Miracle-dz/UniFAR-FTUs huggingface dataset:
Parallel processing relies on a distributed, low-dimensional cortico-cerebellar architecture

A characteristic feature of human cognition is our ability to ‘multi-task’ – performing two or more tasks in parallel – particularly when one task is well-learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain – typically the dorsolateral prefrontal cortex – that are required to navigate information processing bottlenecks. In contrast, we take a systems neuroscience approach to test the hypothesis that the capacity to conduct effective parallel processing relies on a distributed architecture that interconnects the cerebral cortex with the cerebellum. The latter structure contains over half of the neurons in the adult human brain, and is well-suited to support the fast, effective, dynamic sequences required to perform tasks relatively automatically. By delegating stereotyped within-task computations to the cerebellum, the cerebral cortex can be freed up to focus on the more challenging aspects of performing the tasks in parallel. To test this hypothesis, we analysed task-based fMRI data from 50 participants who performed a task in which they either balanced an avatar on a screen (‘Balance’), performed serial-7 subtractions (‘Calculation’) or performed both in parallel (‘Dual-Task’). Using a set of approaches that include dimensionality reduction, structure-function coupling and time-varying functional connectivity, we provide robust evidence in support of our hypothesis. We conclude that distributed interactions between the cerebral cortex and cerebellum are crucially involved in parallel processing in the human brain.
Cystathionine β-synthase gene inactivation dysregulates major urinary protein biogenesis and impairs sexual signaling in mice

Reproductive success in mice depends on major urinary proteins (Mup) that facilitate sexual interactions between females and males. Deletion of cystathionine β-synthase (Cbs) gene, a metabolic gene important for homeostasis of one-carbon metabolism, impairs reproduction by causing female infertility in mice. Here we examined Mup biogenesis and sexual signaling in Cbs−/− vs. Cbs+/− mice. We found that total urinary Mup protein was significantly reduced in male and female Cbs−/− vs. Cbs+/− mice. SDS-PAGE/Western blot, ESIMS, and RT-qPCR analyses of the liver, plasma, and urinary proteins identified a male-specific Mup20 in Cbs−/−, but not Cbs+/− females. As other Mups were significantly reduced, the 18,893 Da Mup20 became the most abundand in urine of Cbs−/− females and males. Effects of Cbs genotype on 18,645 Da, 18,693 Da, and 18,709 Da Mup species abundance were Mup and sex-specific. Cbs-dependent changes in hepatic Mups and Mup20 expression were similar at the protein and mRNA level. Changes in Mups, but not in Mup20, can be explained by downregulation of hepatic Zhx2 and Ghr receptors in Cbs−/− mice. Behavioral testing showed that Cbs+/− females were attracted to Cbs+/− but not to Cbs−/− male urine. Cbs+/− males did not countermark urine of Cbs−/− males but countermarked urine of other Cbs+/− males and were attracted to urines of Cbs−/− as well as Cbs+/− females. Cbs−/− males did not countermark urine of Cbs+/− males but were still attracted to urines of Cbs+/− females. Taken together, these findings show that Cbs, a metabolic gene, plays an important role in the regulation of Mup biogenesis and sexual signaling in mice.
Preparation of large biological samples for high-resolution, hierarchical, multi-modal imaging

Imaging the different scales of biological tissue is essential for understanding healthy organ behavior and pathophysiological changes. X-ray micro-tomography using both laboratory (µCT) and synchrotron sources (sCT) is a promising tool to image the 3D morphology at the macro- and micro-scale of large samples, including intact human organs. Preparation of large samples for high resolution imaging techniques remains a challenge due to limitations with current methods, such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe a protocol to prepare, stabilize, and image large soft-tissue samples with X-ray microtomography. We demonstrate the protocol using intact human organs and Hierarchical Phase-Contrast Tomography (HiP-CT) imaging at the European Synchrotron Radiation Facility, but the protocol is equally applicable to a range of biological samples, including complete organisms, for both laboratory and synchrotron source tomography. Our protocol enhances the contrast of the sample, while preventing sample motion during the scan, even in case of different sample orientations. Bubbles trapped during mounting and those formed during scanning (in case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging (MRI), CT, and histological observation. We describe a protocol for sample preparation and mounting which requires 25 to 34 days for a large organ such as an intact human brain or heart. This preparation time varies depending on the composition, size, and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local pixel size of one micron using HiP-CT.
Hydrogen stable isotope probing of lipids demonstrates slow rates of microbial growth in soil

Significance Growth rate, how quickly organisms grow and reproduce, is a key feature of biology. However, there are few measurements of microbial growth rates in soil, despite its crucial importance to terrestrial ecosystems and global environmental change. By measuring the uptake of isotopically labeled water, we can quantify microbial growth, even at exceedingly slow rates. We find that the growth rates of soil microorganisms are slower than those typically observed in culture as well as most previous estimates in soil. Surprisingly, we observe that lower-biomass soils exhibited faster growth than high-biomass soils and that more abundant microorganisms are not necessarily faster growing. Our results underscore the importance of considering slow and variable growth rates when studying microorganisms and their contributions to ecosystems.
End-to-End deep structure generative model for protein design

Designing protein with desirable structure and functional properties is the pinnacle of computational protein design with unlimited potentials in the scientific community from therapeutic development to combating the global climate crisis. However, designing protein macromolecules at scale remains challenging due to hard-to-realize structures and low sequence design success rate. Recently, many generative models are proposed for protein design but they come with many limitations. Here, we present a VAE-based universal protein structure generative model that can model proteins in a large fold space and generate high-quality realistic 3-dimensional protein structures. We illustrate how our model can enable robust and efficient protein design pipelines with generated conformational decoys that bridge the gap in designing structure conforming sequences. Specifically, sequences generated from our design pipeline outperform native fixed backbone design in 856 out of the 1,016 tested targets(84.3%) through AF2 validation. We also demonstrate our model’s design capability and structural pre-training potential by structurally inpainting the complementarity-determining regions(CDRs) in a set of monoclonal antibodies and achieving superior performance compared to existing methods.
Antiviral function and viral antagonism of the rapidly evolving dynein activating adaptor NINL

Viruses interact with the intracellular transport machinery to promote viral replication. Such host-virus interactions can drive host gene adaptation, leaving signatures of pathogen-driven evolution in host genomes. Here we leverage these genetic signatures to identify the dynein activating adaptor, ninein-like (NINL), as a critical component in the antiviral innate immune response and as a target of viral antagonism. Unique among genes encoding components of active dynein complexes, NINL has evolved under recurrent positive (diversifying) selection, particularly in its carboxy-terminal cargo binding region. Consistent with a role for NINL in host immunity, we demonstrate that NINL knockout cells exhibit an impaired response to interferon, resulting in increased permissiveness to viral replication. Moreover, we show that proteases encoded by diverse picornaviruses and coronaviruses cleave and disrupt NINL function in a host- and virus-specific manner. Our work reveals the importance of NINL in the antiviral response and the utility of using signatures of host-virus conflicts to uncover new components of antiviral immunity and targets of viral antagonism.
Germline protein, Cup, non-cell autonomously limits migratory cell fate in Drosophila oogenesis

Attaining migratory fate from a stationary cell population is complex and indispensable both for the multicellular organism development as well for the pathological condition like tumor metastasis. Though widely prevalent in the metazoans, the molecular understanding of this phenomenon remains elusive. Specification of migratory border cells from the follicular epithelium during Drosophila oogenesis has emerged as one of the excellent model systems to study how motile cell are specified. JAK-STAT activation in 6-10 anterior most follicle cells of the Drosophila egg chamber transforms them to a migratory cluster called the border cells. We show that a nurse cell protein, Cup, non-cell autonomously restricts the domain of JAK-STAT activation in the anterior follicle cells. Further examination suggests that Cup functions through Rab11GTPase to regulate Delta trafficking in the nurse cells potentiating Notch activation in the anterior follicle cells. Since Notch activity in the follicle cells modulates the JAK-STAT, any perturbation in Notch activation affects the border cell fate. Altogether, we propose that germline Cup affects the border cell fate through appropriate activation of Notch and JAK-STAT signaling in the follicle cells.
Bifidobacterium infantis-Mediated Herpes Simplex Virus-TK/Ganciclovir Treatment Inhibits Cancer Metastasis in Mouse Model

Previous studies have found that Bifidobacterium infantis-mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN−45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF−1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV.
Application of Photonic Crystal Ring Resonators for Realizing All Optical Demultiplexers

Abstract Transmission efficiency, quality factor, crosstalk levels and number of output channels are the most crucial parameters in designing optical demultiplexers, suitable for wavelength division multiplexing applications. In this paper we proposed an 8-channel optical demultiplexer based on photonic crystal ring resonator. For performing wavelength selection task we used eight ring resonators. The resonance wavelength of the ring resonators depends on the dimensions of the ring core, therefore we choose eight different values for the lattice constant of the ring resonators core section. The average channel spacing of the structure is about 3 nm the transmission efficiency in most of the channels is equal or more than 99 % except in one channels whose transmission efficiency is 85 %.
Typing of mecD -islands in genetically diverse methicillin-resistant Macrococcus 1 caseolyticus from cattle 2

Macrococcus caseolyticus belongs to the normal bacterial flora of dairy cows and does not 27 usually cause disease. However, methicillin-resistant M. caseolyticus strains were isolated 28 from bovine mastitis milk. These bacteria had acquired a chromosomal island (McRI mecD -1 or 29 McRI mecD -2) encoding the methicillin resistance gene mecD . To gain insight into the 30 distribution of McRI mecD types in M. caseolyticus from cattle, 33 mecD -containing strains 31 from Switzerland were characterized using molecular techniques, including multilocus 32 sequence typing, antibiotic resistance gene identification and PCR-based McRI mecD typing. 33 Additionally, the same genetic features were analyzed in 27 mecD -containing M. caseolyticus 34 strains isolated from bovine bulk milk in England/Wales using publicly available whole 35 genome sequences. The 60 strains belonged to 24 different sequence types (STs), with strains 36 belonging to ST5, ST6, ST21 and ST26 observed in both Switzerland and England/Wales. 37 McRI mecD -1 was found in different STs from Switzerland (n=19) and England/Wales (n=4). 38 McRI mecD -2 was only found in 7 strains from Switzerland, all of which belonged to ST6. A 39 novel island, McRI mecD -3, which contains a complete mecD operon ( mecD-mecR1 m -mecI m ) 40 combined with the left part of McRI mecD -2 and the right part of McRI mecD -1, was found in 41 heterogeneous STs from both collections (Switzerland: n=7; England/Wales: n=21). Two 42 strains from England/Wales carried a truncated McRI mecD -3. Phylogenetic analyses revealed 43 no clustering of strains according to geographical origin or carriage of McRI mecD -1 and 44 McRI mecD -3. Circular excisions were also detected for McRI mecD -1 and McRI mecD -3 by PCR. 45 The analyses indicate that these islands are mobile and may spread by horizontal gene 46 transfer between genetically diverse M. caseolyticus . Since its first description in 2017, the methicillin resistance gene mecD has been detected in 52 M. caseolyticus from different cattle sources and countries. Our study provides new insights 53 into the molecular diversity of mecD -carrying M. caseolyticus strains using two approaches 54 to characterize mecD elements: (i) multiplex PCR for molecular typing of McRI mecD and (ii) 55 read mapping against reference sequences to identify McRI mecD types in silico. In 56 combination with multilocus sequence typing, this approach can be used for molecular 57 characterization and surveillance of M. caseolyticus carrying mecD . 58
Dynamics of the Solar System Meteoroid Population

The purpose of this study is to develop an understanding of the observability of small-scale dynamical Solar System features in meteor orbit radar data, particularly with reference to mean motion resonance effects. Particular focus is placed on the presence of ‘resonant swarms’ in meteoroid streams: the resonant swarm at the 7:2 Jovian meanmotion resonance is used as an example, as it best satisfies radar observability criterion. Furthermore, evidence for this structure exists in visual meteor data. The radar dataset used for this study is that of the Canadian Meteor Orbit Radar (CMOR) as this dataset contains the largest number of meteoroid stream particles. The aim here is to determine whether the Taurid resonant swarm is observable in datasets produced by radars such as CMOR, or what improvements in individual orbital uncertainties are necessary for positive detection to be possible. The observability of the Taurid swarm in radar data depends on the limitations of the radar data (in terms of the individual measurement uncertainties); and on the properties of the resonance itself. Both aspects are investigated in this thesis. A statistical study is first conducted to assess whether evidence for the swarm exists in a dataset containing CMOR Northern and Southern Taurids from the years 2002 to 2007. It is found that the level of variations present is consistent with that expected due to random fluctuations: there is no evidence for a statistically significant resonant feature at the location of the 7:2 Jovian resonance. Additionally, the observability of various sizes of resonant peak for different sizes of dataset and for different levels of measurement uncertainties is investigated by addition of a modelled resonant feature to the data, followed by replacement of individual meteors by Gaussian profiles to simulate the effect of orbital uncertainties. It is clear that the level of broadening resulting from the uncertainties of the CMOR data used will not allow the observation of a resonant peak of the expected size. Detection is expected to be more likely in a ‘swarm encounter year’ (a year in which the geometry between the resonant swarm and Earth is favourable to detection). The velocity uncertainties of a meteor orbit radar (similar to CMOR) need to be improved by a factor of 5 to 10 (relative to the CMOR uncertainties) in order to detect a resonant swarm that is composed of ∼ 30% to ∼ 5% (respectively) of the total number of observed Taurids in a swarm encounter year. An improvement significantly greater than a factor of ∼ 10 is unlikely to result in a significant improvement in the ability to detect the resonant swarm. It is expected that a factor of 10 improvement in radar measurement uncertainties is achievable with the current techniques of radar systems and signal processing. These statistical tests require knowledge of the resonant width of the 7:2 Jovian
Neurodevelopment in Down syndrome: Concordance in humans and models

Great strides have been made over the past 30 years in understanding the neurodevelopmental changes underlying the intellectual disability (ID) in Down syndrome (DS). Detailed studies of human tissue coupled with findings from rodent and induced pluripotent stem cells (iPSCs) model systems have uncovered the changes in neurogenesis, synaptic connectivity, and myelination that drive the anatomical and physiological changes resulting in the disability. However, there remain significant conflicting data between human studies and the models. To fully understand the development of ID in DS, these inconsistencies need to be reconciled. Here, we review the well documented neurodevelopmental phenotypes found in individuals with DS and examine the degree to which widely used models recapitulate these phenotypes. Resolving these areas of discord will further research on the molecular underpinnings and identify potential treatments to improve the independence and quality of life of people with DS.
Remote Healthcare During the COVID-19 Pandemic: Findings for Older Adults in 27 European Countries and Israel

The COVID-19 pandemic exacerbated issues regarding access to healthcare for older people, by far the most vulnerable population group. In particular, older adults avoided seeking medical treatment for fear of infection or had their medical treatments postponed or denied by health facilities or health professionals. In response, remote medical services were recognized as an essential adjustment mechanism to maintain the continuity of healthcare provision. Using the SHARE Corona Survey data, we estimate logistic and multilevel regression models for the remote care of 44,152 persons aged 50 and over in 27 European countries and Israel. Our findings suggest that those aged 80+ were the least likely to use remote healthcare. However, women, better educated individuals, older adults who lived in urban areas, those with no financial strain, and active Internet users used remote medical consultations more often. Those who reported poor or fair health status, two or more chronic diseases, or hospitalization in the last 12 months were significantly more likely to use remote healthcare. Furthermore, remote medical consultations were more frequent for those who had their healthcare postponed or went without it due to fear of coronavirus infection. Finally, older adults used remote care more frequently in countries with less healthcare coverage and lower health expenditures. Health systems should prioritize vulnerable groups in maintaining continuity in access to healthcare, despite the availability of remote care. Policymakers should improve telemedicine regulation and offer incentives for providers of remote healthcare services by adapting reimbursement policies. Remote medical care could play an important role in maintaining healthcare access for older adults and increasing health systems' preparedness in future health emergencies.
The integration of extended reality for student-developed games to support cross-curricular learning

While eXtended Reality (XR) ha s been shown to provide rich promise, its adoption within the educational context for student created games is still limited. Recent advances in XR technology, especially in mobile XR tools, have made XR more accessible. These advances have also enabled the development of student-created XR experiences that provide opportunities for integrating learning with technology skills development. Through the integration of critical digital skills across the curriculum, students can demonstrate a range of learning outcomes across many different learning areas. In this study, we explore how the affordances of XR can be leveraged to enable new learning opportunities, specifically in enabling students to design their own XR learning experiences. We also explore how the added context of XR games provides additional benefits to engage and motivate learners. In this article, we identify and explore twelve affordances framed in the notions of engagement, authenticity and contextualisation. These affordances have been identified in the literature to highlight the benefits of XR and were explored in terms of how the added context of student-created games leveraged these affordances. Drawing on a wider research project, we identify three scenarios that were adopted by three teachers (Mathematics, Science and Language teacher) to teach a range of subjects that drew on XR student-created games. From this analysis, we conclude with six proposed design principles that could be adopted by other teachers to help guide them in applying a similar approach in their teaching.