Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially ...associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.
Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents ...similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen's ability to protect against blood borne pathogens.
Anti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to ...investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR).
Rats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10–10 to 10–4 M) on aortic rings of rats were also assessed.
In Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only).
Rose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.
To measure left ventricular (LV) global longitudinal strain (GLS) using speckle tracking echocardiography in idiopathic inflammatory myopathy (IIM) patients and to determine whether the LV GLS ...predicts outcomes in those patients. Prospective study consisted of a cross-sectional phase with 61 IIM patients and 32 individuals without IIM and longitudinal phase, in which patients were divided into two subgroups: 26 with reduced LV GLS and 35 with normal LV GLS; patients were followed for a mean of 25 months, and the occurrence of cardiovascular events and criteria for IIM activity were compared. The mean LV GLS (18.5 ± 2.9% vs. 21.6 ± 2.5%; p < 0.001) and right ventricle free wall strain (21.9 ± 6.1% vs. 27.5 ± 4.7%; p < 0.001) were lower in patients than in controls. The mean N-terminal pro B-type natriuretic peptide level was higher in patients than in controls. There were no differences regarding other cardiac involvement. Anti-Jo1 antibody was associated with general electrocardiographic abnormality and LV diastolic dysfunction. The subgroup with reduced GLS progressed with higher mean creatine phosphokinase, myositis disease activity assessment visual analogue scales, the physician’s and patient’s visual analogue scales, the health assessment questionnaire, and a higher proportion of relapses than the subgroup with normal GLS. There was no difference between the subgroups regarding cardiovascular events. The LV GLS appears to be useful for evaluating patients with IIM. Abnormal values are associated with more frequent relapses and increased disease activity during follow-up.
An outbreak of poisoning by Lantana camara occurred in cattle when a herd sought refuge in a Eucalyptus forest heavily infested by this plant. The animals showed apathy, elevated serum activities of ...hepatic enzymes, severe photosensitivity, jaundice, hepatomegaly and nephrosis. After a clinical manifestation period of 2–15 days, 74 out of 170 heifers died. The main histological changes were random hepatocellular necrosis, cholestasis, biliary proliferation and, in one animal, centrilobular necrosis. Immunostaining for Caspase 3 detected scattered apoptotic hepatocytes.
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•Lantana spp. poisoning occurs sporadically in cattle and other species.•Cattle can suffer Lantana spp. poisoning when taking refuge, due to storms, in forests invaded by this plant.•Severe jaundice and photosensitization are hallmarks of the poisoning, but hepatic lesions are variable.•Hepatocyte immunostaining by Caspase 3 suggests that Lantana spp. causes apoptosis in these cells.
Predicting student performance as early as possible and analysing to which extent initial student behaviour could lead to failure or success is critical in introductory programming (CS1) courses, for ...allowing prompt intervention in a move towards alleviating their high failure rate. However, in CS1 performance prediction, there is a serious lack of studies that interpret the predictive model's decisions. In this sense, we designed a long-term study using very fine-grained log-data of 2056 students, collected from the first two weeks of CS1 courses. We extract features that measure how students deal with deadlines, how they fix errors, how much time they spend programming, and so forth. Subsequently, we construct a predictive model that achieved cutting-edge results with area under the curve (AUC) of.89, and an average accuracy of 81.3%. To allow an effective intervention and to facilitate human-AI collaboration towards prescriptive analytics, we, for the first time, to the best of our knowledge, go a step further than the prediction itself and leverage this field by proposing an approach to explaining our predictive model decisions individually and collectively using a game-theory based framework (SHAP), (Lundberg et al. , 2020) that allows interpreting our black-box non-linear model linearly. In other words, we explain the feature effects, clearly by visualising and analysing individual predictions, the overall importance of features, and identification of typical prediction paths. This method can be further applied to other emerging competitive models, as the CS1 prediction field progresses, ensuring transparency of the process for key stakeholders: administrators, teachers, and students.
Psychedelics (serotonergic hallucinogens) are psychoactive substances that can alter perception and mood, and affect cognitive functions. These substances activate 5-HT2A receptors and may exert ...therapeutic effects. Some of the disorders for which psychedelic-assisted therapy have been studied include depression, addiction, anxiety and post-traumatic stress disorder. Despite the increasing number of studies reporting clinical effectiveness, with fewer negative symptoms and, additionally, minimal side effects, questions remain to be explored in the field of psychedelic medicine. Although progress has been achieved, there is still little understanding of the relationship among human brain and the modulation induced by these drugs. The present article aimed to describe, review and highlight the most promising findings in the literature regarding the (putative) therapeutic effects of psychedelics.
•Psychedelics are close structural analogs of serotonin (5-HT).•Activation of the 5-HT2A receptor by psychedelics induces glutamate release.•Psychedelics may cause an increase in the connectivity between amygdala and m-PFC.•Psychedelic therapy is associated with decreased frontoparietal connectivity.•Therapy with psychedelics showed that small doses can cause beneficial outcomes.
Lipids, including the diterpenes cafestol and kahweol, are key compounds that contribute to the quality of coffee beverages. We determined total lipid content and cafestol and kahweol concentrations ...in green beans and genotyped 107 Coffea arabica accessions, including wild genotypes from the historical FAO collection from Ethiopia. A genome-wide association study was performed to identify genomic regions associated with lipid, cafestol and kahweol contents and cafestol/kahweol ratio. Using the diploid Coffea canephora genome as a reference, we identified 6,696 SNPs. Population structure analyses suggested the presence of two to three groups (K = 2 and K = 3) corresponding to the east and west sides of the Great Rift Valley and an additional group formed by wild accessions collected in western forests. We identified 5 SNPs associated with lipid content, 4 with cafestol, 3 with kahweol and 9 with cafestol/kahweol ratio. Most of these SNPs are located inside or near candidate genes related to metabolic pathways of these chemical compounds in coffee beans. In addition, three trait-associated SNPs showed evidence of directional selection among cultivated and wild coffee accessions. Our results also confirm a great allelic richness in wild accessions from Ethiopia, especially in accessions originating from forests in the west side of the Great Rift Valley.
New Findings
What is the central question of this study?
In fever, the most striking response in the acute phase
reaction of systemic inflammation, plasma H2S concentration increases. However, the ...role of endogenous peripheral H2S in fever is unknown.
What is the main finding and its importance?
Endogenous peripheral H2S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation).
In recent years, hydrogen sulfide (H2S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H2S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H2S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H2S modulates LPS‐induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220–270 g) to record body core temperature. These animals received an i.p. injection of a systemic H2S inhibitor (propargylglycine; 50 or 75 mg kg−1), immediately followed by an i.p. injection of LPS (50 or 2500 μg kg−1), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg−1 significantly attenuated (P < 0.0001) the fever induced by LPS (50 μg kg−1), indicating a modulatory (permissive) action of endogenous peripheral H2S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H2S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric oxide pathway, and mainly when (iii) we carried out physiological and pharmacological activations of BAT. Endogenous peripheral H2S modulates (permits) BAT activity not only in fever but also during maintenance of thermal homeostasis in cold environments.
The use of unconventional food for animals is becoming more common. The objective was to evaluate the inclusion of Madagascar cockroach (Gromphadorhina portentosa) meal in the diet of cockatiel ...(Nymphicus hollandicus) chicks in captivity. Twenty-eight cockatiel chicks were used during 90 days of experiment. The animals were divided into two groups: a control group (receiving commercial feed + seed mixture) and a test group (receiving a control diet supplemented with Madagascar cockroach meal). The cockroach meal was mixed into commercial feed at a ratio of 14:1 (commercial feed: cockroach meal; 6.6% inclusion). Parents of the chicks were fed the experimental diets 30 days before egg laying to evaluate the influence of the cockroach meal on offspring development in the nest (1 to 30 days of age). Body development of the birds was evaluated every three days from the first to the 30th day of age and then every 15 days from the 31st to the 90th day of age. The cockroach meal did not influence (P > .05) the growth characteristics, body weight, total length or length of the animal's beaks, wings or tails, but increased seed consumption from the 31st to the 90th day of age. It is concluded that the cockroach meal can be used in the diet of growing cockatiels at an addition level of 6.6%.
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