RESUMO
Evaluating domestication signatures beyond model organisms is essential for a thorough understanding of the genotype-phenotype relationship in wild and human-related environments. Structural variations (SVs) can significantly impact phenotypes playing an important role in the physiological adaptation of species to different niches, including during domestication. A detailed characterization of the fitness consequences of these genomic rearrangements, however, is still limited in non-model systems, largely due to the paucity of direct comparisons between domesticated and wild isolates. Here, we used a combination of sequencing strategies to explore major genomic rearrangements in a Lachancea cidri yeast strain isolated from cider (CBS2950) and compared them to those in eight wild isolates from primary forests. Genomic analysis revealed dozens of SVs, including a large reciprocal translocation (~16 kb and 500 kb) present in the cider strain, but absent from all wild strains. Interestingly, the number of SVs was higher relative to single-nucleotide polymorphisms in the cider strain, suggesting a significant role in the strain's phenotypic variation. The set of SVs identified directly impacts dozens of genes and likely underpins the greater fermentation performance in the L. cidri CBS2950. In addition, the large reciprocal translocation affects a proline permease (PUT4) regulatory region, resulting in higher PUT4 transcript levels, which agrees with higher ethanol tolerance, improved cell growth when using proline, and higher amino acid consumption during fermentation. These results suggest that SVs are responsible for the rapid physiological adaptation of yeast to a human-related environment and demonstrate the key contribution of SVs in adaptive fermentative traits in non-model species.IMPORTANCEThe exploration of domestication signatures associated with human-related environments has predominantly focused on studies conducted on model organisms, such as Saccharomyces cerevisiae, overlooking the potential for comparisons across other non-Saccharomyces species. In our research, employing a combination of long- and short-read data, we found domestication signatures in Lachancea cidri, a non-model species recently isolated from fermentative environments in cider in France. The significance of our study lies in the identification of large array of major genomic rearrangements in a cider strain compared to wild isolates, which underly several fermentative traits. These domestication signatures result from structural variants, which are likely responsible for the phenotypic differences between strains, providing a rapid path of adaptation to human-related environments.
Assuntos
Saccharomyces cerevisiae , Saccharomycetales , Humanos , Saccharomyces cerevisiae/genética , Domesticação , Saccharomycetales/genética , Bebidas Alcoólicas , Translocação GenéticaRESUMO
Heat shock protein (HSP)-encoding genes (hsp), part of the highly conserved heat shock response (HSR), are known to be induced by thermal stress in several organisms. In Neurospora crassa, three hsp genes, hsp30, hsp70, and hsp80, have been characterized; however, the role of defined cis elements in their responses to discrete changes in temperature remains largely unexplored. To fill this gap, while also aiming to obtain a reliable fungal heat shock-inducible system, we analyzed different sections of each hsp promoter by assessing the expression of real-time transcriptional reporters. Whereas all three promoters and their resected versions were acutely induced by high temperatures, only hsp30 displayed a broad range of expression and high tunability, amply exceeding other inducible promoter systems existing in Neurospora, such as quinic acid- or light-inducible ones. As proof of concept, we employed one of these promoters to control the expression of clr-2, which encodes the master regulator of Neurospora cellulolytic capabilities. The resulting strain fails to grow on cellulose at 25°C, whereas it grows robustly if heat shock pulses are delivered daily. Additionally, we designed two hsp30 synthetic promoters and characterized them, as well as the native promoters, using a gradient of high temperatures, yielding a wide range of responses to thermal stimuli. Thus, Neurospora hsp30-based promoters represent a new set of modular elements that can be used as transcriptional rheostats to adjust the expression of a gene of interest or for the implementation of regulated circuitries for synthetic biology and biotechnological strategies. IMPORTANCE A timely and dynamic response to strong temperature fluctuations is paramount for organismal biology. At the same time, inducible promoters are a powerful tool for fungal biotechnological and synthetic biology endeavors. In this work, we analyzed the activity of several N. crassa heat shock protein (hsp) promoters at a wide range of temperatures, observing that hsp30 exhibits remarkable sensitivity and a dynamic range of expression as we charted the response of this promoter to subtle increases in temperature, and also as we built and analyzed synthetic promoters based on hsp30 cis elements. As proof of concept, we tested the ability of hsp30 to provide tight control of a central process, cellulose degradation. While this study provides an unprecedented description of the regulation of the N. crassa hsp genes, it also contributes a noteworthy addition to the molecular toolset of transcriptional controllers in filamentous fungi.
Assuntos
Neurospora crassa , Neurospora crassa/genética , Neurospora crassa/metabolismo , Temperatura , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico HSP70/genética , Regiões Promotoras GenéticasRESUMO
Eukaryotic circadian oscillators share a common circuit architecture, a negative feedback loop in which a positive element activates the transcription of a negative one that then represses the action of the former, inhibiting its own expression. While studies in mammals and insects have revealed additional transcriptional inputs modulating the expression of core clock components, this has been less characterized in the model Neurospora crassa, where the participation of other transcriptional components impacting circadian clock dynamics remains rather unexplored. Thus, we sought to identify additional transcriptional regulators modulating the N. crassa clock, following a reverse genetic screen based on luminescent circadian reporters and a collection of transcription factors (TFs) knockouts, successfully covering close to 60% of them. Besides the canonical core clock components WC-1 and -2, none of the tested transcriptional regulators proved to be essential for rhythmicity. Nevertheless, we identified a set of 23 TFs that when absent lead to discrete, but significant, changes in circadian period. While the current level of analysis does not provide mechanistic information about how these new players modulate circadian parameters, the results of this screen reveal that an important number of light and clock-regulated TFs, involved in a plethora of processes, are capable of modulating the clockworks. This partial reverse genetic clock screen also exemplifies how the N. crassa knockout collection continues to serve as an expedite platform to address broad biological questions.
Assuntos
Relógios Circadianos , Neurospora crassa , Neurospora crassa/metabolismo , Relógios Circadianos/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ritmo Circadiano/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
Due to a metadata tagging error the name of author Andrés Esteban San Martín was indexed incorrectly. The author's given name is Andrés Esteban and his family name is San Martín.
RESUMO
Due to a metadata tagging error the name of author Andrés Esteban San Martín was indexed incorrectly. The author's given name is Andrés Esteban and his family name is San Martín.
RESUMO
BACKGROUND: Obesity is a global health problem that also affects older adults. In Chile, as in most of the developing countries, more than half of older adults are overweight or obese, and bariatric surgery may be riskier for this group. The aim of this study is to compare our experience in patients over 60 years of age with a control group to determine associated surgical morbidity and mortality. METHODS: Case-control study of bariatric surgeries performed between 2006 and 2017 in our institution. Patients aged ≥ 60 years for the case group versus control group for patients ≤ 50 years selected randomly, matched by body mass index, type 2 diabetes, hypertension, dyslipidemia, surgical technique, and gender (ratio 1:2). Primary endpoint was surgical morbidity, 30-day readmission, and mortality. RESULTS: Seventy-two patients in case group were matched with 144 patients in control group. Surgical complications rate was the same for both groups. No differences were observed in the conversion to open surgery rate or 30-day readmission rate. There was no mortality in this series. CONCLUSION: In this case-control study, being elderly does not increase the risk of morbidity and mortality associated with bariatric surgery.
Assuntos
Envelhecimento/fisiologia , Cirurgia Bariátrica/efeitos adversos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Fatores Etários , Idoso , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/mortalidade , Cirurgia Bariátrica/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Casos e Controles , Chile/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/mortalidade , Obesidade/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/mortalidade , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Sobrepeso/mortalidade , Sobrepeso/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Fatores de RiscoRESUMO
BACKGROUND: Obesity and rapid weight loss after bariatric surgery (BS) are independent risk factors for development of cholelithiasis (CL), a prevalent disease in the Chilean population. This study aimed to determine the incidence of CL in obese Chilean patients 12 months after BS and identify risk factors for development of gallstones. METHODS: Retrospective study of patients who underwent BS in 2014. Patients with preoperative negative abdominal ultrasound (US) for CL and follow-up for at least than 12 months were included. Patients underwent US at 6 months and 12 months. We analyzed sex, age, hypertension, dyslipidemia, type 2 diabetes mellitus, body mass index (BMI), surgical procedure, percentage of excess BMI loss (%EBMIL) at 6 months, and BMI at 6 months. RESULTS: Of 279 patients who underwent bariatric surgery during 2014, 66 had previous gallbladder disease and 176 met the inclusion criteria (82.6%), while 54.6% were female. The mean age was 37.8 ± 10.5 years and preoperative BMI was 37.5 kg/m2. BMI and %EBMIL at 6 months were 27.8 ± 3.3 kg/m2 and 77.9 ± 33.6%, respectively. At 12 months after BS, CL was found in 65 patients (36.9%). Hypertension turned out to be protective against occurrence of gallstones at 1 year with an OR 0.241. CONCLUSIONS: Incidence of CL was up to one-third of the patients followed up for 12 months after BS. Excessive weight loss and other variables studied did not increase risk. Hypertension seems to be protective against gallstone formation, but this result needs further analysis.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Colelitíase/epidemiologia , Colelitíase/etiologia , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Índice de Massa Corporal , Chile/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Cálculos Biliares/epidemiologia , Cálculos Biliares/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Redução de Peso/fisiologiaRESUMO
Iron, although toxic in excess, is an essential element for biological systems. Therefore, its homeostasis is of critical importance and tight mechanisms participate in its acquisition by microbial organisms. Lately, the relevance of this metal for biomass conversion by wood-degrading fungi has been gaining increasing attention. Iron plays a critical role as cofactor of key enzymes such as lignin and manganese peroxidases in lignin-degrading white-rot fungi, while Fe(II) also serves a pivotal role in Fenton reactions that are central in cellulose depolymerization by brown-rotters. It has been hypothesized that multicopper oxidases with ferroxidase activity might participate in controlling the bioavailability of iron in the hyphal proximity, fine-tuning Fenton chemistry and balancing lignin versus cellulose degradation. In order to further explore the dynamics of iron regulation in the well known white-rot fungus Phanerochaete chrysosporium, we analyzed the mRNA levels of the multicopper oxidases genes (mcos) in response to iron supplementation, confirming down-regulation of their expression in response to this metal. To gain a better understanding on the transcriptional mechanisms mediating this effect, we searched for a gene encoding a GATA-type transcription factor with homology to URBS1, the major transcriptional regulator of iron homeostasis in Ustilago maydis. Due to the limitation of experimental tools in P. chrysosporium, the alleged Phanerochaete iron regulator (PIR1) was studied by complementation of a Neurospora SRE/URBS1-deficient strain, where phenotypic and molecular characteristics of this transcriptional regulator could be easily assessed. In addition, using a genome-wide in silico strategy, we searched for putative cis-acting iron-responsive elements in P. chrysosporium. Some of the identified genes showed reduced transcript levels after 30 min in the presence of the metal, consistent with an SRE/URBS1-mediated mechanism, and suggesting a broad effect of iron on the regulation of several cellular processes.
Assuntos
Fatores de Transcrição GATA/genética , Fatores de Transcrição GATA/metabolismo , Ferro/metabolismo , Phanerochaete/genética , Phanerochaete/metabolismo , Sequência de Bases , Sequência Consenso , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ordem dos Genes , Oxirredutases/genética , Elementos de Resposta , Transcrição GênicaRESUMO
A 40-year-old woman without symptoms, with a three-week amenorrhea, and with no previous pregnancy history. Three months before she followed treatment with clomifeno and no other risk factors. A measure of beta fraction is performed, finding a probable pregnancy of 3-4 weeks. A new measure of beta fraction is made three weeks later with an ultrasound, finding an important increment in measure, but without evidence of intrauterine pregnancy in the ultrasound. A new ultrasound is made seven weeks after her last period, finding a mass in the left ovary, but without increment in beta fraction. At week ten, she presents an uterine bleeding during a trip, which is diagnosed as a probable mole without any further medical treatment and from the 12th week, there is a considerable decrement in the beta fraction measure, without any other symptom, but the persistent adnexal mass at the left ovary, with irregular septum images at ultrasound. A laparotomy is performed finding an ectopic pregnancy surrounded by a serum cystadenoma.
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Cistadenoma/complicações , Neoplasias Ovarianas/complicações , Complicações Neoplásicas na Gravidez , Gravidez Ectópica , Adulto , Cistadenoma/cirurgia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/cirurgia , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/cirurgia , UltrassonografiaRESUMO
Comunicar una presentación inusual de enfermedad diverticular de colon. Descripción del caso clínico que se manifestó semiológicamente como un tumor abdominal y revisión de la literatura. Hospital "Carlos J. Bello", Cruz Roja Venezolana, Caracas. El diagnóstico de un divertículo "gigante" del colon sigmoide es establecido. La manifestación de enfermedad diverticular de colon bajo la forma de divertículo "gigante" es muy rara. Reportes dispersos en la literatura indican su inusual naturaleza. El tratamiento debe ser quirúrgico antes de que aparezcan complicaciones
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Humanos , Masculino , Idoso , Doença Diverticular do Colo/cirurgia , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/terapia , Venezuela , Cirurgia GeralRESUMO
El pólipo inflamatorio o pseudo pólipo es una causa muy rara de obstrucción intestinal. Los reportes a nivel mundial muestran series realmente pequeñas, el diagnóstico es generalmente post operatorio y por anatomía patológica. Presentamos un caso que ingresó como abdomen agudo, encontrándose la lesión a nivel del íleon. Esta ubicación es particularmente infrecuente. El paciente no tenía otros pólipos y se encuentra actualmente asintomático
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Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Pólipos/complicações , GastroenterologiaRESUMO
Se trató de paciente masculino de 57 años de edad sin antecedentes de patología sistemática de base ni antecedente quirúrgico, hospitalizado en nuestro centro con diagnóstico clínico y radiológico de Obstrucción Intestinal. Fué intervenido quirúrgicamente, evidenciándose tumoración adherida al ileón distal. Los hallazgos anatomopatológicos evidenciaron una lesión benigna formada por tejido conectivo, vasos y células inflamatorias (eosinófilos y algunos linfocitos). El diagnóstico final fue un POLIPO FIBROIDE INFLAMATORIO. Una enfermedad inusual en este sitio específico del tracto gastrointestinal