Comparing Capabilities of Shewanella oneidensis MR-1 and the Microbial Community of Iron Caves to Reduce Fe(III)

Caves are generally formed by the erosion and/or dissolution of rock and its subsequent removal by water. Iron ore caves (IOCs) form despite being hosted by relatively insoluble and weathering-resistant rock. Due to the discovery of a microbial community behind the walls of these caves, it was hypothesized that these bacteria could be responsible for speleogenesis. Iron ore exists in an oxidized (Fe(III)) state, but reduced (Fe(II)) form is soluble. It was further reasoned that the bacteria might be able to reduce Fe(III) through direct metabolic activity, which uses iron as an electron acceptor. Here we show that cave microorganisms appear to reduce Fe(III) to a greater degree than a known iron reducer, Shewanella oneidensis MR-1. The results demonstrate that cave formation could be due to microbial activity which provides an additional model for cave formation

The human kindness curriculum: An innovative preclinical initiative to highlight kindness and empathy in medicine.

BackgroundPrior studies have shown a marked drop in empathy among students during their third (clinical) year of medical school. Curricula developed to address this problem have varied greatly in content and have not always been subjected to validated measures of impact.MethodsIn 2015, we initiated a Human Kindness (HK) curriculum for the initial 2 years of medical school. This mandatory 12-h curriculum (6 h/year) included an innovative series of lectures and patient interactions with regard to compassion and empathy in the clinical setting. Both quantitative (Jefferson Scale of Empathy [JSE]) and qualitative data were collected prospectively to evaluate the impact of the HK curriculum.ResultsIn the initial Pilot Year, neither 1st (Group 1) nor 2nd (Group 2) year medical students showed pre-post changes in JSE scores. Substantial changes were made to the curriculum based on faculty and student evaluations. In the following Implementation Year, both the new 1st (Group 3) and the now 2nd year (Group 4) students, who previously experienced the Pilot Year, showed significant improvements in post-course JSE scores; this improvement remained valid across subanalyses of gender, age, and student career focus (e.g., internal medicine, surgery, etc.). Despite the disappointingly flat initial Pilot Year JSE scores, the 3rd year students (Group 2) who experienced only the Pilot Year of the curriculum (i.e., 2nd year students at the time of the Pilot Year) had subsequent JSE scores that did not show the typical decline associated with the clinical years. Students generally evaluated the HK curriculum positively and rated it as being important to their medical education and development as a physician.DiscussionA required preclinical curriculum focused on HK resulted in significant improvements in medical student empathy; this improvement was maintained during the 1st clinical year of training

Using unmanned aerial vehicles (‘drones’) to collect data from tagged fishers in the environment

Fisher (Pekania pennant) belongs to the weasel family. In October 2014, the United States Fish and Wildlife Service proposed to list the West Coast Distinct Population Segment of fisher as threatened under the Endangered Species Act. We wish to better define where fishers live within their habitats and use that information to improve conservation efforts. Previously, to track the behavior of wild fishers, researchers put tracker collars on the animals and relied on networks of fixed antennas on the ground in the environment to collect data. We are experimenting with using unmanned aerial vehicles (‘drones’) to collect data from tagged fishers in the environment. Using drones could offer advantages over antennas that require a dedicated power source and are placed in the field long-term

APOBEC-related mutagenesis and neo-peptide hydrophobicity: implications for response to immunotherapy.

Tumor-associated neo-antigens are mutated peptides that allow the immune system to recognize the affected cell as foreign. Cells carrying excessive mutation load often develop mechanisms of tolerance. PD-L1/PD-1 checkpoint immunotherapy is a highly promising approach to overcome these protective signals and induce tumor shrinkage. Yet, the nature of the neo-antigens driving those beneficial responses remains unclear. Here, we show that APOBEC-related mutagenesis - a mechanism at the crossroads between anti-viral immunity and endogenous nucleic acid editing - increases neo-peptide hydrophobicity (a feature of immunogenicity), as demonstrated by in silico computation and in the TCGA pan-cancer cohort, where APOBEC-related mutagenesis was also strongly associated with immune marker expression. Moreover, APOBEC-related mutagenesis correlated with immunotherapy response in a cohort of 99 patients with diverse cancers, and this correlation was independent of the tumor mutation burden (TMB). Combining APOBEC-related mutagenesis estimate and TMB resulted in greater predictive ability than either parameter alone. Based on these results, further investigation of APOBEC-related mutagenesis as a marker of response to anti-cancer checkpoint blockade is warranted

Sediment dynamics in the lower Mekong River : transition from tidal river to estuary

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 120 (2015): 6363–6383, doi:10.1002/2015JC010754.A better understanding of flow and sediment dynamics in the lowermost portions of large-tropical rivers is essential to constraining estimates of worldwide sediment delivery to the ocean. Flow velocity, salinity, and suspended-sediment concentration were measured for 25 h at three cross sections in the tidal Song Hau distributary of the Mekong River, Vietnam. Two campaigns took place during comparatively high-seasonal and low-seasonal discharge, and estuarine conditions varied dramatically between them. The system transitioned from a tidal river with ephemeral presence of a salt wedge during high flow to a partially mixed estuary during low flow. The changing freshwater input, sediment sources, and estuarine characteristics resulted in seaward sediment export during high flow and landward import during low flow. The Dinh An channel of the Song Hau distributary exported sediment to the coast at a rate of about 1 t s−1 during high flow and imported sediment in a spatially varying manner at approximately 0.3 t s−1 during low flow. Scaling these values results in a yearly Mekong sediment discharge estimate about 65% smaller than a generally accepted estimate of 110 Mt yr−1, although the limited temporal and spatial nature of this study implies a relatively high degree of uncertainty for the new estimate. Fluvial advection of sediment was primarily responsible for the high-flow sediment export. Exchange-flow and tidal processes, including local resuspension, were principally responsible for the low-flow import. The resulting bed-sediment grain size was coarser and more variable during high flow and finer during low, and the residual flow patterns support the maintenance of mid-channel islands.Office of Naval Research Grant Numbers: N00014-12-1-0181 , N00014-13-1-0127 , N00014-13-1-0781, and National Defense Science and Engineering2016-03-2

Harmonization-enriched domain adaptation with light fine-tuning for multiple sclerosis lesion segmentation

Deep learning algorithms utilizing magnetic resonance (MR) images have demonstrated cutting-edge proficiency in autonomously segmenting multiple sclerosis (MS) lesions. Despite their achievements, these algorithms may struggle to extend their performance across various sites or scanners, leading to domain generalization errors. While few-shot or one-shot domain adaptation emerges as a potential solution to mitigate generalization errors, its efficacy might be hindered by the scarcity of labeled data in the target domain. This paper seeks to tackle this challenge by integrating one-shot adaptation data with harmonized training data that incorporates labels. Our approach involves synthesizing new training data with a contrast akin to that of the test domain, a process we refer to as "contrast harmonization" in MRI. Our experiments illustrate that the amalgamation of one-shot adaptation data with harmonized training data surpasses the performance of utilizing either data source in isolation. Notably, domain adaptation using exclusively harmonized training data achieved comparable or even superior performance compared to one-shot adaptation. Moreover, all adaptations required only minimal fine-tuning, ranging from 2 to 5 epochs for convergence

Protocol for Biospecimen Collection and Analysis within the BACPAC Research Program

The Biospecimen Collection and Processing Working Group of the NIH HEAL Initiative BACPAC Research Program was charged with identifying molecular biomarkers of interest to chronic low back pain (cLBP). Having identified biomarkers of interest, the Working Group worked with the New York University Grossman School of Medicine, Center for Biospecimen Research and Development-funded by the Early Phase Pain Investigation Clinical Network Data Coordinating Center-to harmonize consortium-wide and site-specific efforts for biospecimen collection and analysis. Biospecimen collected are saliva, blood (whole, plasma, serum), urine, stool, and spine tissue (paraspinal muscle, ligamentum flavum, vertebral bone, facet cartilage, disc endplate, annulus fibrosus, or nucleus pulposus). The omics data acquisition and analyses derived from the biospecimen include genomics and epigenetics from DNA, proteomics from protein, transcriptomics from RNA, and microbiomics from 16S rRNA. These analyses contribute to the overarching goal of BACPAC to phenotype cLBP and will guide future efforts for precision medicine treatment

Semaphorin-Plexin Signaling Guides Patterning of the Developing Vasculature

AbstractMajor vessels of the vertebrate circulatory system display evolutionarily conserved and reproducible anatomy, but the cues guiding this stereotypic patterning remain obscure. In the nervous system, axonal pathways are shaped by repulsive cues provided by ligands of the semaphorin family that are sensed by migrating neuronal growth cones through plexin receptors. We show that proper blood vessel pathfinding requires the endothelial receptor PlexinD1 and semaphorin signals, and we identify mutations in plexinD1 in the zebrafish vascular patterning mutant out of bounds. These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis

Photoreversible interconversion of a phytochrome photosensory module in the crystalline state.

A major barrier to defining the structural intermediates that arise during the reversible photointerconversion of phytochromes between their biologically inactive and active states has been the lack of crystals that faithfully undergo this transition within the crystal lattice. Here, we describe a crystalline form of the cyclic GMP phosphodiesterases/adenylyl cyclase/FhlA (GAF) domain from the cyanobacteriochrome PixJ in Thermosynechococcus elongatus assembled with phycocyanobilin that permits reversible photoconversion between the blue light-absorbing Pb and green light-absorbing Pg states, as well as thermal reversion of Pg back to Pb. The X-ray crystallographic structure of Pb matches previous models, including autocatalytic conversion of phycocyanobilin to phycoviolobilin upon binding and its tandem thioether linkage to the GAF domain. Cryocrystallography at 150 K, which compared diffraction data from a single crystal as Pb or after irradiation with blue light, detected photoconversion product(s) based on Fobs - Fobs difference maps that were consistent with rotation of the bonds connecting pyrrole rings C and D. Further spectroscopic analyses showed that phycoviolobilin is susceptible to X-ray radiation damage, especially as Pg, during single-crystal X-ray diffraction analyses, which could complicate fine mapping of the various intermediate states. Fortunately, we found that PixJ crystals are amenable to serial femtosecond crystallography (SFX) analyses using X-ray free-electron lasers (XFELs). As proof of principle, we solved by room temperature SFX the GAF domain structure of Pb to 1.55-Å resolution, which was strongly congruent with synchrotron-based models. Analysis of these crystals by SFX should now enable structural characterization of the early events that drive phytochrome photoconversion