bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Particle Size of a Powder upon the Properties and Microstructure of Boron-modified Fe-Ni-Mo-Cu Sinters
Authors: Perek-Nowak Małgorzata , Majchrowska Magdalena , Karwan-Baczewska Joanna , Rosso Mario
Published: June 2023

The article discusses the effect of different particle fractions of prealloyed iron powder on the microstructure, density and hardness of sintered material. Each particle fraction (apart from 160–200 µm, which is a trace fraction) was modified with boron, its contents being, respectively, 0.2 wt.%, 0.4 wt.% and 0.6 wt.%. Next, the powder mixtures were pressed under a pressure of 600 MPa, and the final compacts were subject to sintering at 1200°C for 60 min in a hydrogen atmosphere. It was observed that the higher values of density and hardness were found in samples made from finer fractions of powder. A higher homogeneity of the microstructure and the highest degree of compactness was obtained in sinters from powder of 40–56 µm particle size, with 0.4 wt.% boron. Due to the use of small particle fractions of prealloyed powder, a higher degree of compactness in sinters was obtained with lower boron content. Also indicated was which particle fraction of Fe-Ni-Mo-Cu powder should be applied to obtain density in sinters with boron addition equal to almost 100% of the relative density of the analyzed alloy. The presented studies have both scientific and technological aspects.
Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development
Authors: Nameki Robbin A. , Chang Heidi , Yu Pak , Abbasi Forough , Lin Xianzhi , Reddy Jessica , Haro Marcela , Fonseca Marcos AS , Freedman Matthew L. , Drapkin Ronny , Corona Rosario I. , Lawrenson Kate
Published: June 2023

The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue of origin, the fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq and HiC) data sets and 24 profiles of RNA-seq transcription factor knock-down followed by RNA sequencing in FTSEC and HGSC models to define binding sites and gene sets regulated by these factors in
cis
and
trans
. This revealed that MECOM, PAX8, SOX17 and WT1 are lineage-enriched, super-enhancer associated master regulators whose cooperative DNA-binding patterns and target genes are re-wired during tumor development. All four TFs were indispensable for HGSC clonogenicity and survival but only depletion of PAX8 and WT1 impaired FTSEC cell survival. These four TFs were pharmacologically inhibited by transcriptional inhibitors only in HGSCs but not in FTSECs. Collectively, our data highlights that tumor-specific epigenetic remodeling is tightly related to MECOM, PAX8, SOX17 and WT1 activity and these transcription factors are targetable in a tumor-specific manner through transcriptional inhibitors.
An Unexpected Role of Neutrophils in Clearing Apoptotic Hepatocytes In Vivo
Authors: Cao Luyang , Ma Lixiang , Zhao Juan , Wang Xiangyu , Fan Xinzou , Li Wei , Qi Yawen , Tang Yingkui , Liu Jieya , Peng Shengxian , Yang Li , Zhou Liangxue , Li Li , Hu Xiaobo , Ji Yuan , Hou Yingyong , Zhao Yi , Zhang Xianming , Zhao Youyang , Zhao Yong , Wei Yuquan , Malik Asrar B. , Saiyin Hexige , Xu Jingsong
Published: June 2023

Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term
perforocytosis
, and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.
A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia
Authors: Chen Ming-Ming , Zhao Yue , Yu Kun , Xu Xue-Ling , Zhang Xiao-Sheng , Zhang Jin-Long , Wu Su-Jun , Liu Zhi-Mei , Yuan Yi-Ming , Guo Xiao-Fei , Qi Shi-Yu , Yi Guang , Wang Shu-Qi , Li Huang-Xiang , Wu Ao-Wu , Liu Guo-Shi , Deng Shou-Long , Han Hong-Bing , Lv Feng-Hua , Lian Di , Lian Zheng-Xing
Published: June 2023

Mutations in the well-known Myostatin (MSTN) produce a ‘double-muscle’ phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant ‘double-muscle’ phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.
Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing
Authors: Ibrahim Leena Ali , Wamsley Brie , Alghamdi Norah , Yusuf Nusrath , Sevier Elaine , Hairston Ariel , Sherer Mia , Jaglin Xavier Hubert , Xu Qing , Guo Lihua , Khodadadi-Jamayran Alireza , Favuzzi Emilia , Yuan Yuan , Dimidschstein Jordane , Darnell Robert B , Fishell Gordon
Published: June 2023

Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent. We then investigated the relationship between activity, alternative splicing, and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of somatostatin interneurons, as well as their afferent and efferent connectivity. Within this population, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function independently from its effect on gene expression. Hence, our work demonstrates that the Nova family of proteins through alternative splicing are centrally involved in coupling developmental neuronal activity to cortical circuit formation.
Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange
Authors: Tippett David N , Breen Colum , Butler Stephen J , Sawicka Marta , Dutzler Raimund
Published: June 2023

Members of the SLC26 family constitute a conserved class of anion transport proteins, which encompasses uncoupled transporters with channel-like properties, coupled exchangers and motor proteins. Among the 10 functional paralogs in humans, several participate in the secretion of bicarbonate in exchange with chloride and thus play an important role in maintaining pH homeostasis. Previously, we have elucidated the structure of murine SLC26A9 and defined its function as an uncoupled chloride transporter (Walter et al., 2019). Here we have determined the structure of the closely related human transporter SLC26A6 and characterized it as a coupled exchanger of chloride with bicarbonate and presumably also oxalate. The structure defines an inward-facing conformation of the protein that generally resembles known structures of SLC26A9. The altered anion selectivity between both paralogs is a consequence of a remodeled ion binding site located in the center of a mobile unit of the membrane-inserted domain, which also accounts for differences in the coupling mechanism.
Human attention during goal-directed reading comprehension relies on task optimization
Authors: Zou Jiajie , Zhang Yuran , Li Jialu , Tian Xing , Ding Nai
Published: June 2023

The computational principles underlying attention allocation in complex goal-directed tasks remain elusive. Goal-directed reading, that is, reading a passage to answer a question in mind, is a common real-world task that strongly engages attention. Here, we investigate what computational models can explain attention distribution in this complex task. We show that the reading time on each word is predicted by the attention weights in transformer-based deep neural networks (DNNs) optimized to perform the same reading task. Eye tracking further reveals that readers separately attend to basic text features and question-relevant information during first-pass reading and rereading, respectively. Similarly, text features and question relevance separately modulate attention weights in shallow and deep DNN layers. Furthermore, when readers scan a passage without a question in mind, their reading time is predicted by DNNs optimized for a word prediction task. Therefore, we offer a computational account of how task optimization modulates attention distribution during real-world reading.
Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making
Authors: Oemisch Mariann , Seo Hyojung
Published: June 2023

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine’s potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine’s antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.
Astrocytic Neuroligins Are Not Required for Synapse Formation or a Normal Astrocyte Cytoarchitecture
Authors: Golf Samantha R. , Trotter Justin H. , Nakahara George , Südhof Thomas C.
Published: June 2023

Astrocytes exert multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved remain unclear. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that bind to presynaptic neurexins. A pioneering recent study reported that loss-of-function of neuroligins in astrocytes impairs excitatory synapse formation and astrocyte morphogenesis. This study suggested a crucial synaptic function for astrocytic neuroligins but was puzzling given that constitutive neuroligin deletions do not decrease excitatory synapse numbers. Thus, we here examined the function of astrocytic neuroligins using a rigorous conditional genetic approach with deletion of all major neuroligins (
Nlgn1-3
) in astrocytes. Our results show that early postnatal deletion of neuroligins from astrocytes has no effect on cortical or hippocampal synapses and does not alter the cytoarchitecture of astrocytes. Thus, astrocytic neuroligins are unlikely to shape synapse formation or astrocyte development but may perform other important functions in astrocytes.
Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells
Authors: Liu Silvia , Yu Yan-Ping , Ren Bao-Guo , Ben-Yehezkel Tuval , Obert Caroline , Smith Mat , Wang Wenjia , Ostrowska Alina , Soto-Gutierrez Alejandro , Luo Jian-Hua
Published: June 2023

The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Protein mutation is essential in species evolution and cancer development. Accurate Long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPseq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection (UMAP) analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen (HLA) molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPseq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.
GABAergic synaptic scaling is triggered by changes in spiking activity rather than AMPA receptor activation
Authors: Gonzalez-Islas Carlos , Sabra Zahraa , Fong Ming-fai , Yilmam Pernille , Au Yong Nicholas , Engisch Kathrin , Wenner Peter
Published: June 2023

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here, we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPA receptor (AMPAR) or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.
A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence
Authors: Pabis Kamil , Barardo Diogo , Sirbu Olga , Selvarajoo Kumar , Gruber Jan , Kennedy Brian K
Published: June 2023

Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons. To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells, and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention, and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice. In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data suggest that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.
A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence
Authors: Pabis Kamil , Barardo Diogo , Selvarajoo Kumar , Gruber Jan , Kennedy Brian K.
Published: June 2023

Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons.To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice.In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data shows that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.
N-WASP-dependent branched actin polymerization attenuates B-cell receptor signaling by increasing the molecular density of receptor clusters
Authors: Bhanja Anshuman , Seeley-Fallen Margaret K , Lazzaro Michelle , Upadhyaya Arpita , Song Wenxia
Published: June 2023

Antigen-induced B-cell receptor (BCR) signaling is critical for initiating and regulating B-cell activation. The actin cytoskeleton plays essential roles in BCR signaling. Upon encountering cell-surface antigens, actin-driven B-cell spreading amplifies signaling, while B-cell contraction following spreading leads to signal attenuation. However, the mechanism by which actin dynamics switch BCR signaling from amplification to attenuation is unknown. Here, we show that Arp2/3-mediated branched actin polymerization is required for mouse splenic B-cell contraction. Contracting B-cells generate centripetally moving actin foci from lamellipodial F-actin networks in the plasma membrane region contacting antigen-presenting surfaces. Actin polymerization driven by N-WASP, but not WASP, initiates these actin foci and facilitates non-muscle myosin II recruitment to the contact zone, creating actomyosin ring-like structures. B-cell contraction increases BCR molecular density in individual clusters, leading to decreased BCR phosphorylation. Increased BCR molecular density reduced levels of the stimulatory kinase Syk, the inhibitory phosphatase SHIP-1, and their phosphorylated forms in individual BCR clusters. These results suggest that N-WASP-activated Arp2/3, coordinating with myosin, generates centripetally moving foci and contractile actomyosin ring-like structures from lamellipodial networks, enabling contraction. B-cell contraction attenuates BCR signaling by pushing out both stimulatory kinases and inhibitory phosphatases from BCR clusters, providing novel insights into actin-facilitated signal attenuation.
Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Authors: Wang Huan , Rizvi Syed RA , Dong Danni , Lou Jiaqi , Wang Qian , Sopipong Watanyoo , Su Yufeng , Najar Fares , Agarwal Pratul K , Kozielski Frank , Haider Shozeb
Published: June 2023

The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host’s innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets.
A unique cell division protein critical for the assembly of the bacterial divisome
Authors: Chu Xiao , Wang Lidong , Zhu Yiheng , Feng Zhengshan , Guan Qingtian , Song Lei , Luo Zhaoqing
Published: June 2023

Identification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here, we report a previously unrecognized core component of the Acinetobacter baumannii divisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202K and FtsBE65A mutants effectively bypassed the need of Aeg1 by A. baumannii, as did the activation variants FtsWM254I and FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.
Exploring the K+ binding site and its coupling to transport in the neurotransmitter:sodium symporter LeuT
Authors: Schmidt Solveig G , Nygaard Andreas , Mindell Joseph A , Loland Claus J
Published: June 2023

The neurotransmitter:sodium symporters (NSSs) are secondary active transporters that couple the reuptake of substrate to the symport of one or two sodium ions. One bound Na+ (Na1) contributes to the substrate binding, while the other Na+ (Na2) is thought to be involved in the conformational transition of the NSS. Two NSS members, the serotonin transporter (SERT) and the Drosophila dopamine transporter (dDAT), also couple substrate uptake to the antiport of K+ by a largely undefined mechanism. We have previously shown that the bacterial NSS homologue, LeuT, also binds K+, and could therefore serve as a model protein for the exploration of K+ binding in NSS proteins. Here, we characterize the impact of K+ on substrate affinity and transport as well as on LeuT conformational equilibrium states. Both radioligand binding assays and transition metal ion FRET (tmFRET) yielded similar K+ affinities for LeuT. K+ binding was specific and saturable. LeuT reconstituted into proteoliposomes showed that intra-vesicular K+ dose-dependently increased the transport velocity of [3H]alanine, whereas extra-vesicular K+ had no apparent effect. K+ binding induced a LeuT conformation distinct from the Na+- and substrate-bound conformation. Conservative mutations of the Na1 site residues affected the binding of Na+ and K+ to different degrees. The Na1 site mutation N27Q caused a >10-fold decrease in K+ affinity but at the same time a ~3-fold increase in Na+ affinity. Together, the results suggest that K+ binding to LeuT modulates substrate transport and that the K+ affinity and selectivity for LeuT is sensitive to mutations in the Na1 site, pointing toward the Na1 site as a candidate site for facilitating the interaction with K+ in some NSSs.
Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period
Authors: Bolumar David , Moncayo-Arlandi Javier , Gonzalez-Fernandez Javier , Ochando Ana , Moreno Inmaculada , Monteagudo-Sanchez Ana , Marin Carlos , Diez Antonio , Fabra Paula , Checa Miguel Angel , Espinos Juan Jose , Gardner David K , Simon Carlos , Vilella Felipe
Published: June 2023

The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics. We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production. These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.
Thalamic regulation of ocular dominance plasticity in adult visual cortex
Authors: Qin Yi , Ahmadlou Mehran , Suhai Samuel , Neering Paul , de Kraker Leander , Heimel J Alexander , Levelt Christiaan N
Published: June 2023

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.
Deciphering Neuronal Deficit and Protein Profile Changes in Human Brain Organoids from Patients with Creatine Transporter Deficiency
Authors: Broca-Brisson Léa , Harati Rania , Disdier Clémence , Mozner Orsolya , Gaston-Breton Romane , Maïza Auriane , Costa Narciso , Guyot Anne-Cécile , Sarkadi Balazs , Apati Agota , Skelton Matthew R , Madrange Lucie , Yates Frank , Armengaud Jean , Hamoudi Rifat A. , Mabondzo Aloïse
Published: June 2023

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy.
Finnmark som krigssone gjennom andre verdenskrig
Authors: Fagertun Fredrik
Published: June 2023

Finnmark fikk under andre verdenskrig, i langt større grad enn andre deler av Norge, oppleve reelle krigshandlinger i form av allierte flyangrep og brutale tvangstiltak fra den tyske okkupasjonsmaktens og det norske nazi-regimets side. Tyskerne etablerte seg tungt i Øst-Finnmark som ble et brohode for tyskernes krigføring på Litsa-fronten. Finnmark var viktig for tyskernes militære og strategiske kontroll i nordområdene. Samtidig var norsk og alliert spionasje og overvåking på plass i krigen mot tyskerne på den nordligste flanken.
Multi-user conflict resolution mechanisms for smart home environments
Authors: Aljawarneh Mahmoud Mohammad , Shah Shahid Munir , Dhomeja Lachhman Das , Malkani Yasir Arfat , Jawarneh Mahmoud Saleh
Published: June 2023

Context-awareness is a pervasive computing enabling technology that allows context-aware applications to respond to multiple contexts such as activity, location, temperature, and so on. When many users attempt to access the same context-aware application, user conflicts may emerge. This issue is emphasized, and a conflict resolution approach is presented to address it. Although there are other conflict resolution approaches in the literature, the one presented here is unique in that it considers the users’ special cases such as their sickness, examinations, and so on when resolving conflicts. The proposed approach is helpful when several users with different special cases try to access the same context-aware application. To demonstrate the usefulness of the proposed approach, a conflict manager is integrated with the UbiREAL simulated context-aware home environment. The integrated conflict manager resolves conflicts by taking users special cases into account and employing either automated, mediated, or hybrid conflict resolution approaches. The evaluation of the proposed approach demonstrates that users are satisfied with it and that it is critical and essential to employ users’ special cases in detecting and resolving users conflicts.
Paediatric hospitalizations over three waves of COVID-19 (February 2020 to May 2021) in Italy: determinants and rates
Authors: Martella Manuela , Peano Alberto , Politano Gianfranco , Onorati Roberta , Gianino Maria Michela
Published: June 2023

Background

After a pneumonia outbreak in late 2019 in China, a new virus related to the Coronaviridae strain, called Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was identified as the pathogen of an emerging disease known as COronaVIrus Disease 19 (COVID-19). Preliminary evidence outlines a higher prevalence in adults and lower susceptibility in children. However, recent epidemiologic research highlighted that transmissibility and susceptibility among children and adolescents become higher due to new virus variants. Infections among youth arises with mainly respiratory and gastrointestinal symptoms and malaise. Nevertheless, critical illness affects new-borns and fragile children, requiring hospitalization and possibly intensive care support. Aim of this study was to examine the impact of COVID-19 pandemic on hospital admissions among children and adolescents aged 0 to 17 years over three waves of COVID-19 (from February 2020 to May 2021) in Piedmont, a large Italian region, and to investigate the possible determinants of hospitalizations.

Methods

A meta-analysis for risk assessment was performed over three waves of COVID-19 (from February 2020 to May 2021). Data were extracted from the official Italian National Information System and ISTAT.

Results

Overall, 442 paediatric patients were enrolled and admissions concerned mostly the age group 0–4 years (60.2%). Trends of hospitalization showed a slight increase of paediatric admissions already in March 2020 and a rise during second and third waves (November 2020, March 2021). Paediatric age-grouped hospitalizations (0–4; 12–17; 5–11) reproduced an analogous trend. The children and adolescent hospitalization rate appeared lower than overall population with a moderate slope of increase in comparison with population slope. Monthly hospitalization rate (per 100,000) of children and adolescents aged 0–17 years reproduced the increasing trend of hospitalization numbers. This trend was influenced, in particular, by the trend of hospitalization rates for children aged 0–4 years. The meta-analysis for risk assessment showed a decreased likelihood of rescue of hospitalizations in female, 5–11 and 12–17 age groups. Conversely, the meta-analysis showed a positive association between foreign nationality and hospitalizations.

Conclusions

Our results show a comparable trend of paediatric hospital admissions for COVID-19 and of the entire population hospitalizations over three waves. COVID-19 hospital admissions increase with a bimodal age distribution and the most admissions are among patients aged ≤4 or 5–11 years. Significant predictive factors of hospitalization are identified.
CD4+ and CD8+ cell counts are significantly correlated with absolute lymphocyte count in hospitalized COVID-19 patients: a retrospective study
Authors: Liana Phey , Samosir Aprilia Paskah , Sari Nurmalia Purnama , Andriani Raden Ayu Linda , Verdiansah Verdiansah , Hidayatullah Hidayatullah , Ahmad Zen , Umar Tungki Pratama
Published: June 2023

Background

Coronavirus disease 2019 (COVID-19) is a contagious respiratory illness that was declared a pandemic in March 2020. Lymphopenia is one of the specific laboratory results disturbance in COVID-19 patients. Such findings are frequently associated with substantial changes in T-cell counts, particularly CD4+ and CD8+ T-cells. This study aimed to examine the correlation between CD4+ and CD8+ cell counts and absolute lymphocyte count (ALC) in COVID-19 patients and analyze its difference based on the COVID-19 patients’ severity.

Methods

From March 2022 to May 2022, we conducted a retrospective cohort study using medical records and laboratory data from patients diagnosed with COVID-19 at our hospital who met the inclusion and exclusion criteria. The total sampling method was used to recruit study participants. We conducted bivariate analysis, which consisted of correlation and comparative analysis.

Results

Thirty-five patients met the inclusion and exclusion criteria and were divided into two severity groups (mild-moderate and severe-critical). The findings of this study revealed a significant correlation between CD4+ cell count and ALC on admission (r = 0.69, p < 0.001) and the tenth day of onset (r = 0.559, p < 0.001). Similarly, there was a correlation between CD8+ and ALC at admission (r = 0.543, p = 0.001) and on the tenth day of onset (r = 0.532, p = 0.001). Individuals with severe-critical illness had lower ALC, CD4+, and CD8+ cell counts than those with mild-moderate illness.

Conclusion

According to the findings of this study, there is a correlation between CD4+ and CD8+ cell counts and ALC in COVID-19 patients. All lymphocyte subsets also showed a lower value in severe forms of the disease.
Biostimulant red seaweed (Gracilaria tenuistipitata var. liui) extracts spray improves yield and drought tolerance in soybean
Authors: Mannan Md. Abdul , Yasmin Amir , Sarker Umakanta , Bari Nasimul , Dola Dipanjoli Baral , Higuchi Hirokazu , Ercisli Sezai , Ali Daoud , Alarifi Saud
Published: June 2023

Drought has a deleterious impact on the growth, physiology, and yield of various plants, including soybean. Seaweed extracts are rich in various bioactive compounds, including antioxidants, and can be used as biostimulants for improving yield and alleviating the adverse effect of drought stress. The purpose of this study was to evaluate the effect of soybean growth and yield with different concentrations (0.0%, 5.0%, and 10.0% v/v) of water extracts of the red seaweed Gracilaria tenuistipitata var. liui under well-watered (80% of field capacity (FC) and drought (40% of FC)) conditions. Drought stress decreased soybean grain yield by 45.58% compared to well-watered circumstances but increased the water saturation deficit by 37.87%. It also decreased leaf water, chlorophyll content, plant height, and the fresh weight of the leaf, stem, and petiole. Drought stress decreased soybean grain yield by 45.58% compared to well-watered circumstances but increased the water saturation deficit by 37.87%. It also decreased leaf water, chlorophyll content, plant height, and the fresh weight of the leaf, stem, and petiole. Under both drought and well-watered situations, foliar application of seaweed extracts dramatically improved soybean growth and production. Under drought and well-watered situations, 10.0% seaweed extract increased grain yield by 54.87% and 23.97%, respectively in comparison to untreated plants. The results of this study suggest that red seaweed extracts from Gracilaria tenuistipitata var. liui may be used as a biostimulant to improve soybean yield and drought tolerance in the presence of insufficient water. However, the actual mechanisms behind these improvements need to be further investigated in field conditions.
percepción de gestores municipales brasileños sobre el uso de la bicicleta como transporte post Política de Movilidad Urbana
Authors: Silva de Carvalho Cristiane , Fialho Carvalho Eriane , Rodriguez Rivera Milithza , Gonzalez Ruiz Inti , Delamaro Mauricio César
Published: June 2023

Motivados por la Política Nacional de Movilidad Urbana, los municipios brasileños inician un proceso de implementación de medidas que faciliten el uso de la bicicleta como transporte en sus territorios.  Es de gran relevancia caracterizar las condiciones del uso de este medio de transporte y, a la vez, evaluar cómo los municipios afrontan el desafío planteado a nivel federal para la movilidad urbana. Este trabajo discute las capacidades municipales destinadas a la planificación y gestión de la bicicleta como transporte. Para esto, se analizaron documentos oficiales y se entrevistaron a los responsables de transporte de 11 municipios de la Región Metropolitana do Vale do Paraíba e Litoral Norte. Los resultados muestran que la política y sus directrices han logrado permear en la gestión y planificación municipal resaltando la importancia de la bicicleta como medio de transporte. Sin embargo, sigue siendo la capacidad institucional municipal la brecha a subsanar en la implementación de medidas.
Origens da folga orçamentária: um desafio à efetividade do orçamento organizacional
Authors: Gomes Luciana de Carvalho Reis , Bastos Sérgio Augusto Pereira
Published: June 2023

O objetivo é identificar quais fatores percebidos estimulam a criação da folga orçamentária. Há uma fragmentação na literatura sobre os fatores que levam à folga orçamentária, o que é desafiador para efetividade do orçamento organizacional como instrumento de gestão. O estudo é exploratório, quantitativo, com dados coletados por survey de percepções. Os respondentes são profissionais de diversos setores que lidam direta ou indiretamente com o orçamento organizacional. Os procedimentos analíticos incluem estatística descritiva, análise fatorial e regressão linear múltipla. Os resultados indicam relação positiva entre folga orçamentária e oportunismo gerencial e uma relação negativa entre folga e institucionalização e processos de planejamento e controle. São evidenciados subfatores: estilo de gestão; segurança; oportunidades de negócios; remuneração; avaliação de desempenho; conflitos de interesse; direcionamento estratégico, objetivos e metas; comunicação; formalização do processo de planejamento e controle; e tecnologia da informação. Ao contrário do esperado, os resultados não confirmam a existência do subfator assimetria informacional como parte do oportunismo gerencial. Como o orçamento é central nos modelos de gestão das organizações, estudos sobre distorções do processo orçamentário, com é o caso deste que busca identificar fatores que levam à folga orçamentária, contribuem para a literatura de planejamento e controle de gestão.
Gestão de riscos à integridade: uma análise do Portal de Licitações e Contratos Administrativos
Authors: Da Silva Renan Alves Felix , De Oliveira Alessandro Bandeira
Published: June 2023

O presente estudo apresenta a contribuição do Portal de Licitações e Contratos Administrativos de uma Força Armada do país para a gestão de riscos à integridade. Recentemente instituído, o Portal permite que as Organizações Militares deem publicidade ao inteiro teor de suas contratações públicas, disponibilizando editais, notas fiscais de compras, dentre outros documentos relativos à contratação de serviços e aquisições. Em relação à metodologia, o corpus para a análise foi composto por uma pesquisa documental e uma aplicação de survey, verificando-se a percepção dos Assessores de Controle Interno dessa Força quanto à aderência entre a instituição do Portal e a inibição de riscos de irregularidades e desvios de conduta nas contratações. Constatou-se que a implantação do Portal contribui para o fortalecimento da gestão de riscos à integridade ao possibilitar o fomento a uma cultura de prestação de contas, a promoção à transparência e o estímulo ao controle social.
Qualidade de vida no trabalho e predisposição para Síndrome de Burnout em docentes do ensino superior
Authors: De Sousa Juliana Carvalho , Machado Cyjara Orsano
Published: June 2023

O objetivo desta pesquisa foi averiguar, com base na realidade dos docentes de uma instituição de ensino superior pública, se a Qualidade de Vida do Trabalho pode ser considerada preditora da Síndrome de Burnout. De abordagem quantitativa, os dados foram coletados através de questionário disponibilizado no site da instituição e enviado para o e-mail institucional dos professores, cuja amostra foi realizada com base em 319 respondentes. Sobre a análise e discussão dos resultados, utilizou-se a estatística descritiva, análise fatorial exploratória e Regressão Linear Múltipla. Os resultados revelaram que a população investigada não possui tendência para o desenvolvimento da Síndrome de Burnout, e apresentam alta Qualidade de Vida no Trabalho. Conclui-se, com base nas correlações executadas, que a Qualidade de Vida no Trabalho não pode ser considerada preditora da Síndrome de Burnout, ao passo que as correlações não são significativas.