bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome profiling of histone writers/erasers enzymes across spermatogenesis, mature sperm and pre-cleavage embryo: Implications in paternal epigenome transitions and inheritance mechanisms
Authors: Barbero Gastón , de Sousa Serro Maximiliano , Lujan Camila Perez , Vitullo Alfredo D. , González Candela R. , González Betina 
Published: May 2022

ABSTRACTAccumulating evidence points out that sperm carry epigenetic instructions to embryo in the form of retained histones marks and RNA cargo that can transmit metabolic and behavioral traits to offspring. However, the mechanisms behind epigenetic inheritance of paternal environment are still poorly understood. Here, we curated male germ cells RNA-seq data and analyzed the expression profile of all known histone lysine writers and erasers enzymes across spermatogenesis, unraveling the developmental windows at which they are upregulated, and the specific activity related to canonical and non-canonical histone marks deposition and removal. We also characterized the epigenetic enzymes signature in the mature sperm RNA cargo, showing most of them positive translation at pre-cleavage zygote, suggesting that paternally-derived enzymes mRNA cooperate with maternal factors to embryo chromatin assembly. Our study shows several histone modifying enzymes not described yet in spermatogenesis and even more, important mechanistic aspects behind transgenerational epigenetics. Epigenetic enzymes not only can respond to environmental stressors, but could function as vectors of epigenetic information and participate in chromatin organization during maternal-to-zygote transition.
Potentiating the cross-reactive IFN-γ T cell and polyfunctional T cell responses by heterologous GX-19N DNA booster in mice primed with either a COVID-19 mRNA vaccine or inactivated vaccine
Authors: Seo Yong Bok , Ko Ara , Shin Duckhyang , Kim Junyoung , Suh You Suk , Na Juyoung , Ryu Ji In , Sung Young Chul 
Published: May 2022

SummaryWaning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potentials of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T-cells to the SARS-CoV-2 variant of concern (VOC) compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T-cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.
P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway
Authors: Wang Zhijia , Mačáková Monika , Bugai Andrii , Kuznetsov Sergey G. , Hassinen Antti , Lenasi Tina , Potdar Swapnil , Friedel Caroline C. , Barborič Matjaž 
Published: May 2022

ABSTRACTPositive transcription elongation factor b (P-TEFb) is the crucial player in RNA polymerase II (Pol II) pause release that has emerged as a promising target in cancer. Because single-agent therapy may fail to deliver durable clinical response, targeting of P-TEFb shall benefit when deployed as a combination therapy. We screened a comprehensive oncology library and identified clinically relevant antimetabolites and Mouse double minute 2 homolog (MDM2) inhibitors as top compounds eliciting p53-dependent death of colorectal cancer cells in synergy with selective inhibitors of P-TEFb. While the targeting of P-TEFb augments apoptosis by antimetabolite 5-fluorouracil, it switches the fate of cancer cells by the non-genotoxic MDM2 inhibitor Nutlin-3a from cell-cycle arrest to apoptosis. Mechanistically, the fate switching is enabled by the induction of p53-dependent pro-apoptotic genes and repression of P-TEFb-dependent pro-survival genes of the PI3K-AKT signaling cascade, which stimulates Caspase 9 and intrinsic apoptosis pathway in BAX/BAK-dependent manner. Finally, combination treatments trigger apoptosis of cancer cell spheroids. Together, co-targeting of P-TEFb and suppressors of intrinsic apoptosis could become a viable strategy to eliminate cancer cells.
Defining specific cell states of MPTP-induced Parkinson’s disease by single-nucleus RNA sequencing
Authors: Guo Yunxia , Ma Junjie , Huang Hao , Xu Jitao , Ye Kaiqiang , Chang Ning , Ge Qinyu , Wang Guangzhong , Zhao Xiangwei 
Published: May 2022

AbstractParkinson’s disease (PD), a neurodegenerative disease with the impairment of movement execution that is related to age, genetic and environmental factors. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on cell-gene of PD has not been fully elucidated. By single-nucleus RNA sequencing, we uncovered the PD-specific cells and revealed remarkable changes in their cellular states, including astrocytosis, endothelial cells absence, as well as a cluster of PD-exclusive medium spiny neuron cells. Furthermore, trajectory analysis of astrocyte and endothelial cells populations predicted candidate target gene sets that might be associated with PD. Notably, the detailed regulatory roles of astrocyte-specific transcription factors Dbx2 and Sox13 in PD were first revealed in our work. Finally, we characterized the cell-cell communications of PD-specific cells and found that the overall communication strength was enhanced in PD compared with matched control, especially the signaling pathways of NRXN and NEGR. Our work provides comprehensive overview on the changes of cellular states of the MPTP-induced mouse brain.
Confounding factors of Alzheimer’s disease plasma biomarkers and their impact on clinical performance
Authors: Binette Alexa Pichet , Janelidze Shorena , Cullen Nicholas , Dage Jeffrey L. , Bateman Randall J. , Zetterberg Henrik , Blennow Kaj , Stomrud Erik , Mattsson-Carlgren Niklas , Hansson Oskar 
Published: May 2022

AbstractINTRODUCTIONPlasma biomarkers will likely revolutionize the diagnostic work-up of Alzheimer’s disease (AD) globally. Before widespread use, we need to determine if confounding factors affect the levels of these biomarkers, and their clinical utility.METHODSParticipants with plasma and CSF biomarkers, creatinine, body mass index (BMI), and medical history data were included (BioFINDER-1: n=748, BioFINDER-2: n=421). We measured beta-amyloid (Aβ42, Aβ40), phosphorylated tau (p-tau217, p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).RESULTSIn both cohorts, creatinine and BMI were the main factors associated with NfL, GFAP, and to a lesser extent with p-tau. However, adjustment for BMI and creatinine had only minor effects in models predicting either the corresponding levels in CSF or subsequent development of dementia.DISCUSSIONCreatinine and BMI are related to certain plasma biomarkers levels, but they do not have clinically relevant confounding effects for the vast majority of individuals.
Deciphering the conformational dynamics of gephyrin-mediated collybistin activation
Authors: Imam Nasir , Choudhury Susobhan , Hemmen Katherina , Heinze Katrin G. , Schindelin Hermann 
Published: May 2022

AbstractEfficient neuronal signaling depends on the proper assembly of the postsynaptic neurotransmitter machinery and at inhibitory GABAergic synapses is controlled by the scaffolding protein gephyrin and collybistin, a Dbl-family guanine nucleotide exchange factor and neuronal adaptor protein. Collybistin usually contains an N-terminal SH3 domain and exists in closed/inactive or open/active states. Here, we elucidate the molecular basis of the gephyrin-collybistin interaction with newly designed collybistin FRET sensors. Using fluorescence lifetime-based FRET measurements, we deduce the affinity of the gephyrin-collybistin complex, thereby confirming that the C-terminal dimer-forming E domain binds collybistin, an interaction, which does not require E domain dimerization. Simulations based on fluorescence lifetime and sensor distance distributions reveal a dynamic behavior of the SH3 domain already in the closed state of collybistin. Finally, our data provide strong evidence for a collybistin-gephyrin communication network, where, unexpectedly, switching of collybistin from closed/inactive to open/active states is efficiently triggered by gephyrin.
LOMAR: LOcalization Microscopy Analysis in R
Authors: Theiss Maria , Brazma Alvis , Uhlmann Virginie , Hériché Jean-Karim 
Published: May 2022

SummaryIn single molecule localization microscopy data (SMLM), individual instances of a macromolecular complex come in the form of point sets. Particle averaging, which combines localization data from a large number of instances, is often used to overcome experimental noise and obtain a refined view of the underlying structure. However, SMLM point sets are often heterogeneous due to biological variations in the structure they represent and must be partitioned into groups with similar structure before averaging which calls for being able to compute structurally-relevant similarity measures between sets of points. Here we introduce LOMAR (LOcalization Microscopy Analysis in R) a software package for the R programming language that enables comparison of point sets through implementation of several point sets registration methods and similarity measures derived from topological data analysis. We demonstrate use of the package on real and simulated SMLM data of nuclear pore complexes.
Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila
Authors: Rabah Yasmine , Frances Raquel , Plaçais Pierre-Yves , Preat Thomas 
Published: May 2022

AbstractGlucose is the primary source of energy for the brain. However, it remains controversial whether, upon neuronal activation, glucose is primarily used by neurons for ATP production, or if it is partially oxidized in astrocytes, as proposed by the astrocyte-neuron lactate shuttle model for glutamatergic neurons. Thus, an in vivo picture of glucose metabolism during cognitive processes is missing. Here, we uncover in Drosophila a glia-to-neuron alanine transfer that sustains memory formation. Following associative conditioning, glycolysis in glial cells produces alanine, which is back-converted into pyruvate in mushroom body cholinergic neurons to uphold their increased mitochondrial needs. Alanine, as a mediator of glia-neuron coupling, could be an alternative to lactate in cholinergic systems. In parallel, a dedicated glial glucose transporter imports glucose specifically for long-term memory, by directly transferring it to neurons for use by the pentose phosphate pathway. Our results demonstrate in vivo the compartmentalization of glucose metabolism between neurons and glial cells during memory formation.
The optimal clutch size revisited: separating individual quality from the parental survival costs of reproduction
Authors: Winder Lucy A. , Simons Mirre J.P. , Burke Terry 
Published: May 2022

AbstractLife-history theory, central to our understanding of diversity in morphology, behaviour and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness – reproductive effort and survival – questioning the theory’s general validity. We used a meta-analysis to separate the effects of individual quality (positive survival/reproduction correlation) from the costs of reproduction (negative survival/reproduction correlation) using studies of reproductive effort and parental survival in birds. Experimental enlargement of brood size caused reduced parental survival. However, the effect size of brood size manipulation was small and opposite to the effect of phenotypic quality, as we found that individuals that naturally produced larger clutches also survived better. The opposite effects on parental survival in experimental and observational studies of reproductive effort provides the first meta-analytic evidence for theory suggesting that quality differences mask trade-offs. Fitness projections using the overall effect size revealed that reproduction presented negligible costs, except when reproductive effort was forced beyond the maximum level observed within species, to that seen between species. We conclude that there is little support for the most fundamental life-history trade-off, between reproductive effort and survival, operating within a population. We suggest that within species, the fitness landscape of the reproduction–survival trade-off is flat until it reaches the boundaries of the between-species fast–slow life-history continuum. Our results provide a quantitative explanation as to why the costs of reproduction are not apparent and why variation in reproductive effort persists within species.
Hippocampal-medial entorhinal circuit is differently organized along the dorsoventral axis in rodents
Authors: Ohara Shinya , Rannap Märt , Tsutsui Ken-ichiro , Draguhn Andreas , Egorov Alexei V. , Witter Menno P. 
Published: May 2022

SummaryThe general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projection to the medial EC (MEC). Whereas dorsal hippocampal projections are confined to the dorsal MEC and preferentially target layer Vb (LVb) over layer Va (LVa) neurons, the ventral hippocampus innervates the entire dorsoventral extent of MEC. In the ventral MEC, these projections innervate neurons in both LVa and LVb. In contrast, in the dorsal MEC, ventral hippocampal projections target mainly LVa neurons. As LVa neurons project to telencephalic structures, our findings indicate that the ventral hippocampus regulates LVa-mediated entorhinal-neocortical output from both the dorsal and ventral MEC. Overall, the marked dorsoventral differences in hippocampal-entorhinal connectivity impose important constraints on signal flow in hippocampal-neocortical circuits.
Can venting hamper high emotionally intelligent recipient's reattachment to work?
Authors: Shah Syed Jamal , Huang Cheng 
Published: May 2022

PurposeThis study investigates how healthcare workers' venting - an emotion-focused form of coping during non-working hours - has unintended costs via its effect on spouses' reattachment to work if life partners are dual-earners. Research also examined anxiety as a causal mechanism that connects the receipt of venting with failure in reattachment to work. Lastly, our theory suggests that not everyone has the same experience with venting; the effect varies at different levels of emotional intelligence.Design/methodology/approachMultilevel path analysis using MPlus 8.3 was conducted to examine the daily survey data obtained from 101 spouses of healthcare workers over four consecutive workdays using the experience sampling technique.FindingsThe results suggested that receipt of venting increases anxiety and adversely influences reattachment to work through increased anxiety. The findings supported the suggested model's predictions, indicating that anxiety mediated the link between the receipt of venting and reattachment to work, and the mediation was partial. Further, emotional intelligence buffers the positive effect of receipt of venting on anxiety and the negative on reattachment to work. Lastly, the findings indicate that moderated mediation exists: the indirect effect of receipt of venting on reattachment to work is not as strong at higher levels of emotional intelligence.Originality/valueThis study is the first attempt that identified the receipt of venting as a predictor of reattachment to work. Moreover, up till now, no study has examined the mediating role of anxiety in the relationship between receipt of venting and reattachment to work. Finally, this is the preliminary effort that validated the moderating role of emotional intelligence on the above-mentioned links.
Business model innovation based on new technologies – is it resources driven and dependent?
Authors: Mielcarek Paweł , Dymitrowski Adam 
Published: May 2022

Purpose
The purpose of this paper is to analyse the significance and impact of different resource types and their features on the operation of business model innovation (BMI) based on new technologies and their effects. Specifically, the relationships of nine different types of resources, as well as their features in terms of VRIO and VARIM concepts, and 10 BMI effects of operation were examined. The significance and impact of resources on the operation of BMI are pretty well established in the literature. However, when the analysis is narrowed down to BMI based on new technologies, there is very little research in this field. This is partly because of the subject’s novelty and the wide range and complexity of this phenomenon.

Design/methodology/approach
The research covers 483 Polish companies that implement BMI based on new technology. For gathering data, the computer-assisted telephone interview method was used. Analysis is based on Spearman correlation. Results meet the requirement of p-value = 0.01 and are statistically significant and representative.

Findings
The main findings of this paper is that there is a need for building interdependency and synergy between individual types and features of resources and thus properly arrange and orchestrate them to succeed. Moreover, there are several patterns that stand out from the analysis, with the leading role of employees, technology, dynamic capabilities and know-how being the key enablers of BMI transformation.

Practical implications
The paper presents several compounds and relationships that shed light on the application and effects of BMI based on new technologies in terms of resource utilization, which can help business owners and senior managers to make consistent decisions in matching and orchestrating resources.

Originality/value
This study clarifies theoretical concepts building a resource-based view (VRIO, VARIM, dynamic capabilities, etc.) and their impact on BMI based on new technology. The results expand and complement existing research by shedding new light on resource utilization and orchestration.
The mediating role of self-efficacy in the relationship between emotional intelligence and organizational commitment
Authors: Hameli Kujtim , Ordun Güven 
Published: May 2022

PurposeThis study examines the relationship between emotional intelligence, self-efficacy and organizational commitment, focusing on the mediating role of self-efficacy in the relationship between emotional intelligence and organizational commitment.Design/methodology/approachThe authors used an online survey to collect data for this purpose. The sample consisted of 145 employees of different organizations in Kosovo. To test the hypothetical model, a mediation analysis was conducted using PROCESS Model Type 4.FindingsThe results show that emotional intelligence is positively related to self-efficacy and that self-efficacy is positively related to organizational commitment. Furthermore, the results of the mediation analysis confirm that the relationship between emotional intelligence and organizational commitment is mediated by self-efficacy.Research limitations/implicationsFor future research, the authors recommend using the sub-dimensions of the above variables to test this model, and multiple models could be formulated. At the same time, the survey can be applied to managers to examine their emotional intelligence and to determine whether emotional intelligence influences their organizational commitment through self-efficacy. Consistent with the findings of this study, managers and executives in organizations should consider the emotional intelligence of their employees and that the employees with higher emotional intelligence have higher self-efficacy and can perform better.Originality/valueThis study extends the current literature in organizational behavior and provides a comprehensive understanding of the relationship between emotional intelligence, self-efficacy and organizational commitment. This study was also conducted in a developing country context, which can always lead to different results than studies conducted in developed countries.
A moving average denoise operator and grey discrete production process quality prediction model
Authors: Li Qiang , Liu Sifeng , Lin Changhai 
Published: May 2022

PurposeThe purpose of this paper is to solve the problem of quality prediction in the equipment production process and provide a method to deal with abnormal data and solve the problem of data fluctuation.Design/methodology/approachThe analytic hierarchy process-process failure mode and effect analysis (AHP-PFMEA) structure tree is established based on the analytic hierarchy process (AHP) and process failure mode and effect analysis (PFMEA). Through the failure mode analysis table of the production process, the weight of the failure process and stations is determined, and the ranking of risk failure stations is obtained so as to find out the serious failure process and stations. The spectrum analysis method is used to identify the fault data and judge the “abnormal” value in the fault data. Based on the analysis of the impact, an “offset operator” is designed to eliminate the impact. A new moving average denoise operator is constructed to eliminate the “noise” in the original random fluctuation data. Then, DGM (1,1) model is constructed to predict the production process quality.FindingsIt is discovered the “offset operator” can eliminate the impact of specific shocks effectively, moving average denoise operator can eliminate the “noise” in the original random fluctuation data and the practical application of the shown model is very effective for quality predicting in the equipment production process.Practical implicationsThe proposed approach can help provide a good guidance and reference for enterprises to strengthen onsite equipment management and product quality management. The application on a real-world case showed that the DGM (1,1) grey discrete model is very effective for quality predicting in the equipment production process.Originality/valueThe offset operators, including an offset operator for a multiplicative effect and an offset operator for an additive effect, are proposed to eliminate the impact of specific shocks, and a new moving average denoise operator is constructed to eliminate the “noise” in the original random fluctuation data. Both the concepts of offset operator and denoise operator with their calculation formulas were first proposed in this paper.