bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice
Authors: Hernandez Matthew M. , Fahrny Audrey , Jayaprakash Anitha , Gers-Huber Gustavo , Dillon-White Marsha , Audigé Annette , Mulder Lubbertus C.F. , Sachidanandam Ravi , Speck Roberto F. , Simon Viviana 
Published: September 2019

ABSTRACTHIV diversification facilitates immune escape and complicates antiretroviral therapy. In this study, we take advantage of a humanized mouse model to probe the contribution of APOBEC3 mutagenesis to viral evolution. Humanized mice were infected with isogenic HIV molecular clones (HIV-WT, HIV-45G, HIV-ΔSLQ) that differ only in their ability to counteract APOBEC3G (A3G). Infected mice remained naïve or were treated with the RT inhibitor lamivudine (3TC). Viremia, emergence of drug resistant variants and quasispecies diversification in the plasma compartment were determined throughout infection. While both HIV-WT and HIV-45G achieved robust infection, over time HIV-45G replication was significantly reduced compared to HIV-WT in the absence of 3TC treatment. In contrast, treatment response differed significantly between HIV-45G and HIV-WT infected mice. Antiretroviral treatment failed in 91% of HIV-45G infected mice while only 36% of HIV-WT infected mice displayed a similar negative outcome. Emergence of 3TC resistant variants and nucleotide diversity were determined by analyzing 155,462 single HIV reverse transcriptase (RT) and 6,985vifsequences from 33 mice. Prior to treatment, variants with genotypic 3TC resistance (RT-M184I/V) were detected at low levels in over a third of all animals. Upon treatment, the composition of the plasma quasispecies rapidly changed leading to a majority of circulating viral variants encoding RT-184I. Interestingly, increased viral diversity prior to treatment initiation correlated with higher plasma viremia in HIV-45G but not in HIV-WT infected animals. Taken together, HIV variants with suboptimal anti-A3G activity were attenuated in the absence of selection but display a fitness advantage in the presence of antiretroviral treatment.IMPORTANCEBoth viral (e.g., reverse transcriptase,RT) and host factors (e.g., APOBEC3G (A3G)) can contribute to HIV sequence diversity. This study shows that suboptimal anti-A3G activity shapes viral fitness and drives viral evolution in the plasma compartment of humanized mice.
Offspring production of ovarian organoids derived from spermatogonial stem cells by chromatin reorganization
Authors: Luo Huacheng , Li Xiaoyong , Tian Geng G. , Li Dali , Hou Changliang , Ding Xinbao , Hou Lin , Lyu Qifeng , Yang Yunze , Cooney Austin J. , Xie Wenhai , Xiong Ji , Wang Hu , Zhao Xiaodong , Wu Ji 
Published: September 2019

AbstractFate determination of germline stem cells remains poorly understood at the chromatin structure level1,2. Here, we demonstrate successful production of offspring from oocytes transdifferentiated from mouse spermatogonial stem cells (SSCs) with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs. Furthermore, we demonstrate direct induction of germline stem cells (iGSCs) differentiated into functional oocytes by transduction of H19, Stella, and Zfp57 and inactivation of Plzf in SSCs after screening with ovarian organoids. Using high throughput chromosome conformation, we uncovered extensive chromatin reorganization during SSC conversion into iGSCs, which was highly similar to female germline stem cells. We observed that although topologically associating domains were stable during SSC conversion, chromatin interactions changed in a striking manner, altering 35% of inactive and active chromosomal compartments throughout the genome. These findings have important implications in various areas including mammalian gametogenesis, genetic and epigenetic reprogramming, biotechnology, and medicine.
Test-retest reliability and long-term stability of 3-tissue constrained spherical deconvolution methods for analyzing diffusion MRI data
Authors: Newman Benjamin T. , Dhollander Thijs , Reynier Kristen A. , Panzer Matthew B. , Druzgal T. Jason 
Published: September 2019

AbstractPurposeSeveral recent studies have utilized a 3-tissue constrained spherical deconvolution pipeline to obtain quantitative metrics of brain tissue microstructure from diffusion-weighted MRI data. The three tissue compartments, comprising white matter-, grey matter-, and CSF-like (free water) signals, are potentially useful in the evaluation of brain microstructure in a range of pathologies. However, the reliability and long-term stability of these metrics has not yet been evaluated.MethodsThis study examined estimates of whole brain microstructure for the three tissue compartments, in three separate test-retest cohorts. Each cohort has different lengths of time between baseline and retest, ranging from within the same scanning session in the shortest interval to three months in the longest interval. Each cohort was also collected with different acquisition parameters.ResultsThe CSF-like compartment displayed the greatest reliability across all cohorts, with intraclass correlation coefficient (ICC) values being above 0.95 in each cohort. White matter-like and grey matter-like compartments both demonstrated very high reliability in the immediate cohort (both ICC>0.90), however this declined in the 3 month interval cohort to both compartments having ICC>0.80. Regional CSF-like signal fraction was examined in bilateral hippocampus and had an ICC>0.80 in each cohort.ConclusionThe 3-tissue CSD techniques provide reliable and stable estimates of tissue microstructure composition, up to 3 months longitudinally in a control population. This forms an important basis for further investigations utilizing 3-tissue CSD techniques to track changes in microstructure across a variety of brain pathologies.
Variability in Locomotor Dynamics Reveals the Critical Role of Feedback in Task Control
Authors: Uyanik Ismail , Sefati Shahin , Stamper Sarah A. , Cho Kyoung-A , Ankarali M. Mert , Fortune Eric S. , Cowan Noah J. 
Published: September 2019

AbstractAnimals vary considerably in size, shape, and physiological features across individuals, but yet achieve behavioral performances that are virtually indistinguishable between conspecifics. We examined how animals compensate for morphophysiological variation by measuring the system dynamics of individual knifefish (Eigenmannia virescens) in a refuge tracking task. Kinematic measurements ofEigenmanniawere used to generate individualized estimates of each fish’s locomotor plant and controller revealing substantial variability between fish. To test the impact of this variability on behavioral performance, these models were used to perform simulated ‘brain transplants’—computationally swapping controllers and plants between individuals. We found that simulated closed-loop performance was robust to mismatch between plant and controller. This suggests that animals rely on feedback rather than precisely tuned neural controllers to compensate for morphophysiological variability.
Range of motion and between-measurement variation of spinal kinematics in sound horses at trot on the straight line and on the lunge
Authors: Hardeman A. , Byström A. , Roepstorff L. , Swagemakers J.H. , van Weeren P.R. , Bragança F.M. Serra 
Published: September 2019

AbstractClinical assessment of spinal motion in horses is part of many routine clinical exams but remains highly subjective. A prerequisite for the quantification is the assessment of the expected normal range of motion and variability of back kinematics. The aim of this study was to objectively quantify spinal kinematics and between-measurement, -surface and -day variation in owner-sound horses. In an observational study, twelve owner-sound horses were trotted 12 times on four different paths (hard/soft straight line, soft lunge left and right). Measurements were divided over three days, with five repetitions on day one and two, and two repetitions on day three (recheck) which occurred 28-55 days later. Optical motion capture was used to collect kinematic data. Elements of the outcome were: 1) Ranges of Motion (ROM) with confidence intervals per path and surface, 2) a variability model to calculate between-measurement variation and test the effect of time, surface and path, 3) intraclass correlation coefficients (ICC) to determine repeatability. ROM was lowest on the hard straight line. Cervical lateral bending was doubled on the left compared to the right lunge. Mean variation for the flexion-extension and lateral bending of the whole back were 0.8 and 1 degrees. Pelvic motion showed a variation of 1.0 (pitch), 0.7 (yaw) and 1.3 (roll) degrees. For these five parameters, a tendency for more variation on the hard surface and reduced variation with increased repetitions was observed. More variation was seen on the recheck (p<0.001). ICC values for the pelvis were between 0.76 and 0.93, for the whole back flexion-extension and lateral bending between 0.51 and 0.91. Between-horse variation was substantially higher than within-horse variation. Concluding, ROM and variation in spinal biomechanics are horse-specific and small, necessitating individual analysis and making subjective clinical assessment of spinal kinematics challenging.
Gradients in the cerebellar cortex enable Fourier-like transformation and improve storing capacity
Authors: Straub Isabelle , Witter Laurens , Eshra Abdelmoneim , Hoidis Miriam , Byczkowicz Niklas , Maaß Sebastian , Delvendahl Igor , Dorgans Kevin , Savier Elise , Bechmann Ingo , Eilers Jens , Krüger Martin , Isope Philippe , Hallermann Stefan 
Published: September 2019

AbstractCerebellar granule cells (GCs) making up majority of all the neurons in the vertebrate brain, but heterogeneities among GCs and potential functional consequences are poorly understood. Here, we identified unexpected gradients in the biophysical properties of GCs. GCs closer to the white matter (inner-zone GCs) had higher firing thresholds and could sustain firing with larger current inputs. Dynamic clamp experiments showed that inner- and outer-zone GCs preferentially respond to high- and low-frequency mossy fiber inputs, respectively, enabling to disperse the mossy fiber input into its frequency components as performed by a Fourier transformation. Furthermore, inner-zone GCs have faster axonal conduction velocity and elicit faster synaptic potentials in Purkinje cells. Neuronal network modeling revealed that these gradients improve spike-timing precision of Purkinje cells and decrease the number of GCs required to learn spike-sequences. Thus, our study uncovers biophysical gradients in the cerebellar cortex enabling a Fourier-like transformation of mossy fiber inputs.
Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
Authors: Vilarrasa-Blasi Roser , Soler-Vila Paula , Verdaguer-Dot Núria , Russiñol Núria , Di Stefano Marco , Chapaprieta Vicente , Clot Guillem , Farabella Irene , Cuscó Pol , Agirre Xabier , Prosper Felipe , Beekman Renée , Beà Silvia , Colomer Dolors , Stunnenberg Henk , Gut Ivo , Campo Elias , Marti-Renom Marc A. , Martin-Subero José Ignacio 
Published: September 2019

AbstractDespite recent advances, the dynamics of genome architecture and chromatin function during human cell differentiation and its potential reorganization upon neoplastic transformation remains poorly characterized. Here, we integrate in situ Hi-C and nine additional omic layers to define and biologically characterize the dynamic changes in three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. Beyond conventional active (A) and inactive (B) compartments, an integrative analysis of Hi-C data reveals the presence of a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, we detect that 28% of the compartments change at defined maturation stages and mostly involve the intermediate compartment. The transition from naive to germinal center B cells is associated with widespread chromatin activation, which mostly reverts into the naive state upon further maturation of germinal center cells into memory B cells. The analysis of CLL and MCL neoplastic cells points both to entity and subtype-specific alterations in chromosome organization. Remarkably, we observe that large chromatin blocks containing key disease-specific genes alter their 3D genome organization. These include the inactivation of a 2Mb region containing the EBF1 gene in CLL and the activation of a 6.1Mb region containing the SOX11 gene in clinically aggressive MCL. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.
SIRT6 is a DNA Double-Strand Break Sensor
Authors: Onn Lior , Portillo Miguel , Ilic Stefan , Cleitman Gal , Stein Daniel , Kaluski Shai , Shirat Ido , Slobodnik Zeev , Einav Monica , Erdel Fabian , Akabayov Barak , Toiber Debra 
Published: September 2019

AbstractDNA double strand breaks are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure, with high affinity for double strand breaks. It relocates to sites of damage independently of signalling and known sensors and activates downstream signalling cascades for double strand break repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the Homologous Recombination and Non-Homologous End Joining pathways. Our findings indicate that SIRT6 plays a previously uncharacterized role as DNA damage sensor, which is critical for initiating the DNA damage response (DDR). Moreover, other Sirtuins share some DSB binding capacity and DDR activation. SIRT6 activates the DDR, before the repair pathway is chosen, and prevents genomic instability. Our findings place SIRT6 at the top of the DDR and pave the road to dissect the contributions of distinct double strand break sensors in downstream signalling.
Artifact-free whole-slide imaging with structured illumination microscopy and Bayesian image reconstruction
Authors: Johnson Karl , Hagen Guy M. 
Published: September 2019

AbstractBackgroundStructured illumination microscopy (SIM) is a method which can be used to image biological samples and can achieve both optical sectioning and super-resolution effects. Optimization of the imaging setup and data processing methods results in high quality images without artifacts due to mosaicking or due to the use of SIM methods. Reconstruction methods based on Bayesian estimation can be used to produce images with a resolution beyond that dictated by the optical system.FindingsFive complete datasets are presented including large panoramic SIM images of human tissues in pathophysiological conditions. Cancers of the prostate, skin, ovary, and breast, as well as tuberculosis of the lung, were imaged using SIM. The samples are available commercially and are standard histological preparations stained with hematoxylin and eosin.ConclusionThe use of fluorescence microscopy is increasing in histopathology. There is a need for methods which reduce artifacts when employing image stitching methods or optical sectioning methods such as SIM. Stitched SIM images produce results which may be useful for intraoperative histology. Releasing high quality, full slide images and related data will aid researchers in furthering the field of fluorescent histopathology.
An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries
Authors: Lee Christopher T. , Laughlin Justin G. , Moody John B. , Amaro Rommie E. , McCammon J. Andrew , Holst Michael J. , Rangamani Padmini 
Published: September 2019

ABSTRACTAdvances in imaging methods such as electron microscopy, tomography, and other modalities are enabling high-resolution reconstructions of cellular and organelle geometries. Such advances pave the way for using these geometries for biophysical and mathematical modeling once these data can be represented as a geometric mesh, which, when carefully conditioned, enables the discretization and solution of partial differential equations. In this study, we outline the steps for a naïve user to approachGAMer 2, a mesh generation code written in C++ designed to convert structural datasets to realistic geometric meshes, while preserving the underlying shapes. We present two example cases, 1) mesh generation at the subcellular scale as informed by electron tomography, and 2) meshing a protein with structure from x-ray crystallography. We further demonstrate that the meshes generated byGAMerare suitable for use with numerical methods. Together, this collection of libraries and tools simplifies the process of constructing realistic geometric meshes from structural biology data.SIGNIFICANCEAs biophysical structure determination methods improve, the rate of new structural data is increasing. New methods that allow the interpretation, analysis, and reuse of such structural information will thus take on commensurate importance. In particular, geometric meshes, such as those commonly used in graphics and mathematics, can enable a myriad of mathematical analysis. In this work, we describeGAMer 2, a mesh generation library designed for biological datasets. UsingGAMer 2and associated toolsPyGAMerandBlendGAMer, biologists can robustly generate computer and algorithm friendly geometric mesh representations informed by structural biology data. We expect thatGAMer 2will be a valuable tool to bring realistic geometries to biophysical models.
Why does a flying fish taxi on sea surface before take-off? A hydrodynamic interpretation
Authors: Deng Jian , Wang Shuhong , Zhang Lingxin , Mao Xuerui 
Published: September 2019

AbstractFlying fish have been observed jumping out of warm ocean waters worldwide. Before take-off, the flying fish are seen to taxi on the water surface by rapidly beating their semi-submerged tail fins, which process may help them airborne with enough speed to glide over a long distance. To understand the underlying physical mechanisms, here, we study a flying fish, 0.25 m in length and 0.191 kg in weight, considering both its underwater swimming and surface taxiing locomotion. Its hydrodynamic characteristics are numerically studied by computational fluid dynamics (CFD). Underwater, the fish is assumed to swim at a constant speed of 10 m s−1. Different critical frequencies are identified for various maximum deflected angles, ranging from θ0 = 10° to 30°, at which the fish reaches cruising states, when the horizontal forces are balanced. The corresponding minimum power required for cruising swimming is 350 W, obtained at a deflected angle of 10° and a critical frequency of 145 Hz. In contrast, in the taxiing stage, the minimum power required for a stead-state locomotion at 10 m s−1 is 36 W, occurring at a deflected angle of 15° and a frequency of 50 Hz. We note that the power is significantly smaller than the swimming locomotion. Further, by increasing the flapping power, we find that larger speeds can be achieved. In specific, when the power is brought up to 350 W, it can reach a speed of 16.5 m s−1. Clearly, from the direct comparison between the two locomotive modes, it is apparently evidenced that the flying fish can be further accelerated by taxiing along the water surface.
Using synthetic datasets to better understand and explain health outcomes associated with common single nucleotide polymorphisms
Authors: Wood Thomas R. , Owens Nathan 
Published: September 2019

ABSTRACTDue to decreasing costs and a move towards “personalised medicine”, the use of direct-to-consumer genetic analyses is increasing. Both consumers and healthcare practitioners must therefore be able to understand the true disease risks associated with common genetic single nucleotide polymorphisms (SNPs). However, most population studies of common SNPs only provide average (+/−error) phenotypic or risk descriptions for a given genotype, which hides the true heterogeneity of the population and reduces the ability of an individual to determine how they themselves might truly be effected. Here, we describe the use of synthetic datasets generated from descriptive phenotypic data published on common SNPs associated with obesity, elevated fasting blood glucose, and methylation status. Using both simple statistical theory and full graphical representation of the generated data, we show that single common SNPs are associated with a less than 10% likelihood of effecting final phenotype, even in homozygotes. The significant heterogeneity in the data, as well as the baseline disease risk of Western populations suggests that most disease risk is dominated by the effect of the modern environment.
FAP overexpression induce Epithelial-Mesenchymal Transition (EMT) in oral squamous cell carcinoma by down-regulating DPP9 gene
Authors: Wu Qing-qing , Zhao Meng , Huang Guang-zhao , Zheng Ze-nan , Zeng Wei-sen , Lv Xiao-zhi 
Published: September 2019

AbstractFAP acts as a tumor promoter via epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the interaction proteins with FAP and explore the precise mechanism of FAP promoting EMT in OSCC. IP-MS analysis confirmed that DPP9 was an interacting protein of FAP. DPP9 was down-regulated in OSCC tissue samples compared with MNT using immunohistochemistry and quantitative-PCR detection. Lower DPP9 was correlated with unfavorable overall survival of patients with OSCC. Repressing DPP9 accelerates the proliferation of OSCC cells in vitro and in vivo. Mechanistically, overexpression of FAP downregulate the expression of the DPP9 and the effect of FAP on OSCC proliferation, migration, invasion and EMT could be reversed by up-regulated DPP9. Our study suggests that FAP could induce EMT and promote carcinogenesis in oral squamous cell carcinoma by down-regulating DPP9 gene. That will hint different dimension on therapy for patients with OSCC.
Early career academics’ understanding of library language
Authors: Yesmin Shamima , Ahmed S.M. Zabed 
Published: September 2019

Purpose
The purpose of this paper is to empirically examine the understanding of library terminologies by early career faculty members in a newly established rural university setting at the south coast of Bangladesh.

Design/methodology/approach
A campus-wide survey was conducted using a structured questionnaire consisted of demographic questions and 35 multiple-choice questions on library terminologies. The multiple-choice questions asked faculty members to select the correct answer from a set of five answers.

Findings
The findings indicate that early career university teachers lack adequate understanding of library terms; in fact, many of them either gave incorrect answers or was unsure about the term. It was found that faculty members had relatively better understandings of commonly used library terminologies, but they had real difficulties comprehending computer and technology-related terms. Significant differences were observed for some of the terms in case of their age, designation and teaching experience.

Originality/value
This current study is unique in two ways: first, this is the first time an effort has been made to empirically examine the understanding of library terminologies by early career faculty members; and second, this study was conducted at a university in Bangladesh where the first language is not English.