Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

A New bis(rhodamine)-Based Fluorescent Chemosensor for Fe3+

A new bis(rhodamine)-based fluorescent probe 4 was synthesized, and it exhibited high selectivity for Fe3+ over other commonly coexistent metal ions in both 50% ethanol and Tris–HCl buffer. Upon the addition of Fe3+, the spirocyclic ring of 4 was opened and a significant enhancement of visible color and fluorescence in the range of 500–600 nm was observed

Mild cognitive impairment is associated with poor physical function but not bone structure or density in late adulthood:Findings from the Hertfordshire Cohort Study

Mini Abstract This study investigated the association between mild cognitive impairment (MCI) and physical function and bone health in older adults. MCI was associated with poor physical performance but not bone mineral density or bone microarchitecture. Abstract Purpose: Cross-sectional study to investigate the association between mild cognitive impairment (MCI) and physical performance, and bone health, in a community-dwelling cohort of older adults. Methods: Cognitive function of 222 men and 221 women (mean age 75.5 and 75.8 years in men and women, respectively) was assessed by the Strawbridge questionnaire and Mini Mental State Exam (MMSE). Participants underwent dual-energy x-ray absorptiometry (DXA), peripheral-quantitative computed tomography (pQCT) and high-resolution peripheral-quantitative computed tomography (HR-pQCT) scans to assess their bone density, strength and microarchitecture. Their physical function was assessed and a physical performance (PP) score was recorded. Results: 11.8% of women and 8.1% of men in the study were cognitive impaired on the MMSE (score<24). 24% of women were deemed cognitively impaired on the Strawbridge questionnaire, compared to 22.3% of men. Cognitive impairment on the Strawbridge questionnaire was associated with poorer physical performance score in men but not women in the unadjusted analysis. MMSE <24 was strongly associated with the risk of low physical performance in men (OR 12.9, 95% CI 1.67, 99.8, p=0.01) Higher MMSE score was associated with better physical performance in both sexes. Poorer cognitive function, whether assessed by the Strawbridge questionnaire, or by MMSE score, was not associated with bone density, shape or microarchitecture, in either sex. Conclusion: MCI in older adults was associated with poor physical performance, but not bone density, shape or microarchitecture

Gene Regulation in Giardia lambia Involves a Putative MicroRNA Derived from a Small Nucleolar RNA

Two core microRNA (miRNA) pathway proteins, Dicer and Argonaute, are found in Giardia lamblia, a deeply branching parasitic protozoan. There are, however, no apparent homologues of Drosha or Exportin5 in the genome. Here, we report a 26 nucleotide (nt) RNA derived from a 106 nt Box C/D snoRNA, GlsR2. This small RNA, designated miR5, localizes to the 3′ end of GlsR2 and has a 75 nt hairpin precursor. GlsR2 is processed by the Dicer from Giardia (GlDcr) and generated miR5. Immunoprecipitation of the Argonaute from Giardia (GlAgo) brought down miR5. When a Renilla Luciferase transcript with a 26 nt miR5 antisense sequence at the 3′-untranslated region (3′ UTR) was introduced into Giardia trophozoites, Luciferase expression was reduced ∼25% when synthetic miR5 was also introduced. The Luciferase mRNA level remained, however, unchanged, suggesting translation repression by miR5. This inhibition was fully reversed by introducing also a 2′-O-methylated antisense inhibitor of miR5, suggesting that miR5 acts by interacting specifically with the antisense sequence in the mRNA. A partial antisense knock down of GlDcr or GlAgo in Giardia indicated that the former is needed for miR5 biogenesis whereas the latter is required for miR5-mediated translational repression. Potential targets for miR5 with canonical seed sequences were predicted bioinformatically near the stop codon of Giardia mRNAs. Four out of the 21 most likely targets were tested in the Luciferase reporter assay. miR5 was found to inhibit Luciferase expression (∼20%) of transcripts carrying these potential target sites, indicating that snoRNA-derived miRNA can regulate the expression of multiple genes in Giardia

Osteoinduction of Human Mesenchymal Stem Cells by Bioactive Composite Scaffolds without Supplemental Osteogenic Growth Factors

The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate stem cell differentiation towards osteogenic lineages in the absence of specific chemical treatments. Herein we describe a bioactive composite nanofibrous scaffold, composed of poly-caprolactone (PCL) and nano-sized hydroxyapatite (HA) or beta-tricalcium phosphate (TCP), which was able to support the growth of human bone marrow mesenchymal stem cells (hMSCs) and guide their osteogenic differentiation at the same time. Morphological and physical/chemical investigations were carried out by scanning, transmission electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, mechanical and wettability analysis. Upon culturing hMSCs on composite nanofibers, we found that the incorporation of either HA or TCP into the PCL nanofibers did not affect cell viability, meanwhile the presence of the mineral phase increases the activity of alkaline phosphatase (ALP), an early marker of bone formation, and mRNA expression levels of osteoblast-related genes, such as the Runt-related transcription factor 2 (Runx-2) and bone sialoprotein (BSP), in total absence of osteogenic supplements. These results suggest that both the nanofibrous structure and the chemical composition of the scaffolds play a role in regulating the osteogenic differentiation of hMSCs

Calculating Ensemble Averaged Descriptions of Protein Rigidity without Sampling

Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG) that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars) that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability

Integration of Gene Dosage and Gene Expression in Non-Small Cell Lung Cancer, Identification of HSP90 as Potential Target

BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients

Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia