Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years.
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ABSTRACT:
SUBMITTER: Cho YK
PROVIDER: S-EPMC8145643 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The second law of thermodynamics states that entropy, as a measure of randomness in a system, increases over time. Although studies have investigated biological sequence randomness from different aspects, it remains unknown whether sequence randomness changes over time and whether this change consists with the second law of thermodynamics. To capture the dynamics of randomness in molecular sequence evolution, here we detect sequence randomness based on a collection of eight statistical random tests and investigate the randomness variation of coding sequences with an application to Escherichia coli. Given that core/essential genes are more ancient than specific/non-essential genes, our results clearly show that core/essential genes are more random than specific/non-essential genes and accordingly indicate that sequence randomness indeed increases over time, consistent well with the second law of thermodynamics. We further find that an increase in sequence randomness leads to increasing randomness of GC content and longer sequence length. Taken together, our study presents an important finding, for the first time, that sequence randomness increases over time, which may provide profound insights for unveiling the underlying mechanisms of molecular sequence evolution.
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Project description:The Rakai Community Cohort Study in south central Uganda has surveyed people aged 15-49 since 1994. Antiretroviral therapy (ART) was introduced in 2004. HIV p24 and gp41 subtype distribution and viral diversity were studied from blood samples collected at three surveys in 1994-1995, 2002-2003, and 2008-2009, which were compared with a new survey round from 2011 to 2012. These included 1364 HIV+ individuals. For both p24 and gp41 domains, the genetic diversity within subtypes A and D was significantly increasing in the pre-ART era and decreased between the last two survey rounds in the ART era (p < .01). This study suggests that despite ongoing mixing of viral subtypes, an association with the introduction of ART to a reduction of intra-subtype viral genomic diversity may be occurring, which can be explored in ongoing studies.
| S-EPMC7476391 | biostudies-literature
Project description:INTRODUCTION:In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ensure timely care and help protect the walking blood bank, and initiated the U.S. Military HIV Natural History Study (NHS) to develop epidemiologic, clinical, and basic science evidence to inform military HIV policy and establish a repository of data and specimens for future research. Here, we have reviewed accomplishments of the NHS over the past 30 years and sought to describe relevant trends among NHS subjects over this time, with emphasis on combination antiretroviral therapy (cART) use and non-AIDS comorbidities. METHODS:Subjects who were prospectively enrolled in the NHS from 1986 through 2015 were included in this analysis. Time periods were classified by decade of study conduct, 1986-1995, 1996-2005, and 2006-2015, which also correlate approximately with pre-, early-, and late-combination ART (cART) eras. Analyses included descriptive statistics and comparisons among decades. We also evaluated mean community log10 HIV viral load (CVL) and CD4 counts for each year. RESULTS:A total of 5,758 subjects were enrolled between 1986 and 2015, of whom 92% were male with a median age of 28 years, and 45% were African-American, 42% Caucasian, and 13% Hispanic/other. The proportion of African-Americans remained stable over the decades (45%, 47%, and 42%, respectively), while the proportion of Hispanic/other increased (10%, 13%, and 24%, respectively). The CD4 count at HIV diagnosis has remained high (median 496 cells/uL), while the occurrence of AIDS-defining conditions (excluding low CD4 count) has decreased by decade (36.7%, 5.4%, and 2.9%, respectively). Following the introduction of effective cART in 1996, CVL declined through 2000 as use increased and then plateaued until guidelines changed. After 2004, cART use again increased and CVL declined further until 2012-15 when the vast majority of subjects achieved viral suppression. Non-AIDS comorbidities have remained common, with approximately half of subjects experiencing one or more new diagnoses overall and nearly half of subjects diagnosed between 2006 and 2015, in spite of their relatively young age, shorter median follow-up, and wide use of cART. CONCLUSIONS:The US Military HIV NHS has been critical to understanding the impact of HIV infection among active-duty service members and military beneficiaries, as well as producing insights that are broadly relevant. In addition, the rich repository of NHS data and specimens serves as a resource to investigators in the DoD, NIH, and academic community, markedly increasing scientific yield and identifying novel associations. Looking forward, the NHS remains relevant to understanding host factor correlates of virologic and immunologic control, biologic pathways of HIV pathogenesis, causes and consequences of residual inflammation in spite of effective cART, identifying predictors of and potential approaches to mitigation of excess non-AIDS comorbidities, and helping to understand the latent reservoir.
| S-EPMC6886375 | biostudies-literature
Project description:BackgroundIn-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates.Methods10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting.FindingsOur data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends.InterpretationViral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression.FundingAbbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.
| S-EPMC7992073 | biostudies-literature
Project description:We report here the complete genome sequence of Mycobacterium tuberculosis strain Colonial S-type 1 (CS1), which has been responsible for ongoing outbreaks of tuberculosis in New Zealand over the past 30 years. CS1 appears to be highly transmissible, with greater rates of progression to active disease, compared to other circulating M. tuberculosis strains; therefore, comparison of its genomic content is of interest.
| S-EPMC9670914 | biostudies-literature
Project description:Fear memory is a highly stable and durable form of memory, even over vast (remote) time frames. Nevertheless, some elements of fear memory can be forgotten, resulting in generalization. The purpose of this study is to determine how cued fear memory generalizes over time and measure underlying patterns of cortico-amygdala synaptic plasticity. We established generalization gradients at recent (1-d) and remote (30-d) retention intervals following auditory cued fear conditioning in adult male C57BL/6 mice. Results revealed a flattening of the generalization gradient (increased generalization) that was dissociated from contextual fear generalization, indicating a specific influence of time on cued fear memory performance. This effect reversed after a brief exposure to the novel stimulus soon after learning. Measurements from cortico-amygdala imaging of the activity-regulated cytoskeletal Arc/arg 3.1 (Arc) protein using immunohistochemistry after cued fear memory retrieval revealed a stable pattern of Arc expression in the dorsolateral amygdala, but temporally dynamic expression in the cortex. Over time, increased fear memory generalization was associated with a reduction in Arc expression in the agranular insular and infralimbic cortices while discrimination learning was associated with increased Arc expression in the prelimbic cortex. These data identify the dorsolateral amygdala, medial prefrontal, and insular cortices as loci for synaptic plasticity underlying cued fear memory generalization over time.
| S-EPMC6004064 | biostudies-literature
Project description:Publication and authorship are important in academia for career advancement, obtaining grants, and improved patient care. There has been a recent interest in bibliometric changes over time, especially regarding the gender gap. The purpose of this study was to explore bibliometric changes in the musculoskeletal literature. Bibliometric variables (number of authors, institutions, countries, pages, references, corresponding author position, author gender, geographic region of origin, and editorial board makeup) were analyzed for 5 basic science and 12 clinically oriented musculoskeletal journals from 1985 through 2016. Statistical analyses comprised bivariate analyses, multifactorial ANOVAs, and logistic regression analyses. A p < 0.005 was considered significant. Nearly, all variables increased over time. Asia had the highest number of authors and corresponding author positions, Australia/New Zealand the highest number of institutions and references, North America the highest number of pages, and Europe the highest number of countries. Those with a female first author had more authors, institutions, countries, references, and pages. Likewise, those with a female corresponding author had more authors, institutions, countries, references, and pages. Single-authored manuscripts decreased over time. The percentage of female first authors rose from 10.8% in 1985-1987 to 23.7% in 2015-2016. There were more female 1st authors in the basic science journals compared to the clinical journals (33.2% vs. 12.7%). Single-authored manuscripts were more likely to be written by males (5.1 vs. 2.4%) and decreased over time. The many differences by geographic region of origin likely reflect different socio/cultural attitudes regarding academia and research, as well as the gender composition of the disciplines by geographic region. Overall, there has been an increase in the number of female 1st and corresponding authors, editorial board members, and chief editors, indicating a slow but progressive narrowing of the gender gap.
| S-EPMC8096573 | biostudies-literature
Project description:PurposeLaparoscopic giant hiatus hernia repair is technically difficult with ongoing debate regarding the most effective surgical technique. Repair of small hernia has been well described but data for giant hernia is variable. This study evaluated trends in outcomes of laparoscopic non-mesh repair of giant paraesophageal hernia (PEH) over 30 years.MethodsRetrospective analysis of a single-surgeon prospective database. Laparoscopic non-mesh repairs for giant PEH between 1991 and 2021 included. Three-hundred-sixty-degree fundoplication was performed routinely, evolving into "composite repair" (esophagopexy and cardiopexy to the right crus). Cases were chronologically divided into tertiles based on operation date (Group 1, 1991-2002; Group 2, 2003-2012; Group 3, 2012-2021) with trends in casemix, operative factors and outcomes evaluated. Hernia recurrence was plotted using weighted moving average and cumulative sum (CUSUM) analysis.Results862 giant PEH repairs met selection criteria. There was an increasing proportion of "composite repair" after the first decade (Group 1, 2.7%; Group 2, 81.9%; Group 3, 100%; p < 0.001). There were less anatomical hernia recurrence (Group 1, 36.6%; Group 2, 22.9%; Group 3, 22.7%; p < 0.001) and symptomatic recurrence (Group 1, 34.2%; Group 2, 21.9%; Group 3, 7%; p < 0.001) over time. The incidence of anatomical recurrence declined over time, decreasing from 30.8% and plateauing below 17.6% near the study's end. Median followup (months) in the first decade was higher but followup between the latter two decades comparable (Group 1, 49 [IQR 20, 81]; Group 2, 30 [IQR 15, 65]; Group 3, 24 [14, 56]; p < 0.001). There were 10 (1.2%) Clavien-Dindo grade ≥ III complications including two perioperative deaths (0.2%).ConclusionHernia recurrence rates decreased with increasing case volume. This coincided with the increasing adoption of "composite repair", supporting the possible improvement in recurrence rates with this approach.
| S-EPMC10700453 | biostudies-literature
Project description:UnlabelledBluetongue virus serotype 1 (BTV 1) was first isolated in Australia from cattle blood collected in 1979 at Beatrice Hill Farm (BHF), Northern Territory (NT). From long-term surveillance programs (1977 to 2011), 2,487 isolations of 10 BTV serotypes were made. The most frequently isolated serotype was BTV 1 (41%, 1,019) followed by BTV 16 (17.5%, 436) and BTV 20 (14%, 348). In 3 years, no BTVs were isolated, and in 12 years, no BTV 1 was isolated. Seventeen BTV 1 isolates were sequenced and analyzed in comparison with 10 Australian prototype serotypes. BTV 1 showed an episodic pattern of evolutionary change characterized by four distinct periods. Each period consisted primarily of slow genetic drift which was punctuated from time to time by genetic shifts generated by segment reassortment and the introduction of new genome segments. Evidence was found for coevolution of BTV genome segments. Evolutionary dynamics and selection pressure estimates showed strong temporal and clock-like molecular evolutionary dynamics of six Australian BTV genome segments. Bayesian coalescent estimates of mean substitution rates clustered in the range of 3.5 × 10(-4) to 5.3 × 10(-4) substitutions per site per year. All BTV genome segments evolved under strong purifying (negative) selection, with only three sites identified as under pervasive diversifying (positive) selection. The obligate replication in alternate hosts (insect vector and vertebrate hosts) imposed strong evolutionary constraints. The dominant mechanism generating genetic diversity of BTV 1 at BHF was through the introduction of new viruses and reassortment of genome segments with existing viruses.ImportanceBluetongue virus (BTV) is the causative agent of bluetongue disease in ruminants. It is a disease of concern globally and is transmitted by biting midges (Culicoides species). Analysis of the evolutionary and selection pressures on BTV 1 at a single surveillance site in northern Australia showed strong temporal and clock-like dynamics. Obligate replication in alternate hosts of insect and vertebrate imposed strong evolutionary constraints, with all BTV genome segments evolving under strong purifying (negative) selection. Generation of genetic diversity of BTV 1 in northern Australia is through genome segment reassortment and the introduction of new serotypes.
| S-EPMC4249141 | biostudies-literature
Project description:Organic photovoltaic cells (OPVs) have the potential of becoming a productive renewable energy technology if the requirements of low cost, high efficiency and prolonged lifetime are simultaneously fulfilled. So far, the remaining unfulfilled promise of this technology is its inadequate operational lifetime. Here, we demonstrate that the instability of NFA solar cells arises primarily from chemical changes at organic/inorganic interfaces bounding the bulk heterojunction active region. Encapsulated devices stabilized by additional protective buffer layers as well as the integration of a simple solution processed ultraviolet filtering layer, maintain 94% of their initial efficiency under simulated, 1 sun intensity, AM1.5 G irradiation for 1900 hours at 55 °C. Accelerated aging is also induced by exposure of light illumination intensities up to 27 suns, and operation temperatures as high as 65 °C. An extrapolated intrinsic lifetime of > 5.6 × 104 h is obtained, which is equivalent to 30 years outdoor exposure.
| S-EPMC8440764 | biostudies-literature