Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary ...method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.
Depression is a heterogeneous mental disorder characterized by feelings of sadness and loss of interest that render the subject unable to handle basic daily activities such as sleeping, eating, or ...working. Neurobiological traits leading to depression include genetic background, early life abuse, life stressors, and systemic and central inflammatory profiles. Several clinical and preclinical reports documented that depression shows an increase in pro-inflammatory markers such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor (TNF), and interferon (IFN)-γ; and a decrease in anti-inflammatory IL-4, IL-10, and transforming growth factor (TGF)-β species. Inflammatory activation may trigger and maintain depression. Dynamic crosstalk between the peripheral immune system and the central nervous system (CNS) such as activated endothelial cells, monocytes, monocyte-derived dendritic cells, macrophages, T cells, and microglia has been proposed as a leading cause of neuroinflammation. Notably, pro-inflammatory cytokines disrupt the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic, noradrenergic, dopaminergic, and glutamatergic neurotransmission. While still under investigation, peripheral cytokines can engage brain pathways and affect the central synthesis of HPA hormones and neurotransmitters through several mechanisms such as activation of the vagus nerve, increasing the permeability of the blood-brain barrier (BBB), altered cytokines transport systems, and engaging toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). However, physiological mechanisms that favor time-dependent central inflammation before or during illness are not totally understood. This review will provide preclinical and clinical evidence of DAMPs and the BBB permeability as contributors to depression and neuroinflammation. We will also discuss pharmacologic approaches that could potentially modulate DAMPs and BBB permeability for future interventions against major depression.
•Pro-inflammatory profile in brain triggers and maintains depression.•Mechanisms that reinforce neuroinflammation in brain include DAMPs and BBB permeability.•Neuroinflammation induced by DAMPs is associated to a neurotransmitter imbalance, leading to the development of depression.•Disruption of the BBB contributes to neuroinflammation by causing astrocytes to secrete inflammatory factors.
“On Story is film school in a box, a lifetime’s worth of filmmaking knowledge squeezed into half-hour packages."—Kenneth Turan, film critic for the Los Angeles Times Austin Film Festival (AFF) is the ...first organization to focus on writers’ creative contributions to film and television. Its annual Film Festival and Conference offers screenings, panels, workshops, and roundtable discussions that help new writers and filmmakers connect with mentors and gain advice and insight from masters, as well as reinvigorate veterans with new ideas. To extend the Festival’s reach, AFF produces On Story, a television series currently airing on PBS-affiliated stations and streaming online that presents high-caliber artists talking candidly and provocatively about the art and craft of screenwriting and filmmaking, often using examples from their own work. On Story—The Golden Ages of Television explores the transformation of television’s narrative content over the past several decades through interviews with some of TV’s best creators and writers, including Garry Shandling (The Larry Sanders Show), Carl Reiner (The Dick Van Dyke Show), Issa Rae (Insecure), Vince Gilligan (Breaking Bad), Greg Daniels (The Office), Paula Pell (Saturday Night Live), Noah Hawley (Fargo), Liz Meriwether (New Girl), David Chase (The Sopranos), Alan Yang (Master of None), Marta Kauffman (Friends), Jenji Kohan (Orange Is the New Black), and many more. Their insights, behind-the-scenes looks at the creative process, production tales, responses to audiences’ reactions, and observations on how both TV narratives and the industry have changed make this book ideal for TV lovers, pop culture fans, students taking screenwriting courses, and filmmakers and writers seeking information and inspiration.
Cervical cancer is one of the main causes of female cancer death worldwide, and human papilloma virus (HPV) its causal agent. To investigate viral oncogenesis several studies have focused on the ...effects of HPV oncoproteins E6 and E7 and the mechanisms by which these proteins stimulate the cellular transformation process. However, phenomena such as the physical state of the viral genome (episomal or integrated) and the effects of this integration on cell proliferation contribute new clues to understand how HPV infection causes carcinogenesis. New molecular technologies are currently facilitating these discoveries. This paper reviews the tumor development process initiated by HPV, recent findings on the process of viral integration into the host genome, new methods to detect HPV integration, and derived associated effects.
•Some of the most representative mechanisms of HPV integration are described.•The link between viral integration and the cell transformation is well depicted.•The genes affected are related to several cellular pathways.
Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. ...Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.
In Mexico, actinomycetoma is mainly caused by Nocardia brasiliensis, which is a soil inhabitant actinobacterium. Here, we report for the first time the draft genome of a strain isolated from a human ...case that has largely been found in in vitro and experimental models of actinomycetoma, N. brasiliensis HUJEG-1.
We report the first record of
Lasiurus villosissimus
(É. Geoffroy & St.-Hilaire, 1806) in San Juan prov-ince, Argentina. A male, determined as a juvenile by its degree of ossification of the ...epiphyses of the phalanges and the color and texture of the fur, was found on 31 August 2021 in a suburban area 2.44 km south of the city of San Juan. This new report increases the richness of bat species in the province and expands the distribution of this spe-cies towards the west of the country.
Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains ...controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between
CYP46A1
polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The
CYP46A1
rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002–1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of
CYP46A1
rs4900442. Our study suggests that carriers of the
CYP46A1
rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the
CYP46A1
gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of
CYP46A1
in suicide risk and to develop targeted interventions for at-risk populations.
Olfactomedin-like (OLFML) proteins are members of the olfactomedin domain–containing secreted glycoprotein (OLF) family. OLFML2A and OLFML2B are representative molecules of these glycoproteins. ...Olfactomedins are critical for the development and functional organization of the nervous system and retina, which is a highly conserved structure in vertebrates, having almost identical anatomical and physiological characteristics in multiple taxa. Spotted gar, a member of the
Lepisosteidae
family, is a freshwater fish that inhabits rivers, bayous, swamps, and brackish waters. Recently, the complete genome has been sequenced, providing a unique bridge between fish medical models to human biology, making it an excellent animal model. This study was aimed to understanding the evolution OLFML2A and OLFML2B in the retina of spotted gar through looking for the expression of these genes. Spotted gar retina was analyzed with hematoxylin-eosin staining assays to provide an overall view of the retina structure and an immunofluorescence assay to identify OLFML2A and OLFML2B protein expression. A phylogenetic tree was created using the neighbor-joining method. Forces that direct the evolution of the fish genes were tested. Spotted gar retina, as in other vertebrates, is made of several layers. OLFML2A and OLFML2B proteins were detected in the rod and cone photoreceptor layer (PRL), outer nuclear layer (ONL), and inner nuclear layer (INL). Phylogenetic tree analysis confirms the orthology within the OLFML2A gene. Purifying selection is the evolutionary force that directs the OLFML2A genes. OLFML2A genes have a well-conserved function over time and species.
Abstract
Today drilling wells is one of the biggest capital expenditures and is employed starting from exploration, delineation, initial wells for production, and fresh production incorporation when ...existing wells production have declined. The estimated cost for drilling new wells in Ayatsil field is around 25 MM$, which requires a high level of decision to achieve production goals without exceeding the budget assigned. Therefore, to make the right decision requires an integration of multidisciplinary group of specialists (geologists, geomechanics, reservoir, production and drilling engineers) from well design to execution phases.
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