Succession of Bifidobacterium longum strains in response to the changing early-life nutritional environment reveals specific adaptations to distinct dietary substrates

Diet-microbe interactions play a crucial role in infant development and modulation of the early-life microbiota. The genus Bifidobacterium dominates the breast-fed infant gut, with strains of B. longum subsp. longum (B. longum) and B. longum subsp. infantis (B. infantis) particularly prevalent. Although transition from milk to a more diversified diet later in infancy initiates a shift to a more complex microbiome, specific strains of B. longum may persist in individual hosts for prolonged periods of time. Here, we sought to investigate the adaptation of B. longum to the changing infant diet. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to glycosyl hydrolase families and enzymes, which corresponded to different dietary stages. Complementary phenotypic growth studies indicated strain-specific differences in human milk oligosaccharide and plant carbohydrate utilisation profiles of isolates between and within individual infants, while proteomic profiling identified active polysaccharide utilisation loci involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum subspecies/strain genomic and carbohydrate utilisation diversity, which aligns with a changing nutritional environment: i.e. moving from breast milk to a solid food diet. These data provide additional insights into possible mechanisms responsible for the competitive advantage of this Bifidobacterium species and its long-term persistence in a single host and may contribute to rational development of new dietary therapies for this important developmental window

Succession of Bifidobacterium longum strains in response to a changing early life nutritional environment reveals dietary substrate adaptations

Diet-microbe interactions play a crucial role in modulation of the early life microbiota and infant health. Bifidobacterium dominates the breast-fed infant gut and may persist in individuals during transition from a milk-based to a more diversified diet. Here, we investigated adaptation of B. longum to the changing nutritional environment. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to carbohydrate metabolism, which corresponded to different dietary stages. Complementary phenotypic studies indicated strain-specific differences in utilisation of human milk oligosaccharides and plant carbohydrates, while proteomic profiling identified gene clusters involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum diversity and provide additional insights into possible competitive advantage mechanisms of this Bifidobacterium species and its persistence in a single host

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Staging Bipolar Disorder.

The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodromal (at-risk) to more severe and refractory presentations (Stage IV). A staging model implies a longitudinal appraisal of different aspects: clinical variables, such as number of episodes and subsyndromal symptoms, functional and cognitive impairment, comorbidity, biomarkers, and neuroanatomical changes. Staging models are based on the fact that response to treatment is generally better when it is introduced early in the course of the illness. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in bipolar disorder treatment planning and prognosis, and emphasize the importance of early intervention. Further research is required in this exciting and novel area

“I don’t want to live too long!”: Successful ageing and the failure of longevity in Japan

This chapter examines ‘successful aging’ through its impacts on formal care workers in Japan. It is based on one year of fieldwork conducted in urban Japan and examines the affective, ethical, and cultural forces that result at times in resilience, compassion, and intimacy between carers and elderly clients, and at other times, in violence, abuse, and abandonment. I argue that locating the source of this divergence in individuals (i.e., adverse coping strategy) reproduces the same neoliberal model of success for care workers as it does for the elderly. Instead, care and abuse in formal care settings can be seen as symptoms of broader political and economic transformations that have been occurring in Japan since the 1990s

Controlling tick-borne diseases through domestic animal management: a theoretical approach

Vector-borne diseases are of global importance to human and animal health. Empirical trials of effective methods to control vectors and their pathogens can be difficult for practical, financial and ethical reasons. Here, therefore, we use a mathematical model to predict the effectiveness of a vector-borne disease control method. As a case study, we use the tick-louping ill virus system, where sheep are treated with acaricide in an attempt to control ticks and disease in red grouse, an economically important game bird. we ran the model under different scenarios of sheep flock sizes, alternative host (deer) densities, acaricide efficacies and tick burdens. The model predicted that, with very low deer densities, using sheep as tick mops can reduce the tick population and virus prevalence. However, treatment is ineffective above a certain threshold deer density, dependent on the comparative tick burden on sheep and deer. The model also predicted that high efficacy levels of acaricide must be maintained for effective tick control. This study suggests that benignly managing one host species to protect another host species from a vector and pathogen can be effective under certain conditions. It also highlights the importance of understanding the ecological complexity of a system, in order to target control methods only under certain circumstances for maximum effectiveness

Mother knows best: occurrence and associations of resighted humpback whales suggest maternally derived fidelity to a southern hemisphere coastal feeding ground

Site fidelity is common among migratory cetaceans, including humpback whales (Megaptera novaeangliae). In the Northern Hemisphere it has been found that fidelity to humpback whale feeding grounds is transferred maternally but this has never been shown for the species in the Southern Hemisphere. We examined this in a unique feeding area off west South Africa using resighting data of 68 individually identified humpback whales by means of photographic (tail flukes and dorsal fins) and/or molecular methods (microsatellite genotyping) over an 18 year span. We found short-term association patterns and recurrent visits typical of other feeding grounds. Males and females had different seasonality of attendance. Significant female-dominated presence corresponded to timing of an expected influx of females on their southward migration from the breeding ground: firstly non-nursing (possibly pregnant) females in mid-spring, and mothers and calves in mid-to late summer. The potential benefit of this mid-latitude feeding area for females is illustrated by a record of a cow with known age of at least 23 years that produced calves in three consecutive years, each of which survived to at least six months of age: the first record of successful post-partum ovulation for this species in the Southern Hemisphere. We recorded association of a weaned calf with its mother, and a recurring association between a non-lactating female and male over more than two years. Moreover, three animals first identified as calves returned to the same area in subsequent years, sometimes on the same day as their mothers. This, together with numerous Parent-Offspring relations detected genetically among and between resighted and non-resighted whales is strongly suggestive of maternally derived site fidelity at a small spatial scale by a small sub-population of humpback whales.National Research Foundation (NRF), South Africa [2047517]; PADI Project AWARE (UK) [095]; Earthwatch Institute (project title "Whales of South Africa"

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT