Epigenetic Regulation of Progenitor Cell Commitment by Hdac3

Tissue-specific progenitor cells emerge during development to expand and differentiate into the multiple cell lineages that populate the embryo. Appropriate differentiation of these precursor cells requires coordinated expression of numerous lineage-specific genes and repression of alternative fate programs. Epigenetic regulators are enzymes capable of activating or silencing large genomic domains by altering histone modifications, DNA methylation status and chromatin organization. Although differentiating progenitor cells undergo epigenetic changes and epigenetic factors are required for appropriate cell behavior, the precise mechanism of how these proteins influence cell fate remains unclear. In this dissertation, I examine the role of histone deacetylase 3 in control of neural crest and cardiac progenitor cell commitment. Using Cre-mediated genetic deletion, I generated tissue-specific mouse models to study the function of Hdac3 in both neural crest and cardiac cells. These studies revealed a critical role for Hdac3 in maintaining neural crest proliferation and cell survival through regulation of a core network of factors required for craniofacial development. In cardiac progenitors, Hdac3 maintains appropriate differentiation into the cardiomyocyte, smooth muscle and endothelial cell lineages that make up the developed heart. Hdac3 represses a cardiomyocyte-specific gene program and prevents precocious differentiation of progenitors into the myocyte lineage. Surprisingly, this protein does not require deacetylase activity to repress myocyte commitment, and instead serves as a tether to retain myocyte-specific genomic loci at the nuclear periphery. This novel mechanism of gene repression and lineage specification highlights the role that nuclear architecture plays in controlling transcriptional activity and progenitor cell behavior

Imaging chemokine receptor dimerization with firefly luciferase complementation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154639/1/fsb2fj08116749.pd

Clinical bleeding patterns and management of abnormal uterine bleeding in non-pregnant women: a cross-sectional study

Background: Around 10 to 15 percent of women go through instances of unusual bleeding from their uterus at some point during their reproductive years. Additionally, up to one-third of women may come across irregular menstrual cycles. These irregularities often occur during two crucial phases in a woman's life: firstly, at the beginning of menstruation, which is known as menarche, and secondly, during the transition leading up to menopause, referred to as perimenopause. Aim of study was to determine the clinical bleeding patterns in nonpregnant women and its management. Methods: During the study period spanning from November 2021 to December 2022, a cross-sectional study examined non-pregnant females aged 15 to 55 experiencing abnormal vaginal bleeding (AUB) who provided consent. However, certain exclusion criteria were established to ensure that the study's findings remained pertinent to the target population. Females exhibiting vaginal bleeding attributed to pregnancy or pregnancy-related factors were excluded from the study, as were those with vaginal bleeding stemming from vaginitis, cervical benign, premalignant, or malignant conditions, or traumatic causes. Descriptive statistics were employed in the study. Results: Structural causes [PALM] accounts for 71 (61%) of cases whereas non-structural causes of chronic AUB account for 44 (39%) of cases. AUB-L, 45 (39.2%) was the most frequent finding in females with AUB. The second most common causes are AUB-O 23 (20%) followed by AUB-A 14 (12.2%), AUB-C 08(7%), AUB-M 07 (6.1%), AUB-E 06 (5.2%), AUB-P and AUB-I in 05 (4.3%) each and AUB-N 02 (1.7%). Conclusions: Focusing on Abnormal Uterine Bleeding (AUB), it was observed that AUB-L, attributed to leiomyomas, emerged as the most prevalent cause among affected females. Subsequently, AUB-O, arising from ovulatory dysfunction, and aub-a, linked to adenomyosis, ranked as the second and third most common causes, respectively. Among the clinical manifestations of AUB, prolonged bleeding was identified as the most frequent symptom, followed closely by heavy bleeding.

Proteins Encoded by the gerP Operon Are Localized to the Inner Coat in Bacillus cereus Spores and Are Dependent on GerPA and SafA for Assembly.

The germination of Bacillus spores is triggered by certain amino acids and sugar molecules which permeate the outermost layers of the spore to interact with receptor complexes that reside in the inner membrane. Previous studies have shown that mutations in the hexacistronic gerP locus reduce the rate of spore germination, with experimental evidence indicating that the defect stems from reduced permeability of the spore coat to germinant molecules. Here, we use the ellipsoid localization microscopy technique to reveal that all six Bacillus cereus GerP proteins share proximity with cortex-lytic enzymes within the inner coat. We also reveal that the GerPA protein alone can localize in the absence of all other GerP proteins and that it has an essential role for the localization of all other GerP proteins within the spore. Its essential role is also demonstrated to be dependent on SafA, but not CotE, for localization, which is consistent with an inner coat location. GerP-null spores are shown also to have reduced permeability to fluorescently labeled dextran molecules compared to wild-type spores. Overall, the results support the hypothesis that the GerP proteins have a structural role within the spore associated with coat permeability.IMPORTANCE The bacterial spore coat comprises a multilayered proteinaceous structure that influences the distribution, survival, and germination properties of spores in the environment. The results from the current study are significant since they increase our understanding of coat assembly and architecture while adding detail to existing models of germination. We demonstrate also that the ellipsoid localization microscopy (ELM) image analysis technique can be used as a novel tool to provide direct quantitative measurements of spore coat permeability. Progress in all of these areas should ultimately facilitate improved methods of spore control in a range of industrial, health care, and environmental sectors.1. Engineering and Physical Sciences Research Council Centre for Doctoral Training in Sensor Technologies and Applications (EP/L015889/1) 2. Cambridge Nehru Scholarship 3. Raymond and Beverly Sackler Foundation 4. MedImmun

Imaging of Knee Joint Pathologies: A Comparative Study of Ultrasound and Magnetic Resonance Imaging

Background: Magnetic resonance imaging (MRI) has been accepted as the best non-invasive imaging modality for the evaluation of knee joint pathology but the advantages of ultrasound (US) over magnetic resonance imaging (MRI) are that the ultrasound is readily available, cheap and offers real-time imaging. Aim: To assess the accuracy of ultrasound in diagnosing knee joint pathologies using MRI as a reference. Materials And Methods: 50 patients were evaluated prospectively over a period of 1.5 years by USG followed by MRI of the affected knee. Accuracy of USG was calculated with MRI as reference. Results: In our study, the majority of patients were in age group 21-30 years. Perfect agreement was noted between ultrasound and MRI for detecting Baker’s cyst. Near perfect agreement was noted between ultrasound and MRI for detecting joint effusion, soft tissue edema and osteophytes. Substantial agreement was noted between ultrasound and MRI for Collateral ligaments tear and Meniscal injuries. Moderate agreement was noted between ultrasound and MRI for PCL tear. Fair agreement was noted between ultrasound and MRI for ACL tear. Conclusion: Knee USG has high accuracy in diagnosing pathologies like knee joint effusion, synovitis, popliteal/baker’s cysts, soft tissue edema/cellulitis, arthritic changes, collateral ligament and meniscal tears. Keywords: Knee joint pathologies, Ultrasound, MRI, Ligament

Technology Pipeline for Large Scale Cross-Lingual Dubbing of Lecture Videos into Multiple Indian Languages

Cross-lingual dubbing of lecture videos requires the transcription of the original audio, correction and removal of disfluencies, domain term discovery, text-to-text translation into the target language, chunking of text using target language rhythm, text-to-speech synthesis followed by isochronous lipsyncing to the original video. This task becomes challenging when the source and target languages belong to different language families, resulting in differences in generated audio duration. This is further compounded by the original speaker's rhythm, especially for extempore speech. This paper describes the challenges in regenerating English lecture videos in Indian languages semi-automatically. A prototype is developed for dubbing lectures into 9 Indian languages. A mean-opinion-score (MOS) is obtained for two languages, Hindi and Tamil, on two different courses. The output video is compared with the original video in terms of MOS (1-5) and lip synchronisation with scores of 4.09 and 3.74, respectively. The human effort also reduces by 75%

Influence of resource gradients and habitat edges on density variation in tiger populations in a multi-use landscape

Spatial heterogeneity in the local densities of terrestrial carnivores is driven by multiple interacting biotic and abiotic factors. Space-use patterns of large carnivores reflect the competing demands of resource selection (e.g., exploitation of habitats with abundant prey) and minimization of risks arising from human interactions. Estimating the relative strength of these drivers is essential to understand spatial variation in densities of large carnivores and there are still key knowledge gaps for many large carnivore populations. To better understand the relative roles of environmental and human drivers of spatial variation in tiger (Panthera tigris) densities, we surveyed a 3000 km2 landscape in North India using camera trap data. Over two years, we photo-captured 92 unique adult tigers. Associating spatial covariates with patterns of detection allowed us to test hypotheses about the relative influence of prey abundance, habitat structure and extent, and proximity to habitat edges on spatial variation in tiger densities across a gradient of anthropogenic disturbance. We documented extensive variation in tiger density within and across management units and protected areas. Spatial variation in prey abundance and proximity to grassland habitats, rather than human use (e.g. extent of human-dominated edge habitat and protection status), explained most of the spatial variation in tiger density in two of the five surveyed sites. The region’s largest tiger population occurred in a multi-use forest beyond protected area boundaries, where wild ungulates were abundant. Our results suggest that tigers can occur at high densities in areas with extensive human use, provided sufficiently high prey densities, and tracts of refuge habitats (eg. areas with dense vegetation with low human use). We argue that tiger conservation portfolio can be expanded across multi-use landscapes with a focus on areas that are adaptively managed as “zones of coexistence” and “refuge habitats”. Advancing this conservation strategy is contingent on greatly strengthening systems to effectively and equitably redress human–wildlife conflict and leveraging existing policies to strengthen local participation in conservation planning and forest stewardship. Our insights into the environmental drivers of spatial heterogeneity in tiger populations can inform both local management and guide to species recovery in working landscapes