Miracle-dz/UniFAR-FTUs huggingface dataset:
Reward-Sensitive Basal Ganglia Stabilize the Maintenance of Goal-Relevant Neural Patterns in Adolescents

Abstract Maturation of basal ganglia (BG) and frontoparietal circuitry parallels developmental gains in working memory (WM). Neurobiological models posit that adult WM performance is enhanced by communication between reward-sensitive BG and frontoparietal regions, via increased stability in the maintenance of goal-relevant neural patterns. It is not known whether this reward-driven pattern stability mechanism may have a role in WM development. In 34 young adolescents (12.16–14.72 years old) undergoing fMRI, reward-sensitive BG regions were localized using an incentive processing task. WM-sensitive regions were localized using a delayed-response WM task. Functional connectivity analyses were used to examine the stability of goal-relevant functional connectivity patterns during WM delay periods between and within reward-sensitive BG and WM-sensitive frontoparietal regions. Analyses revealed that more stable goal-relevant connectivity patterns between reward-sensitive BG and WM-sensitive frontoparietal regions were associated with both greater adolescent age and WM ability. Computational lesion models also revealed that functional connections to WM-sensitive frontoparietal regions from reward-sensitive BG uniquely increased the stability of goal-relevant functional connectivity patterns within frontoparietal regions. Findings suggested (1) the extent to which goal-relevant communication patterns within reward-frontoparietal circuitry are maintained increases with adolescent development and WM ability and (2) communication from reward-sensitive BG to frontoparietal regions enhances the maintenance of goal-relevant neural patterns in adolescents' WM. The maturation of reward-driven stability of goal-relevant neural patterns may provide a putative mechanism for understanding the developmental enhancement of WM.
Transnational Perspective and Practices in Early Childhood Education.

This paper explains various good practices and perspectives of Early Childhood Education across the nation. A good number of reviews across the globe has collected from various sources, research projects, PhD thesis and so on which put categorized as knowledge base, developmentally appropriate practice, observation and assessment, positive behavior guidance, inclusive practices, personal professional development. The research mainly focused on the pedagogical process, language development, social and cultural perspectives of preschools. Theses good practices also implemented and recommended at national level of those nations to their preschool/ Early Childhood Education Curriculum policies.
Bioethanol from lignocellulosic materials

Lignocellulosic biomass can be utilised to produce ethanol. There a are two processes involved in the conversion: hydrolysis of cellulose in the cellulosic biomass to produce reducing sugars, and fermentation of the sugars to bioethanol. For this, pretreatments for lignocellulosic materials are required. The goal to any pretreatments is to alter or remove the structural and compositional impediments to hydrolysis and to increase the yields of fermentable sugar. In this work is made a review of the physical or chemical pretreatment methods that could be used to produce bioethanol from cellulosic materials.
Change in Atrial Fibrillation Burden over Time in Patients with Nonpermanent Atrial Fibrillation

Introduction The natural course of atrial fibrillation (AF) is not well defined. We aimed to investigate the change in AF burden over time and its associated risk factors among AF patients. Methods Fifty-four participants with recently documented paroxysmal or persistent AF were enrolled. Main exclusion criteria were permanent AF or previous catheter ablation for AF. AF burden was calculated as time in AF divided by total recording time using yearly continuous 7-day Holter-ECG recordings. A relative change ≥10% or an absolute change >0.5% in AF burden between two yearly Holter-ECG recordings was considered significant. Results Mean age was 67 years, 72% were men. The proportion of patients with no recorded AF increased from 53.7% at baseline to 78.6% (p=0.1) after 4 years of follow-up. In 7-day Holter-ECG recordings performed after baseline, 23.7% of participants had a decrease and 23.7% an increase in AF burden. In separate mixed effect models, AF burden over time was associated with prior stroke (β 42.59, 95% CI (23.40; 61.77); p < 0.0001), BNP (β 0.05, CI (0.02; 0.09); p=0.005) end-diastolic (β 0.49, CI (0.23; 0.74); p=0.0003) as well as end-systolic (β 0.25, CI (0.05; 0.46); p=0.02) left atrial volume, left atrial ejection fraction (β −0.43, CI (−0.76;−0.10); p=0.01), E-wave (β 36.67, CI (12.96; 60.38); p=0.003), and deceleration time (β −0.1, CI (−0.16; −0.05); p=0.002). In a multivariable model, a history of prior stroke (β 29.87, CI (2.61; 57.13); p=0.03) and BNP levels (β 0.05, CI (0.01; 0.08); p=0.007) remained significantly associated with AF burden. Conclusions Few patients with paroxysmal or persistent AF have AF episodes on yearly 7-day Holter-ECG recordings, and AF progression is rare. AF burden was independently associated with a history of prior stroke and BNP levels.
An incoherent feedforward loop interprets NFκB/RelA dynamics to determine TNF‐induced necroptosis decisions

Balancing cell death is essential to maintain healthy tissue homeostasis and prevent disease. Tumor necrosis factor (TNF) not only activates nuclear factor κB (NFκB), which coordinates the cellular response to inflammation, but may also trigger necroptosis, a pro-inflammatory form of cell death. Whether TNF-induced NFκB cross-regulates TNF-induced necroptosis fate decisions is unclear. Live-cell microscopy and model-aided analysis of death kinetics identified a molecular circuit that interprets TNF-induced NFκB/RelA dynamics to control necroptosis decisions. Inducible expression of TNFAIP3/A20 forms an incoherent feedforward loop to interfere with the RIPK3-containing necrosome complex and protect a fraction of cells from transient, but not long-term TNF exposure. Furthermore, dysregulated NFκB dynamics often associated with disease diminish TNF-induced necroptosis. Our results suggest that TNF’s dual roles in either coordinating cellular responses to inflammation, or further amplifying inflammation are determined by a dynamic NFκB-A20-RIPK3 circuit, that could be targeted to treat inflammation and cancer.
THE STORAGE OF FOWL SPERMATOZOA

Polge (1955) stored fowl semen in a glucose-citrate solution with either milk or thin egg albumen. Promising fertility results (50%) were obtained after 24 hr storage. Schlindler, Weinstein, Moses & Gabriel (1955) used synthetic and natural media as diluents and fertility results were poor after 24 hr storage. Lake (1960) used a diluent, calculated to have an osmotic pressure and ionic composition similar to lipidand protein-free seminal plasma, to which was added fructose. Semen, free of transparent fluid, was stored for 24 hr and 64% fertility was obtained. Wilcox & Shorb (1958), Wilcox & Shaffner (1958), Wilcox (1958, 1959a, b, 1960), Wilcox & Wilson (1961) and Wilcox & Clark (1962) used various modifications of a phosphate buffer with antibiotics and diluted the semen in the ratio of 1 part semen to 9 parts diluent for storage. Afterwards the mixture
A Novel Efficient L-Lysine Exporter Identified by Functional Metagenomics

Lack of active export system often limits the industrial bio-based production processes accumulating the intracellular product and hence complexing the purification steps. L-lysine, an essential amino acid, is produced biologically in quantities exceeding two million tons per year; yet, L-lysine production is challenged by efficient export system at high titres during fermentation. To address this issue, new exporter candidates for efficient efflux of L-lysine are needed. Using metagenomic functional selection, we identified 58 genes encoded on 28 unique metagenomic fragments from cow gut microbiome library that improved L-lysine tolerance. These genes include a novel putative L-lysine transporter, belonging to a previously uncharacterized EamA superfamily. Characterization using Xenopus oocyte expression system as well as an Escherichia coli host demonstrates activity as a L-lysine transporter. This novel exporter improved L-lysine tolerance in E. coli by 40% and enhanced the specific productivity of L-lysine in an industrial Corynebacterium glutamicum strain by 12%. Our approach allows the sequence-independent discovery of novel exporters and can be deployed to increase titres and productivity of toxicity-limited bioprocesses.
Disulfide reduction allosterically destabilizes the β-ladder sub-domain assembly within the NS1 dimer of ZIKV

The Zika virus (ZIKV) was responsible for a recent debilitating epidemic that till date has no cure. A potential way to reduce ZIKV virulence is to limit the action of the non-structural proteins involved in its viral replication. One such protein, NS1, encoded as a monomer by the viral genome, plays a major role via symmetric oligomerization. We examine the homodimeric structure of the dominant β-ladder segment of NS1 with extensive all atom molecular dynamics. We find it stably bounded by two spatially separated interaction clusters (C1 and C2) with significant differences in the nature of their interactions. Four pairs of distal, intra-monomeric disulfide bonds are found to be coupled to the stability, local structure, and wettability of the interfacial region. Symmetric reduction of the intra-monomeric disulfides triggers marked dynamical heterogeneity, interfacial wettability and asymmetric salt bridging propensity. Harnessing the model-free Lipari-Szabo based formalism for estimation of conformational entropy (Sconf), we find clear signatures of heterogeneity in the monomeric conformational entropies. The observed asymmetry, very small in the unperturbed state, expands significantly in the reduced states. This allosteric effect is most noticeable in the electrostatically bound C2 cluster that underlies the greatest stability in the unperturbed state. Allosteric induction of conformational and thermodynamic asymmetry is expected to affect the pathways leading to symmetric higher ordered oligomerization, and thereby affect crucial replication pathways. Statement of significance Controlling viral pathogenesis remains a challenge in the face of modern-day epidemics. Though cumbersome and fraught with misleads, most therapeutic endeavors lean towards the design of drug molecules targeting specific proteins involved in viral pathogenesis. This work demonstrates an alternative approach, namely the usage of allosteric intervention to disrupt the binding integrity of the primary domain of the non-structural NS1 protein dimer crucially important in ZIKV virulence. The intervention, triggered by symmetric reduction of the internal monomeric disulfide bonds, results in weakening and distortion of the distal binding interfaces. It further introduces marked structural and entropic asymmetry within the homooligomeric unit, precluding the formation of higher ordered oligomers of high symmetry. The results have important ramifications for consolidated efforts at limiting ZIKV virulence.
Clustering NMR: Machine learning assistive rapid (pseudo) two-dimensional relaxometry mapping

Low-field nuclear magnetic resonance (NMR) relaxometry is an attractive approach for point-of-care testing medical diagnosis, industrial food science, and in situ oil-gas exploration. One of the problem however is, the inherently long relaxation time of the (liquid) sample, (and hence low signal-to-noise ratio) causes unnecessarily long repetition time. In this work, we present a new class of methodology for rapid and accurate object classification using NMR relaxometry with the aid of machine learning. We demonstrate that the sensitivity and specificity of the classification is substantially improved with higher order of (pseudo)-dimensionality (e.g., 2D or multidimensional). This new methodology (termed as Clustering NMR) is extremely useful for rapid and accurate object classification (in less than a minute) using the low-field NMR.
Inclusion of oxidized fish oil in mink diets. 2. The influence on performance and health considering histopathological, clinical‐chemical, and haematological indices

Zusammenfassung Der Einsatz von oxidiertem Fischol im Nerzfutter. 2. Der Einflus auf das Wachstum und einige histologische, klinisch-chemische und hamatologische Parameter In einem Versuch mit 18 ausgewachsenen mannlichen Pastelnerzen uber eine Dauer von 15 Wochen wurde der Einflus von hohen Fischolkonzentrationen (55 % der umsetzbaren Energie) im Futter auf Wachstum und Gesundheit untersucht. Das Fischal wurde dem Basalfutter frisch oder nach vorheriger Oxidation (Peroxidzahl 200 und 400 maqu. O2/kg Ol) zugegeben. Die Vitamin E-Konzentrationen im Futter lagen bei: 74 mg/kg (Gruppe 1, frisches Fischol); 68 mg/kg (Gruppe 2, 200 maqu. O2/kg Ol)); und 64 mg/kg (Gruppe 3, 400 maqu. O2/kg Ol)). Die Selengehalte des Futters waren entsprechend: 0,37 mg, 0,35 mg und 0,42 mg/kg Trockensubstanz, fur Gruppe 1, 2 bzw. 3. Generell stand der Grad der gefundenen pathologischen Veranderungen mit der Qualitat des ver-abreichten Fischols sowie mit der Dauer der Verfutterung in engem Zusammenhang. Die Verfutterung des hoch oxidierten Ols fuhrte zu erheblichen Gewichtseinbusen, die bei zwei Tieren der Versuchsgruppe 3 nach 9 Wochen zum Tode fuhrten. Erhohte Plasmaenzymaktivitaten von CK, ASAT und ALAT wiesen bei dieser Gruppe auf degenerative Veranderungen im Leber- und Muskelgewebe hin. Die Aufnahme von oxidiertem Fischol hatte eine Abnahme der α-Tocopherolgehalte sowie eine Erhohung der GSH-Px-Aktivitat im Blutplasma zur Folge. Unabhangig von der Qualitat des Futterfettes zeigten alle Nerze am Ende des Versuchs niedrige Hamoglobinwerte (5,5–7,9 mmol/l) sowie niedrige Eisenkonzentrationen in der Leber (>300 μg/g Trockensubstanz), welches auf die Entwick-lung einer Eisenmangelanamie hinweist. Die Ergebnisse der histologischen Untersuchung des Darmepithels und des Lebergewebes deuten darauf hin, das oxidiertes Fett lokal sowie systemisch toxisch wirken kann.
Single walled carbon nanotubes induce cytotoxicity and oxidative stress in HEK293 cells

The aim of the present study was to evaluate the potential toxicity and general mechanisms involved in single walled carbon nanotubes (SWCNTs)-induced cytotoxicity using human embryonic kidney cell line (HEK293) cells. Carbon nanotubes (coded as CNT) used in this study were synthesized by the chemical vapor deposition method. To elucidate the possible mechanisms underlying SWCNT-induced cytotoxicity, cell viability, cell membrane damage (lactate dehydrogenase activity (LDH) assay), reduced glutathione (GSH), interleukin-8 (IL-8) and lipid peroxidation products levels were quantitatively assessed following SWCNT exposure for 48 hr using HEK293 cells. Exposure of cells to SWCNT at 3–300 μg/ml produced significant reduction in cell viability in a concentration-dependent manner. The IC50 value of SWCNT was found to be 87.58 μg/ml. Exposure of HEK cells to SWCNT at 10–100 μg/ml resulted in concentration-dependent cell membrane damage, increased production of IL-8, elevated levels of thiobarbituric acid reactive substances like malondialdehyde and decreased intracellular GSH levels. In summary, exposure to SWCNT resulted in a concentration-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.
Interoceptive Awareness and Affective Empathy Share Intrinsic Spatial Connectivity and Temporal Variability

Awareness of internal bodily sensations (interoception, IA) and its connection to complex socio-emotional phenomena like empathy have been postulated, yet its neural basis remains poorly understood. The goal of the present fMRI study employs a data-driven approach to investigate whether Cognitive or Affective empathy and IA share spatial resting state connectivity (rsFC) and/or temporal variability. Healthy participants viewed an abstract movie demonstrated to evoke strong connectivity in intrinsic brain networks (InScapes), and resultant resting-state fMRI spatial connectivity and temporal variability data was correlated with their self-reported empathy and interoception scores (IRI and MAIA, respectively). We demonstrate a complex bidirectional behavioral and neurological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA are distributed across similar spatial and temporal neural systems, while Cognitive empathy and IA are only related temporally. Specifically, increased spatial rsFC within the R IFO was associated with a decreased awareness of inner body sensations, but increased vicarious emotional experience. Furthermore, enhanced information integration between an interoceptive experience network was related to both increased sensitivity of internal sensation, but in addition, to a dampening of discomfort arising from witnessing another’s pain. Finally, improved processing between brain regions part of a mentalizing network related to not only a better sense of mind-body interconnectedness but also an improved ability to take someone’s perspective. Our findings could have implications for understanding differences in empathic and interoceptive functioning without needing to probe participants with specialized tasks or questionnaires.
A mouse model for spinal muscular atrophy provides insights into non-alcoholic fatty liver disease pathogenesis

Background & aims Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and death in children. SMA patients are more susceptible to dyslipidemia as well as liver steatosis, features reproduced in SMA mouse models. As current pre-clinical models of NAFLD are invariably imperfect and generally take a long time to develop, the rapid development of liver steatosis in SMA mice provides a means to identify molecular markers of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Smn2B/- mice, a model of severe SMA, display typical features of NAFLD/non-alcoholic steatohepatitis (NASH). Methods Biochemical, histological, electron microscopy, proteomic, and high-resolution respirometry were used. Results The Smn2B/- mice develop steatohepatitis early in life. The consequent liver damage arises from mitochondrial reactive oxygen species production and results in impaired hepatic function including alterations in protein output, complement, coagulation, iron homeostasis, and IGF-1 metabolism. The steatohepatitis is reversible by AAV9-SMN gene therapy. The NAFLD phenotype is likely due to non-esterified fatty acid (NEFA) overload from peripheral lipolysis, subsequent to hyperglucagonemia compounded by reduced muscle use. Mitochondrial β-oxidation contributed to hepatic damage as we observed enhanced hepatic mitochondrial β-oxidation and reactive oxygen species production. Hepatic mitochondrial content, however, was decreased. In contrast to typical NAFLD/NASH, the Smn2B/- mice lose weight due to their neurological condition, develop hypoglycemia and do not develop hepatic fibrosis. Conclusion The Smn2B/- mice represent a good model of microvesicular steatohepatitis. Like other models, it is not representative of the complete NAFLD/NASH spectrum. Nevertheless, it offers a reliable, low-cost, early onset model that is not dependent on diet to identify molecular players in NAFLD pathogenesis and can serve as one of the very few models of microvesicular steatohepatitis for both adult and pediatric populations.
Priming of MSCs with inflammation-relevant signals affects extracellular vesicle biogenesis, surface markers, and modulation of T cell subsets

Although considerable evidence exists supporting the use of mesenchymal stromal cells (MSCs) for treating immune diseases, successful clinical translation has been challenging and has led researchers to investigate cell-free alternatives. MSC-derived extracellular vesicles (MSC-EVs) have been shown to mediate a significant portion of the observed therapeutic effect, including immunosuppression. MSCs have been shown to respond to different aspects of the injury microenvironment such as inflammatory cytokines and hypoxia, although acidosis has not been investigated and different conditions have not been assessed in terms of their effects on MSC-EV function. This study investigated the effects of acidosis, hypoxia, and inflammatory cytokine priming on MSCs and MSC-EVs. We cultured MSCs in the presence of acidosis, hypoxia, or inflammatory cytokines (Interferon-gamma and Tumor Necrosis Factor-alpha) and compared the characteristics of their EVs as well as their uptake by and suppression of different T cell subsets. MSCs showed a greater effect on suppressing activated CD4+ and CD8+ T cells than MSC-EVs. However, MSC-EVs from MSCs primed with acidosis increased CD4+ and CD8+ regulatory T cell frequency in vitro. This functional response was reflected by MSC-EV uptake. MSC-EVs from acidosis-primed MSCs were taken up by CD4+ and CD8+ regulatory T cells at a significantly higher level than MSC-EVs from control, hypoxic, and inflammatory cytokine groups. These data suggest that a simple low-cost alteration in MSC culture conditions, acidosis, can generate extracelluar vesicles that have a desirable influence on anti inflammatory T cell subtypes.
SARM1 depletion rescues NMNAT1 dependent photoreceptor cell death and retinal degeneration

Leber congenital amaurosis type 9 is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.
Ndel1 promotes keratin assembly and desmosome stability

Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes which provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes actively promote keratin assembly in addition to binding pre-assembled filaments. We recently discovered that Ndel1 is a desmosome-associated protein in differentiated epidermis. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 is necessary for robust desmosome-keratin association and sufficient to reorganize keratins to distinct cellular sites. Lis1, a Ndel1 binding protein, is required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identify Ndel1 as a desmosome-associated protein which promotes local assembly/organization of keratin filaments and is essential for both robust cell adhesion and epidermal barrier function.