bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling pattern of the carnivoran hind limb: Main deviations from a conservative pattern
Authors: Gálvez-López Eloy , Casinos Adrià 
Published: August 2022

AbstractThe scaling pattern of the hind limb in Carnivora was determined using a sample of 13 variables measured on the femur, tibia, and calcaneus, of 429 specimens belonging to 141 species. Standardized major axis regressions on body mass were calculated for all variables, using both traditional regression methods and phylogenetically independent contrasts (PIC). Significant differences were found between the allometric slopes obtained with traditional and PIC regression methods, emphasizing the need to take into account phylogenetic relatedness in scaling studies. Overall, the scaling of the carnivoran hind limb conformed to geometric similarity, although some deviations from its predictions (including differential scaling) were detected, especially in relation with swimming adaptations. The scaling pattern of several phyletic lines and locomotor habits within Carnivora was also determined. Significant deviations from the scaling pattern of the order were found in some phyletic lines, but not in the locomotor habit subsamples. This suggests that the scaling of the carnivoran hind limb is both more heavily influenced by phylogenetic relatedness than by locomotor specializations, and more conservative than that of the forelimb. Finally, together with our previous work on the carnivoran forelimb, the results of the present study suggest that, in large non-aquatic carnivorans, size-related increases in bone stresses are compensated primarily by limb posture changes instead of by modifying limb bone scaling. However, increasing bone robusticity might also occur in the forelimb in response to the heavier stresses acting on the forelimbs due to asymmetrical body weight distribution.
Resolving marine–freshwater transitions by diatoms through a fog of discordant gene trees
Authors: Roberts Wade R. , Ruck Elizabeth C. , Downey Kala M. , Pinseel Eveline , Alverson Andrew J. 
Published: August 2022

ABSTRACTDespite the obstacles facing marine colonists, most lineages of aquatic organisms have colonized and diversified in freshwaters repeatedly. These transitions can trigger rapid morphological or physiological change and, on longer timescales, lead to increased rates of speciation and extinction. Diatoms are a lineage of ancestrally marine microalgae that have diversified throughout freshwater habitats worldwide. We generated a phylogenomic dataset of genomes and transcriptomes for 59 diatom taxa to resolve freshwater transitions in one lineage, the Thalassiosirales. Although most parts of the species tree were consistently resolved with strong support, we had difficulties resolving a Paleocene radiation, which affected the placement of one freshwater lineage. This and other parts of the tree were characterized by high levels of gene tree discordance caused by incomplete lineage sorting and low phylogenetic signal. Despite differences in species trees inferred from concatenation versus summary methods and codons versus amino acids, traditional methods of ancestral state reconstruction supported six transitions into freshwaters, two of which led to subsequent species diversification. Evidence from gene trees, protein alignments, and diatom life history together suggest that habitat transitions were largely the product of homoplasy rather than hemiplasy, a condition where transitions occur on branches in gene trees not shared with the species tree. Nevertheless, we identified a small set of putatively hemiplasious genes, many of which have been associated with shifts to low salinity, indicating that hemiplasy played a small but potentially important role in freshwater adaptation. Accounting for differences in evolutionary outcomes, in which some taxa became locked into freshwaters while others were able to return to the ocean or become salinity generalists, might help further distinguish different sources of adaptive mutation in freshwater diatoms.
A two-process model ofDrosophilasleep reveals an inter-dependence between circadian clock speed and the rate of sleep pressure decay
Authors: Abhilash Lakshman , Shafer Orie Thomas 
Published: August 2022

AbstractSleep is controlled by two processes – a circadian clock that regulates its timing and a homeostat that regulates the drive to sleep.Drosophilahas been an insightful model for understanding both processes. For four decades, Borbély and Daan’s two-process model has provided a powerful framework for understanding how circadian and homeostatic processes regulate sleep. However, the field of fly sleep has not employed such a model as a framework for the investigation of sleep. To this end, we have adapted the two-process model to the fly and establish its utility by showing that it can provide empirically testable predictions regarding the circadian and homeostatic control of fly sleep. We show that the ultradian rhythms previously reported for loss-of-function clock mutants are a predictable consequence of a functional sleep homeostat in the absence of a functioning circadian system. We find that a model in which the circadian clock speed and homeostatic rates act without influencing each other provides imprecise predictions regarding how clock speed influences the strength of sleep rhythms and the amount of daily sleep. We also find that quantitatively good fits between empirical values and model predictions were achieved only when clock speeds were positively correlated with rates of decay of sleep pressure. Our results indicate that longer sleep bouts better reflect the homeostatic process than the current definition of sleep as any inactivity lasting five minutes or more. This two-process model represents a powerful framework for future work on the molecular and physiological regulation of fly sleep.
Learning representations for image-based profiling of perturbations
Authors: Moshkov Nikita , Bornholdt Michael , Benoit Santiago , Smith Matthew , McQuin Claire , Goodman Allen , Senft Rebecca A. , Han Yu , Babadi Mehrtash , Horvath Peter , Cimini Beth A. , Carpenter Anne E. , Singh Shantanu , Caicedo Juan C. 
Published: August 2022

AbstractMeasuring the phenotypic effect of treatments on cells through imaging assays is an efficient and powerful way of studying cell biology, and requires computational methods for transforming images into quantitative data that highlight phenotypic outcomes. Here, we present an optimized strategy for learning representations of treatment effects from high-throughput imaging data, which follows a causal framework for interpreting results and guiding performance improvements. We use weakly supervised learning (WSL) for modeling associations between images and treatments, and show that it encodes both confounding factors and phenotypic features in the learned representation. To facilitate their separation, we constructed a large training dataset with Cell Painting images from five different studies to maximize experimental diversity, following insights from our causal analysis. Training a WSL model with this dataset successfully improves downstream performance, and produces a reusable convolutional network for image-based profiling, which we call Cell Painting CNN-1. We conducted a comprehensive evaluation of our strategy on three publicly available Cell Painting datasets, discovering that representations obtained by the Cell Painting CNN-1 can improve performance in downstream analysis for biological matching up to 30% with respect to classical features, while also being more computationally efficient.
Antiproliferative Effects of Novel Copper (II) Complexes on Lung Cancer Cell Line
Authors: Abdullah Muhammed Fawaz , Cinkilic Nilufer , Vatan Ozgur , Inci Duygu , Aydin Rahmiye 
Published: August 2022

AbstractCopper is an essential metalloelement that plays key fundamental roles in both health and pathology, and is increasingly been implicated in molecular pathogenesis of many cancer types. It has shown promise as a replacement to cisplatin in coordination complexes presently in mainstream chemotherapeutic practices.In this study, two newly synthesized water-soluble ternary copper (II) mixed ligand complexes; complex 1 - (Cu(4-mphen)(tyr)(H2O)]NO3·2H2O)(C.1) and complex 2 - (Cu(5-mphen)(tyr)(H2O)]NO3·2H2O (C.2) where (4-m= 4-methyl; 5-m = 5-methyl; phen-1, 10 = phenanthroline; tyr = tyrosine)), were investigated on adenocarcinomic human alveolar basal epithelial cell, A549 and non-cancerous human bronchial epithelial cell, BEAS-2B for their antiproliferative effects using the XTT assay (cytotoxicity), Comet assay (genotoxicity) and DCFH-DA assay (intracellular ROS) tests.C.1 was significantly more cytotoxic in A549 than C.2. Data from the Comet and ROS assay tests support each other. C.2 caused more copper-induced DNA damage, possibly through significant induction of ROS-mediated oxidative damage in the cancer cell, but a minimal insignificant ROS rise in normal cells. These results can only be preliminary and further studies are required to better understand the cellular effects and functional interactions of these agents, for an efficient therapeutic design and application.
Apolipoprotein E genotype modulates longitudinal atrophy at the temporal lobe after mild traumatic brain injury
Authors: Gan Shuoqiu , Wang Shan , Liu Yuling , Sun Yingxiang , Liu Kejia , Jia Xiaoyan , Li Xuan , Zhang Ming , Bai Lijun 
Published: August 2022

AbstractBackgroundsModerate or severe traumatic brain injury (TBI) is one of the strongest environmental risks for late-life dementia, especially Alzheimer’s disease (AD). However, the interaction between genetic factors and environmental exposure to mild TBI triggering neurodegenerative processes is still unclear. We used longitudinal imaging to differentiate spatial patterns of progressive brain volume loss in individual patients with and without carrying apolipoprotein E (APOE) ε4 carriers.MethodsFor 59 patients with acute mild TBI (mTBI, age: 36.92 ± 11.91 years; 14 APOE ε4 carriers) and 48 matched healthy controls (HCs, age: 37.92 ± 11.72 years; 10 APOE ε4 carriers), longitudinal (6-12 months follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal volume changes in the temporal lobe were characterized by the Jacobian determinant (JD) metric, reflecting spatial warping between the baseline and follow-up scans. JD values were regionally calculated and correlated with neuropsychological measures.ResultsMTBI patients lost a mean of 0.27% (SD = 0.43) of GM and 0.27% (SD = 0.50) of WM volume in the temporal lobe over the 6-12 month follow-up. Patients with a high genetic risk for AD (APOE ε4 allele carries) were associated with severer atrophy in the left superior temporal gyrus and middle temporal gyrus regions than the controls (P < 0.05). Furthermore, atrophy in these regions of gray matter could predict the performance change ratio of the language fluency in mTBI APOE ε4 carriers (β = 0.570, P < 0.05). While, compared with HC APOE ε4 non-carriers, mTBI non-carriers exhibited volume loss in the medial temporal lobe.ConclusionsThis prospective study provided evidence that the APOE ε4 allele interacting with mTBI increased the risk of AD phenotype development with language dysfunction.Graphic Abstract
Species-specific CD4+ T cells Enable Prediction of Mucosal Immune Phenotypes from Microbiota Composition
Authors: Spindler Matthew P. , Mogno Ilaria , Suri Prerna , Britton Graham J. , Faith Jeremiah J. 
Published: August 2022

ABSTRACTHow bacterial strains within a complex human microbiota collectively shape intestinal T cell homeostasis is not well-understood. Methods that quickly identify effector strains or species that drive specific mucosal T cell phenotypes are needed to define general principles for how the microbiota modulates host immunity. We colonize germ-free mice with defined communities of cultured strains and profile antigen-specific responses directed towards individual strains ex vivo. We find that lamina propria T cells are specific to bacterial strains at the species level and can discriminate between strains of the same species. Ex vivo restimulations consistently identify the strains within complex communities that induce Th17 responses in vivo providing the potential to shape baseline immune tone via community composition. Using an adoptive transfer model of colitis, we find that lamina propria T cells respond to different bacterial strains in conditions of inflammation versus homeostasis. Collectively, our approach represents a novel method for efficiently predicting the relative impact of individual bacterial strains within a complex community and for parsing microbiota-dependent phenotypes into component fractions.SIGNIFICANCEDetermining the mechanisms by which the gut microbiome modulates the host immune system has translational potential for treating or preventing immune mediated disease. A key challenge is identifying the immunogenic bacterial strains in the setting of a complex microbiota. We use a combination of anaerobic culturing, in vitro T cell assays, gnotobiotic mouse models, and ex vivo T cell restimulations to explore the influence of species and strain diversity on the specificity of mucosal T cells. Our approach efficiently predicts the relative impact of individual bacterial strains within a complex community and can be used to parse microbiota-dependent phenotypes into component fractions.
Sweat and sebum preferences of the human skin microbiota
Authors: Swaney Mary Hannah , Nelsen Amanda , Sandstrom Shelby , Kalan Lindsay R 
Published: August 2022

ABSTRACTThe microorganisms that inhabit human skin, collectively termed the skin microbiome, must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet, the skin microbiota thrive on the skin and have adapted to these stressful conditions. Limited skin nutrients are available for microbial use in this unique niche, including those from host-derived sweat, sebum, and corneocytes. Here, we have developed physiologically-relevant, skin-like growth media that is composed of compounds present in human sweat and sebum. We find that skin-associated bacterial species exhibit unique growth profiles in different concentrations of sweat and sebum. The majority of strains evaluated demonstrate a preference for high sweat concentrations, while sebum preference is highly variable, suggesting that the capacity for sebum utilization may be an important driver of skin microbial community structure. Furthermore, these findings provide experimental rationale for why different skin microenvironments harbor distinct microbiome communities. In all, our study further emphasizes the importance of studying microorganisms in an ecologically-relevant context, which is critical for our understanding of their physiology, ecology, and function on the skin.
An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues
Authors: Li Nancy T , Wu Nila C , Cao Ruonan , Cadavid Jose L , Latour Simon , Lu Xiaoya , Zhu Yutong , Mijalkovic Mirjana , Roozitalab Reza , McGuigan Alison P 
Published: August 2022

AbstractComplex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening. Here we set out to create a high-throughput, “off-the-shelf” platform which permits the generation of organoid-containing microtissues for standard phenotypic bioassays and image-based readings. To achieve this, we developed the Scaffold-supported Platform for Organoid-based Tissues (SPOT) platform. SPOT is a 3D gel-embedded in vitro platform that can be produced in a 96- or 384-well plate format and enables the generation of flat, thin and dimensionally-defined microgels. SPOT has high potential for adoption due to its reproducible manufacturing methodology, compatibility with existing instrumentation, and reduced within-sample and between-sample variation, which can pose challenges to both data analysis and interpretation. Using SPOT we generate cultures from patient derived pancreatic ductal adenocarcinoma organoids and assess the cellular response to standard-of-care chemotherapeutic compounds, demonstrating our platform’s usability for drug screening. We envision 96/384-SPOT will provide a useful tool to assess drug sensitivity of patient-derived organoids and easily integrate into the drug discovery pipeline.
A desert green alga that thrives at extreme high-light intensities using a unique photoin-hibition protection mechanism
Authors: Levin Guy , Yasmin Michael , Simanowitz Marc C. , Meir Ayala , Tadmor Yaakov , Hirschberg Joseph , Adir Noam , Schuster Gadi 
Published: August 2022

AbstractWhile light is the driving force of photosynthesis, excessive light can be harmful. Photoinhibition, or light-induced photo-damage, is one of the key processes limiting photosynthesis. When the absorbed light exceeds the amount that can be dissipated by photosynthetic electron flow and other processes, damaging radicals are formed that mostly inactivate photosystem II (PSII). A well-defined mechanism that protects the photosynthetic apparatus from photoinhibition has been described in the model green alga Chlamydomonas reinhardtii and plants. Chlorella oha-dii is a green micro-alga, isolated from biological desert soil crusts, that thrives under extreme high light (HL) in which other organisms do not survive. Here, we show that this alga evolved unique protection mechanisms distinct from those of C. reinhardtii and plants. When grown under extreme HL, significant structural changes were noted in the C. ohadii thylakoids, including a drastic reduction in the antennae and the formation of stripped core PSII, lacking its outer and inner antennae. This is accompanied by a massive accumulation of protective carotenoids and proteins that scavenge harmful radicals. At the same time, several elements central to photoinhibition protection in C. reinhardtii, such as psbS, the stress-related light harvesting complex, PSII protein phosphorylation and state-transitions are entirely absent or were barely detected in C. ohadii. Taken together, a unique photoinhibition protection mechanism evolved in C. ohadii, enabling the species to thrive under extreme-light intensities where other photo-synthetic organisms fail to survive.
Asparagine starvation suppresses histone demethylation through iron depletion
Authors: Jiang Jie , Srivastava Sankalp , Liu Sheng , Seim Gretchen , Zhong Minghua , Cao Sha , Davé Utpal , Kapur Reuben , Mosley Amber L. , Zhang Chi , Wan Jun , Fan Jing , Zhang Ji 
Published: August 2022

AbstractNutrient availability can impact epigenome to modify gene expression and dictate cell fate decision (Etchegaray and Mostoslavsky, 2016; Kinnaird et al., 2016). α-ketoglutarate is an indispensable substrate for the Jumonji family of histone demethylases (JHDMs) mediating most of the cellular demethylation reactions on histone subunits (Schvartzman et al., 2018). Since α-ketoglutarate is an intermediate of the tricarboxylic acid (TCA) cycle and a product of transamination, its intracellular levels are regulated by the metabolism of several amino acids (Baksh et al., 2020; Carey et al., 2015; Raffel et al., 2017; Vardhana et al., 2019). Here we show that asparagine starvation suppresses global histone demethylation. This process is neither due to the change of expression of histone modifying enzymes, nor due to the change of intracellular level of α-ketoglutarate. Rather, asparagine starvation reduces intracellular pool of labile iron (Fe2+), which is a key cofactor for the JHDMs to function. Mechanistically, asparagine starvation post-transcriptionally suppresses the expression of iron responsive element binding protein 2 (IREB2), an iron sensing protein, which then reduces the mRNA expression of the transferrin receptor (TFRC), a major carrier for iron uptake (Hentze et al., 2010). Furthermore, iron supplementation to the culture medium restores histone demethylation and alters global gene expression to accelerate cell death under conditions of asparagine starvation. Collectively, our results uncover that suppression of iron-dependent histone demethylation is part of the cellular adaptive response to asparagine starvation.
Delaying quantitative resistance to pesticides and antibiotics
Authors: Hardy Nate B. 
Published: August 2022

AbstractHow can we best vary the application of pesticides and antibiotics to delay resistance evolution? Previous theoretical studies have focused on qualitative resistance traits, and have mostly assumed that resistance alleles are already present in a population. But many real resistance traits are quantitative, and the evolution of resistant genotypes in the field may depend onde novomutation and recombination. Here, I use an individual-based, forward-time, quantitative-genetic simulation model to investigate the evolution of quantitative resistance. I evaluate the performance of four application strategies for delaying resistance evolution, to wit, the (1) sequential, (2) mosaic, (3) periodic, and (4) combined strategies. I find that which strategy is best depends on initial efficacy. When at the onset, xenobiotics completely prevent reproduction in treated demes, a combined strategy is best. On the other hand, when populations are partially resistant, the combined strategy is inferior to mosaic and periodic strategies, especially when resistance alleles are antagonistically pleiotropic. Thus, the optimal application strategy for managing against the rise of quantitative resistance depends on pleiotropy and whether or not partial resistance is already present in a population. This result appears robust to variation in pest reproductive mode and migration rate, direct fitness costs for resistant phenotypes, and the extend of refugial habitats.
IRIS: Integrated Retinal Functionality in Image Sensors
Authors: Yin Zihan , Kaiser Md Abdullah-Al , Camara Lamine Ousmane , Camarena Mark , Parsa Maryam , Jacob Ajey , Schwartz Gregory , Jaiswal Akhilesh 
Published: August 2022

AbstractNeuromorphic image sensors draw inspiration from the biological retina to implement visual computations in electronic hardware. Gain control in phototransduction and temporal differentiation at the first retinal synapse inspired the first generation of neuromorphic sensors, but processing in downstream retinal circuits, much of which has been discovered in the past decade, has not been implemented in image sensor technology. We present a technology-circuit co-design solution that implements two motion computations occurring at the output of the retina that could have wide applications for vision based decision making in dynamic environments. Our simulations on Globalfoundries 22nm technology node show that, by taking advantage of the recent advances in semiconductor chip stacking technology, the proposed retina-inspired circuits can be fabricated on image sensing platforms in existing semiconductor foundries. Integrated Retinal Functionality in Image Sensors (IRIS) technology could drive advances in machine vision applications that demand robust, high-speed, energy-efficient and low-bandwidth real-time decision making.