A Key Role of Dendritic Cells in Probiotic Functionality

BACKGROUND: Disruption of the intestinal homeostasis and tolerance towards the resident microbiota is a major mechanism involved in the development of inflammatory bowel disease. While some bacteria are inducers of disease, others, known as probiotics, are able to reduce inflammation. Because dendritic cells (DCs) play a central role in regulating immune responses and in inducing tolerance, we investigated their role in the anti-inflammatory potential of probiotic lactic acid bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Selected LAB strains, while efficiently taken up by DCs in vitro, induced a partial maturation of the cells. Transfer of probiotic-treated DCs conferred protection against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Protection was associated with a reduction of inflammatory scores and colonic expression of pro-inflammatory genes, while a high local expression of the immunoregulatory enzyme indolamine 2, 3 dioxgenase (IDO) was observed. The preventive effect of probiotic-pulsed DCs required not only MyD88-, TLR2- and NOD2-dependent signaling but also the induction of CD4+ CD25+ regulatory cells in an IL-10-independent pathway. CONCLUSIONS/SIGNIFICANCE: Altogether, these results suggest that selected probiotics can stimulate DC regulatory functions by targeting specific pattern-recognition receptors and pathways. The results not only emphasize the role of DCs in probiotic immune interactions, but indicate a possible role in immune-intervention therapy for IBD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour

Female Collegiate Dancers Body Composition, Macronutrient and Micronutrient Intake Over Two Academic Years: A Longitudinal Analysis

Collegiate dancers face unique challenges to maintain a lean aesthetic, optimal diet, and a high-performance level due to the various stressors in college. The purpose of this study was to examine changes in body composition (BC) and diet over two years. Participants (N = 17, 19.6 ± 1.6 years) completed two laboratory sessions per semester. Sessions included height and weight, BC, dietary intake, and a health history questionnaire. Regardless of rigorous dance training and variations in the academic calendar, no significant changes in BC or diet were observed within semesters of over two years. BMI was normal (24.9 ± 4.1 kg/m2) with fat mass exceeding 30% at all timepoints. Fat mass was negatively correlated with carbohydrate, fat, and protein intake (g/kg/day; r = −0.291, p = 0.004; r = −0.372, p < 0.0001; r = −0.398, p < 0.0001; respectively). Energy intake was within the recommended daily allowance (2040 ± 710 kcal/day), however may be insufficient for an active dance population. Protein (1.1 ± 0.5 g/kg), carbohydrate (3.7 ± 1.6 g/kg), calcium (835 ± 405 mg/day), iron (17 ± 15 mg/day), and potassium (1628 ± 1736 mg/day) intake fell below recommendations for an active population. Alterations in dance training and the demands of the academic calendar may be contributing to suboptimal dietary intake and BC in female collegiate dancers

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism

Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting thatmost effectors represent species-specific adaptations

PICO: Probe of Inflation and Cosmic Origins

The Probe of Inflation and Cosmic Origins (PICO) is a proposed probe-scale space mission consisting of an imaging polarimeter operating in frequency bands between 20 and 800 GHz. We describe the science achievable by PICO, which has sensitivity equivalent to more than 3300 Planck missions, the technical implementation, the schedule and cost

PICO: Probe of Inflation and Cosmic Origins

The Probe of Inflation and Cosmic Origins (PICO) is an imaging polarimeter that will scan the sky for 5 years in 21 frequency bands spread between 21 and 799 GHz. It will produce full-sky surveys of intensity and polarization with a final combined-map noise level of 0.87 $\mu$K arcmin for the required specifications, equivalent to 3300 Planck missions, and with our current best-estimate would have a noise level of 0.61 $\mu$K arcmin (6400 Planck missions). PICO will either determine the energy scale of inflation by detecting the tensor to scalar ratio at a level $r=5\times 10^{-4}~(5\sigma)$, or will rule out with more than $5\sigma$ all inflation models for which the characteristic scale in the potential is the Planck scale. With LSST's data it could rule out all models of slow-roll inflation. PICO will detect the sum of neutrino masses at $>4\sigma$, constrain the effective number of light particle species with $\Delta N_{\rm eff}<0.06~(2\sigma)$, and elucidate processes affecting the evolution of cosmic structures by measuring the optical depth to reionization with errors limited by cosmic variance and by constraining the evolution of the amplitude of linear fluctuations $\sigma_{8}(z)$ with sub-percent accuracy. Cross-correlating PICO's map of the thermal Sunyaev-Zeldovich effect with LSST's gold sample of galaxies will precisely trace the evolution of thermal pressure with $z$. PICO's maps of the Milky Way will be used to determine the make up of galactic dust and the role of magnetic fields in star formation efficiency. With 21 full sky legacy maps in intensity and polarization, which cannot be obtained in any other way, the mission will enrich many areas of astrophysics. PICO is the only single-platform instrument with the combination of sensitivity, angular resolution, frequency bands, and control of systematic effects that can deliver this compelling, timely, and broad science