Deciphering the molecular pathways associated with N‐methyl‐D‐aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of ...schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain‐derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK‐801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK‐801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass‐spectrometry‐based proteomics and systems biology in silico analyses, we found that MK‐801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK‐801‐induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK‐801‐induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK‐801 and antipsychotics in the human brain.
Schizophrenia presents a complex molecular pathophysiology, and the hypofunction of the glutamatergic NMDA receptor is recognized as one of the primary mechanisms. Using adult human brain‐derived slice cultures and proteomics, we have identified altered pathways in NMDA antagonist MK‐801‐treated slices, some of which are associated with schizophrenia in previous works. By co‐treating the slices with MK‐801 and antipsychotics, we showed that clozapine was more effective in attenuating the molecular alterations caused by NMDAr hypofunction than haloperidol.
Understanding Covid-19 pathophysiology is crucial for a better understanding of the disease and development of more effective treatments. Alpha-1-antitrypsin (A1AT) is a constitutive tissue protector ...with antiviral and anti-inflammatory properties. A1AT inhibits SARS-CoV-2 infection and two of the most important proteases in the pathophysiology of Covid-19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). It also inhibits the activity of inflammatory molecules, such as IL-8, TNF-α, and neutrophil elastase (NE). TMPRSS2 is essential for SARS-CoV-2-S protein priming and viral infection. ADAM17 mediates ACE2, IL-6R, and TNF-α shedding. ACE2 is the SARS-CoV-2 entry receptor and a key component for the balance of the renin-angiotensin system, inflammation, vascular permeability, and pulmonary homeostasis. In addition, clinical findings indicate that A1AT levels might be important in defining Covid-19 outcomes, potentially partially explaining associations with air pollution and with diabetes. In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid-19, opening new avenues for investigating effective treatments.
Here, we describe the metagenome and functional composition of a microbial community in a historically metal-contaminated tropical freshwater stream sediment. The sediment was collected from the Mina ...Stream located in the Iron Quadrangle (Brazil), one of the world's largest mining regions. Environmental DNA was extracted and was sequenced using SOLiD technology, and a total of 7.9 Gbp was produced. A taxonomic profile that was obtained by comparison to the Greengenes database revealed a complex microbial community with a dominance of Proteobacteria and Parvarcheota. Contigs were recruited by bacterial and archaeal genomes, especially Candidatus Nitrospira defluvii and Nitrosopumilus maritimus, and their presence implicated them in the process of N cycling in the Mina Stream sediment (MSS). Functional reconstruction revealed a large, diverse set of genes for ammonium assimilation and ammonification. These processes have been implicated in the maintenance of the N cycle and the health of the sediment. SEED subsystems functional annotation unveiled a high degree of diversity of metal resistance genes, suggesting that the prokaryotic community is adapted to metal contamination. Furthermore, a high metabolic diversity was detected in the MSS, suggesting that the historical arsenic contamination is no longer affecting the prokaryotic community. These results expand the current knowledge of the microbial taxonomic and functional composition of tropical metal-contaminated freshwater sediments.
Despite current literature pointing to a link between shortened telomeres and aging, chronic diseases, and geriatric syndromes, the precise implications of this connection remain unclear. The aim of ...this exploratory, cross-sectional, observational study was to investigate the association between the relative telomere length (RTL) of peripheral blood leukocyte subtypes (mononuclear cells and granulocytes) and physical performance using the Short Physical Performance Battery (SPPB) in older adults. A cohort of 95 participants was recruited, which included men and women aged over 60 years (70.48 ± 5.5 years). It was found that mononuclear cell RTL was significantly lower than that of granulocytes (
< 0.0001). Moreover, individuals with good SPPB performance exhibited lower mononuclear cell RTL compared with those with moderate or poor performance. However, no significant differences were observed in granulocyte RTL between different SPPB performance groups. The global SPPB score showed an inverse correlation with mononuclear cell RTL, but this correlation was not present with granulocyte RTL. Similarly, the SPPB sit-to-stand domain correlated with mononuclear cell RTL, but no such correlation was found with granulocyte RTL. Our findings challenge conventional expectations, suggesting that shorter mononuclear cell RTL may be associated with favorable functional capacity. The variations in RTL between mononuclear cells and granulocytes highlight their distinct biological roles and turnover rates. A history of immune responses may influence mononuclear cell RTL dynamics, while telomerase activity may protect granulocyte RTL from significant shortening. The unexpected associations observed in mononuclear cell RTL emphasize the complex interplay between immune responses, cellular aging, and functional capacity in older adults.
The goal was to develop a quinoa milk with increased amount of protein and low glycemic index. The adaptation of a process of rice milk was carried out to increase the extraction of proteins from ...grains to beverage. The product was analyzed for proximate analysis, sodium, starch, sugar, glycemic index, and consumer acceptance in comparison with a commercial rice milk. The inclusion of soaking step and the change of cooking step by replacing water by acidified saline solution (0.03 mol/L sodium chloride, pH 5.0) resulted in about 3 times more protein. Sodium content (20.3 mg/100 g) and lipids (0.2 g/100 g) were lower in comparison with other milks. Quinoa milk presented 5 g/100 g of starch and 9.7 g/100 g of glucose, but the glycemic index was low (52). Sensory acceptance was similar to that of rice milk, but differences were found for attributes and consumers groups. The group that need to consume vegetable milks showed higher acceptance for quinoa milk. The addition of flavor may be recommended to improve odor acceptance. Quinoa milk represents a novel alternative to current milk-substitute products that cause no known adverse effects in humans and which have increased protein content and low glycemic index.
•New insights into the technological requirements to improve protein solubility in quinoa milk.•Soaking quinoa grains and cooking it in acidified saline solution resulted in increased protein content in quinoa milk.•Quinoa milk, like cow and soybean milks, presented a low glycemic index.•Consumers who need to consume vegetable milks preferred quinoa milk to a commercial rice milk.
Objectives
The present study aimed to compare the guided dual technique with the conventional technique in esthetic crown lengthening (ECL).
Materials and methods
The trial registration number is ...NCT04922086. Twenty-four participants diagnosed with altered passive eruption (APE) type I subcategory B were selected and allocated into two groups. In the control group (
n
= 12), the ECL procedure was planned by clinical examination and transgingival probing; in the test group (
n
= 12), the ECL procedure was carried out using digital planning and a double guide. Clinical parameters were assessed at baseline, immediately after the intervention (IAI), and at 4, 8, and 12 months of follow-up.
Results
The clinical crown length (CCL) mean at baseline was 8.09 mm (± 0.77) and increased significantly to 9.92 mm (± 0.62) IAI, with minimal significant reduction after 12 months (9.47 mm ± 0.60) in the control group. Similarly, in the test group, the mean CCL at baseline was 8.04 mm (± 0.69) and increased significantly to 9.94 mm (± 0.57) IAI, with minimal reduction after 12 months (9.35 mm ± 0.80). No differences were found between the mean CCL determined in the digital planning and after 12 months. No correlation was found between gingival thickness and gingival margin stability. High esthetic satisfaction was demonstrated by participants/specialists without differences between groups.
Conclusions
In conclusion, the guided dual technique was as effective as the conventional technique for treatment of APE, with stable results after 12 months of follow-up.
Clinical relevance
The guided dual technique aims to transfer both the gingival and bone resection planned position to facilitate the ECL surgical procedure and increase treatment predictability.
Sulfate-reducing bioreactors are a biotechnological alternative for the treatment of acid mine drainage (AMD). In this study, two separate bioreactors with pH and temperature-controlled (Bio I and ...II) were operated with two different acidophilic microbial consortia to determine their efficiencies in sulfate removal from a synthetic acidic mine water. The bioreactors were operated for 302 days in continuous flow mode under the same parameters: fed with a sulfate solution of ∼30 mM with a pH of 2.5, the temperature at 30°C, stirred gently at 40 rpm and using a continuous stream of nitrogen to help remove the H
S produced in the bioreactor. The glycerol consumption, acetate production, and sulfate removal were monitored throughout the course of the experiment. The community composition and potential metabolic functional groups were analyzed
16S rRNA partial gene sequencing. Bio I consortium reduced the sulfate, achieving a range of sulfate concentration from 4.7 to 19 mM in the effluent liquor. The removal of sulfate in Bio II was between 5.6 and 18 mM. Both bioreactors' communities showed the presence of the genus
as the main sulfate-reducing bacteria (SRB). Despite differences in microbial composition, both bioreactors have similar potential metabolism, with a higher percentage of microorganisms that can use sulfate in respiration. Overall, both bioreactors showed similar performance in treating acidic mine water containing mostly sulfate using two different acidophilic sulfidogenic consortia obtained from different global locations.
Acid Mine Drainage (AMD) is an environmental problem associated with mining activities, which resulted from the exposure of sulfur bearing materials to oxygen and water. AMD is a pollution source due ...to its extreme acidity, high concentration of sulfate, and soluble metals. Biological AMD treatment is one alternative to couple environmental amelioration for valuable dissolved metals recovery, as a new source of raw materials. Covellite (CuS) particles were synthetized from an AMD sample collected in a Brazilian copper mine, after 48 and 96 h of exposure to hydrogen sulfide (H2S) produced in a bioreactor containing acidophilic sulfate reducing bacteria (SRB). The time of exposure affected the morphology, nucleation, and size of CuS crystals. CuS crystals synthetized after 96 h of H2S exposure showed better ordination as indicated by sharp and intense diffractograms obtained by X-ray diffraction (XRD), and the predominance of placoid sheets with hexagonal habit structure as observed by scanning electrons microscopy (SEM). Energy dispersive X-ray fluorescence (EDXRF) spectrometry indicated a Cu:S molar ratio in agreement with CuS. Granulometric analysis demonstrated that 90% of CuS particles were less than 22 µm size. AMD biological treatment is a potential economical CuS recovery option for metallurgical process chain incorporation, or new industrial applications, since the alteration of synthesis conditions can produce different crystal forms with specific characteristics.
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