Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategies of developmental vestibular plasticity after unilateral embryonic ear removal in Xenopus laevis

Appropriate gaze control mechanisms rely on bilateral mirror-symmetric vestibular endorgans, central circuits, and extraocular motor effectors. Embryonic removal of one inner ear prior to the formation of these structures was used to evaluate the extent to which animals can develop appropriate motor outputs in the presence of only a singular inner ear. Near-congenital one-eared tadpoles subjected to separate or combinatorial visuo-vestibular motion stimulation exhibited vestibular-ocular reflexes, though smaller in gain compared to controls, whereas isolated visuo-motor responses remained largely unaltered. Surprisingly, direction-specific responses in one-eared tadpoles revealed a spectrum of vestibulo-ocular reflex performance, where in many cases rather robust responses were observed during head motion towards the missing ear. Rotation toward the remaining ear elicited eye movements which were often severely attenuated. This suggests that embryonically generated one-eared animals develop bidirectional vestibular signal detection and downstream processing capacities that allow activation of robust compensatory eye movements. However, this capability seems to occur at the expense of performance of vestibular reflexes during motion in the canonical activation direction of the singular ear. Consequently, the development of central vestibulo-motor circuits in one-eared animals likely relies on strategies in which the outcome for gaze stabilization is driven by balanced homeostatic levels and individual temporal tuning of abducens motoneuron activity. Despite the lack of bilateral symmetric vestibular afferent input, the developing central nervous system is capable of creating a framework for symmetric sensorimotor transformations.
Molecular insights into human Shieldin complex assembly and recruitment to DSBs

The Shieldin complex represses end resection at DNA double-strand breaks (DSBs) and thereby serves as a pro-non homologous end joining (NHEJ) factor in the G1 phase of the cell cycle. Its components SHLD1, SHLD2, SHLD3 and REV7 are recruited in a hierarchical fashion. SHLD3 and REV7 localize first to DSBs, while the subsequently recruited SHLD2 is the only known DNA binding protein in the complex. The molecular details of the initial recruitment of SHLD3 and REV7, and the subsequent assembly of Shieldin on DSBs are unclear. Here, we report the identification of a promiscuous DNA binding domain in the C-terminal half of SHLD3. At the N-terminus, SHLD3 interacts with a dimer of REV7 molecules. We show that the interaction between SHLD3 and the first REV7 is remarkably slow, which is likely due to the substantial activation energy required to remodel mobile structural elements within the REV7 molecule to allow for binding to SHLD3. In contrast, the interaction between SHLD3 and SHLD2 with a second REV7 molecule is fast and does not require structural remodelling. Overall, these results provide insights into the rate-limiting step of the molecular assembly and recruitment of Shieldin complex at DNA DSBs.
Fine temporal brain network structure modularizes and localizes differently in men and women: Insights from a novel explainability framework

Deep learning has become an effective tool for classifying biological sex based on functional magnetic resonance imaging (fMRI), but research on what features within the brain are most relevant to this classification is still lacking. Model interpretability has become a powerful way to understand “black box” deep-learning models and select features within the input data that are most relevant to the correct classification. However, very little work has been done employing these methods to understand the relationship between the temporal dimension of functional imaging signals and classification of biological sex, nor has there been attention paid to rectifying problems and limitations associated with feature explanation models, e.g. underspecification and instability. We provide a methodology to limit the impact of underspecification on the stability of the measured feature importance, and then, using intrinsic connectivity networks (ICNs) from fMRI data, we provide a deep exploration of sex differences among functional brain networks. We report numerous conclusions, including activity differences in the visual and cognitive domains, as well as major connectivity differences.
Dynamics of mRNA fate during light stress and recovery: from transcription to stability and translation

Transcript stability is an important determinant of its abundance and, consequently, translation. However, it is unclear the extent to which it is modulated between environmental conditions. We previously hypothesised that recovery-induced transcript destabilisation facilitated a phenomenon of rapid recovery gene down-regulation (RRGD) in Arabidopsis thaliana following stress, based on mathematical calculations to account for ongoing transcription. Here, we test this hypothesis, and investigate processes regulating transcript abundance and fate, by quantifying changes in transcription, stability, and translation before, during, and after light stress. We adapt syringe infiltration to apply a transcriptional inhibitor to soil-grown plants in combination with stress. Compared to measurements in juvenile plants and cell culture, we find reduced stability in a range of transcripts. We also observe transcript destabilisation during light stress, followed by stabilisation upon recovery. Alongside fast transcriptional shut-off in recovery, this destabilisation appears to facilitate RRGD. Translation was dynamic over the course of light stress and recovery, with substantial transcript-specific increases in ribosome-association, independent of changes in total transcript abundance, observed after 30 minutes of light stress. Taken together, we provide evidence for the combinatorial regulation of transcription, stability, and translation that occurs to facilitate responses to light stress and recovery.
Interstitial Notch signaling regulates nephron development via the Gata3-Renin axis in the mouse kidney

Notch signaling in the renal interstitium is known to be required for the formation of mesangial cells and Ren1 (Renin)-expressing cells. However, little is known about how interstitial Notch signaling affects nephron development. We found that blocking Notch signaling in the renal interstitium in mice caused developmental arrest of proximal tubules accompanied by defective formation of mesangial cells. We examined the interstitial Pdgfrb mutant kidney which exhibits a similar mesangial cell defect and found that the Pdgfrb mutant kidney showed normal proximal tubule development, suggesting that the absence of mesangial cells was not the cause of defective proximal tubule development. Our single cell RNA-seq analysis of the interstitial Rbpj mutant kidney showed that a subset of proximal tubule genes were downregulated in the mutant kidney and that Gata3 was downregulated in the mutant interstitium during the development of Ren1-expressing cells. We found that deleting Gata3 in the interstitium caused the loss of Renin and the developmental arrest of proximal tubules, phenocopying the interstitial Notch/Rbpj mutants. Our results suggest that interstitial Notch signaling regulates the development of proximal tubules via the Gata3-Renin axis in the mouse kidney.
Cooperation between Imp2p and Cdc15p imparts stiffness to the constricting contractile ring in fission yeast

The contractile ring must anchor to the plasma membrane and cell wall to transmit its tension to the plasma membrane. F-BAR domain containing proteins including Cdc15p and Imp2p in fission yeast are likely candidate anchoring proteins based on their mutant phenotypes. Cdc15p is a node component, links the actin bundle to the plasma membrane, recruits Bgs1p to the division plane, prevents contractile ring sliding, and contributes to the stiffness of the contractile ring. Less is known about Imp2p. We found that similarly to Cdc15p, Imp2p contributes to the stiffness of the contractile ring and assembles into protein clusters. Imp2p clusters contain ∼8 Imp2p dimers and depend on the actin network for their stability at the division plane. Importantly, Imp2p and Cdc15p reciprocally affect the amount of the other in the contractile ring indicating that the two proteins influence each other during cytokinesis and may explain their similar phenotypes.
TMS-evoked responses are driven by recurrent large-scale network dynamics

A major question in systems and cognitive neuroscience is to what extent neurostimulation responses are driven by recurrent activity. This question finds sharp relief in the case of TMS-EEG evoked potentials (TEPs). TEPs are spatiotemporal waveform patterns with characteristic inflections at ∼50ms, ∼100ms, and ∼150-200ms following a single TMS pulse that disperse from, and later reconverge to, the primary stimulated regions. What parts of the TEP are due to recurrent activity? And what light might this shed on more general principles of brain organization? We studied this using source-localized TMS-EEG analyses and whole-brain connectome-based computational modelling. Results indicated that recurrent network feedback begins to drive TEP responses from ∼100ms post-stimulation, with earlier TEP components being attributable to local reverberatory activity within the stimulated region. Subject-specific estimation of neurophysiological parameters additionally indicated an important role for inhibitory GABAergic neural populations in scaling cortical excitability levels, as reflected in TEP waveform characteristics.
A comprehensive survey of ubiquitous manufacturing research

In the past 10 years, ubiquitous manufacturing (UM) has received a growing amount of attention among researchers in the manufacturing community because ubiquitous computing technologies (UCTs) can be applied to address a wide range of issues in the manufacturing industry, e.g. manufacturing processes and equipment, manufacturing management and planning. However, to the best of the authors’ knowledge, there is a lack of comprehensive and critical review from a holistic view of the state-of-the-art UM and its systems. This paper aims to provide a concise overview of the technical features, characteristics and broad range of applications of UM systems published between 1997 and 2017. Among these selected articles, more than 70% of them were published between 2012 and 2017, and they are considered as recent pertinent works which will be discussed in detail. The unique aspects of this paper lie in that this paper summarises and analyses a broad range of the state-of-the-art implementation of UM systems from a holistic and comprehensive view of manufacturing technology, including UM for manufacturing processes, manufacturing control systems, logistics, remanufacturing, cloud manufacturing, production scheduling, production quality control and evaluation, etc. In addition, the current limitation factors and future trends of UM development will also be discussed.
Separation of transcriptional repressor and activator functions in HDAC3

The histone deacetylase HDAC3 is associated with the NCoR/SMRT co-repressor complex and its canonical function is in transcriptional repression, but it can also activate transcription. Here we show that the repressor and activator functions of HDAC3 can be genetically separated in Drosophila. A lysine substitution in the N-terminus (K26A) disrupts its catalytic activity and activator function, whereas a combination of substitutions (HEBI) abrogating the interaction with SMRTER enhance repressor activity beyond wild-type in the early embryo. We conclude that the critical functions of HDAC3 in embryo development involve catalytic-dependent gene activation and non-enzymatic repression by several mechanisms, including tethering of loci to the nuclear periphery.
SARS-CoV-2 type I Interferon modulation by nonstructural proteins 1 and 2

Since the beginning of the COVID-19 pandemic, enormous efforts were devoted to understanding how SARS-CoV-2 escapes the antiviral response. Yet, modulation of type I interferons (IFNs) by this virus is not completely understood. Using in vitro and in vivo approaches, we have characterized the type I IFN response during SARS-CoV-2 infection as well as immune evasion mechanisms. The transcriptional and translational expression of IFNs, cytokines and chemokines were measured in lung homogenates of Wuhan-like, Beta, and Delta SARS-CoV-2 K18-ACE2 transgenic mice. Using in vitro experiments, we measured SARS-CoV-2 and its non-structural proteins 1 and 2 (Nsp1-2) to modulate expression of IFNβ and interferon-stimulated genes (ISG). Our data show that infection of mice with Wuhan-like virus induces robust expression of Ifna and Ifnb1 mRNA and limited type I production. In contrast, Beta and Delta variant infected mice failed to activate and produce IFNα. Using in vitro systems, Ifnβ gene translation inhibition was observed using an Nsp1 expression vector. Conversely, SARS-CoV-2 and its variants induce robust expression of NF-κB-driven genes such as those encoding CCL2 ans CXCL10 chemokines. We also identified Nsp2 as an activator of NF-κB that partially counteracts the inhibitory actions of Nsp1. In summary, our work indicates that SARS-CoV-2 skews the antiviral response in favor of an NF-κB-driven inflammatory response, a hallmark of acute COVID-19, and that Nsp2 is partly responsible for this effect. Importance Several studies suggest that SARS-CoV-2 possess multiple mechanisms aimed shunting the type I interferon response. However, few studies have studied type I IFN modulation in the context of infection. Our work indicates that mice and human cells infected with SARS-CoV-2 produce sufficient type I IFN to activate an antiviral response, despite Nsp1 translational blockade of IFNΒ1 mRNA. In contrast to Wuhan-like virus, Beta and Delta variants failed to induce Ifna gene expression. Our work also showcases the importance of studying protein functions in the context of infection, as demonstrated by the partial antagonizing properties of the Nsp2 protein on the activities of Nsp1. Our studies also highlight that the innate immune response triggered by SARS-CoV-2 is chiefly driven by NF-κB responsive genes for which Nsp2 is partially responsible.
Mitochondrial Defects in Diabetic Mouse Islets Molecular and Metabolic Evidence for Mitochondrial Defects Associated With -Cell Dysfunction in a mouse model of Type 2 Diabetes

This is an uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association, publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals. org. Diabetes Publish Ahead of Print, published online November 10, 2009
Overview of the European "Particulates" Project on the Characterization of Exhaust Particulate Emissions from Road Vehicles: Results for Light-Duty Vehicles

This paper presents an overview of the results on light duty vehicles collected in the “PARTICULATES” project which aimed at the characterization of exhaust particle emissions from road vehicles. A novel measurement protocol, developed to promote the production of nucleation mode particles over transient cycles, has been successfully employed in several labs to evaluate a wide range of particulate properties with a range of light duty vehicles and fuels. The measured properties included particle number, with focus separately on nucleation mode and solid particles, particle active surface and total mass. The vehicle sample consisted of 22 cars, including conventional diesels, particle filter equipped diesels, port fuel injected and direct injection spark ignition cars. Four diesel and three gasoline fuels were used, mainly differentiated with respect to their sulfur content which was ranging from 300 to below 10 mg/kg. All data (both real time and integrated) were collected in a common data base and centrally analyzed using common formats and methodologies, in order to eliminate inconsistencies and optimize comparability. Results show that particulate emissions are dramatically reduced by the combination of particulate traps and low sulfur fuels. However, particulate emissions patterns are also shown to differ between type approval and motorway driving conditions; this applying to both vehicle technology and fuel sulfur effects; the latter becoming more obvious under high temperature conditions. The relevance of the current emissions certification cycle should be considered with regard to next steps in vehicle emissions legislation and the various vehicle technologies that are expected to be introduced. The study provides evidence that both particle number and active surface measurements offer the potential for greater sensitivity in evaluating particulate emissions, without any significant increase in the variability of results. More importantly, the study revealed that the usage of a dedicated sampling procedure is in the position to yield sufficiently repeatable results of solid and total particle populations, especially over transient tests.
Cholesterol Efflux Capacity as a Therapeutic Target

T he majority of efforts to halt atherosclerosis have been focused on limiting cholesterol influx into resident macrophages within the arterial wall by reducing circulating levels of atherogenic lipoproteins, which are collectively reflected by non–high-density lipoprotein cholesterol (non–HDL-C) levels. This strategy has been remarkably effective in reducing the incidence of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention populations, largely through lifestyle modification and use of statin pharmacotherapies. However, reverse cholesterol transport, which is the movement of cholesterol from tissues to the liver and out of the body, is also an important mechanism for maintaining cellular homeostasis. Cholesterol efflux from macrophages is the first critical step of reverse cholesterol transport in the arterial wall. Preclinical and limited human clinical studies support the concept that improving cholesterol efflux promotes plaque regression, shifts macrophages from pro-inflammatory to anti-inflammatory states, promotes egress of lipid-laden macrophages out of the arterial wall, and reduces atherosclerotic lesion size (1). HDL is the key mediator of cholesterol efflux
Expectation-Focused Psychological Interventions (EFPI)

Zusammenfassung Erkenntnisse der Placebo-Forschung legen nahe, dass Erwartungen in Bezug auf die Wirksamkeit einer Behandlung ein entscheidender Prädiktor für den tatsächlichen Behandlungserfolg sind. Dieser Einfluss von Erwartungen wurde sowohl für die Behandlung von körperlichen Erkrankungen als auch von psychischen Störungen nachgewiesen. Bei psychischen Störungen spielen neben den Erwartungen an den Behandlungserfolg noch weitere Erwartungen eine wichtige Rolle. Dazu gehören störungsspezifische Erwartungen (z.B. Erwartungen bezüglich des Eintretens eines katastrophalen Ereignisses bei Patienten mit Angststörungen) ebenso wie Erwartungen über sich selbst und andere (z.B. «Andere werden mich ablehnen, wenn sie meine wahre Persönlichkeit kennenlernen»). Das Modell der Erwartungsverletzung (engl. expectation violation = ViolEx) stellt dar, wie Erwartungen bei psychischen Störungen entstehen, wie sie sich verändern und warum sie trotz gegensätzlicher Erfahrungen oft persistieren. Darauf aufbauend stellen wir einen Behandlungsansatz mit Fallbeispielen vor, der psychotherapeutische Interventionen durch das Fokussieren auf Patientenerwartungen optimieren kann (Erwartungsfokussierte psychotherapeutische Interventionen; EFPI). Zwar beinhalten einige etablierte psychotherapeutische Interventionen bereits (zum Teil implizit) erwartungsmodifizierende Elemente, doch EFPI stellen einen fokussierteren Ansatz dar, mit dessen Hilfe die Gründe für wenig erfolgreich verlaufende Therapien identifiziert werden und Ansatzpunkte für weitere Interventionen gefunden können.
The Factors University Location towards Student Choice to Private Universities

The aim of this research was to evaluate the factors that affected student enrolment in private university in Malaysia. There are huge declining numbers of student who enrol to private university. This present a result from a survey collected through questionnaires which was email to 1,000 students who accept the offer from private university in Kuala Lumpur and Selangor. The finding shows that there is a significant relationship between location and student decision making. Apart from that, this study provides several implications for the management of universities especially for the marketing and admission department as well as the top management of university in which they can identify what exactly the causes of the declining number in their university.
Patients at High and Low Risk During Acute Myocardial Infarction

This prospective study compares the outcome of patients with acute myocardial infarction managed by mobile intensive care (paramedic phase) with that of similar patients managed by basic emergency medical care (control phase) in the same community before the introduction of paramedics. All paramedic-transported patients were managed according to a standard chest pain protocol with use of prophylactic lidocaine and, as needed, treatment for sinus bradycardia, hypotension and life-threatening ventricular arrhythmia. There were no specific interventions for supraventricular tachyarrhythmia or hypertension. All patients were treated under similar in-hospital protocols. Percent mortality in patients with hypotension, the highest risk subgroup in the control phase, was significantly lowered with paramedic-level care (69 versus 10%, p = 0.01). Patients with hypertension, a relatively low risk
Multi Vehicle-Type Right Turning Gap-Acceptance and Capacity Analysis at Uncontrolled Urban Intersections

Intersections are the critical zones where conflicting, merging and diverging movements influence the intersection capacity. Uncontrolled intersections in particular pose dangerous situations to vehicular traffic. During peak vehicular flow, the unpredictable crossing behavior of minor stream vehicles induces delay and reduces the capacity of the intersection. Capacity at uncontrolled intersections is typically measured either by gap acceptance method, empirical regression approaches and conflict technique. Gap acceptance is an important characteristic for analyzing uncontrolled intersections. The behavior of different vehicle types and gap of subject vehicle type from minor street taking right turn to merge with major traffic stream is analyzed using gap acceptance method. The objective of the current study is to analyze the effect of major stream vehicle type combinations on the minor stream vehicle gap-acceptance behavior and to determine the capacity of the minor stream taking into account the influence of the right turning vehicles. The capacity of minor stream calculated using Highway Capacity Manual (HCM) 2010, Luttenin’s model, and Tanner’s model are compared. It is observed that two wheelers are more aggressive than three wheelers for most of the major stream vehicular combinations observed in this study.