bluuebunny/crossref_metadata_2025 huggingface dataset:
A Lockdown a Day Keeps the Doctor Away: The Global Effectiveness of Non-Pharmaceutical Interventions in Mitigating the Covid-19 Pandemic
Authors: Levelu Anthonin , Sandkamp Alexander
Published: January 2024

Countries have employed a variety of non-pharmaceutical interventions (NPIs) in order to curtail the Covid-19 pandemic. However, the success of individual measures in reducing the number of infections remains controversial. This article exploits a panel dataset of 181 countries to estimate the effects of 12 NPIs on the spread of the disease in 2020. The employed fixed effects estimation greatly reduces endogeneity concerns. Estimated coefficients imply that while almost all measures had a dampening effect on the reproduction rate of the virus, school closings and restrictions on gatherings were most effective. The obligation to wear face masks was more effective during the second wave. Measures requiring significant resources, such as testing, were more effective in developed countries. (JEL codes: C13, C23, D04, and I18)
Mask refinement network for tooth segmentation on panoramic radiographs
Authors: Niu Li , Zhong Shengwei , Yang Zhiyu , Tan Baochun , Zhao Junjie , Zhou Wei , Zhang Peng , Hua Lingchen , Sun Weibin , Li Houxuan
Published: January 2024

Objectives

Instance-level tooth segmentation extracts abundant localization and shape information from panoramic radiographs (PRs). The aim of this study was to evaluate the performance of a mask refinement network that extracts precise tooth edges.

Methods

A public dataset which consists of 543 PRs and 16211 labelled teeth was utilized. The structure of a typical Mask Region-based Convolutional Neural Network (Mask RCNN) was used as the baseline. A novel loss function was designed focus on producing accurate mask edges. In addition to our proposed method, 3 existing tooth segmentation methods were also implemented on the dataset for comparative analysis. The average precisions (APs), mean intersection over union (mIoU), and mean Hausdorff distance (mHAU) were exploited to evaluate the performance of the network.

Results

A novel mask refinement region-based convolutional neural network was designed based on Mask RCNN architecture to extract refined masks for individual tooth on PRs. A total of 3311 teeth were correctly detected from 3382 tested teeth in 111 PRs. The AP, precision, and recall were 0.686, 0.979, and 0.952, respectively. Moreover, the mIoU and mHAU achieved 0.941 and 9.7, respectively, which are significantly better than the other existing segmentation methods.

Conclusions

This study proposed an efficient deep learning algorithm for accurately extracting the mask of any individual tooth from PRs. Precise tooth masks can provide valuable reference for clinical diagnosis and treatment. This algorithm is a fundamental basis for further automated processing applications.
A novel regulatory sex-skewing method that inhibits testicular DPY30 expression to increase female rate of dairy goat offspring
Authors: He Huanshan , Li Xiang , Li Jintao , Ning Yong , Luo Jun , Shi Huaiping
Published: January 2024

The demand for goat milk products has increased exponentially with the growth of the global population. The shortage of dairy products will be addressed extraordinarily by manipulating the female rate of goat offspring to expand the goat population and goat milk yield. No studies have reported bioinformatic analyses of X- and Y-bearing sperm of dairy goats, although this will contribute to exploring novel and applied sex-skewing technologies. Regulatory subunit of the histone methyltransferase complex (DPY30) was determined to be the key differentially expressed protein (DEP) among 15 DEPs identified in the present study. The spatiotemporal expression of DPY30 strongly suggested a functional involvement of the protein in spermatogenesis. DPY30 promoted meiosis via upregulating SYCP3, which played a crucial role in mediating sex ratio skewing in goats. Although DPY30 suppressed the self-renewal of spermatogonia stem cells through AKT/PLZF, DPY30 inhibition in the testis did not induce testicular dysgenesis. Based on the biosafety assessment in mice testes, lentivirus-mediated DPY30 knockdown in bucks’ testes increased X-bearing sperm proportion and female kids’ rate (22.8 percentage points) without affecting sperm quality, pregnancy rate, and kidding rate. This study provides the first evidence of the DEGs in the sexed sperm of dairy goats. DPY30 inhibition in the testes of bucks increased the female kids’ rate without influencing reproductive performance. The present study provides evidence for expanding the female dairy goat population to address the concern of dairy product shortage.
Dissolution of ribonucleoprotein condensates by the embryonic stem cell protein L1TD1
Authors: Jin Sang Woo , Seong Youngmo , Yoon Dayoung , Kwon Young-Soo , Song Hoseok
Published: January 2024

L1TD1 is a cytoplasmic RNA-binding protein specifically expressed in pluripotent stem cells and, unlike its mouse ortholog, is essential for the maintenance of stemness in human cells. Although L1TD1 is the only known protein-coding gene domesticated from a LINE-1 (L1) retroelement, the functional legacy of its ancestral protein, ORF1p of L1, and how it is manifested in L1TD1 are still unknown. Here, we determined RNAs associated with L1TD1 and found that, like ORF1p, L1TD1 binds L1 RNAs and localizes to high-density ribonucleoprotein (RNP) condensates. Unexpectedly, L1TD1 enhanced the translation of a subset of mRNAs enriched in the condensates. L1TD1 depletion promoted the formation of stress granules in embryonic stem cells. In HeLa cells, ectopically expressed L1TD1 facilitated the dissolution of stress granules and granules formed by pathological mutations of TDP-43 and FUS. The glutamate-rich domain and the ORF1-homology domain of L1TD1 facilitated dispersal of the RNPs and induced autophagy, respectively. These results provide insights into how L1TD1 regulates gene expression in pluripotent stem cells. We propose that the ability of L1TD1 to dissolve stress granules may provide novel opportunities for treatment of neurodegenerative diseases caused by disturbed stress granule dynamics.
The Use of Lay Drafts as Drafting Instructions: A Case Study of Nigeria
Authors: Dauda Michael Habila
Published: January 2024

Lay drafts as used in Nigeria are erroneously thought to speed up the drafting process but they are insufficient as drafting instruction and they reduce the quality and effectiveness of legislation. Good drafting instructions will lead to good legislation while bad drafting instructions will lead to the drafter’s failure to grasp the fundamentals of the policy, and failure to get the draft right, and ultimately failure to achieve the purpose of the policy. This article is intended to analyse the drafting process in Nigeria to point out the causes of ineffectiveness in legislation and how that can be improved.
Rapid assessment of coverage of doxycycline/azithromycin chemoprophylaxis against leptospirosis following floods, Kozhikode district, Kerala, 2018
Authors: Sasikumar Harishankar , Ganeshkumar Parasuraman , R Sabarinathan , Rubeshkumar Polani , Venkatasamy Vettrichelvan , Murhekar Manoj
Published: January 2024

Background

We estimated coverage of doxycycline chemoprophylaxis (200 mg once weekly) following floods in Kerala, India.

Methods

A cross-sectional survey was conducted to gather data on exposure to flood or stagnant water and receipt and consumption of chemoprophylaxis.

Results

Of 1573 individuals interviewed, 152 (10%) were exposed to flood water. Among these, 119 (78%) were eligible for chemoprophylaxis. Of those eligible, 58 (38.2% [95% confidence interval 30.8 to 46.1]) reported consuming the prescribed chemoprophylaxis.

Conclusions

Despite the availability of chemoprophylaxis, consumption was less than ideal. We recommend targeted interventions to improve chemoprophylaxis coverage and public awareness campaigns to enhance its consumption among the affected population.
Effect of Vitamin D supplementation on blood pressure in hypertensive individuals with hypovitaminosis D: a systematic review and meta-analysis
Authors: Serra Matheus Oliveira , de Macedo Leandro Roberto. , Silva Maísa , Lautner Roberto Queiroga
Published: January 2024

In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of Vitamin D supplementation on SBP and DBP levels in individuals with hypertension and hypovitaminosis D. PubMed, Scopus, Web of Science, and SciELO were systematically searched for relevant publications until January 2023. The review has been registered at PROSPERO (CRD42023400035). To compare the effects of vitamin D with placebo, the mean differences with 95% confidence intervals (95% CIs) were pooled based on the random-effects model. Subgroup analyses were performed to identify the source of heterogeneity, and assessment of study quality was conducted using the GRADE approach. Publication bias was evaluated using funnel plots and Egger's tests. In total, 14 randomized controlled trials (RCTs) were included in this systematic review, and 11 trials were selected for meta-analysis. The data showed that Vitamin D significantly decreased SBP levels; however, it did not affect DBP levels. In subgroup analysis, Vitamin D supplementation significantly decreased in SBP in studies involving individuals over 60 years of age, with a dose greater than 400 000 IU, duration greater than 8 weeks, frequency of weekly supplementation in studies conducted in Asia. In addition, subgroup analysis revealed a significant reduction in DBP in the weekly frequency subgroups and in the studies carried out in Asia. This meta-analysis indicated that Vitamin D significantly reduced the SBP in individuals with hypertension and hypovitaminosis D. Further, well designed trials are necessary to validate these results.
Utility of peak inspiratory flow measurement for dry powder inhaler use in chronic obstructive pulmonary disease
Authors: Loh Chee Hong , Ohar Jill A.
Published: January 2024

Purpose of review

Every type of dry powder inhaler (DPI) device has its own intrinsic resistance. A patient's inspiratory effort produces a pressure drop that determines the inspiratory flow, depending on the inhaler's specific internal resistance. Optimal peak inspiratory flow (PIF) is needed for effective release of dry powder, disaggregation of drug-carrier agglomerates, and optimal deposition of respirable drug particles, particularly generation of a high fine-particle fraction to reach the small airways of the lungs. However, standardized recommendations for PIF measurements are lacking and instructions appeared vague in many instances.

Recent findings

Suboptimal PIFs are common in outpatient chronic obstructive pulmonary disease (COPD) patients and during acute exacerbations of COPD, and are associated with increased healthcare resource utilization. There is significant variation in the results of studies which is in part related to different definitions of optimal flow rates, and considerable variation in how PIF is measured in clinical and real-life studies.

Standardization of technique will facilitate comparisons among studies. Specific recommendations for PIF measurement have been proposed to standardize the process and better ensure accurate and reliable PIF values in clinical trials and clinical practice. Clinicians can then select and personalize the most appropriate inhaler for their patients and help them achieve the optimal PIF needed for effective drug dispersion.
Neurotransmitter Genes in the Nucleus Accumbens that Are Involved in the Development of Behavioral Pathology After Positive Fighting Experiences and Their Deprivation. A Conceptual Paradigm for Neurogenomic Data Analysis
Authors: Kudryavtseva Natalia N. , Smagin Dmitry A. , Redina Olga E. , Kovalenko Irina L. , Galyamina Anna G. , Babenko Vladimir N.
Published: January 2024

It has been shown earlier that repeated positive fighting experience in daily agonistic interactions is accompanied by the development of psychosis-like behavior with signs of an addiction-like state associated with changes in the expression of genes encoding the proteins involved in the main neurotransmitter events in some brain regions of aggressive male mice. Fighting deprivation (a no-fight period of 2 weeks) causes a significant increase in their aggressiveness. This paper is aimed at studying—after a period of fighting deprivation—the involvement of genes (associated with neurotransmitter systems within the nucleus accumbens) in the above phenomena. The nucleus accumbens is known to participate in reward-related mechanisms of aggression. We found the following differentially expressed genes (DEGs), whose expression significantly differed from that in controls and/or mice with positive fighting experience in daily agonistic interactions followed by fighting deprivation: catecholaminergic genesTh,Drd1,Drd2,Adra2c,Ppp1r1b, andMaoa; serotonergic genesMaoa,Htr1a,Htr1f, andHtr3a; opioidergic genesOprk1,Pdyn, andPenk; and glutamatergic genesGrid1,Grik4,Grik5,Grin3a,Grm2,Grm5,Grm7, andGad1.The expression of DEGs encoding proteins of the GABAergic system in experienced aggressive male mice mostly returned to control levels after fighting deprivation except forGabra5. In light of the conceptual paradigm for analyzing data that was chosen in our study, the aforementioned DEGs associated with the behavioral pathology can be considered responsible for consequences of aggression followed by fighting deprivation, including mechanisms of an aggression relapse.
Indirect effects of habitat amount mediated by habitat configuration determine bat diversity at the landscape-scale in Peninsular Malaysia
Authors: Hazard Quentin C.K. , Yoh Natalie , Moore Jonathan , Senawi Juliana , Gibson Luke , Froidevaux Jérémy S.P. , Palmeirim Ana Filipa
Published: January 2024

The impacts of fragmentation are often overlooked in landscape studies investigating how habitat loss impacts biodiversity, despite the casual relationship linking both processes. As habitat loss is the primary cause of fragmentation, understanding the inter-related effects of these twin processes on biodiversity is key to minimise biodiversity loss. Here we assess how habitat amount and configuration influence insectivorous bat assemblages, considering both the direct effects of these processes, as well as the indirect effects of habitat amount mediated through configuration. Bats were acoustically surveyed along independent gradients of habitat amount (forest cover) and configuration (number of patches and edge density) across 28 insular landscapes embedded within a Malaysian hydroelectric reservoir. Using Structural Equation Modelling, the direct and indirect effects of habitat amount were examined on bat sonotype richness, total, and guild-specific activity (forest, edge and open-space foragers). Forest cover had a direct and positive effect on sonotype richness and forest forager activity. The quadratic relationship linking edge density and forest cover was strong and overall positive, but while below 30% of forest cover, increasingly forested landscapes had increasingly high edge densities, the opposite pattern was observed in more forested landscapes. On the other hand, increasingly forested landscapes consistently harboured less patches. Owing to the overall low habitat amount in our landscapes and negative edge effects, the indirect effects of forest cover (mediated through edge density) were therefore negative on sonotype richness, outweighing any positive direct effect. The number of patches had little effect on the bat assemblage, except on total activity which was higher in landscapes harbouring more forest patches. As a result, negative indirect effects of forest cover mediated through number of patches were only observed on total activity. Our results highlight that, in natural settings, habitat amount can hardly be altered without influencing habitat configuration, thereby preventing any independent management of these threats. Minimising habitat loss is therefore essential to balance the associated prevailing negative effects of fragmentation on insectivorous bats across tropical forests.
Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity
Authors: Villa-González Mario , Rubio Marina , Martín-López Gerardo , Mallavibarrena Paula R , Vallés-Saiz Laura , Vivien Denis , Wandosell Francisco , Pérez-Álvarez Maria José
Published: January 2024

Ischemic stroke is a sudden and acute disease characterized by neuronal death, glia activation, and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Microglial activation involves functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such microglial activation is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia.

Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury.

Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.
Decoding of resting-state using task-based multivariate pattern analysis supports the Incentive-Sensitization Theory in nicotine use disorder
Authors: Lor Cindy S. , Steyrl David , Zhang Mengfan , Zhou Feng , Becker Benjamin , Herdener Marcus , Quednow Boris B. , Haugg Amelie , Scharnowski Frank
Published: January 2024

Background

The Incentive-Sensitization Theory postulates that addiction is primarily driven by the sensitization of the brain’s reward system to addictive substances, such as nicotine. According to this theory, exposure to such substances leads to an increase in ‘wanting’, while ‘liking’ the experience remains relatively unchanged. Although this candidate mechanism has been well substantiated through animal brain research, its translational validity for humans has only been partially demonstrated so far, with evidence from human neuroscience data being very limited.

Methods

From fMRI data of N=31 individuals with Nicotine Use Disorder, we created multivoxel patterns capable of capturing wanting and liking-related dimensions from a smoking cue-reactivity task. Using these patterns, we then designed a novel resting-state ‘reading’ method to evaluate how much wanting or liking still persist as a neural trace after watching the cues.

Results

We found that the persistence of wanting-related brain patterns at rest increases with longer smoking history but this was not the case for liking-related patterns. Interestingly, such behavior has not been observed for non-temporal measures of smoking intensity.

Conclusion

This study provides basic human neuroscience evidence that the dissociation between liking and wanting escalates over time, further substantiating the Incentive-Sensitization Theory, at least for Nicotine Use Disorder. These results suggest that treatment approaches could be personalized to account for the variability in individuals’ neural adaptation to addiction by considering how individuals differ in the extent to which their incentive salience system is sensitized.
Three new species in the Onygenaceae isolated from marine environment
Authors: Wang Meng-Meng , Li Qi , Li Wei , Cai Lei
Published: January 2024

Several fungal isolates affiliated withAphanoascusandChrysosporiumwere obtained from the sediments of Chinese seas by us. Among them, one newAphanoascusspecies (A. sedimenticola) and two newChrysosporiumspecies (C. microsporum, C. sphaerospermum) were taxonomically identified and recognized based on phylogenetic analyses and morphological characteristics. This paper provided the detailed descriptions and illustrations of the three new taxa.
A genetically-encoded fluorescent biosensor for visualization of acetyl-CoA in live cells
Authors: Smith Joseph J. , Valentino Taylor R. , Ablicki Austin H. , Banerjee Riddhidev , Colligan Adam R. , Eckert Debra M. , Desjardins Gabrielle A. , Diehl Katharine L.
Published: January 2024

Acetyl-coenzyme A is a central metabolite that participates in many cellular pathways. Evidence suggests that acetyl-CoA production and consumption are highly compartmentalized in mammalian cells. Yet methods to measure acetyl-CoA in living cells are lacking. In this work, we engineer an acetyl-CoA biosensor from the bacterial protein PanZ and circularly permuted green fluorescent protein (cpGFP). We biochemically characterize the sensor and demonstrate its selectivity for acetyl-CoA over other CoA species. We then deploy the biosensor in E. coli and HeLa cells to demonstrate its utility in living cells. In E. coli, we show that the biosensor enables detection of rapid changes in acetyl-CoA levels. In human cells, we show that the biosensor enables subcellular detection and reveals the compartmentalization of acetyl-CoA metabolism.
Mitochondrial choline import regulates purine nucleotide pools via SLC25A48
Authors: Verkerke Anthony R.P. , Shi Xu , Abe Ichitaro , Gerszten Robert E. , Kajimura Shingo
Published: January 2024

Choline is an essential nutrient for cellular metabolism, including the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A critical step of choline catabolism is the mitochondrial import and synthesis of chorine-derived methyl donors, such as betaine. However, the underlying mechanisms and the biological significance of mitochondrial choline catabolism remain insufficiently understood. Here, we report that a mitochondrial inner-membrane protein SLC25A48 controls mitochondrial choline transport and catabolismin vivo. We demonstrate that SLC25A48 is highly expressed in brown adipose tissue and required for whole-body cold tolerance, thermogenesis, and mitochondrial respiration. Mechanistically, choline uptake into the mitochondrial matrix via SLC25A48 facilitates betaine synthesis and one-carbon metabolism. Importantly, cells lacking SLC25A48 exhibited reduced synthesis of purine nucleotides and failed to initiate the G1-to-S phase transition, thereby leading to cell death. Taken together, the present study identified SLC25A48 as a mitochondrial carrier that mediates choline import and plays a critical role in mitochondrial respiratory capacity, purine nucleotide synthesis, and cell survival.

Key points

SLC25A48 is required for mitochondrial choline uptake.

Mitochondrial choline uptake regulates one-carbon contribution to purine nucleotide synthesis.

Brown fat thermogenesis requires mitochondrial choline catabolism for respiratory capacity.

Cancer cells require mitochondrial choline uptake for cell survival.
Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells
Authors: Zuniga Alfredo , Han Jiawei , Miller-Crews Isaac , Agee Laura A. , Hofmann Hans A. , Drew Michael R.
Published: January 2024

Contextual fear conditioning has been shown to activate a set of “fear ensemble” cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells – the “extinction ensemble.” Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.
Functional consequences of reductive protein evolution in a minimal eukaryotic genome
Authors: Jiang Jason , Qu Rui , Grigorescu Maria , Zhao Winnie , Reinke Aaron W.
Published: January 2024

Microsporidia are parasites with the smallest known eukaryotic genomes. The extent of protein loss in these organisms has been well documented, but much less is known about how compaction of microsporidia proteins affects their function. Taking a comparative genomic approach, we identified microsporidia orthologs of budding yeast proteins and show that these orthologs are enriched for essential yeast genes. We show that the median microsporidia protein is 21% shorter than its yeast counterpart and although extensive protein loss occurred after the divergence of microsporidia, reduced protein sizes were already present in microsporidian relatives. Microsporidia proteins are shorter through reduced domain lengths, diminished linker lengths, and domain loss, with 21% of microsporidia orthologs having lost domains present in yeast. On average, 34% of microsporidia orthologs have lost C-terminal residues essential for function in yeast, including 13 essential domains lost per genome. We also found that microsporidia display distinct phylogenetic patterns of domain loss, with losses occurring in a clade-specific manner. To investigate conservation of function, we used yeast complementation assays to test orthologs from several microsporidia species and their relativeRozella allomycis. These experiments reveal that most microsporidia proteins cannot complement their yeast orthologs, the ability to complement is about three-fold less than observed forR. allomycisorthologs, and proteins that do not complement are more reduced in length than their yeast orthologs. Altogether, our results demonstrate the drastic reduction of microsporidia proteins and show that these reductions have resulted in functional divergence from their fungal ancestors.
Basolateral amygdala population coding of a cued reward seeking state depends on orbitofrontal cortex
Authors: Ottenheimer David J. , Vitale Katherine R. , Ambroggi Frederic , Janak Patricia H. , Saunders Benjamin T.
Published: January 2024

Basolateral amygdala (BLA) neuronal responses to conditioned stimuli are closely linked to the expression of conditioned behavior. An area of increasing interest is how the dynamics of BLA neurons relate to evolving behavior. Here, we recorded the activity of individual BLA neurons across the acquisition and extinction of conditioned reward seeking and employed population-level analyses to assess ongoing neural dynamics. We found that, with training, sustained cue-evoked activity emerged that discriminated between the CS+ and CS-and correlated with conditioned responding. This sustained population activity continued until reward receipt and rapidly extinguished along with conditioned behavior during extinction. To assess the contribution of orbitofrontal cortex (OFC), a major reciprocal partner to BLA, to this component of BLA neural activity, we inactivated OFC while recording in BLA and found blunted sustained cue-evoked activity in BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in BLA also reduced reward seeking. Our data suggest that sustained cue-driven activity in BLA, which in part depends on OFC input, underlies conditioned reward-seek-ing states.
Chromatin structure and 3D architecture define differential functions ofPU.1cis regulatory elements in human blood cell lineages
Authors: Qiu Kevin , Vu Duc , Wang Leran , Bookstaver Anna , Dinh Thang N. , Goldfarb Adam N. , Tenen Daniel G. , Trinh Bon Q.
Published: January 2024

The precise spatio-temporal expression of the hematopoietic ETS transcription factorPU.1that determines the hematopoietic cell fates is tightly regulated at the chromatin level. However, it remains elusive as to how chromatin signatures are linked to this dynamic expression patternof PU.1across blood cell lineages. Here we performed an unbiased and in-depth analysis of the relationship between humanPU.1expression, the presence of trans-acting factors, and 3D architecture at various cis-regulatory elements (CRE) proximal to thePU.1locus. We identified multiple novel CREs at the upstream region of the gene following an integrative inspection for conserved DNA elements at the chromatin-accessible regions in primary human blood lineages. We showed that a subset of CREs localize within a 10 kb-wide cluster that exhibits that exhibit molecular features of a myeloid-specific super-enhancer involved in mediatingPU.1autoregulation, including open chromatin, unmethylated DNA, histone enhancer marks, transcription of enhancer RNAs, and occupancy of the PU.1 protein itself. Importantly, we revealed the presence of common 35-kb-wide CTCF-bound insulated neighborhood that contains the CRE cluster, forming the chromatin territory for lineage-specific and CRE-mediated chromatin interactions. These include functional CRE-promoter interactions in myeloid and B cells but not in erythroid and T cells. Our findings also provide mechanistic insights into the interplay between dynamic chromatin structure and 3D architecture in defining certain CREs as enhancers or silencers in chromatin regulation ofPU.1expression. The study lays the groundwork for further examination ofPU.1CREs as well as epigenetic regulation in malignant hematopoiesis.
Deep residual networks for crystallography trained on synthetic data
Authors: Mendez Derek , Holton James M. , Lyubimov Artem Y. , Hollatz Sabine , Mathews Irimpan I. , Cichosz Aleksander , Martirosyan Vardan , Zeng Teo , Stofer Ryan , Liu Ruobin , Song Jinhu , McPhillips Scott , Soltis Mike , Cohen Aina E.
Published: January 2024

The use of artificial intelligence to process diffraction images is challenged by the need to assemble large and precisely designed training data sets. To address this, a codebase called Resonet was developed for synthesizing diffraction data and training residual neural networks on these data. Here, two per-pattern capabilities of Resonet are demonstrated: (i) interpretation of crystal resolution and (ii) identification of overlapping lattices. Resonet was tested across a compilation of diffraction images from synchrotron experiments and X-ray free-electron laser experiments. Crucially, these models readily execute on graphics processing units and can thus significantly outperform conventional algorithms. While Resonet is currently utilized to provide real-time feedback for macromolecular crystallography users at the Stanford Synchrotron Radiation Lightsource, its simple Python-based interface makes it easy to embed in other processing frameworks. This work highlights the utility of physics-based simulation for training deep neural networks and lays the groundwork for the development of additional models to enhance diffraction collection and analysis.
Crypto-wallets revolution! Key factors driving behavioral intention to adopt the Coinbase Wallet using mixed PLS-SEM/fsQCA methodology in the Spanish environment
Authors: Gil-Cordero Eloy , Ledesma-Chaves Pablo , Arteaga Sánchez Rocío , Mariano Ari Melo
Published: January 2024

Purpose

The aim of this study is to examine the behavioral intention (BI) to adopt the Coinbase Wallet by Spanish users.

Design/methodology/approach

A survey was administered to individuals residing in Spain between March and April 2021. There were 301 questionnaires analyzed. This research applies a new predictive model based on technology acceptance model (TAM) 2, the unified theory of acceptance and use of technology (UTAUT) model, the theory of perceived risk and the commitment trust theory. A mixed partial least squares structural equation modeling (PLS-SEM)/fuzzy-set qualitative comparative analysis (fsQCA) methodology was employed for the modeling and data analysis.

Findings

The results showed that all the variables proposed have a direct and positive influence on the intention to use a Coinbase Wallet. The findings present clear directions for traders, investors and academics focused on improving their understanding of the characteristics of these markets.

Originality/value

First, this study addresses important concerns relating to the adoption of crypto-wallets during the global pandemic. Second, this research contributes to the existing literature by adding electronic word of mouth (e-WOM), trust, web quality and perceived risk as new drivers of the intention to use the Coinbase Wallet, providing unique and innovative insights. Finally, the study offers a solid methodological contribution by integrating linear (PLS) and nonlinear (fsQCA) techniques, showing that both methodologies provide a better understanding of the problem and a more detailed awareness of the patterns of antecedent factors.
Commuting while Black: compensating differentials and Black–White wage gap in Canada
Authors: Dilmaghani Maryam
Published: January 2024

Purpose

Using the Canadian Census of 2016, the present study examines the Black and White gap in compensating differentials for their commute to work.

Design/methodology/approach

The data are from the Canadian Census of 2016. The standard Mincerian wage regression, augmented by commute-related variables and their confounders, is estimated by OLS. The estimations use sample weights and heteroscedasticity robust standard errors.

Findings

In the standard Mincerian wage regressions, Black men are found to earn non-negligibly less than White men. No such gap is found among women. When the Mincerian wage equation is augmented by commute duration and its confounders, commute duration is revealed to positively predict wages of White men and negatively associate with wages of Black men. At the same time, in the specifications including commute duration and its confounders, the coefficient for the dummy variable identifying Black men is positive with a non-negligible size. The latter pattern indicates wage discrepancies among Black men by their commute duration. Again, no difference is found between Black and White women in these estimations.

Research limitations/implications

The main caveat is that due to data limitations, causal estimates could not be produced.

Practical implications

For the Canadian working men, the uncovered patterns indicate both between and within race gaps in the impact of commuting on wages. Particularly, Black men seem to commute longer towards relatively lower paying jobs, while the opposite holds for their White counterparts. However, Black men who reside close to their work earn substantially more than both otherwise identical White men and Black men who live far away from their jobs. The implications for research and policy are discussed.

Originality/value

This is the first paper focused on commute compensating differentials by race using Canadian data.
Belt and Road Initiative: legal mechanisms to recover stolen assets
Authors: Tan Veltrice
Published: January 2024

Purpose

This paper aims to determine the types of legal mechanisms that authorities can use to recover stolen assets for and from China.

Design/methodology/approach

Newspaper articles and books are examined as are relevant reports by various regulatory authorities and academic institutions.

Findings

The effectiveness of legal mechanisms in the recovery of stolen assets may be affected by issues such as the difficulties in tracing illicit funds, the ambiguous nature of “value” as well as the rise in technology.

Research limitations/implications

There are limited data available in relation to the prevalence of corrupt officials along the Belt and Road Initiative and the statistical success in the recovery of stolen assets. Any discussions within this paper are based on the impressionistic observations of this author, which may not reflect the true state of affairs of the Belt and Road Initiative.

Practical implications

Those who are interested in examining how authorities could recover stolen assets from and for China will have an interest in this topic.

Originality/value

The value of the paper is to demonstrate the difficulties in recovering stolen assets for and from China.
Land use determines Mediterranean ecosystems' multifunctionality more than plant richness or habitat composition
Authors: Lopezosa Paula , Soliveres Santiago , Serra Lluís , Constán‐Nava Soraya , Berdugo Miguel
Published: January 2024

Local and landscape diversity loss, habitat fragmentation and land‐use changes commonly co‐occur and impair ecosystem multifunctionality, yet they are often studied in isolation. Therefore, we ignore the relative importance of these drivers of ecosystem change or whether or not they interact to determine ecosystem functioning.

We measured how changes in local (plant richness) and landscape (different land uses) diversity, land use (orchards, shrubland, pine, oak and mixed forests) and habitat sise, and their interactions, affected the functioning of Mediterranean ecosystems. At 49 plots, we measured 17 above‐ and below‐ground functions, related to nutrient cycling, carbon sequestration and biotic interactions. Additionally, we generated different combinations of plots to compose artificial landscapes where multifunctionality and biodiversity conservation can be maximised, in order to aid land managers to preserve or design functional and diverse areas.

The relative importance of local and landscape attributes varied slightly depending on the target function, yet land use was by far the strongest predictor of most functions and multifunctionality above local plant biodiversity, habitat sise or landscape diversity. Oak and mixed forest were the most multifunctional land uses but were functionally wcomplemented by other land uses that maximised some individual functions.

The relative proportion of each land use within optimal landscapes varied if the target was biodiversity conservation (with an even dominance of land uses), carbon stocks or multifunctionality (highly dominated by native oak and mixed forests).

Synthesis and applications: Our results highlight the importance of remnant native forest to provide multiple ecosystem functions and the potential to restore them and complement these uses with sustainable agriculture. By merging landscape and ecosystem approaches we provide specific numbers regarding the proportion that each land use should have in order to maximise biodiversity conservation and/or functioning in these charismatic environments.
The Sins of the Fathers: Targeted Sanctions against Family Members of Primary Targets
Authors: Moiseienko Anton
Published: January 2024

Targeted sanctions, such as asset freezes and travel bans, are an increasingly popular response to a wide array of wrongdoing. This article considers an especially problematic aspect of contemporary sanctions law and practice that has received little attention so far, namely the imposition of sanctions on the family members of the primary target. In charting out a coherent and principled approach to such sanctions, the article makes three distinct contributions. First, it offers a comprehensive survey of law, policy and practice related to family‐member sanctions across the US, UK, EU and Australia. Secondly, it identifies the limits that international human rights law places on such sanctions, which effectively preclude automatic family‐member sanctions. Thirdly and finally, it proposes a ‘profit‐based’ sanctions model as an alternative to ‘activity‐based’ and ‘status‐based’ sanctions, as well as outlining its implications for the design of family‐member sanctions.
Stachydrine represses the proliferation and enhances cell cycle arrest and apoptosis of breast cancer cells via PLA2G2A/DCN axis
Authors: Zhai Zhen , Mu Tianlong , Zhao Lina , Zhu Dongsheng , Zhong Xin , Li Yiliang , Liang Chen , Li Wei , Zhou Qingyuan
Published: January 2024

Considering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation‐ and apoptosis‐related factors in BC cells were quantified through quantitative reverse‐transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down‐regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up‐regulated the levels of Cleaved caspase‐3 and Cleaved caspase‐9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis.
Extracellular α‐synuclein impairs sphingosine 1‐phosphate receptor type 3 (S1PR3)‐regulated lysosomal delivery of cathepsin D in HeLa cells
Authors: Nishida Susumu , Matovelo Shubi Ambwene , Kajimoto Taketoshi , Nakamura Shun‐ichi , Okada Taro
Published: January 2024

α‐Synuclein (α‐Syn)‐positive intracellular fibrillar protein deposits, known as Lewy bodies, are thought to be involved in the pathogenesis of Parkinson's disease (PD). Although recent lines of evidence suggested that extracellular α‐Syn secreted from pathogenic neurons contributes to the propagation of PD pathology, the precise mechanism of action remains unclear. We have reported that extracellular α‐Syn caused sphingosine 1‐phosphate (S1P) receptor type 1 (S1PR1) uncoupled from Gi and inhibited downstream G‐protein signaling in SH‐SY5Y cells, although its patho/physiological role remains to be clarified. Here we show that extracellular α‐Syn caused S1P receptor type 3 (S1PR3) uncoupled from G protein in HeLa cells. Further studies indicated that α‐Syn treatment reduced cathepsin D activity while enhancing the secretion of immature pro‐cathepsin D into cell culture medium, suggesting that lysosomal delivery of cathepsin D was disturbed. Actually, extracellular α‐Syn attenuated the retrograde trafficking of insulin‐like growth factor‐II/mannose 6‐phosphate (IGF‐II/M6P) receptor, which is under the regulation of S1PR3. These findings shed light on the understanding of dissemination of the PD pathology, that is, the mechanism underlying how extracellular α‐Syn secreted from pathogenic cells causes lysosomal dysfunction of the neighboring healthy cells, leading to propagation of the disease.
Safety and dose‐finding trial of tadalafil administered for fetus in labor: A phase I clinical study
Authors: Tamaishi Yuya , Tanaka Hiroaki , Hirai Toshinori , Hiramatsu Shun‐ichi , Takakura Sho , Magawa Shoichi , Tanaka Kayo , Kondo Eiji , Iwamoto Takuya , Ikeda Tomoaki
Published: January 2024

Aim

This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic–ischemic encephalopathy.

Methods

The study used a three‐case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil‐associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery.

Results

A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms‐like tyrosine kinase‐1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration.

Conclusions

The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.
Identification of new yeast strains, Candida zeylanoidesY12‐3 and Hyphopichia pseudoburtoniiY12‐1, from the intestinal tract of rainbow trout, Oncorhynchus mykiss, with potential probiotic characteristics
Authors: Çayli Bektaş Özge , Didinen Behire Işıl , Onuk Ertan Emek , Yilmaz Sevdan , Abdel‐Latif Hany M. R.
Published: January 2024

In this study, 2 yeasts, Candida zeylanoides isolate Y12‐3 (MN073455.1) and Hyphopichia pseudoburtonii isolate Y12‐1 (MN073489.1), were isolated from rainbow trout hindguts. Their identity was confirmed by amplification of internal transcribed spacer (ITS) gene regions. Their in vitro probiotic properties showed that they were hydrophobic and did not inhibit bacterial growth. However, they displayed positive co‐aggregation with several bacterial pathogens. It was interesting that Y12‐1 and Y12‐3 isolates survived and grew well in bile salt concentrations ranging from 0.6% to 1.5% and at low pH conditions. After a 35‐day feeding trial, the results of dietary incorporation of the yeast isolates showed that serum myeloperoxidase activity was unchanged in the treated and control groups. Meanwhile, serum lysozyme activity in yeast groups was decreased significantly compared to the control. However, fish fed with Y12‐1 had higher total protein, albumin, and globulin than other groups. Total cholesterol levels were decreased significantly in yeast groups compared to the control. Interestingly, the Y12‐1 and Y12‐3 groups showed higher survival (69.05% and 80.95%) after the challenge with Lactococcus garvieae compared to the control (45.24%). In brief, the aforementioned findings showed that Y12‐1 and Y12‐3 strains could be potential probiotic candidates for use in rainbow trout farming.