Phylogenetic analysis of monkeypox virus genomes showed statistically significant divergence and nascent subclades during the 2022 mpox outbreak. Frequency of G>A/C>T transitions has increased in ...recent years, probably resulting from apolipoprotein B mRNA editing enzyme catalytic polypeptide 3G (APOBEC3) deaminase editing. This microevolutionary pattern most likely reflects community spread of the virus and adaptation to humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Triatoma sanguisuga is one of the major vectors of Trypanosoma cruzi in the southeastern US, where it sustains a robust zoonotic parasite transmission cycle and occasional human infections. A better ...understanding of triatomine development may allow for alternative approaches to insecticide-based vector control. Indeed, the role of the gut microbiota and bacterial endosymbionts in triatomine development and in their vectorial capacity is emerging. We investigated here the differences in microbiota among nymph and adult T. sanguisuga, to shed light on the metabolomic interactions occurring during development. Microbiota composition was assessed by 16s gene amplification and deep sequencing from field-caught adult bugs and their laboratory-raised progeny. Significant differences in microbiota bacterial diversity and composition were observed between nymphs and adults. Laboratory-raised nymphs showed a higher taxonomic diversity, and at least seven families predominated. On the other hand, field-caught adults had a lower bacterial diversity and four families comprised most of the microbiota. These differences in compositions were associated with differences in predicted metabolism, with laboratory-raised nymphs microbiota metabolizing a limited diversity of carbon sources, with potential for resource competition between bacterial families, and the production of lactic acid as a predominant fermentation product. On the other hand, field-caught adult microbiota was predicted to metabolize a broader diversity of carbon sources, with complementarity rather than competition among taxa, and produced a diverse range of products in a more balanced manner. The restricted functionality of laboratory-raised nymph microbiota may be associated with their poor development in captivity, and further understanding of the metabolic interactions at play may lead to alternative vector control strategies targeting triatomine microbiota.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HB43 (FAKLLAKLAKKLL) is a synthetic peptide active against cell lines derived from breast, colon, melanoma, lung, prostate, and cervical cancers. Despite its remarkable spectrum of activity, the ...mechanism of action at the molecular level has never been investigated, preventing further optimization of its selectivity. The alternation of charged and hydrophobic residues suggests amphipathicity, but the formation of alpha‐helical structure seems discouraged by its short length and the large number of positively charged residues. Using different biophysical and in silico approaches we show that HB43 is completely unstructured in solution but assumes alpha‐helical conformation in the presence of DPC micelles and liposomes exposing phosphatidylserine (PS) used as mimics of cancer cell membranes. Membrane permeabilization assays demonstrate that the interaction leads to the preferential destabilization of PS‐containing vesicles with respect to PC‐containing ones, here used as noncancerous cell mimics. ssNMR reveals that HB43 is able to fluidify the internal structure of cancer‐cell mimicking liposomes while MD simulations show its internalization in such bilayers. This is achieved by the formation of specific interactions between the lysine side chains and the carboxylate group of phosphatidylserine and/or the phosphate oxygen atoms of targeted phospholipids, which could catalyze the formation of the alpha helix required for internalization. With the aim of better understanding the peptide biocompatibility and the additional antibacterial activity, the interaction with noncancerous cell mimicking liposomes exposing phosphatidylcholine (PC) and bacterial mimicking bilayers exposing phosphatidylglycerol (PG) is also described.
HB43 is a synthetic peptide active against various cancer cells. HB43 gets internalized in cancer cells mimetic bilayers, destabilizing their internal structure whereas the interaction with erythrocyte mimicking bilayers is much weaker. The exposition of phosphatidylserine carboxylate groups creates an accessible negatively charged surface able to catalyze the formation of the alpha helix, required for HB43 internalization.
Cecropin D is an antimicrobial peptide from Bombyx mori displaying anticancer and pro-apoptotic activities and, together with Cecropin XJ and Cecropin A, one of the very few peptides targeting ...esophageal cancer. Cecropin D displays poor similarity to other cecropins but a remarkable similarity in the structure and activity spectrum with Cecropin A and Cecropin XJ, offering the possibility to highlight key motifs at the base of the biological activity. In this work we show by NMR and MD simulations that Cecropin D is partially structured in solution and stabilizes its two-helix folding upon interaction with biomimetic membranes. Simulations show that Cecropin D strongly interacts with the surface of cancer cell biomimetic bilayers where it recognises the phosphatidylserine headgroup often exposed in the outer leaflet of cancerous cells by means of specific salt bridges. Cecropin D is also able to penetrate deeply in bilayers containing cardiolipin, a phospholipid found in mitochondria, causing significant destabilization in the lipid packing which might account for its pro-apoptotic activity. In bacterial membranes, phosphatidylglycerol and phosphatidylethanolamine act synergically by electrostatically attracting cecropin D and providing access to the membrane core, respectively.
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•CecD is one of the few AMPs with in-vitro and in-vivo activity against esophageal cancer.•The mechanism by which CecD selectively recognises and kills cancer cells is unknown.•CecD selectively interacts with cancer and mitochondrial biomimetic membranes.•The formation of a three helical bundle may facilitate the adaptation of CecD to its target membranes.•Based on NMR and MD data, we propose a mechanism for the induction of apoptosis in cancer cells.
This work focuses on investigating the curing process of an epoxy-based resin-Aerotuf 275-34
, designed for aerospace applications. To study the curing degree of Aerotuf 275-34
under processing ...conditions, woven carbon fiber fabric (WCFF)/Aerotuf 275-34
composite laminates were produced by compression molding using different processing temperatures (110, 135, 160, and 200 °C) during 15 and 30 min. Then, the mechanical behavior of the composite laminates was evaluated by tensile tests and correlated to the resin curing degree through Fourier-transform infrared spectroscopy (FTIR) analysis. The results show the occurrence of two independent reactions based on the consumption of epoxide groups and maleimide (MI) double bonds. In terms of epoxide groups, a conversion degree of 0.91 was obtained for the composite cured at 160 °C during 15 min, while the measured tensile properties of ±45° WCFF/Aerotuf 275-34
laminates confirmed that these epoxy resin curing processing conditions lead to an enhancement of the composite mechanical properties.
We compared the safety of different devices by screening for subclinical intracranial embolic events after pulmonary vein isolation with either conventional irrigated radiofrequency (RF) or ...cryoballoon or multielectrode phased RF pulmonary vein ablation catheter (PVAC).
New devices specifically designed to facilitate pulmonary vein isolation procedures have recently been introduced.
This prospective, observational, multicenter study included patients with symptomatic atrial fibrillation referred for pulmonary vein isolation. Ablation was performed using 1 of the 3 catheters. Strict periprocedural anticoagulation, with intravenous heparin during ablation to achieve an activated clotting time >300 s, was ensured in all patients. Cerebral magnetic resonance imaging was performed before and after ablation.
Seventy-four patients were included in the study: 27 in the irrigated RF group, 23 in the cryoballoon group, and 24 in the PVAC group. Total procedure times were 198 ± 50 min, 174 ± 35 min, and 124 ± 32 min, respectively (p < 0.001 for PVAC vs. irrigated RF and cryoballoon). Findings on neurological examination were normal in all patients before and after ablation. Post-procedure magnetic resonance imaging detected a single new embolic lesion in 2 of 27 patients in the irrigated RF group (7.4%) and in 1 of 23 in the cryoballoon group (4.3%). However, in the PVAC group 9 of 24 patients (37.5%) demonstrated 2.7 ± 1.3 new lesions each (p = 0.003 for the presence of new embolic events among the 3 groups).
The PVAC is associated with a significantly higher incidence of subclinical intracranial embolic events. Further study of the causes and significance of these emboli is required to determine the safety of the PVAC.
Phlebotomine sand flies are remarkable vectors of several etiologic agents (virus, bacterial, trypanosomatid Leishmania), posing a heavy health burden for human populations mainly located at ...developing countries. Their intestinal microbiota is involved in a wide range of biological and physiological processes, and could exclude or facilitate such transmission of pathogens. In this study, we investigated the Eubacterial microbiome from digestive tracts of Lu. evansi adults structure using 16S rRNA gene sequence amplicon high throughput sequencing (Illumina MiSeq) obtained from digestive tracts of Lu. evansi adults. The samples were collected at two locations with high incidence of the disease in humans: peri-urban and forest ecosystems from the department of Sucre, Colombia. 289,068 quality-filtered reads of V4 region of 16S rRNA gene were obtained and clustered into 1,762 operational taxonomic units (OTUs) with 97% similarity. Regarding eubacterial diversity, 14 bacterial phyla and 2 new candidate phyla were found to be consistently associated with the gut microbiome content. Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant phyla in all the samples and the core microbiome was particularly dominated by Methylobacterium genus. Methylobacterium species, are known to have mutualistic relationships with some plants and are involved in shaping the microbial community in the phyllosphere. As a remarkable feature, OTUs classified as Wolbachia spp. were found abundant on peri-urban ecosystem samples, in adult male (OTUs n = 776) and unfed female (OTUs n = 324). Furthermore, our results provide evidence of OTUs classified as Cardinium endosymbiont in relative abundance, notably higher with respect to Wolbachia. The variation in insect gut microbiota may be determined by the environment as also for the type of feeding. Our findings increase the richness of the microbiota associated with Lu. evansi. In this study, OTUs of Methylobacterium found in Lu. evansi was higher in engorged females, suggesting that there are interactions between microbes from plant sources, blood nutrients and the parasites they transmit during the blood intake.
The clinical efficacy of catheter ablation of paroxysmal atrial fibrillation (AF) remains limited by difficulty in achieving durable pulmonary vein isolation (PVI). Suboptimal catheter tip-to-tissue ...contact force (CF) during lesion delivery is believed to reduce clinical efficacy.
To determine the relationship between catheter CF during irrigated catheter ablation for AF and clinical recurrences during follow-up.
Thirty-two patients with paroxysmal AF underwent PVI by using a radiofrequency ablation catheter with a CF sensor integrated at its tip, and they were followed for 12 months. The relationship between the CF and clinical outcomes was determined.
Acute PVI was achieved in 100% of the veins. Thirty-five percent (351 of 1017) of the applications were placed with an average CF of <10 g (low CF). All patients treated with an average CF of <10 g (5 of 5 patients) experienced recurrences, whereas 80% of the patients treated with an average CF of >20 g (8 of 10 patients) were free from AF recurrence at 12 months. The analysis of the average force-time integral showed that 75% of the patients treated with <500 gs were recurrent whereas only 31% of the patients treated with >1000 gs had recurrences at 12 months.
The CF during catheter ablation for AF correlates with clinical outcome. Arrhythmia control is best achieved when ablation lesions are placed with an average CF of >20 g, and clinical failure is universally noted with an average CF of <10 g.
In Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the ...development of Mexico's most vulnerable populations.
The aim of this systematic review and meta-analysis was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 36 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable study scale and geographic coverage. Based on studies reporting confirmed cases (i.e. using at least 2 serological tests), and taking into account the differences in sample sizes, the national estimated seroprevalence of Trypanosoma cruzi infection was 3.38% 95%CI 2.59-4.16, suggesting that there are 4.06 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported an estimated seroprevalence of 2.21% 95%CI 1.46-2.96, suggesting that there are 50,675 births from T. cruzi infected pregnant women per year, and 3,193 cases of congenitally infected newborns per year. Children under 18 years had an estimated seropositivity rate of 1.51% 95%CI 0.77-2.25, which indicate ongoing transmission. Cases of T. cruzi infection in blood donors have also been reported in most states, with a national estimated seroprevalence of 0.55% 95%CI 0.43-0.66.
Our analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the country's most vulnerable populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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