Characterization of secA-sod operon in Borrellia burgdorferi.

Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ70-like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed to be relatively lower amounts than sod. Both genes were expressed in all phases of growth, with greatest expression observed in stationary phase. Because transcription of most sod genes is tightly regulated by iron concentration, the secA-sod gene expression was analyzed in borrelial cells grown in varying amounts of metal. Iron-restriction did not significantly affect growth nor did it affect transcription of secA or sod. Likewise, no major differences in transcription were observed with restricting or supplementing media with manganese. To test the possibility that the borrelial SOD may function with either iron or manganese as a cofactor as in cambialistic SODs, SOD activity was assayed and the highest activity was observed in increased manganese concentrations. Protein expression profiles of Sh-2-82 cultured in metal-defined media were investigated by one- and two-dimensional gel electrophoresis. Approximately 15 proteins were differentially expressed in response to metal concentration

Beyond Bonferroni revisited: concerns over inflated false positive research findings in the fields of conservation genetics, biology, and medicine

In 2006, Narum published a paper in Conservation Genetics emphasizing that Bonferroni correction for multiple testing can be highly conservative with poor statistical power (high Type II error). He pointed out that other approaches for multiple testing correction can control the false discovery rate (FDR) with a better balance of Type I and Type II errors and suggested that the approach of Benjamini and Yekutieli (BY) 2001 provides the most biologically relevant correction for evaluating the signifcance of population diferentiation in conservation genetics. However, there are crucial diferences between the original Benjamini and Yekutieli procedure and that described by Narum. After carefully reviewing both papers, we found an error due to the incorrect implementation of the BY procedure in Narum (Conserv Genet 7:783–787, 2006) such that the approach does not adequately control FDR. Since the incorrect BY approach has been increasingly used, not only in conservation genetics, but also in medicine and biology, it is important that the error is made known to the scientifc community. In addition, we provide an overview of FDR approaches for multiple testing correction and encourage authors frst and foremost to provide efect sizes for their results; and second, to be transparent in their descriptions of multiple testing correction. Finally, the impact of this error on conservation genetics and other felds will be study-dependent, as it is related to the number of true to false positives for each study

Best practices in data analysis and sharing in neuroimaging using MRI

Given concerns about the reproducibility of scientific findings, neuroimaging must define best practices for data analysis, results reporting, and algorithm and data sharing to promote transparency, reliability and collaboration. We describe insights from developing a set of recommendations on behalf of the Organization for Human Brain Mapping, and identify barriers that impede these practices, including how the discipline must change to fully exploit the potential of the world’s neuroimaging data

Best practices in data analysis and sharing in neuroimaging using MRI

Given concerns about the reproducibility of scientific findings, neuroimaging must define best practices for data analysis, results reporting, and algorithm and data sharing to promote transparency, reliability and collaboration. We describe insights from developing a set of recommendations on behalf of the Organization for Human Brain Mapping, and identify barriers that impede these practices, including how the discipline must change to fully exploit the potential of the world’s neuroimaging data

Continuous Glucose Monitors and Automated Insulin Dosing Systems in the Hospital Consensus Guideline.

This article is the work product of the Continuous Glucose Monitor and Automated Insulin Dosing Systems in the Hospital Consensus Guideline Panel, which was organized by Diabetes Technology Society and met virtually on April 23, 2020. The guideline panel consisted of 24 international experts in the use of continuous glucose monitors (CGMs) and automated insulin dosing (AID) systems representing adult endocrinology, pediatric endocrinology, obstetrics and gynecology, advanced practice nursing, diabetes care and education, clinical chemistry, bioengineering, and product liability law. The panelists reviewed the medical literature pertaining to five topics: (1) continuation of home CGMs after hospitalization, (2) initiation of CGMs in the hospital, (3) continuation of AID systems in the hospital, (4) logistics and hands-on care of hospitalized patients using CGMs and AID systems, and (5) data management of CGMs and AID systems in the hospital. The panelists then developed three types of recommendations for each topic, including clinical practice (to use the technology optimally), research (to improve the safety and effectiveness of the technology), and hospital policies (to build an environment for facilitating use of these devices) for each of the five topics. The panelists voted on 78 proposed recommendations. Based on the panel vote, 77 recommendations were classified as either strong or mild. One recommendation failed to reach consensus. Additional research is needed on CGMs and AID systems in the hospital setting regarding device accuracy, practices for deployment, data management, and achievable outcomes. This guideline is intended to support these technologies for the management of hospitalized patients with diabetes

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Structural brain correlates of childhood inhibited temperament: an ENIGMA-Anxiety Mega-analysis

NWORubicon 019.201SG.022Pathways through Adolescenc