Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders.

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10-4 per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs.

Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis.

Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are unclear, although retrotransposon mobilization may contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers.

Assessing the impact of transcriptomics data analysis pipelines on downstream functional enrichment results.

Transcriptomics is widely used to assess the state of biological systems. There are many tools for the different steps, such as normalization, differential expression, and enrichment. While numerous studies have examined the impact of method choices on differential expression results, little attention has been paid to their effects on further downstream functional analysis, which typically provides the basis for interpretation and follow-up experiments. To address this, we introduce FLOP, a comprehensive nextflow-based workflow combining methods to perform end-to-end analyses of transcriptomics data. We illustrate FLOP on datasets ranging from end-stage heart failure patients to cancer cell lines. We discovered effects not noticeable at the gene-level, and observed that not filtering the data had the highest impact on the correlation between pipelines in the gene set space. Moreover, we performed three benchmarks to evaluate the 12 pipelines included in FLOP, and confirmed that filtering is essential in scenarios of expected moderate-to-low biological signal. Overall, our results underscore the impact of carefully evaluating the consequences of the choice of preprocessing methods on downstream enrichment analyses. We envision FLOP as a valuable tool to measure the robustness of functional analyses, ultimately leading to more reliable and conclusive biological findings.

Structural Variation in Cancer: Role, Prevalence, and Mechanisms.

Somatic rearrangements resulting in genomic structural variation drive malignant phenotypes by altering the expression or function of cancer genes. Pan-cancer studies have revealed that structural variants (SVs) are the predominant class of driver mutation in most cancer types, but because they are difficult to discover, they remain understudied when compared with point mutations. This review provides an overview of the current knowledge of somatic SVs, discussing their primary roles, prevalence in different contexts, and mutational mechanisms. SVs arise throughout the life history of cancer, and 55% of driver mutations uncovered by the Pan-Cancer Analysis of Whole Genomes project represent SVs. Leveraging the convergence of cell biology and genomics, we propose a mechanistic classification of somatic SVs, from simple to highly complex DNA rearrangement classes. The actions of DNA repair and DNA replication processes together with mitotic errors result in a rich spectrum of SV formation processes, with cascading effects mediating extensive structural diversity after an initiating DNA lesion has formed. Thanks to new sequencing technologies, including the sequencing of single-cell genomes, open questions about the molecular triggers and the biomolecules involved in SV formation as well as their mutational rates can now be addressed.

Network integration of thermal proteome profiling with multi-omics data decodes PARP inhibition.

Complex disease phenotypes often span multiple molecular processes. Functional characterization of these processes can shed light on disease mechanisms and drug effects. Thermal Proteome Profiling (TPP) is a mass-spectrometry (MS) based technique assessing changes in thermal protein stability that can serve as proxies of functional protein changes. These unique insights of TPP can complement those obtained by other omics technologies. Here, we show how TPP can be integrated with phosphoproteomics and transcriptomics in a network-based approach using COSMOS, a multi-omics integration framework, to provide an integrated view of transcription factors, kinases and proteins with altered thermal stability. This allowed us to recover consequences of Poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer cells on cell cycle and DNA damage response as well as interferon and hippo signaling. We found that TPP offers a complementary perspective to other omics data modalities, and that its integration allowed us to obtain a more complete molecular overview of PARP inhibition. We anticipate that this strategy can be used to integrate functional proteomics with other omics to study molecular processes.

Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Critical evaluation of the potential of ICP-MS-based systems in toxicological studies of metallic nanoparticles.

The extensive application of metallic nanoparticles (NPs) in several fields has significantly impacted our daily lives. Nonetheless, uncertainties persist regarding the toxicity and potential risks associated with the vast number of NPs entering the environment and human bodies, so the performance of toxicological studies are highly demanded. While traditional assays focus primarily on the effects, the comprehension of the underlying processes requires innovative analytical approaches that can detect, characterize, and quantify NPs in complex biological matrices. Among the available alternatives to achieve this information, mass spectrometry, and more concretely, inductively coupled plasma mass spectrometry (ICP-MS), has emerged as an appealing option. This work critically reviews the valuable contribution of ICP-MS-based techniques to investigate NP toxicity and their transformations during in vitro and in vivo toxicological assays. Various ICP-MS modalities, such as total elemental analysis, single particle or single-cell modes, and coupling with separation techniques, as well as the potential of laser ablation as a spatially resolved sample introduction approach, are explored and discussed. Moreover, this review addresses limitations, novel trends, and perspectives in the field of nanotoxicology, particularly concerning NP internalization and pathways. These processes encompass cellular uptake and quantification, localization, translocation to other cell compartments, and biological transformations. By leveraging the capabilities of ICP-MS, researchers can gain deeper insights into the behaviour and effects of NPs, which can pave the way for safer and more responsible use of these materials.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

Modeling oceanic sedimentary methane hydrate growth through molecular dynamics simulation.

The crystallization process of methane hydrates in a confined geometry resembling seabed porous silica sedimentary conditions has been studied using molecular dynamics simulations. With this objective in mind, a fully atomistic quartz silica slit pore has been designed, and the temperature stability of a methane hydrate crystalline seed in the presence of water and guest molecule methane has been analyzed. NaCl ion pairs have been added in different concentrations, simulating salinity conditions up to values higher than average oceanic conditions. The structure obtained when the hydrate crystallizes inside the pore is discussed, paying special attention to the presence of ionic doping inside the hydrate and the subsequent induced structural distortion. The shift in the hydrate stability conditions due to the increasing water salinity is discussed and compared with the case of unconfined hydrate, concluding that the influence of the confinement geometry and pore hydrophilicity produces a larger deviation in the confined hydrate phase equilibria.

Sudden hearing loss secondary to syphilis.

BACKGROUND: Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum, whose incidence has increased significantly in recent years. Some patients may develop sudden hearing loss (SHL) against the background of otosyphilis. OBJECTIVES: The objective of our study was to determine whether routine lues serology is useful in patients presenting with sudden hearing loss. METHODS: For this purpose, all cases of SHL treated in our hospital during a period of 6 years were propectively collected. The frequency of positivity for syphilis in these patients, the treatment received, and their evolution were determined. RESULTS: Of the total number of patients evaluated during that period, 71 underwent serological screening for syphilis, of whom 2 (2.8 %) presented positive screening antibodies. In one of them, the RPR was normal and had been treated with lues a few years before. After treatment there was no improvement. The other patient, diagnosed with otosyphilis with unconfirmed suspected neurological disease, showed normalization of hearing after specific treatment. CONCLUSIONS: Since it is a potentially curable disease, despite the low overall frequency of syphilis in patients with SHL it is advisable to perform serological screening for syphilis in high risk patients (e.g., incarceration, multiple recent sexual partners, men who have sex with men) or atypical clinical presentation (e.g., concurrent neuropathies).

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Molecular Simulation of SO2 Separation and Storage Using a Cryptophane-Based Porous Liquid.

A theoretical molecular simulation study of the encapsulation of gaseous SO2 at different temperature conditions in a type II porous liquid is presented here. The system is composed of cage cryptophane-111 molecules that are dispersed in dichloromethane, and it is described using an atomistic modelling of molecular dynamics. Gaseous SO2 tended to almost fully occupy cryptophane-111 cavities throughout the simulation. Calculations were performed at 300 K and 283 K, and some insights into the different adsorption found in each case were obtained. Simulations with different system sizes were also studied. An experimental-like approach was also employed by inserting a SO2 bubble in the simulation box. Finally, an evaluation of the radial distribution function of cryptophane-111 and gaseous SO2 was also performed. From the results obtained, the feasibility of a renewable separation and storage method for SO2 using porous liquids is mentioned.

Nurses' perceptions of the performance of nurse managers and senior hospital management during the COVID-19 pandemic.

BACKGROUND: The first waves of the COVID-19 pandemic had a negative impact on health systems and health professionals, due to the high number of cases and a lack of preparation. The aim of this study was to understand how nurses working in hospital units and in intensive care perceived the performance of nurse managers and senior hospital management during the first two waves of the pandemic. METHODS: The phenomenological approach proposed by Giorgi was used to investigate perceptions of the performance of nurse managers and senior hospital management during the first two waves of the COVID-19 pandemic in Spain. Fourteen clinical nurses who worked on the front line in inpatient units or intensive care units of the Health Services of Extremadura and Madrid in the first (March-April 2020) and second (October-November 2020) waves of the COVID-19 pandemic participated in this study. The data was collected through semi-structured interviews, following a script of themes, in a theoretical sample of nurses who were worked during the pandemic. RESULTS: Two main themes emerged from the analysis of the data: (1) perceptions about the performance of nurse managers and senior hospital managers during the first and second waves of the pandemic (health system failure; belief that senior hospital management professionals could have managed the pandemic better; recognizing the efforts of middle management (nursing supervisors); insufficient institutional support) and (2) strategies employed by nurses to compensate for the weaknesses in pandemic management. CONCLUSIONS: The clinical nurses perceived that the nurse managers demonstrated better management of the pandemic than the hospital's senior management, which they attribute to their proximity, empathy, accessibility, and ability to mediate between them and the senior management. The nurses also believe that the senior management of the hospitals was to blame for organisational failures and the poor management of the pandemic.

Assessing mucosal recovery in celiac disease - Time to diagnosis and histological severity as determining factors.

Study background and objectives: There is great disparity in mucosal recovery among celiac patients on a gluten-free diet. We report a study to identify associated factors. METHODS: Celiac patient cases were collected that had positive celiac serology and villous atrophy at diagnosis, and had undergone a control biopsy after at least 12 months of follow-up. RESULTS: We included 70 celiac patients. They had experienced symptoms for 9.05 ± 9.48 years before being diagnosed. After follow-up for 2.93 ± 1.94 years, 34.3 % had complete mucosal recovery and 57.1 % had partial mucosal recovery. In the comparative analysis we found no relationship between mucosal recovery and sex, age, clinical manifestations or follow-up time from diagnosis to second biopsy. Time with clinical manifestations before diagnosis was associated with a worse outcome: 2.64 years in patients with full recovery, 4.61 years in patients with partial recovery, and 14.26 years in patients with persistent villous atrophy. Higher transglutaminase antibody titers both at diagnosis and during follow-up were associated with poorer histologic outcomes. We observed higher mucosal recovey rates in patients with mild atrophy versus severe atrophy at diagnosis. CONCLUSIONS: In spite of gluten-free diet a significant proportion of patients have persistent histologic changes. Time with clinical manifestations before diagnosis is key for histological severity and recovery.

Influence of social support and stressful life events on adherence to colorectal cancer screening using faecal occult blood test in Spanish medium risk population.

INTRODUCTION: Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. Five-year survival rate in Spain is 57%. The most important prognostic factor is the stage of the tumor at the diagnosis. CRC can be early diagnosed, but the adherence to screening programs is low (<50%). This study aims to ascertain the influence of social support and stressful life events on the adherence to the population screening of CRC with fecal occult blood test in Spanish average risk population. METHODS: Multicenter case-control study. We conducted a simple random sampling among individuals invited to participate in the colorectal cancer screening program. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors. We performed a descriptive and a bivariant analyses and a logistic regression analysis. RESULTS: Four hundred and eight patients (237 cases and 171 controls) were included. Multivariant analyses showed independent association between higher adherence to the screening program and older age (OR: 1.06; 95% CI: 1.01-1.10), stable partner (OR: 1.77, 95% CI: 1.08-2.89) and wide social network (OR: 1.68; 95% CI: 1.07-2.66). Otherwise, lower adherence was associated to perceiving barriers to participate in the program (OR: 0.92; 95% CI: 0.88-0.96). We find a statistically significant association between lower adherence and high impact stressful life events in the bivariant analyses, and the tendency was maintained (OR: 0.63, 95% CI: 0.37-1.08) in the multivariant. CONCLUSION: Social variables decisively influence the adherence to colorectal cancer screening. The implementation of social interventions that improve social support, reduce impact of stressful life events and the design of screening programs that decrease the perceived barriers, will contribute to increase the participation on these programs. Secondary, the colorectal cancer diagnosis will be made in early-stages with the consequent mortality reduction.

Adaptation and validation of an abbreviated version of the SIPAT integrated psychosocial risk scale in patients with liver cirrhosis candidates for liver transplantation (SIPAT-11). / Adaptación y validación de una versión abreviada de la escala SIPAT de riesgo psicosocial integrado en pacientes con cirrosis hepática candidatos a trasplante hepático (SIPAT-11).

INTRODUCTION: Patients with liver cirrhosis who are candidates for liver transplantation must be evaluated both clinically and socially in order to obtain the optimal outcomes and avoid futile therapeutic measures. For the evaluation of the social aspects in these patients, no validated scale in Spanish is available. The SIPAT (Stanford Integrated Psychosocial Assessment for Transplantation) scale is an instrument that measures the social, family and psychological aspects in candidates for solid organ transplantation. The objective of this study is to adapt and validate an abbreviated version of the SIPAT scale in Spanish for patients with liver cirrhosis. MATERIAL AND METHODS: Prospective observational study carried out in the Hepatology Unit of the La Fe Unversity Hospital in Valencia, by questionnaire validation methodology. To analyze the reliability of the questionnaire, the internal consistency of all variables was calculated, for variability an exploratory factor analysis, and for stability the test-retest test was carried out. RESULTS: 96 patients who were admitted for decompensated cirrhosis to the Hepatology Unit of the La Fe Hospital in Valencia between November 1, 2017 and January 31, 2017 were selected. 84% were men, the mean age was 60.01 (SD 10.12) years. In 73.2% of those admitted, the etiology of cirrhosis was alcoholic. 14.4% had a Child's stage A, 57.7% B and 27.8% C. The internal consistency of all variables reached a Cronbach's Alpha of 0.766. In the exploratory factor analysis, 6 dimensions of the questionnaire were identified that explain 84.27% of the total variability. To see the stability of the instrument, the measurement was repeated at 2 and 6 months of follow-up, obtaining in the test-retest a kappa agreement of 0.612 and 0.565 respectively. CONCLUSION: The SIPAT-11 questionnaire has good psychometric characteristics in cirrhotic patients who are candidates for liver transplantation. It is easy to complete and can be administered by professionals who are not specialists in the area of ​​Mental Health.

Comparison of the effect of autoclaved and non-autoclaved live soil exposure on the mouse immune system : Effect of soil exposure on immune system.

BACKGROUND: . Lack of exposure to the natural microbial diversity of the environment has been linked to dysregulation of the immune system and numerous noncommunicable diseases, such as allergies and autoimmune disorders. Our previous studies suggest that contact with soil material, rich in naturally occurring microbes, could have a beneficial immunoregulatory impact on the immune system in mice and humans. However, differences in the immunomodulatory properties of autoclaved, sterile soil material and non-autoclaved, live soil material have not been compared earlier. RESULTS: . In this study, we exposed C57BL/6 mice to autoclaved and live soil powders that had the same rich microbiota before autoclaving. We studied the effect of the soil powders on the mouse immune system by analyzing different immune cell populations, gene expression in the gut, mesenteric lymph nodes and lung, and serum cytokines. Both autoclaved and live soil exposure were associated with changes in the immune system. The exposure to autoclaved soil resulted in higher levels of Rorγt, Inos and Foxp3 expression in the colon. The exposure to live soil was associated with elevated IFN-γ concentration in the serum. In the mesenteric lymph node, exposure to live soil reduced Gata3 and Foxp3 expression, increased the percentage of CD8 + T cells and the expression of activation marker CD80 in XCR1+SIRPα- migratory conventional dendritic cell 1 subset. CONCLUSIONS: . Our results indicate that exposure to the live and autoclaved soil powders is not toxic for mice. Exposure to live soil powder slightly skews the immune system towards type 1 direction which might be beneficial for inhibiting type 2-related inflammation. Further studies are warranted to quantify the impact of this exposure in experimental type 2 inflammation.

A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.

Integrating knowledge and omics to decipher mechanisms via large-scale models of signaling networks.

Signal transduction governs cellular behavior, and its dysregulation often leads to human disease. To understand this process, we can use network models based on prior knowledge, where nodes represent biomolecules, usually proteins, and edges indicate interactions between them. Several computational methods combine untargeted omics data with prior knowledge to estimate the state of signaling networks in specific biological scenarios. Here, we review, compare, and classify recent network approaches according to their characteristics in terms of input omics data, prior knowledge and underlying methodologies. We highlight existing challenges in the field, such as the general lack of ground truth and the limitations of prior knowledge. We also point out new omics developments that may have a profound impact, such as single-cell proteomics or large-scale profiling of protein conformational changes. We provide both an introduction for interested users seeking strategies to study cell signaling on a large scale and an update for seasoned modelers.

Presence of human adenovirus 36 in visceral fat tissue, viral load, and analysis of its genetic variability.

It has been proposed that infection by adipogenic viruses constitutes a "low risk" factor for obesity. Here, we report the presence of adenovirus 36 (Ad36) and its viral load copy number in fat tissue of participants with obesity and normal weight; phylogenetic analysis was performed to describe their relationship and genetic variability among viral haplotypes. Adipose tissue obtained from 105 adult patients with obesity (cases) and 26 normal-weight adult participants as controls were analyzed by quantitative polymerase chain reaction (qPCR) amplifying the partial Ad36 E1a gene. The amplicons were examined by melting curves and submitted to sequencing. Then, genetic diversity and phylogenetic inferences were performed. Ad36 was identified at rates of 82% and 46% in the case and control groups, respectively (p = 1.1 × 10-4 , odds ratio = 5.28); viral load copies were also significantly different between both groups, being 25% higher in the case group. Melting curve analysis showed clear amplification among positive samples. Phylogenetic inferences and genetic diversity analyses showed that the Ad36 E1a gene exhibits low genetic variability and differentiation with strong gene flow due to an expanding process. Our results suggest that the phenomenon of infectobesity by Ad36 might not be a low-risk factor, as has been previously argued by other authors.