bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemokine receptor 5 signaling in PFC mediates stress susceptibility in female mice
Authors: Lin Hsiao-Yun , Cathomas Flurin , Li Long , Cuttoli Romain Durand-de , Guevara Christopher , Bayrak Cigdem Sevim , Wang Qian , Gupta Swati , Chan Kenny L. , Shimo Yusuke , Parise Lyonna F. , Yuan Chongzhen , Aubry Antonio V. , Chen Fiona , Wong Jean , Morel Carole , Huntley George W. , Zhang Bin , Russo Scott J. , Wang Jun
Published: August 2023

Chronic stress induces changes in the periphery and the central nervous system (CNS) that contribute to neuropathology and behavioral abnormalities associated with psychiatric disorders. In this study, we examined the impact of peripheral and central inflammation during chronic social defeat stress (CSDS) in female mice. Compared to male mice, we found that female mice exhibited heightened peripheral inflammatory response and identified C-C motif chemokine ligand 5 (CCL5), as a stress-susceptibility marker in females. Blocking CCL5 signaling in the periphery promoted resilience to CSDS. In the brain, stress-susceptible mice displayed increased expression of C-C chemokine receptor 5 (CCR5), a receptor for CCL5, in microglia in the prefrontal cortex (PFC). This upregulation was associated with microglia morphological changes, their increased migration to the blood vessels, and enhanced phagocytosis of synaptic components and vascular material. These changes coincided with neurophysiological alterations and impaired blood-brain barrier (BBB) integrity. By blocking CCR5 signaling specifically in the PFC were able to prevent stress-induced physiological changes and rescue social avoidance behavior. Our findings are the first to demonstrate that stress-mediated dysregulation of the CCL5-CCR5 axis triggers excessive phagocytosis of synaptic materials and neurovascular components by microglia, resulting in disruptions in neurotransmission, reduced BBB integrity, and increased stress susceptibility. Our study provides new insights into the role of cortical microglia in female stress susceptibility and suggests that the CCL5-CCR5 axis may serve as a novel sex-specific therapeutic target for treating psychiatric disorders in females.
Advanced image generation for cancer using diffusion models
Authors: Kidder Benjamin L.
Published: August 2023

Deep neural networks have significantly advanced medical image analysis, yet their full potential is often limited by the relatively small dataset sizes. Generative modeling has stimulated attention for its potential applications in the synthesis of medical images. Recent advancements in diffusion models have exhibited a remarkable capacity for producing photorealistic images. Despite this promising development, the application of such models in the generation of medical images remains underexplored. In this study, we explored the potential of using diffusion models to generate medical images, with a particular emphasis on producing brain magnetic resonance imaging (MRI) scans, such as those depicting low-grade gliomas. Additionally, we examined the generation of contrast enhanced spectral mammography (CESM) images, as well as chest and lung X-ray images. Utilizing the Dreambooth platform, we trained stable diffusion models based on text prompts, class and instance images, subsequently prompting the trained models to produce medical images. The generation of medical imaging data presents a viable approach for preserving the anonymity of medical images, effectively reducing the likelihood of patient re-identification during the exchange of data for research. The findings of this study reveal that the application of diffusion models in generating images successfully captures attributes specific to oncology within imaging modalities. Consequently, this research establishes a framework that harnesses the power of artificial intelligence for the generation of cancer medical imagery.
Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS highlights a critical role for lipids
Authors: Suvannapruk Waraporn , Fisher Leanne E , Luckett Jeni C , Edney Max K , Kotowska Anna M , Kim Dong-Hyun , Scurr David J , Ghaemmaghami Amir M , Alexander Morgan R
Published: August 2023

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in modulation of the host immune response and are the major cells responsible for persistent inflammatory reactions to implanted biomaterials. We investigate two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophagesin vitro. These also modulatein vivoforeign body responses (FBR) when implanted subcutaneously in mice as coatings on biomedical grade silicone rubber. The tissue surrounding the implant is mechanically sectioned and imaged to assess the response of the polymers compared to silicone rubber. Immunofluorescent staining reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. We apply 3D OrbiSIMS analysis to provide spatial analysis of the metabolite signature in the tissue surrounding the implant for the first time, providing molecular histology insight into the metabolite response in the host tissue. For the pro-inflammatory coating, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating the number of phospholipid species detected decrease and pyridine and pyrimidine levels were elevated. These findings link to observations of small molecule signature from single cell studies of M2 macrophagesin vitrowhere cell and tissue ion intensities were found to correlate suggesting potential for prediction. This illustrates the power of metabolite characterization by the 3D OrbiSIMS to gain insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials.
Role of Apyrase in Mobilization of Phosphate from Extracellular Nucleotides and in Regulating Phosphate Uptake in Arabidopsis
Authors: Slocum Robert D. , Wang Huan , Tomasevich Alexandra A. , Clark Greg , Roux Stanley J.
Published: August 2023

Apyrase (nucleotide triphosphate diphosphohydrolase, NTPDase; EC 3.6.1.5) functions in a variety of plant growth and developmental processes and responses to pathogens, in part, by regulating extracellular ATP (eATP) concentrations. In this study, we investigated possible roles for apyrase in the recruitment of phosphate (Pi) from extracellular nucleotides inArabidopsis thalianaseedlings that constitutively expressapyrase 1(APY1). Under Pi limitation, both WT andAPY1seedlings had decreased Pi contents and a characteristic remodeling of root system architecture (RSA). This phosphate starvation response (PSR) was prevented by uptake of Pi released by metabolism of extracellular NTP, which supported normal seedling growth. In Pi-sufficient media, Pi contents ofAPY1seedlings were higher than in WT seedlings. Addition of NTP reduced the number of LR and decreased Pi contents of WT seedlings but markedly increased both LR and root hair (RH) formation and Pi contents ofAPY1seedlings. Genome-wide expression profiling revealed the repression of PSR genes inAPY1seedlings, relative to WT seedlings, consistent with their elevated Pi contents. The expanded RSA ofAPY1seedlings was correlated with induction of >100 genes involved in regulation of auxin homeostasis, signaling and transport, which previous studies have shown to be increased whenAPY1is overexpressed.APY1regulation of [eNTP] and purinergic signaling may play a role in regulating this auxin response, resulting in enhanced uptake of Pi from the medium, including Pi released by eNTP metabolism.
A suite of selective pressures supports the maintenance of alleles of aDrosophilaimmune peptide
Authors: Mullinax Sarah R. , Darby Andrea M. , Gupta Anjali , Chan Patrick , Smith Brittny R. , Unckless Robert L.
Published: August 2023

The innate immune system provides hosts with a crucial first line of defense against pathogens. While immune genes are often among the fastest evolving genes in the genome, inDrosophila, antimicrobial peptides (AMPs) are notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles are maintained in populations. In this study, we focus on theDrosophilaantimicrobial peptide Diptericin A, which has a segregating amino acid polymorphism associated with differential survival after infection with the Gram-negative bacteriaProvidencia rettgeri. Diptericin A also helps control opportunistic gut infections by common Drosophila gut microbes, especially those ofLactobacillus plantarum. In addition to genotypic effects on gut immunity, we also see strong sex-specific effects that are most prominent in flies without functionaldiptericin A. To further characterize differences in microbiomes between differentdiptericingenotypes, we used 16S metagenomics to look at the microbiome composition. We used both lab reared and wild caught flies for our sequencing and looked at overall composition as well as the differential abundance of individual bacterial families. Overall, we find flies that are homozygous for one allele ofdiptericin Aare better equipped to survive a systemic infection fromP. rettgeri, but in general have a shorter lifespans after being fed common gut commensals. Our results suggest a possible mechanism for the maintenance of genetic variation ofdiptericin Athrough the complex interactions of sex, systemic immunity, and the maintenance of the gut microbiome.
Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu
Authors: Townsend Julia A. , Fapohunda Oluwaseun , Wang Zhihan , Pham Hieu , Taylor Michael T. , Kloss Brian , Park Sang Ho , Opella Stanley , Aspinwall Craig A. , Marty Michael T.
Published: August 2023

Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry (MS) in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for mechanisms of their biological functions as well as their potential as therapeutic targets.
Phenotypic lags influence rapid evolution throughout a drought cycle
Authors: Branch Haley A. , Anstett Daniel N. , Angert Amy L.
Published: August 2023

Climate anomalies pose strong selection which can lead to rapid evolution. These global mean trends occur on a backdrop of interannual variability that might weaken or even reverse selection. However, the impact of climatic interannual variability on rapid evolution is rarely considered. We study evolution through a seven-year period encompassing a severe drought across 12 populations ofMimulus cardinalis(scarlet monkeyflower). Plants were grown in a common greenhouse environment under wet and dry treatments, where specific leaf area and date of flowering were measured. We compare the ability of different climate metrics to explain the rapid evolution of trait values, examining different time-periods, including the collection year, prior years, and cumulative metrics across sequential years. We find that anomalies in mean annual precipitation best describe rapid evolution over our study period. Past climates, of one-to two-years ago, are often related to trait values in a conflicting direction to collection-year climate. Uncovering these complex climatic impacts on evolution is critical to better predict and interpret the impacts of climate change.
Neural signatures of attentional prioritization and facilitation in accessing repeated items in Visual Working memory
Authors: Narvaria Abhishek Singh , Banerjee Arpan , Roy Dipanjan
Published: August 2023

The top-down goal voluntarily maintains and selectively recalls items in visual working memory (VWM). In contrast, bottom-up attentional selection due to stimulus-driven selection by saliency or relational account, like in perceptually similar items has been found to prioritize items and facilitate recalling them in VWM involuntarily. However, there is a knowledge gap about whether repeated items, a relational property of stimuli can acquire prioritized access in VWM and act as a distractor that hinders recalling not-repeated items even if a valid probe facilitates them. To address this, we designed a novel VWM-based EEG study where human participants respond to a probe for an item’s presence or absence in a memory array containing repeated and not repeated items. Significantly slower response times and comparatively poor accuracy for recalling not-repeated items suggest that they are not prioritized, whereas repeated items are. Using spectral perturbation-based EEG analysis, we identified specific differences for sensor clusters in the power of beta, alpha and theta band as the neural correlate of probe matching for not-repeated vs. repeated conditions reflecting biased access to VWM items. For not-repeated item probe matching, delay in beta desynchronization shows poor memory-guided action selection behaviour. Whereas, higher frontal theta and parietal alpha power demonstrated a demand for stronger cognitive control for recalling items for not-repeated probe matching by shielding them from distracting repeated items. In summary, this opens up avenues for further investigations of distraction due to repetition like the relational property of stimuli and explaining the mechanisms of prioritized access of repeated items over goal-driven relevant not-repeated items in VWM.
NeuronalSNCAtranscription during Lewy body formation
Authors: Kon Tomoya , Forrest Shelley L. , Lee Seojin , Martinez-Valbuena Ivan , Li Jun , Nassir Nasna , Uddin Mohammed J. , Lang Anthony E. , Kovacs Gabor G.
Published: August 2023

Background

Misfolded α-synuclein (α-syn) is believed to contribute to neurodegeneration in Lewy body disease (LBD) based on considerable evidence including a gene-dosage effect observed in relation to point mutations and multiplication ofSNCAin familial Parkinson’s disease. A contradictory concept proposes early loss of the physiological α-syn as the major driver of neurodegeneration. There is a paucity of data onSNCAtranscripts in various α-syn immunoreactive cytopathologies.

Methods

SNCAtranscripts in neurons without and with various α-syn immunoreactive cytopathologies in the substantia nigra and amygdala in LBD (n = 5) were evaluated using RNAscope combined with immunofluorescence for disease-associated α-syn. Single-nucleus RNA sequencing was performed to elucidate cell-type specificSNCAexpression in non-diseased frontal cortex (n = 3).

Results

SNCAtranscripts in neurons with punctate α-syn immunoreactivity were preserved both in the substantia nigra and amygdala but were reduced in neurons with compact α-syn inclusions. Only singleSNCAtranscripts were detected in astrocytes with or without α-syn immunoreactivity in the amygdala. Single-nucleus RNA sequencing revealed that excitatory and inhibitory neurons, oligodendrocyte progenitor cells, oligodendrocytes, and homeostatic microglia expressedSNCAtranscripts, while expression was largely absent in astrocytes and microglia.

Conclusions

The preserved cellularSNCAexpression in the more abundant non-Lewy body type α-syn cytopathologies provides a pool for local protein production that can aggregate and serve as a seed for misfolded α-syn. Successful segregation of disease-associated α-syn is associated with the exhaustion ofSNCAproduction in the terminal cytopathology, the Lewy body. Our observations support a therapeutic strategy incorporating a finely tuned dual approach targeting the elimination of misfolded α-syn along with the reduction of theSNCAtranscription to avoid feeding of pathological α-syn seeding.
The diversity and ecological significance of microbial traits potentially involved in B12biosynthesis in the global ocean
Authors: Zhou Jiayin , Qin Wei , Lu Xinda , Yang Yunfeng , Stahl David , Jiao Nianzhi , Zhou Jizhong , Liu Jihua , Tu Qichao
Published: August 2023

Cobalamin (B12), an essential nutrient and growth cofactor for many living organisms on the Earth, can be fully synthesized only by selected prokaryotes in nature. Therefore, microbial communities related with B12biosynthesis could serve as an example subsystem to disentangle the underlying ecological mechanisms balancing the function and taxonomy of complex functional assemblages. By anchoring microbial traits potentially involved in B12biosynthesis, we depict the biogeographic patterns of B12biosynthesis genes and their carrying taxa in the global ocean, in light of the limitation to detectde novoB12synthesizers via metagenomes alone. Both the taxonomic and functional composition of B12biosynthesis genes were strongly shaped by depth, differentiating epipelagic from mesopelagic zones. The functional genes were relatively stably distributed across different oceans, but their carrying taxa varied considerably, showing clear functional redundancy of microbial systems. Microbial taxa carrying B12biosynthesis genes in the surface water were influenced by environmental factors such as temperature, oxygen and nitrate. However, the composition of functional genes was weakly associated with these environmental factors. Null model analyses demonstrated that determinism governed the compositional variation of B12biosynthesis genes, whereas a higher degree of stochasticity was associated with taxonomic variations. Significant associations were observed between chlorophyllaconcentration and B12biosynthesis traits, indicating their importance in global ocean primary production. Conclusively, this study revealed an essential ecological mechanism governing the assembly of microbes in nature: the environment selects function rather than taxonomy; functional redundancy underlies stochastic community assembly.

Impact Statement

A central question in ecology is how a galaxy of microbial taxa is assembled and distributed across space and through time, executing essential ecosystem functions. By anchoring microbial functional traits potentially involved in B12biosynthesis and their carrying microbial taxa in the global ocean, this study addresses essential ecological questions from functional and taxonomic angles. Integrating multiple lines of evidence, we show that the ecosystem selects functional traits rather than taxonomic groups, and functional redundancy underlies stochastic taxonomic community assembly. Also, microbial communities potentially involved in B12biosynthesis are significantly associated with chlorophyllaconcentration, demonstrating their importance in global ocean primary production. This study provides valuable mechanistic insights into the complex microbial community assembly in natural ecosystems.
The phosphorylation landscape of infection-related development by the rice blast fungus
Authors: Cruz-Mireles Neftaly , Osés-Ruiz Miriam , Derbyshire Paul , Jégousse Clara , Ryder Lauren S. , Bautista Mark Jave , Eseola Alice Bisola , Sklenar Jan , Tang Bozeng , Yan Xia , Ma Weibin , Findlay Kim C. , Were Vincent , MacLean Dan , Talbot Nicholas J. , Menke Frank L.H.
Published: August 2023

Many of the world’s most devastating crop diseases are caused by fungal pathogens which elaborate specialized infection structures to invade plant tissue. Here we present a quantitative mass spectrometry-based phosphoproteomic analysis of infection-related development by the rice blast fungusMagnaporthe oryzae, which threatens global food security. We mapped 8,005 phosphosites on 2,062 fungal proteins, revealing major re-wiring of phosphorylation-based signaling cascades during fungal infection. Comparing phosphosite conservation across 41 fungal species reveals phosphorylation signatures specifically associated with biotrophic and hemibiotrophic fungal infection. We then used parallel reaction monitoring to identify phosphoproteins directly regulated by the Pmk1 MAP kinase that controls plant infection byM. oryzae. We define 33 substrates of Pmk1 and show that Pmk1-dependent phosphorylation of a newly identified regulator, Vts1, is required for rice blast disease. Defining the phosphorylation landscape of infection therefore identifies potential therapeutic interventions for control of plant diseases.
Local activation of CA1 pyramidal cells induces theta phase precession
Authors: Sloin Hadas E. , Spivak Lidor , Levi Amir , Gattegno Roni , Someck Shirly , Stark Eran
Published: August 2023

Hippocampal theta phase precession is involved in spatiotemporal coding and generating multineural spike sequences, but how precession originates remains unresolved. To determine whether precession can be generated directly in CA1 and disambiguate multiple competing mechanisms, we used optogenetic activation to impose artificial place fields in pyramidal cells of mice running on a linear track. More than a third of the CA1 artificial fields exhibited synthetic precession that persisted for a full cycle. In contrast, artificial fields in the parietal cortex did not exhibit synthetic precession. The findings are incompatible with precession models based on inheritance, spreading activation, dual-input, or inhibition-excitation summation. Thus, a precession generator resides locally within CA1.
Identification of human skin microbiome odorants that manipulate mosquito landing behavior
Authors: Coutinho-Abreu Iliano V. , Jamshidi Omid , Raban Robyn , Atabakhsh Katayoon , Merriman Joseph A. , Fischbach Michael A. , Akbari Omar S.
Published: August 2023

The resident human skin microbiome is responsible for the production of most of the human scents that are attractive to mosquitoes. Hence, engineering the human skin microbiome to synthesize less of mosquito attractants or produce repellents could potentially reduce bites and prevent the transmission of deadly mosquito-borne pathogens. In order to further characterize the human skin volatilome, we quantified the major volatiles of 39 strains of skin commensals (StaphylococciandCorynebacterium). Importantly, to validate the behavioral activity of these volatiles, we first assessed landing behavior triggered by human skin bacteria volatiles. We demonstrated that this behavioral step is gated by the presence of carbon dioxide and L-(+)-lactic acid, similar to the combinatorial coding triggering short range attraction. Repellency behavior to selected skin volatiles and the geraniol terpene was tested in the presence of carbon dioxide and L-(+)-lactic acid. In a 2-choice landing behavior context, the skin volatiles 2- and 3-methyl butyric acids reduced mosquito landing by 62.0-81.6% and 87.1-99.6%, respectively. Similarly, geraniol was capable of reducing mosquito landing behavior by 74.9%. We also tested the potential repellency effects of geraniol on mosquitoes at short-range using a 4-port olfactometer. In these assays, geraniol reduced mosquito attraction (69-78%) to a mixture of key human kairomones carbon dioxide, L-(+)-lactic acid, and ammonia. These findings demonstrate that carbon dioxide and L-(+)-lactic acid changes the valence of other skin volatiles towards mosquito landing behavior. Moreover, this study offers candidate odorants to be targeted in a novel strategy to reduce attractants or produce repellents by the human skin microbiota that may curtail mosquito bites, and subsequent mosquito-borne disease.
The current quality and requirements of prehospital and emergency care in Indonesia and Malaysia: a cross-sectional multicenter survey
Authors: Tokita Akio , Nunokawa Hanako , Liu Keibun , Iwamoto Yuta , Sonoo Tomohiro , Hara Konan , Nakajima Mikio , Fukaguchi Kiyomitsu , Takeda Takanori , Sanip Amirudin , Juzar Dafsah A. , Harvendhar Singh Gurjeet Singh a/l , Condro Lukito , Tobing Monalisa , Hasan Muhammad Abdus-Syakur bin Abu , Rahman Nik Hisamuddin NA , Mahisa Orizanov , Zairinal Ramdinal Aviesena , Ramli Mohd Khairulizwan bin , Nor Mohd Afiq Mohd , Goto Tadahiro , Zakaria Mohd Idzwan bin
Published: August 2023

Background

Rapid economic growth in Southeast Asian countries has led to a significant gap between supply and demand of emergency care, which may negatively affect the health outcomes of local populations. The purpose of this study was to identify current challenges faced by emergency care systems in Indonesia and Malaysia.

Methods

An online survey was conducted between August and November 2022. Survey participants consisted of emergency department (ED) doctors, nurses, and other medical staff in 11 hospitals in Indonesia and Malaysia. The survey collected information on respondents’ characteristics, factors associated with the quality of prehospital or ED care, missing clinical information, and factors associated with patients’ length of stay at the ED.

Results

A total of 83 and 109 respondents from Indonesia and Malaysia, respectively, answered the survey. The most important factor affecting prehospital care quality in both countries was “inadequate amount of clinical information from the ambulance.” The most important factor affecting ED care quality was “crowdedness in the emergency room during night shifts.” The clinical information most frequently missing was family history, followed by estimated time of arrival to the hospital or medication history. The primary factor affecting the length of ED stay was diagnostic studies and their turnaround time.

Conclusions

This study identified common challenges in the emergency care systems of Indonesia and Malaysia. Our findings highlight the importance of recognizing both common and country-specific challenges to improve the quality of emergency care in Southeast Asia.
Clinical consequences of a polygenic predisposition to benign lower white blood cell counts
Authors: Mosley Jonathan D. , Shelley John P. , Dickson Alyson L. , Zanussi Jacy , Daniel Laura L. , Zheng Neil S. , Bastarache Lisa , Wei Wei-Qi , Shi Mingjian , Jarvik Gail P. , Rosenthal Elisabeth A. , Khan Atlas , Sherafati Alborz , Kullo Iftikhar J. , Walunas Theresa L. , Glessner Joe , Hakonarson Hakon , Cox Nancy J. , Roden Dan M. , Frangakis Stephan G. , Vanderwerff Brett , Stein C. Michael , Van Driest Sara L. , Borinstein Scott C. , Shu Xiao-Ou , Zawistowski Matthew , Chung Cecilia P. , Kawai Vivian K.
Published: August 2023

Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio=0.55 per standard deviation increase in PGSWBC[95%CI, 0.30 - 0.94], p=0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n=1,724, hazard ratio [HR]=0.78 [0.69 - 0.88], p=4.0×10-5) or immunosuppressant (n=354, HR=0.61 [0.38 – 0.99], p=0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n=1,466, HR=0.62 [0.44 - 0.87], p=0.006). Collectively, these findings suggest that a WBC count polygenic score identifies individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.
Comparative Analysis of Salinity Response Transcriptomes in Salt-Tolerant Pokkali and Susceptible IR29 Rice
Authors: Geniza Matthew , Fox Samuel E. , Sage Abigail , Ansariola Mitra , Megraw Molly , Jaiswal Pankaj
Published: August 2023

Rice is a major cereal crop responsible for feeding the world’s population. To improve grain yield and quality, meet growing demand, and face the challenges posed by abiotic and biotic stress, it is imperative to explore genetic diversity in rice for candidate genes and loci that may contribute to stress tolerance. High salinity abiotic stress in the rice growth environment affects growth, yield, and quality. Therefore, we conducted a salt stress-responsive RNA-Seq-based transcriptome study of two rice (Oryza sativa) varieties, the salt-tolerant Pokkali and the salt-sensitive breeding line IR29. To identify early and late salinity response genes, we collected samples from the treated and untreated plants in this study at 1, 2, 5, 10, and 24 hours after treatment with 300 mM NaCl solution. We identified 7,209 and 6,595 salt-induced differentially expressed transcripts from Pokkali and IR29, respectively, over all time points. We identified ∼190,000 single nucleotide polymorphism (SNP) sites and ∼40,000 simple sequence repeat (SSR) sites, allowing analysis of their consequences on genetic diversity, transcript structure, gene function, and differential expression. We identified and validated the polymorphic SSRs in the differentially expressed salt-responsive genesRespiratory Burst Oxidase Homolog B (RBOHB)andRice Salt Sensitive 1 (RSS1)that underly nearby salt tolerance QTLs. This study provides insight into transcriptional programming during salt stress, evidence for improvingOryzagenome annotations, and reveals SNP and SSR sites associated with differential gene expression and potential gene function.
How to prevent chick culling in the poultry industry? Discovery of a new biomarker forin ovogender screening
Authors: Drouin Nicolas , Elfrink Hyung Lim , Bruins Wouter , Koval Slavik , Harms Amy C , Stutterheim Wil , Hankemeier Thomas
Published: August 2023

Chicken eggs are one of the most consumed foods worldwide. However, the practice of chicken culling in the poultry industry involves unnecessary animal suffering and finding a way to put an end to this has become a societal priority. One approach that has been propagated as acceptable is based on the selection of female eggs early in the incubation process and the devitalization of the male eggs.

It is with this objective in mind that we searched for a biomarker for early gender screening in eggs. Applying an untargeted mass spectrometry approach, we profiled allantoic fluid of different day-old eggs and identified the feature 3-[(2-aminoethyl)sulfanyl]butanoic acid (ASBA) as a strong biomarker forin-ovogender prediction for day-9 old embryos. After validation using LC-APCI-MRM with an internal standard, we found ASBA can predict the female gender with a sensitivity and specificity well above 95% in our experiments.

Highlights

Discovery of a biomarker of chicken embryo gender in allantoic fluid from eggs

Day 9 after laying was determined as optimum for sex prediction and animal welfare

3-[(2-aminoethyl)sulfanyl]butanoic acid was identified using mass spectrometry

The biomarker was validated on large cohorts of different chicken species

Graphical abstract
Insights into RAG evolution from the identification of “missing link” family ARAGLtransposons
Authors: Martin Eliza C. , Targa Lorlane Le , Tsakou-Ngouafo Louis , Fan Tzu-Pei , Lin Che-Yi , Xiao Jianxiong , Su Yi Hsien , Petrescu Andrei-Jose , Pontarotti Pierre , Schatz David G.
Published: August 2023

A series of “molecular domestication” events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events is not well understood, in part because of a dearth of information regarding the invertebrateRAGL-Atransposon family. In contrast to the abundant and divergentRAGL-Btransposon family,RAGL-Amost closely resemblesRAGand is represented by a single orphanRAG1-like(RAG1L) gene in the genome of the hemichordatePtychodera flava(PflRAG1L-A). Here, we provide evidence for the existence of completeRAGL-Atransposons in the genomes ofP. flavaand several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of theRAGL-Atransposons combine features of bothRAGL-Btransposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, PflRAG2L-A and echinoderm RAG2L-A contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g., the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.
Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons
Authors: Bell Andrew M. , Utting Charlotte , Dickie Allen C. , Kucharczyk Mateusz W. , Quillet Raphaëlle , Gutierrez-Mecinas Maria , Razlan Aimi N.B. , Cooper Andrew H. , Lan Yuxuan , Hachisuka Junichi , Weir Greg A. , Bannister Kirsty , Watanabe Masahiko , Kania Artur , Hoon Mark A. , Macaulay Iain C. , Denk Franziska , Todd Andrew J.
Published: August 2023

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord usingin situhybridization. We identify 3 clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 & ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.

Significance Statement

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that underlies perception of pain, itch and skin temperature. It is therefore an important target for the development of new treatments for chronic pain. Our understanding of this system has been hampered by the considerable diversity of its constituent cells. Here we dissect the complex heterogeneity of these cells by using high-resolution RNA sequencing. We reveal five distinct types of ALS neurons, which are differentially distributed within the spinal cord, and probably represent functional populations. Our data provide novel insights into the molecular architecture of the ALS, and will be important for future studies to define the roles of different ALS cell types in sensory processing.
Distractor effects in decision making are related to the individual’s style of integrating choice attributes
Authors: Wong Jing Jun , Bongioanni Alessandro , Rushworth Matthew F S , Chau Bolton K H
Published: August 2023

It is widely agreed that people make irrational decisions in the presence of irrelevant distractor options. However, there is little consensus on whether decision making is facilitated or impaired by the presence of a highly rewarding distractor or whether the distraction effect operates at the level of options’ component attributes rather than at the level of their overall value. To reconcile different claims, we argue that it is important to incorporate consideration of the diversity of people’s ways of decision making. We focus on a recent debate over whether people combine choice attributes in an additive or multiplicative way. Employing a multi-laboratory dataset investigating the same decision making paradigm, we demonstrated that people used a mix of both approaches and the extent to which approach was used varied across individuals. Critically, we identified that this variability was correlated with the effect of the distractor on decision making. Individuals who tended to use a multiplicative approach to compute value, showed a positive distractor effect. In contrast, in individuals who tended to use an additive approach, a negative distractor effect (divisive normalisation) was prominent. These findings suggest that the distractor effect is related to how value is constructed, which in turn may be influenced by task and subject specificities. Our work concurs with recent behavioural and neuroscience findings that multiple distractor effects co-exist.
Expression-based machine learning models for predicting plant tissue identity
Authors: Palande Sourabh , Arsenault Jeremy , Basurto-Lozada Patricia , Bleich Andrew , Brown Brianna N. I. , Buysse Sophia F. , Connors Noelle A. , Adhikari Sikta Das , Dobson Kara C. , Guerra-Castillo Francisco Xavier , Guerrero-Carrillo Maria F. , Harlow Sophia , Herrera-Orozco Héctor , Hightower Asia T. , Izquierdo Paulo , Jacobs MacKenzie , Johnson Nicholas A. , Leuenberger Wendy , Lopez-Hernandez Alessandro , Luckie-Duque Alicia , Martínez-Avila Camila , Mendoza-Galindo Eddy J. , Plancarte David , Schuster Jenny M. , Shomer Harry , Sitar Sidney C. , Steensma Anne K. , Thomson Joanne Elise , Villaseñor-Amador Damián , Waterman Robin , Webster Brandon M. , Whyte Madison , Zorilla-Azcué Sofía , Montgomery Beronda L. , Husbands Aman Y. , Krishnan Arjun , Percival Sarah , Munch Elizabeth , VanBuren Robert , Chitwood Daniel H. , Rougon-Cardoso Alejandra
Published: August 2023

The selection ofArabidopsisas a model organism played a pivotal role in advancing genomic science, firmly establishing the cornerstone of today ‘s plant molecular biology. Competing frameworks to select an agricultural- or ecological-based model species, or to decentralize plant science and study a multitude of diverse species, were selected against in favor of building core knowledge in a species that would facilitate genome-enabled research that could assumedly be transferred to other plants. Here, we examine the ability of models based onArabidopsisgene expression data to predict tissue identity in other flowering plant species. Comparing different machine learning algorithms, models trained and tested onArabidopsisdata achieved near perfect precision and recall values using the K-Nearest Neighbor method, whereas when tissue identity is predicted across the flowering plants using models trained onArabidopsisdata, precision values range from 0.69 to 0.74 and recall from 0.54 to 0.64, depending on the algorithm used. Below-ground tissue is more predictable than other tissue types, and the ability to predict tissue identity is not correlated with phylogenetic distance fromArabidopsis. This suggests that gene expression signatures rather than marker genes are more valuable to create models for tissue and cell type prediction in plants. Our data-driven results highlight that, in hindsight, the assertion that knowledge fromArabidopsisis translatable to other plants is not always true. Considering the current landscape of abundant sequencing data and computational resources, it may be prudent to reevaluate the scientific emphasis onArabidopsisand to prioritize the exploration of plant diversity.
XRE Transcription Factors Conserved inCaulobacterand φCbK Modulate Adhesin Development and Phage Production
Authors: McLaughlin Maeve , Fiebig Aretha , Crosson Sean
Published: August 2023

Upon infection, transcriptional shifts in both a host bacterium and its invading phage determine host and viral fitness. The xenobiotic response element (XRE) family of transcription factors (TFs), which are commonly encoded by bacteria and phages, regulate diverse features of bacterial cell physiology and impact phage infection dynamics. Through a pangenome analysis ofCaulobacterspecies isolated from soil and aquatic ecosystems, we uncovered an apparent radiation of a paralogous XRE TF gene cluster, several of which have established functions in the regulation of holdfast adhesin development and biofilm formation inC. crescentus. We further discovered related XRE TFs across the classAlphaproteobacteriaand its phages, including the φCbK Caulophage, suggesting that members of this gene cluster impact host-phage interactions. Here we show that that a closely related group of XRE proteins, encoded by bothC. crescentusand φCbK, can form heteromeric associations and control the transcription of a common gene set, influencing processes including holdfast development and the production of φCbK virions. The φCbK XRE paralog,tgrL, is highly expressed at the earliest stages of infection and can directly repress transcription ofhfiA, a potent holdfast inhibitor, andgafYZ, a transcriptional activator of prophage-like gene transfer agents (GTAs) encoded on theC. crescentuschromosome. XRE proteins encoded from theC. crescentuschromosome also directly repressgafYZtranscription, revealing a functionally redundant set of host regulators that may protect against spurious production of GTA particles and inadvertent cell lysis. Deleting host XRE transcription factors reduced φCbK burst size, while overexpressing these genes or φCbKtgrLrescued this burst defect. We conclude that an XRE TF gene cluster, shared byC. crescentusand φCbK, plays an important role in adhesion regulation under phage-free conditions, and influences host-phage dynamics during infection.
The focal adhesion protein talin is a mechanically-gated A-kinase anchoring protein (AKAP)
Authors: Kang Mingu , Otani Yasumi , Guo Yanyu , Yan Jie , Goult Benjamin T. , Howe Alan K.
Published: August 2023

The cAMP-dependent protein kinase (Protein Kinase A; PKA) is a ubiquitous, promiscuous kinase whose activity is focused and specified through subcellular localization mediated by A-kinase anchoring proteins (AKAPs). PKA has complex roles as both an effector and a regulator of integrin-mediated cell adhesion to the extracellular matrix (ECM). Recent observations demonstrate that PKA is an active component of focal adhesions (FA), intracellular complexes coupling ECM-bound integrins to the actin cytoskeleton, suggesting the existence of one or more FA AKAPs. Using a combination of a promiscuous biotin ligase fused to PKA type-IIα regulatory (RIIα) subunits and subcellular fractionation, we identify the archetypal FA protein talin1 as an AKAP. Talin is a large, mechanosensitive scaffold that directly links integrins to actin filaments and promotes FA assembly by recruiting additional components in a force-dependent manner. The rod region of talin1 consists of 62 α-helices bundled into 13 rod domains, R1-R13. Direct binding assays and nuclear magnetic resonance spectroscopy identify helix41 in the R9 subdomain of talin as the PKA binding site. PKA binding to helix41 requires unfolding of the R9 domain, which requires the linker region between R9 and R10. Finally, single-molecule experiments with talin1 and PKA, and experiments in cells manipulated to alter actomyosin contractility demonstrate that the PKA-talin interaction is regulated by mechanical force across the talin molecule. These observations identify the first mechanically-gated anchoring protein for PKA, a new force-dependent binding partner for talin1, and thus a new mechanism for coupling cellular tension and signal transduction.
Acquired stress resilience through bacteria-to-nematode horizontal gene transfer
Authors: Pandey Taruna , Kalluraya Chinmay , Wang Bingying , Xu Ting , Huang Xinya , Guang Shouhong , Daugherty Matthew D. , Ma Dengke K.
Published: August 2023

Natural selection drives acquisition of organismal resilience traits to protect against adverse environments. Horizontal gene transfer (HGT) is an important evolutionary mechanism for the acquisition of novel traits, including metazoan acquisition of functions in immunity, metabolism, and reproduction via interdomain HGT (iHGT) from bacteria. We report that the nematode generml-3, which was acquired by iHGT from bacteria, enables exoskeleton resilience and protection against environmental toxins inC. elegans. Phylogenetic analysis reveals that diverse nematode RML-3 proteins form a single monophyletic clade most highly similar to bacterial enzymes that biosynthesize L-rhamnose to build cell wall polysaccharides.C. elegans rml-3is regulated in developing seam cells by heat stress and stress-resistant dauer stage. Importantly,rml-3deficiency impairs cuticle integrity, barrier functions and organismal stress resilience, phenotypes that are rescued by exogenous L-rhamnose. We propose that iHGT of an ancient bacterialrml-3homolog enables L-rhamnose biosynthesis in nematodes that facilitates cuticle integrity and organismal resilience in adaptation to environmental stresses during evolution. These findings highlight the remarkable contribution of iHGT on metazoan evolution that is conferred by the domestication of bacterial genes.
What drives small and medium enterprises to establish and terminate banking relationships?
Authors: Afridi Muhammad Asim , Tahir Muhammad
Published: August 2023

Purpose

This paper investigates the factors crucial for small and medium enterprises (SMEs) in establishing business relationships with banks in Pakistan.

Design/methodology/approach

To investigate how SMEs select banking relationships using criteria, such as decision factors, decision-makers, and decision processes, a comprehensive literature review was used to classify SMEs' decision factors for bank selection. A survey questionnaire was distributed to 200 SMEs, randomly selected from the Small and Medium Enterprise Development Authority database in Pakistan. Probit/Tobit model is estimated to explain the behavior of SMEs.

Findings

The results reveal that SMEs consider a bank's Reputation, Price, and Location essential while establishing bank relationships. SMEs tend to terminate relationships with banks when the Price and Location of the bank are considered essential factors in the relationship with the banks. Price and Location are necessary for SMEs to reduce banking relationships. The SMEs also tend to reduce if they get attractive offers, or the SMEs are recommended to make a banking relationship. This study also provides intuitions for bank policymakers to design policies to retain SME customers and attract new business relationships.

Practical implications

The research emphasizes the importance of competitive and transparent pricing strategies in designing products for SMEs. Banks must prioritize their Reputation and credibility to attract and retain relationships with SMEs.

Originality/value

The study attempts to provide evidence on the SME-Bank relationship focusing on the factors that are crucial for SMEs to decide while establishing business relationships with banks. Also, most of the related literature focuses on developed countries; this research adds to the literature on SMEs' behavior, particularly in a developing country's context.