bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Small Molecule Ligand Binding Sites On and In the ARNT PAS-B Domain
Authors: Xu Xingjian , Closson Joseph , Marcelino Leandro Pimentel , Favaro Denize C. , Silvestrini Marion L. , Solazzo Riccardo , Chong Lillian T. , Gardner Kevin H.
Published: November 2023

Transcription factors are generally challenging to target with small molecule inhibitors due to their structural plasticity and lack of catalytic sites. Notable exceptions include several naturally ligand-regulated transcription factors, including our prior work with the heterodimeric HIF-2 transcription factor which showed that small molecule binding within an internal pocket of the HIF-2α PAS-B domain can disrupt its interactions with its dimerization partner, ARNT. Here, we explore the feasibility of similarly targeting small molecules to the analogous ARNT PAS-B domain itself, potentially opening a promising route to simultaneously modulate several ARNT-mediated signaling pathways. Using solution NMR screening of an in-house fragment library, we previously identified several compounds that bind ARNT PAS-B and, in certain cases, antagonize ARNT association with the TACC3 transcriptional coactivator. However, these ligands have only modest binding affinities, complicating characterization of their binding sites. We address this challenge by combining NMR, MD simulations, and ensemble docking to identify ligand-binding ‘hotspots’ on and within the ARNT PAS-B domain. Our data indicate that the two ARNT/TACC3 inhibitors, KG-548 and KG-655, bind to a β-sheet surface implicated in both HIF-2 dimerization and coactivator recruitment. Furthermore, while KG-548 binds exclusively to the β-sheet surface, KG-655 can additionally bind within a water-accessible internal cavity in ARNT PAS-B. Finally, KG-279, while not a coactivator inhibitor, exemplifies ligands that preferentially bind only to the internal cavity. All three ligands promoted ARNT PAS-B homodimerization, albeit to varying degrees. Taken together, our findings provide a comprehensive overview of ARNT PAS-B ligand-binding sites and may guide the development of more potent coactivator inhibitors for cellular and functional studies.
Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the Study of Muscle, Mobility and Aging (SOMMA)
Authors: Coen Paul M , Huo Zhiguang , Tranah Gregory J , Barnes Haley N , Cawthon Peggy M , Hepple Russell T , Toledo Frederico G S , Evans Daniel S , Fernández Olaya Santiago , Cuervo Ana Maria , Kritchevsky Steven B , Newman Anne B , Cummings Steven R , Esser Karyn A
Published: November 2023

Autophagy is an essential component of proteostasis and a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to autophagy regulation, mitophagy and mTOR/upstream pathways were determined. Associations between gene expression and outcomes including mitochondrial respiration in muscle fiber bundles (MAX OXPHOS), physical performance (VO2peak, 400m walking speed, and leg power), and thigh muscle volume were determined using negative binomial regression models. For autophagy, key transcriptional regulators including TFE3 and NFKB-related genes (RELA, RELB, NFKB1) were negatively associated with outcomes. On the contrary, regulators of oxidative metabolism that also promote overall autophagy, mitophagy and pexophagy (PPARGC1A, PPARA, EPAS1) were positively associated with multiple outcomes. In line with this, several mitophagy, fusion and fission related genes (NIPSNAP2, DNM1L, OPA1) were also positively associated with outcomes. For mTOR pathway and related genes, expression of WDR59 and WDR24, both subunits of GATOR2 complex (an indirect inhibitor of mTORC1) and PRKAG3, which is a regulatory subunit of AMPK, were negatively correlated with multiple outcomes. Our study identifies autophagy and selective autophagy such as mitophagy gene expression patterns in human skeletal muscle related to physical performance, muscle volume and mitochondrial function in older persons which may lead to target identification to preserve mobility and independence.
Knockout of cyclin dependent kinases 8 and 19 leads to depletion of cyclin C and suppresses spermatogenesis and male fertility in mice
Authors: Bruter Alexandra V. , Varlamova Ekaterina A. , Stavskaya Nina I. , Antysheva Zoia G. , Manskikh Vasily N. , Tvorogova Anna V. , Korshunova Diana. S. , Khamidullina Alvina I. , Utkina Marina V. , Bogdanov Viktor P. , Baikova Iuliia P. , Nikiforova Alyona I. , Albert Eugene A. , Maksimov Denis O. , Li Jing , Chen Mengqian , Schools Gary. P , Feoktistov Alexey V. , Shtil Alexander A. , Roninson Igor B. , Mogila Vladislav A. , Silaeva Yulia Y. , Tatarskiy Victor V.
Published: November 2023

Paralogs CDK8 and CDK19 are regulatory kinases associated with the transcriptional Mediator complex. We have e generated mice with the systemic inducibleCdk8knockout on the background ofCdk19constitutive knockout.Cdk8/19double knockout (iDKO) males, but not singleCdk8andCdk19KO, had an atrophic reproductive system and were infertile. The iDKO males lacked postmeiotic spermatids and spermatocytes after meiosis I pachytene. Testosterone levels were decreased whereas the amounts of the luteinizing hormone were unchanged. Single cell RNA sequencing showed marked differences in the expression of steroidogenic genes (such asCyp17a1, StarandFads) in Leydig cells concomitant with alterations in Sertoli cells and spermatocytes likely associated with impaired synthesis of steroids.StarandFadswere also downregulated in cultivated Leydig cells after iDKO. The treatment of primary Leydig cells culture with a CDK8/19 inhibitor did not induce the same changes in gene expression as iDKO, and prolonged treatment of mice with a CDK8/19 inhibitor did not affect the size of testes. iDKO, in contrast to single knockouts or treatment with a CDK8/19 kinase inhibitor, led to depletion of cyclin C (CcnC), the binding partner of CDK8/19 that has been implicated in CDK8/19-independent functions. This suggests that the observed phenotype was likely mediated through kinase-independent activities of CDK8/19, such as CcnC stabilization.
A High-Throughput Data-Independent Acquisition Workflow for Deep Characterisation of thesn-Isomer Lipidome
Authors: Michael Jesse A. , Young Reuben S. E. , Balez Rachelle , Jekimovs Lachlan J. , Marshall David. L. , Poad Berwyck L. J. , Mitchell Todd W. , Blanksby Stephen J. , Ejsing Christer S. , Ellis Shane R.
Published: November 2023

We report a workflow based on ozone-induced dissociation for untargeted characterization of hundreds ofsn-resolved glycerophospholipid isomers from biological extracts in under 20 minutes, coupled with an automated data analysis pipeline. It provides an order of magnitude increase in the number ofsn-isomer pairs identified compared to previous reports, reveals thatsn-isomer populations are tightly regulated and significantly different between cell lines, and enables identification of rare lipids containing ultra-long chain monounsaturated acyl chains.
Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling
Authors: Bolamperti Simona , Saito Hiroaki , Heerdmann Sarah , Hesse Eric , Taipaleenmäki Hanna
Published: November 2023

Osteoblast adherence to bone surfaces is important for remodeling of the bone tissue. This study demonstrates that deficiency of TG-interacting factor 1 (Tgif1) in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matricesin vitro. Furthermore, Tgif1 acts as transcriptional repressor of p21-activated kinase 3 (PAK3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased PAK3 expression, which impairs osteoblast spreading. Additionally, Tgif1 is implicated in osteoblast recruitment and activation of bone surfaces in the context of bone regeneration and in response to parathyroid hormone 1-34 (PTH 1-34) treatmentin vivo. These findings provide important novel insights in the regulation of the cytoskeletal architecture of osteoblasts.
Buffering effects of nonspecifically DNA-bound RNA polymerases in bacteria
Authors: Yan Yichen , Li Tairan , Lin Jie
Published: November 2023

RNA polymerase (RNAP) is the workhorse of bacterial gene expression, transcribing rRNA and mRNA. Experiments found that a significant fraction of RNAPs in bacteria are nonspecifically bound to DNA, which is puzzling as these idle RNAPs could have produced more RNAs. Whether nonspecifically DNA-bound RNAPs have any function or are merely a consequence of passive interaction between RNAP and DNA is unclear. In this work, we propose that nonspecifically DNA-bound RNAPs buffer the free RNAP concentration and mitigate the crosstalk between rRNA and mRNA transcription. We verify our theory using mean-field models and an agent-based model of transcription, showing that the buffering effects are robust against the interaction between RNAPs and sigma factors and the spatial fluctuation and temporal noise of RNAP concentration. We analyze the relevant parameters ofEscherichia coliand find that the buffering effects are significant across different growth rates at a low cost, suggesting that nonspecifically DNA-bound RNAPs are evolutionarily advantageous.
Vina-GPU 2.1: towards further optimizing docking speed and precision of AutoDock Vina and its derivatives
Authors: Tang Shidi , Ding Ji , Zhu Xiangyu , Wang Zheng , Zhao Haitao , Wu Jiansheng
Published: November 2023

AutoDock Vina and its derivatives have established themselves as a prevailing pipeline for virtual screening in contemporary drug discovery. Our Vina-GPU method leverages the parallel computing power of GPUs to accelerate AutoDock Vina, and Vina-GPU 2.0 further enhances the speed of AutoDock Vina and its derivatives. Given the prevalence of large virtual screens in modern drug discovery, the improvement of speed and accuracy in virtual screening has become a longstanding challenge. In this study, we propose Vina-GPU 2.1, aimed at enhancing the docking speed and precision of AutoDock Vina and its derivatives through the integration of novel algorithms to facil-itate improved docking and virtual screening outcomes. Building upon the foundations laid by Vina-GPU 2.0, we introduce a novel algorithm, namely Reduced Iteration and Low Complexity BFGS (RILC-BFGS), designed to expedite the most time-consuming operation. Additionally, we implement grid cache optimization to further enhance the docking speed. Furthermore, we employ optimal strategies to individually optimize the structures of ligands, receptors, and binding pockets, thereby enhancing the docking precision. To assess the performance of Vina-GPU 2.1, we conduct extensive virtual screening experiments on three prominent targets, utilizing two fundamental compound libraries and seven docking tools. Our results demonstrate that Vina-GPU 2.1 achieves an average 4.97-fold acceleration in docking speed and an average 342% improvement in EF1% compared to Vina-GPU 2.0. The source code and tools for Vina-GPU 2.1 are freely available athttps://github.com/DeltaGroupNJUPT/Vina-GPU-2.1, accompanied by comprehensive instructions and illustrative examples.
lociPARSE: a locality-aware invariant point attention model for scoring RNA 3D structures
Authors: Tarafder Sumit , Bhattacharya Debswapna
Published: November 2023

A scoring function that can reliably assess the accuracy of a 3D RNA structural model in the absence of experimental structure is not only important for model evaluation and selection but also useful for scoring-guided conformational sampling. However, high-fidelity RNA scoring has proven to be difficult using conventional knowledge-based statistical potentials and currently-available machine learning-based approaches. Here we present lociPARSE, a locality-aware invariant point attention architecture for scoring RNA 3D structures. Unlike existing machine learning methods that estimate superposition-based root mean square deviation (RMSD), lociPARSE estimates Local Distance Difference Test (lDDT) scores capturing the accuracy of each nucleotide and its surrounding local atomic environment in a superposition-free manner, before aggregating information to predict global structural accuracy. Tested on multiple datasets including CASP15, lociPARSE significantly outperforms existing statistical potentials (rsRNASP, cgRNASP, DFIRE-RNA, and RASP) and machine learning methods (ARES and RNA3DCNN) across complementary assessment metrics. lociPARSE is freely available athttps://github.com/Bhattacharya-Lab/lociPARSE.
Vegetation ofChamaecyparismontane cloud forest in Lalashan Forest Dynamics Plot
Authors: Chen Ting , Lee Yi-Nuo , Lin Po-Yu , Wu Kun-Sung , Zelený David
Published: November 2023

To understand the vegetation-environment relationships within theChamaecyparismontane mixed cloud forest in Taiwan, we established a 1-ha Lalashan Forest Dynamics Plot (LFDP) in northern Taiwan (24°42D N, 121°26D E). We established the plot in July 2019 and finished the first census of all woody species in August 2020. We collected environmental factors related to the topography and soil properties, measured microclimate and soil moisture within the plot, and collected further microclimatic data with a nearby weather station. In total, we recorded 5220 individuals belonging to 65 species, 42 genera and 29 families, with a basal area of 69.1 m2ha−1, dominated byChamaecyparis obtusavar.formosana,Rhododendron formosanumandQuercus sessilifolia. Modified TWINSPAN classified vegetation into three types (ridge, east-facing slope and valley). Unconstrained ordination showed that the main gradients behind compositional changes are related to windwardness and convexity. The prevailing wind direction in the area is from the northeast, linked to the winter monsoon. Both east-facing slope type and valley type have relatively lower temperatures than ridge type, especially during summer. Convexity is related to soil moisture gradient (from dryer convex to wet concave sites). Fog frequency is seasonal, with the highest values during autumn and winter months. From soil properties, pH is negatively and phosphorus is positively related to topographical convexity. Litter decomposition is linked to both topographical, soil and biotic variables. Collected data will serve as a baseline for future resurveys and monitoring changes within this montane cloud forest.
Investigating DNA methylation changes associated with food production using paleogenomes
Authors: Çokoğlu Sevim Seda , Koptekin Dilek , Fidan Fatma Rabia , Somel Mehmet
Published: November 2023

Abstract

The Neolithic transition introduced major diet and lifestyle changes to human populations across continents. Beyond well-documented bioarchaeological and genetic effects, whether these changes also had molecular-level epigenetic repercussions in past human populations has been an open question. In fact, methylation signatures can be inferred from UDG-treated ancient DNA through postmortem damage patterns, but with low signal-to-noise ratios; it is thus unclear whether published paleogenomes would provide the necessary resolution to discover systematic effects of lifestyle and diet shifts. To address this we compiled UDG-treated shotgun genomes of 13 pre-Neolithic hunter-gatherer (HGs) and 21 Neolithic farmer (NFs) individuals from West and North Eurasia, published by six different laboratories and with coverage c.1x-58x (median=9x). We used epiPALEOMIX and a Monte Carlo normalization scheme to estimate methylation levels per genome. Our paleomethylome dataset showed expected genome-wide methylation patterns such as CpG island hypomethylation. However, analysing the data using various approaches did not yield any systematic signals for subsistence type, genetic sex, or tissue effects. Comparing the HG-NF methylation differences in our dataset with methylation differences between hunter-gatherers vs. farmers in modern-day Central Africa also did not yield consistent results. Meanwhile, paleomethylome profiles did cluster strongly by their laboratories of origin. Our results mark the importance of minimizing technical noise for capturing subtle biological signals from paleomethylomes.
Sources of gene expression variation in a globally diverse human cohort
Authors: Taylor Dylan J. , Chhetri Surya B. , Tassia Michael G. , Biddanda Arjun , Battle Alexis , McCoy Rajiv C.
Published: November 2023

Abstract/Summary

Genetic variation influencing gene expression and splicing is a key source of phenotypic diversity. Though invaluable, studies investigating these links in humans have been strongly biased toward participants of European ancestries, diminishing generalizability and hindering evolutionary research. To address these limitations, we developed MAGE, an open-access RNA-seq data set of lymphoblastoid cell lines from 731 individuals from the 1000 Genomes Project spread across 5 continental groups and 26 populations. Most variation in gene expression (92%) and splicing (95%) was distributed within versus between populations, mirroring variation in DNA sequence. We mapped associations between genetic variants and expression and splicing of nearby genes (cis-eQTLs andcis-sQTLs, respective), identifying >15,000 putatively causal eQTLs and >16,000 putatively causal sQTLs that are enriched for relevant epigenomic signatures. These include 1310 eQTLs and 1657 sQTLs that are largely private to previously underrepresented populations. Our data further indicate that the magnitude and direction of causal eQTL effects are highly consistent across populations and that apparent “population-specific” effects observed in previous studies were largely driven by low resolution or additional independent eQTLs of the same genes that were not detected. Together, our study expands understanding of gene expression diversity across human populations and provides an inclusive resource for studying the evolution and function of human genomes.
Aryl hydrocarbon receptor restricts axon regeneration of DRG neurons in response to injury
Authors: Halawani Dalia , Wang Yiqun , Estill Molly , Sefiani Arthur , Ramakrishnan Aarthi , Li Jiaxi , Ni Haofei , Halperin Daniel , Shen Li , Geoffroy Cedric G. , Friedel Roland H , Zou Hongyan
Published: November 2023

Injured neurons sense environmental cues to balance neural protection and axon regeneration, but the mechanisms are unclear. Here, we unveil aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, as a molecular sensor and key regulator of acute stress response at the expense of axon regeneration. We demonstrate responsiveness of DRG sensory neurons to AhR signaling, which functions to inhibit axon regeneration. Conditional Ahr deletion in neurons accelerates axon regeneration after sciatic nerve injury. Ahr deletion partially mimics the conditioning lesion in priming DRG to initiate axonogenesis gene programs; upon peripheral axotomy, Ahr ablation suppresses inflammation and stress signaling while augmenting pro-growth pathways. Moreover, comparative transcriptomics revealed signaling interactions between AhR and HIF-1α, two structurally related bHLH-PAS α units that share the dimerization partner Arnt/HIF-1β. Functional assays showed that the growth advantage of AhR-deficient DRG neurons requires HIF-1α; but in the absence of Arnt, DRG neurons can still mount a regenerative response. We further unveil a link between bHLH-PAS transcription factors and DNA hydroxymethylation in response to peripheral axotomy, while RNA-seq of DRG neurons and neuronal single cell RNA-seq analysis revealed a link of AhR regulon to RNA regulation and integrated stress response (ISR). Altogether, AhR activation favors stress coping and inflammation at the expense of axon regeneration; targeting AhR has the potential to enhance nerve repair.
Cerebral thickness reveals sex differences in verbal and visuospatial memory
Authors: Sang Feng , Zhao Shaokun , Li Zilin , Yang Yiru , Chen Yaojing , Zhang Zhanjun
Published: November 2023

Although sex differences in behavior/cognition and brain have previously been reported and reviewed, a sex difference of verbal and visuospatial memory and the underlying neural basis still need to be explored further. In this study, we used a machine learning model to explore a sex difference of the association between brain structure and verbal/visuospatial memory based on a community older cohort (n = 1153, age ranged from 50.42 to 86.67 years). We found females outperformed males in verbal memory (t= -5.431,p< 0.001), while males outperformed females in visuospatial memory (t= 3.201,p= 0.001). The key regions related to verbal memory in females include medial temporal cortex, orbitofrontal cortex, and some regions around insula. According to the overlapping with Yeo’s 7 networks, those regions are more located in limbic, dorsal attention and default model networks, and they are also associated with face recognition and perception processes. The key regions related to visuospatial memory, which is outstanding in males, include lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and associated with object recognition processes. These findings imply the memory performance advantage of females and males is related to the different memory preprocessing tendencies and its associated network.
Mapping Chromatin Occupancy ofPpp1r1b-lncRNAGenome-Wide Using Chromatin Isolation by RNA Purification (ChIRP)-seq
Authors: Hwang John , Kang Xuedong , Wolf Charlotte , Touma Marlin
Published: November 2023

Long non-coding RNA (lncRNA) mediated transcriptional regulation is increasingly recognized as an important gene regulatory mechanism during development and disease. LncRNAs are emerging as critical regulators of chromatin state; yet the nature and the extent of their interactions with chromatin remain to be fully revealed. We have previously identifiedPpp1r1b-lncRNAas an essential epigenetic regulator of myogenic differentiation in cardiac and skeletal myocytes in mice and humans. We further demonstrated thatPpp1r1b-lncRNAfunction is mediated by the interaction with the chromatin-modifying complex polycomb repressive complex 2 (PRC2) at the promoter of myogenic differentiation transcription factors,TBX5andMyoD1. Herein, we employed an unbiased chromatin isolation by RNA purification (ChIRP) and high throughput sequencing to map the repertoire ofPpp1r1b-lncRNAchromatin occupancy genome-wide in the mouse muscle myoblast cell line. We uncovered a total of 99732 true peaks corresponding toPpp1r1b-lncRNAbinding sites at high confidence (P-value < 1e-5 and enrichment score ≥ 10). ThePpp1r1b-lncRNA-binding sites averaged 558 bp in length and were distributed widely within the coding and non-coding regions of the genome. Approximately 46% of these true peaks were mapped to gene elements, of which 1180 were mapped to experimentally validated promoter sequences. Importantly, the promoter-mapped binding sites were enriched in myogenic transcription factors and heart development while exhibiting focal interactions with known motifs of proximal promoters and transcription initiation by RNA polII, including TATA, transcription initiator, CCAAT-box, and GC-box, supportingPpp1r1b-lncRNArole in transcription initiation of myogenic regulators. Remarkably, nearly 40% ofPpp1r1b-lncRNA-binding sites mapped to gene introns, were enriched with the Homeobox family of transcription factors, and exhibited TA-rich motif sequences, suggesting potential motif specificPpp1r1b-lncRNA-bound introns. Lastly, more than 136521enhancer sequences were detected inPpp1r1b-lncRNA-occupancy sites at high confidence. Among these enhancers,12% exhibited cell type/tissue-specific enrichment in fetal heart and muscles. Together, our findings provide further insights into the genome-widePpp1r1b-lncRNA:Chromatin interactome that may potentially dictate its function in myogenic differentiation and potentially other cellular and biological processes.
Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization
Authors: Ben-Hur Sharon , Afar Sara , Politi Yoav , Gal Liron , Golani Ofra , Sivan Ehud , Haffner-Krausz Rebecca , Maizenberg Elina , Peretz Sima , Roth Zvi , Kalo Dorit , Dezorella Nili , Morgenstern David , Pietrokovski Shmuel , Yacobi-Sharon Keren , Arama Eli
Published: November 2023

Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination (PME) after fertilization are far less clear. UsingDrosophila, we show that special egg-derived multivesicular bodies (MVBs) promote PME by activating LC3-associated phagocytosis (LAP), a cellular defense pathway commonly employed against invading microbes. Upon fertilization, the egg MVBs engage and densely coat the sperm flagellum, forming extended flagellum vesicular sheaths (FVSs), within which the paternal mitochondria degrade. Inactivation of multiple LAP pathway components, such as Rubicon, a LAP-specific class III PI(3)K complex protein, significantly attenuates PME. Furthermore, recruitment of Atg8/LC3 to the FVS requires both Rubicon and the Atg8/LC3 conjugation machinery. Other LAP pathway events, such as production of the phospholipid PtdIns(3)P and reactive oxygen species (ROS), also unfold during PME. Finally, we provide evidence that a similar pathway might also mediate PME in mammals, highlighting the notion that eggs may regard paternal mitochondria as potentially dangerous trespassers.
On prefrontal working memory and hippocampal episodic memory: Unifying memories stored in weights and activity slots
Authors: Whittington James C.R. , Dorrell William , Behrens Timothy E.J. , Ganguli Surya , El-Gaby Mohamady
Published: November 2023

Remembering events in the past is crucial to intelligent behaviour. Flexible memory retrieval, beyond simple recall, requires a cognitive map, or model of how sensations, actions, and latent environmental or task states are all related to one another. Two key brain systems are implicated in this process: the hippocampal episodic memory (EM) system and the prefrontal working memory (WM) system. While an understanding of the hippocampal system, from computation to algorithm and representation, is emerging, less is understood about how the prefrontal WM system can give rise to flexible computations beyond simple memory retrieval, and even less is understood about how the two systems relate to each other. Here we develop a mathematical theory relating the algorithms and representations of EM and WM by unveiling a duality between storing memories in synapses versus neural activity. In doing so, we develop a formal theory of the algorithms and representations of prefrontal WM in terms of structured, and controllable, neural subspaces (termed activity slots) that together can represent a dynamic cognitive map without any need for synaptic plasticity. By building models using this formalism, we elucidate the differences, similarities, and trade-offs between the hippocampal and prefrontal algorithms. Lastly, we show that several prefrontal representations in tasks ranging from list learning to cue dependent recall are unified as controllable activity slots. Our results unify frontal and temporal representations of memory, and offer a new basis for understanding dynamic prefrontal representations of WM.
Challenges in the Biotechnological Implementation of Oral RNA Interference as an Antiviral Strategy inAedes aegypti
Authors: Romoli Ottavia , Henrion-Lacritick Annabelle , Blanc Hervé , Frangeul Lionel , Saleh Maria-Carla
Published: November 2023

Mosquitoes, particularlyAedes aegypti, are critical vectors for globally significant pathogenic viruses. This study examines the limitations of oral RNA interference (RNAi) as a strategy to disrupt viral transmission byAe. aegypti. We hypothesized that double-stranded RNA (dsRNA) targeting the Zika virus (ZIKV) or chikungunya virus (CHIKV) genomes produced by engineered bacterial symbionts could trigger an antiviral response. Mosquitoes mono-colonized withEscherichia coliproducing dsZIK or dsCHIK did not display reduced viral titers following exposure to virus-contaminated bloodmeals and failed to generate dsZIK- or dsCHIK-derived small interfering RNAs. To address potential limitations of bacterial dsRNA release, we explored dsRNA inoculation via feeding and injection. While viral replication was impeded in mosquitoes injected with dsZIK or dsCHIK, no antiviral effect was observed in dsRNA-fed mosquitoes. These findings highlight complexities of implementing oral RNAi as an antiviral strategy inAe. aegyptiand warrant further exploration of local and systemic RNAi mechanisms.
Cortical areas for planning sequences before and during movement
Authors: Ariani Giacomo , Shahbazi Mahdiyar , Diedrichsen Joern
Published: November 2023

Production of rapid movement sequences relies on preparation before (pre-planning) and during (online planning) movement. Here, we asked how different cortical sensorimotor areas contribute to these processes. Human participants performed three single-finger and three multi-finger sequences in a delayed movement paradigm. During preparation, 7T functional MRI revealed that primary motor (M1) and somatosensory (S1) areas showed pre-activation of the first movement, even though the overall activation level did not change from baseline. During production, the activity in M1 and S1 could be explained by temporal summation of activity patterns corresponding to constituent fingers. In contrast, dorsal premotor (PMd) and anterior superior parietal lobule (aSPL) showed substantial activation during preparation of multi-finger as compared to single-finger sequences. The same regions were also more activated during production of multi-finger sequences, suggesting that the same areas are involved in both pre- and online planning. Nonetheless, we observed small but robust differences between the two contrasts, suggesting preferential involvements of these areas in pre- and online planning. Multivariate analysis revealed sequence-specific representations in both PMd and aSPL, which remained stable across both preparation and production phases. This suggests that these areas maintain a sequence-specific representation before and during sequence production, likely guiding the execution-related areas.
The role of dynamic capabilities on the effectiveness of organizational changes in public sector
Authors: Castelo Samuel Leite , Gomes Carlos F.
Published: November 2023

Purpose

Governments worldwide have used administrative reforms to align public organizations with the needs of their key stakeholders. However, despite successfully implementing them, they do not consistently achieve the desired organizational performance. This paper aims to explore the relationship between the implementation of administrative reforms and the performance of public organizations from a comprehensive perspective. For this purpose, the authors analyze the mediation role of three crucial dynamic capabilities.

Design/methodology/approach

This research used a survey-based methodology. Structural equation modeling (SEM) was used to analyze the data obtained from a sample of public officials and managers working in public organizations in the State of Ceará (Brazil).

Findings

The results of this study suggest that dynamic capabilities can have a decisive role in implementing government policy proposals and helping public organizations align their outcomes with stakeholders' needs. In addition, they indicate the existence of two levels of capabilities and identify a road map for their implementation.

Practical implications

From a practical point of view, by identifying these capabilities and their interrelationship, this study provides a roadmap to reduce the complexity of their use and help managers of public organizations deliver desired outcomes relating to the quality of individual and collective stakeholders.

Originality/value

This study makes important contributions to the literature, enabling scholars and practitioners to see the result of government policy proposals beyond the efficient use of public resources. It shows the role of dynamic capabilities as mediation instruments for changing public organizations, which can be used in administrative reform implementations and continuous improvement processes. Finally, it provides empirical research on the interaction between the three dynamic capabilities in the context of public organizations, differentiating these capabilities into two levels, which provides a road map for their implementation and development by public managers.
How critical success factors combine to influence success? A configurational theory approach on multiple social projects
Authors: Crisan Emil Lucian , Dan Madalina , Beleiu Ioana Natalia , Ciocoiu Eugenia , Beudean Paula
Published: November 2023

Purpose

In literature, it is recognized that there is no universal set of critical success factors (CSFs) applicable to all projects. The goal of this research is to validate a theoretical model which considers that CSFs’ influence on project success (PS) is configurational, that CSFs combine to influence PS.

Design/methodology/approach

The authors proposed a theoretical framework which operationalizes CSFs considering contingency and institutional theories' terms, as external contingencies, organizational resources and project strategies, which influence PS. The framework is validated through a qualitative approach on 18 social projects implemented by nongovernmental organizations (NGOs). Based on the conducted semistructured interviews with NGO managers or project managers, 91 instances when CSFs combine to influence PS were identified.

Findings

The dominant path reveals the combination of CSFs in terms of strategies adopted to face contingencies (70 instances), another as resources which moderate managers' strategies (14 instances), and in seven instances positive contingencies and resources combine and influence the PS. The results reveal that CSFs combine in reactive and dynamic ways to influence PS.

Originality/value

The research contributes to the vast literature on projects' success by adopting a different perspective. Configurational theory explains project management and projects' complexity better than the traditional approaches, which have a rather correlational perspective.
Fine‐tuning rice heading date through multiplex editing of the regulatory regions of key genes by CRISPR‐Cas9
Authors: Zhou Shirong , Cai Liang , Wu Haoqin , Wang Baoxiang , Gu Biao , Cui Song , Huang Xiaolong , Xu Zhuang , Hao Benyuan , Hou Haigang , Hu Yuan , Li Chao , Tian Yunlu , Liu Xi , Chen Liangming , Liu Shijia , Jiang Ling , Wan Jianmin
Published: November 2023

Heading date (or flowering time) is a key agronomic trait that affects seasonal and regional adaption of rice cultivars. An unoptimized heading date can either not achieve a high yield or has a high risk of encountering abiotic stresses. There is a strong demand on the mild to moderate adjusting the heading date in breeding practice. Genome editing is a promising method which allows more precise and faster changing the heading date of rice. However, direct knock out of major genes involved in regulating heading date will not always achieve a new germplasm with expected heading date. It is still challenging to quantitatively adjust the heading date of elite cultivars with best adaption for broader region. In this study, we used a CRISPR‐Cas9 based genome editing strategy called high‐efficiency multiplex promoter‐targeting (HMP) to generate novel alleles at cis‐regulatory regions of three major heading date genes: Hd1, Ghd7 and DTH8. We achieved a series of germplasm with quantitative variations of heading date by editing promoter regions and adjusting the expression levels of these genes. We performed field trials to screen for the best adapted lines for different regions. We successfully expanded an elite cultivar Ningjing8 (NJ8) to a higher latitude region by selecting a line with a mild early heading phenotype that escaped from cold stress and achieved high yield potential. Our study demonstrates that HMP is a powerful tool for quantitatively regulating rice heading date and expanding elite cultivars to broader regions.
Complete genome sequence of
Streptomyces
strain VNUA116, a potential biocontrol against phytopathogenic fusarium wilt fungus
Fusarium oxysporum
f. sp.
cubense
Authors: Nguyen Mai Thi Thanh , Dinh Son Truong , Nguyen Canh Xuan
Published: November 2023

Here, we present the whole-genome sequence of
Streptomyces
strain VNUA116 was obtained by combining sequencing data from both PacBio RS II and DNBseq platforms. The complete circular genome is 8,306,919 bp with a GC content of 72.49%.
Investigation of Uncertainty in Organic Carbon Stock Estimates on a Field Scale
Authors: Samsonova V. P. , Meshalkina J. L. , Dobrovolskaya V. A. , Kondrashkina M. I. , Dyadkina S. E. , Filippova O. I. , Krotov D. G. , Morozova T. M. , Krasilnikov P. V.
Published: November 2023

The uncertainty sources in the assessment of organic carbon stocks were studied in a layer of 0–30 cm within the sampling site (100 × 100 m) set on soddy-podzolic cultivated soil (Albic Glossic Retisol (Aric, Loamic, Ochric)). In the experiment, two sampling methods were used – the classic sampling in pits, by 10-cm layers, and sampling with an auger to a depth of 0–30 cm. The soil bulk density was determined by the Kachinsky method and the carbon content was analyzed by the Tyurin method. Some samples were additionally analyzed at the Bryansk State Agrarian University. The uncertainties associated with natural variation, sample preparation and the analytical process proper were estimated. The analytical uncertainty of bulk density measurement did not depend on the sampling depth under the experimental conditions and amounted to about 6%. The analytical error of Tyurin’s method did not differ in two laboratories. Its contribution reached 5–9% of the total variation in soil organic carbon content at the test plot. The uncertainty of sample preparation ranged from 11 to 26%, natural variation—from 49 to 68% to the total variance, respectively. Determination of carbon content in the samples taken with an auger from the depth of 0–30 cm is preferable than layer-by-layer sampling as the number of intermediate operations is fewer, and the obtained results are comparable.
Weight regain does not eliminate the long term benefits of weight management programmes
Authors: Saul Helen , Deeney Brendan , Kwint Jemma , Aveyard Paul
Published: November 2023

The study

Hartmann-Boyce J, Theodoulou A, Oke JL, et al. Long term effect of weight regain following behavioral weight management programs on cardiometabolic disease incidence and risk: systematic review and meta-analysis.
Circ Cardiovasc Qual Outcomes
2023;16:263-76.

To read the full NIHR Alert, go to:

https://evidence.nihr.ac.uk/alert/weight-regain-does-not-eliminate-the-long-term-benefits-of-weight-management-programmes/#:~:text=Study%20author&text=Many%20people%20believe%20that%20if,been%20the%20case%20without%20it
.
Computer Benchmarks: 50 Years Ago and Now
Authors: Freiburger Dana
Published: November 2023

Fifty years ago, computer benchmarks were a common practice. In a 1973 article in Computing Surveys, Eric Timmreck, a recent University of Wisconsin-Madison CS Ph.D. graduate working at Shell Research in Houston, Texas, identified three benchmark types to validate a proposed system: Artificial, Standard, and Live benchmarks [1]. He highlighted the latter type in saying, "There is substantial agreement that the only performance tool which is accurate enough for selection purposes is a well-composed live benchmark." Timmreck left it to readers to pick a methodology, including any of six other approaches he cited "to prove that a system can in fact carry the user's load."
ARIC 2022 Workshop Report: The 5
th
ACM SIGSPATIAL International Workshop on Advances in Resilient and Intelligent Cities Seattle, WA, USA November 1, 2022
Authors: Kar Bandana , Mohebbi Shima , Fu Guangtao , Ye Xinyue , Omitaomu Olufemi A.
Published: November 2023

This report summarizes the focus of the 5
th
ACM SIGSPATIAL International Workshop on Advances in Resilient and Intelligent Cities (ARIC 2022 - https://urbands.github.io/ARIC2022/) that was held in-person in Seattle, Washington on November 1, 2022. The attendance for the workshop was 20. The ARIC workshop started in 2017 with an aim to promote the interdisciplinary discussions among researchers, practitioners and developers to identify techniques and methods that would enable building next generation cities and infrastructures. This workshop has been continuing its mission to bring together researchers and practitioners to address the state-of-the-art techniques/methods, limitations and challenges of making cities that are both smart and resilient to extreme events.
The 15
th
ACM SIGSPATIAL International Workshop on Computational Transportation Science (IWCTS 2022), Seattle, WA, USA - November 1, 2022
Authors: Kurte Kuldeep , Berres Andy , Xu Haowen
Published: November 2023

The 15th International Workshop on Computational Transportation Science (IWCTS 2022) is particularly timely given the prominence of human mobility data, such as probe data from cell phones and connected automated vehicles, volunteered geographic information, and other sensing data. This unprecedented access to sensing data of mobility, and of integration of this analytics into smart cities management has led to innovations in intelligent transportation systems, building information management, and urban planning. Due to the scale of the data, these developments are deeply computational.
An Eco-Friendly, Interference, and Solvent Free Surfactant-Assisted Dual-Wavelength β-CorrectionSpectrometric Method for Total Determination and Speciation of Cu2+ Ions in Water
Authors: Alwael Hassan , Al-Raimi Doaa S. , Al-Ahmary Khairia M. , Nasef Hany A. , Alharthi Amal S. , Abduljabbar Tharawat N. , Mujawar Liyakat H. , Danish Ekram Y. , Soomro Mohammad T. , El-Shahawi Mohammad S.
Published: November 2023

Spectral interference through the presence of uninformative variables, excess reagents, and complications in the refinement of the analyte signal is common in the quest to identify complex species in real samples. Therefore, an economical green, facile, and sensitive strategy has been developed for Cu2+ detection using the anionic surfactant sodium dodecylsulphate- (SDS-) assisted dual-wavelength β-correction spectrophotometric strategy combined with the chromogenic reagent zincon (ZI). The low limits of detection (LOD) and quantification (LOQ) of Cu2+ using ordinary (single wavelength) spectrophotometry were 0.19 (3.02) and 0.63 (10.0) μgmL−1, and these values were improved to 0.08 (1.27) and 0.26 μgmL−1 (4.12 μM)) using β-correction (dual wavelength) spectrophotometry, respectively. The LOD and LOQ were improved from 0.08 (1.27) and 0.26 (4.12) μgmL−1 to 0.02 (0.32) and 0.08 μgmL−1 (1.27 μM) using SDS-assisted dual-β-correction spectrometry, respectively. Ringbom, s, and the corrected absorbance (Ac) versus Cu2+ concentration plots were linear over the concentration range 1.10–2.4 (17.4–38.1) and 0.50–2.40 μgmL−1 (7.94–38.1 μM), respectively. Sandell’s sensitivity index of 3.0 × 10−3 μg/cm2 was achieved. The selectivity was further confirmed via monitoring the impact of common diverse ions and surfactants on the corrected absorbance. Total determination and Cu2+ speciation in water were favorably implemented and validated by ICP-OES at 95% (

P
=
0.05

). Satisfactory Cu2+ recoveries in tap (92.2–98.0%) and mineral (105–111.0%) water samples were achieved. The sensing system is simple, reliable, sensitive, and selective for Cu2+ detection.
Nursing Documentation Practices and Related Factors in Patient Care in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Hardido Temesgen Geta , Kedida Beimnet Desalegn , Kigongo Eustes
Published: November 2023

Background. Ineffective nursing documentation practices have been reported to negatively impact patient outcomes and health professional efficiency. On the prevalence of nurses’ documentation practices in Ethiopia, several separate studies have been carried out. However, there is no pooled prevalence of nurses’ documentation practice. Therefore, this systematic review and meta-analysis aimed to assess the overall prevalence of nursing care documentation practice and related factors in Ethiopia. Methods and Materials. This review only included articles that were published. The main databases were Medline/PubMed, Web of Science, Google Scholar, Scopus, Ethiopian University Repository Online, and the Cochrane Library. Cross-sectional studies that satisfy the criteria and are written in English are included in the review. Using a random effects model, the pooled prevalence of nurses’ documentation practices was determined. The funnel plot and the Eggers test were also used to look into publication bias. All statistical analyses were done with STATA version 14. Result. This review included nine studies with a total of 2,900 participants. The pooled prevalence of nurses’ documentation practice in Ethiopia was 50.01% (95% CI: 42.59 and 57.18; I2 = 93.8%; and

P
≤
0.001

). In terms of subgroup analysis, Addis Ababa had the highest prevalence of nurses’ documentation practice at 84% (95% CI: 77.18 and 90.82), while Southern Ethiopia had the lowest at 40.00% (95% CI: 38.10 and 44.90). Nursing documentation practices were statistically associated with the availability of nursing documentation formats, adequate nurse-to-patient ratio, motivation, and training. Conclusion. This review showed that one in two nurses practiced poor documentation of their daily activities in Ethiopia. Therefore, strict monitoring, evaluation, and supervision of nursing care documentation services are highly recommended for all stakeholders. We strongly recommend improving the identified factors by arranging training for nurses, motivating them, providing adequate documentation formats, and maintaining a nurse-to-patient ratio.
Water Quality Prediction Based on Hybrid Deep Learning Algorithm
Authors: Perumal Bhagavathi , Rajarethinam Niveditha , Velusamy Anusuya Devi , Sundramurthy Venkatesa Prabhu
Published: November 2023

Pollution from many different sources severely affects the quality of our water supply. Over the past few years, a large number of online water quality monitoring stations have been used to gather time series data on water quality monitoring. These numbers are the foundation for deep learning techniques for forecasting water quality. In particular, typical deep learning approaches struggle to accurately estimate water quality in the presence of net promoter system (NPS) contamination. To overcome this shortcoming, a new deep learning model called long short-term memory (LSTM)–gray wolf optimization (GWO)–fish swarm optimization (FSO) was developed to enhance the precision of water quality prediction with NPS pollution. The well-established model may remedy the mechanism models’ inability to foretell changes in water quality on a minute-by-minute basis. Thamirabarani river watershed was used for the model’s application. Based on experimental data, the suggested model outperformed the mechanism model and the LSTM model in predicting extreme values. Maximum relative errors in anticipated against observed dissolved oxygen, chemical oxygen demand, and NH3─N values were 7.58%, 18.45%, and 22.25%, respectively. In comparison to the artificial neural network (ANN), back propagation neural network (BPNN), and recurrent neural network (RNN) models, the created LSTM–GWO–FSO model was shown to have greater computational performance (RNN). LSTM–GWO–FSO outperformed ANN, BPNN, and RNN regarding R2 of 3.1%–38.4% improvements. The suggested approach may provide a fresh perspective when predicting water quality in the presence of NPS contamination.