Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylotranscriptomics Reveals Discordance in the Phylogeny of Hawaiian Drosophila and Scaptomyza (Diptera: Drosophilidae)

Island radiations present natural laboratories for studying the evolutionary process. The Hawaiian Drosophil-idae are one such radiation, with nearly 600 described species and substantial morphological and ecological diversification. These species are largely divided into a few major clades, but the relationship between these clades remains uncertain. Here we present 12 new assembled transcriptomes from across these clades, and use these transcriptomes to resolve the base of the evolutionary radiation. We recover a new hypothesis for the relationship between clades, and demonstrate its support over previously published hypotheses. We then use the evolutionary radiation to explore dynamics of concordance in phylogenetic support, by analyzing the gene and site concordance factors for every possible topological combination of major groups. We show that high bootstrap values mask low evolutionary concordance, and we demonstrate that the most likely topology is distinct from the topology with the highest support across gene trees and from the topology with highest support across sites. We then combine all previously published genetic data for the group to estimate a time-calibrated tree for over 300 species of drosophilids. Finally, we digitize dozens of published Hawaiian Drosophilidae descriptions, and use this to pinpoint probable evolutionary shifts in reproductive ecology as well as body, wing, and egg size. We show that by examining the entire landscape of tree and trait space, we can gain a more complete understanding of how evolutionary dynamics play out across an island radiation.
Improved prediction of behavioral and neural similarity spaces using pruned DNNs

Deep Neural Networks (DNNs) have become an important tool for modeling brain and behaviour. One key area of interest has been to apply these networks to model human similarity judgements. Several previous works have used the embeddings from the penultimate layer of vision DNNs and showed that a reweighting of these features improves the fit between human similarity judgments and DNNs. These studies underline the idea that these embeddings form a good basis set but lack the correct level of salience. Here we re-examined the grounds for this idea and on the contrary, we hypothesized that these embeddings, beyond forming a good basis set, also have the correct level of salience to account for similarity judgments. It is just that the huge dimensional embedding needs to be pruned to select those features relevant for the considered domain for which a similarity space is modeled. In Study 1 we supervised DNN pruning based on a subset of human similarity judgments. We found that pruning: i) improved out-of-sample prediction of human similarity judgments from DNN embeddings, ii) produced better alignment with WordNet hierarchy, and iii) retained much higher classification accuracy than reweighting. Study 2 showed that pruning by neurobiological data is highly effective in improving out-of-sample prediction of brain-derived representational dissimilarity matrices from DNN embeddings, at times fleshing out isomorphisms not otherwise observable. Pruning supervised by human brain/behavior therefore effectively identifies alignable dimensions of semantic knowledge between DNNs and humans and constitutes an effective method for understanding the organization of knowledge in neural networks.
Your head is there to move you around: Goal-driven models of the primate dorsal pathway

Neurons in the dorsal visual pathway of the mammalian brain are selective for motion stimuli, with the complexity of stimulus representations increasing along the hierarchy. This progression is similar to that of the ventral visual pathway, which is well characterized by artificial neural networks (ANNs) optimized for object recognition. In contrast, there are no image-computable models of the dorsal stream with comparable explanatory power. We hypothesized that the properties of dorsal stream neurons could be explained by a simple learning objective: the need for an organism to orient itself during self-motion. To test this hypothesis, we trained a 3D ResNet to predict an agent’s self-motion parameters from visual stimuli in a simulated environment. We found that the responses in this network accounted well for the selectivity of neurons in a large database of single-neuron recordings from the dorsal visual stream of non-human primates. In contrast, ANNs trained on an action recognition dataset through supervised or self-supervised learning could not explain responses in the dorsal stream, despite also being trained on naturalistic videos with moving objects. These results demonstrate that an ecologically relevant cost function can account for dorsal stream properties in the primate brain.
The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative MS analysis. We found that native TRPM7 channels are high molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels. Impact Statement High-resolution proteomics in conjunction with biochemical and electrophysiological experiments revealed that the channel-kinase TRPM7 in the rodent brain forms macromolecular complexes containing the metal transporters CNNM1-4 and a small G protein ARL15.
Unsupervised characterization of dynamic functional connectivity reveals age-associated differences in temporal stability and connectivity states during rest and task

Understanding brain functions as an outcome of underlying neuro-cognitive network mechanisms in rest and task requires accurate spatiotemporal characterization of the relevant functional brain networks. Recent endeavours of the Neuroimaging community to develop the notion of dynamic functional connectivity is a step in this direction. A key goal is to detect what are the important events in time that delimits how one functional brain network defined by known patterns of correlated brain activity transitions into a “new” network. Such characterization can also lead to more accurate conceptual realization of brain states, thereby, defined in terms of time-resolved correlations. Nonetheless, identifying the canonical temporal window over which dynamic functional connectivity is operational is currently based on an ad-hoc selection of sliding windows that can certainly lead to spurious results. Here, we introduce a data-driven unsupervised approach to characterize the high dimensional dynamic functional connectivity into dynamics of lower dimensional patterns. The whole-brain dynamic functional connectivity states bearing functional significance for task or rest can be explored through the temporal correlations, both short and long range. The present study investigates the stability of such short- and long-range temporal correlations to explore the dynamic network mechanisms across resting state, movie viewing and sensorimotor action tasks requiring varied degrees of attention. As an outcome of applying our methods to the fMRI data of a healthy ageing cohort we could quantify whole-brain temporal dynamics which indicates naturalistic movie watching task is closer to resting state than the sensorimotor task. Our analysis also revealed an overall trend of highest short range temporal network stability in the sensorimotor task, followed by naturalistic movie watching task and resting state that remains similar in both young and old adults. However, the stability of neurocognitive networks in the resting state in young adults is higher than their older counterparts. Thus, healthy ageing related differences in quantification of network stability along task and rest provides a blueprint of how our approach can be used for cohort studies of mental health and neurological disorders.
Causes of variability in estimates of mutational variance from mutation accumulation experiments

Characteristics of the new phenotypic variation introduced via mutation have broad implications in evolutionary and medical genetics. Standardised estimates of this mutational variance, VM, span two orders of magnitude, but the causes of this remain poorly resolved. We investigated estimate heterogeneity using two approaches. First, meta-analyses of ~150 estimates from 37 mutation accumulation (MA) studies did not support a difference among taxa (which differ in mutation rate) in standardised VM, but provided equivocal support for standardised VM to vary with trait type (life history versus morphology, predicted to differ in mutation rate). Notably, several experimental factors were confounded with taxon and trait, and further empirical data are required to resolve their influences. Second, we analysed morphological data from an experiment in Drosophila serrata to determine the potential for unintentional heterogeneity among environments in which phenotypes were measured (i.e., among laboratories or time points) or transient segregation of mutations within MA lines to affect standardised VM. Approximating the size of an average MA experiment, variability among repeated estimates of (accumulated) mutational variance was comparable to variation among published estimates of standardised VM for morphological traits. This heterogeneity was (partially) attributable to unintended environmental variation or within line segregation of mutations only for wing size, not wing shape traits. We conclude that sampling error contributed substantial variation within this experiment, and infer that it will also contribute substantially to differences among published estimates. We suggest a logistically permissive approach to improve the precision of estimates, and consequently our understanding of the dynamics of mutational variance of quantitative traits.
Abnormal Degree Centrality in White Matter Hyperintensities: A Resting-State Functional Magnetic Resonance Imaging Study

Background: White matter hyperintensities (WMHs) are a common occurrence with aging and are associated with cognitive impairment. However, the neurobiological mechanisms of WMHs remain poorly understood. Functional magnetic resonance imaging (fMRI) is a prominent tool that helps in non-invasive examinations and is increasingly used to diagnose neuropsychiatric diseases. Degree centrality (DC) is a common and reliable index in fMRI, which counts the number of direct connections for a given voxel in a network and reflects the functional connectivity within brain networks. We explored the underlying mechanism of cognitive impairment in WMHs from the perspective of DC. Methods: A total of 104 patients with WMHs and 37 matched healthy controls (HCs) were enrolled in the current study. All participants underwent individual and overall cognitive function tests and resting-state fMRI (rs-fMRI). WMHs were divided into three groups (39 mild WMHs, 37 moderate WMHs, and 28 severe WMHs) according to their Fazekas scores, and the abnormal DC values in the WMHs and HCs groups were analyzed. Results: There was a significant difference in the right inferior frontal orbital gyrus and left superior parietal gyrus between the WMHs and HCs groups. The functional connectivity between the right inferior frontal orbital gyrus and left inferior temporal gyrus, left superior parietal gyrus, and left parietal inferior gyrus was also different in the WMHs group. Conclusion: The change in DC value may be one of the underlying mechanisms of cognitive impairment in individuals with WMHs, which provides us with a new approach to delaying cognitive impairment in WMHs.
De novo Sequencing and Comparative Transcriptome Analyses Provide First Insights Into Polysaccharide Biosynthesis During Fruiting Body Development of Lentinula edodes

Polysaccharides separated from Lentinula edodes are well known for their medicinal properties. However, the precise molecular mechanisms of polysaccharide biosynthesis in L. edodes remain unclear. In this study, the fruiting bodies of L. edodes in four developmental stages with significant differences in polysaccharide yield were collected, and the characteristics of polysaccharides were studied. De novo sequencing and comparative transcriptomic analysis were performed by using high-throughput Illumina RNA-sequencing. KS1P30, KS2P30, KS3P30, and KS4P30 were obtained from the four developmental stages, respectively, by hot water extraction and 30% ethanol precipitation. These four polysaccharides had good immune activity in vitro; all of them were β-glucopyranose with a high molecular weight. Glucose was the main monosaccharide component of these polysaccharides. High-quality clean reads (57.88, 53.17, 53.28, and 47.56 million for different growth stages) and mapping ratios ranging from 84.75 to 90.11% were obtained. In total, 11,493 (96.56%) unigenes and 18,924 (97.46%) transcripts were successfully annotated in five public databases. The biosynthetic pathway and related genes of LEFP30 were mined. The molecular mechanism of LEFP30 yield change in the different developmental stages was predicted. The results provide some insights into the possible mechanisms involved in the biosynthetic pathway of this kind of polysaccharide in L. edodes fruiting bodies. They also indicate that candidate genes can be used as important resources for biotechnology and molecular breeding to regulate L. edodes fruiting body polysaccharide biosynthesis.
Determinants of Investment Behavior in Mutual Funds: Evidence From Pakistan

This paper aimed to provide empirical evidence on the behavior of the investor toward mutual funds by considering its relationship with risk perception (RP), return perception (Return P), investment criteria (IC), mutual fund awareness (MFA), and financial literacy (FL). Data were collected using a questionnaire from 500 mutual fund investors, from which 460 questionnaires were used for the analysis. In addition, the snowball sampling technique was used to collect data from different cities in Pakistan. The result showed that RP, Return P, and MFA are insignificant and negatively affect the behavior of mutual fund investors. Investment criteria have a negative and significant effect on the behavior of mutual fund investors. Financial literacy has a positive and insignificant effect on the behavior of mutual fund investors. The results provide better information and guidance to investors and policymakers on the factors that affect the behavior of mutual fund investors.
Explaining Recruitment Stochasticity at a Species’ Range Margin

Advancing our understanding of how environmental variability affects the distribution of organisms is crucial for ecology and conservation. The exploration of changes in demographic patterns close to species distribution margins is important as populations here may provide a window into future population changes also elsewhere. However, the knowledge of factors causing recruitment variation is still inadequate in many systems and this deficiency is particularly evident close to species’ distribution borders. We studied the spatiotemporal variability in recruit-adult dynamics in a blue mussel, Mytilus trossulus, population to get insights into how environmental variables drive variation in recruitment and how this variability affects adult population growth. Thirty sites along a wave exposure gradient were monitored during four consecutive years. From each site, mussels were collected both from artificial recruitment units and from natural mussel beds. Our results showed high year-to-year variation in recruitment strength with high spatial variation. Mussel recruitment to artificial units and later recruitment to the benthos correlated highly. Juvenile abundances 1 year later paralleled prior recruitment strengths and caused synchronous but time-lagged changes in adult cohorts. Seawater salinity was the strongest predictor for recruitment variation, whereas sea temperature and wave exposure had low predictive power for this early life stage. For juveniles and for adults in the benthos, wave exposure explained the variation best, whereas temperature and especially salinity explained less. The results indicate that (a) the studied blue mussel population is strongly driven by variation in recruitment strength that (b) drives the size of the later cohorts, and the population is possibly even (c) recruitment limited in some years. Our study predicts a challenging future for this range population, resulting from a higher frequency of recruitment failure caused by a deteriorating sea climate. Knowledge about factors underlying variation in recruitment is thus essential for forecasting the future of this range population and for conserving its future state.
Structural Dynamics and Perspectives of Vitamin B6 Biosynthesis Enzymes in Plasmodium: Advances and Open Questions

Malaria is still today one of the most concerning diseases, with 219 million infections in 2019, most of them in Sub-Saharan Africa and Latin America, causing approx. 409,000 deaths per year. Despite the tremendous advances in malaria treatment and prevention, there is still no vaccine for this disease yet available and the increasing parasite resistance to already existing drugs is becoming an alarming issue globally. In this context, several potential targets for the development of new drug candidates have been proposed and, among those, the de novo biosynthesis pathway for the B6 vitamin was identified to be a promising candidate. The reason behind its significance is the absence of the pathway in humans and its essential presence in the metabolism of major pathogenic organisms. The pathway consists of two enzymes i.e. Pdx1 (PLP synthase domain) and Pdx2 (glutaminase domain), the last constituting a transient and dynamic complex with Pdx1 as the prime player and harboring the catalytic center. In this review, we discuss the structural biology of Pdx1 and Pdx2, together with and the understanding of the PLP biosynthesis provided by the crystallographic data. We also highlight the existing evidence of the effect of PLP synthesis inhibition on parasite proliferation. The existing data provide a flourishing environment for the structure-based design and optimization of new substrate analogs that could serve as inhibitors or even suicide inhibitors.
Passive removal of manganese from acid mine drainage

Removal of manganese (Mn) from mine drainage is difficult due to the abnormal chemistry of the element. The removal requires the oxidation of Mn(II) (the form found in mine drainage) to the more oxidized forms (Mn(III) or Mn(IV)). The more oxidized forms exist only as solids and will not return to Mn(II) spontaneously. Chemical treatment of Mn often requires a pH near 10 to initiate the oxidation quickly. A stabilized pH of 10 normally causes more harm to aquatic organisms than the Mn and is not desirable, making additional steps in the treatment necessary. Biological removal of Mn can be achieved at near neutral pH levels. The Shade Mining site in Somerset County, PA has been treating Mn to discharge limits since the early 1990`s (reducing Mn concentrations from 12 - 25 mg/L in the influent to <2 mg/L in the effluent). The treatment system consists of an anoxic limestone drain discharging into a wetland to remove iron, aluminum, and acidity, while increasing pH and alkalinity. The wetland effluent flows into two limestone beds (Mn removal). The limestone beds developed a black slime coating as the Mn removal increased. This system continues to remove Mn in all weather conditions andmore » has not required chemical treatment since the black coating appeared on the limestone. A laboratory study was conducted using limestone collected from the Shade site to use the same naturally occurring Mn oxidizing microbes. The lab study compared W removal rates of microbial oxidation, MnO{sub 2} catalyzed limestone, and fresh uncoated limestone. The microbial removal performed the best (25 mg/L Mn reduced to <2 mg/L in 72 hours). « less
Impaired Priming of SARS-CoV-2-Specific Naive CD8+ T Cells in Older Subjects

Advanced age is associated with severe symptoms and death upon SARS-CoV-2 infection. Virus-specific CD8+ T-cell responses have shown to be protective toward critical COVID-19 manifestations, suggesting that suboptimal cellular immunity may contribute to the age-pattern of the disease. The induction of a CD8+ T-cell response against an emerging pathogen like SARS-CoV-2 relies on the activation of naive T cells. To investigate whether the primary CD8+ T-cell response against this virus is defective in advanced age, we used an in vitro approach to prime SARS-CoV-2-specific naive CD8+ T cells from healthy, unexposed donors of different age groups. Compared to younger adults, older individuals display a poor SARS-CoV-2-specific T-cell priming capacity in terms of both magnitude and quality of the response. In addition, older subjects recognize a lower number of epitopes. Our results implicate that immune aging is associated with altered primary SARS-CoV-2-specific CD8+ T-cell responses.