bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice
Authors: Liu Shu , Xiu Jianbo , Zhu Caiyun , Meng Kexin , Li Chen , Han Rongrong , Du Tingfu , Li Lanlan , Xu Lingdan , Liu Renjie , Zhu Wanwan , Shen Yan , Xu Qi 
Published: November 2021

AbstractPost-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice.
Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction
Authors: Tüting Christian , Kyrilis Fotis L. , Müller Johannes , Sorokina Marija , Skalidis Ioannis , Hamdi Farzad , Sadian Yashar , Kastritis Panagiotis L. 
Published: November 2021

AbstractFound across all kingdoms of life, 2-keto acid dehydrogenase complexes possess prominent metabolic roles and form major regulatory sites. Although their component structures are known, their higher-order organization is highly heterogeneous, not only across species or tissues but also even within a single cell. Here, we report a cryo-EM structure of the fully active Chaetomium thermophilum pyruvate dehydrogenase complex (PDHc) core scaffold at 3.85 Å resolution (FSC = 0.143) from native cell extracts. By combining cryo-EM with macromolecular docking and molecular dynamics simulations, we resolve all PDHc core scaffold interfaces and dissect the residing transacetylase reaction. Electrostatics attract the lipoyl domain to the transacetylase active site and stabilize the coenzyme A, while apolar interactions position the lipoate in its binding cleft. Our results have direct implications on the structural determinants of the transacetylase reaction and the role of flexible regions in the context of the overall 10 MDa PDHc metabolon architecture.
Transcriptional responses of skeletal stem/progenitor cells to hindlimb unloading and recovery correlate with localized but not systemic multi-systems impacts
Authors: Booker Cori N. , Haga Christopher L. , Boregowda Siddaraju V. , Strivelli Jacqueline , Phinney Donald G. 
Published: November 2021

AbstractDisuse osteoporosis (DO) results from mechanical unloading of weight-bearing bones and causes structural changes that compromise skeletal integrity, leading to increased fracture risk. Although bone loss in DO results from imbalances in osteoblast vs. osteoclast activity, its effects on skeletal stem/progenitor cells (SSCs) is indeterminate. We modeled DO in mice by 8 and 14 weeks of hindlimb unloading (HU) or 8 weeks of unloading followed by 8 weeks of recovery (HUR) and monitored impacts on animal physiology and behavior, metabolism, marrow adipose tissue (MAT) volume, bone density and micro-architecture, and bone marrow (BM) leptin and tyrosine hydroxylase (TH) protein expression, and correlated multi-systems impacts of HU and HUR with the transcript profiles of Lin−LEPR+ SSCs and mesenchymal stem cells (MSCs) purified from BM. Using this integrative approach, we demonstrate that prolonged HU induces muscle atrophy, progressive bone loss, and MAT accumulation that paralleled increases in BM but not systemic leptin levels, which remained low in lipodystrophic HU mice. HU also induced SSC quiescence and downregulated bone anabolic and neurogenic pathways, which paralleled increases in BM TH expression, but had minimal impacts on MSCs, indicating a lack of HU memory in culture-expanded populations. Although most impacts of HU were reversed by HUR, trabecular micro-architecture remained compromised and time-resolved changes in the SSC transcriptome identified various signaling pathways implicated in bone formation that were unresponsive to HUR. These findings indicate that HU-induced alterations to the SSC transcriptome that persist after reloading may contribute to poor bone recovery.
The herd-immunity threshold must be updated for multi-vaccine strategies and multiple variants
Authors: Yadegari Iraj , Omidi Mehdi , Smith Stacey R. 
Published: November 2021

AbstractSeveral vaccines with different efficacies and effectivenesses are currently being distributed across the world to control the COVID-19 pandemic. Having enough doses from the most efficient vaccines in a short time is not possible for all countries. Hence, policymakers may propose using various combinations of available vaccines to control the pandemic with vaccine-induced herd immunity by vaccinating a fraction of the population. The classic vaccine-induced herd-immunity threshold suggests that we can stop spreading the disease by vaccinating a fraction of the population. However, that classic threshold is defined only for a single vaccine and may be invalid and biased when we have multi-vaccine strategies for a disease or multiple variants, potentially leading policymakers to suboptimal vaccine-allocation policies. Here, we determine which combination of multiple vaccines may lead to herd immunity. We show that simplifying the problem and considering the vaccination of the population as a single-vaccine strategy whose effectiveness is the sample mean of all effectivenesses would not be ideal, because many multi-vaccine strategies with a smaller herd-immunity threshold can be proposed. We show that the herd-immunity threshold may vary due to changes in vaccine-uptake proportions. Moreover, we propose methods to determine the optimal combination of multiple vaccines in order to achieve herd immunity and apply our results to the issue of multiple variants. In addition, we determine a condition for reaching herd immunity in the presence of new emerging variants of concern. We show by example that new variants could influence our estimation of the vaccination reproduction number. It follows that the herd-immunity threshold must be updated not only when multi-vaccine strategies are used but also when multiple variants coexist in the population.
A register-based study comparing planned rehabilitation following acute stroke in 2011 and 2017
Authors: Nylén Malin C. , Persson Hanna C. , Abzhandadze Tamar , Sunnerhagen Katharina S. 
Published: November 2021

AbstractThis cross-sectional, register-based study aimed to explore patterns of planned rehabilitation at discharge from stroke units in Sweden in 2011 and 2017 and identify explanatory variables for planned rehabilitation. Multivariable binary logistic regression was used to identify variables that could explain planned rehabilitation. There were 19,158 patients in 2011 and 16,508 patients in 2017 with stroke, included in the study. In 2011, 57% of patients were planned for some form of rehabilitation at discharge from stroke unit, which increased to 72% in 2017 (p < 0.001). Patients with impaired consciousness at admission had increased odds for planned rehabilitation (hemorrhage 2011 OR 1.43, 95% CI 1.13–1.81, 2017 OR 1.66, 95% CI 1.20–2.32), (IS 2011 OR 1.21, 95% CI 1.08–1.34, 2017 OR 1.49, 95% CI 1.28–1.75). Admission to a community hospital (hemorrhage 2011 OR 0.56, 95% CI 0.43–0.74, 2017 OR 0.39, 95% CI 0.27–0.56) (IS 2011 OR 0.63, 95% CI 0.58–0.69, 2017 OR 0.54, 95% CI 0.49–0.61) or to a specialized non-university hospital (hemorrhage 2017 OR 0.66, 95% CI 0.46–0.94), (IS 2011 OR 0.90, 95% CI 0.82–0.98, 2017 OR 0.76, 95% CI 0.68–0.84) was associated with decreased odds of receiving planned rehabilitation compared to admission to a university hospital. As a conclusion severe stroke was associated with increased odds for planned rehabilitation and patients discharged from non-university hospitals had consistently decreased odds for planned rehabilitation.
The reserve of joint torque determines movement coordination
Authors: Faity Germain , Mottet Denis , Pla Simon , Froger Jérôme 
Published: November 2021

AbstractHumans coordinate biomechanical degrees of freedom to perform tasks at minimum cost. When reaching a target from a seated position, the trunk-arm-forearm coordination moves the hand to the well-defined spatial goal, while typically minimising hand jerk and trunk motion. However, due to fatigue or stroke, people visibly move the trunk more, and it is unclear what cost can account for this. Here we show that people recruit their trunk when the torque at the shoulder is too close to the maximum. We asked 26 healthy participants to reach a target while seated and we found that the trunk contribution to hand displacement increases from 11 to 27% when an additional load is handled. By flexing and rotating the trunk, participants spontaneously increase the reserve of anti-gravitational torque at the shoulder from 25 to 40% of maximal voluntary torque. Our findings provide hints on how to include the reserve of torque in the cost function of optimal control models of human coordination in healthy fatigued persons or in stroke victims.
Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy
Authors: Streubel-Gallasch Linn , Zyśk Marlena , Beretta Chiara , Erlandsson Anna 
Published: November 2021

AbstractTraumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level.
Faces and words are both associated and dissociated as evidenced by visual problems in dyslexia
Authors: Sigurdardottir Heida Maria , Arnardottir Alexandra , Halldorsdottir Eydis Thuridur 
Published: November 2021

AbstractFaces and words are traditionally assumed to be independently processed. Dyslexia is also traditionally thought to be a non-visual deficit. Counter to both ideas, face perception deficits in dyslexia have been reported. Others report no such deficits. We sought to resolve this discrepancy. 60 adults participated in the study (24 dyslexic, 36 typical readers). Feature-based processing and configural or global form processing of faces was measured with a face matching task. Opposite laterality effects in these tasks, dependent on left–right orientation of faces, supported that they tapped into separable visual mechanisms. Dyslexic readers tended to be poorer than typical readers at feature-based face matching while no differences were found for global form face matching. We conclude that word and face perception are associated when the latter requires the processing of visual features of a face, while processing the global form of faces apparently shares minimal—if any—resources with visual word processing. The current results indicate that visual word and face processing are both associated and dissociated—but this depends on what visual mechanisms are task-relevant. We suggest that reading deficits could stem from multiple factors, and that one such factor is a problem with feature-based processing of visual objects.
Investigations of proximity-induced superconductivity in the topological insulator Bi2Te3 by microRaman spectroscopy
Authors: Kiphart D. , Harkavyi Y. , Balin K. , Szade J. , Mróz B. , Kuświk P. , Jurga S. , Wiesner M. 
Published: November 2021

AbstractWe used the topological insulator (TI) Bi2Te3 and a high-temperature superconductor (HTSC) hybrid device for investigations of proximity-induced superconductivity (PS) in the TI. Application of the superconductor YBa2Cu3O7-δ (YBCO) enabled us to access higher temperature and energy scales for this phenomenon. The HTSC in the hybrid device exhibits emergence of a pseudogap state for T > Tc that converts into a superconducting state with a reduced gap for T < Tc. The conversion process has been reflected in Raman spectra collected from the TI. Complementary charge transport experiments revealed emergence of the proximity-induced superconducting gap in the TI and the reduced superconducting gap in the HTSC, but no signature of the pseudogap. This allowed us to conclude that Raman spectroscopy reveals formation of the pseudogap state but cannot distinguish the proximity-induced superconducting state in the TI from the superconducting state in the HTSC characterised by the reduced gap. Results of our experiments have shown that Raman spectroscopy is a complementary technique to classic charge transport experiments and is a powerful tool for investigation of the proximity-induced superconductivity in the Bi2Te3.
Megahertz scan rates enabled by optical sampling by repetition-rate tuning
Authors: Bajek D. , Cataluna M. A. 
Published: November 2021

AbstractWe demonstrate, for the first time, optical sampling by repetition-rate tuning (OSBERT) at record megahertz scan rates. A low-cost, tunable and extremely compact 2-section passively mode-locked laser diode (MLLD) is used as the pulsed laser source, whose repetition rate can be modulated electronically through biasing of the saturable absorber section. The pulsed output is split into two arms comparable to an imbalanced Michelson interferometer, where one arm is significantly longer than the other (a passive delay line, or PDL). The resulting electronic detuning of the repetition rate gives rise to a temporal delay between pulse pairs at a detector; the basis for time-resolved spectroscopy. Through impedance-matching, we developed a new system whereby a sinusoidal electrical bias could be applied to the absorber section of the MLLD via a signal generator, whose frequency could be instantly increased from sub-hertz through to megahertz modulation frequencies, corresponding to a ground-breaking megahertz optical sampling scan rate, which was experimentally demonstrated by the real-time acquisition of a cross-correlation trace of two ultrashort optical pulses within just 1 microsecond of real time. This represents scan rates which are three orders of magnitude greater than the recorded demonstrations of OSBERT to date, and paves the way for highly competitive scan rates across the field of time-resolved spectroscopy and applications therein which range from pump probe spectroscopy to metrology.
Observational and genetic evidence highlight the association of human sleep behaviors with the incidence of fracture
Authors: Qian Yu , Xia Jiangwei , Liu Ke-Qi , Xu Lin , Xie Shu-Yang , Chen Guo-Bo , Cong Pei-Kuan , Khederzadeh Saber , Zheng Hou-Feng 
Published: November 2021

AbstractWe combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed 6.4% higher risk of fracture (hazard ratio [HR] = 1.064, 95% CI = 1.038–1.090, P = 7.84 × 10−7), falls and bone mineral density (BMD) mediated 24.6% and 10.6% of the intermediary effect; the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk (P < 0.001) with the lowest risk at sleeping 7–8 h per day. The excessive daytime sleepiness and “evening” chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.087, 95% CI = 1.065–1.111, P = 1.27 × 10−14). Moreover, 17.4% of the fracture cases would be removed if all participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.
Impact of anti-solar differential rotation in mean-field solar-type dynamos
Authors: Noraz Q. , Brun A. S. , Strugarek A. , Depambour G. 
Published: November 2021

Context.Over the course of their lifetimes, the rotation of solar-type stars goes through different phases. Once they reach the zero-age main sequence, their global rotation rate decreases during the main sequence until at least the solar age, approximately following the empirical Skumanich’s law and enabling gyrochronology. Older solar-type stars might then reach a point of transition when they stop braking, according to recent results of asteroseismology. Additionally, recent 3D numerical simulations of solar-type stars show that different regimes of differential rotation can be characterized with the Rossby number. In particular, anti-solar differential rotation (fast poles, slow equator) may exist for high Rossby number (slow rotators). If this regime occurs during the main sequence and, in general, for slow rotators, we may consider how magnetic generation through the dynamo process might be impacted. In particular, we consider whether slowly rotating stars are indeed subject to magnetic cycles.Aims.We aim to understand the magnetic field generation of solar-type stars possessing an anti-solar differential rotation and we focus on the possible existence of magnetic cycles in such stars.Methods.We modeled mean-field kinematic dynamos in solar (fast equator, slow poles) and anti-solar (slow equator, fast poles) differential rotation, using the STELEM code. We consider two types of mean field dynamo mechanisms along with the Ω-effect: the standardα-effect distributed at various locations in the convective envelope and the Babcock-Leighton effect.Results.We find that kinematicαΩ dynamos allow for the presence of magnetic cycles and global polarity reversals for both rotation regimes, but only if theα-effect is saddled on the tachocline. If it is distributed in the convection zone, solar-type cases still possess a cycle and anti-solar cases do not. Conversely, we have not found any possibility for sustaining a magnetic cycle with the traditional Babcock-Leighton flux-transport dynamos in the anti-solar differential rotation regime due to flux addition. Graphic interpretations are proposed in order to illustrate these cases. However, we find that hybrid models containing both prescriptions can still sustain local polarity reversals at some latitudes.Conclusions.We conclude that stars in the anti-solar differential rotation regime can sustain magnetic cycles only for very specific dynamo processes. The detection of a magnetic cycle for such a star would therefore be a particularly interesting constraint in working to decipher what type of dynamo is actually at work in solar-type stars.
Approach to the Patient with Gait Disturbance
Authors: Tarolli Christopher G. , Lizarraga Karlo J. 
Published: November 2021

AbstractThe assessment of patients presenting with disorders of gait can be a daunting task for neurologists given the broad potential localization and differential diagnosis. However, gait disorders are extremely common in outpatient neurology, and all neurologists should be comfortable with the assessment, triage, and management of patients presenting with difficulty walking. Here, we aim to present a manageable framework for neurologists to approach the assessment of patients presenting with gait dysfunction. We suggest a chief complaint-based phenomenological characterization of gait, using components of the neurological history and examination to guide testing and treatment. We present the framework to mirror the outpatient visit with the patient, highlighting (1) important features of the gait history, including the most common gait-related chief complaints and common secondary (medical) causes of gait dysfunction; (2) gait physiology and a systematic approach to the gait examination allowing appropriate characterization of gait phenomenology; (3) an algorithmic approach to ancillary testing for patients with gait dysfunction based on historical and examination features; and (4) definitive and supportive therapies for the management of patients presenting with common neurological disorders of gait.
Approach to Common Visual Complaints Presenting to the Outpatient Neurologist
Authors: Greer Christine , Dinkin Marc 
Published: November 2021

AbstractVisual complaints are commonly encountered by the practicing neurologist. We review assessment of vision loss, diplopia, and positive visual phenomena, all of which require a thoughtful evaluation to localize disease and refine management. While many causative entities are unlikely to cause poor visual outcomes, including dry eyes, migraine, and congenital strabismus, others may threaten vision, life, or both, such as posterior communicating artery aneurysms, pituitary apoplexy, or temporal arteritis. A systematic approach to vision loss and diplopia is reviewed along with focused differential diagnoses.