformation to the strain sensor. The strain sensor was assembled at the edge of Koval beam with a glass bonding technique. Consequently, the developed pressure sensor has achieved a small dispersion of less than 1% F. S. in a temperature range from 0 °C to 85 °C.
Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction
Authors: Zeng Si‐Yu , Liu Hu‐Hu , Shi Tian‐Qiong , Song Ping , Ren Lu‐Jing , Huang He , Ji Xiao‐Jun
Published: January 2018

The non‐conventional yeast Yarrowia lipolytica have been receiving growing attention due to its excellent lipid accumulation capacity. Microbial lipid have attracted widespread interest due to their broad applications as dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. With the development of whole‐genome sequencing, many effective genetic tools, including transformation systems, promoter systems, genomic integration and genome editing tools, have been applied in Y. lipolytica to enhance the overproduction of lipid. It can be genetically engineered for high lipid production via the upregulation of synthetic precursor and lipid synthesis pathways, the downregulation or disruption of competing pathways such as β‐oxidation, and elimination of inhibitory factors. In this review, the lipid metabolism, available genetic tools, and recent advances in metabolic engineering of Y. lipolytica for the overproduction of lipid and lipid‐derived chemicals is summarized. Future prospects of lipid biosynthesis in Y. lipolytica are discussed in light of the current progress, challenges, and trends in this field. Guidelines for future studies are also proposed.

Practical Applications: General concerns about climate change, oil price crisis, and the increasing study for renewable energy are driving bio‐lipid as promising alternatives to fossil fuel. Over the past few decades, microbial lipid have been widely applied in dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. The non‐conventional yeast Yarrowia lipolytica have become an attractive metabolic engineering host for the production of microbial lipids due to its ability to synthesize them in large quantities. This review illuminates the lipid biosynthesis and degradation of Y. lipolytica, and summarizes the metabolic engineering efforts which have targeted a variety of biosynthetic biosynthetic pathway to efficiently convert carbon source to lipid in oleaginous Y. lipolytica.

Schematic diagram of lipid and triacylglyceride biosynthesis, including the native and heterologous biosynthesis pathways of fatty acids in Y. lipolytica.
Bambusurils Bearing Nitro Groups and Their Further Modifications
Authors: Yawer Mirza Arfan , Sleziakova Kristina , Pavlovec Lukas , Sindelar Vladimir
Published: January 2018

Bambusurils are recently developed neutral anion receptors that show a high affinity towards many inorganic anions, not only in organic solvents but also in water. However, the number of water‐soluble bambusurils and also those bearing functional groups is very limited. In this paper we report the synthesis of four‐ and six‐membered bambusurils containing eight and twelve nitro groups. All the nitro groups on the bambusuril portals could be transformed into amino functions, which provided the macrocycles with water solubility and allowed their further modification. For example, we have demonstrated the conversion of amino groups on the bambusurils into the corresponding urea‐functionalized bambusuril derivatives. We also report the first example of a bambusuril bearing only two functional groups, which was prepared by the condensation of two different glycolurils.
It's Time to Celebrate!
Authors: Nijs Anne
Published: January 2018

Managing Editor Anne Nijs reflects on important journal activities of the past year and gives an outlook on the exciting 20th anniversary celebrations and special/virtual issues to watch out for in 2018.
Performance of the Early Access AmpliSeq™ Mitochondrial Panel with degraded DNA samples using the Ion Torrent™ platform
Authors: Wai Ka Tak , Barash Mark , Gunn Peter
Published: January 2018

The Early Access AmpliSeq™ Mitochondrial Panel amplifies whole mitochondrial genomes for phylogenetic and kinship identifications, using Ion Torrent™ technology. There is currently limited information on its performance with degraded DNA, a common occurrence in forensic samples. This study evaluated the performance of the Panel with DNA samples degraded in vitro, to mimic conditions commonly found in forensic investigations. Purified DNA from five individuals was heat‐treated at five time points each (125°C for 0, 30, 60, 120, and 240 min; total n = 25). The quality of DNA was assessed via a real‐time DNA assay of genomic DNA and prepared for massively parallel sequencing on the Ion Torrent™ platform. Mitochondrial sequences were obtained for all samples and had an amplicon coverage averaging between 66X to 2803X. Most amplicons (157/162) displayed high coverages (452 ± 333X), while reads with less than 100X coverage were recorded in five amplicons only (90 ± 5X). Amplicon coverage was decreased with prolonged heating. At 72% strand balance, reads were well balanced between forward and reverse strands. Using a coverage threshold of ten reads per SNP, complete sequences were recovered in all samples and resolved kinship and, haplogroup relations. Additionally, the HV1 and HV2 regions of the reference and 240‐min heat‐treated samples (n = 10) were Sanger‐sequenced for concordance. Overall, this study demonstrates the efficacy of a novel forensic Panel that recovers high quality mitochondrial sequences from degraded DNA samples.
Multi‐site N‐Glycan mapping study 2: UHPLC
Authors: Szekrényes Ákos , Park SungAe Suhr , Cosgrave Eoin , Jones Aled , Haxo Ted , Kimzey Michael , Pourkaveh Shiva , Szabó Zoltán , Sosic Zoran , Feng Peng , Sejwal Preeti , Dent Kelsey , Michels David , Freckleton Gordon , Qian Jun , Lancaster Catherine , Duffy Toni , Schwartz Melissa , Luo Jiann‐Kae , van Dyck Jonathan , Leung Pui‐King , Olajos Marcell , Kowle Ronald , Gao Kai , Wang Wenbo , Wegstein Jo , Tep Samnang , Domokos Apolka , Váradi Csaba , Guttman András
Published: January 2018

In the first part of this publication, the results from an international study evaluating the precision (i.e., repeatability and reproducibility) of N‐glycosylation analysis using capillary electrophoresis of APTS‐labeled N‐glycans were presented. The corresponding results from ultra‐high performance liquid chromatography (UHPLC) with fluorescence detection are presented here from 12 participating sites. All participants used the same lot of samples, reagents, and columns to perform the assays. Elution time, peak area and peak area percent values were determined for all peaks ≥0.1% peak area, and statistical analysis was performed following ISO 5725‐2 guideline principles. The results demonstrated adequate reproducibility, within any given site as well across all sites, indicating that standard UHPLC‐based N‐glycan analysis platforms are appropriate for general use.
Sexual competition and the evolution of condition-dependent ageing
Authors: Hooper Amy K. , Lehtonen Jussi , Schwanz Lisa E. , Bonduriansky Russell
Published: January 2018

Increased individual resources (condition) can be correlated with either increased or decreased longevity. While variation in resource acquisition and allocation can account for some of this variation, the general conditions that select for either pattern remain unclear. Previous models suggest that nonlinearity of payoffs from investment in reproduction (e.g., male secondary sexual traits) can select for high-condition individuals that sacrifice longevity to increase reproductive opportunity. However, it remains unclear what mating systems or patterns of sexual competition might select for such life-history strategies. We used a model of condition-dependent investment to explore how expected payoffs from increased expression of secondary sexual traits affect optimal investment in lifespan. We find that nonlinearity of these payoffs results in a negative relationship between condition and lifespan under two general conditions: first, when there are accelerating marginal benefits from increasing investment; second, when individuals that invest minimally in secondary sexual trait expression can still achieve matings. In the second scenario, the negative relationship occurs due to selection on low-condition individuals to extend lifespan at the cost of secondary sexual trait expression. Our findings clarify the potential role of sexual selection in shaping patterns of condition-dependent ageing, and highlight the importance of considering the strategies of both low- and high-condition individuals when investigating patterns of condition-dependent ageing.
Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)
Authors: Gómez Rosa M. , Sánchez Magdy Y. , Portela‐Lomba Maria , Ghotme Kemel , Barreto George E. , Sierra Javier , Moreno‐Flores M. Teresa
Published: January 2018

The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell‐based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.
To engage or not to engage with host governments: Corporate political activity and host country political risk
Authors: De Villa Maria A. , Rajwani Tazeeb , Lawton Thomas C. , Mellahi Kamel
Published: January 2018

Research summary: We analyze how a host market’s institutional context can influence a multinational enterprise’s (MNE’s) senior management’s choice and deployment of corporate political activity (CPA). First, we argue that a non‐engaged approach to CPA is likely to be chosen when senior management perceives high host country political risk, arising not only from host country political institutions, but also from the distance between home and host government relations. Second, we propose that the deployment of this approach can require active adaptation through four political strategies: low visibility, ensuring a minimal degree of general attention from other actors; rapid compliance, entailing high speed actions to obey the rules; reconfiguration, involving rearranging the MNE’s structure and processes for competitiveness; and anticipation, implying the prediction of public policy and analysis of interest groups to anticipate responses.

Managerial summary: Senior managers of multinational enterprises often examine when and how to engage, or not to engage, with host governments. We argue that senior managers are likely to choose to evade engagement with a host government when they perceive high host country political risk, not only through public political risk ratings, but also via their home and host government relations. We show that this choice can require senior managers to lead active adaptation through four strategies: low visibility, enabling the MNE to operate under the radar of host governments; rapid compliance, entailing high speed actions to obey the rules; reconfiguration, involving rearranging the MNE’s structure and processes for competitiveness; and anticipation, implying the prediction of public policy and analysis of interest groups to anticipate responses.

A video abstract is available at https://youtu.be/DL1LlQEhGU0.
Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1
Authors: Planche Vincent , Koubiyr Ismail , Romero José E. , Manjon José V. , Coupé Pierrick , Deloire Mathilde , Dousset Vincent , Brochet Bruno , Ruet Aurélie , Tourdias Thomas
Published: January 2018

Background

Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate.

Method

We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1‐year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques.

Results

At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (−6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum‐pyramidale and the stratum radiatum‐lacunosum‐moleculare, −5.6%, p < .001 and −6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2 = 0.44 to 0.47, p < .001, with age, T2 lesion‐load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow‐up, independently of T2‐lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05).

Conclusion

The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal‐dependent memory performance.
Controlling the Temporal Structure of Brain Oscillations by Focused Attention Meditation
Authors: Irrmischer Mona , Houtman Simon J. , Mansvelder Huibert D. , Tremmel Michael , Ott Ulrich , Linkenkaer‐Hansen Klaus
Published: January 2018

Our focus of attention naturally fluctuates between different sources of information even when we desire to focus on a single object. Focused attention (FA) meditation is associated with greater control over this process, yet the neuronal mechanisms underlying this ability are not entirely understood. Here, we hypothesize that the capacity of attention to transiently focus and swiftly change relates to the critical dynamics emerging when neuronal systems balance at a point of instability between order and disorder. In FA meditation, however, the ability to stay focused is trained, which may be associated with a more homogeneous brain state. To test this hypothesis, we applied analytical tools from criticality theory to EEG in meditation practitioners and meditation‐naïve participants from two independent labs. We show that in practitioners—but not in controls—FA meditation strongly suppressed long‐range temporal correlations (LRTC) of neuronal oscillations relative to eyes‐closed rest with remarkable consistency across frequency bands and scalp locations. The ability to reduce LRTC during meditation increased after one year of additional training and was associated with the subjective experience of fully engaging one's attentional resources, also known as absorption. Sustained practice also affected normal waking brain dynamics as reflected in increased LRTC during an eyes‐closed rest state, indicating that brain dynamics are altered beyond the meditative state. Taken together, our findings suggest that the framework of critical brain dynamics is promising for understanding neuronal mechanisms of meditative states and, specifically, we have identified a clear electrophysiological correlate of the FA meditation state.
Submental artery island flap with simultaneous level I neck dissection
Authors: Eskander Antoine , Strigenz Daniel , Seim Nolan , Ozer Enver
Published: January 2018

Background

The purpose of this study was to illustrate the submental island flap elevation technique with simultaneous level I neck dissection followed by the inset and reconstruction of an oropharyngeal defect.

Methods

A 63‐year‐old patient with a T2N1M0 human papillomavirus‐positive squamous cell carcinoma of the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A local recurrence 2.5 years after treatment was treated surgically and reconstructed with a submental island flap.

Results

There were no complications and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1 month postoperatively. A video demonstration of the submental island flap elevation is included with a focus on how levels 1A and 1B can be dissected safely and this can be viewed online on Head & Neck's home page at http://onlinelibrary.wiley.com/.

Conclusion

The submental island flap can be performed safely with a level I neck dissection for head and neck reconstruction.
Cellular Membrane Trafficking Machineries Used by the Hepatitis Viruses
Authors: Inoue Jun , Ninomiya Masashi , Shimosegawa Tooru , McNiven Mark A.
Published: January 2018

While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses “hijack” the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are well known as leading causes of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating hepatitis C virus patients have recently been made, patients with HBV continue to require lifelong treatment, which makes a thorough understanding of the HBV life cycle essential. Importantly, these viruses have been observed to “hijack” the secretory and endocytic membrane trafficking machineries of the hepatocyte. These can include the canonical clathrin‐mediated endocytic process that internalizes virus through cell surface receptors. While these receptors are encoded by the host genome for normal hepatocellular functions, they also exhibit virus‐specific recognition. Further, functions provided by the multivesicular body, which include endosomal sorting complexes required for transport, are now known to envelope a variety of different hepatitis viruses. In this review, we summarize the recent findings regarding the cellular membrane trafficking machineries used by HBV in the context of other hepatitis viruses. (Hepatology 2018; 00:000‐000).
Self‐perceived long‐term transfer of learning after postpartum hemorrhage simulation training
Authors: de Melo Brena Carvalho Pinto , Rodrigues Falbo Ana , Sorensen Jette Led , van Merriënboer Jeroen J.G. , van der Vleuten Cees
Published: January 2018

Objective

To explore long‐term transfer (application of acquired knowledge and skills on the job) after postpartum hemorrhage simulation training based on either instructional design (ID) principles or conventional best practice.

Methods

In this qualitative study, semi‐structured interviews with obstetrics and gynecology healthcare practitioners were conducted between August 7 and September 26, 2015, in Recife, Brazil. The participants were randomly selected from each of two postpartum hemorrhage simulations attended 2 years earlier (one ID and one conventional best practice). Thematic analysis was used to explore (1) residents' perceptions of long‐term transfer of learning, (2) ID elements influencing the perceived long‐term transfer, and (3) differences in the participants' perceptions according to the type of simulation attended.

Results

There were 12 interview participants. After either simulation format, residents perceived long‐term transfer effects. Training design factors influencing transfer were, in their opinion, related to trainees' characteristics, simulation design, and workplace environment. Trainees who participated in the ID‐based simulation perceived better communication skills and better overall situational awareness: “I didn't do that before.”

Conclusion

All residents perceived long‐term transfer after simulation training for postpartum hemorrhage. Those who attended the ID format additionally perceived improvements in communication skills and situational awareness, which are fundamental factors in the management of postpartum hemorrhage.
Genetic and Molecular Insights Into Genotype-Phenotype Relationships in Osteopathia Striata With Cranial Sclerosis (OSCS) Through the Analysis of Novel Mouse Wtx Mutant Alleles
Authors: Comai Glenda , Boutet Agnès , Tanneberger Kristina , Massa Filippo , Rocha Ana-Sofia , Charlet Aurelie , Panzolini Clara , Jian Motamedi Fariba , Brommage Robert , Hans Wolfgang , Funck-Brentano Thomas , Hrabe de Angelis Martin , Hartmann Christine , Cohen-Solal Martine , Behrens Jürgen , Schedl Andreas
Published: January 2018

The X-linked WTX/AMER1 protein constitutes an important component of the β-catenin destruction complex that can both enhance and suppress canonical β-catenin signaling. Somatic mutations in WTX/AMER1 have been found in a proportion of the pediatric kidney cancer Wilms’ tumor. By contrast, germline mutations cause the severe sclerosing bone dysplasia osteopathia striata congenita with cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal lethality in male patients. Here we address the developmental and molecular function of WTX by generating two novel mouse alleles. We show that in addition to the previously reported skeletal abnormalities, loss of Wtx causes severe midline fusion defects including cleft palate and ectopic synostosis at the base of the skull. By contrast, deletion of the C-terminal part of the protein results in only mild developmental abnormalities permitting survival beyond birth. Adult analysis, however, revealed skeletal defects including changed skull morphology and an increased whole-body bone density, resembling a subgroup of male patients carrying a milder, survivable phenotype. Molecular analysis in vitro showed that while β-catenin fails to co-immunoprecipitate with the truncated protein, partial recruitment appears to be achieved in an indirect manner using AXIN/AXIN2 as a molecular bridge. Taken together our analysis provides a novel model for WTX-caused bone diseases and explains on the molecular level how truncation mutations in this gene may retain some of WTX-protein functions. © 2018 American Society for Bone and Mineral Research.
Prognostic significance of miR‐21 and PDCD4 in patients with stage II esophageal carcinoma after surgical resection
Authors: Zhang Jiandong , Ma Lei , Shi Daimeng , Zhang Zhen , Yao Chuanshan , Zhao Xulin , Xu Quanxiao , Wen Penghao , He Limin
Published: January 2018

Many studies have shown that randomized clinical trial with long‐term follow‐up found no improvement in stage II esophageal carcinoma (EC) patients receiving preoperative neoadjuvant chemoradiotherapy or chemotherapy treatment, this limitation underscored the urgent need for novel and reliable biomarkers for prognosis and prediction in stage II EC. miR‐21 is frequently over‐expressed while programmed cell death 4 (PDCD4) is often down‐regulated in solid tumors. This study aimed to investigate the clinicopathological and prognostic significance of miR‐21 and PDCD4 expression and to elucidate any correlation between miR‐21 and PDCD4 expression in stage II EC patients. The expression level of miR‐21 was up‐regulated while the PDCD4 protein was down‐regulated in stage II EC tissues compared with the adjacent non‐cancerous tissues. Analyses of the clinicopathological parameters indicated that miR‐21 expression was associated with differentiation grade, T stage, and N stage. PDCD4 protein expression was associated with T stage, N stage, and tumor size. The univariate linear regression analysis suggested a significant negative correlation between miR‐21 and PDCD4 expression. The Kaplan‐Meier curve showed that high miR‐21 expression or low PDCD4 expression predicted poor progression‐free survival (PFS) and overall survival (OS) of patients with stag II EC. In conclusion, both up‐regulated miR‐21 and down‐regulated PDCD4 expression were associated with the aggressive progression and poor prognosis of stage II EC. miR‐21 and PDCD4 might be potential biomarkers of tumor progression and indicators of prognosis of stag II EC.
Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells
Authors: Yang Zhikuan , Wei Danping , Liu Feifei , Liu Jing , Wu Xiaoming , Stevens Malcolm F. G. , Bradshaw Tracey D. , Luo Ying , Zhang Jihong
Published: January 2018

The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6‐methylguanine‐DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8‐methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT‐overexpressing and mismatch repair (MMR)‐deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found that PMX 465 could reduce MGMT expression by increasing the binding of wild‐type p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter.
Journey of oocyte from metaphase‐I to metaphase‐II stage in mammals
Authors: Sharma Alka , Tiwari Meenakshi , Gupta Anumegha , Pandey Ashutosh N. , Yadav Pramod K. , Chaube Shail K.
Published: January 2018

In mammals, journey from metaphase‐I (M‐I) to metaphase‐II (M‐II) is important since oocyte extrude first polar body (PB‐I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M‐I to M‐II stage and extrusion of PB‐I remain ill understood. Several factors drive oocyte meiosis from M‐I to M‐II stage. The mitogen‐activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M‐I to M‐II stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation of anaphase‐promoting complex/cyclosome (APC/C). The active APC/C destabilizes maturation promoting factor (MPF) and induces meiotic resumption. Several signal molecules such as, c‐Jun N‐terminal kinase (JNK2), SENP3, mitotic kinesin‐like protein 2 (MKlp2), regulator of G‐protein signaling (RGS2), Epsin2, polo‐like kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation. Rho family GTPase is another enzyme that along with cell division cycle (Cdc42) to form actomyosin contractile ring required for chromosomal segregation. In the presence of origin recognition complex (ORC4), eccentrically localized haploid set of chromosomes trigger cortex differentiation and determine the division site for polar body formation. The actomyosin contractile activity at the site of division plane helps to form cytokinetic furrow that results in the formation and extrusion of PB‐I. Indeed, oocyte journey from M‐I to M‐II stage is coordinated by several factors and pathways that enable oocyte to extrude PB‐I. Quality of oocyte directly impact fertilization rate, early embryonic development, and reproductive outcome in mammals.
Bradykinin mediates the association of collecting duct cells to form migratory colonies, through B2 receptor activation
Authors: Guaytima Edith d. V. , Brandán Yamila R. , Favale Nicolás O. , Santacreu Bruno J. , Sterin‐Speziale Norma B. , Márquez María G.
Published: January 2018

It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting duct (CD) cells of the newborn rat kidney, but little is known about its role during early postnatal life. Therefore, we hypothesize that BK could participate in the mechanisms that mediate CD formation during the postnatal renal development. Performing primary cultures, combined with biochemical, immunocytochemical, and time‐lapse analysis, we studied the role of BK in CD cell behavior isolated from renal papilla of neonatal rats. A reverse relationship was observed between B2R expression and the degree of CD epithelial cell sheet maturation. BK stimulation induced CD cell association upon B2R activation. The lack of B2R expression in cells showing mature adherens junctions suggested that BK is mostly involved in early adhesive events, thus favoring the initial formation of CD during development. Time‐lapse analysis revealed that BK induced a high protrusive activity of CD cells, denoted by ruffle formation and lamellipodia extension. PI3K was involved in the BK‐induced CD cell‐cell association and the acquisition of the migratory phenotype since, when inhibited, membrane ruffles, and filopodia between cells diminished. Results indicate that the actions of BK mediated by PI3K activation were due to the downstream Akt and Rac pathways. This study, performed with CD cells that were not genetically manipulated, provides new experimental evidence supporting a novel role of BK in rat renal CD organization. As B2R blockade results in abnormal tubular differentiation, our results contribute to better understanding the etiology of human congenital renal malformation and diseases.
Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant Drugs in Healthy Volunteers
Authors: Feng Hwa‐Ping , Caro Luzelena , Fandozzi Christine M. , Guo Zifang , Talaty Jennifer , Wolford Dennis , Panebianco Deborah , Iwamoto Marian , Butterton Joan R. , Yeh Wendy W.
Published: January 2018

Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant drugs in posttransplant people who are infected with hepatitis C virus. The aim of the present study was to assess the safety and pharmacokinetic interactions between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and prednisone. This was a 4‐part, open‐label study in 58 healthy volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus 2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once‐daily EBR 50 mg/GZR 200 mg. Multiple oral doses of EBR + GZR had no significant effect on cyclosporine. However, in the presence of cyclosporine, the 24‐hour area under the concentration‐time curve of GZR was increased by approximately 15‐fold (geometric mean ratio [90%CI] 15.21 [12.83; 18.04]); the concentration of EBR was increased approximately 2‐fold in the presence of cyclosporine. Coadministration of EBR/GZR and tacrolimus did not affect the pharmacokinetics of EBR or GZR, but resulted in an increase in tacrolimus AUC (geometric mean ratio [90%CI] 1.43 [1.24; 1.64]). There were no clinically relevant interactions between EBR/GZR and either MMF or prednisone. Data from the present study indicate that EBR/GZR may be coadministered in people receiving tacrolimus, MMF, and prednisolone. EBR/GZR is contraindicated in people receiving cyclosporine because the significantly higher concentrations of GZR may increase the risk of transaminase elevations.
Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure
Authors: Okour Malek , Jacobson Pamala A. , Ahmed Mariam A. , Israni Ajay K. , Brundage Richard C.
Published: January 2018

Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed to prevent rejection after kidney transplantation. Wide between‐subject variability (BSV) in MPA exposure exists which in part may be due to variability in enterohepatic recirculation (EHC). Several modeling strategies were developed to evaluate EHC as part of MPA pharmacokinetics, however mechanistic representation of EHC is limited. These models have not provided a satisfactory representation of the physiology of EHC in their modeling assumptions. The aim of this study was i) to develop an integrated model of MPA (total and unbound) and its metabolites (MPAG and acyl‐MPAG) in kidney recipients, where this model provides a more physiological representation of EHC process, and ii) to evaluate the effect of donor and recipient clinical covariates and genotypes on MPA disposition. A five‐compartment model with first‐order input into an unbound MPA compartment connected to the MPAG, acyl‐MPAG, and gallbladder compartment best fit the data. To represent the EHC process, the model was built based on the physiological concepts related to the hepatobiliary system and the gallbladder filling and emptying processes. The effect of cyclosporine versus tacrolimus on clearance of unbound MPA was included in the base model. Covariate analysis showed creatinine clearance to be significant on oral clearance of unbound MPA. The hepatic nuclear factor 1 alpha (HNF1A) genetic single nucleotide polymorphism (SNP) (rs2393791) in the recipient significantly affected the fraction of enterohepatically‐circulated drug. Oral clearance of MPAG was affected by recipient IMPDH1 SNP (rs2288553), diabetes at the time of transplant, and donor sex.
Eliminating hepatitis C virus as a public health threat among HIV‐positive men who have sex with men: a multi‐modelling approach to understand differences in sexual risk behaviour
Authors: Scott Nick , Stoové Mark , Wilson David P , Keiser Olivia , El‐Hayek Carol , Doyle Joseph , Hellard Margaret
Published: January 2018

Introduction

Outbreaks of hepatitis C virus (HCV) infections among HIV‐positive men who have sex with men (MSM) have been observed globally. Using a multi‐modelling approach we estimate the time and number of direct‐acting antiviral treatment courses required to achieve an 80% reduction in HCV prevalence among HIV‐positive MSM in the state of Victoria, Australia.

Methods

Three models of HCV transmission, testing and treatment among MSM were compared: a dynamic compartmental model; an agent‐based model (ABM) parametrized to local surveillance and behavioural data (“ABM1”); and an ABM with a more heterogeneous population (“ABM2”) to determine the influence of extreme variations in sexual risk behaviour.

Results

Among approximately 5000 diagnosed HIV‐positive MSM in Victoria, 10% are co‐infected with HCV. ABM1 estimated that an 80% reduction in HCV prevalence could be achieved in 122 (inter‐quartile range (IQR) 112 to 133) weeks with 523 (IQR 479 to 553) treatments if the average time from HCV diagnosis to treatment was six months. This was reduced to 77 (IQR 69 to 81) weeks if the average time between HCV diagnosis and treatment commencement was decreased to 16 weeks. Estimates were consistent across modelling approaches; however ABM2 produced fewer incident HCV cases, suggesting that treatment‐as‐prevention may be more effective in behaviourally heterogeneous populations.

Conclusions

Major reductions in HCV prevalence can be achieved among HIV‐positive MSM within two years through routine HCV monitoring and prompt treatment as a part of HIV care. Compartmental models constructed with limited behavioural data are likely to produce conservative estimates compared to models of the same setting with more complex parametrizations.
The lesion characteristics assessed by LGE‐MRI after the cryoballoon ablation and conventional radiofrequency ablation
Authors: Kurose Jun , Kiuchi Kunihiko , Fukuzawa Koji , Mori Shumpei , Ichibori Hirotoshi , Konishi Hiroki , Taniguchi Yayoi , Hyogo Kiyohiro , Imada Hiroshi , Suehiro Hideya , Nagamatsu Yu‐ichi , Akita Tomomi , Takemoto Makoto , Hirata Ken‐ichi , Shimoyama Shinsuke , Watanabe Yoshiaki , Nishii Tatsuya , Negi Noriyuki , Kyotani Katsusuke
Published: January 2018

Background

Rhythm outcomes after the pulmonary vein isolation (PVI) using the cryoballoon (CB) are reported to be excellent. However, the lesions after CB ablation have not been well discussed. We sought to characterize and compare the lesion formation after CB ablation with that after radiofrequency (RF) ablation.

Methods

A total of 42 consecutive patients who underwent PVI were enrolled (29 in the CB group and 13 in the RF group). The PVI lesions were assessed by late gadolinium enhancement magnetic resonance imaging 1–3 months after the PVI. The region around the PVs was divided into eight segments: roof, anterior‐superior, anterior‐carina, anterior‐inferior, bottom, posterior‐inferior, posterior‐carina, and posterior‐superior segment. The lesion width and lesion gap in each segment were compared between the two groups. Lesion gaps were defined as no‐enhancement sites of >4 mm.

Results

As compared to the RF group, the overall lesion width was significantly wider and lesion gaps significantly fewer at the anterior‐superior segment of the left PV (LAS) and anterior‐inferior segment of the right PV (RAI) in the CB group (lesion width: 8.2 ± 2.2 mm vs 5.6 ± 2.0 mm, P = .001; lesion gap at LAS: 7% vs 38%, P = .02; lesion gap at RAI: 7% vs 46%, P = .006).

Conclusions

The PVI lesions after CB ablation were characterized by extremely wider and more continuous lesions than those after RF ablation.
Characteristics and intestinal immunomodulating activities of water‐soluble pectic polysaccharides from Chenpi with different storage periods
Authors: Tian Changcheng , Xu Hui , Li Jing , Han Zhuo
Published: January 2018

BACKGROUND

The traditional view considers that Chenpi (dried citrus peel) stored over the long‐term has better health efficacies compared to fresh Chenpi, although the detailed mechanism responsible for this remains obscure.

RESULTS

The three water‐soluble pectic polysaccharides (CPP1, CPP5 and CPP10) were obtained from 1‐, 5‐ and 10‐year Chenpi, respectively, and their physicochemical characteristics and intestinal immunomodulating activities were investigated and compared. The results obtained showed that CPP5 and CPP10 demonstrated a lower dynamic viscosity and degree of methylesterification, as well as a higher molecular heterogeneity, compared to CPP1. Monosaccharide composition analysis indicated that CPP1 was composed of arabinose, galacturonic acid and galactose, and a small amount of rhamnose; however, CPP5 and CPP10 consisted of arabinose, galacturonic acid, galactose, glucose and xylose, and a small amount of rhamnose. With the extension of storage period of Chenpi, the content of soluble conjugate phenolic acids increased in the pectic polysaccharide. Furthermore, it was confirmed that the pectic polysaccharides extracted from the 5‐year and 10‐year Chenpi could significantly enhance the proliferation of bone marrow cells via activating the Peyer's patch cells in vitro.

CONCLUSION

The present study demonstrates the differences in the pectic polysaccharides from Chenpi with different storage periods and also confirms that the pectic polysaccharides extracted from Chenpi stored over the long‐term had more significant intestinal activities compared to that obtained from the fresh Chenpi. This phenomenon might partly explain why the Chenpi stored over the long‐term has better healthcare effects. © 2018 Society of Chemical Industry
Determination of phthalate esters in soil using a quick, easy, cheap, effective, rugged, and safe method followed by GC–MS
Authors: Liu Qianjun , Chen Di , Wu Jiyuan , Yin Guangcai , Lin Qintie , Zhang Min , Hu Huawen
Published: January 2018

A quick, easy, cheap, effective, rugged, and safe procedure was designed to extract pesticide residues from fruits and vegetables with a high percentage of water. It has not been used extensively for the extraction of phthalate esters from sediments, soils, and sludges. In this work, this procedure was combined with gas chromatography with mass spectrometry to determine 16 selected phthalate esters in soil. The extraction efficiency of the samples was improved by ultrasonic extraction and dissolution of the soil samples in ultra‐pure water, which promoted the dispersion of the samples. Furthermore, we have simplified the extraction step and reduced the risk of organic solvent contamination by minimizing the use of organic solvents. Different extraction solvents and clean‐up adsorbents were compared to optimize the procedure. Dichloromethane/n‐hexane (1:1, v/v) and n‐hexane/acetone (1:1, v/v) were selected as the extractants from the six extraction solvents tested. C18/primary secondary amine (1:1, m/m) was selected as the sorbent from the five clean‐up adsorbents tested. The recoveries from the spiked soils ranged from 70.00 to 117.90% with relative standard deviation values of 0.67–4.62%. The proposed approach was satisfactorily applied for the determination of phthalate esters in 12 contaminated soil samples.
High‐capacity protein A affinity chromatography for the fast quantification of antibodies: Two‐wavelength detection expands linear range
Authors: Satzer Peter , Jungbauer Alois
Published: January 2018

The high‐throughput analysis of antibodies from processes can be enhanced when the linear range is expanded and sample preparation is kept to a minimum. We developed a fast chromatography method based on a hexameric variant of staphylococcal protein A immobilized on Toyopearl matrix, TSK 5 PW using two wavelengths. A protocol with 5 min runtime and a single‐wavelength detection at 280 nm yielded an upper limit of quantification of 2.10 mg/mL and a lower limit of quantification of 0.06 mg/mL. The optimized method with a runtime of 2 min and two‐wavelength detection at 280 and 300 nm allowed us to span a valid concentration range of 0.01–5.20 mg/mL using two calibration curves. Sample selectivity was tested using mock supernatant mixed with antibody concentrations of 0.1–2.1 mg/mL, sample stability in the autosampler was shown for at least 24 h. We also tested the capabilities of the method to determine purity of an antibody sample by calculating the ratio of peak area of elution to peak area of flow‐through, which correlated well with the expected purity. The method will be very useful for process development and in‐process control, spanning concentrations from seed fermentation to harvest and purification.