Epigenetic barriers to human gynogenesis

There have been leaps in both fields of epigenetics and reproductive technology. This has culminated in the production of bi-maternal mouse offspring through a few studies utilizing direct gene mutations as functional-imprints. While these genetic interventions result in positive results, it has yet to be described, in full, what mechanisms underlie the epigenetic barriers to human gynogenesis. Between maternal and paternal imprints, differences in methylation patterns of CpG island promoters, non-coding regions, microsatellites, transposons, and histones result in differences in higher order chromatin structure, which ultimately impacts expression of certain genes. While the necessary components of a minimal paternal epigenetic program are described, programming this imprint onto m2, a hypothetical, experimentally-produced maternal genome with a paternal epigenome is still not elucidated. Sequential timing of imprint acquisition and maintenance and the numerous regulatory factors associated with them illuminate how difficult potential assisted reproductive epigenetic interventions will be. Other processes like histone-protamine exchange which also plays a crucial factor in structural regulation of imprints, as well as signaling through and after fertilization, pose logistical problems to creating a gynogenote through epigenetic means. Lastly, ethics surrounding the introduction of dangerous mutations and epialleles into the human population add another wall of caution and hesitance in exploring human gynogenesis as a reproductive technology

F21RS SGR No. 6 (Tiger Stadium)

A Resolution To urge and request LSU Board of Supervisors and LSU Athletics to verify the vaccine status of Tiger Stadium guests entering the stadium or verify a negative covid test as per their own polic

Investigating rare genetic variants of unknown significance in LDHA

The exponential expansion and advancement of genetic sequencing has revealed the molecular basis of many genetic diseases. However, many genetic mutations are still classified as variants of unknown significance (VUS). Our lab focused on eleven missense variants in Lactate Dehydrogenase A (LDHA), an enzyme vital in anaerobic respiration. The intent with our research is to produce data on the kinetic functionality of wild type LDHA and compare this to its mutants of unknown significance. This data, supplemented with the structural information of the mutants can help reduce the ambiguity in the diagnosis of genetic disorders involving the LDHA enzyme. Currently, we have recorded the baseline kinetic function of the wild type LDHA based on its ability to convert the coenzyme NADH to NAD+. While we have a general understanding of the kinetic function of our mutant variants, A320T, T309P, L190F, E55K, D46V, P139L, G282R, K119R, T95M, G103E, and I94F, further tests need to be conducted to reduce variability

Contemporary vs. Traditional DNA-Based Mutation Testing to Detect Hereditary Breast and Ovarian Cancer Syndrome (HBOC) in Women: A Meta Narrative Review

https://openworks.mdanderson.org/rmps24/1000/thumbnail.jp

Novel defense by honeybees against mass attack by giant wasps

Trabalho final de mestrado integrado em Medicina (Pediatria), apresentado á Faculdade de Medicina da Universidade de CoimbraIntrodução: A perturbação do espectro do autismo (PEA) é uma patologia complexa do neurodesenvolvimento, muito prevalente, que surge precocemente na infância. Refere-se a uma disfunção neurológica, que clinicamente se manifesta por atraso ou desvio nas aquisições do neurodesenvolvimento e alterações do comportamento. A PEA caracteriza-se por défice na comunicação e interação social e por um padrão de comportamento repetitivo e limitado nos interesses. O recurso à farmacoterapia justifica-se quando existem comportamentos disruptivos, que interferem negativamente no sucesso educativo e na qualidade de vida das crianças e suas famílias. A risperidona foi o primeiro antipsicótico autorizado na PEA e é o mais vezes prescrito. Embora sendo um fármaco seguro e eficaz, preocupações relacionadas com o seu efeito no aumento do peso e distribuição anómala da gordura e a sua interferência no metabolismo da glicose com aumento do nível de hemoglobina glicada A1c (HbA1c) têm emergido, sobretudo durante o crescimento e o processo evolutivo do neurodesenvolvimento. Objetivos: Caracterizar o efeito da risperidona no aumento do peso e distribuição da gordura e nos níveis de HbA1c. Métodos: Procedeu-se um estudo prospetivo de um grupo de 39 crianças e jovens com uma idade que variou entre os 3 a 21,5 anos (média ± DP, 9 ± 4,2) (trinta do sexo masculino (30/39; 77 %) com o diagnóstico de autismo e indicação para tratamento com risperidona por comportamentos disruptivos com significado clínico. A caracterização dos efeitos adversos, através da avaliação do índice de massa corporal, perímetro abdominal e HbA1c, foi realizada no tempo 0 (sem terapêutica) e nos tempos 1, 3, 6 e 12 meses de terapêutica. Resultados: A risperidona associa-se a uma elevação significativa e mantida dos valores de índice de massa corporal e perímetro abdominal, ao longo do tratamento. No entanto, não se verificou um aumento significativo nos níveis de HbA1cBackground: Autism spectrum disorder (ASD) is a complex neurodevelopment disorder, very prevalent, that appears very early in childhood. It is a neurological dysfunction, clinically manifested by a delay or a deviation in neurodevelopment acquisitions and changes in behaviour. ASD is characterized by difficulties in social interaction, limiting on verbal and nonverbal communication and rigid behaviour with repetitive and limited interests. The use of pharmacotherapy is justified when there are disruptive behaviours that negatively interfere with the successful education and quality of life of children and their families. Risperidone is the first antipsychotic authorized in ASD and more often prescribed. Although apparently safe and effective, concerns about its effects on the weight distribution and HbA1c levels have emerged, especially during growth and the evolutionary process of neurodevelopment. Objective: Analyze the impact on weight gain, adipose tissue distribution and HbA1c levels in patients medicated with risperidone. Methods: 39 patients, children and adolescents 3 to 21.5 years old (mean ± SD, 9 ± 4.2) and female/male ratio of 3/10, with previous diagnosis of autism and indication for treatment with risperidone for significant disruptive behaviour were evaluated at time 0 (no treatment) and on 1, 3, 6 and 12 months of therapy, using body mass index (BMI), waist circumference and HbA1c levels. Results: Risperidone was associated with a significant and sustained elevation of BMI values and waist circumference throughout the treatment. However, there was not a significant increase in HbA1c

Comprehensive User Engagement Sites (CUES) in Philadelphia: A Constructive Proposal

This paper is a study about Philadelphia’s comprehensive user engagement sites (CUESs) as the authors address and examine issues related to the upcoming implementation of a CUES while seeking solutions for its disputed questions and plans. Beginning with the federal drug schedules, the authors visit some of the medical and public health issues vis-à-vis safe injection facilities (SIFs). Insite, a successful Canadian SIF, has been thoroughly researched as it represents a paradigm for which a Philadelphia CUES can expand upon. Also, the existing criticisms against SIFs are revisited while critically unpackaged and responded to in favor of the establishment. In the main section, the authors propose the layout and services of the upcoming CUES, much of which would be in congruent to Vancouver’s Insite. On the other hand, the CUES would be distinct from Insite, as the authors emphasize, in that it will offer an information center run by individuals in recovery and place additional emphasis on early education for young healthcare professionals by providing them a platform to work at the site. The paper will also briefly investigate the implementation of a CUES site under an ethical scope of the Harm Reduction Theory. Lastly, the authors recommend some strategic plans that the Philadelphia City government may consider employing at this crucial stage

Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

<p>Abstract</p> <p>Background</p> <p>Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen.</p> <p>Case presentation</p> <p>A case of pulmonary infection with bacteremia due to <it>Tsukamurella tyrosinosolvens </it>in a 54-year old man who underwent a double lung transplantation four years previously is presented.</p> <p>Conclusion</p> <p>The identification by conventional biochemical assays was unsuccessful and <it>hsp </it>gene sequencing was used to identify <it>Tsukamurella tyrosinosolvens</it>.</p

Anion Binding and Sensing Using Cs124-Sensitized Luminescent Terbium Complexes

Two terbium complexes with varying degrees of intramolecular coordination, Tb:DO2A-Cs124 and Tb:DOTA-Cs124, were prepared. Their capacity to detect biologically and environmentally relevant anions through their luminescence changes was investigated. Tb:DOTA-Cs124 demonstrated exceptional selectivity as a sensor for nitrite, while Tb:DO2A-Cs124 detects nitrite, phosphates, and a range of carboxylate-containing anions

Comparison of circulating tumour dna and extracellular vesicle dna by low-pass whole-genome sequencing reveals molecular drivers of disease in a breast cancer patient

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer