bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control
Authors: Dhaliwal Navroop K , Abatti Luis E , Mitchell Jennifer A 
Published: January 2019

AbstractEmbryonic stem (ES) cells are regulated by a network of transcription factors which maintain the pluripotent state. Differentiation relies on downregulation of pluripotency transcription factors disrupting this network. While investigating transcriptional regulation of the pluripotency transcription factorKlf4, we observed homozygous deletion of distal enhancers caused 17 fold decrease inKlf4transcript but surprisingly decreased protein levels by less than 2 fold indicating post-transcriptional control of KLF4 protein overrides transcriptional control. The lack of sensitivity of KLF4 to transcription is due to high protein stability (half-life >24hr). This stability is context dependent and disrupted during differentiation, evidenced by a shift to a half-life of <2hr. KLF4 protein stability is maintained through interaction with other pluripotency transcription factors (NANOG, SOX2 and STAT3) that together facilitate association of KLF4 with RNA polymerase II. In addition, the KLF4 DNA binding and transactivation domains are required for optimal KLF4 protein stability. Post-translational modification of KLF4 destabilizes the protein as cells exit the pluripotent state and mutations that prevent this destabilization also prevent differentiation. These data indicate the core pluripotency transcription factors are integrated by post-translational mechanisms to maintain the pluripotent state, and identify mutations that increase KLF4 protein stability while maintaining transcription factor function.
Vibrotactile perception in the sole of the foot in people with normal glucose tolerance and type 2 diabetes
Authors: Peterson Magnus , Pingel Ronnie , Rolandsson Olov , Dahlin Lars B. 
Published: January 2019

AbstractAimTo evaluate vibrotactile perception thresholds in people with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) in relation to other sensory tests.MethodsNerve function was evaluated in 36 and 42 participants with NGT and T2DM, respectively [mean age 70.0 (1.2) years; males n=40, females n=38]. The mean duration of T2DM was 12.3 (7.3) years. Vibration perception thresholds were measured at four frequencies (8, 16, 32 and 125 Hz) bilaterally on the sole of the foot at first and fifth metatarsal heads using Multifrequency vibrametry and compared to vibration perception thresholds using Biothesiometer (128 Hz) bilaterally (medial malleolus and distal dorsal bony surface of great toes), touch sensation with Semmes-Weinstein monofilament bilaterally (10 g) at three sites on the sole of foot (distal great toe and 1st and 5th metatarsal heads), electrophysiology (amplitude and conduction velocity of sural nerve; right side) and thermal sensory testing (i.e. small diameter nerve fibers; method of limits using Thermotest®).ResultsVibration perception and temperature thresholds in the foot and sural nerve function were different between the NGT and T2DM categories. Measuring vibration perception thresholds at lower frequencies with Multifrequency vibrametry, compared to Biothesiometer, both provided similar correlations to the amplitude of the sural nerve. Temperature thresholds did also correlate with vibration perception thresholds and with sural nerve function. Only 4/42 participants with T2DM showed pathology by monofilament test, none with NGT.ConclusionsVibration perception thresholds have a fair correlation to amplitude of the sural nerve, even when measured at a non-tactile surface. Thus in the present study, measuring vibration perception threshold at a tactile surface does not seem to provide any clear advantage over the traditional way of measuring vibration perception on the medial malleolus. In people with T2DM, both large and small diameter nerve fibers seem to be affected.
Arbuscular Mycorrhizal Fungus (AMF) and reduction of arsenic uptake in lentil crops
Authors: Alam Mohammad Zahangeer , Hoque Md. Anamul , McGee Rebecca , Carpenter-Boggs Lynne 
Published: January 2019

ABSTRACTArsenic (As) is a carcinogenic and hazardous substance that poses a serious risk to human health. Physiological studies have shown that growth of lentil crop have been impaired due to arsenic toxicity, and is transportable into human food chains. Our research focused on the transportation of As in lentil crops and its mitigation using Arbuscular Mycorrhizal Fungus (AMF). Shoot length, fresh and dry weight of shoot and root were found comparatively higher in 5 and 15 mgkg-1 arsenic treated lentil seedlings than in a 100 mgkg-1 As concentrated soil. As accumulation in lentil’s pods of BARI Mashur 1 were found higher than others; but As uptake in root and shoot were increased significantly in all BARI released lentil genotypes. Biomass growth of lentil was found higher in AMF treated soils in compare to non-AMF. AMF effectively reduced the arsenic uptake in root and shoot at 8 and 45 mgkg-1 As concentrated soils compared. As free lentil seeds are significantly important for human consumption through mitigation of As accumulation in lentil roots shoots and pods. AMF shows great potential in providing As free lentil seeds throughout the world.
How many days are needed to estimate accelerometry-assessed physical activity during pregnancy? Methodological analyses based on a cohort study using wrist-worn accelerometer
Authors: da Silva Shana Ginar , Evenson Kelly R , Ekelund Ulf , da Silva Inácio Crochemore Mohsam , Domingues Marlos Rodrigues , da Silva Bruna Gonçalves Cordeiro , de Almeida Mendes Márcio , Cruz Glória Isabel Niño , Hallal Pedro Curi 
Published: January 2019

AbstractBackgroundObjective methods to measure physical activity (PA) can lead to better cross-cultural comparisons, monitoring temporal PA trends, and measuring the effect of interventions. However, when applying this technology in field-work, the accelerometer data processing is prone to methodological issues. One of the most challenging issues relates to standardizing total wear time to provide reliable data across participants. It is generally accepted that at least 4 complete days of accelerometer wear represent a week for adults. It is not known if this same assumption holds true for pregnant women.AimWe assessed the optimal number of days needed to obtain reliable estimates of overall PA and moderate-to-vigorous physical activity (MVPA) during pregnancy using a raw triaxial wrist-worn accelerometer.MethodsCross-sectional analyses were carried out in the antenatal wave of the 2015 Pelotas (Brazil) Birth Cohort Study. Participants wore the wrist ActiGraph wGT3X-BT accelerometer for seven consecutive days. The daily average acceleration, which indicates overall PA, was measured as milli-g (mg), and time spent in MVPA (minutes/day) was analyzed in 5-minute bouts. ANOVA and Kruskal-Wallis tests were used to compare variability across days of the week. Bland-Altman plots and Spearman-Brown Prophecy Formula were applied to determine the reliability coefficient associated with one to seven days of measurement. Analyses were stratified by sociodemographic factors and nutritional status.ResultsAmong 2,082 pregnant women who wore the accelerometer for seven complete days, overall and MVPA were lower on Sundays compared to other days of the week. Reliability of >=0.80 to evaluate overall PA was reached with at least three monitoring days, whereas six days were needed to estimate reliable measures of MVPA.ConclusionsOur findings indicate that the usual approach obtaining one week of accelerometry in adults is also appropriate for pregnant women, particularly to obtain differences on weekend days and reliably estimate MVPA.
Maternal antibodies provide strain-specific protection against infection with the Lyme disease pathogen in a wild rodent
Authors: Gomez-Chamorro Andrea , Heinrich Vanina , Sarr Anouk , Roethlisberger Owen , Genné Dolores , Jacquet Maxime , Voordouw Maarten J. 
Published: January 2019

AbstractThe vertebrate immune system can produce antibodies that protect the host against pathogens. Females can transmit antibodies to their offspring, which provide short-term protection against infection. The tick-borne bacteriumBorrelia afzeliicauses Lyme disease in Europe and consists of multiple strains that cycle between the tick vector (Ixodes ricinus) and vertebrate hosts such as the bank vole (Myodes glareolus). We used a controlled experiment to show that infected female bank voles transmit protective antibodies to their offspring that are specific for the strain ofB. afzelii. To test the specificity of protection, the offspring were challenged with either the same strain to which the mothers had been exposed or a different strain. The maternal antibodies protected the offspring against the same strain, but not against the different strain. The offspring from the uninfected control mothers were equally susceptible to both strains. Our study shows that maternal antibodies provide strong but highly strain-specific protection againstB. afzeliiin an important rodent reservoir host. The transmission of maternal antibodies may have important consequences for the epidemiology of multiple-strain pathogens in nature.Author SummaryMany pathogens that cause infectious disease consist of multiple strains. In vertebrate hosts, the immune system can generate antibodies that are highly specific for different pathogen strains. Mothers can transmit these antibodies to their offspring and thereby protect them from infectious disease. To date, few studies have investigated whether this transgenerational transfer of protective antibodies is important for pathogens that cycle in wild animal populations. The tick-borne spirochete bacteriumBorrelia afzeliicauses Lyme disease in Europe and cycles betweenIxodesticks and wild rodent hosts, such as the bank vole (Myodes glareolus). The purpose of our study was to test whether female bank voles infected withB. afzeliitransmit antibodies to their offspring that protect them from an infected tick bite. Our study found that infected mothers do transmit antibodies, but the offspring were only protected against the strain ofB. afzeliito which their mothers had been exposed and not to a different strain (i.e. protection was highly strain-specific). The broader implications of our study is that the transfer of protective antibodies between generations in the vertebrate host population could be important for organizing the community of pathogen strains that circulate in nature.
Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
Authors: Henríquez-Olguin Carlos , Knudsen Jonas R. , Raun Steffen H. , Li Zhencheng , Dalbram Emilie , Treebak Jonas T. , Sylow Lykke , Holmdahl Rikard , Richter Erik A. , Jaimovich Enrique , Jensen Thomas E. 
Published: January 2019

ABSTRACTReactive oxygen species (ROS) act as intracellular compartmentalized second messengers mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source regulating glucose transport capacity during moderate-intensity exercise.
Motion perception in the common marmoset
Authors: Cloherty Shaun L. , Yates Jacob L. , Graf Dina , DeAngelis Gregory C. , Mitchell Jude F. 
Published: January 2019

AbstractVisual motion processing is a well-established model system for studying neural population codes in primates. The common marmoset, a small new world primate, offers unparalleled opportunities to probe these population codes in key motion processing areas, such as cortical areas MT and MST, because these areas are accessible for imaging and recording at the cortical surface. However, little is currently known about the perceptual abilities of the marmoset. Here, we introduce a paradigm for studying motion perception in the marmoset and compare their psychophysical performance to human observers. We trained two marmosets to perform a motion estimation task in which they provided an analog report of their perceived direction of motion with an eye movement to a ring that surrounded the motion stimulus. Marmosets and humans exhibited similar trade-offs in speed vs. accuracy: errors were larger and reaction times were longer as the strength of the motion signal was reduced. Reverse correlation on the temporal fluctuations in motion direction revealed that both species exhibited short integration windows, however, marmosets had substantially less non-decision time than humans. Our results provide the first quantification of motion perception in the marmoset and demonstrate several advantages to using analog estimation tasks.
Mechanistic Analyses of Supercoiling Behaviors of DNA in Nucleosomes and Chromatins
Authors: Zhang Hao , Li Tianhu 
Published: January 2019

AbstractBesides those in 146-base pair nucleosome core particle DNA, supercoils have been known to be present in 10-base pair arm DNA segments and naked linker DNA segments. The interacting patterns among histone octamers, histone H1, 10-base pair arm DNA segments and linker DNA have, however, not yet been elucidated. In the current report, we examine correlations among constituents of nucleosomes from the mechanistic perspectives and present molecular pathways for elucidating supercoiling behaviors of their component DNA sequences. It is our hope that our new analyses could serve as incentives to further clarify correlations between histones and DNA in the dynamic structures of chromatins in the future.
Predictive markers for Parkinson’s disease using deep neural nets on neuromelanin sensitive MRI
Authors: Shinde Sumeet , Prasad Shweta , Saboo Yash , Kaushick Rishabh , Saini Jitender , Pal Pramod Kumar , Ingalhalikar Madhura 
Published: January 2019

AbstractNeuromelanin sensitive magnetic resonance imaging (NMS-MRI) has been crucial in identifying abnormalities in the substantia nigra pars compacta (SNc) in Parkinson’s disease (PD). PD is characterized by loss of dopaminergic neurons in SNc and current techniques employ estimation of contrast ratios of the SNc visualized on NMS-MRI to discern PD patients from the healthy controls. However, the extraction of these features is time-consuming and laborious and moreover provides lower prediction accuracies. Furthermore, these do not account for patterns of subtle changes in PD in the SNc. To mitigate this, our work establishes a computer-based analysis technique based on convolutional neural networks (CNNs) to create prognostic and diagnostic biomarkers of PD from NMS-MRI. The technique not only performs with a superior cross-validation accuracy (83.7%) as well as testing accuracy (80%) as compared to contrast ratio-based classification (52.7% cross-validation and 56.5% testing accuracy) and radiomics based classifier (81.1% cross-validation and 60.3% testing accuracy); but also locates the most discriminative regions on the neuromelanin contrast images. These discriminative activations demonstrate that the left SNc plays a key role in the classification in comparison to the right SNc, and are in agreement with the concept of asymmetry in PD. Overall, the proposed technique has the potential to support radiological diagnosis of PD while facilitating deeper understanding into the abnormalities in SNc.
Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers
Authors: Balmer Timothy S. , Trussell Laurence O. 
Published: January 2019

AbstractIn vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers to postsynaptic cells determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.
Sequence learning is driven by improvements in motor planning
Authors: Ariani Giacomo , Diedrichsen Jörn 
Published: January 2019

AbstractThe ability to perform complex sequences of movements quickly and accurately is critical for many motor skills. While training improves performance in a large variety of motor-sequence tasks, the precise mechanisms behind such improvements are poorly understood. Here we investigated the contribution of single-action selection, sequence pre-planning, online planning, and motor execution to performance in a discrete sequence production (DSP) task. Five visually-presented numbers cued a sequence of five finger presses, which had to be executed as quickly and accurately as possible. To study how sequence planning influenced sequence production, we manipulated the amount of time that participants were given to prepare each sequence by using a forced-response paradigm. Over 4 days, participants were trained on 10 sequences and tested on 80 novel sequences. Our results revealed that participants became faster in selecting individual finger presses. They also preplanned 3-4 sequence items into the future, and the speed of pre-planning improved for trained, but not for untrained, sequences. Because pre-planning capacity remained limited, the remaining sequence elements had to be planned online during sequence execution, a process that also improved with sequence-specific training. Overall, our results support the view that motor sequence learning effects are best characterized by improvements in planning processes that occur both before and concurrently with motor execution.New & NoteworthyComplex skills often require the production of sequential movements. While practice improves performance, it remains unclear how these improvements are achieved. Our findings show that learning effects in a sequence production task can be attributed to an enhanced ability to plan upcoming movements. These results shed new light on planning processes in the context of movement sequences, and have important implications for our understanding of the neural mechanisms that underlie skill acquisition.
A gold standard method for human cell quantification after xenotransplantation
Authors: Bensalah Mona , Klein Pierre , Riederer Ingo , Chaouch Soraya , Muraine Laura , Savino Wilson , Butler-Browne Gillian , Trollet Capucine , Mouly Vincent , Bigot Anne , Negroni Elisa 
Published: January 2019

AbstractXenotransplantation of human cells into immunodeficient mouse models is a very powerful tool and an essential step for the pre-clinical evaluation of therapeutic cell-and gene-based strategies. Here we describe an optimized protocol combining immunofluorescence and real-time quantitative PCR to both quantify and visualize the fate and localization of human myogenic cells after injection in regenerating muscles of immunodeficient mice. Whereas real-time quantitative PCR-based method provides an accurate quantification of human cells, it does not document their specific localization. The addition of an immunofluorescence approach using human-specific antibodies recognizing engrafted human cells gives information on the localization of the human cells within the host muscle fibres, in the stem cell niche or in the interstitial space.These two combined approaches offer an accurate evaluation of human engraftment including cell number and localization and should provide a gold standard to compare results obtained either using different types of human stem cells or comparing healthy and pathological muscle stem cells between different research laboratories worldwide.
3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients
Authors: Dincer Cansu , Kaya Tugba , Keskin Ozlem , Gursoy Attila , Tuncbag Nurcan 
Published: January 2019

AbstractMutation profiles of Glioblastoma (GBM) tumors are very heterogeneous which is the main challenge in the interpretation of the effects of mutations in disease. Additionally, the impact of the mutations is not uniform across the proteins and protein-protein interactions. The pathway level representation of the mutations is very limited. In this work, we approach these challenges through a systems level perspective in which we analyze how the mutations in GBM tumors are distributed in protein structures/interfaces and how they are organized at the network level. Our results show that out of 14644 mutations, 4392 have structural information and ~13% of them form spatial patches. Despite a small portion of all mutations, 3D patches partially decrease the heterogeneity across the patients. Hub proteins adapt multiple patches of mutations usually with a very large one and connects mutations in multiple binding sites through the core of the protein. We reconstructed patient specific networks for 290 GBM tumors. Network-guided analysis of mutations completes the interaction components that mutated proteins potentially affect, and groups the patients according to the reconstructed networks. As a result, we found 4 tumor clusters that overcome the heterogeneity in mutation profiles, and reveal predominant pathways in each group. Additionally, the network-based similarity analysis shows that each group of patients carries a set of signature 3D mutation patches. We believe that this study provides another perspective to the analysis of mutation effects and a good training towards the network-guided precision medicine.Author SummaryGlioblastoma (GBM) is the most aggressive brain tumor type with a 15 months of survival on average. The mutation distribution of the GBM patients is very heterogeneous and standard treatments fail to consider the inter-tumor heterogeneity. In our study, we follow a systems level approach that integrates mutation profiles with protein-protein interaction networks. We hypothesized that although the mutations are heterogeneous, the mutations that are close in 3D of the same protein may affect the protein function similarly and this information can be used to get meaningful relation between disease state and mutations. Therefore, we spatially grouped these mutations as “patches” and reconstructed patient specific protein interaction networks. When we cluster these networks based on their pathway similarities, we found four patient groups in GBM. Then, the comparison of groups revealed overrepresentation of 3D patches. This finding can be used for patient specific therapy.