101 research outputs found

    Investigation of mitochondrial inheritance in the smut fungus sporisorium reilianum.

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    An important goal in evolutionary biology is to address the origin of Earth‚Äôs immense biodiversity through the evolution of complex sexual reproduction mechanisms in eukaryotes. Inheritance of mitochondria during sexual reproduction has received special attention in recent years, as these organelles cannot be synthesized de novo and must be transmitted from parent to offspring. The importance of these organelles far exceeds its common function as the energy-producing ‚Äúpowerhouse‚ÄĚ of the cell, as it has been found to also be involved in fundamental processes like apoptosis, aging and metabolic homeostasis. Thus, appropriate inheritance of mitochondria is essential for growth and development of progeny. Sexually reproducing eukaryotes present a variety of mechanisms that allow mitochondria from a single parent to be passed on to the offspring (homoplasmy). However, biparental inheritance of mitochondria has also been described in other systems, in which offspring inherit mitochondrial genomes from both parents (heteroplasmy). Presence of different mitochondrial genomes within the same cytoplasm may result in the dissemination of deleterious mutations arising from the individual nature of each mitochondrial genome (e.g. different DNA replication rates, susceptibility to oxidative damage, etc.). The smut fungus Sporisorium reilianum f. sp. zeae is a pathogen of maize that exhibits a dimorphic lifestyle, being able to switch from budding yeast-like haploid sporidia to pathogenic filamentous dikarya that eventually develop into diploid teliospores. Notably, this smut fungus is equipped with genes for the appropriate segregation of mitochondria during sexual reproduction. Mating in S. reilianum may occur between three parental type strains, a1, a2 and a3, of which only a2 contains genes that promote inheritance of its own mitochondrial genetic material. Accordingly, mitochondrial inheritance in offspring resulting from a cross with the a2 parent is expected to follow a uniparental pattern. However, what happens in a cross between the a1 and a3 partners remains unclear. The present work explores the uniparental inheritance system of mitochondria in S. reilianum through the development of reliable and low-cost diagnostic methodologies to discern between mitogenomes. The study was dependent on the investigation of the genetic diversity of different S. reilianum strains through whole-genome sequencing and gene synteny analysis, which proved to be more reliable, and led to cost-effective methodologies for the detection of polymorphisms. Multiple sequence alignment revealed a slew of mutations throughout the mitochondrial DNA molecule. Mutations that were detected in protein-encoding regions needed further investigation, as they could have detrimental consequences on their predicted polypeptides. Furthermore, unique DNA sequence was detected in the cox1 gene of the Chinese isolate mitogenome, with high percent identity to other species related to S. reilianum. This remarkable finding may hint at a complex evolutionary history of S. reilianum, influenced by potential inter- and intraspecific exchange of mitochondrial genetic material. The distinct polymorphic region detected in Chinese strains of S. reilianum also provided the ideal groundwork for the development of simple diagnostic methods to discern between mitotypes following a mating event in the context of mitochondrial inheritance. Exploration of the mitochondrial inheritance mechanism of S. reilianum was based on previous findings from the closely related species, Ustilago maydis, which involves a degradation-mediated mechanism that renders inheritance uniparental. The diagnostic methods developed were based on Polymerase Chain Reaction (PCR) technology and suggested deviation from predicted inheritance patterns in which the Chinese mitotype was always favored. Additionally, this deviation was not affected in the absence of the Lga2/Rga2 system. Finally, the electron transport chain of S. reilianum was further explored. Bioinformatic analysis and growth inhibition assays using specific respiratory inhibitors revealed the presence of a putative alternative oxidase (AOX), which is associated with alternative respiration in the face of inhibition of one or more of the classical mitochondrial complexes. AOX may play a more prominent role in the pathogenic stage of the fungus, as its absence significantly reduced disease severity. Moreover, expression analysis revealed that alternative oxidase is upregulated in the diploid teliospore stage of the fungus. Compared to haploid sporidia that bud or the dikarya that grow filamentously, such teliospores may benefit from reduced respiratory rates due to their mostly quiescent nature. Combined with the findings regarding mitochondrial inheritance, the characterization of alternative routes facilitated by nuclearly-encoded components like alternative oxidase provide an additional perspective from which to study genomic conflicts during sexual reproduction

    Machining and Dimensional Validation Training Using Augmented Reality for a Lean Process

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    AbstractQuality control does not concern only to a finished product, nowadays measuring technologies control all the fabrication process in an active way. If product quality does not meet the customer specifications exists the risk of even lose projects. When multiple or complex operations are required in the fabrication process of a part and its dimensional validation is primordial and also happens that the operator has doubts about which step to follow or that the expert supervisor is not at the workshop for some reason, that is why comes the opportunity of implementing Augmented Reality (A.R.) technology in education and in a lean manufacturing process, as support for technician operators of machine-tools and coordinate-measuring machines, with the objective of helping the technician to perform, in a proper and timely manner, the step sequence of the process. It was proved that having A.R. as ally in the technician's education, the mistakes and time required to fulfill the machining and dimensioning of a part can be considerably reduced, as well as eliminate operator's dependency to the experts. At the end of the implementation, savings were found in the three stages analyzed, generating 27.36% savings in lathe process, 26.54% in milling and 45.16% in dimensional validation

    The Use of Artificial Intelligence in the Management of Intracranial Aneurysms

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    The use of artificial intelligence (AI) has potential benefits in the management of intracranial aneurysms. Early detection of intracranial aneurysms is critical due to their high risk of complications such as rupture, vasospasm, and ischemia with highly impact on morbidity and mortality. The main findings suggest that AI can improve the accuracy of aneurysm detection, rupture risk prediction, and assist neurointervention in planning and performing procedures. This chapter discusses the potential for AI to improve patient care by enabling earlier diagnosis and timely treatment, reducing medical errors, costs, morbidity, and mortality. However, further validation of AI-based applications is necessary in a real-world clinical setting

    Human and Canine Echinococcosis Infection in Informal, Unlicensed Abattoirs in Lima, Peru

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    Echinococcus granulosus infections are a major public health problem in livestock-raising regions around the world. The life cycle of this tapeworm is sustained between dogs (definitive host, canine echinococcosis), and herbivores (intermediary host, cystic hydatid disease). Humans may also develop cystic hydatid disease. Echinococcosis is endemic in rural areas of Peru; nevertheless, its presence or the extension of the problem in urban areas is basically unknown. Migration into Lima, an 8-million habitant's metropolis, creates peripheral areas where animals brought from endemic areas are slaughtered without veterinary supervision. We identified eight informal, unlicensed abattoirs in a peripheral district of Lima and performed a cross-sectional study in to assess the prevalence of canine echinococcosis, evaluated by coproELISA followed by PCR evaluation and arecoline purge. Eight of 22 dogs (36%) were positive to coproELISA, and four (18%) were confirmed to be infected with E. granulosus tapeworms either by PCR or direct observation (purge). Later evaluation of the human population living in these abattoirs using abdominal ultrasound, chest X-rays and serology, found 3 out of 32 (9.3%) subjects with echinococcal cysts in the liver (two viable, one calcified), one of whom had also lung involvement and a strongly positive antibody response. Autochthonous transmission of E. granulosus is present in Lima. Informal, unlicensed abattoirs may be sources of infection to neighbouring people in this urban environment

    Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

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    Background: Approximately 450‚ÄČ000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2¬∑1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13¬∑0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63‚ÄČ093 individuals in the FHSC registry, 11‚ÄČ848 (18¬∑8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50¬∑2%) of 11‚ÄČ476 included individuals were female and 5720 (49¬∑8%) were male. Sex data were missing for 372 (3¬∑1%) of 11‚ÄČ848 individuals. Median age at registry entry was 9¬∑6 years (IQR 5¬∑8-13¬∑2). 10‚ÄČ099 (89¬∑9%) of 11‚ÄČ235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10¬∑1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5¬∑2%) of 11‚ÄČ848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92¬∑4%] of 10‚ÄČ202) than in children and adolescents from non-high-income countries (199 [48¬∑0%] of 415). 3414 (31¬∑6%) of 10‚ÄČ804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72¬∑4%) of 10‚ÄČ428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5¬∑00 mmol/L (IQR 4¬∑05-6¬∑08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

    Consistent patterns of common species across tropical tree communities

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    Trees structure the Earth‚Äôs most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10‚ÄČcm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth‚Äôs 800 billion tropical trees with trunk diameters of at least 10‚ÄČcm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world‚Äôs most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium‚Äďglucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin‚Äďangiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
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