bluuebunny/crossref_metadata_2025 huggingface dataset:
Poverty-environment relationships under market heterogeneity: cash transfers and rural livelihoods in Zambia
Authors: Lawlor Kathleen , Handa Sudhanshu , Davis Benjamin , Seidenfeld David ,   the Zambia Cash Transfer Evaluation Team
Published: October 2019

We examine the environmental impacts of a cash transfer program in rural Zambia and investigate whether variation in market access is associated with heterogeneous impacts on natural resource use. We consider households’ use of firewood, charcoal, bushmeat and land for farming, as well as their ownership of non-farm businesses. We find that cash transfers increase the likelihood of charcoal consumption as well as the amount consumed for those living close to paved roads. The transfers also enable households to increase the size of their farms and establish non-farm businesses. These impacts are most pronounced for those living far from paved roads. While remoteness is associated with farm expansion in response to the cash transfer, more education causes those receiving the transfer to decrease the size of their farms. This impact heterogeneity has important implications for sustainable development.
RC-POSITIVITY, VANISHING THEOREMS AND RIGIDITY OF HOLOMORPHIC MAPS
Authors: Yang Xiaokui
Published: October 2019

Let $M$ and $N$ be two compact complex manifolds. We show that if the tautological line bundle ${\mathcal{O}}_{T_{M}^{\ast }}(1)$ is not pseudo-effective and ${\mathcal{O}}_{T_{N}^{\ast }}(1)$ is nef, then there is no non-constant holomorphic map from $M$ to $N$. In particular, we prove that any holomorphic map from a compact complex manifold $M$ with RC-positive tangent bundle to a compact complex manifold $N$ with nef cotangent bundle must be a constant map. As an application, we obtain that there is no non-constant holomorphic map from a compact Hermitian manifold with positive holomorphic sectional curvature to a Hermitian manifold with non-positive holomorphic bisectional curvature.
Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet
Authors: Draycott Sally A. V. , Daniel Zoe , Khan Raheela , Muhlhausler Beverly S. , Elmes Matthew J. , Langley-Evans Simon C.
Published: October 2019

Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3–30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.
Canopy and Terrain Interactions Affecting Snowpack Spatial Patterns in the Sierra Nevada of California
Authors: Zheng Zeshi , Ma Qin , Jin Shichao , Su Yanjun , Guo Qinghua , Bales Roger C.
Published: October 2019

Airborne light detection and ranging is an emerging measurement tool for snowpack estimation, and data are now emerging to better assess multiscale snow depth patterns. We used airborne light detection and ranging measurements from four sites in the southern Sierra Nevada to determine how snow depth varies with canopy structure and the interactions between canopies and terrain. We processed the point clouds into snow depth rasters at 0.5×0.5‐m2 resolution and performed statistical analysis on the processed snow depth data, terrain attributes, and vegetation attributes, including the individual tree bole locations, canopy crown area, and canopy height. We studied the snow depth at such a fine scale due in part to the spatial heterogeneity introduced by canopy interception and enhanced melting caused by tree trunks in forested areas. We found that the dominant direction of a tree well, the area around the tree bole that has shallower snowpack, is correlated with the local aspect of the terrain, and the gradient of the snow surface in a tree well is correlated with the tree's crown area. The regression‐tree based XGBoost model was fitted with the topographic variables and canopy variables, and about 71% of snow depth variability can be explained by the model.
Exposing Los Angeles’s Shaky Geologic Underbelly
Authors: Clayton Robert , Persaud Patricia , Denolle Marine , Polet Jascha
Published: October 2019

Current calculations might underestimate the susceptibility of Los Angeles to earthquake shaking, so researchers and volunteers are deploying seismic networks near the city to remedy a data shortage.
Why Is Crustal Underplating Beneath Many Hot Spot Islands Anisotropic?
Authors: Park Jeffrey , Rye Danny M.
Published: October 2019

High‐frequency harmonic regression (2.0–4.0‐Hz cutoff) of receiver functions at two long‐running seismic observatories at mid‐Pacific hot spot islands confirms earlier detections of underplated material with seismic velocities intermediate to crust and mantle, and reveals it to be multilayered and anisotropic within ~30 km of the surface. Magmatic underplating beneath the oceanic Moho has been proposed to accompany basaltic melt that erupts at the seafloor and (eventually) atop a subaerial volcano. An alternate hypothesis is “metasomatic underplating” whereby crustal fractures developed during magma ascent allow seawater to infiltrate and to serpentinize the sub‐Moho mantle partially. Metasomatic underplating would lower seismic wave speeds, promote the buoyancy of the hot spot swell, and induce textural anisotropy as metamorphic expansion of olivine‐rich peridotite promotes a crack network along which serpentinization spreads. Differential expansion of mantle peridotite and crustal gabbro promotes cracks in the crust that offer new pathways for seawater to descend to the Moho, allowing metasomatic underplating to expand laterally and to contribute anisotropy to the underplated layer. Rare serpentinized mantle xenoliths confirm that crack textures can develop during serpentinization at depth. The discovery of iron‐oxidizing microbial mats on the seafloor flank of the Loihi volcano, and many locations of diffuse low‐temperature venting worldwide, is consistent with the circulation of metasomatic fluids with reducing chemistry, sourced from serpentinization at depth. Posteruptive uplift of Santa Maria Island (Azores), and asymmetry of the Hawaiian swell, suggests that underplating requires 2–4 Myr to complete, suggesting that fluid infiltration is slow, subject to cycles of blockage and fresh fracturing.
Saturn's Plasmapause: Signature of Magnetospheric Dynamics
Authors: Thomsen M.F. , Coates A.J.
Published: October 2019

We explore the paradigm that Saturn's plasmapause marks the boundary between the magnetic flux tubes that have been circulating around the planet for some time, accumulating a dense load of Enceladus‐sourced material, and those that have recently undergone tail reconnection, shedding the bulk of the cold plasma and retaining a more tenuous, heated population. A centrifugally driven interchange instability should develop at this boundary, producing fingers of outward propagating dense plasma and of inward propagating hot, tenuous plasma. The plasmapause should thus be identifiable as a transition from mostly‐dense‐with‐some‐tenuous to mostly‐tenuous‐with‐some‐dense plasma populations. Electron densities from the Cassini Plasma Spectrometer/Electron Spectrometer (CAPS/ELS) instrument are used to identify the location of this transition for all of the low‐latitude (<5° from the magnetic equator) passes through Saturn's inner/middle magnetosphere. The boundary is typically found near and somewhat beyond L=10 (i.e., at ~10 Rs from the planet), with a local time asymmetry such that it is closer to the planet on the night side than on the day side.
Spatially Extensive Ground‐Penetrating Radar Snow Depth Observations During NASA's 2017 SnowEx Campaign: Comparison With In Situ, Airborne, and Satellite Observations
Authors: McGrath Daniel , Webb Ryan , Shean David , Bonnell Randall , Marshall Hans‐Peter , Painter Thomas H. , Molotch Noah P. , Elder Kelly , Hiemstra Christopher , Brucker Ludovic
Published: October 2019

Seasonal snow is an important component of Earth's hydrologic cycle and climate system, yet it remains challenging to consistently and accurately measure snow depth and snow water equivalent (SWE) across the range of diverse snowpack conditions that exist on Earth. The NASA SnowEx campaign is focused on addressing the primary gaps in snow remote sensing in order to gain an improved spatiotemporal understanding of this important resource and to further efforts toward a future satellite‐based snow remote sensing mission. Ground‐penetrating radar (GPR) is an efficient and mature approach for measuring snow depth and SWE. We collected ~1.3 million GPR snow depth observations during the NASA SnowEx 2017 campaign, yielding a spatially extensive (~133‐km total length) and high‐resolution (~10‐cm lateral spacing) validation data set to assess various remote sensing and modeling approaches. We found high correlation between the GPR and manual snow probe derived snow depths (r = 0.89, p < 0.0001, root‐mean‐square error (RMSE) = 18 cm), but a median difference of −10 cm, which we attribute, in part, to probe penetration into the unfrozen subsurface. We also compared GPR‐derived snow depths to two other independent estimates of snow depth, as an example of how this data set can be used for validation of remote sensing techniques: Airborne Snow Observatory lidar‐derived snow depths (r = 0.90, p < 0.0001, median difference = −1 cm, RMSE = 14 cm) and preliminary DigitalGlobe WorldView‐3 satellite‐derived snow depths (r = 0.70, p < 0.0001, median difference = −3 cm, RMSE = 24 cm).
PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1
Authors: Ji Jianxiong , Ding Kaikai , Luo Tao , Xu Ran , Zhang Xin , Huang Bin , Chen Anjing , Zhang Di , Miletic Hrvoje , Bjerkvig Rolf , Thorsen Frits , Wang Jian , Li Xingang
Published: October 2019

The Hippo signaling pathway controls organ development and is also known, in cancer, to have a tumor suppressing role. Within the Hippo pathway, we here demonstrate, in human gliomas, a functional interaction of a transmembrane protein, prostate transmembrane protein, androgen induced 1 (PMEPA1) with large tumor suppressor kinase 1 (LATS1). We show that PMEPA1 is upregulated in primary human gliomas. The PMEPA1 isoform PMEPA1a was predominantly expressed in glioma specimens and cell lines, and ectopic expression of the protein promoted glioma growth and invasion in vitro and in an orthotopic xenograft model in nude mice. In co-immunoprecipitation experiments, PMEPA1a associated with the Hippo tumor suppressor kinase LATS1. This interaction led to a proteasomal degradation of LATS1 through recruitment of the ubiquitin ligase, neural precursor cell expressed, developmentally downregulated 4 (NEDD4), which led to silencing of Hippo signaling. Alanine substitution in PMEPA1a at PY motifs resulted in failed LATS1 degradation. Targeting of a downstream component in the Hippo signaling pathway, YAP, with shRNA, interfered with the growth promoting activities of PMEPA1a in vitro and in vivo. In conclusion, the presented work shows that PMEPA1a contributes to glioma progression by a dysregulation of the Hippo signaling pathway and thus represents a promising target for the treatment of gliomas.
The rostroventral part of the thalamic reticular nucleus modulates fear extinction
Authors: Lee Joon-Hyuk , Latchoumane Charles-Francois V. , Park Jungjoon , Kim Jinhyun , Jeong Jaeseung , Lee Kwang-Hyung , Shin Hee-Sup
Published: October 2019

The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. Here, in mice, we show that the rostroventral part of the TRN (TRNrv) is critically involved in the extinction of tone-dependent fear memory. Optogenetic excitation of TRNrv neurons during extinction learning dramatically facilitated, whereas the inhibition disrupted, the fear extinction. Single unit recordings demonstrated that TRNrv neurons selectively respond to conditioned stimuli but not to neutral stimuli. TRNrv neurons suppressed the spiking activity of the medial part of the dorsal midline thalamus (dMTm), and a blockade of this inhibitory pathway disrupted fear extinction. Finally, we found that the suppression of dMTm projections to the central amygdala promotes fear extinction, and TRNrv neurons have direct connections to this pathway. Our results uncover a previously unknown function of the TRN and delineate the neural circuit for thalamic control of fear memory.
RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype
Authors: Cai Demin , Wang Junjian , Gao Bei , Li Jin , Wu Feng , Zou June X. , Xu Jianzhen , Jiang Yuqian , Zou Hongye , Huang Zenghong , Borowsky Alexander D. , Bold Richard J. , Lara Primo N. , Li Jian Jian , Chen Xinbin , Lam Kit S. , To Ka-Fai , Kung Hsing-Jien , Fiehn Oliver , Zhao Ruqian , Evans Ronald M. , Chen Hong-Wu
Published: October 2019

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC.
Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide
Authors: Wu Lin-Ping , Ahmadvand Davoud , Su Junan , Hall Arnaldur , Tan Xiaolong , Farhangrazi Z. Shadi , Moghimi S. Moein
Published: October 2019

The filamentous bacteriophage fd bind a cell target with exquisite specificity through its few copies of display peptides, whereas nanoparticles functionalized with hundreds to thousands of synthetically generated phage display peptides exhibit variable and often-weak target binding. We hypothesise that some phage peptides in a hierarchical structure rather than in monomeric form recognise and bind their target. Here we show hierarchial forms of a brain-specific phage-derived peptide (herein as NanoLigand Carriers, NLCs) target cerebral endothelial cells through transferrin receptor and the receptor for advanced glycation-end products, cross the blood-brain-barrier and reach neurons and microglial cells. Through intravenous delivery of NLC-β-secretase 1 (BACE1) siRNA complexes we show effective BACE1 down-regulation in the brain without toxicity and inflammation. Therefore, NLCs act as safe multifunctional nanocarriers, overcome efficacy and specificity limitations in active targeting with nanoparticles bearing phage display peptides or cell-penetrating peptides and expand the receptor repertoire of the display peptide.
ZC3H18 specifically binds and activates the BRCA1 promoter to facilitate homologous recombination in ovarian cancer
Authors: Kanakkanthara Arun , Huntoon Catherine J. , Hou Xiaonan , Zhang Minzhi , Heinzen Ethan P. , O’Brien Daniel R. , Oberg Ann L. , John Weroha S. , Kaufmann Scott H. , Karnitz Larry M.
Published: October 2019

Reduced BRCA1 expression causes homologous recombination (HR) repair defects in high-grade serous ovarian cancers (HGSOCs). Here, we demonstrate thatBRCA1is transcriptionally activated by a previously unknown function of ZC3H18. We show that ZC3H18 is a DNA-binding protein that interacts with an E2F site in theBRCA1promoter where it facilitates recruitment of E2F4 to an adjacent E2F site to promoteBRCA1transcription. Consistent with ZC3H18 role in activating BRCA1 expression, ZC3H18 depletion inducesBRCA1promoter methylation, reduces BRCA1 expression, disrupts HR, and sensitizes cells to DNA crosslinkers and poly(ADP-ribose) polymerase inhibitors. Moreover, in patient-derived xenografts and primary HGSOC tumors,ZC3H18andE2F4mRNA levels are positively correlated withBRCA1mRNA levels, further supporting ZC3H18 role in regulatingBRCA1. Given thatZC3H18lies within 16q24.2, a region with frequent copy number loss in HGSOC, these findings suggest thatZC3H18copy number losses could contribute to HR defects in HGSOC.
Sex-biased gene expression is repeatedly masculinized in asexual females
Authors: Parker Darren J. , Bast Jens , Jalvingh Kirsten , Dumas Zoé , Robinson-Rechavi Marc , Schwander Tanja
Published: October 2019

Males and females feature strikingly different phenotypes, despite sharing most of their genome. A resolution of this apparent paradox is through differential gene expression, whereby genes are expressed at different levels in each sex. This resolution, however, is likely to be incomplete, leading to conflict between males and females over the optimal expression of genes. Here we test the hypothesis that gene expression in females is constrained from evolving to its optimum level due to sexually antagonistic selection on males, by examining changes in sex-biased gene expression in five obligate asexual species of stick insect, which do not produce males. We predicted that the transcriptome of asexual females would be feminized as asexual females do not experience any sexual conflict. Contrary to our prediction we find that asexual females feature masculinized gene expression, and hypothesise that this is due to shifts in female optimal gene expression levels following the suppression of sex.
Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer
Authors: Parker Joanne L. , Corey Robin A. , Stansfeld Phillip J. , Newstead Simon
Published: October 2019

Nucleotide sugars are the activated form of monosaccharides used by glycosyltransferases during glycosylation. In eukaryotes the SLC35 family of solute carriers are responsible for their selective uptake into the Endoplasmic Reticulum or Golgi apparatus. The structure of the yeast GDP-mannose transporter, Vrg4, revealed a requirement for short chain lipids and a marked difference in transport rate between the nucleotide sugar and nucleoside monophosphate, suggesting a complex network of regulatory elements control transport into these organelles. Here we report the crystal structure of the GMP bound complex of Vrg4, revealing the molecular basis for GMP recognition and transport. Molecular dynamics, combined with biochemical analysis, reveal a lipid mediated dimer interface and mechanism for coordinating structural rearrangements during transport. Together these results provide further insight into how SLC35 family transporters function within the secretory pathway and sheds light onto the role that membrane lipids play in regulating transport across the membrane.
High efficiency and fast van der Waals hetero-photodiodes with a unilateral depletion region
Authors: Wu Feng , Li Qing , Wang Peng , Xia Hui , Wang Zhen , Wang Yang , Luo Man , Chen Long , Chen Fansheng , Miao Jinshui , Chen Xiaoshuang , Lu Wei , Shan Chongxin , Pan Anlian , Wu Xing , Ren Wencai , Jariwala Deep , Hu Weida
Published: October 2019

Van der Waals (vdW) heterodiodes based on two-dimensional (2D) materials have shown tremendous potential in photovoltaic detectors and solar cells. However, such 2D photovoltaic devices are limited by low quantum efficiencies due to the severe interface recombination and the inefficient contacts. Here, we report an efficient MoS2/AsP vdW hetero-photodiode utilizing a unilateral depletion region band design and a narrow bandgap AsP as an effective carrier selective contact. The unilateral depletion region is verified via both the Fermi level and the infrared response measurements. The device demonstrates a pronounced photovoltaic behavior with a short-circuit current of 1.3 μA and a large open-circuit voltage of 0.61 V under visible light illumination. Especially, a high external quantum efficiency of 71%, a record high power conversion efficiency of 9% and a fast response time of 9 μs are achieved. Our work suggests an effective scheme to design high-performance photovoltaic devices assembled by 2D materials.
Individualized recovery of gut microbial strains post antibiotics
Authors: Koo Hyunmin , Hakim Joseph A. , Crossman David K. , Kumar Ranjit , Lefkowitz Elliot J. , Morrow Casey D.
Published: October 2019

To further understand the impact of antibiotics on the gastrointestinal tract microbial community, the intra-individual recovery pattern of specific microbial strains was determined using metagenomic sequencing coupled with strain-tracking analyses. In a study where 18 individuals were administered a single antibiotic (cefprozil), new microbial genomic variants (herein strains) were transiently detected in 15 individuals, while in a second study that used a cocktail of three antibiotics (meropenem, gentamicin, and vancomycin), all 12 participants had either permanent or transient strain changes. The presence of distinct microbial genomic variants indicates a pattern of strain recovery that is intra-individual specific following disruption of the human gastrointestinal tract with antibiotics.
Changes in soil bacterial community diversity following the removal of invasive feral pigs from a Hawaiian tropical montane wet forest
Authors: Wehr Nathaniel H. , Kinney Kealohanuiopuna M. , Nguyen Nhu H. , Giardina Christian P. , Litton Creighton M.
Published: October 2019

Nonnative, invasive feral pigs (Sus scrofa) modify habitats by disturbing soils and vegetation, which can alter biogeochemical processes. Soil microbial communities drive nutrient cycling and therefore also play important roles in shaping ecosystem structure and function, but the responses of soil microbes to nonnative ungulate removal remains poorly studied. We examined changes in the soil bacterial community over a ~25 year chronosequence of feral pig removal in tropical montane wet forests on the Island of Hawai’i. We extracted bacterial eDNA from soil samples collected inside and outside of ungulate exclosures along this chronosequence and sequenced the eDNA using the Illumina platform. We found that ungulate removal increased diversity of soil bacteria, with diversity scores positively correlated with time since removal. While functional and phylogenetic diversity were not significantly different between pig present and pig removed soils, soil bulk density, which decreases following the removal of feral pigs, was a useful predictor of dissimilarity among sites and correlated to changes in functional diversity. Additionally, increases in soil porosity, potassium, and calcium were correlated to increases in functional diversity. Finally, sites with greater mean annual temperatures were shown to have higher scores of both functional and phylogenetic diversity. As such, we conclude that feral pigs influence overall bacterial community diversity directly while influencing functional diversity indirectly through alterations to soil structure and nutrients. Comparatively, phylogenetic differences between communities are better explained by mean annual temperature as a climatic predictor of community dissimilarity.
Assessing effects from four years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle, 2013–2017
Authors: Downs Sara H. , Prosser Alison , Ashton Adam , Ashfield Stuart , Brunton Lucy A. , Brouwer Adam , Upton Paul , Robertson Andrew , Donnelly Christl A. , Parry Jessica E.
Published: October 2019

The objective was to measure the association between badger culling and bovine tuberculosis (TB) incidents in cattle herds in three areas of England between 2013–2017 (Gloucestershire and Somerset) and 2015–2017 (Dorset). Farming industry-selected licensed culling areas were matched to comparison areas. A TB incident was detection of new Mycobacterium bovis infection (post-mortem confirmed) in at least one animal in a herd. Intervention and comparison area incidence rates were compared in central zones where culling was conducted and surrounding buffer zones, through multivariable Poisson regression analyses. Central zone incidence rates in Gloucestershire (Incidence rate ratio (IRR) 0.34 (95% CI 0.29 to 0.39, p < 0.001) and Somerset (IRR 0.63 (95% CI 0.58 to 0.69, p < 0.001) were lower and no different in Dorset (IRR 1.10, 95% CI 0.96 to 1.27, p = 0.168) than comparison central zone rates. The buffer zone incidence rate was lower for Gloucestershire (IRR 0.64, 95% CI 0.58 to 0.70, p < 0.001), no different for Somerset (IRR 0.97, 95% CI 0.80 to 1.16, p = 0.767) and lower for Dorset (IRR 0.45, 95% CI 0.37 to 0.54, p < 0.001) than comparison buffer zone rates. Industry-led culling was associated with reductions in cattle TB incidence rates after four years but there were variations in effects between areas.
Heart Rate and Heart Rate Variability Correlate with Clinical Reasoning Performance and Self-Reported Measures of Cognitive Load
Authors: Solhjoo Soroosh , Haigney Mark C. , McBee Elexis , van Merrienboer Jeroen J. G. , Schuwirth Lambert , Artino Anthony R. , Battista Alexis , Ratcliffe Temple A. , Lee Howard D. , Durning Steven J.
Published: October 2019

Cognitive load is a key mediator of cognitive processing that may impact clinical reasoning performance. The purpose of this study was to gather biologic validity evidence for correlates of different types of self-reported cognitive load, and to explore the association of self-reported cognitive load and physiologic measures with clinical reasoning performance. We hypothesized that increased cognitive load would manifest evidence of elevated sympathetic tone and would be associated with lower clinical reasoning performance scores. Fifteen medical students wore Holter monitors and watched three videos depicting medical encounters before completing a post-encounter form and standard measures of cognitive load. Correlation analysis was used to investigate the relationship between cardiac measures (mean heart rate, heart rate variability and QT interval variability) and self-reported measures of cognitive load, and their association with clinical reasoning performance scores. Despite the low number of participants, strong positive correlations were found between measures of intrinsic cognitive load and heart rate variability. Performance was negatively correlated with mean heart rate, as well as single-item cognitive load measures. Our data signify a possible role for using physiologic monitoring for identifying individuals experiencing high cognitive load and those at risk for performing poorly during clinical reasoning tasks.
A paradox of local abundance amidst regional rarity: the value of montane refugia for Persian leopard conservation
Authors: Farhadinia Mohammad S. , McClintock Brett T. , Johnson Paul J. , Behnoud Pouyan , Hobeali Kaveh , Moghadas Peyman , Hunter Luke T. B. , Macdonald David W.
Published: October 2019

The population densities of leopards vary widely across their global range, influenced by prey availability, intraguild competition and human persecution. In Asia, particularly the Middle East and the Caucasus, they generally occur at the lower extreme of densities recorded for the species. Reliable estimates of population density are important for understanding their ecology and planning their conservation. We used a photographic spatial capture-recapture (SCR) methodology incorporating animal movement to estimate density for the endangered Persian leopardPanthera pardus saxicolorin three montane national parks, northeastern Iran. We combined encounter history data arising from images of bilaterally asymmetrical left- and right-sided pelage patterns using a Bayesian spatial partial identity model accommodating multiple “non-invasive” marks. We also investigated the effect of camera trap placement on detection probability. Surprisingly, considering the subspecies’ reported low abundance and density based on previous studies, we found relatively high population densities in the three national parks, varying between 3.10 ± SD 1.84 and 8.86 ± SD 3.60 individuals/100 km2. The number of leopards detected in Tandoureh National Park (30 individuals) was larger than estimated during comparable surveys at any other site in Iran, or indeed globally. Capture and recapture probabilities were higher for camera traps placed near water resources compared with those placed on trails. Our results show the benefits of protecting even relatively small mountainous areas, which accommodated a high density of leopards and provided refugia in a landscape with substantial human activity.
Circular RNA differential expression in blood cell populations and exploration of circRNA deregulation in pediatric acute lymphoblastic leukemia
Authors: Gaffo Enrico , Boldrin Elena , Dal Molin Anna , Bresolin Silvia , Bonizzato Annagiulia , Trentin Luca , Frasson Chiara , Debatin Klaus-Michael , Meyer Lueder H. , te Kronnie Geertruij , Bortoluzzi Stefania
Published: October 2019

Circular RNAs (circRNAs) are abundantly expressed in the haematopoietic compartment, but knowledge on their diversity among blood cell types is still limited. Nevertheless, emerging data indicate an array of circRNA functions exerted through interactions with other RNAs and proteins, by translation into peptides, and circRNA involvement as regulatory molecules in many biological processes and cancer mechanisms. Interestingly, the role of specific circRNAs in leukemogenesis has been disclosed by a few studies, mostly in acute myeloid leukemia. In this study, circRNA expression in B-cells, T-cells and monocytes of healthy subjects is described, including putative new circRNA genes. Expression comparison considered 6,228 circRNAs and highlighted cell population-specific expression and exon usage patterns. Differential expression has been confirmed by qRT-PCR for circRNAs specific of B-cells (circPAX5, circAFF3, circIL4R, and circSETBP1) or T-cells (circIKZF1, circTNIK, circTXK, and circFBXW7), and for circRNAs from intronic (circBCL2) and intergenic regions that were overexpressed in lymphocytes. Starting from this resource of circRNA expression in mature blood cell populations, targeted examination identified striking and generalized upregulated expression of circPAX5, circPVT1 and circHIPK3 in pediatric B-precursor acute lymphoblastic leukemia, and disclosed circRNAs with variable expression across cytogenetic subtypes.
RNA sequencing for ligature induced periodontitis in mice revealed important role of S100A8 and S100A9 for periodontal destruction
Authors: Maekawa Shogo , Onizuka Satoru , Katagiri Sayaka , Hatasa Masahiro , Ohsugi Yujin , Sasaki Naoki , Watanabe Kazuki , Ohtsu Anri , Komazaki Rina , Ogura Kohei , Miyoshi-Akiyama Tohru , Iwata Takanori , Nitta Hiroshi , Izumi Yuichi
Published: October 2019

Periodontitis is an inflammatory disease caused by pathogenic oral microorganisms that induce the destruction of periodontal tissue. We sought to identify the relevant differentially expressed genes (DEGs) and clarify the mechanism underlying the rapid alveolar bone loss by using ligature-induced periodontitis in mice. A silk ligature was tied around the maxillary left second molar in 9-week-old C57BL/6 J male mice.In-vivomicro-CT analysis revealed that ligation induced severe bone loss. RNA-sequencing analysis, to examine host responses at 3 days post-ligation, detected 12,853 genes with fragments per kilobase of exon per million mapped reads ≥ 1, and 78 DEGs. Gene ontology term enrichment analysis revealed the expression profiles related to neutrophil chemotaxis and inflammatory responses were significantly enriched in the ligated gingiva. The expression levels of innate immune response-related genes, includingS100a8andS100a9, were significantly higher in the ligated side. S100A8 was strongly detected by immunohistochemistry at the attached epithelium in ligated sites. Inhibition ofS100A8andS100A9expression revealed that they regulatedIL1BandCTSKexpression in Ca9-22 cells. Thus, innate immune response-related molecules might be associated with the burst-destruction of periodontal tissue in ligature-induced periodontitis. Especially, S100A8 and S100A9 may play an important role in alveolar bone resorption.
Predicting shockwave lithotripsy outcome for urolithiasis using clinical and stone computed tomography texture analysis variables
Authors: Cui Helen W. , Silva Mafalda D. , Mills Andrew W. , North Bernard V. , Turney Benjamin W.
Published: October 2019

We aimed to develop and evaluate a statistical model, which included known pre-treatment factors and new computed tomography texture analysis (CTTA) variables, for its ability to predict the likelihood of a successful outcome after extracorporeal shockwave lithotripsy (SWL) treatment for renal and ureteric stones. Up to half of patients undergoing SWL may fail treatment. Better prediction of which cases will likely succeed SWL will help patients to make an informed decision on the most effective treatment modality for their stone. 19 pre-treatment factors for SWL success, including 6 CTTA variables, were collected from 459 SWL cases at a single centre. Univariate and multivariable analyses were performed by independent statisticians to predict the probability of a stone free (both with and without residual fragments) outcome after SWL. A multivariable model had an overall accuracy of 66% on Receiver Operator Curve (ROC) analysis to predict for successful SWL outcome. The variables most frequently chosen for the model were those which represented stone size. Although previous studies have suggested SWL can be reliably predicted using pre-treatment factors and that analysis of CT stone images may improve outcome prediction, the results from this study have not produced a useful model for SWL outcome prediction.
Prognostic nutritional index may not be a good prognostic indicator for acute myocardial infarction
Authors: Cheng Yisong , Li Hong , Li Dongze , Liang Lianjing , Jia Yu , Zou Liqun , Li Fanghui , Zhu Xingyu , Qian Hong , He Na , Zeng Zhi , Zeng Rui , Cao Yu , Wan Zhi
Published: October 2019

The prognostic nutritional index (PNI) has been applied in acute myocardial infarction (AMI) recently.However, the application of PNI in AMI needs verification. This was a prospective cohort study. Patients diagnosed with AMI were enrolled. PNI was calculated as (serum albumin (SA in g/L)) + (5 × total lymphocyte count (TLC) × 109/L). Modified PNI (mPNI) was analyzed by logistic regression analysis to reset the proportion of SA and TLC. The primary outcome was all-cause death. A total of 598 patients were enrolled; 73 patients died during follow-up. The coefficient of SA and TLC in the mPNI formula was approximately 2:1. The area under the receiver operating characteristic curve of SA, TLC, PNI, mPNI and GRACE in predicting death for patients with AMI was 0.718, 0.540, 0.636, 0.721 and 0.825, respectively. Net reclassification improvement (NRI) between PNI and mPNI was 0.230 (p < 0.001). Integrated discrimination improvement (IDI) was 0.042 (p = 0.001). Decision curve analysis revealed that mPNI had better prognostic value for patients with AMI than PNI; however, it was not superior to SA. Thus, PNI may not a reliable prognostic predictor of AMI; after resetting the formula, the value of PNI in predicting prognosis of AMI is almost entirely due to SA.
The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases
Authors: Guevara Tibisay , Körschgen Hagen , Cuppari Anna , Schmitz Carlo , Kuske Michael , Yiallouros Irene , Floehr Julia , Jahnen-Dechent Willi , Stöcker Walter , Gomis-Rüth F. Xavier
Published: October 2019

Human fetuin-B plays a key physiological role in human fertility through its inhibitory action on ovastacin, a member of the astacin family of metallopeptidases. The inhibitor consists of tandem cystatin-like domains (CY1 and CY2), which are connected by a linker containing a “CPDCP-trunk” and followed by a C-terminal region (CTR) void of regular secondary structure. Here, we solved the crystal structure of the complex of the inhibitor with archetypal astacin from crayfish, which is a useful model of human ovastacin. Two hairpins from CY2, the linker, and the tip of the “legumain-binding loop” of CY1 inhibit crayfish astacin following the “raised-elephant-trunk mechanism” recently reported for mouse fetuin-B. This inhibition is exerted by blocking active-site cleft sub-sites upstream and downstream of the catalytic zinc ion, but not those flanking the scissile bond. However, contrary to the mouse complex, which was obtained with fetuin-B nicked at a single site but otherwise intact, most of the CTR was proteolytically removed during crystallization of the human complex. Moreover, the two complexes present in the crystallographic asymmetric unit diverged in the relative arrangement of CY1 and CY2, while the two complexes found for the mouse complex crystal structure were equivalent. Biochemical studies in vitro confirmed the differential cleavage susceptibility of human and mouse fetuin-B in front of crayfish astacin and revealed that the cleaved human inhibitor blocks crayfish astacin and human meprin α and β only slightly less potently than the intact variant. Therefore, the CTR of animal fetuin-B orthologs may have a function in maintaining a particular relative orientation of CY1 and CY2 that nonetheless is dispensable for peptidase inhibition.
Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells
Authors: Basavaraja Raghavendra , Madusanka Senasige Thilina , Drum Jessica N. , Shrestha Ketan , Farberov Svetlana , Wiltbank Milo C. , Sartori Roberto , Meidan Rina
Published: October 2019

Interferon-tau (IFNT), serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. We investigated here whether IFNT directly affects the function of luteinized bovine granulosa cells (LGCs), a model for large-luteal cells. Recombinant ovine IFNT (roIFNT) induced the IFN-stimulated genes (ISGs; MX2, ISG15, and OAS1Y). IFNT induced a rapid and transient (15–45 min) phosphorylation of STAT1, while total STAT1 protein was higher only after 24 h. IFNT treatment elevated viable LGCs numbers and decreased dead/apoptotic cell counts. Consistent with these effects on cell viability, IFNT upregulated cell survival proteins (MCL1, BCL-xL, and XIAP) and reduced the levels of gamma-H2AX, cleaved caspase-3, and thrombospondin-2 (THBS2) implicated in apoptosis. Notably, IFNT reversed the actions of THBS1 on cell viability, XIAP, and cleaved caspase-3. Furthermore, roIFNT stimulated proangiogenic genes, including FGF2, PDGFB, and PDGFAR. Corroborating the in vitro observations, CL collected from day 18 pregnant cows comprised higher ISGs together with elevated FGF2, PDGFB, and XIAP, compared with CL derived from day 18 cyclic cows. This study reveals that IFNT activates diverse pathways in LGCs, promoting survival and blood vessel stabilization while suppressing cell death signals. These mechanisms might contribute to CL maintenance during early pregnancy.
Measurement of the hysteretic thermal properties of W-doped and undoped nanocrystalline powders of VO2
Authors: Gomez-Heredia C. L. , Ramirez-Rincon J. A. , Bhardwaj D. , Rajasekar P. , Tadeo I. J. , Cervantes-Lopez J. L. , Ordonez-Miranda J. , Ares O. , Umarji A. M. , Drevillon J. , Joulain K. , Ezzahri Y. , Alvarado-Gil J. J.
Published: October 2019

Hysteresis loops exhibited by the thermal properties of undoped and 0.8 at.% W-doped nanocrystalline powders of VO2 synthesized by means of the solution combustion method and compacted in pellets, are experimentally measured by photothermal radiometry. It is shown that: (i) the W doping reduces both the hysteresis loops of VO2 and its transition temperature up to 15 °C. (ii) The thermal diffusivity decreases (increases) until (after) the metallic domains become dominant in the VO2 insulating matrix, such that its variation across the metal-insulation transition is enhanced by 23.5% with W-0.8 at.% doping. By contrast, thermal conductivity (thermal effusivity) increases up to 45% (40%) as the metallic phase emerges in the VO2 structure due to the insulator-to-metal transition, and it enhances up to 11% (25%) in the insulator state when the local rutile phase is induced by the tungsten doping. (iii) The characteristic peak of the VO2 specific heat capacity is observed in both heating and cooling processes, such that the phase transition of the 0.8 at.% W-doped sample requires about 24% less thermal energy than the undoped one. (iv) The impact of the W doping on the four above-mentioned thermal properties of VO2 mainly shows up in its insulator phase, as a result of the distortion of the local lattice induced by the electrons of tungsten. W doping at 0.8 at.% thus enhances the VO2 capability to transport heat but diminishes its thermal switching efficiency.
Superoxide dismutase down-regulation and the oxidative stress is required to initiate pupation in Bombyx mori
Authors: Nojima Yosui , Bono Hidemasa , Yokoyama Takeshi , Iwabuchi Kikuo , Sato Ryoichi , Arai Katsuhiko , Tabunoki Hiroko
Published: October 2019

Perhaps, oxidative stress progresses pupation in some Lepidopteran insects; however, the reasons for this remain obscure. In our previous study, we clarifiedBombyx moriSOD1 (BmSOD1) andB. moriSOD2 (BmSOD2) proteins respond in common to ultraviolet irradiation (UV) oxidative stress and metamorphosis. This result strongly suggested pupation initiates by oxidative stress and might mediate by down-regulation of expression of BmSOD1 and BmSOD2 proteins. Thus, we examined about these relationships inB. moriin this study. In the microarray data reanalysis, we found the Notch signaling pathways as the common pathways in pupation and UV oxidative stress inB. mori. Also, we showed a molting hormone, 20-hydroxyecdysone, leads not only generation of superoxide but also downregulation of the expression of BmSOD proteins during pupation inB. mori. Our findings can contribute to a deeper understanding of how biological defense systems work against environmental oxidative stress.
Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing
Authors: Wang Qinggang , More Shyam K. , Vomhof-DeKrey Emilie E. , Golovko Mikhail Y. , Basson Marc D.
Published: October 2019

GI mucosal healing requires epithelial sheet migration. The non-receptor tyrosine kinase focal adhesion kinase (FAK) stimulates epithelial motility. A virtual screen identified the small drug-like FAK mimic ZINC40099027, which activates FAK. We assessed whether ZINC40099027 promotes FAK-Tyr-397 phosphorylation and wound healing in Caco-2 monolayers and two mouse intestinal injury models. Murine small bowel ulcers were generated by topical serosal acetic acid or subcutaneous indomethacin in C57BL/6J mice. One day later, we began treatment with ZINC40099027 or DMSO, staining the mucosa for phosphorylated FAK and Ki-67 and measuring mucosal ulcer area, serum creatinine, ALT, and body weight at day 4. ZINC40099027 (10–1000 nM) dose-dependently activated FAK phosphorylation, without activating Pyk2-Tyr-402 or Src-Tyr-419. ZINC40099027 did not stimulate proliferation, and stimulated wound closure independently of proliferation. The FAK inhibitor PF-573228 prevented ZINC40099027-stimulated wound closure. In both mouse ulcer models, ZINC40099027accelerated mucosal wound healing. FAK phosphorylation was increased in jejunal epithelium at the ulcer edge, and Ki-67 staining was unchanged in jejunal mucosa. ZINC40099027 serum concentration at sacrifice resembled the effective concentration in vitro. Weight, creatinine and ALT did not differ between groups. Small molecule FAK activators can specifically promote epithelial restitution and mucosal healing and may be useful to treat gut mucosal injury.
Patterns of at-sea behaviour at a hybrid zone between two threatened seabirds
Authors: Austin Rhiannon E. , Wynn Russell B. , Votier Stephen C. , Trueman Clive , McMinn Miguel , Rodríguez Ana , Suberg Lavinia , Maurice Louise , Newton Jason , Genovart Meritxell , Péron Clara , Grémillet David , Guilford Tim
Published: October 2019

Patterns of behavioural variation and migratory connectivity are important characteristics of populations, particularly at the edges of species distributions, where processes involved in influencing evolutionary trajectories, such as divergence, mutual persistence, and natural hybridization, can occur. Here, we focused on two closely related seabird species that breed in the Mediterranean: Balearic shearwaters (Puffinus mauretanicus) and Yelkouan shearwaters (Puffinus yelkouan). Genetic and phenotypic evidence of hybridization between the two species on Menorca (the eastern and westernmost island in the breeding ranges of the two shearwaters, respectively) has provided important insights into relationships between these recently diverged species. Nevertheless, levels of behavioural and ecological differentiation amongst these populations remain largely unknown. Using geolocation and stable isotopes, we compared the at-sea movement behaviour of birds from the Menorcan ‘hybrid’ population with the nearest neighbouring populations of Balearic and Yelkouan shearwaters. The Menorcan population displayed a suite of behavioural features intermediate to those seen in the two species (including migration strategies, breeding season movements and limited data on phenology). Our findings provide new evidence to support suggestions that the Menorcan population is admixed, and indicate a role of non-breeding behaviours in the evolutionary trajectories ofPuffinusshearwaters in the Mediterranean.