bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning identifies heterogeneous subpopulations in breast cancer cell lines
Authors: Jost Tyler A. , Gardner Andrea L. , Morgan Daylin , Brock Amy 
Published: July 2024

AbstractMotivationCells exhibit a wide array of morphological features, enabling computer vision methods to identify and track relevant parameters. Morphological analysis has long been implemented to identify specific cell types and cell responses. Here we asked whether morphological features might also be used to classify transcriptomic subpopulations withinin vitrocancer cell lines. Identifying cell subpopulations furthers our understanding of morphology as a reflection of underlying cell phenotype and could enable a better understanding of how subsets of cells compete and cooperate in disease progression and treatment.ResultsWe demonstrate that cell morphology can reflect underlying transcriptomic differencesin vitrousing convolutional neural networks. First, we find that changes induced by chemotherapy treatment are highly identifiable in a breast cancer cell line. We then show that the intra cell line subpopulations that comprise breast cancer cell lines under standard growth conditions are also identifiable using cell morphology. We find that cell morphology is influenced by neighborhood effects beyond the cell boundary, and that including image information surrounding the cell can improve model discrimination ability.
Tumor- and immune-derivedN-acetyl-β-D-hexosaminidase drive colorectal cancer and stratify patient risk
Authors: Kawahara Rebeca , Kautto Liisa , Bansal Naaz , Dipta Priya , Chau The Huong , Liquet-Weiland Benoit , Ahn Seong Beom , Thaysen-Andersen Morten 
Published: July 2024

SummaryNon-invasive prognostic markers are needed to improve survival of colorectal cancer (CRC) patients. Towards this goal, we applied integrative systems glycobiology approaches to tumor tissues and PBMCs from CRC patients and matching controls as well as to a CRC patient-derived cell line. Firstly, quantitative glycomics and glycoproteomics revealed that non-canonical paucimannosidic proteins from monocytic and cancer cell origins are prominent signatures in CRC tumor tissues, and that their expression associates with CRC progression. Guided by these associations, we then showed thatN-acetyl-β-D-hexosaminidase (Hex) facilitates paucimannosidic protein biosynthesis in CRC cells and is intimately involved in processes underpinning CRC metastasis (adhesion, migration, invasion, proliferation). Finally, Hex activity was found to be elevated in PBMCs and plasma from patients with advanced CRC relative to matching controls while plasma Hex activity correlated strongly with CRC patient survival. Our study opens avenues for better prognostication, disease risk stratification and therapeutic interventions in CRC.Highlights•Non-canonical truncated glycans of immune and cancer origins dominate in CRC tumors•N-acetyl-β-D-hexosaminidase, a truncating glycoenzyme, drives tumorigenesis in CRC•Activity of plasmaN-acetyl-β-D-hexosaminidase stratifies risk in CRC patients
Effect of zinc supplementation on certain serum biochemical parameters in growing pigs
Authors: Borah S. , Soren S , Deka SS , Kalita L , Pame K , Borah B 
Published: July 2024

ABSTRACTTwenty-four healthy and uniform crossbred (Hampshire × Assam Local) pigs, 4 months of age, were selected to study the effect of 500 ppm Zn supplementation on certain serum biochemical parameters for a period of four months. The animals were divided into three groups (n=8/group): group C (basal diet), group T1(basal diet + 100 ppm Zn + calcium carbonate @ 1.5% DM) and group T2(basal diet + 500 ppm Zn). Serum samples were collected at 15-day intervals and analysed for serum Zn, copper, total serum protein, albumin, globulin, and glucose cholesterol. The serum Zn concentration in the T1group decreased significantly (P<0.01) from day 30 until day 120 of treatment, whereas in the T2group, the level increased significantly (P<0.01) from day 15 onwards. The serum copper concentration did not change groups. The total protein concentration in the serum showed a significant (P<0.01) increasing trend in the T2group from day 45 of treatment, and a significant (P<0.01) decreasing trend was observed in the T1group compared to the C group. The serum globulin concentration decreased significantly (P< 0.05) in the T1group compared with the C and T2groups during the treatment period. An increasing trend in glucose and cholesterol levels was recorded at T2during the treatment period. However, decrease, (P<0.01) in glucose and cholesterol levels was recorded in the T1group from day 30 to day 120 of treatment. The haemoglobin concentration showed a significant (p<0.01) decreasing trend in the T1group from day 45 onwards.
Lack of Synergistic Outcomes with Roflumilast Combined with Levetiracetam or Adipose Stem Cell Secretome After Spinal Cord Injury
Authors: Sousa Carla , Lima Rui , Gomes Eduardo D. , Silva Deolinda , Cibrão Jorge , Pinho Tiffany , Jorge Diogo , Afonso João , Martins-Macedo Joana , Monteiro Andreia , Salgado António J. , Silva Nuno A. 
Published: July 2024

AbstractThe Spinal Cord Injury (SCI) pathophysiology is highly complex, contributing to a poor prognosis and lack of effective treatments. Previously, we demonstrated that Roflumilast (Rof), leads to functional recovery when tested in a SCI contusion model. However, it is unlikely that Rof treatment on its own could fully restore the spinal cord. Therefore, our objective was to scrutinize the synergistic effects of combining Rof with neuroprotective approaches. Herein we tested two therapies, firstly, Rof combined with Levetiracetam (Lev), and in a second phase, the complementary interplay between Rof and Adipose Stem Cells secretome (Sec). We induced SCI using a weight drop trauma model at the T8 level. Functional recovery was assessed according to the Basso, Beattie, and Bresnahan scale, Activity Box Test, Motor Swimming Test, and Von Frei test. Results indicate that the unilateral use of Rof, Lev, or Sec was effective in promoting functional recovery. However, the combination of Rof + Lev or Rof + Sec did not lead to an improvement in functional outcomes when compared to standalone treatments. Moreover, the combination of Rof + Sec actually led to worst functional outcome than the single treatments. Further studies are needed to find a combinatorial treatment that can lead to superior therapeutic effects with potential clinical application.
Ecology not genetics explains correlated trait divergence during speciation
Authors: de Carvalho Clarissa F. , Planidin Nicholas P. , Villoutreix Romain , Soria-Carrasco Víctor , Riesch Rüdiger , Feder Jeffrey L. , Parchman Thomas L. , Slate Jon , Gompert Zachariah , Nosil Patrik 
Published: July 2024

AbstractThe formation of new species often involves the correlated divergence of multiple traits and genetic regions. However, the mechanisms by which such trait covariation builds up remain poorly understood. In this context, we consider two non-exclusive hypotheses. First, genetic covariance between traits can cause divergent selection on one trait to promote population divergence in correlated traits (a genetic covariation hypothesis). Second, correlated environmental pressures can generate selection on multiple traits, facilitating the evolution of trait complexes (an environmental covariation hypothesis). Here, we test these hypotheses using cryptic coloration (controlled by an incipient supergene) and chemical traits (i.e.,cuticular hydrocarbons, CHCs) involved in desiccation resistance and mate choice inTimema cristinaestick insects. We first demonstrate that population divergence in color-pattern is correlated with divergence in some (but not all) CHC traits. We show that when correlated population divergence does occur, it is unlikely to be explained by genetic covariation because within-population genetic covariance between color-pattern and CHCs traits is weak. In contrast, we find that correlated variation in climate and host plant likely generates selection jointly on color-pattern and some CHC traits. This supports the environmental covariation hypothesis, likely via the effects of two correlated environmental axes selecting on different traits. Finally, we provide evidence that misalignment between natural and sexual selection also contributes to patterns of correlated trait divergence. Our results shed light into transitions between phases of speciation by showing that environmental factors can promote population divergence in trait complexes, even without strong genetic covariance.
A genome engineered tool set forDrosophilaTGF-β/BMP signaling studies
Authors: Ell Clara-Maria , Safyan Abu , Chayengia Mrinal , Kustermann Manuela M. M. , Lorenz Jennifer , Schächtle Melanie , Pyrowolakis George 
Published: July 2024

AbstractLigands of the TGF-β/BMP superfamily are critically involved in the regulation of growth, patterning and organogenesis and can act as long-range morphogens. Essential for understanding TGF-β/BMP signaling dynamics and regulation are tools that allow monitoring and manipulating pathway components expressed at physiological levels and endogenous spatiotemporal patterns. We used genome engineering to generate a comprehensive library of endogenously epitope-or fluorescently-tagged versions of receptors, co-receptors, transcription factors and key feedback regulators of theDrosophilaBMP and Activin signaling pathways. We demonstrate that the generated alleles are biologically active and can be utilized for assessing tissue and subcellular distribution of the corresponding proteins. Further, we show that the genomic platforms can be used forin locusstructure-function andcis-regulatory analyses. Finally, we present a complementary set of protein binder-based tools, which allow visualization as well as manipulation of the stability and subcellular localization of epitope-tagged proteins, providing new tools for the analysis of BMP signaling and beyond.
Evidence of a Slower-Z effect inSchistosoma japonicum
Authors: Mrnjavac Andrea , Vicoso Beatriz 
Published: July 2024

AbstractSex-linked and autosomal loci experience different selective pressures and evolutionary dynamics. X (or Z) chromosomes are often hemizygous, as Y (or W) chromosomes often degenerate. Such hemizygous regions can be under greater efficacy of selection, as recessive mutations are immediately exposed to selection in the heterogametic sex (the so-called Faster-X or Faster-Z effect). However, in young non-recombining regions, Y/W chromosomes often have many functional genes, and many X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on the X/Z by the Y/W homolog is expected to drive a Slower-X (Slower-Z) effect for diploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect has been studied extensively, much less is known empirically about the evolutionary dynamics of diploid X or Z chromosomes. Here, we took advantage of published population genomic data in the female-heterogametic human parasiteSchistosoma japonicumto characterize the gene content and diversity levels of the diploid and hemizygous regions of the Z chromosome. We used different metrics of selective pressures acting on genes to test for differences in the efficacy of selection in hemizygous and diploid Z regions, relative to autosomes. We found consistent patterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both hemizygous and diploid Z regions. Moreover, relaxed selection was particularly pronounced for female-biased genes on the diploid Z, as predicted by Slower-Z theory.
A ready-to use workflow for automated, sound-based bird identification and localization
Authors: Buchmann Carsten M. , Schurr Frank M. 
Published: July 2024

AbstractField studies of bird communities typically require the fine-scale mapping of individuals. Passive acoustic monitoring combined with localization of individuals is a promising approach to gather such data. While various approaches for identification of species and localization of individuals have been proposed, no fully automated ready-to-use workflow is available so far. We here present a novel approach based on sound recordings with multiple cost-efficient automated recording units (Audiomoths). The workflow uses a well-established AI model (BirdNET; other models possible) for species identification and localizes the sources of all identified bird sounds with high accuracy. Tests with replayed sounds of different bird species in an agricultural landscape show that - after filtering out identifications with low identification confidence - the algorithm localizes more than 90% of the sounds within 5 m of the true location (85 % < 2 m). Recording and localization of wild birds demonstrate the applicability of the approach for avian ecology. This workflow is completely automated and ready-to-use, also for non-experts and can also be used when strong winds affect the speed of sound or if 3D localizations are of interest. By making data on individual bird locations accessible the presented work will help to advance fundamental and applied ecology as well as conservation.
Substrate Rigidity Modulates Segmentation Clock Dynamics in Isolated Presomitic Mesoderm Cells
Authors: Sung Chun-Yen , Kadiyala Usha , Blanchard Owen , Yourston Liam , Walker Derek , Li Linyuan , Fu Jianping , Yang Qiong 
Published: July 2024

SummaryThe segmentation clock, a genetic oscillator in the presomitic mesoderm (PSM), is known to be influenced by biochemical signals, yet its potential regulation by mechanical cues remains unclear. The complex PSM microenvironment has made it challenging to isolate the effects of mechanical perturbations on clock behavior. Here we investigated how mechanical stimuli affect clock oscillations by culturing zebrafish PSM cells on PDMS micropost arrays with tunable rigidities (0.6-1200 kPa). We observed an inverse sigmoidal relationship between surface rigidity and both the percentage of oscillating cells and the number of oscillation cycles, with a switching threshold between 3-6 kPa. The periods of oscillating cells showed a consistently broad distribution across rigidity changes. Moreover, these cells exhibited distinct biophysical properties, such as reduced motility, contractility, and sustained circularity. These findings highlight the crucial role of cell-substrate interactions in regulating segmentation clock behavior, providing insights into the mechanobiology of somitogenesis.HighlightsThe oscillatory behaviors of single PSM cells respond to substrate rigidity in a switch-like manner, with a critical threshold between 2.9 kPa and 6 kPa.As rigidity increases, both the oscillation percentage and the number of cycles decrease, while the period does not show a clear dependency on rigidity.Oscillating cells exhibit distinct biophysical properties compared to non-oscillating cells, including higher and more sustained circularity, lower motility, and reduced contractility.Cell aggregates exhibit similar trends in response to rigidity, except for significantly increased oscillation percentages across different rigidity conditions, suggesting a potential interplay between cell-cell communications and rigidity in influencing cell aggregate behavior.
Chaotropic Agent-assisted Supported Lipid Bilayer Formation
Authors: Cawley Jennie L. , Santa Dane E. , Singh Aarshi N. , Odudimu Adeyemi T. , Berger Brett A. , Wittenberg Nathan J. 
Published: July 2024

ABSTRACTSupported lipid bilayers (SLBs) are useful structures for mimicking cellular membranes, and they can be integrated with a variety of sensors. While there are a variety of methods for forming SLBs, many of these methods come with limitations in terms of the lipid compositions that can be employed and the substrates upon which the SLBs can be deposited. Here we demonstrate the use of an all-aqueous chaotropic agent exchange process that can be used to form SLBs on two different substrate materials: SiO2, which is compatible with traditional SLB formation by vesicle fusion and Al2O3, which is not compatible with vesicle fusion. When examined with quartz crystal microbalance with dissipation monitoring, the SLBs generated by chaotropic agent exchange (CASLBs) have similar frequency and dissipation shifts to SLBs formed by the vesicle fusion technique. The CASLBs block nonspecific protein adsorption on the substrate and can be used to sense protein-lipid interactions. Fluorescence microscopy was used to examine the CASLBs, and we observed long-range lateral diffusion of fluorescent probes, which confirmed the CASLBs were composed of a continuous, planar lipid bilayer. Our CASLB method provides another option for forming planar lipid bilayers on a variety of surfaces, including those that are not amenable to the widely used vesicle fusion method.
IGF-1 Acts through Kiss1-expressing Cells to Influence Metabolism and Reproduction
Authors: Wang Mengjie , Pugh Seamus M. , Daboul Judy , Miller David , Xu Yong , Hill Jennifer W. 
Published: July 2024

ABSTRACTObjectiveKisspeptin, encoded by theKiss1gene, ties puberty and fertility to energy status; however, the metabolic factors that controlKiss1-expressing cells need to be clarified.MethodsTo evaluate the impact of IGF-1 on the metabolic and reproductive functions of kisspeptin producing cells, we created mice with IGF-1 receptor deletion driven by theKiss1promoter (IGF1RKiss1mice). Previous studies have shown IGF-1 and insulin can bind to each other’s receptor, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we also generated mice with simultaneous deletion of the IGF1R and insulin receptor (IR) inKiss1-expressing cells (IGF1R/IRKiss1mice).ResultsLoss of IGF1R inKiss1cells caused stunted body length. In addition, female IGF1RKiss1mice displayed lower body weight and food intake plus higher energy expenditure and physical activity. This phenotype was linked to higher proopiomelanocortin (POMC) expression and heightened brown adipose tissue (BAT) thermogenesis. Male IGF1RKiss1mice had mild changes in metabolic functions. Moreover, IGF1RKiss1mice of both sexes experienced delayed puberty. Notably, male IGF1RKiss1mice had impaired adulthood fertility accompanied by lower gonadotropin and testosterone levels. Thus, IGF1R inKiss1-expressing cells impacts metabolism and reproduction in a sex-specific manner. IGF1R/IRKiss1mice had higher fat mass and glucose intolerance, suggesting IGF1R and IR inKiss1-expressing cells together regulate body composition and glucose homeostasis.ConclusionsOverall, our study shows that IGF1R and IR inKiss1have cooperative roles in body length, metabolism, and reproduction.
Reciprocal interactions between CA1 pyramidal and axo-axonic cells control sharp wave-ripple events
Authors: Gilbert Earl T. , Klaver Lianne M.F. , Arndt Kaiser C. , Kim Jongwoon , Jia Xiaoting , McKenzie Sam , English Daniel Fine 
Published: July 2024

AbstractDiverse sources of inhibition serve to modulate circuits and control cell assembly spiking across various timescales. For example, in hippocampus area CA1 the competition between inhibition and excitation organizes spike timing of pyramidal cells (PYR) in network events, including sharp wave-ripples (SPW-R). Specific cellular-synaptic sources of inhibition in SPW-R remain unclear, as there are >20 types of GABAergic interneurons in CA1. Axo-axonic cells (AAC) are defined by their synaptic targeting of the axon initial segment of pyramidal cells, potently controlling spike output. The impact of AAC activity on SPW-R is controversial, due mainly to ambiguity of AAC identification. Here we monitored and manipulated opto-tagged AACs in behaving mice using silicon probe recordings. We found a large variability of AAC neurons, varying from enhanced to suppressed spiking during SPW-Rs, in contrast to the near-uniform excitation of other parvalbumin-expressing interneurons. AACs received convergent monosynaptic inputs from local pyramidal cell assemblies, which strongly influenced their participation in SPW-Rs. Optogenetic silencing of AACs increased power and duration of SPW-Rs, recruiting a greater number of PYR, suggesting AACs control SPW-R dynamics. We hypothesize that lateral inhibition by reciprocal PYR-AAC interactions thus supports the organization of cell assemblies in SPW-R.
Metagenomic peek into a corn mummy
Authors: Solymosi Norbert , Pap Bernadett , Nagy Sára Ágnes , Tóth Adrienn Gréta , Kevély Flóra Judit , Maróti Gergely , Csabai István , Kóthay Katalin , Magyar Donát 
Published: July 2024

ABSTRACTNumerous studies have shown that metagenomics has opened up a new dimension in reading the contents of archaeological remains as time capsules. Corn mummies are ritual objects made in ancient Egypt by forming human-shaped figures made of cereal grains grown in a mixture of water and earth. We performed metagenomic analyses on samples from a corn mummy dated to the second half of the 3rd century BC. Alongside a number of clearly modern contaminants, we identified organisms that cannot be excluded as being of historical origin. Besides considerable amounts of bacterial sequences belonging to the generaBacillus, Coprococcus, Metabacillus, NialliaandRoseburia, we also found traces of plants, animals, and humans. Sequences assigned to the genusTriticumshowed the highest similarity to ancientT. turgidumssp.dicoccumspecimens from Egypt and the southern Levant. Sequences classified in the genusPopulusshowed the highest identity with the genome ofP. nigra. The fragments that were identified as being of Lepidopteran origin showed the greatest similarity to the genomes of the Sphingidae. Haplotype analysis ofH. sapienssequences suggests haplogroups L3 and E, based on the mitogenome and Y chromosome, respectively, which are the two common lineages in sub-Saharan Africa today.
EPILEPTOGENESIS INHIBITS THE CIRCADIAN CLOCK AND RESHAPES THE DIURNAL TRANSCRIPTOMIC RHYTHMICITY IN THE MOUSE HIPPOCAMPUS
Authors: Benvenutti Radharani , Bruno Danielle C. F. , Gallas-Lopes Matheus , Venø Morten T. , Bruxel Estela Maria , Strickland Tammy , Ramsook Arielle , Wadgaonkar Aditi , Jiang Yiyue , Sanz-Rodriguez Amaya , Sinkkonen Lasse , Alvim Marina K.M. , Yasuda Clarissa L. , Rogerio Fabio , Cendes Fernando , Henshall David C. , Curtis Annie M. , Kobow Katja , Lopes-Cendes Iscia , Reschke Cristina R. 
Published: July 2024

ABSTRACTEpileptogenesis is the process that leads the brain into epileptic activity. Clinical evidence shows that ∼90% of people with epilepsy present rhythmicity in the timing of their seizures presentation. However, whether the circadian clock is a key player during epileptogenesis remains unknown. Here, we triggered epileptogenesis in mice by the intra-amygdala injection of kainic acid and profiled by RNA sequencing their hippocampal diurnal mRNA rhythmicity. We show that epileptogenesis largely reshapes the hippocampal transcriptomic rhythmicity and that the molecular clock machinery is inhibited due to the disruption of the core clock geneBmal1. We identified relevant dysregulated pathways and their dynamics in epileptogenesis, predicting a key role for microglial-driven neuroinflammation. We predicted the genes thatBmal1is directly controlling over time. Finally, we sought for translational relevance evidence by performing RNA sequencing in hippocampal samples resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and cross-analyzing datasets.