Miracle-dz/UniFAR-FTUs huggingface dataset:
A Genetic Model Therapy Proposes a Critical Role for Liver Dysfunction in Mitochondrial Biology and Disease

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Here we present a new animal model that recapitulates key components of Leigh Syndrome, French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the Leucine Rich Pentatricopeptide repeat-containing motif (LRPPRC) gene. LRPPRC has native functions related to mitochondrial mRNA polyadenylation and translation as well as a role in gluconeogenesis. We used the Gene-Breaking Transposon (GBT) cassette to create a revertible, insertional mutant zebrafish line in the LRPPRC gene. lrpprc zebrafish homozygous mutants displayed impaired muscle development, liver function and lowered levels of mtDNA transcripts and are lethal by 12dpf, all outcomes similar to clinical phenotypes observed in patients. Investigations using an in vivo lipidomics approach demonstrated accumulation of non-polar lipids in these animals. Transcript profiling of the mutants revealed dysregulation of clinically important nuclearly encoded and mitochondrial transcripts. Using engineered liver-specific rescue as a genetic model therapy, we demonstrate survival past the initial larval lethality, as well as restored normal gut development, mitochondrial morphology and triglyceride levels functionally demonstrating a critical role for the liver in the pathophysiology of this model of mitochondrial disease. Understanding the molecular mechanism of the liver-mediated genetic rescue underscores the potential to improve the clinical diagnostic and therapeutic developments for patients suffering from these devastating disorders.
Associations Between Habitat Quality And Body Size In The Carpathian Land Snail Vestia turgida: Species Distribution Model Selection And Assessment Of Performance

Species distribution models (SDMs) are generally thought to be good indicators of habitat suitability, and thus of species’ performance, consequently SDMs can be validated by checking whether the areas projected to have the greatest habitat quality are occupied by individuals or populations with higher than average fitness. We hypothesized a positive and statistically significant relationship between observed in the field body size of the snail V. turgida and modelled habitat suitability, tested this relationship with linear mixed models, and found that indeed, larger individuals tend to occupy high-quality areas, as predicted by the SDMs. However, by testing several SDM algorithms, we found varied levels of performance in terms of expounding this relationship. Marginal R2, expressing the variance explained by the fixed terms in the regression models, was adopted as a measure of functional accuracy, and used to rank the SDMs accordingly. In this respect, the Bayesian additive regression trees (BART) algorithm (Carlson, 2020) gave the best result, despite the low AUC and TSS. By restricting our analysis to the BART algorithm only, a variety of sets of environmental variables commonly or less used in the construction of SDMs were explored and tested according to their functional accuracy. In this respect, the SDM produced using the ENVIREM data set (Title, Bemmels, 2018) gave the best result.
Circulating levels of luteinizing hormone and steroid hormones in relation to social status in the cooperatively breeding white‐browed sparrow weaver, Plocepasser mahali

We have begun an intensive series of investigations into the environmental and endocrine mechanisms regulating cooperative breeding in a semi-arid tropical environment. A colour-marked population of white-browed sparrow weavers (Plocepasser mahali) was studied at a field site near Nyamaluma Camp, Luangwa Valley, Zambia (13dG S). This species breeds from October to April, although some clutches may be found as early as August and young may be fed until May. Non-disruptive techniques were employed to monitor annual cycles of gonadal development, body mass and fat reserves, and small blood samples were collected to measure circulating levels of reproductive hormones and corticosterone. All individuals were released after sampling and the social and reproductive activities recorded by systematic behavioural observations. Each individual could thus be identified as: (1) a breeding adult; (2) a related helper (i.e. offspring of the breeding male and female within the group); or (3) a non-related (=invader) helper (these birds helped defend territory but did not help feed young; they were not related to the breeding pair and usually originated from outside the group). Breeding males had larger testes and higher levels of testosterone than either related helpers or invader helpers. In females, all status groups had follicles up to 2 mm in diameter, but only breeding females ovulated. There were no differences in plasma levels of reproductive hormones among different status females, except for higher circulating luteinizing hormone (LH) in invader female helpers during the first part of the breeding season. Although plasma levels of testosterone were highest in breeding males, the maximum titres were two orders of magnitude less than in males of passerine species from temperate regions. Furthermore, injections of a peptide hormone GnRH (gonadotropin-releasing hormone) increased plasma LH levels in both males and females, and were followed by rises in testosterone levels only in males, but not over the normal maximum seen in February. GnRH-induced high levels of LH did not affect testosterone concentrations in the blood of females. Results obtained thus far indicate that the hormonal control of aggression in white-browed sparrow weavers is different from that predicted by investigations on north temperate species. Whether these phenomena are typical of tropical species, particularly cooperative breeders, remains to be determined. Since most of the world's species of birds live in the tropics, and a substantial fraction of them breed cooperatively, more investigations are needed to establish the hormonal basis of reproductive behaviour and cooperative breeding. Given the baseline data already collected, the white-browed sparrow weaver will be a useful model.
L-bodies are novel RNA-protein condensates driving RNA transport in Xenopus oocytes

RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.
Diverse deep neural networks all predict human IT well, after training and fitting

Deep neural networks (DNNs) trained on object recognition provide the best current models of high-level visual areas in the brain. What remains unclear is how strongly network design choices, such as architecture, task training, and subsequent fitting to brain data contribute to the observed similarities. Here we compare a diverse set of nine DNN architectures on their ability to explain the representational geometry of 62 isolated object images in human inferior temporal (hIT) cortex, as measured with functional magnetic resonance imaging. We compare untrained networks to their task-trained counterparts, and assess the effect of fitting them to hIT using a cross-validation procedure. To best explain hIT, we fit a weighted combination of the principal components of the features within each layer, and subsequently a weighted combination of layers. We test all models across all stages of training and fitting for their correlation with the hIT representational dissimilarity matrix (RDM) using an independent set of images and subjects. We find that trained models significantly outperform untrained models (accounting for 57% more of the explainable variance), suggesting that features representing natural images are important for explaining hIT. Model fitting further improves the alignment of DNN and hIT representations (by 124%), suggesting that the relative prevalence of different features in hIT does not readily emerge from the particular ImageNet object-recognition task used to train the networks. Finally, all DNN architectures tested achieved equivalent high performance once trained and fitted. Similar ability to explain hIT representations appears to be shared among deep feedforward hierarchies of nonlinear features with spatially restricted receptive fields.
Novel antiproliferative tripeptides block AP-1 transcriptional complex by in silico approach

BACKGROUND The complexity and heterogeneity at genetic, epigenetic and microenvironment levels are key attributes of tumors. Genetic heterogeneity encompasses one of key factors at transcriptional gene regulation that promote abnormal proliferation, invasiveness and metastasis. Among various key pro-tumor transcriptional complexes, activating protein-1 (AP-1) transcriptional complex controls the transcriptional expression of key oncogenes in cancer cells. Therefore, an avenue to search for a chemical inhibition approach of the AP-1 transcriptional complex is warranted in cancer therapeutics. METHODS To achieve chemical inhibition of AP-1 transcriptional complex, we report novel tripeptides identified from the goat urine DMSO fraction as potential agents that bind to AP-1 responsive TPA element and heterodimer c-Jun:c-Fos. Novel tripeptides enriched GUDF were tested against DNA substrates to assess DNA metabolizing activity. Further, Novel tripeptides enriched GUDF were treated upon HCT-116 cells to estimate the nature of tripeptides entered into the intracellular compartment of HCT-116 cells. Here, we report on a novel methodology that employ VTGE assisted intracellular metabolite purification and is analyzed with the help of LC-HRMS technique. Post purification of intracellular metabolites that included tripeptides of GUDF, these tripeptides from DMSO and GUDF treated HCT-116 cells were subjected to molecular docking and ligand-DNA:AP-1 (PDB ID: 1FOS) interaction study by using bioinformatics tools AutoDock Vina and PyMol. RESULTS GUDF enriched with tripeptides and other metabolites show appreciable instability of DNA substrates plasmid and genomic DNA to an extent of 90%. Interestingly, LC-HRMS analysis of intracellular metabolite profiling of GUDF treated HCT-116 cells reveal the appreciable abundance of tripeptides Glu-Glu-Arg, Gly-Arg-Pro, Gln-Lys-Arg, Glu-Glu-Lys, Trp-Trp-Val. On the other hand, DMSO treated HCT-116 cells show the presence of Ser-Trp-Lys, Glu-Glu-Gln, Glu-Glu-Lys, Ser-Leu-Ser. Interestingly, GUDF treated HCT-116 cells show inhibition of proliferation by more than 70%. Among the identified intracellular tripeptides, Glu-Glu-Arg (9.1 Kcal/Mol), Gly-Arg-Pro (8.8 Kcal/Mol), and Gln-Lys-Arg (6.8) show a precise and strong binding to heptameric TPA response element 5’ TGAGTCA 3’ and key amino acid residue within the AP-1 transcriptional complex. CONCLUSION In summary, this study suggests the potential of novel tripeptides, those are reported from GUDF intracellularly in HCT-116 cells to destabilize the AP-1 transcriptional complex. Data indicate that cellular arrest in HCT-116 cells treated by GUDF is well supported by the molecular docking observations that destabilization of AP-1 complex is linked to reduced growth and proliferation.
Strategy guides feature recall of a single object in working memory task

Over past couple of decades our understanding of visual working memory (VWM), and working memory in general, has been predominantly in line with the capacity debate. We recently opened a new line of inquiry regarding the recall of a single object to go beyond the capacity debate, and showed that a series of feature probe questions about a single object yields poorer recall later in the sequence (Sengupta et al, 2020). In the current work we focused on another aspect of sequential feature recall - mainly regarding whether recall can be improved by asking the same question twice. To that end, we chose to focus on two features - color and location, and we contrasted repeat and non-repeat (from the standpoint of feature questions) trials in a series of two experiments. In repeat trials either color or location would be probed twice consecutively. In non-repeat trials color and location probes were presented one after the other in random order. In all trials the stimulus was a small colored oriented line presented for 1 sec in a location within 4o of visual angle. The recall of color and location were mapped onto continuous variable like Sengupta et al, 2020 - for instance, color recall was mapped onto a color wheel. In the first experiment, we used an unaltered color wheel when the color question was repeated. For the second experiment, we used a rotated color wheels for two consecutive color recall trials. We observed an increase in recall error for both repeat and non-repeat condition for location when the probe was at the second question in both experiments. However, color recall error did not increase for second repeat question condition in Experiment 1 as opposed to the non-repeat condition. On the other hand, in Experiment 2 we observed the expected increase in recall error for both repeat and non repeat condition for color probe at the second question. This maybe due to the fact that participants used an ‘anchoring’ strategy in Experiment 1 by remembering where they clicked on the color wheel in the first question. The rotation of color wheel in second experiment destroys the anchor leading to the aforementioned result. The results show that trying to recall the same feature again leads to degradation of recall accuracy for both color and location, and human beings may use different strategies for recall in working memory tasks.
Developmental niche structure in the gregarine assemblage parasitizing Tenebrio molitor

The exogenous developmental niche spaces of Gregarina cuneata and Gregarina polymorpha, parasites restricted to larval Tenebrio molitor, and Gregarina niphandrodes, a parasite restricted to adult T. molitor, were determined along temperature and humidity axes and associated with parasite niche space on the host resource axis. Gregarine gametocysts were incubated at controlled humidity (0, 10, and 20 mm Hg vapor pressure deficit) at 20, 25, 30, and 35 C to determine the environmental limits to survival and sporulation
Comparison of Zebra Mussel Veliger Laboratory Enumeration and Sampling Techniques

Zebra mussel (Dreissena polymorpha) invasion greatly impacts aquatic systems, with economic and ecological consequences. Monitoring zebra mussel density and reproductive timing are essential for effective detection, management, and control of this invasive species. Veligers, the free-floating planktonic life stage of zebra mussels, are often monitored to estimate reproductive effort and as a first indicator of zebra mussel invasion. Although many veliger monitoring methods exist and vary greatly in cost and effort, no study has compared results yielded by different sampling techniques. We compared estimated veliger densities collected with offshore vertical plankton net tows and oblique plankton net tows taken from shore from April through October 2011 in Marion Reservoir, Kansas. Secondarily, we compared enumeration results returned by an established laboratory and a laboratory that had recently begun enumerating veligers. Using ANOVA testing, we found no significant difference between sampling methods or laboratories. We recommend using oblique plankton net tows taken from shore because of their potential to reduce monitoring costs compared to other sampling techniques by reducing equipment, time, and manpower expenses.
Feeding behavior: selection of both wet and dry food for increased growth in Schistocerca gregaria nymphs

An apparent fluctuating preference in acridids for food of different water contents is confirmed for Schistocerca gregaria nymphs. Short‐ and long‐term preference tests reveal that previous diet, through its effect on locust water balance and overall food intake, can influence feeding behavior on high‐water content (wet) and low‐water content (dry) food. Locusts given only wet or dry food for 3 days prior to testing initially chose the food not received in pretreatment when given a choice of the two. They had decreased latencies to feed, increased meal length and decreased switching between food types as compared with locusts given the option to regulate water intake before testing. It is suggested that the behavior of the single‐diet locusts has several related causes, among them, deterrence of the food, disturbed water balance in the locust, and chronic hunger. Long‐term preference tests reveal that fifth‐instar locusts given a continuous choice between wet and dry food take significantly more of their total dry matter from dry food each day until the last feeding day of the instar (day 9), when they take 97% of their total dry matter from wet food. This behavioral regulation of water and dry matter intake is adaptive: locusts with access to a mixed diet of wet and dry food have increased growth as compared with ones given only wet food. The growth increase is due largely to increased dry matter consumption, with some contribution from increased digestive efficiency and reduction in respiratory rate.
Are occlusal contact area asymmetry and masticatory muscle activity asymmetry related in adults with normal dentition?

ABSTRACT Objective: To examine whether asymmetry in the area of occlusal contact and near contact (ACNC) and asymmetrical masticatory muscle electromyographic activity are correlated in healthy dentate adults. Methods: Ninety-one healthy subjects with full dentition were included. Seven levels of ACNC were registered, and the asymmetry indexes (AsI) for each level of ACNC (AsI-ACNC) were determined. Surface EMG was used to record bilateral anterior temporalis activity and masseter muscle activity. The AsI for the anterior temporalis, masseter, and the combination of both muscles were calculated. Results: Pearson’s correlation analysis revealed all levels of AsI-ACNC were significantly, negatively correlated with the AsI of the anterior temporalis and the combination of both muscles (p < 0.05), but not the AsI of the masseter muscle (p > 0.05). Conclusion: The side with greater ACNC has significantly lower anterior temporalis activity and combined anterior temporalis and masseter muscle activity on the ipsilateral side.
Infectious load of Aeromonas salmonicida subsp. salmonicida during the initial phase of a cohabitant infection experiment with Atlantic salmon, Salmo salar L.

The abundances of Aeromonas salmonicida subsp. salmonicida in the water and in the surface microlayer was studied during the initial phase of a cohabitant infection experiment with Atlantic salmon, Salmo salar L. , smolt. Aeromonas salmonicida was detected in the water samples only until the intraperitoneally infected smolt were dead and had been removed. In the lipid rich surface microlayer, A. salmonicida was detected in high concentrations from the day of the first fish mortality and throughout the rest of the experiment. The significance of the high cell surface hydrophobicity is discussed as a possible reason for enrichment of A. salmonicida at the air-water interface.
Comparison between Tibetan and Small-tailed Han sheep in adipocyte phenotype, lipid metabolism and energy homoeostasis regulation of adipose tissues when consuming diets of different energy levels

Abstract This study aimed to gain insight into how adipose tissue of Tibetan sheep regulates energy homoeostasis to cope with low energy intake under the harsh environment of the Qinghai-Tibetan Plateau (QTP). We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), all wethers and 1·5 years of age, which were each divided randomly into four groups and offered diets of different digestible energy (DE) densities: 8·21, 9·33, 10·45 and 11·57 MJ DE/kg DM. When the sheep lost body mass and were assumed to be in negative energy balance: (1) adipocyte diameter in subcutaneous adipose tissue was smaller and decreased to a greater extent in Tibetan than in Small-tailed Han sheep, but the opposite occurred in the visceral adipose tissue; (2) Tibetan sheep showed higher insulin receptor mRNA expression and lower concentrations of catabolic hormones than Small-tailed Han sheep and (3) Tibetan sheep had lower capacity for glucose and fatty acid uptake than Small-tailed Han sheep. Moreover, Tibetan sheep had lower AMPKα mRNA expression but higher mammalian target of rapamycin mRNA expression in the adipocytes than Small-tailed Han sheep. We concluded that Tibetan sheep had lower catabolism but higher anabolism in adipose tissue and reduced the capacity for glucose and fatty acid uptake to a greater extent than Small-tailed Han sheep to maintain energy homoeostasis when in negative energy balance. These responses provide Tibetan sheep with a high ability to cope with low energy intake and with the harsh environment of the QTP.
Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis

Abstract Purpose To evaluate the kinetics of apical periodontitis development in vivo , induced either by contamination of the root canals by microorganisms from the oral cavity or by inoculation of bacterial lipopolysaccharide (LPS) and the regulation of major enzymes and receptors involved in the arachidonic acid metabolism. Methodology Apical periodontitis was induced in C57BL6 mice (n=96), by root canal exposure to oral cavity (n=48 teeth) or inoculation of LPS (10 µL of a suspension of 0.1 µg/µL) from E. coli into the root canals (n= 48 teeth). Healthy teeth were used as control (n=48 teeth). After 7, 14, 21 and 28 days the animals were euthanized and tissues removed for histopathological and qRT-PCR analyses. Histological analysis data were analyzed using two-way ANOVA followed by Sidak’s test, and qRT-PCR data using two-way ANOVA followed by Tukey’s test (α=0.05). Results Contamination by microorganisms led to the development of apical periodontitis, characterized by the recruitment of inflammatory cells and bone tissue resorption, whereas inoculation of LPS induced inflammatory cells recruitment without bone resorption. Both stimuli induced mRNA expression for cyclooxygenase-2 and 5-lipoxygenase enzymes. Expression of prostaglandin E 2 and leukotriene B 4 cell surface receptors were more stimulated by LPS. Regarding nuclear peroxisome proliferator-activated receptors (PPAR), oral contamination induced the synthesis of mRNA for PPARδ, differently from inoculation of LPS, that induced PPARα and PPARγ expression. Conclusions Contamination of the root canals by microorganisms from oral cavity induced the development of apical periodontitis differently than by inoculation with LPS, characterized by less bone loss than the first model. Regardless of the model used, it was found a local increase in the synthesis of mRNA for the enzymes 5-lipoxygenase and cyclooxygenase-2 of the arachidonic acid metabolism, as well as in the surface and nuclear receptors for the lipid mediators prostaglandin E2 and leukotriene B4.