bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
Authors: Bosshart Patrick D. , Kalbermatter David , Bonetti Sara , Fotiadis Dimitrios 
Published: June 2019

AbstractIn human and other mammalian cells, transport of L-lactate across plasma membranes is mainly catalyzed by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family. MCTs play an important role in cancer metabolism and are promising targets for tumor treatment. Here, we report the crystal structures of an SLC16 family homologue with two different bound ligands at 2.54 and 2.69 Å resolution. The structures show the transporter in the pharmacologically relevant outward-open conformation. Structural information together with a detailed structure-based analysis of the transport function provide important insights into the molecular working mechanisms of ligand binding and L-lactate transport.
Convergent allostery in ribonucleotide reductase
Authors: Thomas William C. , Brooks F. Phil , Burnim Audrey A. , Bacik John-Paul , Stubbe JoAnne , Kaelber Jason T. , Chen James Z. , Ando Nozomi 
Published: June 2019

AbstractRibonucleotide reductases (RNRs) use a conserved radical-based mechanism to catalyze the conversion of ribonucleotides to deoxyribonucleotides. Within the RNR family, class Ib RNRs are notable for being largely restricted to bacteria, including many pathogens, and for lacking an evolutionarily mobile ATP-cone domain that allosterically controls overall activity. In this study, we report the emergence of a distinct and unexpected mechanism of activity regulation in the sole RNR of the model organism Bacillus subtilis. Using a hypothesis-driven structural approach that combines the strengths of small-angle X-ray scattering (SAXS), crystallography, and cryo-electron microscopy (cryo-EM), we describe the reversible interconversion of six unique structures, including a flexible active tetramer and two inhibited helical filaments. These structures reveal the conformational gymnastics necessary for RNR activity and the molecular basis for its control via an evolutionarily convergent form of allostery.
Deterministic processes structure bacterial genetic communities across an urban landscape
Authors: Hassell J. M. , Ward M. J. , Muloi D. , Bettridge J. M. , Phan H. , Robinson T. P. , Ogendo A. , Imboma T. , Kiiru J. , Kariuki S. , Begon M. , Kang’ethe E. K. , Woolhouse M. E. J. , Fèvre E. M. 
Published: June 2019

AbstractLand-use change is predicted to act as a driver of zoonotic disease emergence through human exposure to novel microbial diversity, but evidence for the effects of environmental change on microbial communities in vertebrates is lacking. We sample wild birds at 99 wildlife-livestock-human interfaces across Nairobi, Kenya, and use whole genome sequencing to characterise bacterial genes known to be carried on mobile genetic elements (MGEs) within avian-borne Escherichia coli (n = 241). By modelling the diversity of bacterial genes encoding virulence and antimicrobial resistance (AMR) against ecological and anthropogenic forms of urban environmental change, we demonstrate that communities of avian-borne bacterial genes are shaped by the assemblage of co-existing avian, livestock and human communities, and the habitat within which they exist. In showing that non-random processes structure bacterial genetic communities in urban wildlife, these findings suggest that it should be possible to forecast the effects of urban land-use change on microbial diversity.
Voltage-dependent gating of SV channel TPC1 confers vacuole excitability
Authors: Jaślan Dawid , Dreyer Ingo , Lu Jinping , O’Malley Ronan , Dindas Julian , Marten Irene , Hedrich Rainer 
Published: June 2019

AbstractIn contrast to the plasma membrane, the vacuole membrane has not yet been associated with electrical excitation of plants. Here, we show that mesophyll vacuoles from Arabidopsis sense and control the membrane potential essentially via the K+-permeable TPC1 and TPK channels. Electrical stimuli elicit transient depolarization of the vacuole membrane that can last for seconds. Electrical excitability is suppressed by increased vacuolar Ca2+ levels. In comparison to wild type, vacuoles from the fou2 mutant, harboring TPC1 channels insensitive to luminal Ca2+, can be excited fully by even weak electrical stimuli. The TPC1-loss-of-function mutant tpc1-2 does not respond to electrical stimulation at all, and the loss of TPK1/TPK3-mediated K+ transport affects the duration of TPC1-dependent membrane depolarization. In combination with mathematical modeling, these results show that the vacuolar K+-conducting TPC1 and TPK1/TPK3 channels act in concert to provide for Ca2+- and voltage-induced electrical excitability to the central organelle of plant cells.
Neural effects of transcranial magnetic stimulation at the single-cell level
Authors: Romero Maria C. , Davare Marco , Armendariz Marcelo , Janssen Peter 
Published: June 2019

AbstractTranscranial magnetic stimulation (TMS) can non-invasively modulate neural activity in humans. Despite three decades of research, the spatial extent of the cortical area activated by TMS is still controversial. Moreover, how TMS interacts with task-related activity during motor behavior is unknown. Here, we applied single-pulse TMS over macaque parietal cortex while recording single-unit activity at various distances from the center of stimulation during grasping. The spatial extent of TMS-induced activation is remarkably restricted, affecting the spiking activity of single neurons in an area of cortex measuring less than 2 mm in diameter. In task-related neurons, TMS evokes a transient excitation followed by reduced activity, paralleled by a significantly longer grasping time. Furthermore, TMS-induced activity and task-related activity do not summate in single neurons. These results furnish crucial experimental evidence for the neural effects of TMS at the single-cell level and uncover the neural underpinnings of behavioral effects of TMS.
Multiferroicity in atomic van der Waals heterostructures
Authors: Gong Cheng , Kim Eun Mi , Wang Yuan , Lee Geunsik , Zhang Xiang 
Published: June 2019

AbstractMaterials that are simultaneously ferromagnetic and ferroelectric – multiferroics – promise the control of disparate ferroic orders, leading to technological advances in microwave magnetoelectric applications and next generation of spintronics. Single-phase multiferroics are challenged by the opposite d-orbital occupations imposed by the two ferroics, and heterogeneous nanocomposite multiferroics demand ingredients’ structural compatibility with the resultant multiferroicity exclusively at inter-materials boundaries. Here we propose the two-dimensional heterostructure multiferroics by stacking up atomic layers of ferromagnetic Cr2Ge2Te6 and ferroelectric In2Se3, thereby leading to all-atomic multiferroicity. Through first-principles density functional theory calculations, we find as In2Se3 reverses its polarization, the magnetism of Cr2Ge2Te6 is switched, and correspondingly In2Se3 becomes a switchable magnetic semiconductor due to proximity effect. This unprecedented multiferroic duality (i.e., switchable ferromagnet and switchable magnetic semiconductor) enables both layers for logic applications. Van der Waals heterostructure multiferroics open the door for exploring the low-dimensional magnetoelectric physics and spintronic applications based on artificial superlattices.
Hsp70 molecular chaperones: multifunctional allosteric holding and unfolding machines
Authors: Clerico Eugenia M. , Meng Wenli , Pozhidaeva Alexandra , Bhasne Karishma , Petridis Constantine , Gierasch Lila M. 
Published: June 2019

Abstract
The Hsp70 family of chaperones works with its co-chaperones, the nucleotide exchange factors and J-domain proteins, to facilitate a multitude of cellular functions. Central players in protein homeostasis, these jacks-of-many-trades are utilized in a variety of ways because of their ability to bind with selective promiscuity to regions of their client proteins that are exposed when the client is unfolded, either fully or partially, or visits a conformational state that exposes the binding region in a regulated manner. The key to Hsp70 functions is that their substrate binding is transient and allosterically cycles in a nucleotide-dependent fashion between high- and low-affinity states. In the past few years, structural insights into the molecular mechanism of this allosterically regulated binding have emerged and provided deep insight into the deceptively simple Hsp70 molecular machine that is so widely harnessed by nature for diverse cellular functions. In this review, these structural insights are discussed to give a picture of the current understanding of how Hsp70 chaperones work.
Probing the initial conditions of high-mass star formation
Authors: Zhang Chuan-Peng , Csengeri Timea , Wyrowski Friedrich , Li Guang-Xing , Pillai Thushara , Menten Karl M. , Hatchell Jennifer , Thompson Mark A. , Pestalozzi Michele R. 
Published: June 2019

Context. Fragmentation and feedback are two important processes during the early phases of star formation.
Aims. Massive clumps tend to fragment into clusters of cores and condensations, some of which form high-mass stars. In this work, we study the structure of massive clumps at different scales, analyze the fragmentation process, and investigate the possibility that star formation is triggered by nearby H ii regions.
Methods. We present a high angular resolution study of a sample of massive proto-cluster clumps G18.17, G18.21, G23.97N, G23.98, G23.44, G23.97S, G25.38, and G25.71. Combining infrared data at 4.5, 8.0, 24, and 70 μm, we use a few arcsecond resolution, radiometer and millimeter inteferometric data taken at 1.3 cm, 3.5 mm, 1.3 mm, and 870 μm to study their fragmentation and evolution. Our sample is unique in the sense that all the clumps have neighboring H ii regions. Taking advantage of that, we tested triggered star formation using a novel method where we study the alignment of the center of mass traced by dust emission at multiple scales.
Results. The eight massive clumps, identified based on single-dish observations, have masses ranging from 228 to 2279 M⊙ within an effective radius of Reff ~ 0.5 pc. We detect compact structures towards six out of the eight clumps. The brightest compact structures within infrared bright clumps are typically associated with embedded compact radio continuum sources. The smaller scale structures of Reff ~ 0.02 pc observed within each clump are mostly gravitationally bound and massive enough to form at least a B3-B0 type star. Many condensations have masses larger than 8 M⊙ at a small scale of Reff ~ 0.02 pc. We find that the two infrared quiet clumps with the lowest mass and lowest surface density with <300 M⊙ do not host any compact sources, calling into question their ability to form high-mass stars. Although the clumps are mostly infrared quiet, the dynamical movements are active at clump scale (~1 pc).
Conclusions. We studied the spatial distribution of the gas conditions detected at different scales. For some sources we find hints of external triggering, whereas for others we find no significant pattern that indicates triggering is dynamically unimportant. This probably indicates that the different clumps go through different evolutionary paths. In this respect, studies with larger samples are highly desired.
Mass transfer on a nuclear timescale in models of supergiant and ultra-luminous X-ray binaries
Authors: Quast M. , Langer N. , Tauris T. M. 
Published: June 2019

Context. The origin and number of the Galactic supergiant X-ray binaries is currently not well understood. They consist of an evolved massive star and a neutron star or black-hole companion. X-rays are thought to be generated from the accretion of wind material donated by the supergiant, while mass transfer due to Roche-lobe overflow is mostly disregarded because the high mass ratios of these systems are thought to render this process unstable.
Aims. We investigate how the proximity of supergiant donor stars to the Eddington limit, and their advanced evolutionary stage, may influence the evolution of massive and ultra-luminous X-ray binaries with supergiant donor stars (SGXBs and ULXs).
Methods. We constructed models of massive stars with different internal hydrogen and helium gradients (H/He gradients) and different hydrogen-rich envelope masses, and exposed them to slow mass-loss to probe the response of the stellar radius. In addition, we computed the corresponding Roche-lobe overflow mass-transfer evolution with our detailed binary stellar evolution code, approximating the compact objects as point masses.
Results. We find that a H/He gradient in the layers beneath the surface, as it is likely present in the well-studied donor stars of observed SGBXs, can enable mass transfer in SGXBs on a nuclear timescale with a black-hole or a neutron star accretor, even for mass ratios in excess of 20. In our binary evolution models, the donor stars rapidly decrease their thermal equilibrium radius and can therefore cope with the inevitably strong orbital contraction imposed by the high mass ratio. We find that the orbital period derivatives of our models agree well with empirical values. We argue that the SGXB phase may be preceded by a common-envelope evolution. The envelope inflation near the Eddington limit means that this mechanism more likely occurs at high metallicity.
Conclusion. Our results open a new perspective for understanding that SGBXs are numerous in our Galaxy and are almost completely absent in the Small Magellanic Cloud. Our results may also offer a way to find more ULX systems, to detect mass transfer on nuclear timescales in ULX systems even with neutron star accretors, and shed new light on the origin of the strong B-field in these neutron stars.
Global mapping of lunar refractory elements: multivariate regression vs. machine learning
Authors: Bhatt M. , Wöhler C. , Grumpe A. , Hasebe N. , Naito M. 
Published: June 2019

Context.The quantitative estimation of elemental concentrations at the spatial resolution of hyperspectral near-infrared (NIR) images of the lunar surface is an important tool for understanding the processes relevant for the origin and evolution of the Moon.Aims.We aim to map the abundances of the elements Fe, Ca, and Mg at a typical accuracy of about 1 wt.% at the spatial resolution of the Moon Mineralogy Mapper (M3) instrument on-board Chandrayaan-1 lunar mission.Methods.The NIR reflectance of the lunar regolith is an integrated response to the presence of refractory elements and soil alteration processes. Our approach was to define a combination of spectral parameters that are robust with respect to the effects of soil maturity. We calibrated the spectral parameters with respect to elemental abundances measured by the Lunar Prospector Gamma Ray Spectrometer (LP GRS) and the Kaguya GRS (KGRS). For this purpose, we compared a classical multivariate linear regression (MLR) approach and the machine learning based support vector regression (SVR) technique applied to M3global observations.Results.The M3-based global elemental maps are consistent in distribution and range with the LP GRS and KGRS elemental maps and do not show artifacts in immature areas such as small fresh craters. The results derived using MLR and SVR are compared to sample-based ground truth data of the Apollo and Luna sample-return sites, where the root-mean-square deviations obtained by the two regression models are similar.Conclusions.The main advantage of the proposed new algorithm is its ability to minimize artifacts due to space-weathering effects. The elemental maps of Mg and Ca provide additional information and reveal structures not always visible in the Fe map. The global elemental abundance maps derived for the fully calibrated M3observations might thus serve as important tools to investigate the lunar geology and evolution.
Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus
Authors: Untch Michael , Thomssen Christoph , Bauerfeind Ingo , Braun Michael , Brucker Sara Y. , Felberbaum Ricardo , Hagemann Friederike , Haidinger Renate , Hönig Arnd , Huober Jens , Jackisch Christian , Kolberg Hans-Christian , Kolberg-Liedtke Cornelia , Kühn Thorsten , Lüftner Diana , Maass Nicolai , Reimer Toralf , Schneeweiss Andreas , Schumacher-Wulf Eva , Schütz Florian , Thill Marc , Wuerstlein Rachel , Fasching Peter A. , Harbeck Nadia 
Published: June 2019

AbstractThe results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this yearʼs St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This yearʼs 16th St. Gallen conference featured the motto “Magnitude of clinical benefit”. In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patientʼs individual situation and be discussed with the patient.
Cerebroplacental and Uterine Doppler Indices in Pregnancies Complicated by Congenital Heart Disease of the Fetus
Authors: Graupner Oliver , Koch Jessica , Enzensberger Christian , Götte Malena , Wolter Aline , Müller Vera , Kawecki Andreea , Herrmann Johannes , Axt-Fliedner Roland 
Published: June 2019

AbstractPurpose Children with congenital heart disease (CHD) are known to have impaired neurodevelopment possibly influenced by altered cerebroplacental hemodynamics antenatally. We compared fetomaternal Doppler patterns in different CHD groups with published normative values during gestation.Materials and Methods Retrospective cohort study consisting of 248 CHD fetuses. Subgroups were generated according to the expected ascending aorta oxygen saturation: low portion of high oxygenated umbilical venous (UV) blood (group 1: n = 108), intermediate portion of UV blood due to intracardiac mixing with oxygen poor systemic blood (group 2: n = 103), high (group 3: n = 13) and low portion of UV blood without mixing of blood (group 4: n = 24). Doppler examination included umbilical artery and middle cerebral artery pulsatility index (UA-PI, MCA-PI), cerebroplacental ratio (CPR) and mean uterine artery (mUtA) PI. For mean comparisons at different gestational ages (GA), estimated marginal means from regression models are reported for GA 22 weeks (wks), GA 30 wks and GA 38 wks.Results Z-score transformed values of MCA-PI (zMCA-PI) were significantly lower in group 1 compared to all other subgroups at GA 30 wks (p < 0.05). At 38 wks, group 1 had significantly lower values of zMCA-PI and zCPR compared to groups 2 and 4. Group 1 fetuses showed a significant association between zMCA-PI and zCPR (negative) and GA as well as zmUtA-PI (positive) and GA compared to reference values.Conclusion Our data confirm that CHD fetuses have a higher rate of cerebral redistribution in the third trimester. Changes in Doppler patterns were mainly observed in CHD with a low portion of UV blood in the ascending aorta.
The Impact of Fetal Anomalies on Contemporary Labor Patterns
Authors: McCormick Anna C. , McIntosh Jennifer J. , Gao Weihua , Hibbard Judith U. , Cruz Meredith O. 
Published: June 2019

Objective To compare labor patterns in pregnancies affected by fetal anomalies to low-risk singletons.
Study Design Labor data from the Consortium on Safe Labor, a multicenter retrospective study from 19 U.S. hospitals, including 98,674 low-risk singletons compared with 6,343 pregnancies with fetal anomalies were analyzed. Repeated-measures analysis constructed mean labor curves by parity, gestational age, and presence of fetal anomaly in women who reached full dilation. Interval-censored regression analysis adjusted for covariables was used to determine the median traverse times for labor progression.
Results Labor curves for all groups indicated slower labor progress for patients with fetal anomalies. The most significant trends in median traverse times were observed in the preterm nulliparous and term multiparous groups. The median traverse times from 4 cm to complete dilation in the preterm nulliparous control versus anomaly groups were 5.0 and 5.4 hours (p < 0.0001).
Conclusion Labor proceeds at a slower rate in pregnancies affected by anomalies.
Correction of Biapical Tibial Deformity by True Spherical Osteotomy, Modified Circular External Skeletal Fixation and Distraction Osteogenesis
Authors: Walmsley Darby , Fitzpatrick Noel , Black Cameron 
Published: June 2019

Objectives The aim of this study was to describe a case of biapical tibial deformity as a result of premature distal physeal closure corrected by true spherical osteotomy, circular external skeletal fixation and distraction osteogenesis.
Methods A 6-month-old male Labrador Retriever was presented for the evaluation and treatment of angular limb deformity of the left pelvic limb, with radiography and computed tomography revealing a multiplanar, biapical, compensatory tibial growth deformity, with marked distal tibial recurvatum and varus. A true spherical osteotomy was performed at the distal tibial centre of rotation of angulation (CORA), allowing for correction of the deformity in three planes, with a transverse osteotomy performed at the most proximal CORA. A circular external skeletal fixator was applied and distraction osteogenesis performed at the transverse osteotomy. Latency, distraction osteogenesis, and consolidation were performed over a 113-day period.
Results At frame removal, tibial length discrepancy improved from 16.8% to 0.6% and frontal plane varus angulation improvement from 20° to 5°, when compared with the contralateral limb. Long-term evaluation revealed a satisfactory clinical and cosmetic outcome, judged by the clinician and owners, with force plate analysed symmetry index of the pelvic limb within reported normal limits.
Clinical significance To our knowledge this is the first case report illustrating the value of true spherical osteotomy for the treatment of an angular limb deformity when performed in combination with distraction osteogenesis in a canine pelvic limb.
原始閩北區方言裡的*ə
Authors: Akitani Hiroyuki 
Published: June 2019

抽象
本文在Jerry Norman (1969)和孫順(2016)的基礎上，在原始閩北區方言的韻母系統裡構擬了*ə組韻母(*ə、*iə、*əu、*əŋ、*iəŋ)。
Iso-α-acids and matured hop bitter acids in beer improve obesity-induced cognitive impairment
Authors: Ayabe Tatsuhiro , Ohya Rena , Ano Yasuhisa 
Published: June 2019

ABSTRACT
Dementia and cognitive decline have become public health issues worldwide and life-style-related diseases and obesity have recently been reported as key risk factors. We have recently demonstrated that short-term administration of iso-α-acids (IAAs), hop-derived bitter components of beer, improves spatial and object recognition memory. However, the short-term effects of IAAs on obesity-induced cognitive impairment remain to be investigated. Furthermore, although matured hop bitter acids (MHBAs) are also derived from hops, their effect on obesity-induced cognitive decline remains unknown. In the present study, the short-term administration of IAAs improved memory deficits in high-fat diet (HFD)-fed mice, as assessed in the novel object recognition test (NORT). Dietary MHBAs supplementation administered to HFD-fed mice prevented obesity and improved memory deficits in the NORT. Moreover, the short-term administration of MHBAs improved episodic and spatial reference memory in obese mice. These hop-derived bitter acids may contribute toward improving obesity-induced cognitive impairments.
Abbreviations: IAAs: iso-α-acids; MHBAs: matured hop bitter acids; HFD: high fat diet; NORT: novel object recognition test; NOLT: novel object location test