Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Size and Geographical Origin on Atlantic salmon, Salmo salar, Mucin O-Glycan Repertoire

Mucin glycans govern pathogen adhesion, growth and virulence. We analyzed the O-glycome from six Atlantic salmon cohorts grown under various conditions from Sweden, Norway and Australia using LC-MS. The low interindividual variation identified may be a concern because interindividual variation is considered a population based defense against infection. The 169 identified structures represent a library for identifying structures important for host-pathogen interactions, understanding population differences of salmon mucin glycosylation in resistance to diseases and during breeding and selection of strains. Graphical Abstract Highlights Atlantic salmon O-glycome expanded to 169 structures in three epithelia. Low interindividual variation amongst all populations and geographical regions. Small variations in glycosylation between geographical locations and fish size. Prominent fucosylation in gastrointestinal mucins from Tasmanian fish. Diseases cause ethical concerns and economic losses in the Salmonid industry. The mucus layer comprised of highly O-glycosylated mucins is the first contact between pathogens and fish. Mucin glycans govern pathogen adhesion, growth and virulence. The Atlantic salmon O-glycome from a single location has been characterized and the interindividual variation was low. Because interindividual variation is considered a population-based defense, hindering the entire population from being wiped out by a single infection, low interindividual variation among Atlantic salmon may be a concern. Here, we analyzed the O-glycome of 25 Atlantic salmon from six cohorts grown under various conditions from Sweden, Norway and Australia (Tasmania) using mass spectrometry. This expanded the known Atlantic salmon O-glycome by 60% to 169 identified structures. The mucin O-glycosylation was relatively stable over time within a geographical region, but the size of the fish affected skin mucin glycosylation. The skin mucin glycan repertoires from Swedish and Norwegian Atlantic salmon populations were closely related compared with Tasmanian ones, regardless of size and salinity, with differences in glycan size and composition. The internal mucin glycan repertoire also clustered based on geographical origin and into pyloric cecal and distal intestinal groups, regardless of cohort and fish size. Fucosylated structures were more abundant in Tasmanian pyloric caeca and distal intestine mucins compared with Swedish ones. Overall, Tasmanian Atlantic salmon mucins have more O-glycan structures in skin but less in the gastrointestinal tract compared with Swedish fish. Low interindividual variation was confirmed within each cohort. The results can serve as a library for identifying structures of importance for host-pathogen interactions, understanding population differences of salmon mucin glycosylation in resistance to diseases and during breeding and selection of strains. The results could make it possible to predict potential vulnerabilities to diseases and suggest that inter-region breeding may increase the glycan diversity.
Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction.

RATIONALE Hypoxic pulmonary vasoconstriction (HPV) optimizes systemic oxygen delivery by matching ventilation to perfusion. HPV is intrinsic to pulmonary artery smooth muscle cells (PASMCs). Hypoxia dilates systemic arteries, including renal arteries. Hypoxia is sensed by changes in mitochondrial-derived reactive oxygen species, notably hydrogen peroxide (H2O2) ([H2O2]mito). Decreases in [H2O2]mito elevate pulmonary vascular tone by increasing intracellular calcium ([Ca2+]i) through reduction-oxidation regulation of ion channels. Although HPV is mimicked by the Complex I inhibitor, rotenone, the molecular identity of the O2 sensor is unknown. OBJECTIVE To determine the role of Ndufs2 (NADH [nicotinamide adenine dinucleotide] dehydrogenase [ubiquinone] iron-sulfur protein 2), Complex I's rotenone binding site, in pulmonary vascular oxygen-sensing. METHODS AND RESULTS Mitochondria-conditioned media from pulmonary and renal mitochondria isolated from normoxic and chronically hypoxic rats were infused into an isolated lung bioassay. Mitochondria-conditioned media from normoxic lungs contained more H2O2 than mitochondria-conditioned media from chronic hypoxic lungs or kidneys and uniquely attenuated HPV via a catalase-dependent mechanism. In PASMC, acute hypoxia decreased H2O2 within 112±7 seconds, followed, within 205±34 seconds, by increased intracellular calcium concentration, [Ca2+]i. Hypoxia had no effects on [Ca2+]i in renal artery SMC. Hypoxia decreases both cytosolic and mitochondrial H2O2 in PASMC while increasing cytosolic H2O2 in renal artery SMC. Ndufs2 expression was greater in PASMC versus renal artery SMC. Lung Ndufs2 cysteine residues became reduced during acute hypoxia and both hypoxia and reducing agents caused functional inhibition of Complex I. In PASMC, siNdufs2 (cells/tissue treated with Ndufs2 siRNA) decreased normoxic H2O2, prevented hypoxic increases in [Ca2+]i, and mimicked aspects of chronic hypoxia, including decreasing Complex I activity, elevating the nicotinamide adenine dinucleotide (NADH/NAD+) ratio and decreasing expression of the O2-sensitive ion channel, Kv1.5. Knocking down another Fe-S center within Complex I (Ndufs1, NADH [nicotinamide adenine dinucleotide] dehydrogenase [ubiquinone] iron-sulfur protein 1) or other mitochondrial subunits proposed as putative oxygen sensors (Complex III's Rieske Fe-S center and COX4i2 [cytochrome c oxidase subunit 4 isoform 2] in Complex IV) had no effect on hypoxic increases in [Ca2+]i. In vivo, siNdufs2 significantly decreased hypoxia- and rotenone-induced constriction while enhancing phenylephrine-induced constriction. CONCLUSIONS Ndufs2 is essential for oxygen-sensing and HPV.
A primer on dichotic listening as a paradigm for the assessment of hemispheric asymmetry

ABSTRACT Dichotic listening is a well-established method to non-invasively assess hemispheric specialization for processing of speech and other auditory stimuli. However, almost six decades of research also have revealed a series of experimental variables with systematic modulatory effects on task performance. These variables are a source of systematic error variance in the data and, when uncontrolled, affect the reliability and validity of the obtained laterality measures. The present review provides a comprehensive overview of these modulatory variables and offers both guiding principles as well as concrete suggestions on how to account for possible confounding effects and avoid common pitfalls. The review additionally provides guidance for the evaluation of past studies and help for resolving inconsistencies in the available literature.
Don't throw the fish out with the respirometry water

Dr Wood's Commentary ([Wood, 2018][1]) provides six reasons to question the usefulness of P crit and proposes alternative Ṁ O2 versus P O2 analyses as its replacement. While we agree with some of Dr Wood's arguments, we feel that none of them warrant abandoning P crit, especially in favour of
Predictive validity of developmental milestones for detecting limited intellectual functioning

Developmental milestones are commonly used in child health care, although from many milestones the predictive validity has not been adequately assessed. We aimed to determine the predictive validity of 75 developmental milestones for detecting limited intellectual functioning that can be obtained before the age of 4 years. We performed a case-control study with 148 children aged 5–10 years with limited intellectual functioning (IQ 50–69), who were in special education (cases) and a random sample of 300 children aged 5–10 years who were in regular elementary education (controls). Developmental milestones scores were retrieved from Child Healthcare files. We calculated sensitivity, specificity, positive likelihood ratios (LR+) and diagnostic odds ratios (DOR) for limited intellectual functioning. The LR+ determines whether a test result changes the probability that a condition exists. Given the prevalence of intellectual disability (1–3%), we considered that an LR+ > 10 would be clinically useful, as it increases the a priori probability of limited intellectual functioning from 2% to a posteriori probability of at least 17%. Out of 75 assessed milestones, 50 were included in the analysis. We found nine milestones to have a significant adjusted (for socio-economic status and prematurity) DOR > 1 and a significant LR+ > 10 (assessment age in months between brackets): ‘says "dada-baba‴ (9), ‘balances head well while sitting’ (9), ‘sits on buttocks while legs stretched’ (9), ‘babbles while playing’ (12), ‘sits in stable position without support’ (12), ‘walks well alone’ (24), ‘says "sentences" of 3 or more words’ (36), ‘places 3 forms in form-box’ (36) and ‘copies circle’ (48). Sensitivities of these 9 milestones varied from 8–54%, specificities of these 9 milestones varied from 95–100%. Combining these milestones at 9, 12, and 36 months respectively resulted in sensitivities of 27–60% and specificities of 94–99%. These nine developmental milestones have substantial predictive validity for limited intellectual functioning.
A Ferrite Synaptic Transistor with Topotactic Transformation

Hardware implementation of artificial synaptic devices that emulate the functions of biological synapses is inspired by the biological neuromorphic system and has drawn considerable interest. Here, a three‐terminal ferrite synaptic device based on a topotactic phase transition between crystalline phases is presented. The electrolyte‐gating‐controlled topotactic phase transformation between brownmillerite SrFeO2.5 and perovskite SrFeO3−δ is confirmed from the examination of the crystal and electronic structure. A synaptic transistor with electrolyte‐gated ferrite films by harnessing gate‐controllable multilevel conduction states, which originate from many distinct oxygen‐deficient perovskite structures of SrFeOx induced by topotactic phase transformation, is successfully constructed. This three‐terminal artificial synapse can mimic important synaptic functions, such as synaptic plasticity and spike‐timing‐dependent plasticity. Simulations of a neural network consisting of ferrite synaptic transistors indicate that the system offers high classification accuracy. These results provide insight into the potential application of advanced topotactic phase transformation materials for designing artificial synapses with high performance.
An N-terminal Ca2+-binding motif regulates the secretory pathway Ca2+/Mn2+-transport ATPase SPCA1

The Ca2+/Mn2+ transport ATPases 1a and 2 (SPCA1a/2) are closely related to the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and are implicated in breast cancer and Hailey–Hailey skin disease. Here, we purified the human SPCA1a/2 isoforms from a yeast recombinant expression system and compared their biochemical properties after reconstitution. We observed that the purified SPCA1a displays a lower Ca2+ affinity and slightly lower Mn2+ affinity than SPCA2. Remarkably, the turnover rates of SPCA1a in the presence of Mn2+ and SPCA2 incubated with Ca2+ and Mn2+ were comparable, whereas the turnover rate of SPCA1a in Ca2+ was 2-fold higher. Moreover, we noted an unusual biphasic activation curve for the SPCA1a ATPase and autophosphorylation activity, not observed with SPCA2. We also found that the biphasic pattern and low apparent ion affinity of SPCA1a critically depends on ATP concentration. We further show that the specific properties of SPCA1a at least partially depend on an N-terminal EF-hand–like motif, which is present only in the SPCA1a isoform and absent in SPCA2. This motif binds Ca2+, and its mutation lowered the Ca2+ turnover rate relative to that of Mn2+, increased substrate affinity, and reduced the level of biphasic activation of SPCA1a. A biochemical analysis indicated that Ca2+ binding to the N-terminal EF-hand–like motif promotes the activity of SPCA1a by facilitating autophosphorylation. We propose that this regulation may be physiologically relevant in cells with a high Ca2+ load, such as mammary gland cells during lactation, or in cells with a low ATP content, such as keratinocytes.
Critique of the 2017 epileptic seizure and epilepsy classifications

This article critiques the International League Against Epilepsy (ILAE) 2015‐2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four‐level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.
A randomized clinical prospective trial comparing split-dose picosulfate/ magnesium citrate and polyethylene glycol for colonoscopy preparation

Background Colonoscopy remains the gold standard for the investigation of abnormalities within the colon. However, its success is highly dependent on the quality of bowel preparation. The objective of this study was to compare the bowel preparation efficacy of picosulfate/magnesium citrate (PMC) vs polyethylene glycol (PEG) in a one-day vs two-day split dose regimen. Methods A prospective, randomized, controlled trial was conducted at the Forzani & MacPhail Colon Cancer Screening Centre in Calgary, Canada. 171 colonoscopy outpatients were randomized to split-dose PMC or PEG lavage as well as into one-day split or two-day split regimens in blocks of eight. Bowel preparation quality was recorded in a blinded manner by the endoscopist using the Ottawa Bowel Preparation Scale (OBPS) prior to washing or suctioning. The scale results were analyzed using a two-factor analysis of variance. Results 141 patients received complete colonoscopies (PMC-71; PEG-70). PEG was found to be superior to PMC (mean OBPS: 4.14 ± 2.64 vs 5.11 ± 3.44, p = 0.019), when adjusted for administration regimen, leading to significantly more adequate bowel preparations (79.7% vs 59.7%, p = 0.007). A two-day split dose was superior to a one-day split dose regimen (mean OBPS: 3.68± 2.82 vs 5.69 ± 3.06, p<0.001). Two-day split dosing also resulted in a better right colon cleanliness score (right bowel OBPS 1.27±0.11 vs 2.10±0.12 for one-day split, P<0.001). Conclusions Optimal bowel preparation was achieved with the use of PEG lavage when administered in a two-day split dose regimen. This trial is registered with ClinicalTrials.gov under identifier NCT01415687.
Ubiquitin C-terminal hydrolase L1 (UCH-L1) loss causes neurodegeneration by altering protein turnover in the first postnatal weeks

Significance Ubiquitin C-terminal hydrolase L1 (UCH-L1) is important for neuronal development. Mechanistically, UCH-L1 has an inhibitory effect on mTOR-containing complexes thereby controlling protein synthesis and degradation. Neurodegeneration arising from UCH-L1 deficiency is the result of an early increased protein turnover (synthesis and decay), which strains neurons by increasing energy requirement and endoplasmic reticulum stress. Rapamycin treatment during a critical developmental period partially rescues motor degeneration in adulthood. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is one of the most abundant and enigmatic enzymes of the CNS. Based on existing UCH-L1 knockout models, UCH-L1 is thought to be required for the maintenance of axonal integrity, but not for neuronal development despite its high expression in neurons. Several lines of evidence suggest a role for UCH-L1 in mUB homeostasis, although the specific in vivo substrate remains elusive. Since the precise mechanisms underlying UCH-L1–deficient neurodegeneration remain unclear, we generated a transgenic mouse model of UCH-L1 deficiency. By performing biochemical and behavioral analyses we can show that UCH-L1 deficiency causes an acceleration of sensorimotor reflex development in the first postnatal week followed by a degeneration of motor function starting at periadolescence in the setting of normal cerebral mUB levels. In the first postnatal weeks, neuronal protein synthesis and proteasomal protein degradation are enhanced, with endoplasmic reticulum stress, and energy depletion, leading to proteasomal impairment and an accumulation of nondegraded ubiquitinated protein. Increased protein turnover is associated with enhanced mTORC1 activity restricted to the postnatal period in UCH-L1–deficient brains. Inhibition of mTORC1 with rapamycin decreases protein synthesis and ubiquitin accumulation in UCH-L1–deficient neurons. Strikingly, rapamycin treatment in the first 8 postnatal days ameliorates the neurological phenotype of UCH-L1–deficient mice up to 16 weeks, suggesting that early control of protein homeostasis is imperative for long-term neuronal survival. In summary, we identified a critical presymptomatic period during which UCH-L1–dependent enhanced protein synthesis results in neuronal strain and progressive loss of neuronal function.
Bayesian Inference for Reliability Function of Gompertz Distribution

In this paper, some Bayes estimators of the reliability function of Gompertz distribution have been derived based on generalized weighted loss function. In order to get a best understanding of the behaviour of Bayesian estimators, a non-informative prior as well as an informative prior represented by exponential distribution is considered. Monte-Carlo simulation have been employed to compare the performance of different estimates for the reliability function of Gompertz distribution based on Integrated mean squared errors. It was found that Bayes estimators with exponential prior information under the generalized weighted loss function were generally better than the estimators based on Jeffreys prior information.
Epidermal development requires ninein for spindle orientation and cortical microtubule organization

In the epidermis, ninein affects spindle orientation of progenitor cells, as well as cortical microtubule organization, desmosome assembly, and lamellar body secretion in differentiating cells. In mammalian skin, ninein localizes to the centrosomes of progenitor cells and relocates to the cell cortex upon differentiation of keratinocytes, where cortical arrays of microtubules are formed. To examine the function of ninein in skin development, we use epidermis-specific and constitutive ninein-knockout mice to demonstrate that ninein is necessary for maintaining regular protein levels of the differentiation markers filaggrin and involucrin, for the formation of desmosomes, for the secretion of lamellar bodies, and for the formation of the epidermal barrier. Ninein-deficient mice are viable but develop a thinner skin with partly impaired epidermal barrier. We propose two underlying mechanisms: first, ninein contributes to spindle orientation during the division of progenitor cells, whereas its absence leads to misoriented cell divisions, altering the pool of progenitor cells. Second, ninein is required for the cortical organization of microtubules in differentiating keratinocytes, and for the cortical re-localization of microtubule-organizing proteins, and may thus affect any mechanisms that depend on localized microtubule-dependent transport.
Experimental research of the dosing device and the process of nonmixing of tubular long dimensions at the automatic conveyor unit

Paper presents pilot studies of the automatic conveyor mixer (nonmixer) and batchers for receiving mix of the single, piece tubular elements having similar standard overall dimensions, but differing in internal properties at effective end use. The relevance and novelty of development are shown on the example of receiving the general party of composite tubular product from small similar parties, at the determined forming of its uniformity, with the set qualitative and quantitative characteristics from heterogeneous tubular components.
Alcohol Production by Fish Spoilage Bacteria.

Bacterial isolates (244) identified to genera were tested for their ability to produce ethanol, isopropanol and propanol in a fish tissue extract. All of the isolates produced ethanol and 241 and 227 produced isopropanol and propanol, respectively. One high alcohol producing member of each of the groups Moraxella -like, Pseudomonas , Flavobacterium , Micrococcus and coryneforms was selected for utilization of fish components as substrates in production of alcohol. The substrates tested included four sugars, nine amino acids and lactic and pyruvic acids. Although there were some variations in the levels of alcohols produced by the test organisms from the substrates, the organisms appeared to prefer simple 5 and 6 carbon sugars and then utilized the free amino acids. The level of oxygenation greatly affected the levels of alcohols produced.
Packing of apolar side chains enables accurate design of highly stable membrane proteins

Precise packing for membrane proteins Although nonpolar amino acid side chains pack efficiently in membrane proteins, it has been difficult to determine how much this contributes to membrane protein stability. Designed membrane proteins have largely relied on other stabilizing interactions such as metal-ligand interactions and hydrogen bonds. Mravic et al. uncovered a steric packing code underlying the folding of the natural protein phospholamban, which they used to design stable membrane proteins with nonpolar interfaces. They suggest that packing of nonpolar residues plays a role in the folding and stability of many membrane proteins. Science, this issue p. 1418 Precise packing of amino acid side chains plays an important role in membrane protein folding and stability. The features that stabilize the structures of membrane proteins remain poorly understood. Polar interactions contribute modestly, and the hydrophobic effect contributes little to the energetics of apolar side-chain packing in membranes. Disruption of steric packing can destabilize the native folds of membrane proteins, but is packing alone sufficient to drive folding in lipids? If so, then membrane proteins stabilized by this feature should be readily designed and structurally characterized—yet this has not been achieved. Through simulation of the natural protein phospholamban and redesign of variants, we define a steric packing code underlying its assembly. Synthetic membrane proteins designed using this code and stabilized entirely by apolar side chains conform to the intended fold. Although highly stable, the steric complementarity required for their folding is surprisingly stringent. Structural informatics shows that the designed packing motif recurs across the proteome, emphasizing a prominent role for precise apolar packing in membrane protein folding, stabilization, and evolution.