Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Comparison of Muscle Onset Activation Sequences between a Golf or Tennis Swing and Common Training Exercises Using Surface Electromyography: A Pilot Study

Aim. The purpose of this pilot study is to use surface electromyography to determine an individual athlete’s typical muscle onset activation sequence when performing a golf or tennis forward swing and to use the method to assess to what degree the sequence is reproduced with common conditioning exercises and a machine designed for this purpose. Methods. Data for 18 healthy male subjects were collected for 15 muscles of the trunk and lower extremities. Data were filtered and processed to determine the average onset of muscle activation for each motion. A Spearman correlation estimated congruence of activation order between the swing and each exercise. Correlations of each group were pooled with 95% confidence intervals using a random effects meta-analytic strategy. Results. The averaged sequences differed among each athlete tested, but pooled correlations demonstrated a positive association between each exercise and the participants’ natural muscle onset activation sequence. Conclusion. The selected training exercises and Turning Point™ device all partially reproduced our athletes’ averaged muscle onset activation sequences for both sports. The results support consideration of a larger, adequately powered study using this method to quantify to what degree each of the selected exercises is appropriate for use in both golf and tennis

Dependence of open-circuit voltage in hydrogenated protocrystalline silicon solar cells on carrier recombination in p/i interface and bulk regions

Contribution of carrier recombination from the p/i interface regions and the bulk to the dark current-voltage (JD-V) and short-circuit current-open-circuit voltage (Jsc-Voc) characteristics of hydrogenated amorphous-silicon (a-Si:H) p-i-n and n-i-p solar cells have been separated, identified, and quantified. Results are presented and discussed here which show that a maximum 1 sun Voc for a given bulk material can be validly extrapolated from bulk dominated Jsc-Voc characteristics at low illumination intensities. © 2000 American Institute of Physics

A coordinated multi-study analysis of the longitudinal association between handgrip strength and cognitive function in older adults

OBJECTIVE: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis. METHODS: We performed coordinated analysis on nine cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis. RESULTS: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44 - 0.56). We also found a high level of heterogeneity in this association across studies. DISCUSSION: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers

ERp29 Restricts Connexin43 Oligomerization in the Endoplasmic Reticulum

Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus

Cryptococcosis in Patients With Cirrhosis of the Liver and Posttransplant Outcomes

BACKGROUND: The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known. METHODS: We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care. RESULTS: In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%. CONCLUSIONS: Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable

Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P \u3c .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers