bluuebunny/crossref_metadata_2025 huggingface dataset:
Counter-gradient variation in gene expression between fish populations facilitates colonization of low-dissolved oxygen environments
Authors: Fox Janay A. , Hunt David A. G. A. , Hendry Andrew P. , Chapman Lauren J. , Barrett Rowan D. H.
Published: November 2023

The role of phenotypic plasticity during colonization remains unclear due to the shifting importance of plasticity across timescales. Over time, genetic responses can reduce plasticity such that species in a novel environment show higher levels of plasticity than those with a longer evolutionary timescale in the environment. Therefore, comparing species in the early stages of colonization to long-established species provides a powerful approach for uncovering the role of phenotypic plasticity during different stages of colonization. We compared gene expression between the cyprinid fishEnteromius apleurogramma, a species that has undergone a recent range expansion, andE. neumayeri, a long-established native species in the same region, caught from low-dissolved oxygen (DO) and high-DO habitats. We sampled tissue either immediately after capture from the field or after a two-week acclimation under high-DO conditions, allowing us to test for both evolved and plastic differences in low-DO vs high-DO populations of each species. We found that most genes showing evolved differences in gene expression did not overlap with those showing plastic differences in gene expression. However, in the genes that did overlap, there was counter-gradient variation such that plastic and evolved gene expression responses were in opposite directions in both species. Additionally,E. apleurogrammahad higher levels of plasticity and evolved divergence in gene expression between field populations. We suggest that the higher level of plasticity and counter-gradient variation may have allowed rapid genetic adaptation inE. apleurogrammaand facilitated colonization. This study shows how counter-gradient variation may impact colonization of divergent oxygen environments.
TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma
Authors: Tian Maojin , Yang Le , Zhao Ziqian , Li Jigang , Wang Lianqing , Yin Qingqing , Hu Wei , Lou Yunwei , Du Jianxin , Zhao Peiqing
Published: November 2023

TIPE (TNFAIP8) has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1α activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an ERK-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1α signaling pathway plays a pivotal role in promoting cancer stem cell properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.
Maternal cardiovascular and haematological complications alter the risk associations between environmental exposure and adverse pregnancy outcomes
Authors: Sun Jason , Tang Haiyang , Zhao Huan , Xiang Qingyi , Tian Yijia , van Daalen Kim Robin , Tang Kun , Loo Evelyn Xiu-Ling , Shek Lynette P , Archibald Alexander T , Xu Wei , Guo Yuming , Bai Xiaoxia
Published: November 2023

Given China’s recent introduction of the “three-child policy” in response to population ageing1, safeguarding perinatal health has become an urgent priority2. Previous epidemiological research seldom explored the risk factors of maternal cardiovascular and haematological diseases, or its impact on adverse pregnancy outcomes (APO). To fill the literature gap, here we conducted systematic epidemiological analyses on 121,090 pregnant women and their neonates from the ZEBRA Chinese prospective maternity cohort. We find that incremental exposure in PM2.5, O3, and green space modify the risks of APO, including congenital heart disease, by 11.2%, 7.8%, and –5.5%, respectively. Maternal cardiovascular and haematological complications during pregnancy significantly aggravate the risk of APO by 66.2%, and also modify the environment-APO risk associations by amplifying the hazards of air pollution and weakening the protective effect of greenness accessibility. Our research findings support the Sustainable Development Goals (e.g. SDG3)3,4by providing first-hand epidemiological evidence and clinical guidance for protecting maternal and neonatal health.
Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation
Authors: Fu Jianing , Hsiao Thomas , Waffarn Elizabeth , Meng Wenzhao , Long Katherine D. , Frangaj Kristjana , Jones Rebecca , Gorur Alaka , Shtewe Areen , Li Muyang , Muntnich Constanza Bay , Rogers Kortney , Jiao Wenyu , Velasco Monica , Matsumoto Rei , Kubota Masaru , Wells Steven , Danzl Nichole , Ravella Shilpa , Iuga Alina , Vasilescu Elena-Rodica , Griesemer Adam , Weiner Joshua , Farber Donna L. , Luning Prak Eline T. , Martinez Mercedes , Kato Tomoaki , Hershberg Uri , Sykes Megan
Published: November 2023

It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of gut lymphocyte populations. Using polychromatic flow cytometry that includes HLA allele group-specific mAbs distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. We confirm the early presence of naïve donor B cells in the circulation and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa. Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in healthy control adults. Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of establishment of a stable mucosal B cell repertoire.
‘Whose quality of life is it anyway?’ – Evaluation of quality of life tools for children with complex needs accessing specialist leisure provision
Authors: Astill Fiona , Collins Bethan , McGrath Nicole , Kemp Alison , Hurt Lisa , Maguire Sabine
Published: November 2023

Studies of quality of life (QoL) routinely exclude children with complex needs. These children struggle to access leisure activities, particularly those with severe communication needs or challenging behaviour. Sparkle provides specialised leisure services to children and young people (0-17 years) with complex needs in South Wales, UK. We aimed to evaluate previously validated tools to measure QoL with this population.

Three tools were assessed over a 6-year period – PedsQL, KINDLRand QI-Disability. PedsQL (41) and KINDLR(10) were attempted by the children attending the clubs (5-17 years old), and QI-Disability by caregivers (96). The majority of child participants had a neurodevelopmental diagnosis, a proportion of whom were non-verbal.

Neither KINDLRnor PedsQL were appropriate for the population, with children unable to understand the questions and answers. The QI-Disability scores showed a statistically significant improvement in parents’ estimate of their child’s positive emotions, but results were severely limited by drop off.

Existing validated QoL tools cannot be meaningfully used by children with complex needs. While the caregiver tool showed some benefit of specialist leisure provision, it is recognised that caregivers may perceive a child’s QoL differently to the child themselves, and caregivers clearly found repeat measurements onerous.
75 years’ journey of malaria publications: what and where?
Authors: Deora Nimita , Kar Sonalika , Pande Veena , Sinha Abhinav
Published: November 2023

Background

Malaria is a life-threatening and ancient disease that has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South East Asian and South American countries. Proportionally, malaria has attracted global research priorities amongst infectious diseases and this is evident from the number of publications directly or indirectly related to malaria from across the globe, irrespective of the endemicity of the disease. However, formal and exhaustive analyses of these ‘malaria publications’ are rarely done and published.

Methods

We therefore did a systematic analyses of the literature published on malaria with an intent to retrieve information on what has been published on malaria, where is it published and which countries are major contributors in malaria research. The study presents malaria publications from 1945 to 2020 retrieved using three global databases: Web of Science™, Embase® and Scopus®. Exported data was examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.

Results

The total number of published records on malaria ranged from 90,282-1,12,698. On the basis of the number of publications, the United States, United Kingdom, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene and PLoS One were the most preferred journals whereas the University of London, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organizations.

Conclusion

The study concluded that a disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases were found to be incomparable and must be standardized on multiple dimensions before making a comparison. There are still some pertinent outstanding questions that need to be addressed: why there is still a research mismatch between endemic and non-endemic regions? why a standardized and comparable information is still not available for direct and quick analyses? is less case-based research conducted as compared to in-vitro or in animal models?
Iron status, thyroid dysfunction and iron deficiency anemia: a two-sample Mendelian randomization study
Authors: Huang Xianjun , Guo Tianhong , Wu Yuqin , Xu Qi , Dai Junliang , Huang Yuanshuai
Published: November 2023

Objective

Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aims to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction.

Methods

A two-sample Mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based GWAS databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK biobank). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.

Results

The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (OR = 1.101, 95% CI = 1.048-1.157,p< 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035,p< 0.001). Sensitivity analysis supported that the MR estimates were robust.

Conclusion

In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.
Portrait of Mental Health Identified by People with the Post-Covid Syndrome
Authors: Mayo Nancy , Hum Stanley , Matout Mohamad , Fellows Lesley K , Brouillette Marie-Josée
Published: November 2023

Aims

The Post-COVID-19 syndrome (PCS) represents an epidemic within the COVID-19 pandemic, with potentially serious consequences for affected individuals, the healthcare system, and society at large. Facing a new and poorly understood health condition, this study aimed to produce a patient-centered understanding of mental health symptom patterns, functional impact, and intervention priorities.

Methods

A cross-sectional analysis of the first 414 participants in a longitudinal study recruited over a 5- month from September 2022 to January 2023 was carried out involving people from Quebec who self-identified as having symptoms of PCS. People were asked to name areas of their mental health affected by PCS using the structure of the Patient Generated Index (PGI), an individualized measure suited to eliciting the most frequent and most bothersome symptoms. The PGI was supplemented with a set of patient-reported outcome measures across the rubrics of the Wilson- Cleary model. The text threads from the PGI were grouped into topics using BERTopic analysis.

Results

Twenty topics were identified from 818 text threads referring to PCS mental health symptoms nominated using the PGI format. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation.

Conclusion

This novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate the extent to which existing measures cover the content identified by people with PCS or to justify the development of a new measure of the mental health impact of PCS.
Delivery of mRNA encoding an anti-tau monoclonal antibody and engineered scFv intrabody results in functional antibody expression in SH-SY5Y cells
Authors: Wongsodirdjo Patricia , Caruso Alayna C. , Yong Alicia , Lester Madeleine A. , Vella Laura J. , Hung Ya Hui , Nisbet Rebecca M.
Published: November 2023

Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer’s disease. In the last year, two anti-amyloid monoclonal antibodies, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer’s disease, whilst several tau-targeting monoclonal antibodies are currently in clinical trials. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Syntheticin vitro-transcribed mRNA encoding antibodies for endogenous protein expression holds the potential to overcome many of the limitations associated with protein antibody production. Here, we have generated syntheticin vitro-transcribed mRNA encoding a tau specific monoclonal antibody as a full-sized IgG and as a single chain variable fragment (scFv).In vitrotransfection of human neuroblastoma SH-SY5Y cells demonstrated the ability of the synthetic mRNA to be translated into functional tau-specific antibodies. Furthermore, we show that the translation of the tau-specific scFv as an intrabody results in the specific engagement of intracellular tau. This work highlights the utility of mRNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of tau in tauopathies.
Tissue-specific sex difference in the metabolism of fatty acid esters of hydroxy fatty acids
Authors: Riecan Martin , Domanska Veronika , Lupu Cristina , Patel Maulin , Vondrackova Michaela , Rossmeisl Martin , Saghatelian Alan , Lupu Florea , Kuda Ondrej
Published: November 2023

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related toAdtrpmRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels.Adtrpdeletion had minimal impact on both sexes’ metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex effects on FAHFA metabolism in humans.
Bioinformatic, enzymatic and structural characterization ofTrichuris suishexosaminidase HEX-2
Authors: Dutkiewicz Zuzanna , Varrot Annabelle , Breese Karen J. , Stubbs Keith A. , Nuschy Lena , Adduci Isabella , Paschinger Katharina , Wilson Iain B. H.
Published: November 2023

Hexosaminidases are key enzymes in glycoconjugate metabolism and occur in all kingdoms of life. Here, we have investigated the phylogeny of the GH20 glycosyl hydrolase family in nematodes and identified a β-hexosaminidase subclade only present in the Dorylaimia. We have expressed one of these, HEX-2 fromTrichuris suis, a porcine parasite, and shown that it prefers an aryl β-N-acetylgalactosaminidein vitro. HEX-2 has an almost neutral pH optimum and is best inhibited by GalNAc-isofagomine. Towards N-glycan substrates, it displays a preference for the removal of GalNAc residues from LacdiNAc motifs as well as the GlcNAc attached to the α1,3-linked core mannose. Thereby, it has a broader specificity than insect fused lobes (FDL) hexosaminidases, but one narrower than distant homologues from plants. Its X-ray crystal structure, the first of any subfamily 1 GH20 hexosaminidase to be determined, is closest toStreptococcus pneumoniaeGH20C and the active site is predicted to be compatible with accommodating both GalNAc and GlcNAc. The new structure extends our knowledge about this large enzyme family, particularly asT. suisHEX-2 also possesses the key glutamate residue found in human hexosaminidases of either GH20 subfamily, including HEXD whose biological function remains elusive.
Cell Spotter (CSPOT): A machine-learning approach to automated cell spotting and quantification of highly multiplexed tissue images
Authors: Nirmal Ajit J. , Yapp Clarence , Santagata Sandro , Sorger Peter K.
Published: November 2023

Highly multiplexed tissue imaging and in situ spatial profiling aim to extract single-cell data from specimens containing closely packed cells of diverse morphology. This is challenging due to the difficulty of accurately assigning boundaries between cells (segmentation) and then generating per-cell staining intensities. Existing methods use gating to convert per-cell intensity data to positive and negative scores; this is a common approach in flow cytometry, but one that is problematic in imaging. In contrast, human experts identify cells in crowded environments using morphological, neighborhood, and intensity information. Here we describe a computational approach (Cell Spotter or CSPOT) that uses supervised machine learning in combination with classical segmentation to perform automated cell type calling. CSPOT is robust to artifacts that commonly afflict tissue imaging and can replace conventional gating. The end-to-end Python implementation of CSPOT can be integrated into cloud-based image processing pipelines to substantially improve the speed, accuracy, and reproducibility of single-cell spatial data.
Age-related fornix decline predicts conservative response strategy-based slowing in perceptual decision-making
Authors: Revie Lauren , Metzler-Baddeley Claudia
Published: November 2023

Aging leads to increased response latencies but the underpinning cognitive and neural mechanisms remain elusive. We modelled older and younger adults’ response time (RT) data from a 2-choice flanker task with a diffusion drift model (DDM) and employed multi-shell diffusion weighted magnetic resonance imaging and spectroscopy to study neurobiological predictors of DDM components thought to govern RTs: drift rate, boundary separation and non-decision time. Microstructural indices of fractional anisotropy (FA), diffusivities and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED) were derived from white matter pathways of visuo-perceptual and attention networks (optic radiation, inferior and superior longitudinal fasciculi, fornix) and estimates of metabolite concentrations [N-acetyl aspartate (NAA), glutamate (Glx), γ-aminobutyric acid (GABA), creatine (Cr), choline (Cho) and myoinositol (mI)] were measured from occipital (OCC), anteri- or and posterior cingulate cortices (ACC, PPC). Ageing was associated with increased RT, boundary separation, and non-decision time. Differences in boundary separation but not non-decision time mediated age-related response slowing. Regression analyses revealed a network of brain regions involved in top-down (fornix FA, diffusivities in right SLF) and bottom-up processing (mI in OCC, AD in left optic radiation) and verbal intelligence as significant predictors of RTs and non-decision time (NAA in ACC, AD in the right ILF, creatine in the OCC) while fornix FA was the only predictor for boundary separation. Fornix FA mediated the effects of age on RTs but notvice versa. These results provide novel insights into the cognitive and neural underpinnings of age-related slowing.
A long-read draft assembly of the Chinese mantis (Mantodea: Mantidae:Tenodera sinensis) genome reveals patterns of ion channel gain and loss across Arthropoda
Authors: Goldberg JK , Godfrey RK , Barrett M
Published: November 2023

Praying mantids (Mantodea: Mantidae) are iconic insects that have captivated biologists for decades, especially the species with cannibalistic copulatory behavior. This behavior has been cited as evidence that insects lack nociceptive capacities and cannot feel pain; however, this behaviorally-driven hypothesis has never been rigorously tested at the genetic or functional level. To enable future studies of nociceptive capabilities in mantids, we sequenced and assembled a draft genome of the Chinese praying mantis (Tenodera sinensis) and identified multiple classes of nociceptive ion channels by comparison to orthologous gene families in Arthropoda. Our assembly - produced using PacBio HiFi reads - is not chromosome-scale (Total size = 3.03Gb; N50 = 1.8Mb; 4966 contigs), but is highly complete with respect to gene content (BUSCO complete = 98.7% [odb10_insecta]). The size of our assembly is substantially larger than that of most other insects, but is consistent with the size of other mantid genomes. We found that most families of nociceptive ion channels are present in theT. sinensisgenome; that they are most closely related to those found in the damp-wood termite (Zootermopsis nevadensis); and that some families have expanded inT. sinensiswhile others have contracted relative to nearby lineages. Our findings suggest that mantids are likely to possess nociceptive capabilities and provide a foundation for future experimentation regarding ion channel functions and their consequences for insect behavior.
Architectural underpinnings of stochastic intergenerational homeostasis
Authors: Joshi Kunaal , Wright Charles S. , Biswas Rudro R. , Iyer-Biswas Srividya
Published: November 2023

Living systems are naturally complex and adaptive, and offer unique insights into the strategies for achieving and sustaining stochastic homeostasis in different conditions. Here, we focus on homeostasis in the context of stochastic growth and division of individual bacterial cells. We take advantage of high-precision longterm dynamical data that have recently been used to extract emergent simplicities and to articulate empirical intra- and in-tergenerational scaling laws governing these stochastic dynamics. We identify the core motif in the mechanistic coupling between division and growth, which naturally yields these precise rules, thus also bridging the intra- and intergenerational phenomenologies. By developing and utilizing novel techniques for solving a broad class of first passage processes, we derive the exact analytic necessary and sufficient condition for sustaining stochastic intergenerational cell size homeostasis within this framework. Furthermore, we provide predictions for the precision kinematics of cell size homeostasis, and the shape of the interdivision time distribution, which are compellingly borne out by the high-precision data. Taken together, these results provide insights into the functional architecture of control systems that yield robust yet flexible stochastic homeostasis.
Co-inoculation with novel nodule-inhabiting bacteria reduces the benefits of legume-rhizobium symbiosis
Authors: Kosmopoulos James C. , Batstone-Doyle Rebecca T. , Heath Katy D.
Published: November 2023

The ecologically and economically vital symbiosis between nitrogen-fixing rhizobia and leguminous plants is often thought of as a bi-partite interaction, yet studies increasingly show the prevalence of non-rhizobial endophytes (NREs) that occupy nodules alongside rhizobia. Yet, what impact these NREs have on plant or rhizobium fitness remains unclear. Here, we investigated four NRE strains found to naturally co-occupy nodules of the legumeMedicago truncatulaalongsideSinorhizobium melilotiin native soils. Our objectives were to (1) examine the direct and indirect effects of NREs onM. truncatulaandS. melilotifitness, and (2), determine whether NREs can re-colonize root and nodule tissues upon reinoculation. We identified one NRE strain (522) as a novelPaenibacillusspecies, another strain (717A) as a novelBacillusspecies, and the other two (702A and 733B) as novelPseudomonasspecies. Additionally, we found that two NREs (Bacillus 717A and Pseudomonas 733B) reduced the fitness benefits obtained from symbiosis for both partners, while the other two (522, 702A) had little effect. Lastly, we found that NREs were able to co-infect host tissues alongsideS. meliloti. This study demonstrates that variation of NREs present in natural populations must be considered to better understand legume-rhizobium dynamics in soil communities.
Cross-talk between tissues is critical for intergenerational acclimation to environmental change
Authors: Suresh Sneha , Welch Megan J , Munday Philip L , Ravasi Timothy , Schunter Celia
Published: November 2023

An organism’s reaction to environmental changes is mediated by coordinated responses of multiple tissues. Additionally, parental priming may increase offsprings’ acclimation potential to changing environmental conditions. As the effects of human-induced climate change, such as ocean acidification (OA), continue to intensify it is critical to assess the acclimation potential of species at the whole organismal scale. For this we need to understand the cross-talk between tissues in regulating and responding to pH changes. Here by using a multi-tissue approach we determine the influence of 1) variation in parental behavioural tolerance and 2) parental environment, on molecular responses of their offspring in a coral reef fish. The gills and liver showed the highest transcriptional response to OA conditions in juvenile fish regardless of the parental environment, while the brain and liver showed the greatest signal of intergenerational acclimation. Key functional pathways that were altered in the brain upon within-generational CO2exposure were restored to control levels when parents were exposed to OA conditions. Furthermore, the expression of a new complement of genes involved in key functions was altered in the offspring only when parents were previously exposed to OA conditions. Therefore, previous parental conditioning to OA can reprogram tissue transcriptomic profiles of the offspring enabling them to better cope in an environment with elevated CO2levels. Overall, our results reveal tissue-specific transcriptional changes underlying intergenerational plastic responses to elevated CO2exposure and highlight the integration of these changes in promoting organismal acclimation to OA.
Reduction of coastal lighting decreases seabird strandings
Authors: Burt Tori V. , Collins Sydney M. , Green Sherry , Doiron Parker B. , Wilhelm Sabina I. , Montevecchi William A.
Published: November 2023

Leach’s Storm-Petrels (Hydrobates leucorhous) are small, threatened seabirds with an extensive breeding range in the North Atlantic and North Pacific Oceans. The Atlantic population, which represents approximately 40 - 48% of the global population, is declining sharply. Positive phototaxis, the movement towards artificial light at night (ALAN), is considered to be a key contributing factor. Many seabirds exhibit positive phototaxis, which can result in stranding on land. The Leach’s Storm-Petrel is the seabird most often found stranded around ALAN in the North Atlantic, though there is little experimental evidence showing that reducing ALAN will decrease the occurrence of stranded storm-petrels. During a two-year study at a large, brightly illuminated seafood processing plant adjacent to the Leach’s Storm-Petrel’s largest colony, we compared the number of birds that stranded when the lights at the plant were turned on versus off. We recorded survival, performed carcass counts of both adults and juveniles, and released any rescued individuals. Turning the lights off reduced strandings by 39.15% (CI: 11.45% - 58.19%). The peak stranding period occurred from 25 September to 28 October, and most of the stranded birds were fledglings. These results provide evidence to support the widespread reduction and modification of coastal artificial light, especially during avian fledging and migration periods.
Corythauma ayyari(Insecta, Heteroptera, Tingidae) depends on its host plant to invade Europe
Authors: Durand Manon , Guilbert Eric
Published: November 2023

Biological invasions increase with the intensity of globalization, human activities, and climate change. Insects represent a high potential of invasive species due to their adaptability to new environment. We analysed here the invasiveness of an Asian phytophagous bug,Corythauma ayyari(Heteroptera, Tingidae), recently recorded in Europe, and that depends onJasminumspp., an ornamental plant widespread in Europe. We modelled its current distribution, projected it into the future and tested its niche overlap between native and invaded areas. When considering the host plant as environmental variable, the analysis shows thatC. ayyarishifted to a new ecological niche but its distribution is restricted by its host plant distribution. Including or excluding the host plant as environmental variable has an impact on species distribution and should be considered when dealing with phytophagous species.
Point mutations in Arf1 reveal cooperative effects of the N-terminal region and myristate for GTPase-activating protein catalytic activity
Authors: Rosenberg Eric M. , Jian Xiaoying , Soubias Olivier , Jackson Rebekah A. , Gladu Erin , Andersen Emily , Esser Lothar , Sodt Alexander J. , Xia Di , Byrd R. Andrew , Randazzo Paul A.
Published: November 2023

The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable N-terminal extension of the G domain modified with myristate. Arf proteins, including Arf1, have roles in membrane trafficking and cytoskeletal dynamics. While screening for Arf1:small molecule co-crystals, we serendipitously solved the crystal structure of the non-myristoylated engineered mutation [L8K]Arf1 in complex with a GDP analogue. Like wild-type (WT) non-myristoylated Arf1•GDP, we observed that [L8K]Arf1 exhibited an N-terminal helix that occludes the hydrophobic cavity that is occupied by the myristoyl group in the GDP-bound state of the native protein. However, the helices were offset from one another due to the L8K mutation, with a significant change in position of the hinge region connecting the N-terminus to the G domain. Hypothesizing that the observed effects on behavior of the N-terminus affects interaction with regulatory proteins, we mutated two hydrophobic residues to examine the role of the N-terminal extension for interaction with guanine nucleotide exchange factors (GEFs) and GTPase Activating Proteins (GAPs). Different than previous studies, all mutations were examined in the context of myristoylated Arf. Mutations had little or no effect on spontaneous or GEF-catalyzed guanine nucleotide exchange but did affect interaction with GAPs. [F13A]myrArf1 was less than 1/2500, 1/1500, and 1/200 efficient as substrate for the GAPs ASAP1, ARAP1 and AGAP1; however, [L8A/F13A]myrArf1 was similar to WT myrArf1. We hypothesized that the myristate moiety associates with the N-terminal extension to alter its structure, thereby affecting its function. Using molecular dynamics simulations, the effect of the mutations on forming alpha helices was examined, yet no differences were detected. The results indicate that lipid modifications of GTPases and consequent anchoring to a membrane influences protein function beyond simple membrane localization. Hypothetical mechanisms are discussed.
Baseline resting EEG measures differentiate rTMS treatment responders and non-responders
Authors: Kaewpijit Pakin , Fitzgerald Paul B , Hoy Kate , Bailey Neil W
Published: November 2023

Background

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used worldwide in the treatment of depression, however, we currently lack the means to reliably predict whether patients will respond to the treatment. Recent research suggests that the neurophysiological measures of beta power and correlation dimension may have predictive potential, however, studies of beta power and correlation dimension to differentiate rTMS group response in individuals with major depression are limited.

Methods

Fifty treatment-resistant patients with major depressive disorder were recruited. Forty-two participants underwent baseline resting EEG sessions and 5-8 weeks of rTMS treatments and 12 participants were responders to the treatment. Beta power and correlation dimension from baseline resting EEG were compared between responders and non-responders.

Results

Responders demonstrated significantly lower beta power in baseline resting EEG, however, correlation dimension did not show a significant difference between groups.

Limitations

There were a small number of responders in this study.

Conclusion

Baseline resting beta power may help to differentiate responders from non-responders to rTMS treatment. However, further studies are needed with larger sample sizes.
Fully automatic segmentation of brain lacunas resulting from resective surgery using a 3D deep learning model
Authors: Casseb Raphael F , de Campos Brunno M , Loos Wallace S , Barbosa Marcelo E R , Alvim Marina K M , Paulino Gabriel C L , Pucci Francesco , Worrell Samuel , de Souza Roberto M , Jehi Lara , Cendes Fernando
Published: November 2023

The rapid and constant development of deep learning (DL) strategies is pushing forward the quality of object segmentation in images from diverse fields of interest. In particular, these algorithms can be very helpful in delineating brain abnormalities (lesions, tumors, lacunas, etc), enabling the extraction of information such as volume and location, that can inform doctors or feed predictive models. Here, we describe ResectVol DL, a fully automatic tool developed to segment resective lacunas in brain images of patients with epilepsy. ResectVol DL relies on the nnU-Net framework that leverages the 3D U-Net deep learning architecture. T1-weighted MRI datasets from 120 patients (57 women; 31.5 ± 15.9 years old at surgery) were used to train (n=78) and test (n=48) our tool. Manual segmentations were carried out by five different raters and were considered as ground truth for performance assessment. We compared ResectVol DL with two other fully automatic methods: ResectVol 1.1.2 and DeepResection, using the Dice similarity coefficient (DSC), Pearson′s correlation coefficient, and relative difference to manual segmentation. ResectVol DL presented the highest median DSC (0.92 vs. 0.78 and 0.90), the highest correlation coefficient (0.99 vs. 0.63 and 0.94), and the lowest median relative difference (9 vs. 44 and 12 %). Overall, we demonstrate that ResectVol DL accurately segments brain lacunas, which has the potential to assist in the development of predictive models for postoperative cognitive and seizure outcomes.
Clinical Characteristics and Laboratory Biomarkers in ICU-admitted Septic Patients with and without Bacteremia: A Predictive Analysis
Authors: Baek Sangwon , Lee Seung Jun
Published: November 2023

Background

Few studies have investigated the diagnostic utilities of biomarkers for predicting bacteremia among septic patients admitted to intensive care units (ICU). Therefore, this study evaluated the prediction power of laboratory biomarkers to utilize those markers with high performance to optimize the predictive model for bacteremia.

Methods

A retrospective cross-sectional study was conducted at the ICU department of Gyeongsang National University Changwon Hospital in 2019. Adult patients qualifying SEPSIS-3 (increase in sequential organ failure score ≥ 2) criteria with at least two sets of blood culture were selected. Collected data was initially analyzed independently to identify the significant predictors, which was then used to build the multivariable logistic regression (MLR) model.

Results

A total of 218 patients with 48 cases of true bacteremia were analyzed in this research. Both CRP and PCT showed a substantial area under the curve (AUC) value for discriminating bacteremia among septic patients (0.757 and 0.845, respectively). To further enhance the predictive accuracy, we combined PCT, bilirubin, neutrophil-lymphocyte ratio (NLR), platelets, lactic acid, erythrocyte sedimentation rate (ESR), and Glasgow Coma Scale (GCS) score to build the predictive model with an AUC of 0.907 [0.843–0.956]. In addition, a high association between bacteremia and mortality rate was discovered through the survival analysis (P=0.004).

Conclusions

While PCT is certainly a useful index for distinguishing patients with and without bacteremia by itself, our MLR model indicates that the accuracy of bacteremia prediction substantially improves by the combined use of PCT, bilirubin, NLR, platelets, lactic acid, ESR, and GCS score.
Characterization of sleep apnea among a sample of adults from Samoa
Authors: Heinsberg Lacey W. , Pomer Alysa , Cade Brian E. , Carlson Jenna C. , Naseri Take , Reupena Muagututia Sefuiva , Viali Satupa’itea , Weeks Daniel E. , McGarvey Stephen T. , Redline Susan , Hawley Nicola L.
Published: November 2023

Sleep apnea is a public health concern around the world, but little research has been dedicated to examining this issue in low- and middle-income countries, including Samoa. Using data collected through theSoifua Manuia(“Good Health”) study, which aimed to investigate the impact of the body mass index (BMI)-associated genetic variant rs373863828 in CREB3 Regulatory Factor (CREBRF) on metabolic traits in Samoan adults, we examined the sample prevalence and characteristics of sleep apnea using data collected with a validated home sleep apnea device (WatchPAT, Itamar). A total of 330 participants (sampled to overrepresent the obesity-risk allele of interest) had sleep data available. Participants (53.3% female) had a mean (SD) age of 52.0 (9.9) years and BMI of 35.5 (7.5) kg/m2and 36.3% of the sample had type 2 diabetes. Based on the 3% and 4% apnea hypopnea indices (AHI) and the 4% oxygen desaturation index (ODI), descriptive analyses revealed that many participants had potentially actionable sleep apnea defined as >5 events/hr (87.9%, 68.5%, and 71.2%, respectively) or clinically actionable sleep apnea defined as ≥15 events/hr (54.9%, 31.5%, and 34.5%, respectively). Sleep apnea was more severe in men; for example, clinically actionable sleep apnea (≥15) based on the AHI 3% definition was observed in 61.7% of men and 48.9% of women. Correction for non-representational sampling related to theCREBRFobesity-risk allele resulted in only slightly lower estimates. Across the AHI 3%, AHI 4%, and ODI 4%, multiple linear regression revealed associations between a greater number of events/hr and higher age, male sex, higher body mass index, higher abdominal-hip circumference ratio, and geographic region of residence. Our study identified a much higher frequency of sleep apnea in Samoa compared with published data from other studies, but similar predictors. Continued research addressing generalizability of these findings, as well as a specific focus on diagnosis and affordable and equitable access to treatment, is needed to alleviate the burden of sleep apnea in Samoa and around the world.
Anatomical, Functional, and Hemodynamic Determinants of Increased Pulmonary Capillary Wedge Pressure V-Wave Amplitude
Authors: Torosoff Mikhail , Khorolsky Ciril , Banerjee Riju , Yager Neil
Published: November 2023

Introduction

Increased pulmonary capillary wedge pressure (PCWP) V-wave amplitude has been traditionally associated with significant mitral regurgitation (MR). However, increased PCWP V-waves may also occur in patients with elevated left ventricular end-diastolic pressure (LVEDP) or with dilated left atrium (LA). Interactions between MR, increased LVEDP, and LA dilatation in the genesis of increased PCWP V-waves were not well investigated.

Material and Methods

It was a single-center cohort study of 153 consecutive hemodynamically stable patients referred for invasive hemodynamic evaluation of dyspnea. Patients with significant valvular disease other than MR, acute coronary syndromes (ACS), hemodynamic instability, pericardial disease, and mechanical ventilation or mechanical LV support were excluded.

Results

Study cohort included 41% males, 68.4+/-11.9 years old, 60% were on beta-adrenergic antagonists and 69.3% were on afterload reduction therapy. PCWP V-wave amplitude was significantly increased in patients with moderate or more severe MR (p<0.001), dilated LA (p=0.002), with a trend towards increased V-wave amplitude in elevated >12 mmHg LVEDP (p=0.117). There were no significant differences in age, gender, prevalence of LV dysfunction, other co-morbidities, and/or E/e’ ratio according to the MR degree, LA volume, and LVEDP. In patients categorized according to moderate or more severe MR, dilated LA, and increased >12 mmHg LVEDP - the presence of any two of these abnormal parameters was associated with 50-65% prevalence of elevated V-waves and reached 100% when all three were parameters were abnormal (p<0.002).

Conclusions

In euvolemic patients undergoing elective invasive hemodynamic evaluation of dyspnea, elevated PCWP V-waves are determined by three major pathophysiological parameters: moderate or more severe MV regurgitation, LA dilatation, and elevated LVEDP.
Decoding the complexity of delayed wound healing followingEnterococcus faecalisinfection
Authors: Celik Cenk , Lee Stella Yue Ting , Tanoto Frederick Reinhart , Veleba Mark , Kline Kimberly A. , Thibault Guillaume
Published: November 2023

Wound infections are highly prevalent, and can lead to delayed or failed healing, causing significant morbidity and adverse economic impacts. These infections occur in various contexts, including diabetic foot ulcers, burns, and surgical sites.Enterococcus faecalisis often found in persistent non-healing wounds, but its contribution to chronic wounds remains understudied. To address this, we employed single-cell RNA sequencing (scRNA-seq) on infected wounds in comparison to uninfected wounds in a mouse model. Examining over 23,000 cells, we created a comprehensive single-cell atlas that captures the cellular and transcriptomic landscape of these wounds. Our analysis revealed unique transcriptional and metabolic alterations in infected wounds, elucidating the distinct molecular changes associated with bacterial infection compared to the normal wound healing process. We identified dysregulated keratinocyte and fibroblast transcriptomes in response to infection, jointly contributing to an anti-inflammatory environment. Notably,E. faecalisinfection prompted a premature, incomplete epithelial-to-mesenchymal transition in keratinocytes. Additionally,E. faecalisinfection modulated M2-like macrophage polarization by inhibiting pro-inflammatory resolutionin vitro,in vivo,and in our scRNA-seq atlas. Furthermore, we discovered macrophage crosstalk with neutrophils, which regulates chemokine signaling pathways, while promoting anti-inflammatory interactions with endothelial cells. Overall, our findings offer new insights into the immunosuppressive role ofE. faecalisin wound infections.