bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex Vivo 1H NMR study of pituitary adenomas to differentiate various immunohistochemical subtypes
Authors: Ijare Omkar B. , Baskin David S. , Pichumani Kumar
Published: February 2019

Pituitary adenomas (PAs) are benign growths arising from epithelial cells in the adenohypophysis of the pituitary gland. To date, there has been no detailed metabolic characterization of PAs of various subtypes. In this study, we report nuclear magnetic resonance (NMR) based metabolomic analysis of surgically resected tumors from forty five pituitary tumor patients [gonadotropic (LH/FSH-secreting) = 17; prolactinomas (PRL-secreting) = 11, Cushing’s disease (ACTH-secreting) = 4, non-functional = 5, and mixed = 8] who underwent transsphenoidal selective adenomectomy. Compared to LH/FSH-secreting tumors, PRL-secreting tumors showed statistically significant decrease in the levels of N-acetylaspartate (NAA), myo-inositol (mI), scyllo-inositol (sI), glycine, taurine, phosphoethanolamine (PE) and increase in the levels of glutamine. When compared with LH/FSH-secreting tumors, ACTH-secreting tumors showed statistically significant decrease in the levels of sI, glycine, PE and increase in the levels of aspartate. Although lipid extracts of PAs showed the presence of many common lipid molecules, only glycerophosphoethanolamine (GPE) showed statistically significant decrease in PRL, ACTH and non-functional subtypes when compared to LH/FSH-secreting tumors. Changes observed in these metabolite concentrations among various subtypes of PAs reflect metabolic heterogeneity in these tumors and may pave the way towards the development of metabolic markers to distinguish various immunohistochemical subtypes of PAs.
Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specific antibiotics
Authors: Heesterbeek D. A. C. , Martin N. I. , Velthuizen A. , Duijst M. , Ruyken M. , Wubbolts R. , Rooijakkers S. H. M. , Bardoel B. W.
Published: February 2019

Gram-negative bacteria are refractory to the action of many antibiotics due to their impermeable outer membrane. An important player of the immune system is the complement system, a protein network in serum that directly kills Gram-negative bacteria through pore-formation by the Membrane Attack Complexes (MAC). We here show that the MAC rapidly perforates the outer membrane but that inner membrane damage, which is essential for killing, is relatively slow. Importantly, we demonstrate that MAC-induced outer membrane damage sensitizes Gram-negative bacteria to otherwise ineffective, Gram-positive-specific, antimicrobials. Synergy between serum and nisin was observed for 22 out of 53 tested Gram-negative clinical isolates and for multi-drug resistant (MDR) blood isolates. The in vivo relevance of this process is further highlighted by the fact that blood sensitizes a MDR K. pneumoniae strain to vancomycin. Altogether, these data imply that antibiotics that are considered ineffective to treat infections with Gram-negatives may have different functional outcomes in patients, due to the presence of the complement system.
Neonatal outcomes following different ovarian stimulation protocols in fresh single embryo transfer
Authors: Jwa Seung Chik , Nakashima Akira , Kuwahara Akira , Saito Kazuki , Irahara Minoru , Sakumoto Tetsuro , Ishihara Osamu , Saito Hidekazu
Published: February 2019

Previous studies suggested ovarian stimulation was associated with lower birth weight and higher risk of preterm delivery (PTD) from fresh embryo transfers (ETs). However, whether the increased risk differs between distinct ovarian stimulation protocols remains unknown. A retrospective cohort study of 38,220 singleton deliveries after fresh single ETs from 2007 to 2013 was conducted. Main outcomes were birth weight and gestational length. Compared with the natural cycle, all ovarian stimulation protocols were associated with a significantly increased risk for PTD, low birth weight (LBW) and small for gestational age (SGA). In subgroup analysis of maternal age under 35 years, luteal support using progesterone, and early cleavage ETs, the significant associations remained for LBW and SGA in gonadotropin-releasing hormone (GnRH) antagonist protocol and for LBW in GnRH agonist protocol. Ovarian stimulation using clomiphene citrate (CC) had the highest increased risks for LBW (Adjusted odds ratio [AOR], 1.58, 95% confidence interval [95% CI], 1.43−1.73) and SGA (AOR, 1.65, 95% CI, 1.50−1.82) compared with natural cycles, and was further associated with PTD and cesarean section. These findings suggest ovarian stimulation was associated with lower birth weight, and CC may have adverse effect on neonatal outcomes in fresh cycles.
An efficient and cost-effective method for primer-induced nucleotide labeling for massive sequencing on next-generation sequencing platforms
Authors: Guo Junjie , Cheng Tao , Xu Han , Li Yide , Zeng Jie
Published: February 2019

Next generation sequencing (NGS) technologies play a powerful role in the preparation of large DNA databases such as DNA barcoding since it can produce a large number of sequence reads. Here we demonstrate a primer-induced sample labeling method aiming at sequencing a large number of samples simultaneously on NGS platforms. The strategy is to label samples with a unique oligo attached to the 5′-ends of primers. As a case study, 894 unique pentanucleotide oligoes were attached to the 5′-ends of three pairs of primers (for amplifying ITS, matK and rbcL) to label 894 samples. All PCR products of three barcodes of 894 samples were mixed together and sequenced on a high throughput sequencing platform. The results showed that 87.02%, 89.15% and 95.53% of the samples were successfully sequenced for rbcL, matK and ITS, respectively. The mean ratio of label mismatches for the three barcodes was 5.68%, and a sequencing depth of 30 ×to 40× was enough to obtain reliable sequences. It is flexible to label any number of samples simply by adjusting the length of oligoes. This easy, reliable and cost efficient method is useful in sequencing a large number of samples for construction of reference libraries for DNA barcoding, population biology and community phylogenetics.
Bone-inspired enhanced fracture toughness of de novo fiber reinforced composites
Authors: Libonati Flavia , Vellwock Andre E. , Ielmini Francesco , Abliz Dilmurat , Ziegmann Gerhard , Vergani Laura
Published: February 2019

Amplification in toughness and balance with stiffness and strength are fundamental characteristics of biological structural composites, and a long sought-after objective for engineering design. Nature achieves these properties through a combination of multiscale key features. Yet, emulating all these features into synthetic de novo materials is rather challenging. Here, we fine-tune manual lamination, to implement a newly designed bone-inspired structure into fiber-reinforced composites. An integrated approach, combining numerical simulations, ad hoc manufacturing techniques, and testing, yields a novel composite with enhanced fracture toughness and balance with stiffness and strength, offering an optimal lightweight material solution with better performance than conventional materials such as metals and alloys. The results also show how the new design significantly boosts the fracture toughness compared to a classic laminated composite, made of the same building blocks, also offering an optimal tradeoff with stiffness and strength. The predominant mechanism, responsible for the enhancement of fracture toughness in the new material, is the continuous deviation of the crack from a straight path, promoting large energy dissipation and preventing a catastrophic failure. The new insights resulting from this study can guide the design of de novo fiber-reinforced composites toward better mechanical performance to reach the level of synergy of their natural counterparts.
Serum amyloid A binds to fibrin(ogen), promoting fibrin amyloid formation
Authors: Page Martin J. , Thomson Greig J. A. , Nunes J. Massimo , Engelbrecht Anna-Mart , Nell Theo A , de Villiers Willem J. S. , de Beer Maria C. , Engelbrecht Lize , Kell Douglas B. , Pretorius Etheresia
Published: February 2019

Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer’s disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation. To study the role of SAA in coagulation and thrombosis, in vitro experiments were performed where purified human SAA, in concentrations resembling a modest acute phase response, was added to platelet-poor plasma (PPP) and whole blood (WB), as well as purified and fluorescently labelled fibrinogen. Results from thromboelastography (TEG) suggest that SAA causes atypical coagulation with a fibrin(ogen)-mediated increase in coagulation, but a decreased platelet/fibrin(ogen) interaction. In WB scanning electron microscopy analysis, SAA mediated red blood cell (RBC) agglutination, platelet activation and clumping, but not platelet spreading. Following clot formation in PPP, the presence of SAA increased amyloid formation of fibrin(ogen) as determined both with auto-fluorescence and with fluorogenic amyloid markers, under confocal microcopy. SAA also binds to fibrinogen, as determined with a fluorescent-labelled SAA antibody and correlative light electron microscopy (CLEM). The data presented here indicate that SAA can affect coagulation by inducing amyloid formation in fibrin(ogen), as well as by propelling platelets to a more prothrombotic state. The discovery of these multiple and complex effects of SAA on coagulation invite further mechanistic analyses.
Understanding the hidden relations between pro- and anti-inflammatory cytokine genes in bovine oviduct epithelium using a multilayer response surface method
Authors: Kowsar Rasoul , Keshtegar Behrooz , Miyamoto Akio
Published: February 2019

An understanding gene-gene interaction helps users to design the next experiments efficiently and (if applicable) to make a better decision of drugs application based on the different biological conditions of the patients. This study aimed to identify changes in the hidden relationships between pro- and anti-inflammatory cytokine genes in the bovine oviduct epithelial cells (BOECs) under various experimental conditions using a multilayer response surface method. It was noted that under physiological conditions (BOECs with sperm or sex hormones, such as ovarian sex steroids and LH), the mRNA expressions of IL10, IL1B, TNFA, TLR4, and TNFA were associated with IL1B, TNFA, TLR4, IL4, and IL10, respectively. Under pathophysiological + physiological conditions (BOECs with lipopolysaccharide + hormones, alpha-1-acid glycoprotein + hormones, zearalenone + hormones, or urea + hormones), the relationship among genes was changed. For example, the expression of IL10 and TNFA was associated with (IL1B, TNFA, or IL4) and TLR4 expression, respectively. Furthermore, under physiological conditions, the co-expression of IL10 + TNFA, TLR4 + IL4, TNFA + IL4, TNFA + IL4, or IL10 + IL1B and under pathophysiological + physiological conditions, the co-expression of IL10 + IL4, IL4 + IL10, TNFA + IL10, TNFA + TLR4, or IL10 + IL1B were associated with IL1B, TNFA, TLR4, IL10, or IL4 expression, respectively. Collectively, the relationships between pro- and anti-inflammatory cytokine genes can be changed with respect to the presence/absence of toxins, sex hormones, sperm, and co-expression of other gene pairs in BOECs, suggesting that considerable cautions are needed in interpreting the results obtained from such narrowly focused in vitro studies.
Successful Genetic Transfection of the Colonic Protistan Parasite Blastocystis for Reliable Expression of Ectopic Genes
Authors: Li Feng-Jun , Tsaousis Anastasios D. , Purton Tracy , Chow Vincent T. K. , He Cynthia Y. , Tan Kevin S. W.
Published: February 2019

The microbial parasite Blastocystis colonizes the large intestines of numerous animal species and increasing evidence has linked Blastocystis infection to enteric diseases with signs and symptoms including abdominal pain, constipation, diarrhea, nausea, vomiting, and flatulence. It has also recently been reported to be an important member of the host intestinal microbiota. Despite significant advances in our understanding of Blastocystis cell biology and host-parasite interactions, a genetic modification tool is absent. In this study, we successfully established a robust gene delivery protocol for Blastocystis subtype 7 (ST7) and ectopic protein expression was further tested using a high sensitivity nano-luciferase (Nluc) reporter system, with promoter regions from several genes. Among them, a strong promoter encompassing a region upstream of the legumain 5′ UTR was identified. Using this promoter combined with the legumain 3′ UTR, which contains a conserved, precise polyadenylation signal, a robust transient transfection technique was established for the first time in Blastocystis. This system was validated by ectopic expression of proteins harbouring specific localization signals. The establishment of a robust, reproducible gene modification system for Blastocystis is a significant advance for Blastocystis research both in vitro and in vivo. This technique will spearhead further research to understand the parasite’s biology, its role in health and disease, along with novel ways to combat the parasite.
The Angular Spectrum of the Scattering Coefficient Map Reveals Subsurface Colorectal Cancer
Authors: Zeng Yifeng , Rao Bin , Chapman William C. , Nandy Sreyankar , Rais Rehan , González Iván , Chatterjee Deyali , Mutch Matthew , Zhu Quing
Published: February 2019

Colorectal cancer diagnosis currently relies on histological detection of endoluminal neoplasia in biopsy specimens. However, clinical visual endoscopy provides no quantitative subsurface cancer information. In this ex vivo study of nine fresh human colon specimens, we report the first use of quantified subsurface scattering coefficient maps acquired by swept-source optical coherence tomography to reveal subsurface abnormities. We generate subsurface scattering coefficient maps with a novel wavelet-based-curve-fitting method that provides significantly improved accuracy. The angular spectra of scattering coefficient maps of normal tissues exhibit a spatial feature distinct from those of abnormal tissues. An angular spectrum index to quantify the differences between the normal and abnormal tissues is derived, and its strength in revealing subsurface cancer in ex vivo samples is statistically analyzed. The study demonstrates that the angular spectrum of the scattering coefficient map can effectively reveal subsurface colorectal cancer and potentially provide a fast and more accurate diagnosis.
Efficient cell penetration and delivery of peptide nucleic acids by an argininocalix[4]arene
Authors: Gasparello Jessica , Manicardi Alex , Casnati Alessandro , Corradini Roberto , Gambari Roberto , Finotti Alessia , Sansone Francesco
Published: February 2019

The application of Peptide Nucleic Acids (PNAs), mimics of DNA lacking the sugar-phosphate backbone, for antisense/anti-gene therapy and gene editing is limited by their low uptake by cells. Currently, no simple and efficient delivery systems and methods are available to solve this open issue. One of the most promising approach is the modification of the PNA structure through the covalent linkage of poliarginine tails, but this means that every PNA intended to be internalized must be modified. Herein we report the results relative to the delivery ability of a macrocyclic multivalent tetraargininocalix[4]arene (1) used as non-covalent vector for anti-miR-221-3p PNAs. High delivery efficiency, low cytotoxicity, maintenance of the PNA biological activity and ease preparation of the transfection formulation, simply attained by mixing PNA and calixarene, candidate this vector as universal delivery system for this class of nucleic acid analogues.
A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green
Authors: Inagaki Yoshinori , Kokudo Takashi , Kamiya Mako , Uno Shin-nosuke , Sato Masumitsu , Kaneko Junichi , Kokudo Norihiro , Urano Yasuteru , Hasegawa Kiyoshi
Published: February 2019

Indocyanine green (ICG) accumulates only in hepatocytes and their malignant counterpart, hepatocellular carcinoma (HCC). We have developed ICG-conjugated anti-cancer drugs and noted their significant accumulation in HCC cells both in vitro and in vivo. ICG-conjugated gemcitabine was less toxic to normal cells and it had superior anti-tumor action compared to gemcitabine alone in a subcutaneous tumor xenograft. ICG conjugation can provide a novel fluorescent drug delivery system for treatment of liver cancer and this system can be used to both diagnose and treat HCC.
Quantum coherence, many-body correlations, and non-thermal effects for autonomous thermal machines
Authors: Latune C. L. , Sinayskiy I. , Petruccione F.
Published: February 2019

One of the principal objectives of quantum thermodynamics is to explore quantum effects and their potential beneficial role in thermodynamic tasks like work extraction or refrigeration. So far, even though several papers have already shown that quantum effect could indeed bring quantum advantages, a global and deeper understanding is still lacking. Here, we extend previous models of autonomous machines to include quantum batteries made of arbitrary systems of discrete spectrum. We establish their actual efficiency, which allows us to derive an efficiency upper bound, called maximal achievable efficiency, shown to be always achievable, in contrast with previous upper bounds based only on the Second Law. Such maximal achievable efficiency can be expressed simply in term of the apparent temperature of the quantum battery. This important result appears to be a powerful tool to understand how quantum features like coherence but also many-body correlations and non-thermal population distribution can be harnessed to increase the efficiency of thermal machines.
The benefit of secondary prevention with oat fiber in reducing future cardiovascular event among CAD patients after coronary intervention
Authors: Wu Jia-Ru , Leu Hsin-Bang , Yin Wei-Hsian , Tseng Wei-Kung , Wu Yen-Wen , Lin Tsung-Hsien , Yeh Hung-I , Chang Kuan-Cheng , Wang Ji-Hung , Wu Chau-Chung , Chen Jaw-Wen
Published: February 2019

There is limited information about the association between oat fiber intake and future cardiovascular events in CAD patients after coronary intervention for secondary prevention. This study enrolled 716 patients after coronary intervention in clinical stable status from the CAD cohort biosignature study. Patients were analyzed according to whether the presence of regular oat fiber intake during the follow-up period, and the association with endpoints including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and revascularization procedures were analyzed. The average follow-up period is 26.75 ± 8.11 months. Patients taking oat fiber were found to have lower serum levels of LDL, triglycerides, ratio of TC/HDL, as well as lower inflammatory markers values. After adjusting for confounders in the proportional hazard Cox model, oat fiber intake was associated with a lower risk of future revascularization (HR = 0.54, 95% CI 0.35–0.85; p = 0.007), and lower risk of major adverse cardiovascular events (HR = 0.62, 95% CI 0.43–0.88; p = 0.008), suggesting the association of oat fiber use and lower risk of future adverse event in CAD patients after coronary intervention.
Mercury Spikes Indicate a Volcanic Trigger for the Late Ordovician Mass Extinction Event: An Example from a Deep Shelf of the Peri-Baltic Region
Authors: Smolarek-Lach Justyna , Marynowski Leszek , Trela Wiesław , Wignall Paul B.
Published: February 2019

The Late Ordovician mass extinction (LOME) was the second largest Phanerozoic crisis, but its cause remains elusive. Several triggering mechanisms have been proposed over the years, including bioevolutionary events, oceanographic changes, and geotectonic processes. Here, we report the presence of Hg spikes in the Zbrza PIG-1 borehole from the Upper Ordovician deep shelf sections of the peri-Baltic region. A strong positive anomaly in the lower late Katian (Hg/TOC = 2537.3 ppb/wt%) was noted. No correlation between Hg and TOC (R2 = 0.07) was distinguished in the Hirnantian, although several positive anomalies were found. Because the Hg/Mo ratio showed trends very similar to those of Hg/TOC, it seems likely that TOC values reflect the redox conditions. In order to evaluate the role of anoxia in levels of Hg enrichment several redox indicators were measured. These showed that the elevated mercury values in the Hirnantian are not caused by anoxia/euxinia because euxinic biomarkers (maleimides and aryl isoprenoids) are present in very low abundance and pyrite framboids are absent. In total, positive Hg/TOC anomalies occur in the lower late Katian, at the Katian - Hirnantian boundary, and in the late Hirnantian. The lack of a strong Hg/TOC correlation, Ni enrichments, and the absence of ‘anoxic indicators’ (no biomarkers, no framboids, low Mo concentration) at these levels, supports the interpretation that Hg enrichment is due to enhanced environmental loading. We conclude that our Hg and Hg/TOC values were associated with volcanic pulses which triggered the massive environmental changes resulting in the Late Ordovician mass extinction.
Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus
Authors: Thongkorn Surangrat , Kanlayaprasit Songphon , Jindatip Depicha , Tencomnao Tewin , Hu Valerie W. , Sarachana Tewarit
Published: February 2019

Autism spectrum disorder (ASD) is a neurodevelopmental disorder inexplicably biased towards males. Although prenatal exposure to bisphenol A (BPA) has recently been associated with the ASD risk, whether BPA dysregulates ASD-related genes in the developing brain remains unclear. In this study, transcriptome profiling by RNA-seq analysis of hippocampi isolated from neonatal pups prenatally exposed to BPA was conducted and revealed a list of differentially expressed genes (DEGs) associated with ASD. Among the DEGs, several ASD candidate genes, includingAuts2andFoxp2, were dysregulated and showed sex differences in response to BPA exposure. The interactome and pathway analyses of DEGs using Ingenuity Pathway Analysis software revealed significant associations between the DEGs in males and neurological functions/disorders associated with ASD. Moreover, the reanalysis of transcriptome profiling data from previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with ASD-related genes. The findings from this study indicate that prenatal BPA exposure alters the expression of ASD-linked genes in the hippocampus and suggest that maternal BPA exposure may increase ASD susceptibility by dysregulating genes associated with neurological functions known to be negatively impacted in ASD, which deserves further investigations.
Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease
Authors: Lee Chi Fung , Caudal Arianne , Abell Lauren , Nagana Gowda G. A. , Tian Rong
Published: February 2019

Leigh syndrome is a mitochondrial disease characterized by neurological disorders, metabolic abnormality and premature death. There is no cure for Leigh syndrome; therefore, new therapeutic targets are urgently needed. In Ndufs4-KO mice, a mouse model of Leigh syndrome, we found that Complex I deficiency led to declines in NAD+ levels and NAD+ redox imbalance. We tested the hypothesis that elevation of NAD+ levels would benefit Ndufs4-KO mice. Administration of NAD+ precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated lactic acidosis. NMN increased lifespan by normalizing NAD+ redox imbalance and lowering HIF1a accumulation in Ndufs4-KO skeletal muscle without affecting the brain. NMN up-regulated alpha-ketoglutarate (KG) levels in Ndufs4-KO muscle, a metabolite essential for HIF1a degradation. To test whether supplementation of KG can treat Ndufs4-KO mice, a cell-permeable KG, dimethyl ketoglutarate (DMKG) was administered. DMKG extended lifespan of Ndufs4-KO mice and delayed onset of neurological phenotype. This study identified therapeutic mechanisms that can be targeted pharmacologically to treat Leigh syndrome.
Genetic analysis of a Piezo-like protein suppressing systemic movement of plant viruses in Arabidopsis thaliana
Authors: Zhang Zhen , Tong Xin , Liu Song-Yu , Chai Long-Xiang , Zhu Fei-Fan , Zhang Xiao-Peng , Zou Jing-Ze , Wang Xian-Bing
Published: February 2019

As obligate intracellular phytopathogens, plant viruses must take advantage of hosts plasmodesmata and phloem vasculature for their local and long-distance transports to establish systemic infection in plants. In contrast to well-studied virus local transports, molecular mechanisms and related host genes governing virus systemic trafficking are far from being understood. Here, we performed a forward genetic screening to identify Arabidopsis thaliana mutants with enhanced susceptibility to a 2b-deleted mutant of cucumber mosaic virus (CMV-2aT∆2b). We found that an uncharacterized Piezo protein (AtPiezo), an ortholog of animal Piezo proteins with mechanosensitive (MS) cation channel activities, was required for inhibiting systemic infection of CMV-2aT∆2b and turnip mosaic virus tagged a green fluorescent protein (GFP) (TuMV-GFP). AtPiezo is induced by virus infection, especially in the petioles of rosette leaves. Thus, we for the first time demonstrate the biological function of Piezo proteins in plants, which might represent a common antiviral strategy because many monocot and dicot plant species have a single Piezo ortholog.
Water molecular structure underpins extreme desiccation tolerance of the resurrection plant Haberlea rhodopensis
Authors: Kuroki Shinichiro , Tsenkova Roumiana , Moyankova Daniela , Muncan Jelena , Morita Hiroyuki , Atanassova Stefka , Djilianov Dimitar
Published: February 2019

Haberlea rhodopensisis a resurrection plant with an extremely high desiccation tolerance. Even after long periods of almost full desiccation, its physiological functions are recovered shortly upon re-watering. In order to identify physiological strategies which contribute to its remarkable drought stress tolerance we used near infrared spectroscopy to investigate the state of water in the leaves of this plant and compared it to its relative, non-resurrection plant speciesDeinostigma eberhardtii. Here we show, using a novel aquaphotomics spectral analysis, thatH.rhodopensisperforms a dynamic regulation of water molecular structure during dehydration directed at drastic decrease of free water molecules, increase of water molecules with 4 hydrogen bonds, and a massive accumulation of water dimers in the full desiccation stage. Our findings suggest that changes in water structure mirror the changes in major metabolites and antioxidants which together constitute a robust defense system underlying the desiccation tolerance of the resurrection plant, while the water dimer may hold special importance for the “drying without dying” ability.
Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction
Authors: Das Sarbashis , Frisk Christoffer , Eriksson Maria J. , Walentinsson Anna , Corbascio Matthias , Hage Camilla , Kumar Chanchal , Asp Michaela , Lundeberg Joakim , Maret Eva , Persson Hans , Linde Cecilia , Persson Bengt
Published: February 2019

Heart failure affects 2–3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.
Optic disc cupping characteristics of normal pressure hydrocephalus patients with normal-tension glaucoma
Authors: Igarashi Nozomi , Honjo Megumi , Asano Shotaro , Takagi Kiyoshi , Aihara Makoto
Published: February 2019

We examined the potential association of idiopathic normal pressure hydrocephalus (iNPH) with the generation of normal-tension glaucoma (NTG), to explore possible relationships between intracranial pressure (ICP) and the presence of glaucoma, and to compare disc morphology of NTG patients with or without iNPH. We investigated 20 iNPH patients, examined the prevalence of glaucoma, and compared the optic discs of NTG patients with iNPH (n = 11) and age-matched NTG patients without iNPH (n = 16). All data were collected prior to the treatment of iNPH, to eliminate the possibility that the treatment may have contributed to the progression of NTG. The diagnoses of NTG were made using visual field data, intraocular pressure measurements, fundoscopy, and optical coherence tomography (OCT). Using OCT, the optic nerve disc depth was also measured. The ICP was higher in the iNPH with NTG compared to iNPH without NTG (p = 0.0425), and the cupping depths of the discs of NTG patients with iNPH were significantly shallower compared with those of NTG patients without iNPH (p = 0.0097). Based on the difference in cupping depth, NTG patients with iNPH may have a different morphology from typical glaucoma patients, which could in turn reflect a different pathogenesis compared to NTG patients without iNPH.
Electrical Transition in Isostructural VO2 Thin-Film Heterostructures
Authors: Moatti Adele , Sachan Ritesh , Cooper Valentino R , Narayan Jagdish
Published: February 2019

Control over the concurrent occurrence of structural (monoclinic to tetragonal) and electrical (insulator to the conductor) transitions presents a formidable challenge for VO2-based thin film devices. Speed, lifetime, and reliability of these devices can be significantly improved by utilizing solely electrical transition while eliminating structural transition. We design a novel strain-stabilized isostructural VO2 epitaxial thin-film system where the electrical transition occurs without any observable structural transition. The thin-film heterostructures with a completely relaxed NiO buffer layer have been synthesized allowing complete control over strains in VO2 films. The strain trapping in VO2 thin films occurs below a critical thickness by arresting the formation of misfit dislocations. We discover the structural pinning of the monoclinic phase in (10 ± 1 nm) epitaxial VO2 films due to bandgap changes throughout the whole temperature regime as the insulator-to-metal transition occurs. Using density functional theory, we calculate that the strain in monoclinic structure reduces the difference between long and short V-V bond-lengths (ΔV−V) in monoclinic structures which leads to a systematic decrease in the electronic bandgap of VO2. This decrease in bandgap is additionally attributed to ferromagnetic ordering in the monoclinic phase to facilitate a Mott insulator without going through the structural transition.
DGAT1 Inhibitor Suppresses Prostate Tumor Growth and Migration by Regulating Intracellular Lipids and Non-Centrosomal MTOC Protein GM130
Authors: Nardi Francesca , Franco Omar E. , Fitchev Philip , Morales Alejandro , Vickman Renee E. , Hayward Simon W. , Crawford Susan E.
Published: February 2019

Acyl-CoA:diacylglycerol acyltransferase I (DGAT1) is a key enzyme in lipogenesis which is increased in metabolically active cells to meet nutrient requirements. DGAT1 has been recognized as an anti-obesity target; however, its role in the tumor microenvironment remains unclear. We postulated that, in prostate cancer (PCa) cells, augmented lipogenesis and growth are due to increased DGAT1 expression leading to microtubule-organizing center (MTOC) amplification. Thus, therapeutic targeting of DGAT1 potentially has tumor suppressive activity. We tested whether blocking DGAT1 in PCa cells altered MTOC and lipid signaling. Western blot and immunofluorescence were performed for MTOC and triglyceride mediators. Treatment with a DGAT1 inhibitor was evaluated. We found a stepwise increase in DGAT1 protein levels when comparing normal prostate epithelial cells to PCa cells, LNCaP and PC-3. Lipid droplets, MTOCs, and microtubule-regulating proteins were reduced in tumor cells treated with a DGAT1 inhibitor. Depletion of the non-centrosomal MTOC protein GM130 reduced PCa cell proliferation and migration. Inhibition of DGAT1 reduced tumor growth both in vitro and in vivo, and a negative feedback loop was discovered between DGAT1, PEDF, and GM130. These data identify DGAT1 as a promising new target for suppressing PCa growth by regulating GM130, MTOC number and disrupting microtubule integrity.
Metagenome-assembled genomes provide new insight into the microbial diversity of two thermal pools in Kamchatka, Russia
Authors: Wilkins Laetitia G. E. , Ettinger Cassandra L. , Jospin Guillaume , Eisen Jonathan A.
Published: February 2019

Culture-independent methods have contributed substantially to our understanding of global microbial diversity. Recently developed algorithms to construct whole genomes from environmental samples have further refined, corrected and revolutionized understanding of the tree of life. Here, we assembled draft metagenome-assembled genomes (MAGs) from environmental DNA extracted from two hot springs within an active volcanic ecosystem on the Kamchatka peninsula, Russia. This hydrothermal system has been intensively studied previously with regard to geochemistry, chemoautotrophy, microbial isolation, and microbial diversity. We assembled genomes of bacteria and archaea using DNA that had previously been characterized via 16S rRNA gene clone libraries. We recovered 36 MAGs, 29 of medium to high quality, and inferred their placement in a phylogenetic tree consisting of 3,240 publicly available microbial genomes. We highlight MAGs that were taxonomically assigned to groups previously underrepresented in available genome data. This includes several archaea (Korarchaeota, Bathyarchaeota and Aciduliprofundum) and one potentially new species within the bacterial genus Sulfurihydrogenibium. Putative functions in both pools were compared and are discussed in the context of their diverging geochemistry. This study adds comprehensive information about phylogenetic diversity and functional potential within two hot springs in the caldera of Kamchatka.
Probing the Behaviour of Cas1-Cas2 upon Protospacer Binding in CRISPR-Cas Systems using Molecular Dynamics Simulations
Authors: Wan Hua , Li Jianming , Chang Shan , Lin Shuoxin , Tian Yuanxin , Tian Xuhong , Wang Meihua , Hu Jianping
Published: February 2019

Adaptation in CRISPR-Cas systems enables the generation of an immunological memory to defend against invading viruses. This process is driven by foreign DNA spacer (termed protospacer) selection and integration mediated by Cas1-Cas2 protein. Recently, different states of Cas1-Cas2, in its free form and in complex with protospacer DNAs, were solved by X-ray crystallography. In this paper, molecular dynamics (MD) simulations are employed to study crystal structures of one free and two protospacer-bound Cas1-Cas2 complexes. The simulated results indicate that the protospacer binding markedly increases the system stability, in particular when the protospacer containing the PAM-complementary sequence. The hydrogen bond and binding free energy calculations explain that PAM recognition introduces more specific interactions to increase the cleavage activity of Cas1. By using principal component analysis (PCA) and intramolecular angle calculation, this study observes two dominant slow motions associated with the binding of Ca1-Cas2 to the protospacer and potential target DNAs respectively. The comparison of DNA structural deformation further implies a cooperative conformational change of Cas1-Cas2 and protospacer for the target DNA capture. We propose that this cooperativity is the intrinsic requirement of the CRISPR integration complex formation. This study provides some new insights into the understanding of CRISPR-Cas adaptation.
Effects of stand age on carbon storage in dragon spruce forest ecosystems in the upper reaches of the Bailongjiang River basin, China
Authors: Cao Jianjun , Gong Yifan , Adamowski Jan F. , Deo Ravinesh C. , Zhu Guofeng , Dong Xiaogang , Zhang Xiaofang , Liu Haibo , Xin Cunlin
Published: February 2019

At an ecosystem level, stand age has a significant influence on carbon storage (CS). Dragon spruce (Picea asperataMast.) situated along the upper reaches of the Bailongjiang River in northwest China were categorized into three age classes (29–32 years, Y1; 34–39 years, Y2; 40–46 years, Y3), and age-related differences in total carbon storage (TCS) of the forest ecosystem were investigated for the first time. Results showed that TCS for the Y1, Y2, and the Y3age groups were 323.64, 240.66 and 174.60 Mg ha−1, respectively. The average TCS of the three age groups was 255.65 Mg C ha−1, with above-ground biomass, below-ground biomass, litter, and soil in the top 0.6 m contributing 15.0%, 3.7%, 12.1%, and 69.2%, respectively. CS in soil and TCS of the Y1age group both significantly exceeded those of the Y3age group (P < 0.05). Contrary to other recent findings, the present study supports the hypothesis that TCS is likely to decrease as stand age increases. This indicates that natural resource managers should rejuvenate forests by routinely thinning older stands, thereby not only achieving vegetation restoration, but also allowing these stands to create a long-term carbon sink for this important eco-region.
Development and validation of a new standardised data collection tool to aid in the diagnosis of canine skin allergies
Authors: Harvey N. D. , Shaw S. C. , Blott S. C. , Vàzquez-Diosdado J. A. , England G. C. W.
Published: February 2019

Canine atopic dermatitis (cAD) is a common hereditary clinical syndrome in domestic dogs with no definitive diagnostic tests, which causes marked morbidity and has a high economic impact internationally. We created a novel questionnaire for Labrador (LR) and Golden retriever (GR) owners to evaluate canine skin health with respect to clinical signs of cAD. 4,111 dogs had fully completed questionnaires (2,803 LR; 1,308 GR). ‘Cases’ (793) had a reported veterinary diagnosis of cAD, and ‘controls’ (1652) had no current or past clinical signs of cAD and were aged >3 years. Remaining dogs (1666) were initially categorised as ‘Other’. Simulated annealing was used comparing ‘Cases’ and ‘Others’ to select a novel set of features able to classify a known case. Two feature sets are proposed, one for use on first evaluation and one for dogs with a history of skin problems. A sum for each list when applied to the whole population (including controls) was able to classify ‘Cases’ with a sensitivity of 89% to 94% and specificity of 71% to 69%, respectively, and identify potentially undiagnosed cases. Our findings demonstrate for the first time that owner questionnaire data can be reliably used to aid in the diagnostic process of cAD.
Maize productivity and soil properties in the Loess Plateau in response to ridge-furrow cultivation with polyethylene and straw mulch
Authors: Deng Hao-Liang , Xiong You-Cai , Zhang Heng-Jia , Li Fu-Qiang , Zhou Hong , Wang Yu-Cai , Deng Zhan-Rui
Published: February 2019

Ridge-furrow with full film mulching (RFFM) is widely used in the Loess Plateau (LP) to increase maize yield. However, continuous RFFM application may cause excessive depletion of soil organic carbon (SOC) and soil water storage (SWS). The present study tested four production systems, namely, (1) RFFM; (2) ridge-furrow with polyethylene film and straw mulching (RFFSM); (3) non-contoured seedbed with film mulching (FFM); and (4) non-contoured seedbed without mulching (CK) in 2013 and 2014 to identify an optimal technique to increase maize yield yet minimizing the negative effects. SWS under RFFSM was significantly higher by 5.4% and 13.4% compared to RFFM and CK, respectively. The changes in SOC were −0.2, −0.2, and −0.4 g·kg−1 for RFFM, FFM, and CK, respectively, and 0.3 g·kg−1 for RFFSM. Increased root residue and extra external carbon input to soil under RFFSM directly contributed to SOC recovery. RFFSM had a comparable grain yield but higher water use efficiency compared to RFFM. The combination of RFFSM is promising for improving SOC stocks, water storage, and maize productivity.
Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2
Authors: Duciel Laura , Anezo Océane , Mandal Kalpana , Laurent Cécile , Planque Nathalie , Coquelle Frédéric M. , Gentien David , Manneville Jean-Baptiste , Saule Simon
Published: February 2019

Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.
Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea
Authors: Li Ji , Xu Yi-Wen , Jiang Jing-Jing , Song Qing-Kun
Published: February 2019

This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: −2.70, −0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.
Comparative analysis of differentially secreted proteins in serum-free and serum-containing media by using BONCAT and pulsed SILAC
Authors: Shin Jihye , Rhim Jiheon , Kwon Yumi , Choi Sun Young , Shin Sungho , Ha Chul-Won , Lee Cheolju
Published: February 2019

Despite the increased interest in secretomes associated with paracrine/autocrine mechanisms, the majority of mass spectrometric cell secretome studies have been performed using serum-free medium (SFM). On the other hand, serum-containing medium (SCM) is not recommended very much because the secretome obtained with SCM is easily contaminated with fetal bovine serum (FBS) proteins. In this study, through the combination of bioorthogonal non-canonical amino acid tagging (BONCAT) and pulsed-SILAC (pSILAC), we analyzed differentially secreted proteins between SFM and SCM in a cancer-derived human cell, U87MG, and a mesenchymal stem cell derived from human Wharton’s jelly (hWJ-MSCs). In most cases, the bioinformatic tools predicted a protein to be truly secretory when the secretion level of the protein was more in SCM than in SFM. In the case of hWJ-MSCs, the amount of proteins secreted in SCM for 24 hours was larger than that of SFM (log2 fold change = 0.96), even considering different cell proliferation rates. hWJ-MSCs proteins secreted more in SCM included several positive markers of MSC paracrine factors implicated in angiogenesis, neurogenesis and osteogenesis, and upstream regulators of cell proliferation. Our study suggests the analysis of the secretome should be processed in SCM that promotes cell proliferation and secretion.
Climate and landscape changes as driving forces for future range shift in southern populations of the European badger
Authors: Rosalino Luís M. , Guedes Diana , Cabecinha Diogo , Serronha Ana , Grilo Clara , Santos-Reis Margarida , Monterroso Pedro , Carvalho João , Fonseca Carlos , Pardavila Xosé , Virgós Emílio , Hipólito Dário
Published: February 2019

Human-Induced Rapid Environmental Change (HIREC), particularly climate change and habitat conversion, affects species distributions worldwide. Here, we aimed to (i) assess the factors that determine range patterns of European badger (Meles meles) at the southwestern edge of their distribution and (ii) forecast the possible impacts of future climate and landcover changes on those patterns. We surveyed 272 cells of 5 × 5 km, to assess badger presence and confirmed its occurrence in 95 cells (35%). Our models estimate that badger’s presence is promoted by the occurrence of herbaceous fields and shrublands (5%–10%), and low proportions of Eucalyptus plantations (<~15%). Regions with >50% of podzols and eruptive rocks, higher sheep/goat density (>4 ind/km2), an absence of cattle, intermediate precipitation regimes (800–1000 mm/year) and mild mean temperatures (15–16 °C) are also more likely to host badgers. We predict a decrease in favourability of southern areas for hosting badgers under forecasted climate and landcover change scenarios, which may lead to a northwards retraction of the species southern distribution limit, but the overall landscape favourability is predicted to slightly increase. The forecasted retraction may affect community functional integrity, as its role in southern ecological networks will be vacant.