A case of chronic myeloid leukemia with Philadelphia chromosome variant

En 5-10% de los casos de Leucemia Mieloide Crónica (LMC), el cromosoma Philadelphia (Ph1) se origina como producto de translocaciones variantes (Ph1 variante). Estas últimas involucran otros autosomas además del 9 y 22 clásicamente implicados. Se presenta aquí un caso de LMC cuyo cromosoma Ph1 variante fue originado a partir de una translocación compleja que involucró los cromosomas 3, 9 y 22 [t(3;9;22)(p21,q34;q11)]. El análisis mediante FISH sugiere un mecanismo de formación en una etapa única, mientras el análisis por RT-PCR mostró la presencia del rearreglo molecular BCR/ABL1 correspondiente a la isoforma p210. El paciente no presentó variaciones significativas en los parámetros de respuesta clínica (respuesta hematológica, respuesta citogenética y respuesta molecular) respecto de aquellos pacientes con el Ph1 estándar.Among the CML there is a fraction of cases (5–10%) in which the Philadelphia chromosome (Ph1) originates from variant translocations (Ph1 variant), in which there are autosomes involved other than the classic 9 and 22. Here we report a case of CML where a variant Ph1 chromosome was originated from a complex translocation involving chromosomes 3, 9 and 22 [t(3,9,22)(p21,q34,q11)]. FISH analysis suggests that the mechanism of translocation occurred in a single step. Furthermore, the RT-PCR analysis also showed the presence of the classical molecular rearrangement corresponding to the BCR/ABL1 p210 isoform. The patient showed no significant variations in the parameters of clinical response (hematologic, cytogenetic, and molecular response) from those patients carrying a standard Ph1 chromosome.Fil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Dos Santos, Patricia Carolina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Rolón, Amada. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Melnichuk, Ana M.. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Argüelles, Carina F.. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Fenocchio, Alberto Sergio. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; Argentin

Acute HIV-1 and SARS-CoV-2 infections Share Slan+ Monocyte Depletion - evidence from an hyperacute HIV-1 case report

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “Apoio Especial Research4COVID-19”, project numbers 125 to S.M.F. and 803 to A.C.T. Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag Farmacêutica were received by A.M.C.G. and G.B.F., respectively.info:eu-repo/semantics/publishedVersio

No visit, no interest: How COVID-19 has affected public interest in world's national parks

The use of digital content has become a powerful tool to evaluate and track macro-scale trends in human-nature relations. This is an emerging field of study known as conservation culturomics, that seeks to understand human culture through quantitative analysis in large bodies of digital content. Here, we used relative search volume on Google Search as a culturomic metric of public interest to investigate the global impact of the 2020 COVID-19 pandemic on national parks (NPs). Specifically, we focus on the impacts of limiting people?s mobility (through social isolation and lock-down measures) on public interest in NPs, since this is likely to have a strong causal relationship with park visitation. We generated public interest data for 2411 NPs from around the world for the period January 2016 to July 2020, to explore the relationship between relative search volume and periods of greater and lesser mobility restrictions due to the COVID-19 pandemic. We observed a global trend of declining public interest in national parks during the initial phase of the coronavirus pandemic, although there was considerable variation between both parks and countries. For example, contrary to the global trend public interest in NPs increased in Finland during the first lock-down. Significantly, countries whose national parks are highly dependent on international visitors (e.g., South Africa and India) had very severe declines in public interest. Our study reinforces the key role that visitation plays in driving public interest in national parks and illustrates the utility of culturomic methods for monitoring human-park interactions at scale.Peer reviewe

Are we still chasing molecules that were never there? The role of quantum chemical simulations of NMR parameters in structural reassignment of natural products

Covering: 2019 to 2023. Even with the advent of modern and complementary spectroscopy techniques, comprehensive characterization of natural product continues to represent an onerous and time-consuming task, being far away to become rather “routine”. Mainly due to their highly complex structures and small amount of isolated sample, in milligram or sub-milligram quantities, structural misassignment of natural products are still a recurrence theme in the modern literature. Since the seminal paper from Nicolau and Snider, in 2005, evaluating the various cases of reassignment of natural products, from the present era, in which NMR parameters calculations play such an important role in the structural elucidation of natural products, helping to uncover and ultimately revise the structure of previously reported compounds, a pertinent question arises: are we still chasing molecules that were never there? In this minireview, we intent to discuss the current state of computational NMR parameter calculations, with a particular focus on their application in the structural determination of natural products. Additionally, we have conducted a comprehensive survey of the literature spanning the years 2019–2023, in order to select and discuss recent noteworthy cases of incorrectly assigned structures that were revised through NMR calculations. Therefore, our main goal is to show what can be done through computational simulations of NMR parameters, currently user-friendly and easily implemented by non-expert users with basic skills in computational chemistry, before venturing into complex and time-consuming total synthesis projects. In conclusion, we anticipate a promising future for NMR parameter calculations, fueled by the ongoing development of user-friendly tools and the integration of artificial intelligence. The emergence of these advancements is poised to broaden the applications of NMR simulations, offering a more accessible and reliable means to address the persistent challenge of structural misassignments in natural product chemistry

Biodegradable chitosan films with ZnO nanoparticles synthesized using food industry by-products—production and characterization

UIDB/04077/2020 PTDC/BTM‐SAL/29335/2017 UIDB/04138/2020 UIDP/04138/2020 grant (2020.04441.BD) of C.R.This work aimed to produce bionanocomposites of chitosan incorporated with zinc oxide nanoparticles (ZnO NPs) synthesized using food industry by-products and to characterize them. Such nanoparticles are highlighted due to their low cost, antimicrobial activity, accessibility, and sustainability synthesis. Four different levels of ZnO NPs (0, 0.5, 1.0, and 2.0% w/w of chitosan) were tested, and the bionanocomposites were characterized in terms of their hydrophobicity, mechanical, optical, and barrier properties. Overall, the incorporation of ZnO NPs changed the composites from brittle to ductile, with enhanced elongation at break and reduced Young Modulus and tensile strength. Thus, ZnO NPs acted as plasticizer, turning the films more flexible, due to the presence of organic compounds on the NPs. This also favored permeability of oxygen and of water vapor, but the good barrier properties were maintained. Optical properties did not change statistically with the ZnO NPs incorporation. Thus, the characterization presented in this paper may contribute to support a decision on the choice of the material’s final application.publishersversionpublishe

A survey of modulation of gut microbiota by dietary polyphenols

Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects. This review aims to update the current information about the modulation of the gut microbiota by dietary phenolic compounds, from a perspective based on the experimental approaches used. After referring to general aspects of gut microbiota and dietary polyphenols, studies related to this topic are presented according to their experimental design: batch culture fermentations, gastrointestinal simulators, animal model studies, and human intervention studies. In general, studies evidence that dietary polyphenols may contribute to the maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficial bacteria (i.e., lactobacilli and bifidobacteria) and the inhibition of pathogenic bacteria, exerting prebiotic-like effects. Combination of in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangle and elucidate the implications of polyphenols on human health. From a technological point of view, supplementation with richpolyphenolic stuffs (phenolic extracts, phenolic-enriched fractions, etc.) could be an effective option to improve health benefits of functional foods such as the case of dairy fermented foods.The authors of this review were funded by the Spanish MINECO through different projects (AGL2012-40172-C02-01, AGL2010-17499, and BFU2012-35228) and the CONSOLIDER INGENIO 2010 programme (project FUN-CFOOD, CSD2007-063), as well as Comunidad de Madrid (project ALIBIRD P2009/AGR-1469). Montserrat Duenas would like to thank the Spanish “Ramon y Cajal” Programme for a contract.Peer Reviewe

A Survey of Modulation of Gut Microbiota by Dietary Polyphenols

Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects. This review aims to update the current information about the modulation of the gut microbiota by dietary phenolic compounds, from a perspective based on the experimental approaches used. After referring to general aspects of gut microbiota and dietary polyphenols, studies related to this topic are presented according to their experimental design: batch culture fermentations, gastrointestinal simulators, animal model studies, and human intervention studies. In general, studies evidence that dietary polyphenols may contribute to the maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficial bacteria (i.e., lactobacilli and bifidobacteria) and the inhibition of pathogenic bacteria, exerting prebiotic-like effects. Combination of in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangle and elucidate the implications of polyphenols on human health. From a technological point of view, supplementation with rich-polyphenolic stuffs (phenolic extracts, phenolic-enriched fractions, etc.) could be an effective option to improve health benefits of functional foods such as the case of dairy fermented foods

Pathophysiological Mechanisms In Gaseous Therapies For Severe Malaria.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patients' clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO) and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.8