Mayer-Rokitansky-Küster-Hauser (MRKH) is a rare Disorder of Sexual Development (DSD) that results in the lack of a uterus and vagina in women. Receiving this diagnosis during adolescence can cause various forms of psychological distress in patients and families.<br/>Specifically, this condition could affect a women’s gender identity, body image, romantic relationships, family relationships, and psychological wellbeing. Parents are also put in a stressful<br/>position as they now have to navigate the healthcare system, disclosure, and the relationship with their child. This study aims to expand the knowledge of psychosocial adjustment by studying body<br/>image, gender identity, and mental health in individuals living with MRKH as well as parental disclosure, parental support systems, and parental perceptions of their child’s mental health.
Alzheimer’s disease is a disease that can affect cognition, perception and behavior and is currently untreatable. It was discovered in the early 20th century and while significant scientific advancements have occurred, there is ambiguity that remains to be researched and understood. Latinos are the largest ethnic minority in the United States and while data still needs to be uncovered, possible risk factors for developing Alzheimer’s include heart issues, poverty and obesity, age and education level, to name a few. Poverty is linked to obesity, diabetes and a low education level, which in turn have been found to have an impact on Alzheimer’s and all factors impact cardiovascular and vascular health. Due to the collectivistic culture that is deeply rooted in Latinos, there is a strong sense of family that is upheld when caring for relatives who are afflicted and may be hesitant to receive the care that is needed. Other barriers include financial stability, linguistic and cultural barriers, underutilizing resources and health literacy. There are still research gaps that are yet to be filled like brain health and longitudinal studies for Latinos, but current treatments like diet and culturally competent professionals can help with the prognosis. Alzheimer’s is a complex disease, but with the numerous efforts made thus far, such as creating the LatinosAgainstAlzheimer’s Network, it will soon be able to be understood and hopefully eradicated.
Bermuda Land Snails make up a genus called Poecilozonites that is endemic to Bermuda and is extensively present in its fossil record. These snails were also integral to the creation of the theory of punctuated equilibrium. The DNA of mollusks is difficult to sequence because of a class of proteins called mucopolysaccharides that are present in high concentrations in mollusk tissue, and are not removed with standard DNA extraction methods. They inhibit Polymerase Chain Reactions (PCRs) and interfere with Next Generation Sequencing methods. This paper will discuss the DNA extraction methods that were designed to remove the inhibitory proteins that were tested on another gastropod species (Pomacea canaliculata). These were chosen because they are invasive and while they are not pulmonates, they are similar enough to Bermuda Land Snails to reliably test extraction methods. The methods that were tested included two commercially available kits: the Qiagen Blood and Tissue Kit and the Omega Biotek Mollusc Extraction Kit, and one Hexadecyltrimethylammonium Bromide (CTAB) Extraction method that was modified for use on mollusk tissue. The Blood and Tissue kit produced some DNA, the mollusk kit produced almost none, and the CTAB Extraction Method produced the highest concentrations on average, and may prove to be the most viable option for future extractions. PCRs attempted with the extracted DNA have all failed, though it is likely due to an issue with reagents. Further spectrographic analysis of the DNA from the test extractions has shown that they were successful at removing mucopolysaccharides. When the protocol is optimized, it will be used to extract DNA from the tissue from six individuals from each of the two extant species of Bermuda Land Snails. This DNA will be used in several experiments involving Next Generation Sequencing, with the goal of assembling a variety of genome data. These data will then be used to a construct reference genome for Bermuda Land Snails. The genomes generated by this project will be used in population genetic analyses between individuals of the same species, and between individuals of different species. These analyses will then be used to aid in conservation efforts for the species.
Improvements in sequencing technology now allow easy acquisition of large datasets; however, analyzing these data for phylogenetics can be challenging. We have developed a novel method to rapidly obtain homologous genomic data for phylogenetics directly from next-generation sequencing reads without the use of a reference genome. This software, called SISRS, avoids the time consuming steps of de novo whole genome assembly, multiple genome alignment, and annotation.
Results
For simulations SISRS is able to identify large numbers of loci containing variable sites with phylogenetic signal. For genomic data from apes, SISRS identified thousands of variable sites, from which we produced an accurate phylogeny. Finally, we used SISRS to identify phylogenetic markers that we used to estimate the phylogeny of placental mammals. We recovered eight phylogenies that resolved the basal relationships among mammals using datasets with different levels of missing data. The three alternate resolutions of the basal relationships are consistent with the major hypotheses for the relationships among mammals, all of which have been supported previously by different molecular datasets.
Conclusions
SISRS has the potential to transform phylogenetic research. This method eliminates the need for expensive marker development in many studies by using whole genome shotgun sequence data directly. SISRS is open source and freely available at https://github.com/rachelss/SISRS/releases.
Minocycline is a tetracycline class broad spectrum antibiotic commonly used to treat severe acne and other skin infections. Propranolol is a beta blocker type heart medication primarily used to treat high blood pressure and irregular heartbeat. Chlorpromazine is a phenothiazine antipsychotic usually used for schizophrenia. Metformin is the most widely used first-line oral treatment for type-2 diabetes. Based on a literature survey, minocycline is expected to prevent the phosphorylation of STAT3, a transcription factor downstream of EGFR; propranolol is expected to disrupt EGFR trafficking; chlorpromazine is expected to target the PI3K/mTOR/Akt signaling pathway; metformin is believed to exploit vulnerabilities in cancer cell metabolism, as well as upregulate AMPK against the PI3K/mTOR/Akt pathway.
Efficacy of minocycline in inhibiting EGFR-driven STAT3 activation was investigated using western blot analysis. Our results demonstrate that Minocycline effectively inhibits activation of EGFR-driven STAT3 in U373 glioma cells at 100μM. The ability of chlorpromazine to inhibit the PI3K/mTOR/Akt pathway was similarly tested via western blot, which showed inhibition of phosphorylated Akt and S6 at 10μM. Efficacy of propranolol in perturbing EGFR trafficking was evaluated using flow cytometry and immunofluorescence, which failed to depict altered membrane-associated EGFR abundance. Finally, concentration-dependent inhibition of colony formation was tested for all four drugs. Propranolol and minocycline showed potential biphasic stimulatory effects at 10μM, but all drugs inhibited cell growth at 50μM and higher. Efficacy of these drugs in the treatment of GBM is being further evaluated using in vitro neurosphere cultures from patients identified as having the cellular vulnerabilities potentially targeted by these drugs. Successful completion of this project will lead to in vivo efficacy testing of these four drugs in orthotopic GBM PDX models.
