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Identifying mechanisms that drive population divergence under varying geographic and ecological scenarios can inform our understanding of evolution and speciation. In particular, analysis of genetic data from island populations with known colonisation timelines allows us to identify potential source populations of diverging island subspecies and current relationships among populations. Silvereyes (Zosterops lateralis) are a small passerine that have served as a valuable study system to investigate evolutionary patterns on both large and small geographic scales. We examined genetic relatedness and diversity of two silvereye subspecies, the mainland Z. l. cornwalli and island Z. l. chlorocephalus, and used 18 077 single nucleotide polymorphisms (SNPs), to compare locations across southeast Queensland, Australia. Although silvereyes are prolific island colonisers our findings revealed population divergence over relatively small spatial scales was strongly influenced by geographic isolation mediated by water barriers. Strong genetic connectivity was displayed between mainland sites, but minimal inter-island connectivity was shown despite comparable sampling distances. Genetic diversity analysis showed little difference in heterozygosity between island and mainland populations, but lower inbreeding scores among the island populations. Our study confirmed the range of the Z. l. chlorocephalus subspecies throughout the southern Great Barrier Reef. Our results show that water barriers and not geographic distance per se are important in driving incipient divergence in island populations. This helps to explain the relatively high number of phenotypically differentiated, but often geographically proximate, island silvereye subspecies compared to a lower number of phenotypically less well-defined Australian continental subspecies.
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Variación Genética , Polimorfismo de Nucleótido Simple , Animales , Passeriformes/genética , Queensland , Genética de Población , Islas , Geografía , AustraliaRESUMEN
Primary antibody deficiencies are characterized by the inability to effectively produce antibodies and may involve defects in B-cell development or maturation. Primary antibody deficiencies can occur at any age, depending on the disease pathology. Certain primary antibody deficiencies affect males and females equally, whereas others affect males more often. Patients typically present with recurrent sinopulmonary and gastrointestinal infections, and some patients can experience an increased risk of opportunistic infections. Multidisciplinary collaboration is important in the management of patients with primary antibody deficiencies because these patients require heightened monitoring for atopic, autoimmune, and malignant comorbidities and complications. The underlying genetic defects associated with many primary antibody deficiencies have been discovered, but, in some diseases, the underlying genetic defect and inheritance are still unknown. The diagnosis of primary antibody deficiencies is often made through the evaluation of immunoglobulin levels, lymphocyte levels, and antibody responses. A definitive diagnosis is obtained through genetic testing, which offers specific management options and may inform future family planning. Treatment varies but generally includes antibiotic prophylaxis, vaccination, and immunoglobulin replacement. Hematopoietic stem cell transplantation is also an option for certain primary antibody deficiencies.
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Síndromes de Inmunodeficiencia , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/terapia , Trasplante de Células Madre Hematopoyéticas , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/terapia , Masculino , Femenino , Linfocitos B/inmunologíaRESUMEN
BACKGROUND: Use of standardized feeding protocols and donor breast milk (DBM) have been studied primarily in infants born <1500 g and not examined exclusively in infants born >1500 g. METHODS: In this retrospective pre-post-implementation cohort study, we evaluated a protocol for preterm infants born >1500 g that was implemented clinically to standardize feeding advancements at 30 mL/kg/day, with infants born <33 weeks eligible to receive DBM. We compared placement of peripherally inserted central catheters for parenteral nutrition, feeding tolerance, growth, and maternal milk provision in the 18 months before/after implementation. The association between DBM intake and growth was evaluated using multivariable linear regression. RESULTS: We identified 133 and 148 eligible infants pre/post-implementation. Frequency of peripherally inserted central catheters and rate of maternal milk provision was not statistically different. While there was no difference in median days to full enteral volume, there was a narrower distribution post-implementation (p < 0.001). Growth was similar between eras, but each 10% increase in DBM was associated with 1.0 g/d decrease in weight velocity (p < 0.001). CONCLUSIONS: A feeding protocol for preterm infants >1500 g is associated with more consistent time to full enteral volume. Further investigation is needed to clarify DBM's impact on growth in this population. IMPACT: Despite practice creep, no study has examined the use of standardized feeding protocols or pasteurized donor breast milk exclusively in infants >1500 g. A feeding protocol in this population may achieve full enteral feedings more consistently. With appropriate fortification, donor breast milk can support adequate growth in infants born >1500 g but warrants further study.
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Microbes rarely exist in isolation and instead form complex polymicrobial communities. As a result, microbes have developed intricate offensive and defensive strategies that enhance their fitness in these complex communities. Thus, identifying and understanding the molecular mechanisms controlling polymicrobial interactions is critical for understanding the function of microbial communities. In this study, we show that the gram-negative opportunistic human pathogen Pseudomonas aeruginosa, which frequently causes infection alongside a plethora of other microbes including fungi, encodes a genetic network which can detect and defend against gliotoxin, a potent, disulfide-containing antimicrobial produced by the ubiquitous filamentous fungus Aspergillus fumigatus. We show that gliotoxin exposure disrupts P. aeruginosa zinc homeostasis, leading to transcriptional activation of a gene encoding a previously uncharacterized dithiol oxidase (herein named as DnoP), which detoxifies gliotoxin and structurally related toxins. Despite sharing little homology to the A. fumigatus gliotoxin resistance protein (GliT), the enzymatic mechanism of DnoP from P. aeruginosa appears to be identical that used by A. fumigatus. Thus, DnoP and its transcriptional induction by low zinc represent a rare example of both convergent evolution of toxin defense and environmental cue sensing across kingdoms. Collectively, these data provide compelling evidence that P. aeruginosa has evolved to survive exposure to an A. fumigatus disulfide-containing toxin in the natural environment.
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Aspergillus fumigatus , Gliotoxina , Pseudomonas aeruginosa , Gliotoxina/metabolismo , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/genética , Zinc/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Interacciones Microbianas , Humanos , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genéticaRESUMEN
BACKGROUND: In 2019, following a large outbreak of typhoid fever, the Zimbabwe Ministry of Health and Child Care conducted a typhoid conjugate vaccine (TCV) vaccination campaign in nine high-risk suburbs of Harare. We aimed to evaluate TCV vaccination coverage, vaccine perceptions, and adverse events reported after vaccination. METHODS: We conducted a two-stage cluster survey to estimate vaccination coverage in the campaign target areas among children aged 6 months-15 years and to classify coverage as either adequate (≥75 % coverage) or inadequate (<75 % coverage) among adults aged 16-45 years in one suburb. Questionnaires assessed socio-demographic factors, TCV vaccination history, reasons for receiving or not receiving TCV, adverse events following immunization, and knowledge and attitudes regarding typhoid and TCV. RESULTS: A total of 1,917 children from 951 households and 298 adults from 135 households enrolled in the survey. Weighted TCV coverage among all children aged 6 months-15 years was 85.3 % (95 % CI: 82.1 %-88.0 %); coverage was 74.8 % (95 % CI: 69.4 %-79.5 %) among children aged 6 months-4 years and 89.3 % (95 % CI: 86.2 %-91.7 %) among children aged 5-15 years. Among adults, TCV coverage was classified as inadequate with a 95 % confidence interval of 55.0 %-73.1 %. Among vaccinated persons, the most reported reason for receiving TCV (96 % across all age groups) was protection from typhoid fever; the most common reasons for non-vaccination were not being in Harare during the vaccination campaign and not being aware of the campaign. Adverse events were infrequently reported in all age groups (10 %) and no serious events were reported. CONCLUSIONS: The 2019 TCV campaign achieved high coverage among school-aged children (5-15 years). Strategies to increase vaccination coverage should be explored for younger children as part of Zimbabwe's integration of TCV into the routine immunization program, and for adults during future post-outbreak campaigns.
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Conocimientos, Actitudes y Práctica en Salud , Programas de Inmunización , Fiebre Tifoidea , Vacunas Tifoides-Paratifoides , Cobertura de Vacunación , Vacunas Conjugadas , Humanos , Zimbabwe , Adolescente , Vacunas Tifoides-Paratifoides/administración & dosificación , Vacunas Tifoides-Paratifoides/inmunología , Vacunas Tifoides-Paratifoides/efectos adversos , Niño , Adulto , Fiebre Tifoidea/prevención & control , Femenino , Masculino , Preescolar , Lactante , Cobertura de Vacunación/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Encuestas y Cuestionarios , Programas de Inmunización/estadística & datos numéricos , Vacunación/estadística & datos numéricosRESUMEN
INTRODUCTION: Standardizing case definitions for priority vaccine safety conditions facilitates uniform evaluation and consolidation of data obtained from different settings. The Brighton Collaboration case definitions (BCCD) were created to support this harmonization and enable classification from level 1 (most certain) to level 5 (not a case) of certainty. Assessing the performance of BCCD in practice is critical, particularly in resource-limited settings, where many new vaccines may be introduced without prior monitoring in high-income countries. We assessed the performance of BCCD in Addis Ababa, Ethiopia, as applicable to COVID-19 and other vaccines. METHODS: Active surveillance was conducted at Tikur Anbessa Specialized Hospital, the largest referral hospital in Ethiopia. During June 1, 2022-May 31, 2023, three trained physicians prospectively identified patients eligible for COVID-19 vaccination (regardless of vaccine receipt) who presented with one or more of eleven pre-specified adverse events of special interest (AESI) from the emergency department and inpatient wards. Standardized data collection forms were used to capture patient information and assign level of certainty (LOC), regardless of vaccination status for COVID-19. We conducted descriptive analysis to characterize cases and the LOCs reached for each AESI. RESULTS: We detected 203 AESI cases. The most detected conditions were thrombosis and thromboembolism (n = 100, 49 %) and generalized convulsions (n = 38, 19 %). Ninety-six percent of the cases were confirmed at levels 1-3 (n = 187) or level 5 (n = 9) LOC. Non-classifiable (level 4) cases were observed for pericarditis (n = 2), encephalitis (n = 2), myelitis (n = 2), and generalized convulsion (n = 1). CONCLUSION: The BCCD were successfully applied in > 95 % of cases in a large referral hospital in Ethiopia, with generalized convulsion, pericarditis, and encephalomyelitis as the exceptions. We recommend further evaluation in other low-resource settings, particularly in rural or non-referral hospitals, to gain additional insights into performance of these definitions for revision or adaptation, as needed.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Etiopía/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Femenino , Estudios Prospectivos , Adulto , Masculino , Persona de Mediana Edad , Adolescente , Adulto Joven , Vacunas contra la COVID-19/administración & dosificación , Anciano , Niño , Preescolar , SARS-CoV-2/inmunología , Vacunación/estadística & datos numéricos , Lactante , Hospitales/estadística & datos numéricosRESUMEN
Adeno-associated Virus (AAV) is a promising vector for gene therapy. However, few studies have focused on producing virus-like particles (VLPs) of AAV in cells, especially in E. coli. In this study, we describe a method to produce empty VP3-only VLPs of AAV2 in E. coli by co-expressing VP3 and assembly-activating protein (AAP) of AAV2. Although the yields of VLPs produced with our method were low, the VLPs were able to self-assemble in E. coli without the need of in vitro capsid assembly. The produced VLPs were characterized by immunological detection and transmission electron microscopy (TEM). In conclusion, this study demonstrated that capsid assembly of AAV2 is possible in E. coli, and E. coli may be a candidate system for production of VLPs of AAV.
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Proteínas de la Cápside , Dependovirus , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Dependovirus/genética , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/biosíntesis , Virión/genética , Virión/metabolismo , Ensamble de Virus , Vectores Genéticos/metabolismo , Vectores Genéticos/genética , Vectores Genéticos/química , Parvovirinae/genética , HumanosRESUMEN
Biology as a field has transformed since the time of its foundation from an organized enterprise cataloging the diversity of the natural world to a quantitatively rigorous science seeking to answer complex questions about the functions of organisms and their interactions with each other and their environments. As the mathematical rigor of biological analyses has improved, quantitative models have been developed to describe multi-mechanistic systems and to test complex hypotheses. However, applications of quantitative models have been uneven across fields, and many biologists lack the foundational training necessary to apply them in their research or to interpret their results to inform biological problem-solving efforts. This gap in scientific training has created a false dichotomy of "biologists'' and "modelers" that only exacerbates the barriers to working biologists seeking additional training in quantitative modeling. Here, we make the argument that all biologists are modelers, and are capable of using sophisticated quantitative modeling in their work. We highlight four benefits of conducting biological research within the framework of quantitative models, identify the potential producers and consumers of information produced by such models, and make recommendations for strategies to overcome barriers to their widespread implementation. Improved understanding of quantitative modeling could guide the producers of biological information to better apply biological measurements through analyses that evaluate mechanisms, and allow consumers of biological information to better judge the quality and applications of the information they receive. As our explanations of biological phenomena increase in complexity, so too must we embrace modeling as a foundational skill.
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BACKGROUND: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. METHODS: From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. RESULTS: The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. CONCLUSIONS: The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.
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Hígado Graso , Procesamiento de Lenguaje Natural , Humanos , Cirrosis Hepática/diagnóstico , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Algoritmos , BiopsiaRESUMEN
Woody plants rely on the remobilization of carbon (C) and nitrogen (N) reserves to support growth and survival when resource demand exceeds supply at seasonally predictable times like spring leaf flush and following unpredictable disturbances like defoliation. However, we have a poor understanding of how reserves are regulated and whether distance between source and sink tissues affects remobilization. This leads to uncertainty about which reserves-and how much-are available to support plant functions like leaf growth. To better understand the source of remobilized reserves and constraints on their allocation, we created aspen saplings with organ-specific labeled reserves by using stable isotopes (13C,15N) and grafting unlabeled or labeled stems to labeled or unlabeled root stocks. We first determined which organs had imported root or stem-derived C and N reserves after spring leaf flush. We then further tested spatial and temporal variation in reserve remobilization and import by comparing 1) upper and lower canopy leaves, 2) early and late leaves, and 3) early flush and re-flush leaves after defoliation. During spring flush, remobilized root C and N reserves were preferentially allocated to sinks closer to the reserve source (i.e., lower vs upper canopy leaves). However, the reduced import of 13C in late versus early leaves indicates reliance on C reserves declined over time. Following defoliation, re-flush leaves imported the same proportion of root N as spring flush leaves, but they imported a lower proportion of root C. This lower import of reserve C suggests that, after defoliation, leaf re-flush rely more heavily on current photosynthate, which may explain the reduced leaf mass recovery of re-flush canopies (31% of initial leaf mass). The reduced reliance on reserves occurred even though roots retained significant starch concentrations (~5% dry wt), suggesting aspen prioritizes the maintenance of root reserves at the expense of fast canopy recovery.
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Osteogenesis imperfecta (OI), a disorder of type I collagen, causes skeletal deformities as well as defects in dental tissues, which lead to increased enamel wear and smaller teeth with shorter roots. Mice with OI exhibit similar microstructural dentin changes, including reduced dentin tubule density and dentin cross-sectional area. However, the effects of these mutations on gross dental morphology and dental tissue volumes have never been characterized in the osteogenesis imperfecta murine (OIM) mouse model. Here we compare mineralized dental tissue measurements of OIM mice and unaffected wild type (WT) littermates at the juvenile and adult stages. The maxillary and mandibular incisors and first molars were isolated from microCT scans, and tissue volumes and root length were measured. OIM mice have smaller teeth with shorter roots relative to WT controls. Maxillary incisor volumes differed significantly between OIM and WT mice at both the juvenile and young adult stage, perhaps due to shortening of the maxilla itself in OIM mice. Additionally, adult OIM mice have significantly less crown enamel volume than do juveniles, potentially due to loss through wear. Thus, OIM mice demonstrate a dental phenotype similar to humans with OI, with decreased tooth size, decreased root length, and accelerated enamel wear. Further investigation of dental development in the OIM mouse may have important implications for the development and treatment of dental issues in OI patients.
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Osteogénesis Imperfecta , Ratones , Humanos , Animales , Osteogénesis Imperfecta/genética , Colágeno Tipo I , Fenotipo , Mutación , Incisivo , Modelos Animales de EnfermedadRESUMEN
Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation. The OI craniofacial phenotype includes midfacial underdevelopment, as well as neurocranial changes (e.g., macrocephaly and platybasia) that may also affect underlying nervous tissues. This study aims to better understand how OI affects the integrated development of the neurocranium and the brain. Juvenile and adult mice with OI (OIM) and unaffected wild type (WT) littermates were imaged using in vivo micro-computed tomography (microCT). Virtual endocast models were used to measure brain volume, and 3D landmarks were collected from the cranium and brain endocasts. Geometric morphometric analyses were used to compare brain shape and integration between the genotypes. OIM mice had increased brain volumes (relative to cranial centroid size) only at the juvenile stage. No significant difference was seen in cranial base angle (CBA) between OIM and WT mice. However, CBA was higher in juvenile than in adult OIM mice. Brain shape was significantly different between OIM and WT mice at both stages, with OIM mice having more globular brains than WT mice. Neurocranial and brain morphology were strongly integrated within both genotypes, while adult OIM mice tended to have lower levels of skull-brain integration than WT mice. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Decreased skull-brain integration in adult mice suggests that compensatory mechanisms may exist during postnatal growth to maintain neurological function despite significant changes in neurocranial morphology.
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Osteogénesis Imperfecta , Ratones , Animales , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/genética , Microtomografía por Rayos X , Colágeno Tipo I , Cráneo/diagnóstico por imagen , Fenotipo , Modelos Animales de Enfermedad , OsteogénesisRESUMEN
Mucormycosis, also known as black fungus, is a rare but aggressive fungal disease with high morbidity and mortality rates that tends to affect patients who are severely immunocompromised. Early recognition of the infection and prompt intervention is critical for treatment success. In recent years the coronavirus disease of 2019 (COVID-19) pandemic has resulted in a surge in the number of cases of mucormycosis. This study aims to report an unfortunate event involving an immunocompromised elderly man with mucormycosis of the foot who died as a result of sepsis caused by COVID-19. It is important to have a high clinical suspicion for mucormycosis when a clinical lesion develops, and to appropriately perform biopsy the lesion in question, particularly in the context of COVID-19. Raising awareness of COVID-19-associated mucormycosis may allow for early detection of the disease, thus enabling the initiation of rapid treatment, ultimately saving lives.
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COVID-19 , Mucormicosis , Anciano , Masculino , Humanos , Mucormicosis/diagnóstico , Pie , Extremidad Inferior , HongosRESUMEN
Aberrant activation of the PI3K-AKT pathway is common in many cancers, including melanoma, and AKT1, 2 and 3 (AKT1-3) are bona fide oncoprotein kinases with well-validated downstream effectors. However, efforts to pharmacologically inhibit AKT have proven to be largely ineffective. In this study, we observed paradoxical effects following either pharmacologic or genetic inhibition of AKT1-3 in melanoma cells. Although pharmacological inhibition was without effect, genetic silencing of all three AKT paralogs significantly induced melanoma cell death through effects on mTOR. This phenotype was rescued by exogenous AKT1 expression in a kinase-dependent manner. Pharmacological inhibition of PI3K and mTOR with a novel dual inhibitor effectively suppressed melanoma cell proliferation in vitro and inhibited tumor growth in vivo. Furthermore, this single-agent-targeted therapy was well-tolerated in vivo and was effective against MAPK inhibitor-resistant patient-derived melanoma xenografts. These results suggest that inhibition of PI3K and mTOR with this novel dual inhibitor may represent a promising therapeutic strategy in this disease in both the first-line and MAPK inhibitor-resistant setting.
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Melanoma , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular , Muerte CelularRESUMEN
Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (tet2), a dioxygenase enzyme that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, is a recurrently mutated tumor suppressor gene in MDS and other myeloid malignancies. Previously, we reported a stable zebrafish line with a loss-of-function mutation in the tet2 gene. The tet2m/m-mutant zebrafish developed a pre-MDS state with kidney marrow dysplasia, but normal circulating blood counts by 11 months of age and accompanying anemia, signifying the onset of MDS, by 24 months of age. Methods: In the current study, we collected progenitor cells from the kidney marrows of the adult tet2m/m and tet2wt/wt fish at 4 and 15 months of age and conducted enhanced reduced representation of bisulfite sequencing (ERRBS) and bulk RNA-seq to measure changes in DNA methylation and gene expression of hematopoietic stem and progenitor cells (HSPCs). Results and discussion: A global increase in DNA methylation of gene promoter regions and CpG islands was observed in tet2m/m HSPCs at 4 months of age when compared with the wild type. Furthermore, hypermethylated genes were significantly enriched for targets of SUZ12 and the metal-response-element-binding transcription factor 2 (MTF2)-involved in the polycomb repressive complex 2 (PRC2). However, between 4 and 15 months of age, we observed a paradoxical global decrease in DNA methylation in tet2m/m HSPCs. Gene expression analyses identified upregulation of genes associated with mTORC1 signaling and interferon gamma and alpha responses in tet2m/m HSPCs at 4 months of age when compared with the wild type. Downregulated genes in HSPCs of tet2-mutant fish at 4 months of age were enriched for cell cycle regulation, heme metabolism, and interleukin 2 (IL2)/signal transducer and activator of transcription 5 (STAT5) signaling, possibly related to increased self-renewal and clonal advantage in HSPCs with tet2 loss of function. Finally, there was an overall inverse correlation between overall increased promoter methylation and gene expression.
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This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of "persistency" in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex.
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Síntomas del Sistema Urinario Inferior , Diafragma Pélvico , Humanos , Puntos Disparadores , Síntomas del Sistema Urinario Inferior/diagnóstico , Hipertonía MuscularRESUMEN
OBJECTIVE: Traumatic brain injury (TBI) is a significant public health concern and has implications for people directly impacted by the criminal legal system during arrest, conviction, incarceration, and community supervision. This meta-analysis estimated the lifetime prevalence of TBI among people supervised by the criminal legal system across settings. HYPOTHESES: Building on previous research, we hypothesized that prevalence estimates would be impacted by methodological, clinical, and demographic factors. METHOD: Eligible studies included those with adult participants supervised by the criminal legal system (i.e., prison, jail, probation, parole, inpatient/forensic hospital) and that provided sample TBI prevalence and method of ascertaining TBI history. We employed subgroup analyses and metaregression to investigate the effects of setting, TBI definition and method of detection, lifetime history of mental illness and substance use disorders, and gender. RESULTS: The sample ultimately included 64 studies totaling 52,540 participants. Using a random-effects model and logit transformation, we found that the overall estimate of TBI prevalence was 45.8% (95% confidence interval, CI [37.8, 54.1], 95% prediction interval, PI [5.5, 92.5]) across all studies and 32.0% (95% CI [25.0, 39.8], 95% PI [11.2, 63.6]) for moderate-to-severe TBI. Significant effects were found for TBI definition and method of detection on the pooled estimate. CONCLUSIONS: The prevalence of TBI among people impacted by the criminal legal system may be larger than in the general population. However, despite recent and ongoing progress in this area of study, the reliability of prevalence estimates remains limited by methodological factors related to TBI definitions and detection methods. Implications for TBI research and clinical service provision are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Lesiones Traumáticas del Encéfalo , Criminales , Adulto , Humanos , Prevalencia , Reproducibilidad de los Resultados , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios LongitudinalesRESUMEN
Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10-10 per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.
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Tasa de Mutación , Tiburones , Animales , Tiburones/genética , EcosistemaRESUMEN
A fundamental goal in evolutionary biology is to understand the genetic architecture of adaptive traits. Using whole-genome data of 3955 of Darwin's finches on the Galápagos Island of Daphne Major, we identified six loci of large effect that explain 45% of the variation in the highly heritable beak size of Geospiza fortis, a key ecological trait. The major locus is a supergene comprising four genes. Abrupt changes in allele frequencies at the loci accompanied a strong change in beak size caused by natural selection during a drought. A gradual change in Geospiza scandens occurred across 30 years as a result of introgressive hybridization with G. fortis. This study shows how a few loci with large effect on a fitness-related trait contribute to the genetic potential for rapid adaptive radiation.