Notes

Prebiotic components involving potato starch dextrins.
Despite their critical roles in autonomic functions, individual hypothalamic nuclei have not been extensively investigated in humans using functional magnetic resonance imaging, partly due to the difficulty in resolving individual nuclei contained in the small structure of the hypothalamus. Areal parcellation analyses enable discrimination of individual hypothalamic nuclei but require a higher spatial resolution, which necessitates long scanning time or large amounts of data to compensate for the low signal-to-noise ratio in 3T or 1.5T scanners. In this study, we present analytic procedures to estimate likely locations of individual nuclei in the standard 2-mm resolution based on our higher resolution dataset. The spatial profiles of functional connectivity with the cerebral cortex for each nucleus in the medial hypothalamus were calculated using our higher resolution dataset. Voxels in the hypothalamus in standard resolution images from the Human Connectome Project (HCP) database that predominantly shared connectivity profiles with the same nucleus were subsequently identified. Voxels representing individual nuclei, as identified with the analytic procedures, were reproducible across 20 HCP datasets of 20 subjects each. Furthermore, the identified voxels were spatially separate. These results suggest that these analytic procedures are capable of refining voxels that represent individual hypothalamic nuclei in standard resolution. Our results highlight the potential utility of these procedures in various settings such as patient studies, where lengthy scans are infeasible.Misfolded proteins trapped in the endoplasmic reticulum (ER) are specifically recognized and retrotranslocated to the cytosol by the ER-Associated Degradation (ERAD) system and delivered to the proteasome for destruction. This process was recently described in Trypanosoma brucei (T. brucei) using the misfolded epitope tagged Transferrin Receptor subunits ESAG7Ty and HAESAG6 (HAE6). Critical to this work was the proteasomal inhibitor MG132. However, MG132 has off-target inhibitory effects on lysosomal Cathepsin L that could cause misinterpretation of turnover results. Here, we evaluate an orally bioavailable p97 inhibitor, CB-5083, for use in T. brucei. p97 is a ubiquitous protein involved in many cellular events including the membrane extraction step of ERAD. CB-5083 strongly inhibits turnover of HAE6, with comparable protein recovery to MG132 treatment. Interestingly, little deglycosylated cytoplasmic species accumulates, though it normally emerges with MG132 treatment. This suggests that CB-5083 blocks ERAD upstream of the proteasome, as expected for inhibition of the trypanosomal p97 orthologue TbVCP. Under CB-5083 treatment, HAE6 is also strongly membrane-associated, suggesting ER localization. Finally, we provide an experimental example where CB-5083 treatment offers clarity to the off-target effects of MG132 treatment.A new cytorhabdovirus was identified in zucchini (Cucurbita pepo) in Greece with the aid of high-throughput sequencing technology. The negative-sense, single-stranded genomic RNA of the new virus was determined and includes seven open reading frames in the order 3'-N-P-P3-P4-M-G-L-5' in the antigenomic orientation. Typical rhabdovirus-like particles were observed in infected leaf material. Comparative sequence analysis and phylogenetic reconstructions suggested that the described virus is a new member of the genus Cytorhabdovirus, and it was tentatively named cucurbit cytorhabdovirus 1 (CuCV1). To our knowledge CuCV1 is the first cytorhabdovirus infecting cucurbits in nature. Our surveys indicated that it occurs in a percentage of 36.7 % in zucchini crops in Greece.Fuchs endothelial corneal dystrophy (FECD) is a common cause for heritable visual loss in the elderly. Since the first description of an association between FECD and common polymorphisms situated within the transcription factor 4 (TCF4) gene, genetic and molecular studies have implicated an intronic CTG trinucleotide repeat (CTG18.1) expansion as a causal variant in the majority of FECD patients. To date, several non-mutually exclusive mechanisms have been proposed that drive and/or exacerbate the onset of disease. These mechanisms include (i) TCF4 dysregulation; (ii) toxic gain-of-function from TCF4 repeat-containing RNA; (iii) toxic gain-of-function from repeat-associated non-AUG dependent (RAN) translation; and (iv) somatic instability of CTG18.1. However, the relative contribution of these proposed mechanisms in disease pathogenesis is currently unknown. In this review, we summarise research implicating the repeat expansion in disease pathogenesis, define the phenotype-genotype correlations between FECD and CTG18.1 expansion, and provide an update on research tools that are available to study FECD as a trinucleotide repeat expansion disease. Furthermore, ongoing international research efforts to develop novel CTG18.1 expansion-mediated FECD therapeutics are highlighted and we provide a forward-thinking perspective on key unanswered questions that remain in the field.
Chronic amino acid (AA) deficiency, as in kwashiorkor, reduces the size of the pancreas through an effect on mammalian target of rapamycin complex 1 (mTORC1). Because of the physiological importance of AAs and their role as a substrate, a stimulant of mTORC1, and protein synthesis, we studied the effect of acute protein and AA deficiency on the response to feeding.

ICR/CD-1 mice were fasted overnight and refed for 2 hours with 4 different isocaloric diets control (20% Prot); Protein-free (0% Prot); control (AA-based diet), and a leucine-free (No Leu). Protein synthesis, polysomal profiling, and the activation of several protein translation factors were analyzed in pancreas samples.

All diets stimulated the Protein Kinase-B (Akt)/mTORC1 pathway, increasing the phosphorylation of the kinase Akt, the ribosomal protein S6 (S6) and the formation of the eukaryotic initiation factor 4F (eIF4F) complex. Total protein synthesis and polysome formation were inhibited in the 0% Prot and No Leu groups to a similar extent, compared with the 20% Prot group. The 0% Prot diet partially reduced the Akt/mTORC1 pathway and the activity of the guanine nucleotide exchange factor eIF2B, without affecting eIF2α phosphorylation. The No Leu diet increased the phosphorylation of eIF2α and general control nonderepressible 2, and also inhibited eIF2B activity, without affecting mTORC1. Essential and nonessential AA levels in plasma and pancreas indicated a complex regulation of their cellular transport mechanisms and their specific effect on the synthesis of digestive enzymes.

These studies show that dietary AAs are important regulators of postprandial digestive enzyme synthesis, and their deficiency could induce pancreatic insufficiency and malnutrition.
These studies show that dietary AAs are important regulators of postprandial digestive enzyme synthesis, and their deficiency could induce pancreatic insufficiency and malnutrition.The patterns of collective behaviour in a population emerging from individual animal movement have long been of interest to ecologists, as has the emergence of heterogeneous patterns among a population. In this paper we will consider these phenomena by using an individual-based modelling approach to simulate a population whose individuals undergo density-dependent movement in 2D spatial domains. We first show that the introduction of density-dependent movement in the form of two parameters, a perception radius and a probability of directed movement, leads to the formation of clusters. We then show that the properties of the clusters and their stability over time are different between populations of Brownian and non-Brownian walkers and are also dependent on the choice of parameters. Finally, we consider the effect of the probability of directed movement on the temporal stability of clusters and show that while clusters formed by Brownian and non-Brownian walkers may have similar properties with certain parameter sets, the spatio-temporal dynamics remain different.The interaction between the angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a pivotal role in virus entry into the host cells. Since recombinant ACE2 protein has been suggested as an anti-SARS-CoV-2 therapeutic agent, this study was conducted to design an ACE2 protein with more desirable properties. In this regard, the amino acids with central roles in enzymatic activity of the ACE2 were substituted. Moreover, saturation mutagenesis at the interaction interface between the ACE2 and RBD was performed to increase their interaction affinity. Phosphoramidon The best mutations to increase the structural and thermal stability of the ACE2 were also selected based on B factors and mutation effects. The obtained resulted revealed that the Arg273Gln and Thr445Gly mutation have drastically reduced the binding affinity of the angiotensin-II into the active site of ACE2. The Thr27Arg mutation was determined to be the most potent mutation to increase the binding affinity. The Asp427Arg mutation was done to decrease the flexibility of the region with high B factor. The Pro451Met mutation along with the Gly448Trp mutation was predicted to increase the thermodynamic stability and thermostability of the ACE2. The designed therapeutic ACE2 would have no enzymatic activity while it could bear stronger interaction with Spike glycoprotein of the SARS-CoV-2. Moreover, decreased in vivo enzymatic degradation would be anticipated due to increased thermostability. This engineered ACE2 could be exploited as a novel therapeutic agent against COVID-19 after necessary evaluations.Group defense is a phenomenon that occurs in many predator-prey systems. Different functional responses with substantially different properties representing such a mechanism exist. Here, we develop a functional response using timescale separation. A prey-dependent catch rate represents the group defense. The resulting functional response contains a single parameter that controls whether the group defense functional response is saturating or dome-shaped. Based on that, we show that the catch rate must not increase monotonically with increasing prey density to lead to a dome-shaped functional response. We apply bifurcation analysis to show that non-monotonic group defense is usually more successful. However, we also find parameter regions in which a paradox occurs. In this case, higher group defense can give rise to a stable limit cycle, while for lower values, the predator would go extinct. The study does not only provide valuable insight on how to include functional responses representing group defense in mathematical models, but it also clarifies under which circumstances the usage of different functional responses is appropriate.Poverty has consistently been linked to poor mental health and risky health behaviors, yet few studies evaluate the effectiveness of programs and policies to address these outcomes by targeting poverty itself. We test the hypothesis that the earned income tax credit (EITC)-the largest U.S. poverty alleviation program-improves short-term mental health and health behaviors in the months immediately after income receipt. We conducted parallel analyses in two large longitudinal national data sets the National Health Interview Survey (NHIS, 1997-2016, N = 379,603) and the Panel Study of Income Dynamics (PSID, 1985-2015, N = 29,808). Outcomes included self-rated health, psychological distress, tobacco use, and alcohol consumption. We employed difference-in-differences analysis, a quasi-experimental technique. We exploited seasonal variation in disbursement of the EITC, which is distributed as a tax refund every spring we compared outcomes among EITC-eligible individuals interviewed immediately after refund receipt (Feb-Apr) with those interviewed in other months more distant from refund receipt (May-Jan), "differencing out" seasonal trends among non-eligible individuals.
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