Identifying Important Juvenile Dusky Shark Habitat in the Northwest Atlantic Ocean Using Acoustic Telemetry and Spatial Modeling

Highly mobile species can be challenging for fisheries management and conservation due to large home ranges combined with dependence on discrete habitat areas where they can be easily targeted or vulnerable to anthropogenic disturbances. Management of the Dusky Shark Carcharhinus obscurus in the northwest Atlantic Ocean has been particularly challenging due to the species\u27 inherent vulnerability to overfishing and poorly understood habitat associations. To better understand habitat associations and seasonal distributions, we combined telemetry and remotely sensed environmental data to spatially model juvenile Dusky Shark presence probability in the northwest Atlantic Ocean. To accomplish this, 22 juvenile Dusky Sharks (107-220 cm TL) that were tagged with acoustic transmitters at different locations within the U.S. Middle Atlantic Bight region were tracked through networked arrays of acoustic receivers. Tag detections were summarized as daily presence records, and data describing environmental conditions, including depth, chlorophyll-a concentration, salinity, and sea surface temperature, were extracted at detection locations. These data were used in boosted regression tree models to predict juvenile Dusky Shark presence probability based on environmental parameters during fall 2017 and summer 2018. Telemetry observations and modeled presence probability showed consistent associations with temperatures between 16 degrees C and 26 degrees C and chlorophyll-a concentrations between 2 and 7 mg/m(3), which were associated with seasonal migration timing and monthly spatial distributions. Dusky Shark tag detections and predicted distributions during summer and early fall overlapped areas in the Middle Atlantic Bight that were affected by fisheries and potential offshore energy development. Our methodology provides a framework for assessing climate change effects on distribution

Risk Factors for Kala-Azar in Bangladesh

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3–45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15–44 within household; OR 3.2 95% CI 1.7–6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53–0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70–0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar

Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

Objective: To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods: In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results: The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R[superscript 2] = 0.38±0.05, and that between EHR-derived and true BPF has a mean R[superscript 2] = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10[superscript −12]). Conclusion: Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders.National Institute of General Medical Sciences (U.S.) (NIH U54-LM008748

The Cancer Recognition (CARE) Antibody Test

The cancer recognition (CARE) antibody (Ab) test is a serologic assay for a specific IgM that is elevated in cancer patients. All tests are measured using an indirect enzyme-linked immunosorbent assay (ELISA) of human serum. The target polypeptide in the CARE Ab test is the IgM binding epitope (LT-11) of the CARE antigen (Ag) consisting of a 16 mer structure that has been produced synthetically. The mean relative concentration (MRC) is determined relative to standard, normalized human plasma. Non-parametric analysis showed median MRC values of healthy volunteers (HVs) with no history of cancer (n=47), family history of cancer (n=126) and a previous cancer history (n=24) to be 26, 34 and 46, respectively. It was determined that there was no significance found among the medians of the three HV groups (P=0.53). The specificity of the HV types was between 87 and 98%. Benign/non-cancer surgical patients (n=27) had a median value of 20 with a specificity of 96%. The cancer patients (n=61) had a median value of 246 with a sensitivity of 89%. There was a significant difference between the HV and cancer patients (P\u3c0.0001) as well as between the benign/surgical non-cancerous group and cancer patients (P\u3c0.0001). The IgM antibody is heat stable at room temperature for two days versus being frozen at -80°C (r2=0.97). Either serum or plasma samples may be used in the CARE Ab test (r2=0.92). The CARE Ab was almost exclusively IgM with no serum conversion to IgG in sequential measurements of patients with cancer over a six-month period. Preliminary data from patients undergoing post-operative cancer treatment showed that decreasing Ab levels revealed patients negative for residual cancer or undergoing remission, while relapsing patients show an increase in Ab levels. A return to a positive Ab level shortly after treatment is a poor prognostic sign while in advanced cancers the Ab levels may be depressed significantly

Structure–Activity Relationships and Biological Evaluation of 7-Substituted Harmine Analogs for Human β-Cell Proliferation

Recently, we have shown that harmine induces β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. We explore structure–activity relationships of the 7-position of harmine for both DYRK1A kinase inhibition and β-cell proliferation based on our related previous structure–activity relationship studies of harmine in the context of diabetes and β-cell specific targeting strategies. 33 harmine analogs of the 7-position substituent were synthesized and evaluated for biological activity. Two novel inhibitors were identified which showed DYRK1A inhibition and human β-cell proliferation capability. The DYRK1A inhibitor, compound 1-2b, induced β-cell proliferation half that of harmine at three times higher concentration. From these studies we can draw the inference that 7-position modification is limited for further harmine optimization focused on β-cell proliferation and cell-specific targeting approach for diabetes therapeutics

Administrative Files - Video Documentary - Where Do You Stand?

Video produced by Toward A Fair Michigan to spur debate on the passage of the Michigan Civil Rights Initiative. Features various activists and academics discussing the issues at stake in the ballot initiative.http://deepblue.lib.umich.edu/bitstream/2027.42/96446/1/Where-Do-You-Stand.mp

Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1

In humans, a single enzyme 2-aminoadipic semialdehyde synthase (AASS) catalyses the initial two critical reactions in the lysine degradation pathway. This enzyme evolved to be a bifunctional enzyme with both lysine-2-oxoglutarate reductase (LOR) and saccharopine dehydrogenase domains (SDH). Moreover, AASS is a unique drug target for inborn errors of metabolism such as glutaric aciduria type 1 that arise from deficiencies downstream in the lysine degradation pathway. While work has been done to elucidate the SDH domain structurally and to develop inhibitors, neither has been done for the LOR domain. Here, we purify and characterize LOR and show that it is activated by alkylation of cysteine 414 by N-ethylmaleimide. We also provide evidence that AASS is rate-limiting upon high lysine exposure of mice. Finally, we present the crystal structure of the human LOR domain. Our combined work should enable future efforts to identify inhibitors of this novel drug target

Species of Dickeya and Pectobacterium Isolated during an Outbreak of Blackleg and Soft Rot of Potato in Northeastern and North Central United States

An outbreak of bacterial soft rot and blackleg of potato has occurred since 2014 with the epicenter being in the northeastern region of the United States. Multiple species of Pectobacterium and Dickeya are causal agents, resulting in losses to commercial and seed potato production over the past decade in the Northeastern and North Central United States. To clarify the pathogen present at the outset of the epidemic in 2015 and 2016, a phylogenetic study was made of 121 pectolytic soft rot bacteria isolated from symptomatic potato; also included were 27 type strains of Dickeya and Pectobacterium species, and 47 historic reference strains. Phylogenetic trees constructed based on multilocus sequence alignments of concatenated dnaJ, dnaX and gyrB fragments revealed the epidemic isolates to cluster with type strains of D. chrysanthemi, D. dianthicola, D. dadantii, P. atrosepticum, P. brasiliense, P. carotovorum, P. parmentieri, P. polaris, P. punjabense, and P. versatile. Genetic diversity within D. dianthicola strains was low, with one sequence type (ST1) identified in 17 of 19 strains. Pectobacterium parmentieri was more diverse, with ten sequence types detected among 37 of the 2015–2016 strains. This study can aid in monitoring future shifts in potato soft rot pathogens within the U.S. and inform strategies for disease management