bluuebunny/crossref_metadata_2025_split huggingface dataset:
TDP-43 subcellular mislocalisation is correlated with loss of optineurin binding for frontotemporal dementia and amyotrophic lateral sclerosis associated TBK1 missense variants
Authors: Oyston Lisa J. , Boccanfuso Lauren M. , Fitzpatrick Lauren , Zhang Johnny , Hallupp Marianne , Kwok John B. , Dobson-Stone Carol 
Published: June 2022

AbstractBackgroundFrontotemporal dementia (FTD) is one of the most common forms of younger-onset dementia. FTD is genetically, pathologically and clinically related to amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disorder. Mutations in TANK-binding kinase 1 (TBK1) have been identified as a rare cause of FTD and ALS. TBK1 has known roles in inflammation and autophagy and interacts with other FTD and ALS proteins such as optineurin (OPTN): however, which of its roles are important to FTD/ALS pathogenesis remains undetermined. To date, >90 TBK1 rare variants have been identified in FTD/ALS patients: >50% of these are missense variants of unknown significance (VUS).MethodsIn this study, we have used a functional assay pipeline to investigate the effect of 16 TBK1 VUS with in-silico evidence of pathogenicity, together with two known pathogenic mutations and a common benign TBK1 polymorphism. Our assay pipeline evaluated the effect of TBK1 VUS on steady-state levels of TBK1, kinase activity and binding to OPTN. We also assessed the impact of TBK1 VUS on a key neuropathological feature of FTD and ALS cases: mislocalisation of neuronal TDP-43 from the nucleus to the cytoplasm.ResultsWe observed some TBK1 VUS that had similar effects to TBK1 loss-of-function mutations, demonstrating decreased kinase activity and loss of OPTN binding. Both known pathogenic mutations and several TBK1 VUS also increased the cytoplasmic/nuclear ratio of TDP-43 and this inversely correlated with their degree of OPTN binding but not with kinase activity.ConclusionsThese results suggest that loss of the direct interaction between TBK1 and OPTN is more critical to FTD and ALS pathogenesis than TBK1’s kinase activity. However, further studies are needed to elucidate exactly how loss of TBK1 binding to OPTN leads to TDP-43 pathology and ultimately neurodegeneration.
Neurotransmission-Related Gene Expression in the Frontal Pole (Brodmann Area 10) is Altered in Subjects with Bipolar Disorder and Schizophrenia
Authors: Medina Adriana M. , Hagenauer Megan Hastings , Krolewski David M. , Hughes Evan , Thew Forrester Liam Cannon , Walsh David M. , Waselus Maria , Richardson Evelyn , Turner Cortney A. , Sequeira P. Adolfo , Cartagena Preston M. , Thompson Robert C. , Vawter Marquis P. , Bunney Blynn G. , Myers Richard M. , Barchas Jack D. , Lee Francis S.Y. , Schatzberg Alan F. , Bunney William E. , Akil Huda , Watson Stanley J. 
Published: June 2022

AbstractBrodmann Area 10 (BA10) is the largest cytoarchitectonic region of the human cortex, performing complex integrative functions. BA10 undergoes intensive adolescent grey matter pruning around the average age of onset for Bipolar disorder (BP) and Schizophrenia (SCHIZ), and its dysfunction is likely to underly aspects of their shared symptomology. In this study, we investigated the role of BA10 neurotransmission-related gene expression in BP and SCHIZ. We performed qPCR to measure the expression of 115 neurotransmission-related targets in control, BP, and SCHIZ post-mortem samples (n=72). We chose this method for its high sensitivity to detect low-level expression. We then bolstered our findings by performing a meta-analysis of publicly-released BA10 microarray data (n=101) and identified sources of convergence with our qPCR results. To improve interpretation, we compiled an unusually large database of clinical metadata for our samples. We used this data to explore the relationship between BA10 gene expression, therapeutics, substances of abuse, and symptom profiles, and validated these findings with publicly-available datasets. Using these convergent sources of evidence, we identified 20 neurotransmission-related genes that were differentially expressed in BP and SCHIZ in BA10. These results included a large diagnosis-related decrease in two important therapeutic targets with low-levels of expression, HTR2B and DRD4, as well as other findings related to dopaminergic, GABA-ergic and astrocytic function. We also observed that therapeutics may produce differential expression that opposes the effects of diagnosis. In contrast, substances of abuse showed similar effects on BA10 gene expression as BP and SCHIZ, potentially amplifying diagnosis-related dysregulation.
Increased aperiodic neural activity during sleep in major depressive disorder
Authors: Rosenblum Yevgenia , Bovy Leonore , Weber Frederik D. , Steiger Axel , Zeising Marcel , Dresler Martin 
Published: June 2022

AbstractBackgroundIn major depressive disorder (MDD), patients often express subjective sleep complaints while polysomnographic studies report only subtle alterations in neural oscillations. We hypothesize that the study of aperiodic electroencephalographic (EEG) dynamics, a marker of excitation-to-inhibition balance, may bring new insights into our understanding of sleep abnormalities in MDD. Specifically, we investigate aperiodic neural activity during sleep and its relationships with the time of sleep, depression severity, and responsivity to antidepressant treatment.MethodsPolysomnography was recorded in 38 MDD patients (in unmedicated and 7d medicated states) and 38 age-matched healthy controls (N1=76). Aperiodic EEG activity was evaluated using the Irregularly Resampled Auto-Spectral Analysis with slopes’ means and intra-individual variability as outcome measures. Depression severity was assessed with the Hamilton Depression Rating Scale. We replicated the analysis using two independently collected datasets of medicated patients and controls (N2=60, N3=80).ResultsUnmedicated patients showed flatter aperiodic slopes compared to controls during N2 (p-value=0.002) and steeper slopes compared to their later medicated state (p-values<0.02) during all sleep stages. Within unmedicated patients, slopes were flatter during late compared to early N2 sleep (p-value=0.006). Late N2 slopes further correlated with depression severity after 7d of antidepressant treatment (r=-0.34, p-value=0.04). Variability of slopes was increased in both unmedicated (p-values<0.03) and medicated states (p-values <0.006) of patients’ N2, N3, and REM sleep compared to controls.ConclusionFlatter slopes of aperiodic EEG power with increased variability may reflect unstable, noisy neural activity due to increased excitation-to-inhibition balance, representing a new disease-relevant feature of sleep in MDD.
Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering
Authors: Noshay Jaclyn M. , Walker Tyler , Romero Jonathon , Prates Erica , Eckert Carrie , Irle Stephan , Kainer David , Jacobson Daniel A. 
Published: June 2022

AbstractCRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been established for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model; iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for E. coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapien genomes. These novel encodings of sgRNAs greatly enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.
MCRS1 modulates the heterogeneity of microtubule minus-end morphologies in mitotic spindles
Authors: Laguillo-Diego Alejandra , Kiewisz Robert , Martí-Gómez Carlos , Baum Daniel , Müller-Reichert Thomas , Vernos Isabelle 
Published: June 2022

AbstractFaithful chromosome segregation requires the assembly of a bipolar spindle, consisting of two antiparallel microtubule (MT) arrays having most of their minus ends focused at the spindle poles and their plus ends overlapping in the spindle midzone. Spindle assembly, chromosome alignment and segregation require highly dynamic MTs. The plus ends of MTs have been extensively investigated; instead, their minus end structure remains poorly characterized. Here, we used large-scale electron tomography to study the morphology of the MT minus ends in 3D-reconstructed metaphase spindles in HeLa cells. In contrast to the homogeneous open morphology of the MT plus ends at the kinetochores, we found that MT minus ends are heterogeneous showing either open or closed morphologies. Silencing the minus-end specific stabilizer, MCRS1 increased the proportion of open MT minus ends. Altogether, these data suggest a correlation between the morphology and the dynamic state of the MT ends. Taking this heterogeneity of the MT minus end morphologies into account, our work indicates an unsynchronized behavior of MTs at the spindle poles, thus laying the ground for further studies on the complexity of MT dynamics regulation.
Composition of a low erucic acid, low fiber field pennycress (Thlaspi arvenseL) grain referred to as CoverCress™ developed through breeding and gene editing
Authors: Hartnell Gary , Lemke Shawna , Aulbach Chris 
Published: June 2022

AbstractField pennycress (Thlaspi arvenseL.) can be domesticated and cultivated as an annual in a corn / pennycress / soybean rotation where pennycress is sown and harvested as a cash cover crop. To improve the nutritional profile, pennycress was modified in two ways to achieve the same alterations in characteristics: 1) through selection of mutants and 2) through gene editing. These alterations resulted in a low erucic acid, lower fiber phenotype and the resulting products from these combinations are referred to as CoverCress CCWG-1 and CoverCress CCWG-2, respectively. CCWG-1 and CCWG-2 were planted as cover crops in five U.S. locations in the fall and the grain was harvested in the subsequent June. The grain was treated with 83 mM copper sulfate solution as a potential palatability agent for the naturally high glucosinolate levels, and was subsequently analyzed for nutrient (proximates, minerals, fatty acids, amino acids, and vitamins) and anti-nutrient (sinapine, glucosinolates, mold) content. The low erucic acid, lower fiber phenotype was consistently achieved across five lots. Generally, the nutrient content for both CCWG-1 and CCWG-2 were similar to canola grain. Canola grain contains the anti-nutrient sinapine but is significantly reduced to below the level of detection in CoverCress grain. As expected, CoverCress grain contains about 10 times more glucosinolates than canola. Based on the composition of CoverCress grain, it may provide a source of energy and amino acids to animals with restricted inclusion based on the glucosinolate content.
Modulation of Arm Swing Frequency and Gait Using Rhythmic Tactile Feedback
Authors: Noghani Mohsen Alizadeh , Hossain Md. Tanzid , Hejrati Babak 
Published: June 2022

AbstractDue to the neural coupling between upper and lower limbs and the importance of interlimb coordination in human gait, it has been recommended that focusing on appropriate arm swing should be a part of gait rehabilitation in individuals with walking impairments. Despite its vital importance, there is a lack of effective methods to exploit the potential of arm swing inclusion for gait rehabilitation. In this work, we present a lightweight and wireless haptic feedback system that provides highly synchronized vibrotactile cues to the arms to manipulate arm swing and investigate the effects of this manipulation on the subjects’ gait in a study with 12 participants (20-44 years). We found the developed system effectively adjusted the subjects’ arm swing and stride cycle times by significantly reducing and increasing those parameters by up to 20% and 35%, respectively, compared to their baseline values during normal walking with no feedback. Particularly, the reduction of arms’ and legs’ cycle times translated into a substantial increase of about 19.3% (on average) in walking speed. The response of the subjects to the feedback was also quantified in both transient and steady-state walking. The analysis of settling times from the transient responses revealed a fast and similar adaptation of both arms’ and legs’ movements to the feedback for reducing cycle time (i.e., increasing speed). Conversely, larger settling times and the time differences between arms’ and legs’ responses were observed due to feedback for increasing cycle times (i.e., reducing speed). The results clearly demonstrate the potential of the developed system to induce different arm-swing patterns as well as the ability of the proposed method to modulate key gait parameters through capitalizing on the interlimb neural coupling with implications for gait training.
Identification of gene fusions associated with amyotrophic lateral sclerosis
Authors: Raghav Yogindra , Dilliott Allison A. , Petrozziello Tiziana , Kim Spencer E. , Berry James D. , Cudkowicz Merit E. , Vakili Khashayar ,   NYGC ALS Consortium, Fraenkel Ernest , Farhan Sali M.K. , Sadri-Vakili Ghazaleh 
Published: June 2022

AbstractGenetics is an import risk factor for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease affecting motor neurons. Recent findings demonstrate that, in addition to specific genetic mutations, structural variants caused by genetic instability can also play a causative role in ALS. Genomic instability can lead to deletions, duplications, insertions, inversions, and translocations in the genome, and these changes can sometimes lead to fusion of distinct genes into a single transcript. While such gene fusion events have been studied extensively in cancer, they have not been thoroughly investigated in ALS. We leveraged bulk RNA-Seq data from human post-mortem samples to determine whether fusion events occur in ALS. We report for the first time the presence of gene fusion events in several brain regions as well as in spinal cord samples in ALS. Although most gene fusions were intra-chromosomal events between neighboring genes and present in both ALS and control samples, there was a significant increase in the number of unique gene fusion in ALS compared to controls. Lastly, we have identified specific gene fusions with a significant burden in ALS, that were absent from both control samples and known cancer gene fusion databases. Collectively, our findings reveal an enrichment of gene fusion in ALS and suggest that these events may be an additional genetic cause linked to ALS pathogenesis.
Acute stress impairs sensorimotor gating via the neurosteroid allopregnanolone in the prefrontal cortex
Authors: Cadeddu Roberto , Mosher Laura J , Nordkild Peter , Gaikwad Nilesh , Ratto Gian Michele , Scheggi Simona , Bortolato Marco 
Published: June 2022

ABSTRACTBackground and purposeAmple evidence indicates that environmental stress impairs information processing, yet the underlying mechanisms remain partially elusive. We showed that, in several rodent models of psychopathology, the neurosteroid allopregnanolone (AP) reduces the prepulse inhibition (PPI) of the startle, a well-validated index of sensorimotor gating. Since this GABAAreceptor activator is synthesized in response to acute stress, we hypothesized its participation in stress-induced PPI deficits.Experimental approachWe studied whether and how AP influences PPI in mice and rats; thereafter, we tested AP’s implication in the PPI deficits produced by several complementary regimens of acute and short-term stress (footshock, restraint, predator exposure, and sleep deprivation).Key resultsSystemic AP administration reduced PPI in C57BL/6J mice and Long-Evans, but not Sprague-Dawley, rats. These effects were reversed by isoallopregnanolone (isoAP), an endogenous AP antagonist, and the GABAAreceptor antagonist bicuculline and mimicked by AP infusions in the medial prefrontal cortex (mPFC). PPI was reduced by acute footshock, sleep deprivation as well as the combination of restraint and predator exposure in a time- and intensity-dependent fashion. Acute stress increased AP concentrations in the mPFC, and its detrimental effects on PPI were countered by systemic and intra-mPFC administration of isoAP.Conclusions and implicationsThese results collectively indicate that acute stress impairs PPI by increasing AP content in the mPFC. The confirmation of these mechanisms across distinct animal models and several acute stressors strongly supports the translational value of these findings and warrants future research on the role of AP in information processing.
Identification of ASPDH as a novel NAADP-binding protein
Authors: He Xiao , Kang Yunlu , Chen Lei 
Published: June 2022

AbstractNAADP is a signaling molecule that can induce calcium release from intracellular acidic stores. However, proteins that bind to NAADP are understudied. Here, we identify ASPDH as an NAADP-binding protein through biochemical purification from pig livers. ITC experiment using the recombinantly expressed protein shows a 1:1 binding stoichiometry and a Kd of 455 nM between NAADP and mouse ASPDH. In contrast, recombinantly expressed JPT2 and LSM12, two proteins previously identified as NAADP-receptors, show no binding in ITC experiments.
The effect of talent management and leadership styles on firms’ sustainable performance
Authors: Kafetzopoulos Dimitrios , Gotzamani Katerina 
Published: June 2022

PurposeThis study aims to develop a framework that examines how different leadership styles influence talent management (TM) and how these leadership styles and TM influence firms’ sustainable performance considering the moderating role of environmental dynamism.Design/methodology/approachTo achieve these objectives, an empirical survey was conducted among 480 participant firms in Greece. Hierarchical regression was performed to test the hypotheses.FindingsThis study reveals the significance of authoritative and transformational leadership on TM. The results also show the positive effect of talent development on sustainability. Moreover, entrepreneurial leadership is found to be the most influential style for economic sustainability, whereas transformational and transactional leaderships are the most influential leadership styles for social and environmental sustainability performance.Research limitations/implicationsThe data was collected at only one point in time, while sustainability is a continuous process. Moreover, only four leadership styles were addressed.Practical implicationsProper leadership style should be selected to facilitate different sustainability dimensions. Talent development is a valuable investment toward sustainable performance of firms.Originality/valueThis study contributes to the upper echelon theory, identifying whether and how different leadership styles affect TM and sustainability. The study also advances the human recourse development literature by critically reviewing and identifying the influence of TM on firms’ sustainable performance. Moreover, the role of environmental dynamism is revealed on all the above relationships.
A systematic review of women’s entrepreneurship in the sports industry: has anything changed?
Authors: Costa Carla , Miragaia Dina Alexandra Marques 
Published: June 2022

Purpose
Gender equity in entrepreneurship has been a global issue in several areas, and the sports context is no exception. Therefore, the present study aims to carry out a systematic review of the literature to analyze how female entrepreneurship in the context of sports organizations has been studied in the scientific community.

Design/methodology/approach
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was used to ensure the structure and quality of the study. Articles were obtained through a search in the Web of Science and Scopus databases, by using a set of inclusion/exclusion criteria (e.g. research equation, studies published only in English and classified as an article or review). A Microsoft Excel database was developed, from which tables and graphs were generated to help interpret the results.

Findings
The search resulted in 19 articles, grouped into four clusters: education and entrepreneurship, sports and entrepreneurial skills development, barriers to entrepreneurship and social entrepreneurship. The results indicate that despite all the efforts that have been made thus far, several barriers to female entrepreneurship remain. However, physical activity and sports have been found to aid the development of skills and abilities that may be fundamental to entrepreneurial initiatives. Formation in the context of higher education has also been identified as a fundamental tool for stimulating female entrepreneurship.

Practical implications
This study can have a positive impact on employment opportunities for women in the sport industry.

Originality/value
Besides providing ideas for future research, the results could support the development of policies to address gender equity issues and encourage women to take initiatives in sports entrepreneurship.
Exploring the first steps of retirement engagement: a conceptual model and field evidence
Authors: Eberhardt Wiebke , Post Thomas , Hoet Chantal , Brüggen Elisabeth 
Published: June 2022

PurposeThe authors develop and validate a conceptual model, the retirement engagement model (REM), to understand the relationships between behavioral engagement (retirement information search), cognitive factors and engagement (e.g. beliefs and financial knowledge), emotional engagement (e.g. anxiety), and socio-demographic factors. Approach: The authors derive the REM through a three-step procedure: (1) an extensive literature review, (2) interactive feedback sessions with experts to confirm the model's academic and managerial relevance, and (3) an empirical test of the REM with field data (N = 583). The authors use a partial least squares (PLS) structural equation model and examine heterogeneity through a finite mixture model.Design/methodology/approachAround the globe, people are insufficiently engaged with retirement planning. The customer engagement literature offers rich insights into antecedents, outcomes, and barriers to engagement. However, customer engagement literature lacks insights into cognitive, emotional and behavioral factors that drive engagement in retirement planning, a utilitarian service context, which is important for financial well-being.FindingsBeliefs such as perceived susceptibility, severity, benefits, barriers, and self-efficacy, together with trust and retirement anxiety, explain people's search for pension information. These factors can be used to define three clear, actionable segments of consumers.Originality/valueThe findings advance the customer engagement and transformative service research literature by generating insights on engagement with retirement planning, a utilitarian rather than hedonic service context that is especially relevant for financial well-being. The findings inform managerial practice and emphasize the relevance of including cognitive and emotional engagement factors that trigger behavioral engagement. The REM can help to improve pension communication. For example, the results indicate that marketers should stress the benefits of, rather than the barriers to, acquiring information.