bluuebunny/crossref_metadata_2025 huggingface dataset:
U‐Th Dating of Syntectonic Calcite Veins Reveals the Dynamic Nature of Fracture Cementation and Healing in Faults
Authors: Williams Randolph T. , Mozley Peter S. , Sharp Warren D. , Goodwin Laurel B.
Published: November 2019

Fracture cementation is an important control on the recovery of prefailure levels of permeability and strength in faults. The timescales of this process, however, are almost entirely unknown from direct analysis of the rock record. We report U‐Th dating results that quantify rates of fracture cementation in syntectonic calcite veins from the Loma Blanca fault, New Mexico, USA. Measured rates vary from ~0.05 to 0.80 mm/ka and exhibit a power function correlation with minimum fracture apertures. We argue that this correlation is the result of crystal growth in a transport‐limited system, where cementation rates were proportional to rates of postseismic fluid flow in individual fractures. We further argue that such transport‐limited, flux‐dependent cementation necessarily leads to a heterogeneous distribution of permeability and strength recovery as fluids migrate through fault‐zone fracture networks. These heterogeneities may influence rupture propagations pathways and the continual development of fault‐zone architecture/complexity.
Paleoseismic Evidence for Climatic and Magmatic Controls on the Teton Fault, WY
Authors: Larsen Darren J. , Crump Sarah E. , Abbott Mark B. , Harbert William , Blumm Aria , Wattrus Nigel J. , Hebberger John J.
Published: November 2019

Geologic records of past earthquakes are rare but critical for identifying long‐term patterns in fault behavior and assessing modern earthquake hazards. We present a continuous 14,000‐year paleoearthquake reconstruction using precisely dated lacustrine sediments and landslide deposits from a lake basin positioned directly on the Teton normal fault, which cuts across Grand Teton National Park, WY, and is among the most hazardous intraplate faults in the western United States. We show that beginning immediately after deglaciation, a series of at least seven major fault ruptures occurred at regular intervals of ~1,050 years (± ~250 years), followed by >5,000 years of inactivity. These results are consistent with trench data and model simulations and suggest that faulting was variably influenced by climate‐controlled glacial fluctuations and magmatic activity of the nearby Yellowstone hotspot.
Roles of Irrigation and Reservoir Operations in Modulating Terrestrial Water and Energy Budgets in the Indian Subcontinental River Basins
Authors: Shah Harsh L. , Zhou Tian , Sun Ning , Huang Maoyi , Mishra Vimal
Published: November 2019

Water management activities affect the terrestrial water cycle by increasing water supply and redistributing the water and energy budgets over irrigated agricultural land. However, the dynamics of how water management activities interact with the terrestrial water and energy budgets have not been sufficiently studied over Indian subcontinental Basins. In this study, we applied a well‐evaluated water management model, coupled with a large‐scale land surface hydrological model with irrigation and reservoir operation schemes to examine the impacts of irrigation and reservoir operations on terrestrial water and energy budgets over the Indian subcontinental basins. We conducted two simulations: NATURAL (i.e., no irrigation and no reservoirs) and water management scenario (i.e., with irrigation and with reservoir regulations, referred to as MANAGED) over 18 basins from 1951 to 2012. The water management impacts were evaluated by comparing a number of key water and energy budget terms such as evapotranspiration (ET), total runoff, land surface temperature (LST), latent heat flux (LHF), sensible heat flux (SHF), reservoir storage, and discharge. Our results show that water management activities have significant (pvalue <0.05) impacts on ET, LHF, and LST in most of the river basins during the pre‐monsoon season (February–May). Comparing to the NATURAL scenario, ET and LHF under the MANAGED scenario are significantly increased in most basins during pre‐monsoon and post‐monsoon seasons, especially in semiarid regions. Therefore, the influence of irrigation on water and energy budget can be an overestimation in comparison to the constrained irrigation, which is a more realistic scenario.
Genetic evidence for assortative mating on alcohol consumption in the UK Biobank
Authors: Howe Laurence J. , Lawson Daniel J. , Davies Neil M. , St. Pourcain Beate , Lewis Sarah J. , Davey Smith George , Hemani Gibran
Published: November 2019

Alcohol use is correlated within spouse-pairs, but it is difficult to disentangle effects of alcohol consumption on mate-selection from social factors or the shared spousal environment. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection. Here, we find strong evidence that an individual’s self-reported alcohol consumption and their genotype at rs1229984, a missense variant in ADH1B, are associated with their partner’s self-reported alcohol use. Applying Mendelian randomization, we estimate that a unit increase in an individual’s weekly alcohol consumption increases partner’s alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P = 8.20 × 10−6). Furthermore, we find evidence of spousal genotypic concordance for rs1229984, suggesting that spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest some concordance independent of population stratification. Our findings suggest that alcohol behaviour directly influences mate selection.
HPV infection and the genital cytokine milieu in women at high risk of HIV acquisition
Authors: Liebenberg Lenine J. P. , McKinnon Lyle R. , Yende-Zuma Nonhlanhla , Garrett Nigel , Baxter Cheryl , Kharsany Ayesha B. M. , Archary Derseree , Rositch Anne , Samsunder Natasha , Mansoor Leila E. , Passmore Jo-Ann S. , Abdool Karim Salim S. , Abdool Karim Quarraisha
Published: November 2019

Human papillomavirus (HPV) infection correlates with higher rates of HIV acquisition, but the underlying biological mechanisms are unclear. Here we study associations between HPV and HIV acquisition and relate these to vaginal cytokine profiles in an observational cohort of women at high risk of HIV infection (CAPRISA 004, n = 779) and with 74% HPV prevalence. We report here that HPV infection associates with a 2.5-fold increase in HIV acquisition risk in this population (95% CI: 1.2–5.3). Among 48 vaginal cytokines profiled, cytokines associated with HPV infection overlap substantially with cytokines associated with HIV risk, but are distinct from those observed in HPV negative women. Although our data do not establish a causative link between HPV status and the risk of HIV, we suggest that increasing HPV vaccination coverage may carry an additional benefit of reducing the risk of contracting HIV infection, particularly in regions with high HPV prevalence.
Genome-wide analysis of Cushion willow provides insights into alpine plant divergence in a biodiversity hotspot
Authors: Chen Jia-hui , Huang Yuan , Brachi Benjamin , Yun Quan-zheng , Zhang Wei , Lu Wei , Li Hong-na , Li Wen-qing , Sun Xu-dong , Wang Guang-yan , He Jun , Zhou Zhuo , Chen Kai-yun , Ji Yun-heng , Shi Ming-ming , Sun Wen-guang , Yang Yong-ping , Zhang Ren-gang , Abbott Richard J. , Sun Hang
Published: November 2019

The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix brachista (Cushion willow), a common component of subnival assemblages. We produce a high-quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM.
Intrinsically distinct hole and electron transport in conjugated polymers controlled by intra and intermolecular interactions
Authors: Pace Giuseppina , Bargigia Ilaria , Noh Yong-Young , Silva Carlos , Caironi Mario
Published: November 2019

It is still a matter of controversy whether the relative difference in hole and electron transport in solution-processed organic semiconductors is either due to intrinsic properties linked to chemical and solid-state structure or to extrinsic factors, as device architecture. We here isolate the intrinsic factors affecting either electron or hole transport within the same film microstructure of a model copolymer semiconductor. Relatively, holes predominantly bleach inter-chain interactions with H-type electronic coupling character, while electrons’ relaxation more strongly involves intra-chain interactions with J-type character. Holes and electrons mobility correlates with the presence of a charge transfer state, while their ratio is a function of the relative content of intra- and inter-molecular interactions. Such fundamental observation, revealing the specific role of the ground-state intra- and inter-molecular coupling in selectively assisting charge transport, allows predicting a more favorable hole or electron transport already from screening the polymer film ground state optical properties.
Neurons in the Nucleus papilio contribute to the control of eye movements during REM sleep
Authors: Gutierrez Herrera C. , Girard F. , Bilella A. , Gent T. C. , Roccaro-Waldmeyer D. M. , Adamantidis A. , Celio M. R.
Published: November 2019

Rapid eye movements (REM) are characteristic of the eponymous phase of sleep, yet the underlying motor commands remain an enigma. Here, we identified a cluster of Calbindin-D28K-expressing neurons in the Nucleus papilio (NPCalb), located in the dorsal paragigantocellular nucleus, which are active during REM sleep and project to the three contralateral eye-muscle nuclei. The firing of opto-tagged NPCalb neurons is augmented prior to the onset of eye movements during REM sleep. Optogenetic activation of NPCalb neurons triggers eye movements selectively during REM sleep, while their genetic ablation or optogenetic silencing suppresses them. None of these perturbations led to a change in the duration of REM sleep episodes. Our study provides the first evidence for a brainstem premotor command contributing to the control of eye movements selectively during REM sleep in the mammalian brain.
High-throughput screening of the static friction and ideal cleavage strength of solid interfaces
Authors: Wolloch Michael , Losi Gabriele , Ferrario Mauro , Righi M. Clelia
Published: November 2019

We present a comprehensiveab initio, high-throughput study of the frictional and cleavage strengths of interfaces of elemental crystals with different orientations. It is based on the detailed analysis of the adhesion energy as a function of lateral,γ(x,y), and perpendicular displacements,γ(z), with respect to the considered interface plane. We use the large amount of computed data to derive fundamental insight into the relation of the ideal strength of an interface plane with its adhesion. Moreover, the ratio between the frictional and cleavage strengths is provided as good indicator for the material failure mode – dislocation propagation versus crack nucleation. All raw and curated data are made available to be used as input parameters for continuum mechanic models, benchmarks, or further analysis.
Neural correlates of the DMT experience assessed with multivariate EEG
Authors: Timmermann Christopher , Roseman Leor , Schartner Michael , Milliere Raphael , Williams Luke T. J. , Erritzoe David , Muthukumaraswamy Suresh , Ashton Michael , Bendrioua Adam , Kaur Okdeep , Turton Samuel , Nour Matthew M. , Day Camilla M. , Leech Robert , Nutt David J. , Carhart-Harris Robin L.
Published: November 2019

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
Silicon photonics waveguide array sensor for selective detection of VOCs at room temperature
Authors: Janeiro Ricardo , Flores Raquel , Viegas Jaime
Published: November 2019

We report on the fabrication and characterization of a volatile organic compound sensor architecture addressing common drawbacks of photonic integrated sensors such as reusability and specificity. The proposed sensor, built on a silicon-on-insulator platform and based on arrayed waveguide interference, has a chemically selective polydimethylsiloxane polymer cladding, which encapsulates the waveguides and provides an expandable and permeable low refractive index material. This cladding material acts as the chemical transducer element, changing its optical properties when in contact with specific volatile organic compounds, whose presence in the context of environmental and public health protection is important to monitor. The sensor operates at room temperature and its selectivity was confirmed by multiple tests with water, toluene, chlorobenzene, and hexane, through which the sturdiness of the sensor was verified. A maximum spectral shift of about 22.8 nm was measured under testing with chlorobenzene, at a central wavelength of 1566.7 nm. In addition, a sensitivity of 234.8 pm/% was obtained for chlorobenzene mass percent concentrations, with a limit of detection of 0.24%m/m. The thermal sensitivity of the sensor has been found to be 0.9 nm/°C.
Novel gRNA design pipeline to develop broad-spectrum CRISPR/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients
Authors: Sullivan Neil T. , Dampier Will , Chung Cheng-Han , Allen Alexander G. , Atkins Andrew , Pirrone Vanessa , Homan Greg , Passic Shendra , Williams Jean , Zhong Wen , Kercher Katherine , Desimone Mathew , Li Luna , C. Antell Gregory , Mell Joshua Chang , Ehrlich Garth D. , Szep Zsofia , Jacobson Jeffrey M. , Nonnemacher Michael R. , Wigdahl Brian
Published: November 2019

The CRISPR/Cas9 system has been proposed as a cure strategy for HIV. However, few published guide RNAs (gRNAs) are predicted to cleave the majority of HIV-1 viral quasispecies (vQS) observed within and among patients. We report the design of a novel pipeline to identify gRNAs that target HIV across a large number of infected individuals. Next generation sequencing (NGS) of LTRs from 269 HIV-1-infected samples in the Drexel CARES Cohort was used to select gRNAs with predicted broad-spectrum activity. In silico, D-LTR-P4-227913 (package of the top 4 gRNAs) accounted for all detectable genetic variation within the vQS of the 269 samples and the Los Alamos National Laboratory HIV database. In silico secondary structure analyses from NGS indicated extensive TAR stem-loop malformations predicted to inactivate proviral transcription, which was confirmed by reduced viral gene expression in TZM-bl or P4R5 cells. Similarly, a high sensitivity in vitro CRISPR/Cas9 cleavage assay showed that the top-ranked gRNA was the most effective at cleaving patient-derived HIV-1 LTRs from five patients. Furthermore, the D-LTR-P4-227913 was predicted to cleave a median of 96.1% of patient-derived sequences from other HIV subtypes. These results demonstrate that the gRNAs possess broad-spectrum cutting activity and could contribute to an HIV cure.
Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies
Authors: Ortiz Christopher Llynard D. , Completo Gladys C. , Nacario Ruel C. , Nellas Ricky B.
Published: November 2019

A strategy in the discovery of anti-tuberculosis (anti-TB) drug involves targeting the enzymes involved in the biosynthesis of Mycobacterium tuberculosis’ (Mtb) cell wall. One of these enzymes is Galactofuranosyltransferase 2 (GlfT2) that catalyzes the elongation of the galactan chain of Mtb cell wall. Studies targeting GlfT2 have so far produced compounds showing minimal inhibitory activity. With the current challenge of designing potential GlfT2 inhibitors with high inhibition activity, computational methods such as molecular docking, receptor-ligand mapping, molecular dynamics, and Three-Dimensional-Quantitative Structure-Activity Relationship (3D-QSAR) were utilized to deduce the interactions of the reported compounds with the target enzyme and enabling the design of more potent GlfT2 inhibitors. Molecular docking studies showed that the synthesized compounds have binding energy values between −3.00 to −6.00 kcal mol−1. Two compounds, #27 and #31, have registered binding energy values of −8.32 ± 0.01, and −8.08 ± 0.01 kcal mol−1, respectively. These compounds were synthesized as UDP-Galactopyranose mutase (UGM) inhibitors and could possibly inhibit GlfT2. Interestingly, the analogs of the known disaccharide substrate, compounds #1–4, have binding energy range of −10.00 to −19.00 kcal mol−1. The synthesized and newly designed compounds were subjected to 3D-QSAR to further design compounds with effective interaction within the active site. Results showed improved binding energy from −6.00 to −8.00 kcal mol−1. A significant increase on the binding affinity was observed when modifying the aglycon part instead of the sugar moiety. Furthermore, these top hit compounds were subjected to in silico ADMETox evaluation. Compounds #31, #70, #71, #72, and #73 were found to pass the ADME evaluation and throughout the screening, only compound #31 passed the predicted toxicity evaluation. This work could pave the way in the design and synthesis of GlfT2 inhibitors through computer-aided drug design and can be used as an initial approach in identifying potential novel GlfT2 inhibitors with promising activity and low toxicity.
Prevalence of and factors related to anemia among Japanese adult women: Secondary data analysis using health check-up database
Authors: Hisa Kanako , Haruna Megumi , Hikita Naoko , Sasagawa Emi , Yonezawa Kaori , Suto Maiko , Ota Erika
Published: November 2019

The issue of anemia is important in terms of a woman’s preconception health. This study aimed to conduct an exploratory investigation of the prevalence of and factors related to anemia in non-pregnant Japanese women. Secondary data analysis was conducted using a database of women aged 20–49 years old who had attended an annual health check-up at a hospital in Tokyo (n = 10,598). A multiple logistic regression analysis was performed to identify factors related to anemia in two age groups: women aged 34 and under and those aged 35 and over. Anemia was defined as hemoglobin concentration levels <12.0 g/dL. The overall proportion of women with Hb <12.0 g/dL was 17.1%. Women aged 35 and over with a current medical history of uterine myoma were found to be at a higher risk of anemia. Women aged 35 and over who were overweight had a lower risk of anemia than women with normal weights. Current and past smoking habits affected hemoglobin levels among women aged 35 and over. In both age groups, those who drank alcohol habitually were at a lower risk than those who did not. Related factors of anemia should take into consideration a woman’s age and lifestyle.
Selection of an optimal macrocyclic chelator improves the imaging of prostate cancer using cobalt-labeled GRPR antagonist RM26
Authors: Mitran Bogdan , Thisgaard Helge , Rinne Sara , Dam Johan Hygum , Azami Frishta , Tolmachev Vladimir , Orlova Anna , Rosenström Ulrika
Published: November 2019

Gastrin-releasing peptide receptors (GRPRs) are promising targets in oligometastatic prostate cancer. We have recently used 55Co (T1/2 = 17.5 h) as a label for next day PET imaging of GRPR expression obtaining high imaging contrast. The radionuclide-chelator combination can significantly influence the biodistribution of radiopeptides. Therefore, in this study, we hypothesized that the properties of 55Co-labeled PEG2-RM26 can be improved by identifying the optimal macrocyclic chelator. All analogues (X-PEG2-RM26, X = NOTA,NODAGA,DOTA,DOTAGA) were successfully labeled with radiocobalt with high yields and demonstrated high stability. The radiopeptides bound specifically and with picomolar affinity to GRPR and their cellular processing was characterized by low internalization. The best binding capacity was found for DOTA-PEG2-RM26. Ex vivo biodistribution in PC-3 xenografted mice was characterized by rapid blood clearance via renal excretion. Tumor uptake was similar for all conjugates at 3 h pi, exceeding the uptake in all other organs. Higher kidney uptake and longer retention were associated with N-terminal negative charge (DOTAGA-containing conjugate). Tumor-to-organ ratios increased over time for all constructs, although significant chelator-dependent differences were observed. Concordant with affinity measurements, DOTA-analog had the best retention of activity in tumors, resulting in the highest tumor-to-blood ratio 24 h pi, which translated into high contrast PET/CT imaging (using 55Co).
The potential for polyphosphate metabolism in Archaea and anaerobic polyphosphate formation in Methanosarcina mazei
Authors: Paula Fabiana S. , Chin Jason P. , Schnürer Anna , Müller Bettina , Manesiotis Panagiotis , Waters Nicholas , Macintosh Katrina A. , Quinn John P. , Connolly Jasmine , Abram Florence , McGrath John W. , O’Flaherty Vincent
Published: November 2019

Inorganic polyphosphate (polyP) is ubiquitous across all forms of life, but the study of its metabolism has been mainly confined to bacteria and yeasts. Few reports detail the presence and accumulation of polyP in Archaea, and little information is available on its functions and regulation. Here, we report that homologs of bacterial polyP metabolism proteins are present across the major taxa in the Archaea, suggesting that archaeal populations may have a greater contribution to global phosphorus cycling than has previously been recognised. We also demonstrate that polyP accumulation can be induced under strictly anaerobic conditions, in response to changes in phosphate (Pi) availability, i.e. Pi starvation, followed by incubation in Pi replete media (overplus), in cells of the methanogenic archaeon Methanosarcina mazei. Pi-starved M. mazei cells increased transcript abundance of the alkaline phosphatase (phoA) gene and of the high-affinity phosphate transport (pstSCAB-phoU) operon: no increase in polyphosphate kinase 1 (ppk1) transcript abundance was observed. Subsequent incubation of Pi-starved M. mazei cells under Pi replete conditions, led to a 237% increase in intracellular polyphosphate content and a > 5.7-fold increase in ppk1 gene transcripts. Ppk1 expression in M. mazei thus appears not to be under classical phosphate starvation control.
Ubiquitin carboxyl-terminal hydrolases are required for period maintenance of the circadian clock at high temperature in Arabidopsis
Authors: Hayama Ryosuke , Yang Peizhen , Valverde Federico , Mizoguchi Tsuyoshi , Furutani-Hayama Ikuyo , Vierstra Richard D. , Coupland George
Published: November 2019

Protein ubiquitylation participates in a number of essential cellular processes including signal transduction and transcription, often by initiating the degradation of specific substrates through the 26S proteasome. Within the ubiquitin-proteasome system, deubiquitylating enzymes (DUBs) not only help generate and maintain the supply of free ubiquitin monomers, they also directly control functions and activities of specific target proteins by modulating the pool of ubiquitylated species. Ubiquitin carboxyl-terminal hydrolases (UCHs) belong to an enzymatic subclass of DUBs, and are represented by three members in Arabidopsis, UCH1, UCH2 and UCH3. UCH1 and UCH2 influence auxin-dependent developmental pathways in Arabidopsis through their deubiquitylation activities, whereas biological and enzymatic functions of UCH3 remain unclear. Here, we demonstrate that Arabidopsis UCH3 acts to maintain the period of the circadian clock at high temperatures redundantly with UCH1 and UCH2. Whereas single uch1, uch2 and uch3 mutants have weak circadian phenotypes, the triple uch mutant displays a drastic lengthening of period at high temperatures that is more extreme than the uch1 uch2 double mutant. UCH3 also possesses a broad deubiquitylation activity against a range of substrates that link ubiquitin via peptide and isopeptide linkages. While the protein target(s) of UCH1-3 are not yet known, we propose that these DUBs act on one or more factors that control period length of the circadian clock through removal of their bound ubiquitin moieties, thus ensuring that the clock oscillates with a proper period even at elevated temperatures.
Femtosecond laser fabrication of silver nanostructures on glass for surface enhanced Raman spectroscopy
Authors: MacKenzie Mark , Chi Haonan , Varma Manoj , Pal Parama , Kar Ajoy , Paterson Lynn
Published: November 2019

We report on an optimized fabrication protocol for obtaining silver nanoparticles on fused silica substrates via laser photoreduction of a silver salt solution. We find that multiple scans of the laser over the surface leads to a more uniform coverage of densely packed silver nanoparticles of approximately 50 nm diameter on the fused silica surface. Our substrates yield Raman enhancement factors of the order of 1011 of the signal detected from crystal violet. We use a theoretical model based on scanning electron microscope (SEM) images of our substrates to explain our experimental results. We also demonstrate how our technique can be extended to embedding silver nanoparticles in buried microfluidic channels in glass. The in situ laser inscription of silver nanoparticles on a laser machined, sub-surface, microfluidic channel wall within bulk glass paves the way for developing 3D, monolithic, fused silica surface enhance Raman spectroscopy (SERS) microfluidic sensing devices.
Modeling the role of endoplasmic reticulum-mitochondria microdomains in calcium dynamics
Authors: Moshkforoush Arash , Ashenagar Baarbod , Tsoukias Nikolaos M. , Alevriadou B. Rita
Published: November 2019

Upon inositol trisphosphate (IP3) stimulation of non-excitable cells, including vascular endothelial cells, calcium (Ca2+) shuttling between the endoplasmic reticulum (ER) and mitochondria, facilitated by complexes called Mitochondria-Associated ER Membranes (MAMs), is known to play an important role in the occurrence of cytosolic Ca2+ concentration ([Ca2+]Cyt) oscillations. A mathematical compartmental closed-cell model of Ca2+ dynamics was developed that accounts for ER-mitochondria Ca2+ microdomains as the µd compartment (besides the cytosol, ER and mitochondria), Ca2+ influx to/efflux from each compartment and Ca2+ buffering. Varying the distribution of functional receptors in MAMs vs. the rest of ER/mitochondrial membranes, a parameter called the channel connectivity coefficient (to the µd), allowed for generation of [Ca2+]Cytoscillations driven by distinct mechanisms at various levels of IP3 stimulation. Oscillations could be initiated by the transient opening of IP3 receptors facing either the cytosol or the µd, and subsequent refilling of the respective compartment by Ca2+ efflux from the ER and/or the mitochondria. Only under conditions where the µd became the oscillation-driving compartment, silencing the Mitochondrial Ca2+ Uniporter led to oscillation inhibition. Thus, the model predicts that alternative mechanisms can yield [Ca2+]Cyt oscillations in non-excitable cells, and, under certain conditions, the ER-mitochondria µd can play a regulatory role.
Prediction and associations of preterm birth and its subtypes with eicosanoid enzymatic pathways and inflammatory markers
Authors: Aung Max T. , Yu Youfei , Ferguson Kelly K. , Cantonwine David E. , Zeng Lixia , McElrath Thomas F. , Pennathur Subramaniam , Mukherjee Bhramar , Meeker John D.
Published: November 2019

Endogenous signaling molecules derived from lipids, peptides, and DNA, are important regulators of physiological processes during pregnancy. The effect of their collective impact on preterm birth (delivery < 37 weeks gestation) is understudied. We aimed to characterize the associations and predictive capacity of an extensive panel of eicosanoids, immune biomarkers, oxidative stress markers, and growth factors towards preterm birth and its subtypes. We conducted a cross-sectional study of pregnant women (recruited < 15 weeks gestation) in the LIFECODES birth cohort, which included 58 cases of preterm birth and 115 controls that delivered term. Among the cases there were 31 cases who had a spontaneous preterm birth (cases who had spontaneous preterm labor and/or preterm premature rupture of membranes) and 25 that had preterm birth associated with aberrant placentation (cases who had preeclampsia and/or intrauterine growth restriction) and 2 cases that could not be sufficiently categorized as either. We analyzed single biomarker associations with each preterm birth outcome using multiple logistic regression. Adaptive elastic-net was implemented to perform a penalized multiple logistic regression on all biomarkers simultaneously to identify the most predictive biomarkers. We then organized biomarkers into biological groups and by enzymatic pathways and applied adaptive elastic-net and random forest to evaluate the accuracy of each group for predicting preterm birth cases. The majority of associations we observed were for spontaneous preterm birth, and adaptive elastic-net identified 5-oxoeicosatetraenoic acid, resolvin D1, 5,6-epoxy-eicsatrienoic acid, and 15-deoxy-12,14-prostaglandin J2 as most predictive. Overall, lipid biomarkers performed the best at separating cases from controls compared to other biomarker categories (adaptive elastic-net AUC = 0.78 [0.62, 0.94], random forest AUC = 0.84 [0.72, 0.96]). Among the enzymatic pathways that differentiate eicosanoid metabolites, we observed the highest prediction of overall preterm birth by lipoxygenase metabolites using random forest (AUC = 0.83 [0.69, 0.96]), followed by cytochrome p450 metabolites using adaptive elastic-net (AUC = 0.74 [0.52, 0.96]). In this study we translate biological hypothesis into the language of modern machine learning. Many lipid biomarkers were highly associated with overall and spontaneous preterm birth. Among eicosanoids, lipoxygenase and cytochrome p450 products performed best in identifying overall and spontaneous preterm birth. The combination of lipid biomarkers may have good utility in clinical settings to predict preterm birth.
A simple, high-throughput stabilization assay to test HIV-1 uncoating inhibitors
Authors: Dostálková Alžběta , Hadravová Romana , Kaufman Filip , Křížová Ivana , Škach Kryštof , Flegel Martin , Hrabal Richard , Ruml Tomáš , Rumlová Michaela
Published: November 2019

Shortly after entering the cell, HIV-1 copies its genomic RNA into double-stranded DNA in a process known as reverse transcription. This process starts inside a core consisting of an enclosed lattice of capsid proteins that protect the viral RNA from cytosolic sensors and degradation pathways. To accomplish reverse transcription and integrate cDNA into the host cell genome, the capsid shell needs to be disassembled, or uncoated. Premature or delayed uncoating attenuates reverse transcription and blocks HIV-1 infectivity. Small molecules that bind to the capsid lattice of the HIV-1 core and either destabilize or stabilize its structure could thus function as effective HIV-1 inhibitors. To screen for such compounds, we modified our recently developed FAITH assay to allow direct assessment of the stability of in vitro preassembled HIV-1 capsid-nucleocapsid (CANC) tubular particles. This new assay is a high-throughput fluorescence method based on measuring the amount of nucleic acid released from CANC complexes under disassembly conditions. The amount of disassembled CANC particles and released nucleic acid is proportional to the fluorescence signal, from which the relative percentage of CANC stability can be calculated. We consider our assay a potentially powerful tool for in vitro screening for compounds that alter HIV disassembly.
Hunter-Gatherers Harvested and Heated Microbial Biogenic Iron Oxides to Produce Rock Art Pigment
Authors: MacDonald Brandi Lee , Stalla David , He Xiaoqing , Rahemtulla Farid , Emerson David , Dube Paul A. , Maschmann Matthew R. , Klesner Catherine E. , White Tommi A.
Published: November 2019

Red mineral pigment use is recognized as a fundamental component of a series of traits associated with human evolutionary development, social interaction, and behavioral complexity. Iron-enriched mineral deposits have been collected and prepared as pigment for use in rock art, personal adornment, and mortuary practices for millennia, yet little is known about early developments in mineral processing techniques in North America. Microanalysis of rock art pigments from the North American Pacific Northwest reveals a sophisticated use of iron oxide produced by the biomineralizing bacterium Leptothrix ochracea; a keystone species of chemolithotroph recognized in recent advances in the development of thermostable, colorfast biomaterial pigments. Here we show evidence for human engagement with this bacterium, including nanostructural and magnetic properties evident of thermal enhancement, indicating that controlled use of pyrotechnology was a key feature of how biogenic iron oxides were prepared into paint. Our results demonstrate that hunter-gatherers in this area of study prepared pigments by harvesting aquatic microbial iron mats dominated by iron-oxidizing bacteria, which were subsequently heated in large open hearths at a controlled range of 750 °C to 850 °C. This technical gesture was performed to enhance color properties, and increase colorfastness and resistance to degradation. This skilled production of highly thermostable and long-lasting rock art paint represents a specialized technological innovation. Our results contribute to a growing body of knowledge on historical-ecological resource use practices in the Pacific Northwest during the Late Holocene.

Figshare link to figures: https://figshare.com/s/9392a0081632c20e9484.
Tensor decomposition of TMS-induced EEG oscillations reveals data-driven profiles of antiepileptic drug effects
Authors: Tangwiriyasakul C. , Premoli I. , Spyrou L. , Chin R. F. , Escudero J. , Richardson M. P.
Published: November 2019

Transcranial magnetic stimulation combined with electroencephalography is a powerful tool to probe human cortical excitability. The EEG response to TMS stimulation is altered by drugs active in the brain, with characteristic “fingerprints” obtained for drugs of known mechanisms of action. However, the extraction of specific features related to drug effects is not always straightforward as the complex TMS-EEG induced response profile is multi-dimensional. Analytical approaches can rely on a-priori assumptions within each dimension or on the implementation of cluster-based permutations which do not require preselection of specific limits but may be problematic when several experimental conditions are tested. We here propose an alternative data-driven approach based on PARAFAC tensor decomposition, which provides a parsimonious description of the main profiles underlying the multidimensional data. We validated reliability of PARAFAC on TMS-induced oscillations before extracting the features of two common anti-epileptic drugs (levetiracetam and lamotrigine) in an integrated manner. PARAFAC revealed an effect of both drugs, significantly suppressing oscillations in the alpha range in the occipital region. Further, this effect was stronger under the intake of levetiracetam. This study demonstrates, for the first time, that PARAFAC can easily disentangle the effects of subject, drug condition, frequency, time and space in TMS-induced oscillations.
CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata
Authors: Huang Mian , Khan Jibran , Kaur Manpreet , Vanega Julian Daniel Torres , Patiño Orlando Andres Aguilar , Ramasubramanian Anand K. , Kao Katy C.
Published: November 2019

Candida glabrata is a human commensal and an opportunistic human fungal pathogen. It is more closely related to the model yeast Saccharomyces cerevisiae than other Candida spp. Compared with S. cerevisiae, C. glabrata exhibits higher innate tolerance to various environmental stressors, including hyperthermal stress. Here we investigate the molecular mechanisms of C. glabrata adaptation to heat stress via adaptive laboratory evolution. We show that all parallel evolved populations readily adapt to hyperthermal challenge (from 47 °C to 50 °C) and exhibit convergence in evolved phenotypes with extensive cross-tolerance to various other environmental stressors such as oxidants, acids, and alcohols. Genome resequencing identified fixation of mutations in CgSTE11 in all parallel evolved populations. The CgSTE11 homolog in S. cerevisiae plays crucial roles in various mitogen-activated protein kinase (MAPK) signaling pathways, but its role is less understood in C. glabrata. Subsequent verification confirmed that CgSTE11 is important in hyperthermal tolerance and the observed extensive cross-tolerance to other environmental stressors. These results support the hypothesis that CgSTE11 mediates cross-talks between MAPK signaling pathways in C. glabrata in response to environmental challenges.
Ventricular Distribution Pattern of the Novel Sympathetic Nerve PET Radiotracer 18F-LMI1195 in Rabbit Hearts
Authors: Werner Rudolf A. , Wakabayashi Hiroshi , Chen Xinyu , Hayakawa Nobuyuki , Lapa Constantin , Rowe Steven P. , Javadi Mehrbod S. , Robinson Simon , Higuchi Takahiro
Published: November 2019

We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer 18F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of 18F-LMI1195. In healthy rabbits, 18F-LMI1195 was administered followed by the reference perfusion marker 201Tl for a dual-radiotracer analysis. After 20 min of 18F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-μm short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine 18F-LMI1195 distribution (exposure for 3 h). After complete 18F decay, sections were re-exposed to determine 201Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. 18F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 ± 2, 94 ± 5, 94 ± 4 and 97 ± 3%LV, respectively, n.s.). Subepicardial 201Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90 ± 3, 96 ± 2 and *80 ± 5%LV, respectively, *p < 0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of 18F-LMI1195 (90 ± 4, 96 ± 5 and 84 ± 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of 201Tl in comparison to 18F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts.
Electrophysiological assessment of plant status outside a Faraday cage using supervised machine learning
Authors: Tran Daniel , Dutoit Fabien , Najdenovska Elena , Wallbridge Nigel , Plummer Carrol , Mazza Marco , Raileanu Laura Elena , Camps Cédric
Published: November 2019

Living organisms have evolved complex signaling networks to drive appropriate physiological processes in response to changing environmental conditions. Amongst them, electric signals are a universal method to rapidly transmit information. In animals, bioelectrical activity measurements in the heart or the brain provide information about health status. In plants, practical measurements of bioelectrical activity are in their infancy and transposition of technology used in human medicine could therefore, by analogy provide insight about the physiological status of plants. This paper reports on the development and testing of an innovative electrophysiological sensor that can be used in greenhouse production conditions, without a Faraday cage, enabling real-time electric signal measurements. The bioelectrical activity is modified in response to water stress conditions or to nycthemeral rhythm. Furthermore, the automatic classification of plant status using supervised machine learning allows detection of these physiological modifications. This sensor represents an efficient alternative agronomic tool at the service of producers for decision support or for taking preventive measures before initial visual symptoms of plant stress appear.
Assessing the effect on the generation of environmentally persistent free radicals in hydrothermal carbonization of sewage sludge
Authors: Zhu Yuhan , Wei Jia , Liu Yitao , Liu Xiaohui , Li Jun , Zhang Jing
Published: November 2019

Environmentally persistent free radicals (EPFRs) have attracted increasing research interest in recent years. Herein, the generation of EPFRs during the hydrothermal carbonization of sewage sludge (SS) was studied. First, the surface morphology, functional groups, constituent elements and free radicals were characterized for a holistic description of the raw SS and the selected hydrochar obtained from hydrothermal carbonization of SS (SHC). Then, the impact of hydrothermal temperature, residence time and initial pH on the formation of EPFRs was explored in detail through the investigation of g-factors and intensities of EPFRs identified in SHC. The results have shown that the formation of EPFRs was affected by the factors mentioned above, in which the impact of temperature is the greatest. Two types of EPFRs were spotted in the hydrochar, oxygen-centered (O-centered) and carbon-centered (C-centered) EPFRs, which were caught in 120–150 °C and 260–280 °C, respectively. Moreover, the intensities of Electron Paramagnetic Resonance (EPR) signals enhanced with increasing hydrothermal temperature. Whereas, residence time and initial pH only affected the amount of EPFRs in a manner. Additionally, the half-life of the O-centered EPFRs and the C-centered EPFRs was determined as long as 160.45 days and 401.10 days, respectively, indicating that EPFRs are stable in a long time.
Glucose isomerization in dioxane/water with Sn-β catalyst: improved catalyst stability and use for HMF production
Authors: Guo Qiang , Ren Limin , Alhassan Saeed M. , Tsapatsis Michael
Published: November 2019

The stability of zeolite Sn-β was greatly improved for glucose isomerization to fructose when dioxane/water was used as solvent, and fructose yield (ca.41.5%) close to that of the immobilized enzymes has been achieved.
Enhanced charge transport in ReSe2-based 2D/3D electrodes for efficient hydrogen evolution reaction
Authors: Li Jing , Liu Yuanwu , Liu Chen , Huang Wentian , Zhang Ying , Wang Minjie , Hou Zhipeng , Wang Xin , Jin Mingliang , Zhou Guofu , Gao Xingsen , Zhang Zhang , Liu Junming
Published: November 2019

Ultra-high-density ReSe2 nanoflakes with uniform small 2D size were grown on porous carbon cloth by CVD. The 2D/3D construction gave more active catalytic sites, and the small size effect and the interfacial C–Se bonding facilitated electron transport between ReSe2 and PCC.
A tetranuclear calcium hydride cluster with a highly symmetric [Ca4H6]2+ core
Authors: Schuhknecht Danny , Spaniol Thomas P. , Douair Iskander , Maron Laurent , Okuda Jun
Published: November 2019

The NNN-type macrocycle Me3TACN stabilizes a highly symmetric calcium hydride with a tetranuclear [Ca4H6]2+ core. It can be classified as a nido-cluster with a highly delocalized system including d-orbital contribution.
A palladium-hinged organometallic square with a perfect-sized cavity for the encapsulation of three heteroguests
Authors: Martínez-Agramunt Víctor , Peris Eduardo
Published: November 2019

A nanometer-sized tetrapalladium metallosquare with a pyrene-bisimidazolylidene ligand was found to display a perfect-sized cavity for the encapsulation of three heteroguests, enabling the formation of quintuple D–A–D–A–D stacks.
Halogen bonding (HaB) in E–I⋯X–M systems: influence of the halogen donor on the HaB nature
Authors: Dortéz Silvia , Fernández-Palacio Francisco , Damián Jesús , Gaiteiro Carlos , Ramos Javier , Gómez-Sal Pilar , Mosquera Marta E. G.
Published: November 2019

A study on how the covalent character of the halogen bond can be modulated by using different halogen donors.
Interpenetration isomers in isoreticular amine-tagged zinc MOFs
Authors: Khansari Afsaneh , Bryant Macguire R. , Jenkinson Daniel R. , Jameson Geoffrey B. , Qazvini Omid T. , Liu Lujia , Burrows Andrew D. , Telfer Shane G. , Richardson Christopher
Published: November 2019

Subtleties of interpenetration are exposed and classified in the IRMOF-9 system.
Time-resolved FTIR study on the structural switching of human galectin-1 by light-induced disulfide bond formation
Authors: Kuroi Kunisato , Kamijo Mana , Ueki Mutsuki , Niwa Yusuke , Hiramatsu Hirotsugu , Nakabayashi Takakazu
Published: November 2019

The light-induced disulfide bond technique, which we have previously developed, has enabled the time-resolved measurement of the disulfide-induced conformational switching of the lectin protein human galectin-1.
Understanding the effect of nanoconfinement on the structure of water hydrogen bond networks
Authors: Oh Myong In , Gupta Mayuri , Oh Chang In , Weaver Donald F.
Published: November 2019

Dynamic hydrogen bond trails in water confined between two phospholipid membranes traced by the information flow model.
Characterisation of peroxidation products arising from culinary oils exposed to continuous and discontinuous thermal degradation processes
Authors: Le Gresley Adam , Ampem Gilbert , Grootveld Martin , Percival Benita C. , Naughton Declan P.
Published: November 2019

High-resolution NMR analysis has been used, for the first time, to identify, putatively, two new secondary aldehydic lipid oxidation products in culinary oils.
Radioiodinated 9-fluorenone derivatives for imaging α7-nicotinic acetylcholine receptors
Authors: Gao Hang , Wang Shuxia , Qiang Bingchao , Wang Sixuan , Zhang Huabei
Published: November 2019

A series of 9H-fluoren-9-one substituents were synthesized and the radioiodinated meta-substituent was studied in vitro/vivo.