Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal.

Low protein synthesis is a feature of somatic stem cells that promotes regeneration in multiple tissues. Modest increases in protein synthesis impair stem cell function, but the mechanisms by which this occurs are largely unknown. We determine that low protein synthesis within hematopoietic stem cells (HSCs) is associated with elevated proteome quality in vivo. HSCs contain less misfolded and unfolded proteins than myeloid progenitors. Increases in protein synthesis cause HSCs to accumulate misfolded and unfolded proteins. To test how proteome quality affects HSCs, we examine Aarssti/sti mice that harbor a tRNA editing defect that increases amino acid misincorporation. Aarssti/sti mice exhibit reduced HSC numbers, increased proliferation, and diminished serial reconstituting activity. Misfolded proteins overwhelm the proteasome within Aarssti/sti HSCs, which is associated with increased c-Myc abundance. Deletion of one Myc allele partially rescues serial reconstitution defects in Aarssti/sti HSCs. Thus, HSCs are dependent on low protein synthesis to maintain proteostasis, which promotes their self-renewal

Holographic aspects of three dimensional QCD from string theory

We study two aspects of 3D QCD with massless fermions in a holographic set-up from string theory, based on D3/D7 branes; parity anomaly and baryons as baby Skyrmions. We first give a novel account of parity anomaly of 3D QCD with odd number of flavors from the IR holographic viewpoint by observing a subtle point in D7 brane embeddings with a given fixed UV theory. We also discuss its UV origin in terms of weakly coupled D-brane pictures. We then focus on the parity-symmetric case of even number of N_F flavors, and study baryons in the holographic model. We identify the monopoles of U(N_F) gauge theory dynamically broken down to U(N_F/2)x U(N_F/2) in the holographic 4 dimensional bulk as a holographic counter-part of 3D baby-Skyrmions for baryons in large N limit, and work out some details how the mapping goes. In particular, we show that the correct baryon charges emerge from the Witten effect with a space-varying theta angle.Comment: 33 pages, 10 figures; v2: references added with comments, typos corrected; v3: more references added; v4: holographic baryon profile and the analysis of its baryon charge is significantly revised, correcting errors in the previous discussio

Improving the performance of bright quantum dot single photon sources using amplitude modulation

Single epitaxially-grown semiconductor quantum dots have great potential as single photon sources for photonic quantum technologies, though in practice devices often exhibit non-ideal behavior. Here, we demonstrate that amplitude modulation can improve the performance of quantum-dot-based sources. Starting with a bright source consisting of a single quantum dot in a fiber-coupled microdisk cavity, we use synchronized amplitude modulation to temporally filter the emitted light. We observe that the single photon purity, temporal overlap between successive emission events, and indistinguishability can be greatly improved with this technique. As this method can be applied to any triggered single photon source, independent of geometry and after device fabrication, it is a flexible approach to improve the performance of solid-state systems, which often suffer from excess dephasing and multi-photon background emission

Altered Neural and Behavioral Dynamics in Huntington's Disease: An Entropy Conservation Approach

Background: Huntington’s disease (HD) is an inherited condition that results in neurodegeneration of the striatum, the forebrain structure that processes cortical information for behavioral output. In the R6/2 transgenic mouse model of HD, striatal neurons exhibit aberrant firing patterns that are coupled with reduced flexibility in the motor system. The aim of this study was to test the patterns of unpredictability in brain and behavior in wild-type (WT) and R6/2 mice. Methodology/Principal Findings: Striatal local field potentials (LFP) were recorded from 18 WT and 17 R6/2 mice (aged 8– 11 weeks) while the mice were exploring a plus-shaped maze. We targeted LFP activity for up to 2 s before and 2 s after each choice-point entry. Approximate Entropy (ApEn) was calculated for LFPs and Shannon Entropy was used to measure the probability of arm choice, as well as the likelihood of making consecutive 90-degree turns in the maze. We found that although the total number of choice-point crossings and entropy of arm-choice probability was similar in both groups, R6/2 mice had more predictable behavioral responses (i.e., were less likely to make 90-degree turns and perform them in alternation with running straight down the same arm), while exhibiting more unpredictable striatal activity, as indicated by higher ApEn values. In both WT and R6/2 mice, however, behavioral unpredictability was negatively correlated with LFP ApEn. Conclusions/Significance: HD results in a perseverative exploration of the environment, occurring in concert with mor

The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) prevalence of the metabolic syndrome in a Chinese population

To assess the prevalence of the metabolic syndrome disease cluster in the Hong Kong Chinese population we applied the US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) guidelines. This was present if ≥3 of the following conditions were present: Hypertension (≥130/85 mmHg); fasting plasma glucose was ≥6.1 mmol/L; fasting plasma triglycerides ≥1.69 mmol/L; fasting HDL-cholesterol 88 or 102 cm (Asian WHO criteria ≥80 or 90 cm) in females and males, respectively. A total of 16.7% (17.1 (95%CI 15.7-18.5)% age and gender-adjusted) of the 2893 subjects had the metabolic syndrome. The prevalence of having at least 2, 3, 4 or 5 components was 34.5, 16.7, 6.4 and 1.4%, respectively. The prevalence increased from 3.1% in those aged 25-29 years to 41.0% in those aged over 70 years. Using the 2001 Census, 880,499 Hong Kong residents would have the metabolic syndrome. If the WHO recommended waist circumference for Asians is used, the age and gender-adjusted prevalence is significantly higher at 21.2% (21.9 (95%CI 20.4-23.4)%). In summary, the high prevalence of the metabolic syndrome in adult Hong Kong Chinese, particularly in the elderly, forewarns a rapidly increasing problem in Mainland China, and other Asian populations, which may have overwhelming public health ramifications. © 2004 Elsevier Ireland Ltd. All rights reserved.postprin

Encrusted and incarcerated urinary bladder catheter: what are the options?

Urinary bladder catheter encrustations are known complications of long-term urinary catheterisation, which is commonly seen in clinical practice. These encrustations can impede deflation of the balloon and therefore cause problems in the removal of the catheter. The options in managing an encrusted and incarcerated urinary bladder catheter include extracorporeal shock wave lithotripsy and lithoclast. We describe here another technique of dealing with a stuck and encrustated catheter, via direct crushing of the encrustations with a rigid cystoscope inserted through a suprapubic cystostomy tract

Developmental Defects of Enamel in Primary Teeth and Association with Early Life Course Events: A Study of 6--36 Month old Children in Manyara, Tanzania.

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).Focusing 6--36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child's early illness episodes and mothers' perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.22 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue