Analysis of success in beginning reading in relation to knowledge of letter names, experiential background and school adjustment.

Thesis (Ed.M.)--Boston Universit

Comparative analysis of the regulation of rovA from the pathogenic Yersiniae

RovA is a MarR/SlyA-type regulator that mediates the transcription of inv in Yersinia enterocolitica and Y. pseudotuberculosis. In Y. pseudotuberculosis, rovA transcription is controlled primarily by H-NS and RovA, which bind to similar regions within the rovA promoter. At 37°C, rovA transcription is repressed by H-NS. Transcription of rovA results when RovA relieves H-NS-mediated repression. The region of the rovA promoter that H-NS and RovA bind is not conserved in the Y. enterocolitica promoter. Using green fluorescent protein reporters, we determined that the Y. enterocolitica rovA (rovA(Yent)) promoter is weaker than the Y. pseudotuberculosis promoter. However, despite the missing H-NS/RovA binding site in the rovA(Yent) promoter, H-NS and RovA are still involved in the regulation of rovA(Yent). DNA binding studies suggest that H-NS and RovA bind with a higher affinity to the Y. pseudotuberculosis/Y. pestis rovA (rovA(Ypstb/Ypestis)) promoter than to the rovA(Yent) promoter. Furthermore, H-NS appears to bind to two regions in a cooperative fashion within the rovA(Yent) promoter that is not observed with the rovA(Ypstb/Ypestis) promoter. Finally, using a transposon mutagenesis approach, we identified a new positive regulator of rovA in Y. enterocolitica, LeuO. In Escherichia coli, LeuO regulates gene expression via changes in levels of RpoS and H-NS, but LeuO-mediated regulation of rovA(Yent) appears to be independent of either of these two proteins. Together, these data demonstrate that while the rovA regulatory factors are conserved in Yersinia, divergence of Y. enterocolitica and Y. pseudotuberculosis/Y. pestis during evolution has resulted in modifications in the mechanisms that are responsible for controlling rovA transcription

Birth seasonality studies in a large Prader-Willi syndrome cohort.

Prader-Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11-q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11-q13 deletion seen in PWS. Certain occupations such as hydrocarbon-exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11-q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation

Sex and Gender in Medical Education, and proceedings from the 2015 Sex and Gender Education Summit

The Sex and Gender Medical Education Summit: a roadmap for curricular innovation was a collaborative initiative of the American Medical Women\u27s Association, Laura W. Bush Institute for Women’s Health, Mayo Clinic, and Society for Women\u27s Health Research (www.sgbmeducationsummit.com). It was held on October 18–19, 2015 to provide a unique venue for collaboration among nationally and internationally renowned experts in developing a roadmap for the incorporation of sex and gender based concepts into medical education curricula. The Summit engaged 148 in-person attendees for the 1 1/2-day program. Pre- and post-Summit surveys assessed the impact of the Summit, and workshop discussions provided a framework for informal consensus building. Sixty-one percent of attendees indicated that the Summit had increased their awareness of the importance of sex and gender specific medicine. Other comments indicate that the Summit had a significant impact for motivating a call to action among attendees and provided resources to initiate change in curricula within their home institutions. These educational efforts will help to ensure a sex and gender basis for delivery of health care in the future

Low copy expression vectors for use in Yersinia sp. and related organisms

In Yersinia, the most commonly used expression vectors for genetic studies such as gene complementation do not effectively allow for both induction and repression of gene expression. Additionally, there is no expression system available that can be induced in bacteria growing in vitro as well as in vivo, e.g. in eukaryotic cell lines or in living animal models. Here, we present a series of novel inducible low copy expression vectors that are well suited for use in the Yersinia species. Their tet operator/promoter/repressor system makes them distinct from other vectors, and gene transcription in bacteria can easily be induced by addition of anhydrotetracyline (ATc) either to the growth medium, to tissue culture medium during bacterial infections of cell lines or by injection into animals infected with bacteria. Researchers can choose between two different antibiotic resistances (kanamycin or spectinomycin), between two copy numbers (5 or 12-22) as well as between two different versions for expression from either the native RBS and ATG or RBS and ATG encoded in the plasmid. The whole vector series contains the same multi-cloning site from pBluescript II KS+ that allows for easy subcloning. Moreover, these vectors are built in a modular fashion that makes it simple to adapt them for other purposes. Finally, in addition to their use in Yersinia they are suitable for use in many other Enterobacteriaceae

Early Diagnosis in Prader-Willi Syndrome Reduces Obesity and Associated Co-Morbidities.

Prader-Willi syndrome (PWS) is an imprinting genetic disorder characterized by lack of expression of genes on the paternal chromosome 15q11-q13 region. Growth hormone (GH) replacement positively influences stature and body composition in PWS. Our hypothesis was that early diagnosis delays onset of obesity in PWS. We studied 352 subjects with PWS, recruited from the NIH Rare Disease Clinical Research Network, to determine if age at diagnosis, ethnicity, gender, and PWS molecular class influenced the age they first become heavy, as determined by their primary care providers, and the age they first developed an increased appetite and began seeking food. The median ages that children with PWS became heavy were 10 years, 6 years and 4 years for age at diagnosis < 1 year, between 1 and 3 years, and greater than 3 years of age, respectively. The age of diagnosis and ethnicity were significant factors influencing when PWS children first became heavy (p < 0.01), however gender and the PWS molecular class had no influence. Early diagnosis delayed the onset of becoming heavy in individuals with PWS, permitting early GH and other treatment, thus reducing the risk of obesity-associated co-morbidities. Non-white individuals had an earlier onset of becoming heavy

The YsrS Paralog DygS Has the Capacity To Activate Expression of the Yersinia enterocolitica Ysa Type III Secretion System

ABSTRACT The Yersinia enterocolitica Ysa type III secretion system (T3SS) is associated with intracellular survival, and, like other characterized T3SSs, it is tightly controlled. Expression of the ysa genes is only detected following growth at low temperatures (26°C) and in high concentrations of sodium chloride (290 mM) in the medium. The YsrSTR phosphorelay (PR) system is required for ysa expression and likely responds to NaCl. During our investigations into the Ysr PR system, we discovered that genes YE3578 and YE3579 are remarkably similar to ysrR and ysrS , respectively, and are probably a consequence of a gene duplication event. The amino acid differences between YE3578 and ysrR are primarily clustered into two short regions. The differences between YE3579 and ysrS are nearly all located in the periplasmic sensing domain; the cytoplasmic domains are 98% identical. We investigated whether these paralogs were capable of activating ysa gene expression. We found that the sensor paralog, named DygS, is capable of compensating for loss of ysrS , but the response regulator paralog, DygR, cannot complement a ysrR gene deletion. In addition, YsrR, but not DygR, interacts with the histidine phosphorelay protein YsrT. Thus, DygS likely activates ysa gene expression in response to a signal other than NaCl and provides an example of a phosphorelay system in which two sensor kinases feed into the same regulatory pathway. IMPORTANCE All organisms need mechanisms to promote survival in changing environments. Prokaryotic phosphorelay systems are minimally comprised of a histidine kinase (HK) that senses an extracellular stimulus and a response regulator (RR) but can contain three or more proteins. Through gene duplication, a unique hybrid HK was created. We show that, while the hybrid appears to retain all of the phosphorelay functions, it responds to a different signal than the original. Both HKs transmit the signal to the same RR, which activates a promoter that transcribes a set of genes encoding a type III secretion system (T3SS) whose function is not yet evident. The significance of this work lies in finding that two HKs regulate this T3SS, highlighting its importance

A Serendipitous Mutation Reveals the Severe Virulence Defect of a Klebsiella pneumoniae fepB Mutant

ABSTRACT Klebsiella pneumoniae is considered a significant public health threat because of the emergence of multidrug-resistant strains and the challenge associated with treating life-threatening infections. Capsule, siderophores, and adhesins have been implicated as virulence determinants of K. pneumoniae , yet we lack a clear understanding of how this pathogen causes disease. In a previous screen for virulence genes, we identified a potential new virulence locus and constructed a mutant ( smr ) with this locus deleted. In this study, we characterize the smr mutant and show that this mutation renders K. pneumoniae avirulent in a pneumonia model of infection. The smr mutant was expected to have a deletion of three genes, but subsequent genome sequencing indicated that a much larger deletion had occurred. Further analysis of the deleted region indicated that the virulence defect of the smr mutant could be attributed to the loss of FepB, a periplasmic protein required for import of the siderophore enterobactin. Interestingly, a Δ fepB mutant was more attenuated than a mutant unable to synthesize enterobactin, suggesting that additional processes are affected. As FepB is highly conserved among the members of the family Enterobacteriaceae , therapeutic targeting of FepB may be useful for the treatment of Klebsiella and other bacterial infections. IMPORTANCE In addition to having a reputation as the causative agent of several types of hospital-acquired infections, Klebsiella pneumoniae has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among Klebsiella strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target

Acquisition of omptin reveals cryptic virulence function of autotransporter YapE in Yersinia pestis

Autotransporters, the largest family of secreted proteins in Gram negative bacteria, perform a variety of functions, including adherence, cytotoxicity, and immune evasion. In Yersinia pestis the autotransporter YapE has adhesive properties and contributes to bubonic infection of the mouse model. Here, we demonstrate that omptin cleavage of Y. pestis YapE is required to mediate bacterial aggregation and adherence to eukaryotic cells. We demonstrate that omptin cleavage is specific for the Y. pestis and Y. pseudotuberculosis YapE orthologs but is not conserved in the Y. enterocolitica protein. We also show that cleavage of YapE occurs in Y. pestis but not in the enteric Yersinia species, and requires the omptin Pla (plasminogen activator protease), which is encoded on the Y. pestis-specific plasmid pPCP1. Together, these data show that post-translation modification of YapE appears to be specific to Y. pestis, was acquired along with the acquisition of pPCP1 during the divergence of Y. pestis from Y. pseudotuberculosis, and are the first evidence of a novel mechanism to regulate bacterial adherence

Neuroanatomy of expressive suppression: The role of the insula.

Expressive suppression is a response-focused regulatory strategy aimed at concealing the outward expression of emotion that is already underway. Expressive suppression requires the integration of interoception, proprioception, and social awareness to guide behavior in alignment with personal and interpersonal goals-all processes known to involve the insular cortex. Frontotemporal dementia (FTD) provides a useful patient model for studying the insula's role in socioemotional regulation. The insula is a key target of early atrophy in FTD, causing patients to lose the ability to represent the salience of internal and external conditions and to use these representations to guide behavior. We examined a sample of 59 patients with FTD, 52 patients with Alzheimer's disease (AD), and 38 neurologically healthy controls. Subjects viewed 2 disgust-eliciting films in the laboratory. During the first film, subjects were instructed to simply watch (emotional reactivity trial); during the second, they were instructed to hide their emotions (expressive suppression trial). Structural images from a subsample of participants (n = 42; 11 FTD patients, 11 AD patients, and 20 controls) were examined in conjunction with behavior. FreeSurfer was used to quantify regional gray matter volume in 41 empirically derived neural regions in both hemispheres. Of the 3 groups studied, FTD patients showed the least expressive suppression and had the smallest insula volumes, even after controlling for age, gender, and emotional reactivity. Among the brain regions examined, the insula was the only significant predictor of expressive suppression ability, with lower insula gray matter volume in both hemispheres predicting less expressive suppression. (PsycInfo Database Record (c) 2021 APA, all rights reserved)