Dynamic modeling of nitrogen losses in river networks unravels the coupled effects of hydrological and biogeochemical processes

The importance of lotic systems as sinks for nitrogen inputs is well recognized. A fraction of nitrogen in streamflow is removed to the atmosphere via denitrification with the remainder exported in streamflow as nitrogen loads. At the watershed scale, there is a keen interest in understanding the factors that control the fate of nitrogen throughout the stream channel network, with particular attention to the processes that deliver large nitrogen loads to sensitive coastal ecosystems. We use a dynamic stream transport model to assess biogeochemical (nitrate loadings, concentration, temperature) and hydrological (discharge, depth, velocity) effects on reach-scale denitrification and nitrate removal in the river networks of two watersheds having widely differing levels of nitrate enrichment but nearly identical discharges. Stream denitrification is estimated by regression as a nonlinear function of nitrate concentration, streamflow, and temperature, using more than 300 published measurements from a variety of US streams. These relations are used in the stream transport model to characterize nitrate dynamics related to denitrification at a monthly time scale in the stream reaches of the two watersheds. Results indicate that the nitrate removal efficiency of streams, as measured by the percentage of the stream nitrate flux removed via denitrification per unit length of channel, is appreciably reduced during months with high discharge and nitrate flux and increases during months of low-discharge and flux. Biogeochemical factors, including land use, nitrate inputs, and stream concentrations, are a major control on reach-scale denitrification, evidenced by the disproportionately lower nitrate removal efficiency in streams of the highly nitrate-enriched watershed as compared with that in similarly sized streams in the less nitrate-enriched watershed. Sensitivity analyses reveal that these important biogeochemical factors and physical hydrological factors contribute nearly equally to seasonal and stream-size related variations in the percentage of the stream nitrate flux removed in each watershed

Chordoma: The Nonsarcoma Primary Bone Tumor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139965/1/onco1344.pd

Nodular Fasciitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135180/1/jum2014334565.pd

Sonography of Cat Scratch Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135329/1/jum2015343387.pd

Blood lead level and dental caries in school-age children.

The association between blood lead level and dental caries was evaluated in cross-sectional analyses of baseline data for 543 children 6-10 years old screened for enrollment in the Children's Amalgam Trial, a study designed to assess potential health effects of mercury in silver fillings. Approximately half of the children were recruited from an urban setting (Boston/Cambridge, MA, USA) and approximately half from a rural setting (Farmington, ME, USA). Mean blood lead level was significantly greater among the urban subgroup, as was the mean number of carious tooth surfaces. Blood lead level was positively associated with number of caries among urban children, even with adjustment for demographic and maternal factors and child dental practices. This association was stronger in primary than in permanent dentition and stronger for occlusal, lingual, and buccal tooth surfaces than for mesial or distal surfaces. In general, blood lead was not associated with caries in the rural subgroup. The difference between the strength of the associations in the urban and rural settings might reflect the presence of residual confounding in the former setting, the presence of greater variability in the latter setting in terms of important caries risk factors (e.g., fluoride exposure), or greater exposure misclassification in the rural setting. These findings add to the evidence supporting a weak association between children's lead exposure and caries prevalence. A biologic mechanism for lead cariogenicity has not been identified, however. Our data are also consistent with residual confounding by factors associated with both elevated lead exposure and dental caries

In Situ Activation and Heterologous Production of a Cryptic Lantibiotic from an African Plant Ant-Derived Saccharopolyspora Species.

Most clinical antibiotics are derived from actinomycete natural products discovered at least 60 years ago. However, the repeated rediscovery of known compounds led the pharmaceutical industry to largely discard microbial natural products (NPs) as a source of new chemical diversity. Recent advances in genome sequencing have revealed that these organisms have the potential to make many more NPs than previously thought. Approaches to unlock NP biosynthesis by genetic manipulation of strains, by the application of chemical genetics, or by microbial cocultivation have resulted in the identification of new antibacterial compounds. Concomitantly, intensive exploration of coevolved ecological niches, such as insect-microbe defensive symbioses, has revealed these to be a rich source of chemical novelty. Here, we report the new lanthipeptide antibiotic kyamicin, which was generated through the activation of a cryptic biosynthetic gene cluster identified by genome mining Saccharopolyspora species found in the obligate domatium-dwelling ant Tetraponera penzigi of the ant plant Vachellia drepanolobium Transcriptional activation of this silent gene cluster was achieved by ectopic expression of a pathway-specific activator under the control of a constitutive promoter. Subsequently, a heterologous production platform was developed which enabled the purification of kyamicin for structural characterization and bioactivity determination. This strategy was also successful for the production of lantibiotics from other genera, paving the way for a synthetic heterologous expression platform for the discovery of lanthipeptides that are not detected under laboratory conditions or that are new to nature.IMPORTANCE The discovery of novel antibiotics to tackle the growing threat of antimicrobial resistance is impeded by difficulties in accessing the full biosynthetic potential of microorganisms. The development of new tools to unlock the biosynthesis of cryptic bacterial natural products will greatly increase the repertoire of natural product scaffolds. Here, we report a strategy for the ectopic expression of pathway-specific positive regulators that can be rapidly applied to activate the biosynthesis of cryptic lanthipeptide biosynthetic gene clusters. This allowed the discovery of a new lanthipeptide antibiotic directly from the native host and via heterologous expression

Histologic Alterations from Neoadjuvant Chemotherapy in High‐Grade Extremity Soft Tissue Sarcoma: Clinicopathological Correlation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139918/1/onco0451.pd

Epidermal Growth Factor Receptor Expression and Mutational Analysis in Synovial Sarcomas and Malignant Peripheral Nerve Sheath Tumors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140003/1/onco0459.pd

Geriatric Conditions Are Associated With Decreased Anticoagulation Use in Long-Term Care Residents With Atrial Fibrillation

Background Anticoagulation is the mainstay for stroke prevention in patients with atrial fibrillation, but concerns about bleeding inhibit its use in residents of long-term care facilities. Risk-profiling algorithms using comorbid disease information (eg, CHADS2 and ATRIA [Anticoagulation and Risk Factors in Atrial Fibrillation]) have been available for years. In the long-term care setting, however, providers and residents may place more value on geriatric conditions such as mobility impairment, activities of daily living dependency, cognitive impairment, low body mass index, weight loss, and fall history. Methods and Results Using a retrospective cohort design, we measured the association between geriatric conditions and anticoagulation use and type. After merging nursing home assessments containing information about geriatric conditions (Minimum Data Set 2015) with Medicare Part A 2014 to 2015 claims and prescription claims (Medicare Part D) 2015 to 2016, we identified 228 741 residents with atrial fibrillation and elevated stroke risk (CHA2DS2-VASc score \u3e /=2) for our main analysis. Recent fall, activities of daily living dependency, moderate and severe cognitive impairment, low body mass index, and unintentional weight loss were all associated with lower anticoagulation use even after adjustment for multiple predictors of stroke and bleeding (odds ratios ranging from 0.51 to 0.91). Residents with recent fall, low body mass index, and unintentional weight loss were more likely to be using a direct oral anticoagulant, although the magnitude of this effect was smaller. Conclusions Geriatric conditions were associated with lower anticoagulation use. Preventing stroke in these residents with potential for further physical and cognitive impairment would appear to be of paramount significance, although the net benefit of anticoagulation in these individuals warrants further research