Gene transcription is a highly regulated process, and deregulation of transcription factors activity underlies numerous pathologies including cancer. Albeit near four decades of studies have established that the E2F pathway is a core transcriptional network that govern cell division in multi-cellular organisms, the molecular mechanisms that underlie the functions of E2F transcription factors remain incompletely understood. FOXK1 and FOXK2 transcription factors have recently emerged as important regulators of cell metabolism, autophagy and cell differentiation.
View Article and Find Full Text PDFPioneer transcription factors direct cell differentiation by deploying new enhancer repertoires through their unique ability to target and initiate remodelling of closed chromatin. The initial steps of their action remain undefined, although pioneers have been shown to interact with nucleosomal target DNA and with some chromatin-remodeling complexes. We now define the sequence of events that enables the pioneer Pax7 with its unique abilities.
View Article and Find Full Text PDFPioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening.
View Article and Find Full Text PDFThe causative agent of Chagas disease () is transmitted to mammals, including humans, mainly by insect vectors of the subfamily Triatominae (Hemiptera: Reduviidae). Also known as "kissing bugs", the subfamily currently includes 157 validated species (154 extant and three extinct), in 18 genera and five tribes. Here, we present a subdataset (7852 records) of American triatomine occurrences; an update to the most complete and integrated database available to date at a continental scale.
View Article and Find Full Text PDFVector-borne diseases are responsible for more than 17% of human cases of infectious diseases. In most situations, effective control of debilitating and deadly vector-bone diseases (VBDs), such as malaria, dengue, chikungunya, yellow fever, Zika and Chagas requires up-to-date, robust and comprehensive information on the presence, diversity, ecology, bionomics and geographic spread of the organisms that carry and transmit the infectious agents. Huge gaps exist in the information related to these vectors, creating an essential need for campaigns to mobilise and share data.
View Article and Find Full Text PDFNat Rev Mol Cell Biol
July 2022
Pioneer factors are transcription factors with the unique ability to initiate opening of closed chromatin. The stability of cell identity relies on robust mechanisms that maintain the epigenome and chromatin accessibility to transcription factors. Pioneer factors counter these mechanisms to implement new cell fates through binding of DNA target sites in closed chromatin and introduction of active-chromatin histone modifications, primarily at enhancers.
View Article and Find Full Text PDFObjective: To analyze the impact of gestational age (GA) at the time of fetal open spinal dysraphism (OSD) repair through a mini-hysterotomy on the ability of children to walk.
Methods: Children who underwent in utero repair of OSD and had formal neurological assessment after 2.5 years of age were compared regarding their ability to walk in relation to pre-surgical predictors.
The pioneer transcription factor Pax7 contains two DNA binding domains (DBD), a paired and a homeo domain. Previous work on Pax7 and the related Pax3 showed that each DBD binds a cognate DNA sequence, thus defining two targets of binding and possibly modalities of action. Genomic targets of Pax7 pioneer action leading to chromatin opening are enriched for composite DNA target sites containing juxtaposed sites for both paired and homeo domains.
View Article and Find Full Text PDFMeis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis.
View Article and Find Full Text PDFYellow fever is an endemic disease in America caused by an arbovirus that circulates in the sylvatic cycle between nonhuman primates and mosquitoes of the genera Sabethes Robineau-Desvoidy and Haemagogus Williston. The main goal of this work is to report the distribution patterns of these genera in Argentina through an updated database built from published records as well as from own sample collections. These genera are represented in Argentina by a total of 18 species distributed in 14 provinces and 10 ecoregions.
View Article and Find Full Text PDFObjective: Development of a risk-stratification model to predict severe Covid-19 related illness, using only presenting symptoms, comorbidities and demographic data.
Materials And Methods: We performed a case-control study with cases being those with severe disease, defined as ICU admission, mechanical ventilation, death or discharge to hospice, and controls being those with non-severe disease. Predictor variables included patient demographics, symptoms and past medical history.
Translation is a basic cellular process and its capacity is adapted to cell function. In particular, secretory cells achieve high protein synthesis levels without triggering the protein stress response. It is unknown how and when translation capacity is increased during differentiation.
View Article and Find Full Text PDFPioneer transcription factors are characterized by having the unique property of enabling the opening of closed chromatin sites, for implementation of cell fates. We previously found that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire, which allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigate the relation between these two factors in the pioneer mechanism.
View Article and Find Full Text PDFSince Aujeszky`s disease (pseudorabies), which is caused by Suid herpesvirus type 1 (SuHV-1), was first notified in Argentina in 1978, many SuHV-1 strains have been isolated from swine. However, this disease can affect other vertebrates, such as dogs (secondary hosts), and lead to fatal neurological disease. The objective of the current work is to report the first isolation and molecular characterization of SuHV-1 from a dead domestic dog from Santa Fe Province (Argentina), which had had nervous signs compatible with pseudorabies.
View Article and Find Full Text PDFTrypanosoma cruzi, the causative agent of Chagas disease, is transmitted to mammals - including humans - by insect vectors of the subfamily Triatominae. We present the results of a compilation of triatomine occurrence and complementary ecological data that represents the most complete, integrated and updated database (DataTri) available on triatomine species at a continental scale. This database was assembled by collecting the records of triatomine species published from 1904 to 2017, spanning all American countries with triatomine presence.
View Article and Find Full Text PDFAedes aegypti (L.) (Diptera: Culicidae) is a vector of many medically significant viruses in the Americas, including dengue virus, chikungunya virus, and Zika virus. Traits such as longevity, fecundity, and feeding behavior contribute to the ability of Ae.
View Article and Find Full Text PDFIn tetrapods, , and Hox cluster genes are crucial for forelimb and hindlimb development and mutations in these genes are responsible for congenital limb defects. The molecular basis of their integrated mechanisms of action in the context of limb development remains poorly understood. We studied Tbx4 and Hoxc10 owing to their overlapping loss-of-function phenotypes and colocalized expression in mouse hindlimb buds.
View Article and Find Full Text PDFPioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification of one pituitary lineage.
View Article and Find Full Text PDFTriatoma virus occurs infecting Triatominae in the wild (Argentina) and in insectaries (Brazil). Pathogenicity of Triatoma virus has been demonstrated in laboratory; accidental infections in insectaries produce high insect mortality. When more than one microorganism enters the same host, the biological interaction among them differs greatly depending on the nature and the infection order of the co-existing species of microorganisms.
View Article and Find Full Text PDFThe cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for mutations.
View Article and Find Full Text PDFDysfunction of midbrain dopaminergic (mDA) neurons is involved in Parkinson's disease (PD) and neuropsychiatric disorders. Pitx3 is expressed in mDA neuron subsets of the substantia nigra compacta (SNc) and of the ventral tegmental area (VTA) that are degeneration-sensitive in PD. The genetic network(s) and mode(s) of action of Pitx3 in these mDA neurons remain poorly characterized.
View Article and Find Full Text PDFContext: Cushing disease (CD) is due to pituitary corticotrope adenomas that produce unrestrained ACTH secretion and have lost the negative feedback exerted by glucocorticoids (GCs). GCs also restrain corticotrope proliferation, and the mechanisms of this inhibition are poorly understood.
Objective: The aim of the study was to identify cell cycle regulatory genes that are regulated by GCs and the glucocorticoid receptor and to assess regulatory genes that have a rate-limiting action on corticotrope proliferation and may be disregulated in CD.
Triatoma infestans (Klug, 1834) (Hemiptera: Reduviidae), the main vector of Chagas disease in South America, feeds primarily on humans, but ethical reasons preclude carrying out demographical studies using people. Thus, most laboratory studies of T. infestans are conducted using bird or mammal live hosts that may result in different demographic parameters from those obtained on human blood.
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