Miracle-dz/UniFAR-FTUs huggingface dataset:
Connecting Crabs, Currents, and Coastal Communities: Examining the Impacts of Changing Ocean Conditions on the Distribution of U.S. West Coast Dungeness Crab Commercial Catch

Dungeness crab (Cancer magister) is one of the most lucrative fisheries on the United States (U.S.) west coast. There have been large spatial and temporal fluctuations in catch, which reflect the interconnected influences of the coupled natural-human fishery system. Changing ocean conditions are likely to further alter the magnitude and distribution of Dungeness crab catch, the impacts of which will propagate ecologically and through the social systems of fishing communities. Therefore, the effect of changing ocean conditions on U.S. west coast Dungeness crab catch per unit effort (CPUE) was used as an interdisciplinary case study to examine the susceptibility, a metric that integrates Dungeness crab reliance and social vulnerability indices, of coastal communities to changes in the fishery. Statistical models indicated that ocean conditions influence commercial CPUE 3–5 years later and that CPUE is likely to decline in the future as ocean conditions change. In particular, sea surface temperature scenarios for 2080 (+1.7 and +2.8°C) reduced Dungeness crab CPUE by 30–100%, depending on fishing port latitude. Declines in Dungeness crab CPUE were greater for southern port communities than for northern port communities under both scenarios – demonstrating greater exposure at the southern end of the species range. We show that U.S. west coast communities are differentially susceptible to a decline in Dungeness crab catch, with Washington communities being at least five times more susceptible than California communities. Our overall assessment showed varying levels of risk (a combination of exposure and susceptibility) for Dungeness crab fishing ports that do not necessarily align with regional or fishery management boundaries.
Microfluidic Multielectrode Arrays for Spatially Localized Drug Delivery and Electrical Recordings of Primary Neuronal Cultures

Neuropathological models and neurological disease progression and treatments have always been of great interest in biomedical research because of their impact on society. The application of in vitro microfluidic devices to neuroscience-related disciplines provided several advancements in therapeutics or neuronal modeling thanks to the ability to control the cellular microenvironment at spatiotemporal level. Recently, the introduction of three-dimensional nanostructures has allowed high performance in both in vitro recording of electrogenic cells and drug delivery using minimally invasive devices. Independently, both delivery and recording have let to pioneering solutions in neurobiology. However, their combination on a single chip would provide further fundamental improvements in drug screening systems and would offer comprehensive insights into pathologies and diseases progression. Therefore, it is crucial to develop platforms able to monitor progressive changes in electrophysiological behavior in the electrogenic cellular network, induced by spatially localized injection of biochemical agents. In this work, we show the application of a microfluidic multielectrode array (MEA) platform to record spontaneous and chemically stimulated activity in primary neuronal networks. By means of spatially localized caffeine injection via microfluidic nanochannels, the device demonstrated its capability of combined localized drug delivery and cell signaling recording. The platform could detect activity of the neural network at multiple sites while delivering molecules into just a few selected cells, thereby examining the effect of biochemical agents on the desired portion of cell culture.
Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism

Background The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n = 662) and low/moderate (n = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P = 1.43 × 10−8, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA + AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10–05) including the testosterone precursor androstenediol (3beta,17beta) disulfate. Conclusions This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
Differential Effects of Orientation and Spatial-Frequency Spectra on Visual Unpleasantness

Increasing psychophysical evidence suggests that specific image features – or statistics – can appear unpleasant or induce visual discomfort in humans. Such unpleasantness tends to be particularly profound if the image’s amplitude spectrum deviates from the regular 1/f spatial-frequency falloff expected in natural scenes. Here, we show that profound unpleasant impressions also result if the orientation spectrum of the image becomes flatter. Using bandpass noise with variable orientation and spatial-frequency bandwidths, we found that unpleasantness ratings decreased with spatial- frequency bandwidth but increased with orientation bandwidth. Similarly, a subsequent experiment revealed that sinusoidal modulations in the amplitude spectrum of 1/f noise along the spatial frequency increased unpleasantness, but modulations along the orientation decreased it. Given that natural scenes tend to have a linear slope along the spatial frequency but an uneven spectrum along the orientation dimension, our opposing results in the spatial-frequency and orientation domains commonly support the idea that images deviating from the spectral regularity of natural scenes can give rise to unpleasant impressions.
Neuromechanisms of SARS-CoV-2: A Review

Recent studies have suggested the neuroinvasive potential of severe acute respiratory coronavirus 2 (SARS-CoV-2). Notably, neuroinvasiveness might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). Some studies have demonstrated that synapse-connected routes may enable coronaviruses to access the central nervous system (CNS). However, evidence related to the presence of SARS-CoV-2 in the CNS, its direct impact on the CNS, and the contribution to symptoms suffered, remain sparse. Here, we review the current literature that indicates that SARS-CoV-2 can invade the nervous system. We also describe the neural circuits that are potentially affected by the virus and their possible role in the progress of COVID-19. In addition, we propose several strategies to understand, diagnose, and treat the neurological symptoms of COVID-19.
Palaeomicrobiology: Application of Ancient DNA Sequencing to Better Understand Bacterial Genome Evolution and Adaptation

Next generation sequencing (NGS) has unlocked access to the wide range of non-cultivable microorganisms, including those present in the ancient past. The study of microorganisms from ancient sources (palaeomicrobiology) using DNA sequencing now provides a unique opportunity to examine ancient microbial genomic content, explore pathogenicity, and understand microbial evolution in greater detail than ever before. As a result, current studies have focused on reconstructing the evolutionary history of a number of human pathogens involved in ancient and historic pandemic events. These studies have opened the door for a variety of future palaeomicrobiology studies, which can focus on commensal microorganisms, species from non-human hosts, information from host-genomics, and the use of bacteria as proxies for additional information about past human health, behavior, migration, and culture. Here, we describe the origin and the historical and recent advances in the field of palaeomicrobiology, review some of the most notable ancient pathogenic microorganism studies, and provide perspectives on how NGS and whole genome information from ancient microorganisms contributes to our understanding of bacterial evolution on a broader scale. We conclude by exploring the application of newly developed tools in palaeomicrobiology and discussing how future studies can improve our current understanding of non-pathogenic microbes.
Behavioral Phenotype in the TgF344-AD Rat Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease resulting in cognitive decline. A unique rat model, TgF344-AD, recapitulates pathological hallmarks of AD. We used a longitudinal design to address the timing of expression of behavioral phenotypes in male and female TgF344-AD rats. In both sexes, we confirmed an age-dependent buildup of amyloid-β. In the open field, female, but not male, TgF344-AD rats were hypoactive at 6 and 12 months of age but at 18 months the two genotypes were similar in levels of activity response. Both male and female TgF344-AD rats had a deficit in performance on a learning and memory task. Male TgF344-AD, but not female, rats had evidence of hyposmia regardless of age. Rest-activity rhythms followed the typical active/inactive phase in all rats regardless of genotype or age. In males, home cage activity was similar across age and genotype; in females, regardless of genotype animals were less active as they aged. These changes highlight some behavioral markers of disease in the rat model. Early markers of disease may be important in early diagnosis and assessment of efficacy when treatment becomes available.
The Complete Plastomes of Five Hemiparasitic Plants (Osyris wightiana, Pyrularia edulis, Santalum album, Viscum liquidambaricolum, and V. ovalifolium): Comparative and Evolutionary Analyses Within Santalales

Most species of Santalales (the sandalwood order) are hemiparasites, including both facultative and obligate hemiparasites. Despite its rich diversity, only a small fraction of the species in the sandalwood order have sequenced plastomes. The evolution of parasitism–associated plastome reduction in Santalales remains under-studied. Here, we report the complete plastomes of three facultative hemiparasites (Pyrularia edulis, Cervantesiaceae; Osyris wightiana, and Santalum album, Santalaceae), and two obligate hemiparasites (Viscum liquidambaricolum and Viscum ovalifolium, Viscaceae). Coupled with publicly available data, we investigated the dynamics of plastome degradation in Santalales hemiparasites. Our results indicate that these hemiparasites can be characterized by various degrees of plastome downsizing, structural rearrangement, and gene loss. The loss or pseudogenization of ndh genes was commonly observed in Santalales hemiparasites, which may be correlated to the lifestyle shift from photoautotroph to hemiparasitism. However, the obligate hemiparasites did not exhibit a consistently higher level of gene loss or pseudogenization compared to facultative hemiparasites, which suggests that the degree of plastome reduction is not correlated with the trophic level facultative or obligate hemiparasitism. Instead, closely related taxa tend to possess highly similar plastome size, structure, and gene content. This implies the parasitism-associated plastome degradation in Santalales may evolve in a lineage-specific manner.
Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki)

Aim Insulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated by peroxisome-proliferator activated receptor δ (PPARδ). Although it is established that PPARδ contributes to the alteration of energy metabolism, it is not clear whether it plays a role in mitochondrial fuel competition. While nutrient overload may impair metabolic flexibility by fuel congestion within mitochondria, in absence of obesity defects at a mitochondrial level have not yet been excluded. We sought to determine whether reduced PPARδ content in insulin-resistant rat skeletal muscle of a non-obese rat model of T2DM (Goto-Kakizaki, GK) ameliorate the inhibitory effect of fatty acid (i.e., palmitoylcarnitine) on mitochondrial carbohydrate oxidization (i.e., pyruvate) in muscle fibers. Methods Bioenergetic function was characterized in oxidative soleus (S) and glycolytic white gastrocnemius (WG) muscles with measurement of respiration rates in permeabilized fibers in the presence of complex I, II, IV, and fatty acid substrates. Mitochondrial content was measured by citrate synthase (CS) and succinate dehydrogenase activity (SDH). Western blot was used to determine protein expression of PPARδ, PDK isoform 2 and 4. Results CS and SDH activity, key markers of mitochondrial content, were reduced by ∼10–30% in diabetic vs. control, and the effect was evident in both oxidative and glycolytic muscles. PPARδ (p < 0.01), PDK2 (p < 0.01), and PDK4 (p = 0.06) protein content was reduced in GK animals compared to Wistar rats (N = 6 per group). Ex vivo respiration rates in permeabilized muscle fibers determined in the presence of complex I, II, IV, and fatty acid substrates, suggested unaltered mitochondrial bioenergetic function in T2DM muscle. Respiration in the presence of pyruvate was higher compared to palmitoylcarnitine in both animal groups and fiber types. Moreover, respiration rates in the presence of both palmitoylcarnitine and pyruvate were reduced by 25 ± 6% (S), 37 ± 6% (WG) and 63 ± 6% (S), 57 ± 8% (WG) compared to pyruvate for both controls and GK, respectively. The inhibitory effect of palmitoylcarnitine on respiration was significantly greater in GK than controls (p < 10–3). Conclusion With competing fuels, the presence of fatty acids diminishes mitochondria ability to utilize carbohydrate derived substrates in insulin-resistant muscle despite reduced PPARδ content.
Sex-Specific Response to Caloric Restriction After Reproductive Investment in Microcebus murinus: An Integrative Approach

In seasonal environments, males and females usually maintain high metabolic activity during the whole summer season, exhausting their energy reserves. In the global warming context, unpredictability of food availability during summer could dramatically challenge the energy budget of individuals. Therefore, one can predict that resilience to environmental stress would be dramatically endangered during summer. Here, we hypothesized that females could have greater capacity to survive harsh conditions than males, considering the temporal shift in their respective reproductive energy investment, which can challenge them differently, as well as enhanced flexibility in females' physiological regulation. We tackled this question on the gray mouse lemur (Microcebus murinus), focusing on the late summer period, after the reproductive effort. We monitored six males and six females before and after a 2-weeks 60% caloric restriction (CR), measuring different physiological and cellular parameters in an integrative and comparative multiscale approach. Before CR, females were heavier than males and mostly characterized by high levels of energy expenditure, a more energetic mitochondrial profile and a downregulation of blood antioxidants. We observed a similar energy balance between sexes due to CR, with a decrease in metabolic activity over time only in males. Oxidative damage to DNA was also reduced by different pathways between sexes, which may reflect variability in their physiological status and life-history traits at the end of summer. Finally, females' mitochondria seemed to exhibit greater flexibility and greater metabolic potential than males in response to CR. Our results showed strong differences between males and females in response to food shortage during late summer, underlining the necessity to consider sex as a factor for population dynamics in climate change models.
Quantification of Major Bacteria and Yeast Species in Kefir Consortia by Multiplex TaqMan qPCR

Kefir grains are complex microbial systems of several groups of microorganisms. The identification and quantification of the microbial composition of milk kefirs was described in several studies, which provided an insight into the microbial consortia in this complex ecosystem. Nevertheless, the current methods for identification and quantification are not appropriate for deeper studies on kefir consortia, e.g., population dynamics and microbial interactions in kefir grains. This requires another sensitive and reliable quantitative method. Therefore, this study aims to develop multiplexed qPCR assays to specifically detect and quantify, as an example, several microorganisms of the milk kefir microbial community. Primer-probe sets, which target species-specific genes in six bacteria and five yeasts, were designed, and their sensitivity and specificity to the target species was analyzed in simplex as well as four multiplex qPCR assays. The self-designed multiplex assays were applied for the detection of target bacteria and yeast species in milk kefirs, in both, grain and beverage fractions. Detection of all target microorganisms in simplex and multiplex qPCR was achieved by good linearity, efficiency, repeatability and reproducibility in all assays. When the designed assays were applied on six kefirs, all target microorganisms were detected in different samples, but not all in one kefir sample. The two ubiquitous lactobacilli Lactobacillus kefiranofaciens and Lb. kefiri were present in all six kefirs studied, but were associated with different other yeasts and bacteria. Especially on the yeast community a significant diversity was observed. In general, multiplex TaqMan qPCR as developed here was proven to have high potential for specific identification of target microorganisms in kefir samples and for the first time, eleven target bacteria and yeasts of kefir microbiota were rapidly detected and quantified. This study, thus, provides a fast and reliable protocol for future studies on kefir and other similar microbial ecosystems.
Loss of TP53 mediates suppression of Macrophage Effector Function via Extracellular Vesicles and PDL1 towards Resistance against Chemoimmunotherapy in B-cell malignancies

Chemoimmunotherapy (CIT) is the standard of care in B-cell malignancies. It is relying on synergistic effects of alkylating chemotherapy and monoclonal antibodies via secretory crosstalk with effector macrophages. Here, we observed that loss of p53 function mediates resistance to CIT by suppressing macrophage phagocytic function. Loss of p53 leads to an upregulation of PDL1 and an increased formation of extracellular vesicles (EVs). EVs directly inhibit macrophage phagocytosis by PDL1 surface expression. Suppression of phagocytic function by lymphoma cell-derived EVs could be abrogated by pre-incubation of EVs with anti-PDL1 antibodies, CRISPR-KO of PDL1 and abrogation of EV formation by RAB27A-KO in lymphoma cells. Immune checkpoint inhibition represents a viable strategy to overcome EV-mediated resistance to chemoimmunotherapy in lymphoma. Significance Loss of TP53 mediates cell autonomous resistance to genotoxic chemotherapy, moreover non-cell autonomous effects may cause therapy resistance mediated by the tumor microenvironment. We identify a TP53-dependent mechanism that mediates resistance to synergistic chemoimmunotherapy by increasing formation of EVs and expression of the PDL1 immune checkpoint. PDL1 on EVs is directly responsible for macrophage suppression, preventing the exertion of the essential effector function of antibody-dependent cellular phagocytosis. This novel mechanism of resistance is in turn targetable by PDL1 checkpoint inhibition. Enhanced EV-release and immune checkpoint expression in lymphoma are novel mechanisms of macrophage modulation in the lymphoma microenvironment. We provide a novel principle of resistance to chemoimmunotherapy (CIT) representing of immediate relevance to treatment of refractory B-cell lymphoma. Highlights Loss of TP53 in B-cell lymphoma induces resistance towards chemoimmunotherapy (CIT) by inhibition of macrophage effector function through PDL1 upregulation Loss of TP53 increases formation of extracellular vesicles (EVs) carrying PDL1 EVs inhibit antibody-mediated cellular phagocytosis (ADCP), a key macrophage effector function in CIT Targeting PDL1 on EVs with immune checkpoint inhibitors overcomes TP53-mediated resistance to CIT
TIP60 acetylates H2AZ and regulates doxorubicin-induced DNA damage sensitivity through RAD51 transcription

TIP60, a lysine acetyltransferase and H2AZ, a histone H2A variant are involved in transcription and DNA repair. Recent studies suggest that H2AZ acetylation is dependent on TIP60. Here, we show that TIP60 acetylates both isoforms of H2AZ in vitro and in cells. Utilizing ChIP-seq and RNA-seq to identify the genes regulated by TIP60-dependent acetylation of H2AZ, we find that TIP60-dependent acetylation of H2AZ correlates with the expression of genes involved in DNA damage repair, amongst several other pathways. In line with this, TIP60-depleted cells exhibit increased sensitivity to the DNA damage-inducing drug doxorubicin. Restoring the expression level of RAD51, one of the genes involved in the DNA damage repair pathway, partially rescues the doxorubicin sensitivity due to TIP60 depletion. Overall, our study uncovers a role for TIP60 in regulating doxorubicin-induced DNA damage sensitivity in a manner dependent on RAD51 transcription.
Anatomical correlates of face patches in macaque inferotemporal cortex

Primate brains typically have regions within the ventral visual stream that are selectively responsive to faces. These face patches are located in similar parts of macaque inferotemporal (IT) cortex across individuals though correspondence with particular anatomical features has not been previously reported. Here, using high resolution functional and anatomical imaging, we show that small “bumps” along the lower bank of the superior temporal sulcus are predictive of the location of face-selective regions. Recordings from implanted multi-electrode arrays verified that these bumps contain face-selective neurons. These bumps were present in monkeys raised without seeing faces and that lack face patches, indicating that these anatomical landmarks are predictive, of but not sufficient for, the presence of face selectivity. These bumps are found across primate species, indicating common evolutionary developmental mechanisms.