Efficient oxide phosphors for light upconversion; green emission from Yb3+ and Ho3+ co-doped Ln(2)BaZnO(5) (Ln = Y, Gd)

This is the author's accepted version of the article. The final published article can be found here: http://dx.doi.org/10.1039/C0JM01652

A customized monocyte cDNA microarray for diagnosis of rheumatoid arthritis and prognosis of anti-TNF-α therapy

Background In rheumatoid arthritis (RA) macrophages (Mf) play a pivotal role. They become highly activated in synovitis and at the cartilage–pannus junction. Furthermore, therapeutic neutralization of molecules produced by activated Mf lead to clinical improvement in RA, and circulating monocytes (MO) of the peripheral blood in patients with RA spontaneously express proinflammatory genes (IL-1β, IL-6, TNF). Methods A custom RA-MO cDNA microarray was generated using differentially expressed genes obtained from gene subtraction and from comparative whole genome wide U133A analysis in normal donors, active and anti-TNF-α created RA patients. Genes were selected using MAS 5.0, multtest and PAM. The custom microarray consists of 313 genes including guide dots, and positive (housekeeping genes and spike controls) and negative controls for image and statistical analysis. Each probe was spotted in 16 replicates. Results The RA-MO chipset-II was validated using the following: non-stimulated and LPS, PMA, Vit.D3+LPS, PMA+LPS stimulated U937 cells; nonstimulated and LPS stimulated healthy donor MO; MO from normal donors (n = 3) and RA patients before and during anti-TNF-α treatment (n = 5 each); and synovial tissue from normal individuals (n = 2) and RA patients (n = 2). Not only LPS/PMA regulated genes but also RA specific and anti-TNF-α regulated genes were validated. In addition, we could clarify whether these genes are differentially transcribed only in MO or whether they can also be found in RA tissue Mf. Our data indicate a high degree of reproducibility that is sufficient for diagnostic applications and therapy monitoring. Conclusion The RA-MO chipset-II microarray is competitive and flexible for enlargement of the number of genes. The current gene selection will contribute to validating the role of monocytes in disease activity, to therapeutic interventions, and may improve the knowledge on the regulation of pathways in activated monocytes in chronic inflammation

Using the wax moth larva Galleria mellonella infection model to detect emerging bacterial pathogens

This is the final version. Available from PeerJ via the DOI in this recordData Availability: The following information was supplied regarding data availability: Using the wax moth larva Galleria mellonella infection model to detect emerging bacterial pathogens. Dryad Digital Repository DOI 10.5061/dryad.130q4qb.Climate change, changing farming practices, social and demographic changes and rising levels of antibiotic resistance are likely to lead to future increases in opportunistic bacterial infections that are more difficult to treat. Uncovering the prevalence and identity of pathogenic bacteria in the environment is key to assessing transmission risks. We describe the first use of the Wax moth larva Galleria mellonella, a well-established model for the mammalian innate immune system, to selectively enrich and characterize pathogens from coastal environments in the South West of the UK. Whole-genome sequencing of highly virulent isolates revealed amongst others a Proteus mirabilis strain carrying the Salmonella SGI1 genomic island not reported from the UK before and the recently described species Vibrio injenensis hitherto only reported from human patients in Korea. Our novel method has the power to detect bacterial pathogens in the environment that potentially pose a serious risk to public health.Natural Environment Research Council (NERC

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

Background and Goals:Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.Methods:We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.Results:HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.Conclusions:Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines. © 2013 Thudi et al

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Ecology of Sleeping: The Microbial and Arthropod Associates of Chimpanzee Beds

The indoor environment created by the construction of homes and other buildings is often considered to be uniquely different from other environments. It is composed of organisms that are less diverse than those of the outdoors and strongly sourced by, or dependent upon, human bodies. Yet, no one has ever compared the composition of species found in contemporary human homes to that of other structures built by mammals, including those of non-human primates. Here we consider the microbes and arthropods found in chimpanzee beds, relative to the surrounding environment (n = 41 and 15 beds, respectively). Based on the study of human homes, we hypothesized that the microbes found in chimpanzee beds would be less diverse than those on nearby branches and leaves and that their beds would be primarily composed of body-associated organisms. However, we found that differences between wet and dry seasons and elevation above sea level explained nearly all of the observed variation in microbial diversity and community structure. While we can identify the presence of a chimpanzee based on the assemblage of bacteria, the dominant signal is that of environmental microbes. We found just four ectoparasitic arthropod specimens, none of which appears to be specialized on chimpanzees or their structures. These results suggest that the life to which chimpanzees are exposed while in their beds is predominately the same as that of the surrounding environment

Direct exfoliation and dispersion of two-dimensional materials in pure water via temperature control

The high-volume synthesis of two-dimensional (2D) materials in the form of platelets is desirable for various applications. While water is considered an ideal dispersion medium, due to its abundance and low cost, the hydrophobicity of platelet surfaces has prohibited its widespread use. Here we exfoliate 2D materials directly in pure water without using any chemicals or surfactants. In order to exfoliate and disperse the materials in water, we elevate the temperature of the sonication bath, and introduce energy via the dissipation of sonic waves. Storage stability greater than one month is achieved through the maintenance of high temperatures, and through atomic and molecular level simulations, we further discover that good solubility in water is maintained due to the presence of platelet surface charges as a result of edge functionalization or intrinsic polarity. Finally, we demonstrate inkjet printing on hard and flexible substrates as a potential application of water-dispersed 2D materials.close1

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Clinical and Immunologic Investigations in Patients With Stiff-Person Spectrum Disorder

Importance: Symptoms of stiff-person syndrome (SPS), stiff-limb syndrome (SLS), or progressive encephalomyelitis with rigidity, myoclonus, or other symptoms (SPS-plus) can occur with several autoantibodies, but the relative frequency of each antibody, syndrome specificity, and prognostic implications are unclear. Objective: To report the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD), including SPS, SLS, and SPS-plus. Design, Setting, and Patients: This study retrospectively examined a case series (January 1, 1998, through December 31, 2014) of immunologic investigations performed in a neuroimmunology referral center. The study included 121 patients with clinical features of SPSD. Data analysis was performed from July 1, 2015, through November 1, 2015. Main Outcomes and Measures: Analysis of clinical-immunologic associations, including autoantibodies to 8 proteins expressed in inhibitory synapses. Results: The median age of the patients was 51 years (interquartile range, 40-61 years), and 75 (62.0%) were female. Fifty (41.3%) had SPS, 37 (30.6%) had SPS-plus, 24 (19.8%) had SLS, and 10 (8.3%) had SPS or SLS overlapping with ataxia, epilepsy, or encephalitis. Fifty-two patients (43.0%) had glutamic acid decarboxylase (GAD65) antibodies (2 with γ-aminobutyric acid-A [GABA-A] receptor antibodies), 24 (19.8%) had α1-subunit of the glycine receptor (GlyR) antibodies (2 with GAD65 antibodies), 5 (4.1%) had other antibodies, and 40 (33.1%) tested negative for antibodies. None had gephyrin or glycine transporter antibodies. Among the main immunologic groups (GAD65 antibodies, GlyR antibodies, and antibody negative), those with GAD65 antibodies were more likely to be female (45 [86.5%] of 52, 8 [36.4%] of 22, and 18 [45.0%] of 40, respectively; P < .001), have systemic autoimmunity (34 [65.4%] of 52, 7 [31.8%] of 22, and 13 [32.5%] of 40, respectively; P = .004), and have longer delays in being tested for antibodies (median, 3 vs 0.5 and 1 year; P < .001). Patients with GAD65 antibodies were more likely to develop SPS (27 [51.9%] of 52) or overlapping syndromes (8 [15.4%] of 52) than patients with GlyR antibodies (5 [22.7%] and 0 [0%] of 22, respectively), who more often developed SPS-plus (12 [54.5%] of 22 vs 7 [13.5%] in those with GAD65 antibodies); antibody-negative patients had an intermediate syndrome distribution. In multivariable analysis, symptom severity (P = .001) and immunologic group (P = .01) were independently associated with outcome. Compared with patients with GlyR antibodies, those with GAD65 antibodies (odds ratio, 11.1, 95% CI, 2.3-53.7; P = .003) had worse outcome. Patients without antibodies had similar outcome than patients with GlyR antibodies (odds ratio, 4.2, 95% CI, 0.9-20.0; P = .07). Conclusions and Relevance: In SPSD, symptom severity and presence and type of antibodies are predictors of outcome