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Aggressive escalations were not common, but more frequent in Japanese macaques. Finally, a higher frequency of play faces during play sessions predicted the occurrence of more reciprocal play-bites, but not the proportion of time spent in contact play behaviors. Additional studies on other groups and species will allow a better understanding of the link between dominance style and social play.The aim of this prospective experimental study was to investigate the effects of pregabalin (PG) administration and withdrawal on testicular structures and functions in rats. A total of 24 male Wistar rats were divided into two groups (n = 12 each) a control group received normal saline, and PG-treated group received 62 mg kg-1 day-1 PG for 2 months. Half the animals of each group were sacrificed for the collection of blood and testicular samples. The remaining animals were bred for another 2 months without treatment before collection of blood and testicular samples. PG administration decreased testosterone and increased luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels versus controls. PG withdrawal led to a decrease in both FSH and LH and an increase in testosterone levels versus saline withdrawal. Compared to controls, PG administration caused degeneration of seminiferous tubules and decreased the number of spermatogenic but increased the number of Leydig cells. After PG withdrawal, these cells showed a rebound reverse. Reduced glutathione levels increased with PG administration while PG withdrawal increased malondialdehyde levels. Conclusion PG administration affected testicular morphometry, gonadotrophic and sex hormones; however, there was a rebound reversal in all these parameters and a significant oxidative stress in PG withdrawal.Classic galactosemia (CG) is a rare metabolic disorder that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection by newborn screening and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad constellation of long-term complications. The mechanisms underlying these complications remain unclear and likely differ by tissue. Here we conducted a pilot study testing the safety and efficacy of GALT gene replacement using our recently-described GALT-null rat model for CG. Specifically, we administered AAV9.CMV.HA-hGALT to seven GALT-null rat pups via tail vein injection on day 3 of life; eight GALT-null pups injected with PBS served as the negative control, and four GALT+ heterozygous pups injected with PBS served as the positive control. All pups were returned to their nursing mothers, weighed daily, and euthanized for tissue collection 2 weeks later. Among the AAV9-injected pups in this study, we achieved GALT levels in liver ranging from 64% to 595% wild-type, and in brain ranging from 3% to 42% wild-type. In liver, brain, and blood samples from these animals we also saw a striking drop in galactose, galactitol, and gal-1P. Finally, all treated GALT-null pups showed dramatic improvement in cataracts relative to their mock-treated counterparts. Combined, these results demonstrate that GALT restoration in both liver and brain of GALT-null rats by neonatal tail vein administration using AAV9 is not only attainable but effective.Bile salts are secreted into the gastrointestinal tract to aid in the absorption of lipids. In addition, bile salts show potent antimicrobial activity in part by mediating bacterial protein unfolding and aggregation. Here, using a protein folding sensor, we made the surprising discovery that the Escherichia coli periplasmic glycerol-3-phosphate (G3P)-binding protein UgpB can serve, in the absence of its substrate, as a potent molecular chaperone that exhibits anti-aggregation activity against bile salt-induced protein aggregation. The substrate G3P, which is known to accumulate in the later compartments of the digestive system, triggers a functional switch between UgpB's activity as a molecular chaperone and its activity as a G3P transporter. A UgpB mutant unable to bind G3P is constitutively active as a chaperone, and its crystal structure shows that it contains a deep surface groove absent in the G3P-bound wild-type UgpB. Our work illustrates how evolution may be able to convert threats into signals that first activate and then inactivate a chaperone at the protein level in a manner that bypasses the need for ATP.Studies from China on COVID-19 revealed that nonsurvivors had cytokine storm with high IL-6 and hyperferritinemia. Iron liberated from necrotic cells may catalyze free radical production and amplify lipid peroxidation causing membrane dysfunction and multiorgan failure. Consequently, iron chelators have been successfully utilized in various experimental and clinical models of cytokine storm and multiorgan damage, such as in ischemia-reperfusion injury, sepsis, and infections. Since viral replication may be influenced by iron accumulation, iron chelation has been proven beneficial in a variety of viral infections, such as HIV-1, hepatitis B virus, Mengovirus, Marburg hemorrhagic fever, Enterovirus 71, and West Nile virus. In this commentary, we elaborate on the idea of considering iron chelation as a therapeutic modality in patients with severe COVID-19 infection. For critically ill patients in the ICU, intravenous deferoxamine would provide sufficient and rapid iron chelation to ameliorate cytokine storm, whereas in less severe cases an oral chelator could prevent the development of excessive inflammatory response.The domain-based local pair natural orbital coupled-cluster with single, double, and perturbative triples excitation (DLPNO-CCSD(T)) method was employed to portray the activation and reaction energies of four ubiquitous enzymatic reactions, and its performance was confronted to CCSD(T)/complete basis set (CBS) to assess its accuracy and robustness in this specific field. The DLPNO-CCSD(T) results were also confronted to those of a set of density functionals (DFs) to understand the benefit of implementing this technique in enzymatic quantum mechanics/molecular mechanics (QM/MM) calculations as a second QM component, which is often treated with DF theory (DFT). On average, the DLPNO-CCSD(T)/aug-cc-pVTZ results were 0.51 kcal·mol-1 apart from the canonic CCSD(T)/CBS, without noticeable biases toward any of the reactions under study. All DFs fell short to the DLPNO-CCSD(T), both in terms of accuracy and robustness, which suggests that this method is advantageous to characterize enzymatic reactions and that its use in QM/MM calculations, either alone or in conjugation with DFT, in a two-region QM layer (DLPNO-CCSD(T)DFT), should enhance the quality and faithfulness of the results.Sulfite oxidase (SO) deficiency is a disorder caused either by isolated deficiency of SO or by defects in the synthesis of its molybdenum cofactor. It is characterized biochemically by tissue sulfite accumulation. Patients present with seizures, progressive neurological damage, and basal ganglia abnormalities, the pathogenesis of which is not fully established. Treatment is supportive and largely ineffective. To address the pathophysiology of sulfite toxicity, we examined the effects of intrastriatal administration of sulfite in rats on antioxidant defenses, energy transfer, and mitogen-activated protein kinases (MAPK) and apoptosis pathways in rat striatum. Sulfite administration decreased glutathione (GSH) concentration and glutathione peroxidase, glucose-6-phosphate dehydrogenase, glutathione S-transferase, and glutathione reductase activities in striatal tissue. Creatine kinase (CK) activity, a crucial enzyme for cell energy transfer, was also decreased by sulfite. Superoxide dismutase-1 (SOD1) and catalase (CAT) proteins were increased, while heme oxygenase-1 (HO-1) was decreased. Additionally, sulfite altered phosphorylation of MAPK by decreasing of p38 and increasing of ERK. 1-Deoxynojirimycin Sulfite further augmented the content of GSK-3β, Bok, and cleaved caspase-3, indicating increased apoptosis. JP4-039 is a mitochondrial-targeted antioxidant that reaches higher intramitochondrial levels than other traditional antioxidants. Intraperitoneal injection of JP4-039 before sulfite administration preserved activity of antioxidant enzymes and CK. It also prevented or attenuated alterations in SOD1, CAT, and HO-1 protein content, as well as changes in p38, ERK, and apoptosis markers. In sum, oxidative stress and apoptosis induced by sulfite injection are prevented by JP4-039, identifying this molecule as a promising candidate for pharmacological treatment of SO-deficient patients.

Mistletoes parasitize many hardwood and softwood tree species; however, they play key roles in forest ecosystems. Adult individuals of Psittacanthus schiedeanus take up water and xylem nutrients from both deciduous and evergreen host trees, suggesting the ability to modify its physiology according to the availability of host resources. Yet, there is little information regarding the effects of mistletoes on their host trees from the eophyll stage to reproductive phases of the parasite.

Taking advantage of the fact that P. schiedeanus can reach sexual maturity in 1 year, we investigated its physiological performance during development on deciduous (Liquidambar styraciflua) and evergreen (Quercus germana) host trees in a cloud forest in eastern Mexico. Variables related to chlorophyll fluorescence, carbon assimilation, photosynthetic pigments, and nitrogen, phosphorus, and carbon contents of the parasite and non-infected and infected hosts were analyzed in a nursery experiment.

Mistletoe had lower water-use efficiency and higher transpiration rates than the host species did. Despite the fact that P. schiedeanus obtained resources from species with differing phenology and resource availability, the parasite steadily improved its CO

assimilation, electron transport rate, and nutrient content from seedling establishment to adult life stages. Mistletoe decreased the photosynthetic reactions of carbon metabolism in the deciduous host, photosynthetic light reactions in the evergreen host, and nutritional status of both host species, mostly in the evergreen host.

The hypothesis that mistletoes adjust their physiology according to the availability of host resources could extend to the early growth of the parasite.

The hypothesis that mistletoes adjust their physiology according to the availability of host resources could extend to the early growth of the parasite.The continuous search for new allergens and the design of allergen derivatives improves the understanding of their allergenicity and aids the design of novel diagnostic and immunotherapy approaches. This article discusses the recent developments in allergen and epitope discovery, allergy diagnostics and immunotherapy. Structural information is crucial for the elucidation of cross-reactivity of marker allergens such as the walnut Jug r 6 or that of nonhomologous allergens, as shown for the peanut allergens Ara h 1 and 2. High-throughput sequencing, liposomal nanoallergen display, bead-based assays, and protein chimeras have been used in epitope discovery. The binding of natural ligands by the birch pollen allergen Bet v 1 or the mold allergen Alt a 1 increased the stability of these allergens, which is directly linked to their allergenicity. We also report recent findings on the use of component-resolved approaches, basophil activation test, and novel technologies for improvement of diagnostics. New strategies in allergen-specific immunotherapy have also emerged, such as the use of virus-like particles, biologics or novel adjuvants.

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