Cardiovascular and ventilatory interactions in the facultative air-breathing teleost Pangasianodon hypophthalmus

Journal of Comparative Physiology B - All vertebrates possess baroreceptors monitoring arterial blood pressure and eliciting reflexive changes in vascular resistance and heart rate in response to...     

BaSIQS - basic scale on insomnia complaints and quality of sleep: reliability,norms, validity,and accuracy studies,based on clinical and community samples

This research focused on the Basic Scale on Insomnia Symptoms and Quality of Sleep (BaSIQS), formerly validated in undergraduates using the Pittsburgh Sleep Quality Index (PSQI), and aimed to expand internal consistency analysis, examine thoroughly its validity, and determine its clinical accuracy. Considering objective and subjective measures, recruiting non-clinical and clinical samples, this research implemented a comprehensive approach to examine convergent and discriminant validity, confirmatory factor analyses, and the BaSIQS sensitivity and specificity. The BaSIQS was filled out along with the Insomnia Severity Index (ISI), questions on sleep-wake schedules, Composite Scale of Morningness (CSM) and Brief Symptom Inventory-18 (BSI-18) by 1198 adults, 18–64 years old, plus another 30 who wore actimeters, recruited in community settings. A clinical group of 30 chronic insomnia disorder patients also participated. Cronbach alpha coefficient was 0.80. A two-factor structure was confirmed. The association between BaSIQS and ISI was large, whereas actigraphy correlations were medium or small. Medium to non-significant correlations were found concerning conceptually different self-report measures. Comparing the clinic and control groups, the former showed poorer sleep, with a large effect size. Receiver operating characteristic analysis revealed an area under curve = 0.9, and an optimal cut-off score >15. In conclusion, results on reliability, validity, and accuracy provide support to the utility of the BaSIQS both in community and clinical settings, for research and practical purposes.     

MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors

Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen-activated protein kinase (MAPK) signaling pathways (extracellular signal-regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK-MAPK-ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho-p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK-MAPK-ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.     

Exogenous expression of caveolin-1 is sufficient for hepatic stellate cell activation

Caveolin-1 (Cav-1) expression is increased in hepatic stellate cells (HSC) upon liver cirrhosis and it functions as an integral membrane protein of lipid rafts and caveolae that regulates and integrates multiple signals as a platform. This study aimed to evaluate the role of Cav-1 in HSC. Thus, the effects of exogenous expression of Cav-1 in GRX cells, a model of activated HSC, were determined. Here, we demonstrated through evaluating well-known HSC activation markers – such as α-smooth muscle actin, collagen I, and glial fibrillary acidic protein – that up regulation of Cav-1 induced GRX to a more activated phenotype. GRX^EGFP-Cav1 presented an increased migration, an altered adhesion pattern, a reorganization f-actin cytoskeleton, an arrested cell cycle, a modified cellular ultrastructure, and a raised endocytic flux. Based on this, GRX ^EGFP-Cav1 represents a new cellular model that can be an important tool for understanding of events related to HSC activation. Furthermore, our results reinforce the role of Cav-1 as a molecular marker of HSC activation.     

Essential oils as vespid wasp repellents: Implications for their use as a management strategy

Recently, plant‐based repellents have been proposed as a potential alternative to classic pesticides against pest wasps, in certain scenarios. Here, the repellent effect of Dysphania multifida essential oil and one of its main terpenoid components, α‐terpinene, were tested under field conditions with natural populations of wasps in Patagonia Argentina. D. multifida essential oil (paico), as well as α‐terpinene, repelled V. germanica wasps in the field. A strong avoidance of food baits treated with the essential oil or α‐terpinene was observed in choice and no‐choice tests. In no‐choice tests, the time it took wasps to arrive at the bait was significantly greater in treated baits than in control baits. Also, the total number of arriving wasps in 30 min was significantly greater in untreated baits in comparison with treated baits, under similar environmental conditions and wasp density. As the wasps’ flight season progressed, wasp density and motivation for proteinaceous food sources increased. This was evidenced by a greater total number of wasps in untreated baits with time. On the contrary, the number of wasps in treated baits remained low throughout the peak season. Both the paico essential oil and the α‐terpinene act as powerful repellents for V. germanica wasps, generating an avoidance response to treated food sources. Thus, these compounds have potential to be used as repellents to prevent wasps’ approaches and foraging, when applied in close proximity to a food source.     

Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10. Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.     

SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice

Acute and chronic inflammations are key homeostatic events in health and disease. Sirtuins (SIRTs), a family of NAD-dependent protein deacylases, play a pivotal role in the regulation of these inflammatory responses. Indeed, SIRTs have anti-inflammatory effects through a myriad of signaling cascades, including histone deacetylation and gene silencing, p65/RelA deacetylation and inactivation, and nucleotide‑binding oligomerization domain, leucine rich repeat, and pyrin domain‑containing protein 3 inflammasome inhibition. Nevertheless, recent findings show that SIRTs, specifically SIRT6, are also necessary for mounting an active inflammatory response in macrophages. SIRT6 has been shown to positively regulate tumor necrosis factor alpha (TNFα) secretion by demyristoylating pro-TNFα in the cytoplasm. However, how SIRT6, a nuclear chromatin-binding protein, fulfills this function in the cytoplasm is currently unknown. Herein, we show by Western blot and immunofluorescence that in macrophages and fibroblasts there is a subpopulation of SIRT6 that is highly unstable and quickly degraded via the proteasome. Upon lipopolysaccharide stimulation in Raw 264.7, bone marrow, and peritoneal macrophages, this population of SIRT6 is rapidly stabilized and localizes in the cytoplasm, specifically in the vicinity of the endoplasmic reticulum, promoting TNFα secretion. Furthermore, we also found that acute SIRT6 inhibition dampens TNFα secretion both in vitro and in vivo, decreasing lipopolysaccharide-induced septic shock. Finally, we tested SIRT6 relevance in systemic inflammation using an obesity-induced chronic inflammatory in vivo model, where TNFα plays a key role, and we show that short-term genetic deletion of SIRT6 in macrophages of obese mice ameliorated systemic inflammation and hyperglycemia, suggesting that SIRT6 plays an active role in inflammation-mediated glucose intolerance during obesity.     

Characterization of the complete chloroplast genome of Zephyranthes phycelloides (Amaryllidaceae,tribe Hippeastreae) from Atacama region of Chile

Sporadic rains in the Atacama Desert reveal a high biodiversity of plant species that only occur there. One of these rare species is the “Red añañuca” (Zephyranthes phycelloides), formerly known as Rhodophiala phycelloides. Many species of Zephyranthes in the Atacama Desert are dangerously threatened, due to massive extraction of bulbs and cutting of flowers. Therefore, studies of the biodiversity of these endemic species, which are essential for their conservation, should be conducted sooner rather than later. There are some chloroplast genomes available for Amaryllidaceae species, however there is no complete chloroplast genome available for any of the species of Zephyranthes subgenus Myostemma. The aim of the present work was to characterize and analyze the chloroplast of Z. phycelloides by NGS sequencing. The chloroplast genome of the Z. phycelloides consists of 158,107 bp, with typical quadripartite structures: a large single copy (LSC, 86,129 bp), a small single copy (SSC, 18,352 bp), and two inverted repeats (IR, 26,813 bp). One hundred thirty-seven genes were identified: 87 coding genes, 8 rRNA, 38 tRNA and 4 pseudogenes. The number of SSRs was 64 in Z. phycelloides and a total of 43 repeats were detected. The phylogenetic analysis of Z. phycelloides shows a distinct subclade with respect to Z. mesochloa. The average nucleotide variability (Pi) between Z. phycelloides and Z. mesochloa was of 0.02000, and seven loci with high variability were identified: psbA, trnS^GCU-trnG^UCC, trnD^GUC-trnY^GUA, trnL^UAA-trnF^GAA, rbcL, psbE-petL and ndhG-ndhI. The differences between the species are furthermore confirmed by the high amount of SNPs between these two species. Here, we report for the first time the complete cp genome of one species of the Zephyranthes subgenus Myostemma, which can be used for phylogenetic and population genomic studies.     

Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro—Brazil

IntroductionPure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature.ObjectiveThis paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT).MethodsFifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS.ResultsParesthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT.DiscussionThe classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.