Miracle-dz/UniFAR-FTUs huggingface dataset:
Valine and isoleucine supplementation improve performance and serum biochemical concentrations in growing gilts fed low-protein diets

Abstract: This study evaluated the effects of valine and isoleucine supplementation in low-crude-protein (CP) diets on performance, serum parameters, and carcass traits in growing gilts. Two-hundred gilts (29.1 ± 1.7 kg) were allotted randomly to one of five diets that included a control CP (177 g kg-1) or four low-CP (135 g kg-1) diets for 45 d. The low-CP diets were added with lysine + threonine + methionine (LCM), LCM+ tryptophan (LCT), LCT + valine (LCV), or LCV + isoleucine (LCI), respectively. Non significant difference in average daily gain was obtained in gilts receiving the control, LCV, or LCI diets, which was higher than that of pigs fed the LCM or LCT diets (P < 0.05). The supplementation of crystalline tryptophan, valine, and isoleucine improved the average daily feed intake and serum levels of total protein, tryptophan, and isoleucine (linear and quadratic effects, P < 0.05) and serum valine concentration (linear effect, P < 0.05). The results indicated that the valine supplementation, or the both combination of valine and isoleucine, could further improve the performance in 29–62 kg gilts fed the 135 g kg-1 CP diet.
An Out-of-Patagonia dispersal explains most of the worldwide genetic distribution in Saccharomyces eubayanus

Saccharomyces eubayanus represents missing cryotolerant ancestor of lager yeast hybrid and can be found in Patagonia in association with Nothofagus forests. The limited number of isolates and associated genomes available has prevented to resolve the S. eubayanus origin and evolution. Here, we present a sampling effort at an unprecedented scale and report the isolation of 160 strains from ten sampling sites along 2,000 km distance in South America. We sequenced the genome of 82 strains and, together with other 25 available genomes, performed comprehensive phylogenetic analysis. Our results revealed the presence of three main Patagonia-B lineages together with dozens of admixed strains distributed in three mosaic clusters. The PB-1 lineage isolated from Tierra del Fuego exhibited the highest genetic diversity, lowest LD blocks and highest Fis values compared to the other lineages, suggesting a successful adaptation to cold temperatures in extreme environments and greater inbreeding rates in Tierra del Fuego. Differences between lineages and strains were found in terms of aneuploidy and pangenome content, evidencing a lateral gene transfer event in PB-2 strains from an unknown donor species. Overall, the Patagonian lineages, particularly southern populations, showed a greater global genetic diversity compared to Holarctic and Chinese lineages, supporting the scenario of a S. eubayanus colonization from Patagonia and then spread towards northern and western regions, including the Holarctic (North America and China) and New Zealand. Interestingly, fermentative capacity and maltose consumption resulted negatively correlated with latitude, indicating a better fermentative performance in norther populations. Our genome analysis together with previous reports in the sister species S. uvarum strongly suggests that the S. eubayanus ancestor could have originated in Patagonia or the Southern Hemisphere, rather than China, yet further studies are needed to resolve this conflicting scenario. Understanding S. eubayanus evolutionary history is crucial to resolve the unknown origin of the lager yeast and might open new avenues for biotechnological applications.
The Role of PAK Signaling in Synaptic Transmission and Plasticity and Social Memory in Mice

Social interactions are essential to our mental health and their deficits are hallmark characteristics in numerous brain disorders. Various subregions within the medial temporal lobe have been implicated in social memory, however, the underlying molecular and cellular mechanisms that tune these particular neural circuits in memory processing remain unclear. PAKs (p21-activated kinases) are a family of serine/threonine protein kinases that are target enzymes of the Rho family small GTPases and central regulators of both the actin cytoskeleton and neuronal morphology. PAK 1 and 3 are involved in the regulation of the structural and functional properties of the synapse, including dendritic spine morphology, synaptic transmission and plasticity, and learning and memory. Recent human and animal studies have revealed that perturbations in PAKs are implicated in several neurological and mental disorders including autism spectrum disorders (ASD) and intellectual disability (ID). These disorders are often characterized by social impairments, yet the cellular correlates within the neural circuits that subserve PAK function in social behaviour remains unknown. In this thesis, I explore five objectives which elucidates the role of PAK signaling in the entorhinal cortical perforant projections to the dentate gyrus (EC-DG) in social memory retrieval. First, I characterize the
“Plasma Membrane Calcium Atpase downregulation in dopaminergic neurons alters cellular physiology and behavior in Drosophila melanogaster”

Accumulation of calcium is proposed to account for selective dopaminergic neuron (DN) dysfunctionality, a characteristic of Parkinson’s Disease (PD). To test the in vivo impact of calcium increment in DN physiology we downregulated the Plasma Membrane Calcium ATPase (PMCA), a bomb that extrudes cytosolic calcium, in those neurons in Drosophila melanogaster. Using th-GAL4>PMCARNAi, PMCA was selectively reduced, leading to increased cytosolic calcium and mitochondrial oxidative stress with no neurodegeneration. In the eye, PMCARNAi expression provoked a subtle disorganization, suggesting scarce toxicity. Interestingly, we observed several locomotor alterations and a higher level of dopamine in brains. Finally, flies presented a reduction of lifespan and a perimortem non-motor phenotype characterized by abdominal swelling, possibly due to constipation. We conclude that elevated cytosolic calcium in DN could trigger cellular dysfunction generating mitochondrial oxidative stress and motor and non-motor symptoms, typical of PD.
In Vivo Large Scale Mapping Of Protein Turnover In The Human Cerebrospinal Fluid

The extraction of accurate physiological parameters from clinical samples provides a unique perspective to understand disease etiology and evolution, including under therapy. We introduce a new proteomics framework to map patient proteome dynamics in vivo, either proteome wide or in large targeted panels. We applied it to ventricular cerebrospinal fluid (CSF) and could determine the turnover parameters of almost 200 proteins, whereas a handful were known previously. We covered a large number of neuron biology- and immune system-related proteins including many biomarkers and drug targets. This first large data set unraveled a significant relationship between turnover and protein origin that relates to our ability to investigate the central nervous system physiology precisely in future studies. Our data constitute a reference in CSF biology as well as a repertoire of peptides for the community to design new proteome dynamics analyses. The disclosed methods apply to other fluids or tissues provided sequential sample collection can be performed.
Dietary vs non-dietary fatty acid profiles of lake trout morphs from Lake Superior and Great Bear Lake: Are fish really what they eat?

Fatty acids are well-established biomarkers used to characterize trophic ecology, food-web linkages, and organismal niche for a diversity of taxa. Most often, fatty acids examined include only those previously identified as “dietary” or “extended dietary”. Consequently, non-dietary fatty acids are commonly discarded, representing approximately half of the fatty acids that can be extracted from fish muscle. In this study, we explored whether non-dietary fatty acids can provide worthwhile information by assessing their ability to discriminate intraspecific diversity within and between lakes. Non-dietary fatty acids delineated variation geographically (between lakes), between locations within a lake, and among morphs within a species. Non-dietary fatty acids were useful in delineating morphs of lake trout in both lakes and, for Lake Superior, performed better than dietary fatty acids. Physiological differences that arise from dynamic differences in energy processing can be adaptive and linked to habitat use (i.e., shallow vs. deep depths) by species morphs, and likely explains why non-dietary fatty acids can be a relevant tool to delineate intraspecific diversity in lake trout, which are known to inhabit a large range of habitats. The level of differences in non-dietary fatty acids were as pronounced among morphs within Great Bear Lake as observed in Lake Superior. Little is known what causes non-dietary-mediated differences in fatty acid composition, but our results showed that assessing non-dietary fatty acids can be useful in delineating intraspecific diversity and spatial variation.
Implicit Visuomotor Adaptation Remains Limited after Several Days of Training

Abstract Learning in sensorimotor adaptation tasks has been viewed as an implicit learning phenomenon. The implicit process affords recalibration of existing motor skills so that the system can adjust to changes in the body or environment without relearning from scratch. However, recent findings suggest that the implicit process is heavily constrained, calling into question its utility in motor learning and the theoretical framework of sensorimotor adaptation paradigms. These inferences have been based mainly on results from single bouts of training, where explicit compensation strategies, such as explicitly re-aiming the intended movement direction, contribute a significant proportion of adaptive learning. It is possible, however, that the implicit process supersedes explicit compensation strategies over repeated practice sessions. We tested this by dissociating the contributions of explicit re-aiming strategies and the implicit process in human participants over five consecutive days of training. Despite a substantially longer duration of training, the implicit process still plateaued at a value far short of complete learning and, as has been observed in previous studies, was inappropriate for a mirror-reversal task. Notably, we find significant between subject differences that call into question traditional interpretation of these group-level results.
Adaptability of cotton (Gossypium hirsutum) genotypes analysed using a Bayesian AMMI model

Abstract. Cotton (Gossypium spp.) provides ∼90% of the world’s textile fibre. The aim of this study was to use the principal additive effects and multiplicative interaction (AMMI) model under the Bayesian approach to recommend cotton genotypes for the Central-West region of Brazil. Eight trials with upland cotton genotypes were conducted during the 2008–09 harvest in the State of Mato Grosso, Brazil. The experiment included a randomised block design with 16 genotypes. The genotypes were evaluated for fibre yield, length and strength. Chains were simulated via the Markov chain Monte Carlo method with 300 000 iterations for the parameters of the Bayesian AMMI model. From the chains generated, the first 20 000 burn-in observations were discarded and samples were taken by jumping every 20 observations (thin). Bayesian analysis provided additional results to those obtained by the frequentist approach, highlighting the credibility regions in the biplot for the genotypic and environmental scores. Bayesian AMMI model allowed identification of a genotype that can be widely recommended; this genotype has genotypic values above the overall mean for the three evaluated traits and did not contribute to the genotype × environment interactions observed in these traits. In addition, adaptability of genotypes to specific environments was observed, which makes it possible to capitalise the positive effect of the genotype × environment interaction.
Three-Dimensional Musculoaponeurotic Architecture of the Human Lower Limb and its Functional Implications

The musculoaponeurotic architecture of the human lower limb has not been previously investigated in three-dimension (3D) at the fiber bundle (FB) level. As musculoaponeurotic architecture is a primary determinant of muscle function, the lack of architectural data has limited our understanding of functional characteristics of lower limb musculature and the development of high-fidelity simulation and biomechanical models. The overall objective of this thesis is to capture the 3D musculoaponeurotic architecture of all of the lower limb muscles, and to use this data to elucidate functional capabilities of muscle groups, individual muscles, and/or intramuscular partitions. In the first study, 48,000 FBs and all of the tendinous/aponeurotic components of 59 lower limb muscles were digitized and modelled, as in situ, to construct an architecturally comprehensive 3D lower limb muscle model. A detailed architectural analysis of three lower limb muscles demonstrated that each had unique spatial arrangement and morphology of the musculoaponeurotic elements resulting in functionally relevant intramuscular partitioning. The second study captured the 3D musculoaponeurotic architecture of vastus medialis obliquus (VMO) and longus (VML) in 12 specimens. The comparison of architectural
Changes in China’s lakes: climate and human impacts

Abstract Lakes have played a critical role in providing water and ecosystem services for people and other organisms in China for millennia. However, accelerating climate change and economic boom have resulted in unprecedented changes in these valuable lakes. Using Landsat images covering the entity of the country, we explored the changes in China’s lakes and the associated driving forces over the last 30 years (i.e. mid-1980s to 2015). We discovered that China’s lakes have changed with divergent regional trends: in the sparsely populated Tibetan Plateau, lakes are abundant and the lake area has increased dramatically from 38 596 to 46 831 km2 (i.e. increased by 8235 km2, or 21.3%), whereas, in the densely populated northern and eastern regions, lakes are relatively scarce and the lake area has decreased from 36 659 to 33 657 km2 (i.e. decreased by 3002 km2, or 8.2%). In particular, severe lake decreases occurred in the Mongolia-Xinjiang Plateau and the Eastern Plain (−2151 km2). Statistical analyses indicated that climate was the most important factor controlling lake changes in the Tibetan Plateau, the Yun-Gui Plateau and the Northeast Plain. However, the strength of climatic control on lake changes was low in the Eastern Plain and the Mongolia-Xinjiang Plateau, where human activities, e.g. impoldering, irrigation and mining, have caused serious impacts on lakes. Further lake changes will exacerbate regional imbalances between lake resources and population distribution, and thus may increase the risk of water-resource crises in China.
CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells

Aims Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.
Perturbation of the Monocyte Compartment in Human Obesity

Circulating monocytes can be divided into classical (CM), intermediate (IM), and non-classical monocytes (NCM), and the classical monocytes also contain CD56+ monocytes and monocytic myeloid-derived suppressor cells (M-MDSC). The aim of the study was to evaluate the occurrence of the monocyte subpopulations in human obesity. Twenty-seven normal, 23 overweight, and 60 obese individuals (including 17 obese individuals with normal glucose tolerance and 27 with type 2 diabetes) were included into this study. Peripheral blood mononuclear cells were isolated from human blood, and surface markers to identify monocyte subpopulations were analyzed by flow cytometry. Obese individuals had higher numbers of total monocytes, CM, IM, CD56+ monocytes, and M-MDSCs. The number of CM, IM, CD56+ monocytes, and M-MDSCs, correlated positively with body mass index, body fat, waist circumference, triglycerides, C-reactive protein, and HbA1c, and negatively with high-density lipoprotein cholesterol. Individuals with obesity and type 2 diabetes had higher numbers of IM, NCM, and M-MDSCs, whereas those with obesity and impaired glucose tolerance had higher numbers of CD56+ monocytes. In summary, the comprehensive analysis of blood monocytes in human obesity revealed a shift of the monocyte compartment toward pro-inflammatory monocytes which might contribute to the development of low-grade inflammation in obesity, and immune-suppressive monocytes which might contribute to the development of cancer in obesity.
Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Sphingolipids are major components of cellular membranes, and at steady-state level, their metabolic fluxes are tightly controlled. On challenge by external signals, they undergo rapid turnover, which substantially affects the biophysical properties of membrane lipid and protein compartments and, consequently, signaling and morphodynamics. In T cells, external cues translate into formation of membrane microdomains where proximal signaling platforms essential for metabolic reprograming and cytoskeletal reorganization are organized. This review will focus on sphingomyelinases, which mediate sphingomyelin breakdown and ensuing ceramide release that have been implicated in T-cell viability and function. Acting at the sphingomyelin pool at the extrafacial or cytosolic leaflet of cellular membranes, acid and neutral sphingomyelinases organize ceramide-enriched membrane microdomains that regulate T-cell homeostatic activity and, upon stimulation, compartmentalize receptors, membrane proximal signaling complexes, and cytoskeletal dynamics as essential for initiating T-cell motility and interaction with endothelia and antigen-presenting cells. Prominent examples to be discussed in this review include death receptor family members, integrins, CD3, and CD28 and their associated signalosomes. Progress made with regard to experimental tools has greatly aided our understanding of the role of bioactive sphingolipids in T-cell biology at a molecular level and of targets explored by a model pathogen (measles virus) to specifically interfere with their physiological activity.
Genome-wide survey of ribosome collision

In protein synthesis, ribosome movement is not always smooth and is rather often impeded for numerous reasons. Although the deceleration of the ribosome defines the fates of the mRNAs and synthesizing proteins, fundamental issues remain to be addressed, including where ribosomes pause in mRNAs, what kind of RNA/amino acid sequence causes this pause, and the physiological significance of this slowdown of protein synthesis. Here, we surveyed the positions of ribosome collisions caused by ribosome pausing in humans and zebrafish on a genome-wide level using modified ribosome profiling. The collided ribosomes, i.e., disomes, emerged at various sites: the proline-proline-lysine motif, stop codons, and the 3′ untranslated region (UTR). The number of ribosomes involved in a collision is not limited to two, but rather four to five ribosomes can form a queue of ribosomes. In particular, XBP1, a key modulator of the unfolded protein response, shows striking queues of collided ribosomes and thus acts as a substrate for ribosome-associated quality control (RQC) to avoid the accumulation of undesired proteins in the absence of stress. Our results provide an insight into the causes and consequences of ribosome slowdown by dissecting the specific architecture of ribosomes.
In Vitro Evaluation of Anticancer Potential of Echispyramidum Venom (Viperidae) and Related Genetic and Apoptotic Profile Alterations

Background: cancer is basically a disease of uncontrolled cell division. Its development and progression are usually linked to a series of changes in the activity of cell cycle regulators. Objective: the present study aimed to investigate the anticancer potential of Echispyramidum venom against HepG2 and HCT 116 cancer cell lines in comparison with the Cisplatin as positive control. Patients and Methods: cell viability performed using MTT assay was cell type and concentration dependent was inversely proportional with the tow substances (Echispyramidum) venom as well as Cisplatin had IC50 of 11.8 and 112.7 µg/mL and 13.4 and 71.2 µg/mL developed in HCT116 and HepG2 cell lines respectively. Results: both of Echispyramidum venom and Cisplatin showed DNA accumulation at the Pre-G1 and G2/ M Phases of cell cycle. Apoptotic profile of treated cells showed up regulation of apoptotic genes (P53, Bax and Casp-3) and down regulation of anti-apoptotic gene (Bcl-2) in a significant way compared with untreated cell control. Also, apoptotic profile was assured via cellular changes detected microscopically in H&E stained cells. Microscopic examination showed apoptotic and slightly necrotic features in case of venoms while Cisplatin induced a number of apoptotic bodies and necrotic cell colonies. Conclusion: it can be concluded that Echispyramidum venom has a clear anticancer potential to human liver and colorectal cancer cells that was proven through the cell cycle arrest profile, induced apoptosis detected via detection of the levels of expression of pro and anti-apoptotic genes, as well as histological alteration detected.
More Than the Sum of Its Parts: Microbiome Biodiversity as a Driver of Plant Growth and Soil Health

Microorganisms drive several processes needed for robust plant growth and health. Harnessing microbial functions is thus key to productive and sustainable food production. Molecular methods have led to a greater understanding of the soil microbiome composition. However, translating species or gene composition into microbiome functionality remains a challenge. Community ecology concepts such as the biodiversity–ecosystem functioning framework may help predict the assembly and function of plant-associated soil microbiomes. Higher diversity can increase the number and resilience of plant-beneficial functions that can be coexpressed and unlock the expression of plant-beneficial traits that are hard to obtain from any species in isolation. We combine well-established community ecology concepts with molecular microbiology into a workable framework that may enable us to predict and enhance soil microbiome functionality to promote robust plant growth in a global change context.