Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulatory feedback determines attentional object segmentation in a model of the ventral stream

Studies in neuroscience inspired progress in the design of artificial neural networks (ANNs), and, vice versa, ANNs provide new insights into the functioning of brain circuits. So far, the focus has been on how ANNs can help to explain the tuning of neurons at various stages of the visual cortical hierarchy. However, the role of modulatory feedback connections, which play a role in attention and perceptual organization, has not been resolved yet. The present study presents a biologically plausible neural network that performs scene segmentation and can shift attention using modulatory feedback connections from higher to lower brain areas. The model replicates several neurophysiological signatures of recurrent processing. Specifically, figural regions elicit more activity in model units than background regions. The modulation of activity by figure and ground occurs at a delay after the first feedforward response, because it depends on a loop through the higher model areas. Importantly, the figural response enhancement is enhanced by object-based attention, which stays focused on the figural regions and does not spill over to the adjacent background, just as is observed in the visual cortex. Our results indicate how progress in artificial intelligence can be used to garner insight into the recurrent cortical processing for scene segmentation and object-based attention. Author Summary Recent feedforward networks in artificial intelligence provide unmatched models of tuning of neurons in the visual cortex. However, these feedforward models do not explain the influences of object-based attention and image segmentation on neuronal responses, which rely on feedback interactions between cortical regions that are not included in the feedforward networks. In particular, the role of feedback connections from higher brain regions that modulate neural activity in lower cortical regions has not yet been studied extensively so that we still lack an in silico model of the role of these connections. Here, we present a biologically plausible neural network that successfully performs image segmentation and can shift object-based attention using modulatory feedback connections. The model evolved representations that mirror the properties of neurons in the visual cortex, including orientation tuning, shape-selectivity, surround suppression and a sensitivity to figure-ground organization, while trained only on a segmentation task. The new model provides insight into how the perception of coherent objects can emerge from the interaction between lower and higher visual cortical areas.
Minimal impact of proprioceptive loss on implicit sensorimotor adaptation and perceived movement outcome

Implicit sensorimotor adaptation keeps our movements well-calibrated amid changes in the body and environment. We have recently postulated that implicit adaptation is driven by a perceptual error: the difference between the desired and perceived movement outcome. According to this perceptual re-alignment model, implicit adaptation ceases when the perceived movement outcome – a multimodal percept determined by a prior belief conveying the intended action, the motor command, and feedback from proprioception and vision – is aligned with the desired movement outcome. Here, we examined the role of proprioception in implicit motor adaptation and perceived movement outcome by examining individuals who lack proprioception. We used a modified visuomotor rotation task designed to isolate implicit adaptation and probe perceived outcome throughout the experiment. Surprisingly, implicit adaptation and perceived outcome were minimally impacted by deafferentation, posing a challenge to the perceptual re-alignment model of implicit adaptation.
Abnormal chondrocyte intercalation in a zebrafish model of cblC syndrome restored by an MMACHC cobalamin binding mutant

Variants in the MMACHC gene cause combined methylmalonic acidemia and homocystinuria cblC type, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism. cblC is associated with neurodevelopmental, hematological, ocular, and biochemical abnormalities. In a subset of patients, mild craniofacial dysmorphia has also been described. Mouse models of Mmachc deletion are embryonic lethal but cause severe craniofacial phenotypes such as facial clefts. MMACHC encodes an enzyme required for cobalamin processing and variants in this gene result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC). Interestingly, other inborn errors of cobalamin metabolism, such as cblX syndrome, are associated with mild facial phenotypes. However, the presence and severity of MMA and HC accumulation in cblX syndrome is not consistent with the presence or absence of facial phenotypes. Thus, the mechanisms by which mutation of MMACHC cause craniofacial defects have not been completely elucidated. Here we have characterized the craniofacial phenotypes in a zebrafish model of cblC (hg13) and performed restoration experiments with either wildtype or a cobalamin binding deficient MMACHC protein. Homozygous mutants did not display gross morphological defects in facial development, but did have abnormal chondrocyte intercalation, which was fully penetrant. Abnormal chondrocyte intercalation was not associated with defects in the expression/localization of neural crest specific markers, sox10 or barx1. Most importantly, chondrocyte organization was fully restored by wildtype MMACHC and a cobalamin binding deficient variant of MMACHC protein. Collectively, these data suggest that mutation of MMACHC causes mild to moderate craniofacial phenotypes that are independent of cobalamin binding.
Interaction between mutation type and gene pleiotropy drives parallel evolution in the laboratory

What causes evolution to be repeatable is a fundamental question in evolutionary biology. Pleiotropy, i.e. the effect of an allele on multiple traits, is thought to enhance repeatability by constraining the number of available beneficial mutations. Additionally, pleiotropy may promote repeatability by allowing large fitness benefits of single mutations via adaptive combinations of phenotypic effects. Yet, this latter evolutionary potential may be reaped solely by specific types of mutations able to realize optimal combinations of phenotypic effects while avoiding the costs of pleiotropy. Here, we address the interaction of gene pleiotropy and mutation type on evolutionary repeatability in a meta-analysis of experimental evolution studies with Escherichia coli. We hypothesize that single-nucleotide polymorphisms are principally able to yield large fitness benefits by targeting highly pleiotropic genes, whereas indels and structural variants provide smaller benefits and are restricted to genes with lower pleiotropy. By using gene connectivity as proxy for pleiotropy, we show that nondisruptive single-nucleotide polymorphisms (SNPs) in highly pleiotropic genes yield the largest fitness benefits, since they contribute more to parallel evolution, especially in large populations, than inactivating SNPs, indels and structural variants. Our findings underscore the importance of considering genetic architecture together with mutation type for understanding evolutionary repeatability.
Malaria parasite proliferation implicates a resource-dependent counter mechanism

Malaria is caused by the rapid proliferation of Plasmodium parasites in patients and disease severity correlates with the number of infected red blood cells in circulation. Parasite 20 multiplication within red blood cells is called schizogony and occurs through an atypical multinucleated cell division mode. The mechanisms regulating the number of daughter cells produced by a single progenitor are poorly understood. We investigated underlying regulatory principles by quantifying nuclear multiplication dynamics in Plasmodium falciparum and knowlesi using super-resolution time-lapse microscopy. This revealed that the number of 25 daughter cells was statistically independent of the duration of the nuclear division phase, indicating that a counter mechanism, rather than a timer, regulates multiplication. P. falciparum cell volume at the start of nuclear division correlated with the final number of daughter cells. As schizogony progressed, the nucleocytoplasmic volume ratio, which has been found to be constant in all eukaryotes characterized so far, increased significantly, possibly to 30 accommodate the exponentially multiplying nuclei. Depleting nutrients by dilution of culture medium caused parasites to produce less merozoites and reduced proliferation but did not affect cell volume or total nuclear volume at the end of schizogony. Our findings suggest that malaria parasites use a resource-dependent counter mechanism to optimize their progeny number during blood stage infection.
Novel genetically encoded tools for imaging or silencing neuropeptide release from presynaptic terminals in vivo

Neurons produce and release neuropeptides to communicate with one another. Despite their profound impact on critical brain functions, circuit-based mechanisms of peptidergic transmission are poorly understood, primarily due to the lack of tools for monitoring and manipulating neuropeptide release in vivo. Here, we report the development of two genetically encoded tools for investigating peptidergic transmission in behaving mice: a genetically encoded large dense core vesicle (LDCV) sensor that detects the neuropeptides release presynaptically, and a genetically encoded silencer that specifically degrades neuropeptides inside the LDCV. Monitoring and silencing peptidergic and glutamatergic transmissions from presynaptic terminals using our newly developed tools and existing genetic tools, respectively, reveal that neuropeptides, not glutamate, are the primary transmitter in encoding unconditioned stimulus during Pavlovian threat learning. These results show that our sensor and silencer for peptidergic transmission are reliable tools to investigate neuropeptidergic systems in awake behaving animals.
A novel description of the network dynamics underpinning working memory

Working memory (WM) plays a central role in cognition, prompting neuroscientists to investigate its functional and structural substrates. The WM dynamic recruits large-scale frequency-specific brain networks that unfold over a few milliseconds – this complexity challenges traditional neuroimaging analyses. In this study, we unravel the WM network dynamics in an unsupervised, data-driven way, applying the time delay embedded-hidden Markov model (TDE-HMM). We acquired MEG data from 38 healthy subjects performing an n-back working memory task. The TDE-HMM model inferred four task-specific states with each unique temporal (activation), spectral (phase-coherence connections), and spatial (power spectral density distribution) profiles. A theta frontoparietal state performs executive functions, an alpha temporo-occipital state maintains the information, and a broad-band and spatially complex state with an M300 temporal profile leads the retrieval process and motor response. The HMM states can be straightforwardly interpreted within the neuropsychological multi-component model of WM, significantly improving the comprehensive description of WM. Highlights Working memory recruits different frequency-specific brain networks that wax and wane at a millisecond scale. Through the time-delay embedded hidden (TDE-HMM) we are able to extract data-driven functional networks with unique spatial, spectral, and temporal profiles. We demonstrate the existence of four task-specific brain networks that can be interpreted within the well-known Baddeley’s multicomponent model of working memory. This novel WM description unveils new features that will lead to a more in-depth characterization of cognitive processes in MEG data.
T helper cells exhibit a dynamic and reversible 3′-UTR landscape

3’ untranslated regions (3’UTRs) are critical elements of messenger RNAs, as they contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of the RNA life cycle including transcript stability and cellular localisation. In response to T cell receptor activation, T cells undergo massive expansion during the effector phase of the immune response and dynamically modify their 3’UTRs. Whether this serves to directly regulate the abundance of specific mRNAs or is a secondary effect of proliferation remains unclear. To study 3’UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation (APA). We generated 3’ end UTR sequencing data from naïve, activated, memory and regulatory CD4+ T cells. 3’UTR length changes were estimated using a non-negative matrix factorization approach and were compared with those inferred from long-read PacBio sequencing. We found that APA events were transient and reverted after effector phase expansion. Using an orthogonal bulk RNAseq dataset, we did not find evidence of APA association with differential gene expression or transcript usage, indicating that APA has only a marginal effect on transcript abundance. 3’UTR sequence analysis revealed conserved binding sites for T cell-relevant microRNAs and RBPs in the alternative 3’UTRs. These results indicate that polyA site usage could play an important role in the control of cell fate decisions and homeostasis.
The catalytic activity of microRNA Argonautes plays a modest role in microRNA star strand destabilization in C. elegans

Many Argonaute proteins can cleave RNA (“slicing”) as part of the microRNA-induced silencing complex (miRISC), even though miRNA-mediated target repression is generally independent of target cleavage. Here we use genome editing in C. elegans to examine the role of miRNA-guided slicing in organismal development. In contrast to previous work, slicing-inactivating mutations did not interfere with normal development when introduced by CRISPR. We find that unwinding and decay of miRNA star strands is weakly defective in the absence of slicing, with the largest effect observed in embryos. Argonaute-Like Gene 2 (ALG-2) is more dependent on slicing for unwinding than ALG-1. The miRNAs that displayed the greatest (albeit minor) dependence on slicing for unwinding tend to form stable duplexes with their star strand, and in some cases, lowering duplex stability alleviates dependence on slicing. Gene expression changes were consistent with negligible to moderate loss of function for miRNA guides whose star strand was upregulated, suggesting a reduced proportion of mature miRISC in slicing mutants. While a few miRNA guide strands are reduced in the mutant background, the basis of this is unclear since changes were not dependent on EBAX-1, a factor in the Target-Directed miRNA Degradation (TDMD) pathway. Overall, this work defines a role for miRNA Argonaute slicing in star strand decay; future work should examine whether this role could have contributed to the selection pressure to conserve catalytic activity of miRNA Argonautes across the metazoan phylogeny.
The influence of distributive and procedural justice on work–family conflict, enrichment, and mental health of Indian police

ABSTRACT Employing the conservation of resources theory as a theoretical framework, the present research investigates a model that studies the influence of distributive and procedural justice on work–family conflict, work–family enrichment, and mental health. The model also evaluates the impact of work–family conflict and enrichment on mental health. The purposive sampling technique and a survey instrument were used to collect data from Rajasthan (India) police and analyzed using structural equation modeling. The results indicate that perceptions of justice (distributive and procedural) reduce work–family conflict and foster work–family enrichment in the police. Additionally, work–family conflict and enrichment predict mental health. The results further suggest the mediating mechanisms of work–family conflict and enrichment between distributive (partial), procedural (full) justice, and mental health.
Practices of cooperative training in the Amhara Regional State TVET colleges and companies, Ethiopia

Abstract The purpose of this study was to examine the practice of CT, companies’ involvement in CT, TVET Colleges’ and companies’ trainers’ engagement in CT from trainers’ and trainees’ perspectives and to determine whether their perspectives are significantly different. The current study also examined the influence of the involvement or engagement level of company/enterprise, company supervisors and TVET College trainers in CT program implementation. For this purpose, the convergent parallel mixed-methods design was employed. A sample of 207 trainers and 211 trainees were involved in this study. Questionnaire and semi-structured interviews were employed to collect quantitative and qualitative data, respectively. Cronbach’s alpha value for the reliability of the instrument ranged between . 74 and . 94. The independent-sample t-test, Pearson’s correlation, and regression methods were used to analyze quantitative data. The thematic analysis method was used to analyze qualitative data using research questions as core themes. In this study, we found that the CT practice, company, and TVET trainers’ engagement in CT-related tasks were at a medium level, but the companies’ involvement in CT implementation was low. The TVET trainers and trainees had significantly different views regarding the level of CT practice, companies’ involvement, supervisors’ and trainers’ engagement in CT activities. In conclusion, the companies’ involvement level and TVET trainers’ engagement level showed large influences on CT practice. Based on these findings, we recommended the need for devising binding rules and regulations in a way that enforces accountability amongst all stakeholders of the CT program in the TVET system.
Toddler and preschool teachers’ beliefs and perceptions about the use of developmentally appropriate practice

Abstract A developmentally appropriate learning environment provides learning experiences that support whole child development as young children are provided with opportunities to engage in meaningful experiences that promote inquiry, exploration, problem solving, and discovery. The intent of developmentally appropriate practice (DAP) is shifting the K–12 pushdown curriculum in early childhood education (ECE) to a child-centered approach to learning. Qualification in fields unrelated to ECE might result in a lack of knowledge about child growth and development and in childcare centers functioning like K–12 programs. The purpose of this qualitative explanatory multi-case study was to examine toddler and preschool teachers’ beliefs and perceptions about the use of DAP within toddler and preschool classrooms. Data were collected from a purposeful sample of 16 teachers on their beliefs and perceptions about classroom practices and the forces that shape such practices in toddler and preschool classrooms. Findings suggest that a disturbing amount of toddler and preschool teachers endorsed a K–12 pushdown curriculum with the belief that young children should be able to sit and complete worksheets.
Microglia Proliferation Underlies Synaptic Dysfunction in the Prefrontal Cortex: Implications for the Pathogenesis of HIV-1-Associated Neurocognitive and Affective Alterations

Microglia, which are productively infected by HIV-1, are critical for brain development and maturation, as well as synaptic plasticity. The pathophysiology of HIV-infected microglia and their role in the pathogenesis of HIV-1-associated neurocognitive and affective alterations, however, remains understudied. Three complementary aims were undertaken to critically address this knowledge gap. First, the predominant cell type expressing HIV-1 mRNA in the dorsolateral prefrontal cortex of postmortem HIV-1 seropositive individuals with HAND was investigated. Utilization of a combined RNAscope multiplex fluorescent and immunostaining assay revealed prominent HIV-1 mRNA in microglia of postmortem HIV-1 seropositive individuals with HAND. Second, measures of microglia proliferation and neuronal damage were evaluated in chimeric HIV (EcoHIV) rats. Eight weeks after EcoHIV innoculation, enhanced microglial proliferation was observed in the medial prefrontal cortex (mPFC) of EcoHIV rats, evidenced by an increased number of cells co-localized with both Iba1+ and Ki67+ relative to control animals. Neuronal damage in EcoHIV infected rats was evidenced by pronounced decreases in both synaptophysin and post synaptic density protein 95 (PSD-95), markers of pre-synaptic and post-synaptic damage, respectively. Third, regression analyses were conducted to evaluate whether microglia proliferation mechanistically underlies neuronal damage in EcoHIV and control animals. Indeed, microglia proliferation accounts for 42-68.6% of the variance in synaptic dysfunction. Collectively, microglia proliferation induced by chronic HIV-1 viral protein exposure may underlie the profound synaptodendritic alterations in HIV-1. Understanding how microglia are involved in the pathogenesis of HAND and HIV-1-associated affective disorders affords a key target for the development of novel therapeutics.
High tunability barium strontium titanate thin films for rf circuit applications

Large variations in the permittivity of rf magnetron sputtered thin-film barium strontium titanate have been obtained through optimization of growth conditions for maximum dielectric strength and zero-field permittivity in a parallel-plate capacitor structure. Using nominal target compositions of Ba0.5Sr0. 5TiO3, and Pt electrodes on c-plane sapphire substrates, adjustment of the O2 partial pressure during deposition was used to vary the excess Ti incorporation into the films, which influenced the low-field permittivity, loss tangent, and dielectric strength. By balancing the benefits of a high permittivity with dielectric strength and loss, we have produced films capable of sustaining short-duration fields greater than 4MV∕cm with over 13:1 (>90%) change in dielectric constant, and greater than 5:1 tunability in bias fields under 1MV∕cm.
The impact of selected abiotic factors on zooplankton hatching process through real-time, in-situ observation

Current studies on abiotic impacts on marine microorganisms often focus on endpoint analysis (e.g., hatching rates, survival). Here, we demonstrate that a mechanistic understanding can be obtained through real-time measurement of respiration and morphology in controlled microenvironments over extended time periods. As a demonstration, temperature and salinity are chosen to represent critical abiotic parameters that are also threatened by climate change and a target species of Artemia, a prominent zooplankton whose reproduction can affect the marine food pyramid. Different temperatures (20, 35, and 30ºC) and salinities (0, 25, 50, and 75 ppt) are shown to significantly alter the duration of hatching stages, metabolic rates, and hatchability. Higher temperatures and moderate salinity boosted metabolic reactivation of latent cysts, while higher temperatures alone sped up the process. Hatchability is inversely related to the duration of the differentiation stage of hatching, which persisted longer at lower temperatures and salinities. Initial oxygen availability affects respiration but not hatchability owing to temperature and salinity interactions. Graphical abstract