bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepSomatic: Accurate somatic small variant discovery for multiple sequencing technologies
Authors: Park Jimin , Cook Daniel E. , Chang Pi-Chuan , Kolesnikov Alexey , Brambrink Lucas , Mier Juan Carlos , Gardner Joshua , McNulty Brandy , Sacco Samuel , Keskus Ayse , Bryant Asher , Ahmad Tanveer , Shetty Jyoti , Zhao Yongmei , Tran Bao , Narzisi Giuseppe , Helland Adrienne , Yoo Byunggil , Pushel Irina , Lansdon Lisa A. , Bi Chengpeng , Walter Adam , Gibson Margaret , Pastinen Tomi , Farooqi Midhat S. , Robine Nicolas , Miga Karen H. , Carroll Andrew , Kolmogorov Mikhail , Paten Benedict , Shafin Kishwar
Published: August 2024

Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples. To help address the dearth of publicly available training and benchmarking data for somatic variant detection, we generated and make openly available a dataset of five matched tumor-normal cell line pairs sequenced with Illumina, PacBio HiFi, and Oxford Nanopore Technologies, along with benchmark variant sets. Across samples and technologies (short-read and long-read), DeepSomatic consistently outperforms existing callers, particularly for indels.
The congenital multiple organ malformation syndrome, Ritscher-Schinzel syndrome is an endosomal recyclinopathy
Authors: Kato Kohji , Nishio Yosuke , McMillan Kirsty J , Al-Maraghi Aljazi , Kroes Hester Y , Abdel-Hamid Mohamed S , Jones Emma , Shaw Shrestha , Yoshida Aya , Otsuji Shiomi , Murofushi Yuka , Aamer Waleed H. O. , Bhat Ajaz A , AlRayahi Jehan , Akil Ammira Al-Shabeeb , van Binsbergen Ellen , Janssen Etienne J , Oishi Hisashi , Kobayashi Ryosuke , Horii Takuro , Hatada Izuho , Saito Akihiko , Hattori Mitsuharu , Kawano Yoshihiko , Lewis Philip A , Heesom Kate J , Takarada Takeshi , Sawamoto Kazunobu , Matsushita Masaki , Ogi Tomoo , Butkovic Rebeka , Danson Chris , Wilkinson Kevin A , Fakhro Khalid A , Zaki Maha S , Saitoh Shinji , Cullen Peter J
Published: August 2024

Ritscher-Schinzel syndrome (RSS) is a congenital malformation syndrome characterized by cerebellar, cardiac, and craniofacial malformations and phenotypes associated with liver, skeletal and kidney dysfunction. The genetic cause of RSS remains to be fully defined, and limited information is available regarding the root cause of the multiple tissue phenotypes. Here, we combine genetic and clinical analysis in patient cohorts with in-cellulo analysis and in vivo phenotypic analysis of a mouse model of RSS, to identify novel causative genes for RSS within the Commander endosomal recycling pathway. We reveal how perturbed endosomal recycling reduces tissue-specific presentation of cell surface integral membrane proteins essential for kidney, bone and brain development and how this leads to major RSS-associated clinical phenotypes including proteinuria, skeletal malformation, and neurological impairment. Our data establishes RSS as a 'recyclinopathy' that arises from a dysfunction in the Commander endosomal recycling pathway.
Hospitalizations for Body Dysmorphic Disorder Across the U.S: Insights From the Nationwide Inpatient Sample Database
Authors: Olaomi Oluwatobi , Anona Kenechukwu , Udegbe Silvia , Uwumiro Fidelis , Okafor Nnenna , Obijuru Chinwendu , Yayehyirad Halleluya , Opeyemi Mojeed , Bojerenu Micheal , Okpujie Victory , Umeani Nnaedozie
Published: August 2024

Background/Aim: Body dysmorphic disorder (BDD) has been associated with significant psychiatric comorbidity and suicidal ideation in the outpatient setting. We examined the hospitalization rates, resource utilization, comorbidities, and outcomes of BDD using inpatient data. In addition, we compared the outcomes of BDD hospitalizations with those of patients with other mental disorders. Methods: Adult hospitalizations for a primary diagnosis of BDD were identified from the 2017-2020 nationwide inpatient sample database using the ICD-10 code (F45.22). We used χ2 analysis to compare categorical variables. For continuous variables, we used t-tests and the Wilcoxon rank-sum test to analyze data with normal and nonnormal distributions. Using rank commands and ICD-10-CM/PCS codes, we identified the most recurring comorbidities and procedures associated with hospitalizations for BDD. The study endpoints included hospitalization rates, secondary indications for hospitalization, most recurring comorbidities and procedures, and outcomes (hospitalization costs, length of stay, and discharge disposition). Results: 3,384 BDD hospitalizations were analyzed (67 cases per 100,000 hospitalizations for mental disorders). 67.6% were female, whereas non-BDD admissions had a male preponderance (67.5%). 71.4% of BDD hospitalizations were for individuals aged between 18 and 40 years. Hospitalizations for BDD were younger than those for other mental disorders (median age: 33 [IQR, 24-50] vs 37 [IQR, 24-54], P<0.001). Approximately 94.6% of BDD hospitalizations had at least one other psychiatric comorbidity. The most common comorbidities were social anxiety disorder (40%), major depressive disorder (22.8%), bipolar II disorder (2.2%), and substance use disorder (18.9%). 17 individuals (O.5%) had attempted suicide, while 10.3% received various cosmetic procedures. BDD was associated with a longer mean hospital stay compared with other mental disorders combined (9 vs 7.8 days; P=0.002). 89.8% of BDD hospitalizations were discharged home routinely, and no mortality was recorded over the period. BDD hospitalizations were associated with higher mean hospital costs than hospitalizations for other mental disorders combined ($34,314 vs. $27,770; P<0.001). Conclusion: BDD hospitalizations are most common among young women, and involve significant psychiatric comorbidities, longer hospital stays, and higher costs than other mental health conditions.
A florigen-expressing subpopulation of companion cells expresses other small proteins and reveals a nitrogen-sensitiveFTrepressor
Authors: Takagi Hiroshi , Ito Shogo , Shim Jae Sung , Kubota Akane , Hempton Andrew K. , Lee Nayoung , Suzuki Takamasa , Yang Chansie , Nolan Christine T. , Bubb Kerry L. , Alexandre Cristina M. , Kurihara Daisuke , Sato Yoshikatsu , Tada Yasuomi , Kiba Takatoshi , Pruneda-Paz Jose L. , Queitsch Christine , Cuperus Josh T. , Imaizumi Takato
Published: August 2024

The precise onset of flowering is crucial to ensure successful plant reproduction. The geneFLOWERING LOCUS T(FT) encodes florigen, a mobile signal produced in leaves that initiates flowering at the shoot apical meristem. In response to seasonal changes,FTis induced in phloem companion cells located in distal leaf regions. Thus far, a detailed molecular characterization of theFT-expressing cells has been lacking. Here, we used bulk nuclei RNA-seq and single nuclei RNA (snRNA)-seq to investigate gene expression inFT-expressing cells and other phloem companion cells. Our bulk nuclei RNA-seq demonstrated thatFT-expressing cells in cotyledons and in true leaves differed transcriptionally. Within the true leaves, our snRNA-seq analysis revealed that companion cells with highFTexpression form a unique cluster in which many genes involved in ATP biosynthesis are highly upregulated. The cluster also expresses other genes encoding small proteins, including the flowering and stem growth inducer FPF1-LIKE PROTEIN 1 (FLP1) and the anti-florigen BROTHER OF FT AND TFL1 (BFT). In addition, we found that the promoters ofFTand the genes co-expressed withFTin the cluster were enriched for the consensus binding motifs of NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1 (NIGT1). Overexpression of the paralogousNIGT1.2andNIGT1.4repressedFTexpression and significantly delayed flowering under nitrogen-rich conditions, consistent with NIGT1s acting as nitrogen-dependentFTrepressors. Taken together, our results demonstrate that majorFT-expressing cells show a distinct expression profile that suggests that these cells may produce multiple systemic signals to regulate plant growth and development.
ER stress and mitochondrial dynamics: a tale of a wandering phosphatase DUSP28
Authors: Bhansali Priyanka , Gangi Setty Subba Rao
Published: August 2024

Fission and fusion processes maintain the mitochondrial dynamics at a steady state and are altered during various cellular stresses. The mechanisms that regulate mitochondrial dynamics during ER stress are critically unknown. Here, we identified a dual specificity phosphatase DUSP28 with a novel role in regulating mitochondrial morphology during ER stress. Cytosolic DUSP28 translocates to mitochondria during ER stress via PERK activation and further promotes mitochondrial fission in a Drp1-dependent manner. Interestingly, the knockdown of DUSP28 activates PERK signaling and enhances ER expansion following mitochondrial elongation by enhancing S637 phosphorylation of Drp1. Overexpression of DUSP28-GFP could not rescue the loss of Drp1 function, indicating its necessity for mitochondrial fission. Further, the presence of DUSP28 on mitochondria prevents Parkin recruitment during CCCP-induced mitochondrial damage and follows STX17-dependent mitophagy. These findings illustrate the novel crosstalk between ER stress and DUSP28 phosphatase in maintaining the mitochondrial dynamics to sustain cellular stress.
Balancing Selectivity and Generality in Object Recognition through Structured Interconnectivity
Authors: Zhang Yiyuan , Liu Jirui , Liu Jia
Published: August 2024

Balancing selectivity and generality in object recognition is a significant challenge, as it requires the ability to discern fine details that set objects apart while simultaneously embracing the common threads that classify them into one single category. Here we investigated how the brain addresses this challenge by examining the relationship between the interconnectivity of neural networks, the dimensionality of neural space, and the balance of selectivity and generality using neurophysiological data and computational modeling. We found that higher interconnectivity in the TEa of macaques’ IT cortex was associated with lower dimensionality and increased generality, while lower interconnectivity in the TEO correlated with higher dimensionality and enhanced selectivity. To establish the causal link, we developed a brain-inspired computational model formed through Hebbian and anti-Hebbian rules, with wiring length constraints derived from biological brains. The resulting structured interconnectivity created an optimal dimensionality of the neural space, allowing for efficient energy distribution across the representational manifold embedded in the neural space to balance selectivity and generality. Interestingly, this structured interconnectivity placed the network in a critical state that balances adaptability and stability, and fostered a cognitive module with cognitive impenetrability. In summary, our study underscores the importance of structured interconnectivity in achieving a balance between selectivity and generality, providing a unifying view of balancing two extreme demands in object recognition.
Homoploid Hybrid Speciation in a Marine Pelagic FishMegalaspis cordyla(Carangidae)
Authors: Muto Nozomu , Su Yong-Chao , Hata Harutaka , Quan Nguyen Van , Vilasri Veera , Ghaffar Mazlan Abd. , Babaran Ricardo P.
Published: August 2024

Homoploid hybrid speciation (HHS) is an enigmatic evolutionary process where new species arise through hybridization of divergent lineages without changes in chromosome number. Although increasingly documented in various taxa and ecosystems, convincing cases of HHS in marine fishes have been lacking. This study presents evidence of HHS in Torpedo scadMegalaspis cordylabased on comprehensive genomic, morphological, and ecological analyses. A Principal Component Analysis using thousands of SNPs identified three sympatric clusters in the western Pacific. Genome-wide differentiation between the clusters and the admixed nature of a cluster between the others were evident from population genomic analyses, species tree estimation, mitochondrial DNA divergence, and tests of introgression. Multiple statistical methods for hybrid detection also supported the admixed ancestry of this cluster. Moreover, model-based demographic inference favored a hybrid speciation scenario over introgression. Examination of occurrence data and ecologically relevant morphological characters suggested ecological differences between the clusters, potentially contributing to reproductive isolation and niche partitioning in sympatry. The clusters are morphologically distinguishable and thus can be taxonomically recognized as separate species. The hybrid cluster is restricted to the coasts of Taiwan and Japan, where all three clusters coexist. The parental clusters are additionally found in lower latitudes such as the coasts of the Philippines, Vietnam, Thailand, and Malaysia, where they display non-overlapping distributions. Given the geographical distributions, estimated times of the species formation, and patterns of historical demographic changes, we propose that the Pleistocene glacial cycles were the primary driver of HHS in this system. Based on this argument, we develop an ecogeographic model of HHS in marine coastal ecosystems, including a novel hypothesis to explain the initial stages of HHS.
Behavioral and Eye-Tracking Evidence for Disrupted Event Segmentation during Continuous Memory Encoding Due to Short Video Watching
Authors: Li Hongxiao , Li Jiashen , Hao Xin , Liu Wei
Published: August 2024

The widespread use of short-video platforms (e.g., TikTok), with over one billion monthly active users worldwide in 2023, necessitates an examination of their effects on cognitive functions. We hypothesized that because of the frequent, user-driven shifts in content during short-video watching, it mainly impairs event segmentation, a critical cognitive process in continuous perception and memory formation. To investigate this, we integrated memory encoding-retrieval tasks, eye-tracking technology, self-report questionnaires, and advanced machine learning analyses of eye movements. Our experiments (Study1 N=113, Study2 N=60), which varied the types of videos (random vs. personalized) and memory stimuli (continuous movies vs. static images), demonstrated that watching randomly selected short videos, particularly when integrated into daily viewing patterns, detrimentally affects memory encoding, especially in the initial and middle phases of continuous memory encoding. However, this impairment was not evident in trial-based image encoding tasks, suggesting a selective disruption in continuous memory processes. Intersubject correlation (ISC) analysis of eye movements revealed decreased synchronization at event boundaries during movie watching after exposure to random short videos. Furthermore, Hidden Markov Model (HMM) analyses indicated that participants were more likely to experience fragmented event segmentation during continuous memory encoding following exposure to random short videos. These findings underscore the potentially harmful impact of short-video watching on event segmentation and memory formation, emphasizing the role of recommendation algorithms in modulating human cognition.
The Generalized 3+3 (G3+3) Design for Phase I Dose-Finding Trials
Authors: Ji Yuan , Zhang Yunxuan , Ji Andrew Liu
Published: August 2024

PURPOSE We propose and demonstrate the feasibility and desirability of a novel model-free dose-finding design for phase I clinical trials. METHODS The Generalized 3+3 (G3+3) design uses a set of simple rules summarized as follows: For 3 or 6 patients at a dose, apply the 3+3 design for making dosing decisions. For other numbers, if the observed toxicity rate (OTR) is less than 0.2, escalate to the next higher dose; if the OTR is greater than 0.29, de-escalate to the next lower dose; otherwise, stay at the current dose. RESULTS The G3+3 design is the only design that can replicate the decisions of the 3+3 design for 3 or 6 patients among the popular designs compared like BOIN and i3+3. G3+3 generates desirable decisions when the number of patients treated is not 3 or 6, like the popular designs. Computer simulation verifies the superior operating characteristics of the G3+3 design. CONCLUSION The G3+3 design generalizes the popular 3+3 design so that desirable decisions can be made for any number of patients at a dose. Since G3+3 does not rely on statistical models, is simple and transparent, and can be implemented without a software tool, it is expected to facilitate and enhance modern phase I dose-finding trials and early-phase drug development.
Characterization of Natural Killer Cell Subpopulations in the Blood of Single Ventricle/Hypoplastic Left Heart Syndrome Patients Using Single-Cell RNA Sequencing
Authors: Qu Hui-Qi , Goel Kushagra , Ostberg Kayleigh , Slater Diana J , Wang Fengxiang , Snyder James , Hou Cuiping , Connolly John J , March Michael , Glessner Joseph T , Kao Charlly , Hakonarson Hakon
Published: August 2024

We utilized single-cell RNA sequencing (scRNA-seq) to examine peripheral blood mononuclear cells (PBMCs) from patients with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS), and demonstrated a more pronounced correlation between gene expression in Natural Killer (NK) cells and SV/HLHS compared to other PBMC cell types. Our scRNA-seq analysis of NK cells in this study identified two distinct clusters with gene expression patterns linked to immune responsiveness and adaptation to stress. While this finding underscores the heterogeneity of NK cells, it provides new insights into fine-tuning of immune modulation that could prevent complications in SV/HLHS. Specifically, our study suggests that while NK cells in SV/HLHS are adapting to support survival in a challenging physiological environment, these adaptations may compromise their ability to manage additional stresses such as infections and inflammation.
Molecular and physiological characterization of tillering and shade tolerance of dwarf mutants of perennial ryegrass
Authors: Kumar Rahul , Yer Huseyin , Li Wei , Jiang Xiangning , Gai Ying , Duan Hui , Li Yi
Published: August 2024

Tillering and shade tolerance are important traits in turfgrass, influenced by environmental factors, nutrients, and hormones. Shade stress negatively affects tillering. In this study, two dwarf mutants,shadow-1andshadow-2, developed via Gamma-ray and fast-neutron mutagenesis, respectively, showed significantly higher tillering than the wild-type under greenhouse conditions. Both mutants demonstrated shade tolerance in plant height, grass quality, and color under 85% and 95% shade conditions, while shade-induced inhibition of tillering was observed in both the mutants and the wild-type. In comparison to wild-type plants under 95% shade conditions, we observed that the cytokinin biosynthetic geneIPT8is upregulated, while the cytokinin inactivating geneCKX2is downregulated inshadow-1. Similarly, the GA biosynthetic genesCPS1, GA2ox3, and GA20ox1are upregulated, while the GA inactivating geneGA20ox8is downregulated in theshadow-1mutant. Furthermore, the ethylene biosynthetic genesACSandACOare also downregulated in theshadow-1mutant. Consistently, we observed that wild-type plants exhibit increased GA and reduced CK levels, whileshadow-1mutant plants have reduced GA but increased CK levels. This explains theshadow-1mutant’s shade tolerance in terms of plant height, grass quality, and color. Conversely, the tillering inhibitor genesCRY1, MAX2,andSnRK1are upregulated in both wild-type andshadow-1mutant plants. Our results provide novel insights into the mechanisms behind tillering and shade tolerance in turfgrasses under shade conditions.
The glycolytic reaction PGAM unexpectedly restrains Th17 pathogenicity and Th17-dependent autoimmunity
Authors: Wang Chao , Wagner Allon , Fessler Johannes , DeTomaso David , Zaghouani Sarah , Zhou Yulin , Pierce Kerry , Sobel Raymond A. , Clish Clary , Yosef Nir , Kuchroo Vijay K.
Published: August 2024

Glucose metabolism is a critical regulator of T cell function, largely thought to support their activation and effector differentiation. Here, we investigate the relevance of individual glycolytic reactions in determining the pathogenicity of T helper 17 (Th17) cells using single-cell RNA-seq and Compass, an algorithm we previously developed for estimating metabolic flux from single-cell transcriptomes. Surprisingly, Compass predicted that the metabolic shunt between 3-phosphoglycerate (3PG) and 2-phosphoglycerate (2PG) is inversely correlated with pathogenicity in these cells, whereas both its upstream and downstream reactions were positively correlated. Perturbation of phosphoglycerate mutase (PGAM), an enzyme required for 3PG to 2PG conversion, resulted in an increase in protein expression of IL2, IL17, and TNFa, as well as induction of a pathogenic gene expression program. Consistent with PGAM playing a pro-regulatory role, inhibiting PGAM in Th17 cells resulted in exacerbated autoimmune responses in the adoptive transfer model of experimental autoimmune encephalomyelitis (EAE). Finally, we further investigated the effects of modulating glucose concentration on Th17 cells in culture. Th17 cells differentiated under high- and low-glucose conditions substantially differed in their metabolic and effector transcriptomic programs, both central to Th17 function. Importantly, the PGAM-dependent gene module marks the least pathogenic state of Th17 cells irrespective of glucose concentration. Overall, our study identifies PGAM, contrary to other glycolytic enzymes, as a negative regulator of Th17 pathogenicity.
Kinetics of i-motif folding within the duplex context
Authors: Alieva Rugiya , Keshek Anna , Zatsepin Timofei , Orlov Victor , Aralov Andrey , Zavyalova Elena
Published: August 2024

Non-canonical nucleic acid structures possess an ability to interact selectively with proteins, thereby exerting influence over various intracellular processes. Numerous studies indicate that genomic G-quadruplexes and i-motifs are involved in the regulation of transcription. These structures are formed temporarily during the unwinding of the DNA double helix; and their direct determination is a rather difficult task. In addition, i-motif folding is pH-dependent, with most i-motifs having low stability at neutral pH. However, some genomic i-motifs with long cytosine repeats were shown to be stable at pH 7.3, suggesting their functionality within the nucleus. Here we studied pH-dependent behavior of a model i-motif with flanking sequences that forms a duplex motif. Kinetic studies on bimodular structures with cytosine residues replaced with an environment-sensitive fluorescent label reveal the stabilization of the i-motif structure near the i-motif-duplex junction. These results highlight the importance of the natural environment of i-motifs for the correct assessment of their stability.
Dietary Analysis of Vespula shidai in Reared and Wild Nests
Authors: Saga Tatsuya
Published: August 2024

This study examines the dietary behaviors of both reared and wild nests of Vespula shidai in Central Japan, a region known for its rich biodiversity and unique entomophagy culture, particularly the consumption of wasp larvae and pupae, known locally as "hachinoko." This study reveal that these wasps exhibit remarkable dietary versatility, consuming a wide range of vertebrates, more varied than their counterparts in Hawaii and New Zealand. The study notes that wild nests, unlike their reared nests, consume a significantly greater variety of vertebrate species, even without supplementation. This suggests that vertebrate carcasses provide crucial nutrients that contribute substantially to wasp development. Additionally, this research highlights individual foraging preferences among nests, which are influenced by both the availability and nutritional value of prey, as well as human feeding practices. This variation in prey composition, particularly evident between reared and wild nests, underscores the complex interaction between wasps' natural dietary habits and human intervention.
Universal high-throughput image quantification of subcellular structure dynamics and spatial distributions within cells
Authors: Martin Andrew , Zhang Sue , Williamson Amanda , Tingley Brett , Pickus Mira , Zurakowski David , Nia Hadi T. , Shirihai Orian , Han Xue , Grinstaff Mark W.
Published: August 2024

Image analysis of subcellular structures and biological processes relies on specific, context-dependent pipelines, which are labor-intensive, constrained by the intricacies of the specific biological system, and inaccessible to broader applications. Here we introduce the application of dispersion indices, a statistical tool traditionally employed by economists, to analyze the spatial distribution and heterogeneity of subcellular structures. This computationally efficient high-throughput approach, termed GRID (Generalized Readout of Image Dispersion), is highly generalizable, compatible with open-source image analysis software, and adaptable to diverse biological scenarios. GRID readily quantifies diverse structures and processes to include autophagic puncta, mitochondrial clustering, and microtubule dynamics. Further, GRID is versatile, applicable to both 2D cell cultures and 3D multicellular organoids, and suitable for high-throughput screening and performance metric measurements, such as half-maximal effective concentration (EC50) values. The approach enables mechanistic analysis of critical subcellular structure processes of relevance for diseases ranging from metabolic and neuronal diseases to cancer as well as a first-pass screening method for identifying biologically active agents for drug discovery.

Statement of Significance

Current methods for image analysis in microscopy are tailored to specific biological contexts, which creates challenges in implementation and efficiency for researchers studying a diverse range of subcellular processes. Our application of dispersion indices, traditionally used in economics, offers a universal framework for high throughput quantification of biological structures, enabling easier and more consistent analysis across various biological contexts. By transforming pixel intensity and count into meaningful statistical measures, our method simplifies the quantification of subcellular structures such as autophagic puncta, microtubule dynamics, and mitochondrial clustering. This approach accelerates the quantitative analysis of sub-cellular processes in disease as well as imaged-based drug discovery.

Classification:Bioengineering, Cell Biology, Applied Biological Sciences
Inner membrane components of the plasmid pKM101 type IV secretion system TraE and TraD are DNA-binding proteins
Authors: Jemouai Zakaria , Sverzhinsky Aleksandr , Sygusch Jurgen , Pascal John , Baron Christian
Published: August 2024

The increase of antimicrobial resistance constitutes a significant threat to human health. One of the mechanisms responsible for the spread of resistance to antimicrobials is the transfer of plasmids between bacteria by conjugation. This process is mediated by type IV secretion systems (T4SS) and previous studies have provided in vivo evidence for interactions between DNA and components of the T4SS. Here, we purified TraD and TraE, two inner membrane proteins from the Escherichia coli pKM101 T4SS. Using electrophoretic mobility shift assays and fluorescence polarization we showed that the purified proteins both bind single-stranded and double-stranded DNA in the nanomolar affinity range. The previously identified conjugation inhibitor BAR-072 inhibits TraE DNA binding in vitro, providing evidence for its mechanism of action. Site-directed mutagenesis identified conserved amino acids that are required for conjugation that may be targets for the development of more potent conjugation inhibitors.
Developmental plasticity and genetic selection shaped cereal evolution in the Early Holocene southern Levant
Authors: Whitlam Jade , Flohr Pascal , Bogaard Amy , Charles Mike , Finlayson Bill , Makarewicz Cheryl A.
Published: August 2024

The domestication of plants in southwest Asia was an evolutionary process that took place over several millennia in the Early Holocene. During this time domestic species developed distinct traits that distinguish them from their wild counterparts. Current models of plant domestication emphasise the role of genetic selection in the evolution of these traits, viewing these as heritable adaptations that arose in response to selective pressures associated with human cultivation. In cereals, domestication resulted in the evolution of non-shattering rachis and increased grain size, two traits that can be tracked directly in the archaeobotanical record. Measurements of cereal grains from Early Neolithic sites indicate that grain size increase occurred prior to the evolution of non-shattering rachis, and it has been proposed that this reflects selection for larger grains under tillage, signifying pre-domestication cultivation. Here we combine morphological and metrical analysis of cereal remains, stable carbon isotope analysis, and weed ecology to test this hypothesis, using three assemblages from the southern Levant: Pre-Pottery Neolithic A Sharara (c. 9250-9200 cal BCE), Pre-Pottery Neolithic A el-Hemmeh (c. 9400-8700 cal BCE) and Late Pre-Pottery Neolithic B el-Hemmeh (c. 7500-7000 cal BCE). Our findings indicate that increased grain size in the Early Holocene is better understood as a plastic response to variation in growing conditions (specifically moisture), rather than a result of genetic selection for increased grain size under cultivation (i.e., tillage). We argue that cereal evolution in southwest Asia was initially driven by developmental plasticity, followed by genetic selection.
Metadichol, a modulator that controls expression of Toll Like Receptors in Cancer Cell Lines
Authors: Raghavan P.R.
Published: August 2024

Toll-like receptors are essential players in the innate immune signaling system and play critical roles in recognizing pathogen-associated and damage-associated molecular patterns. Its presence in various cancer cells, including breast, ovarian, cervical, colon, hepatocellular carcinoma, prostate, lung cancer, melanoma, and neuroblastoma cells, has been associated with cancer progression, immune evasion, apoptosis, and chemoresistance. Despite extensive research, no small molecules can induce the expression of all TLRs in cancer cells have been identified. This study investigated the effects of metadichol, a nanoemulsion of long-chain alcohols, on the expression of TLR receptor families 1–10 in cancer cell lines. Using quantitative polymerase chain reaction (qPCR) and other molecular biology techniques, we assessed the concentration-dependent effects of metadichol on TLR expression, which ranged from 1 picogram per ml to 100 nanograms per ml. Our results show that metadichol can modulate TLR expression in a cancer cell type-specific manner, with TLR4 being upregulated in lung cancer cells, enhancing antitumor effects but downregulated in other cancer lines, reducing inflammation.

Furthermore, TLR7, TLR8, and TLR9 are upregulated in certain cell lines. Importantly, metadichol induced the downregulation of MYD88, TRAF6, and IRAK4 across various cell lines, suggesting considerable potential to inhibit tumor growth, enhance apoptosis, and reduce metastasis. This broad-spectrum gene activation supports a multitarget therapeutic approach, making metadichol the first molecule to target the entire TLR family without the need for complex biological methods such as CRISPR—alternatively, virus grafting techniques. Our findings underscore the potential of metadichol in treating complex diseases involving multiple pathways, such as cancer, chronic inflammatory pathways, and infectious diseases, highlighting noteworthy advancements in cancer therapy.
Network influence determines the impact of cortical ensembles on stimulus detection
Authors: Bounds Hayley A , Adesnik Hillel
Published: August 2024

Observation of neural firing patterns can constrain theories for the types of activity patterns that the brain uses to guide behavior. However, directly perturbing these patterns, ideally with great specificity, is required to causally test any particular theory. We combined two-photon imaging and cellular resolution optogenetic photo-stimulation to causally test how neural activity in the mouse visual cortex is read out to detect visual stimuli. Contrary to expectations, targeted activation of highly sensitive neural ensembles did not preferentially modify behavior compared to random ensembles, contradicting a longstanding hypothesis for how neural activity drives stimulus detection. Instead, the main predictor of a targeted neural ensemble's impact on perception was its effect on network activity. This argues that downstream regions summate visual cortex activity without preferentially weighting more informative neurons to make sensory detection decisions. Comparing mouse behavioral performance to decoding models of neural activity implies that mice employ this simple, albeit suboptimal strategy to solve the task. This work challenges conventional notions for how sensory representations mediate perception and demonstrates that specific neural perturbations are critical for determining which features of neural activity drive behavior.
Identifiability of heterogeneous phenotype adaptation from low-cell-count experiments and a stochastic model
Authors: Browning Alexander P , Crossley Rebecca M , Villa Chiara , Maini Philip K , Jenner Adrianne L , Cassidy Tyler , Hamis Sara
Published: August 2024

Adaptive resistance contributes significantly to treatment failure in many cancers. Despite the increased prevalence of experimental studies that interrogate this phenomenon, there remains a lack of applicable quantitative tools to characterise data, and importantly to distinguish between resistance as a discrete phenotype and a (potentially heterogeneous) continuous distribution of phenotypes. To address this, we develop a stochastic individual-based model of adaptive resistance in low-cell-count proliferation assays. That our model corresponds probabilistically to common partial differential equation models of resistance allows us to formulate a likelihood that captures the intrinsic noise ubiquitous to such experiments. We apply our framework to assess the identifiability of key model parameters in several population-level data collection regimes; in particular, parameters relating to the adaptation velocity and within-population heterogeneity. Significantly, we find that heterogeneity is practically non-identifiable from both cell count and proliferation marker data, implying that population-level behaviours may be well characterised by homogeneous ordinary differential equation models. Additionally, we demonstrate that population-level data are insufficient to distinguish resistance as a discrete phenotype from a continuous distribution of phenotypes. Our results inform the design of both future experiments and future quantitative analyses that probe adaptive resistance in cancer.
Mycn regulates vascular development through PI3K signaling pathway in zebrafish
Authors: Zhao Guo-Qin , Cheng Tao , Wang Peng-Yun , Mo Jing , Yu Feng , Dong Yang , Li Yun-Fei , Feng Yu , Xu Peng-Fei , Shu Li-Ping
Published: August 2024

Mycn, a MYC gene family member, is implicated in both carcinogenesis through amplification and Feingold syndrome through its deficiency. Previous studies have indicated that increased Mycn expression enhances vascularization in human neuroblastomas, yet its precise role in vascular development remains elusive. In this study, we utilized single-cell RNA-seq and live imaging analyses to confirm thatmycnis expressed during zebrafish vasculogenesis. We investigated vascular development in zebrafish using a genetically engineeredmycnmutation. Our findings reveal thatmycn-deficient zebrafish exhibit reduced intersegmental vessels and malformed subintestinal vessels, primarily due to decreased cell proliferation in vascular cells. Importantly, we discovered that activation of PI3K signaling significantly ameliorates these vascular abnormalities.
Multivalent hydrogen-bonded architectures directed by self-complementarity between [Cu(2,2′-biimidazole)] and malonate building blocks
Authors: Atencio Reinaldo , Linares Marciel M. , González Teresa , Briceño Alexander
Published: August 2024

The synthesis and structural characterization of four novel supramolecular hydrogen-bonded arrangements based on self-assembly from molecular `[Cu(2,2′-biimidazole)]' modules and malonate anions are presented, namely, tetrakis(2,2′-biimidazole)di-μ-chlorido-dimalonatotricopper(II) pentahydrate, [Cu3(C3H2O4)2Cl2(C6H6N4)4]·5H2O or [Cu(H2biim)2(μ-Cl)Cu0.5(mal)]2·5H2O, aqua(2,2′-biimidazole)malonatocopper(II) dihydrate, [Cu(C3H2O4)(C6H6N4)(H2O)]·2H2O or [Cu(H2biim)(mal)(H2O)]·2H2O, bis[aquabis(2,2′-biimidazole)copper(II)] dimalonatodiperchloratocopper(II) 2.2-hydrate, [Cu(C6H6N4)2(H2O)]2[Cu(C3H2O4)(ClO4)2]·2.2H2O or [Cu(H2biim)2(H2O)]2[Cu(mal)2(ClO4)2]·2.2H2O, and bis(2,2′-biimidazole)copper(II) bis[bis(2,2′-biimidazole)(2-carboxyacetato)malonatocopper(II)] tridecahydrate, [Cu(C6H6N4)2][Cu(C3H2O4)(C3H3O4)(C6H6N4)2]·13H2O or [Cu(H2biim)2][Cu(H2biim)2(Hmal)(mal)]2·13H2O. These assemblies are characterized by self-complementary donor–acceptor molecular interactions, demonstrating a recurrent and distinctive pattern of hydrogen-bonding preferences among the carboxylate, carboxylic acid and N—H groups of the coordinated 2,2′-biimidazole and malonate ligands. Additionally, coordination of the carboxylate group with the metallic centre helps sustain remarkable supramolecular assemblies, such as layers, helices, double helix columns or 3D channeled architectures, including mixed-metal complexes, into a single structure.
Relationship between teacher ideals and attitudes toward peers with autism spectrum disorder among teacher college students
Authors: Suzuki Kota , Oi Yuhei , Mitsuhashi Shota , Hirata Shogo , Goto Takaaki
Published: August 2024

Purpose

This study aims to examine the relationship between teacher ideals and attitudes toward peers with autism spectrum disorder (ASD) among teacher college students, and the effect of knowledge of ASD identification on this relationship.

Design/methodology/approach

This study used a quantitative approach and included 341 teacher college students. A vignette was used to assess social and professional attitudes toward peers with ASD. The participants were divided into identification and nonidentification groups based on how accurately they identified the peer depicted in the vignette as having ASD. A teacher ideals questionnaire consisting of two subscales indicating different ideal teachers − a dedicated/engaging teacher (e.g. a teacher who can work with enthusiasm) and a skillful teacher (e.g. a teacher who is knowledgeable) − was developed and administered to evaluate the participants’ teacher ideals and self-perceptions of a teacher.

Findings

In the nonidentification group, ideals of a skillful teacher were significantly correlated with social attitudes toward peers with ASD. The identification group exhibited no significant correlations between ideals and social attitudes. Furthermore, the self-perceptions of being a dedicated/engaging teacher was significantly correlated with professional attitudes toward peers with ASD in the identification group.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the relationship between teacher ideals and attitudes toward peers with ASD. Teacher ideals were related to negative social attitudes toward peers with ASD. While knowledge of ASD identification weakens this relationship, it may drive the relationship between self-perceptions of a teacher and professional attitudes toward peers with ASD. Therefore, ASD education is important for reducing the stigma toward ASD in teacher education.
Student engagement and concerns on studies and future professions: exploratory research in a Palestinian higher education context
Authors: Korhonen Vesa , Aldahdouh Tahani , Holubek Vesna , Abou-dagga Sanaa , Al-Masri Nazmi
Published: August 2024

Purpose

Student engagement evaluation is considered to be connected to many aspects of the management of higher education, but outside Western higher education, research and evaluation on student engagement and experiences has been limited so far. Our study focuses on the underexplored aspects of Palestinian higher education with the aim of gaining an actionable understanding from the overall student engagement situation to enhance the management and development of local teaching and learning practices.

Design/methodology/approach

A quantitatively oriented, sequential mixed-methods design was adopted. With the applied and validated engagement measurement we collected 946 engagement questionnaire responses from Palestinian university students. Quantitative data were analysed using structural equation modelling, K-means cluster analysis and chi-squared tests. Inductive and deductive thematic analysis was employed for the open answers.

Findings

With the three validated student engagement dimensions, the applied cluster analysis allowed three different engagement profile groups to be distinguished: strongly, moderately and loosely engaged. In the subsequent statistical and qualitative thematic analyses, these three engagement clusters differ in the degree to which they had a clear vision of a future profession or in their academic engagement with their studies. Moreover, qualitative analysis brought up many shared concerns regarding theoretically oriented studies and uncertain professional and career prospects in the Palestinian higher education context.

Originality/value

This study is one of the first attempts to develop tools for student engagement management in Palestinian higher education. The study findings are particularly significant for developing micro- and meso-level management practices in Palestinian higher education institutions.
Are Islamic banks really resilient to crises: new evidence from the COVID-19 pandemic
Authors: Chazi Abdelaziz , Mirzaei Ali , Zantout Zaher
Published: August 2024

Purpose

Proponents of Islamic banking believe that this banking model is relatively superior in times of financial crises. This study aims to examine whether Islamic banks were more resilient to the coronavirus 2019 (COVID-19) pandemic than their conventional peers, especially in terms of two of the most important banking risks, capital and liquidity risks.

Design/methodology/approach

The authors use a regression model to examine whether Islamic banks were more resilient to the recent health crisis, as compared to their conventional counterparts. The results are robust to alternative crisis time periods, the use of different model specifications and the inclusion of different control variables.

Findings

Unlike during the 2007–2008 global financial crisis (GFC), Islamic banks have not performed relatively well during the more recent crisis caused by the COVID-19 pandemic. The results show that Islamic banks experienced an increase in both capital and liquidity risks. The results also indicate a decrease in bank profitability, improved solvency and asset quality and a decrease in operational risk.

Originality/value

This study contributes to the literature on banking business model and resilience to economic crises. Contrary to some expectations and to their performance during the GFC of 2007–2008, Islamic banks were found to be more vulnerable during the COVID-19 pandemic than conventional banks.
Academic stress, well-being and students' friendship quality amid crisis: lessons from COVID-19 pandemic
Authors: Adjanor-Doku Charlotte , Mensah Philip Opoku , Ellis Florence Yaa Akyiah
Published: August 2024

Purpose

Through the lens of the Social Exchange Theory, this study investigates the role of emotional and psychological well-being in explaining the relationship between academic stress and friendship quality.

Design/methodology/approach

Using a cross-sectional quantitative research design, the study gathered data from 298 tertiary students. Statistical analysis was conducted using Hayes Process Macro in SPSS.

Findings

Results from the study challenge conventional assumptions, indicating a positive and significant relationship between academic stress and friendship quality. In addition, the study revealed that psychological well-being partially mediates the relationship between academic stress and friendship quality, while emotional well-being fully mediates the relationship between academic stress and friendship quality.

Research limitations/implications

This study is limited to the tertiary institutions in Ghana. Future studies may consider expanding the scope to other levels of education to gain a more comprehensive perspective of the variables of the study.

Originality/value

This study presents a novel approach by examining the proposed model within the Ghanaian setting. It offers valuable perspectives on the interplay between academic stress, well-being, and friendship quality.
A bibliometric perspective: three stages of green knowledge management thematic evolution in business literature
Authors: Phung Phuong Thanh , Luu Nghia Thi Minh , Nguyen Anh T.V. , Siriwardana Anushka , Halibas Alrence
Published: August 2024

Purpose

Green knowledge management (GKM) has become a more prominent research topic because of its ability to balance business sustainability, performance and society's well-being. The purpose of this paper is to study how GKM literature evolved before and after two major events: the introduction of sustainable development goals (SDGs) and the first conceptualization of GKM. In this paper, GKM is holistically examined following the stages of the knowledge management cycle, a framework for organizational knowledge-processing phases.

Design/methodology/approach

This study performed a bibliometric analysis of 1,274 papers related to GKM from 1995 until January 2024.

Findings

Over the three decades, this research outlined the intertwined relationships between core themes in the domain such as knowledge management in the context of corporate social responsibilities, sustainable development (SD), competitive advantage and so on, and popular theories. GKM evolved from an “industrial and technical view” of knowledge management to a more emerging perspective of a “social process.” Emerging themes were identified such as green innovation, information security or organizational learning sub-themes with key technologies like block-chain, big data analytics and artificial intelligence. Future research can explore themes such as green knowledge integration, green entrepreneurship, green supply chain and green knowledge integration capabilities.

Practical implications

This review offers practitioners a holistic picture of GKM to tackle emerging environmental concerns and increase businesses' competitive advantages. This study provides insights into the future practices of GKM, incorporating emerging technological advancement, to gain green intellectual capital and build dynamic capabilities for sustainability.

Originality/value

To the best of authors’ knowledge, this study is the first to provide a comprehensive picture of the GKM literature, from its earliest forms of corporate social responsibility and SD until the introduction of SDGs, and in combination with the evolution of knowledge management cycle stages.