Studies on the Hemoglobin of Cooley's Anemia and Cooley's Trait

The diseases sickle cell anemia and Cooley's anemia (also known as thalassemia or Mediterranean anemia) have associated with them "minor" or "trait" forms of the disease in which the symptomatology is minimal, and the abnormalities in the red cells are correspondingly less. Extensive genetic studies carried out on these diseases [1-4] have led to the conclusion that in each case the trait is inherited as a Mendalian dominant, the person being heterozygous in the sickle cell gene or Cooley's gene. Homozygosity in either of these genes leads to the corresponding anemia. Our understanding of sickle cell anemia has improved considerably with the discovery of an abnormal hemoglobin and a molecular interpretation of the pathological behavior of the red cell. [5] In that disease it was possible to demonstrate heterozygosity and homozygosity directly, by observing varying amounts of the abnormal hemoglobin. Liquori [6] has recently reported the pr'esence of fetal hemoglobin in cases of Cooley's anemia. We have carried out a number of experiments which support his findings, and have extended the investigation to include cases of Cooley's trait, for which no fetal hemoglobin was found. A hypothesis is advanced to explain these facts

Different forms of the double helix: architecture and function

The DNA double helix was discovered 50 years ago. This motif was found in several other places, most notably in RNA molecules. It is also found in DNA-RNA hybrids as well as transfer RNA molecules where double helical segments combine to form a more complex structure. A distinct variant of the DNA molecule was discovered in which the helix turns left-handed, which has led to practical consequences in the treatment of certain viral diseases. Since the molecule readily converted from A to B form, it clearly suggested that there was another form the double helix could adopt in the A form. Thus, the initial mystery ?why are there two such forms? It was known at the time that there are two major nucleic acids, one DNA and the other RNA, in which the sugar phosphate backbone contained ribose rather than the deoxyribose of DNA. One of the early questions that arose immediately after the Watson-Crick formulation was related to the nature of the RNA molecule-could it form a double helix

Corey Rich

This project initially started out as a collection of found wood pieces, which I then sorted, sanded, and painted. I took some parts from recycling bins at Fisher and UBS as well as finding some random chunks at my house. Other wood was either collected in similar ways except for 3 2x4’s which I purchased. Through the process of mixing and matching the color and shape of each wooden chunk I found it easier for each piece to find its place among the rest. Like a puzzle for me to find the correct spot for the item at hand. It wasn’t until I had made a few of these bright pieces with individually painted parts that I came to the realization that I was trying to fix something that had already been broken once before (by myself or another). Through this understanding, I started breaking the wood up myself. I believe this trial of material mash helped me think about the wood differently than I had before and seriously try to make this 2x4 mine. Trying out more combinations with less vocal colors. Once I started using textiles throughout the first semester I started to pick up on the fact that I was likely making my work as some sort of memorial and connecting with feelings of nostalgia both positive and negative from my childhood. I make these pieces with the idea of a “family” in mind. The pieces belong to one another, or one is related to another but not the rest. I want to fix the broken family and in order to figure out how it works it must be destroyed and put back together. Not just by breaking, but pounding, destroying, obliterating, until what was left could only be understood as wood. And once this wood is unfamiliar, mend it back together with the tools at hand. S, P, C Snapping, playing and crunching Like feet stomping in the forest Chirping children Tattered twigs Scraping, prying and clipping Like opening a gift From surprise To shock Salvaging, patching and crafting Like a Surgeon From static To stagnant Splitting, popping and cracking Like bones From the Earth Back to the dirt Sanding, polishing and cleaning Like Morticians From the bed Into the coffin Saving, protecting and cubbying Like a mourning Mother From disbelief To grief Smothering, priming and coating Like a role model Gone now Never forgotten Spraying, pigmenting and coloring Like flowers From vibrant bloom To Winter’s grey Searching, prowling and collecting Like a hungry animal Once stuffed Now empty Stoning, plummeting and cascading Like a landslide Head under a boulder And it feels real Sleeping, psychoanalyzing and cuddling Like a velvet couch The ceilings are always grey And they’re never comfortable Sparking, pitter-pattering and catching Like a fuse Tik-tik Boom Speeding, producing and cruising Like a machine Gears squeaky Gunky stuck Slipping, parading and crashing Like a drunk All smiles at day Cries at night Salting, powdering and crusting Like a grill master Mouthwatering sweet With a fiery kick Splintering, pulling and creaking Like a heavy wind Trees falling down Precious wood In the ground is a birch tree Planted along with half of me

BUILDING AND EVALUATING DETAILED GRAPHICAL FINANCIAL CONFLICT OF INTEREST DISCLOSURES IN MEDICAL RESEARCH

Bias in medical research poses a serious threat to public health. Conflicts of Interest create the risk of conscious or subconscious bias in research article authors. Financial Conflict of Interest (FCOI) are widely recognized as relatively as objective, quantifiable, and fairly regulated form of COI. Many medical journals have adopted FCOI disclosure is a means of communicating the potential for bias in research to readers. Research on the impact of FCOI disclosure on the attitudes readers develop toward an article has thus far focused on text-based FCOI disclosure without details on the nature of dollar value of payments received.In this work, I developed an algorithm to match authors to a federal database of payments they received from industry during the FCOI disclosure windows for an article. I have four goals: First, I establish that algorithmic matching of authors to federal payments profile is feasible. Second, I evaluate the impact of detailed graphical FCOI disclosure on the attitudes that readers develop toward a publication. Third, I evaluate the perspectives and opinions or medical journal article authors when presented with graphical FCOI disclosure of their own payments and those of their author teams. Fourth, I gather the perspectives, possible objections, requirements, and desires of key opinion leaders among academia and medical publishing regarding the potential adoption of graphical FCOI disclosures as a standard in academic medical publishing. My findings suggest that the adoption of semi-automated systems for graphical FCOI disclosure may enhance the ability of many stakeholders to detect the potential for bias in medical research without undue harm to authors or corporations.Doctor of Philosoph

Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome

RNA editing by adenosine deamination generates RNA and protein diversity through the posttranscriptional modification of single nucleotides in RNA sequences. Few mammalian A-to-I edited genes have been identified despite evidence that many more should exist. Here we identify intramolecular pairs of Alu elements as a major target for editing in the human transcriptome. An experimental demonstration in 43 genes was extended by a broader computational analysis of more than 100,000 human mRNAs. We find that 1,445 human mRNAs (1.4%) are subject to RNA editing at more than 14,500 sites, and our data further suggest that the vast majority of pre-mRNAs (greater than 85%) are targeted in introns by the editing machinery. The editing levels of Alu-containing mRNAs correlate with distance and homology between inverted repeats and vary in different tissues. Alu-mediated RNA duplexes targeted by RNA editing are formed intramolecularly, whereas editing due to intermolecular base-pairing appears to be negligible. We present evidence that these editing events can lead to the posttranscriptional creation or elimination of splice signals affecting alternatively spliced Alu-derived exons. The analysis suggests that modification of repetitive elements is a predominant activity for RNA editing with significant implications for cellular gene expression

Origin and evolutionary plasticity of the gastric caecum in sea urchins (Echinodermata: Echinoidea)

Background: The digestive tract of many metazoan invertebrates is characterized by the presence of caeca or diverticula that serve secretory and/or absorptive functions. With the development of various feeding habits, distinctive digestive organs may be present in certain taxa. This also holds true for sea urchins (Echinodermata: Echinoidea), in which a highly specialized gastric caecum can be found in members of a derived subgroup, the Irregularia (cake urchins, sea biscuits, sand dollars, heart urchins, and related forms). As such a specialized caecum has not been reported from "regular" sea urchin taxa, the aim of this study was to elucidate its evolutionary origin. Results: Using morphological data derived from dissection, magnetic resonance imaging, and extensive literature studies, we compare the digestive tract of 168 echinoid species belonging to 51 extant families. Based on a number of characters such as topography, general morphology, mesenterial suspension, and integration into the haemal system, we homologize the gastric caecum with the more or less pronounced dilation of the anterior stomach that is observed in most "regular" sea urchin taxa. In the Irregularia, a gastric caecum can be found in all taxa except in the Laganina and Scutellina. It is also undeveloped in certain spatangoid species. Conclusions: According to our findings, the sea urchin gastric caecum most likely constitutes a synapomorphy of the Euechinoidea. Its occurrence in "regular" euechinoids is linked to the presence of an additional festoon of the anterior stomach in ambulacrum III. Both structures, the additional festoon and the gastric caecum, are absent in the sister taxon to the Euechinoidea, the Cidaroida. Since the degree of specialization of the gastric caecum is most pronounced in the predominantly sediment-burrowing irregular taxa, we hypothesize that its evolution is closely linked to the development of more elaborate infaunal lifestyles. We provide a comprehensive study of the origin and evolutionary plasticity of a conspicuous digestive tract structure, the gastric caecum, in a major taxon of the extant invertebrate macrozoobenthos. © 2010 Ziegler et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A 6 bp Z-DNA hairpin binds two Zα domains from the human RNA editing enzyme ADAR1

AbstractThe Zα domain of the human RNA editing enzyme double-stranded RNA deaminase I (ADAR1) binds to left-handed Z-DNA with high affinity. We found by analytical ultracentrifugation and CD spectroscopy that two Zα domains bind to one d(CG)3T4(CG)3 hairpin which contains a stem of six base pairs in the Z-DNA conformation. Both wild-type Zα and a C125S mutant show a mean dissociation constant of 30 nM as measured by surface plasmon resonance and analytical ultracentrifugation. Our data suggest that short (≥6 bp) segments of Z-DNA within a gene are able to recruit two ADAR1 enzymes to that particular site

Uncovering and Mitigating Algorithmic Bias through Learned Latent Structure

Recent research has highlighted the vulnerabilities of modern machine learning based systems to bias, especially for segments of society that are under-represented in training data. In this work, we develop a novel, tunable algorithm for mitigating the hidden, and potentially unknown, biases within training data. Our algorithm fuses the original learning task with a variational autoencoder to learn the latent structure within the dataset and then adaptively uses the learned latent distributions to re-weight the importance of certain data points while training. While our method is generalizable across various data modalities and learning tasks, in this work we use our algorithm to address the issue of racial and gender bias in facial detection systems. We evaluate our algorithm on the Pilot Parliaments Benchmark (PPB), a dataset specifically designed to evaluate biases in computer vision systems, and demonstrate increased overall performance as well as decreased categorical bias with our debiasing approach

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of the cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhib-itors concurrently with the antibioti