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

Multicore implementation of a fixed-complexity tree-search detector for MIMO communications

[EN] Multicore systems allow the efficient implementation of signal processing algorithms for communication systems due to their high parallel processing capabilities. In this paper, we present a high-throughput multicore implementation of a fixed-complexity tree-search-based detector interesting for MIMO wireless communication systems. Experimental results confirm that this implementation allows to accelerate the data detection stage for different constellation sizes and number of subcarriers.This work was supported by the TEC2009-13741 project of the Spanish Ministry of Science, by the PROMETEO/2009/013 project and ACOMP/2012/076 of the Generalitat Valenciana, and the Vicerrectorado de Investigacion de la UPV through Programa de Apoyo a la Investigacion y desarrollo (PAID-05-11-2898).Ramiro Sánchez, C.; Roger Varea, S.; Gonzalez, A.; Almenar Terré, V.; Vidal Maciá, AM. (2013). Multicore implementation of a fixed-complexity tree-search detector for MIMO communications. The Journal of Supercomputing (Online). 65(3):1010-1019. https://doi.org/10.1007/s11227-012-0839-xS10101019653Paulraj AJ, Gore DA, Nabar RU, Bölcskei H (2004) An overview of MIMO communications—a key to gigabit wireless. Proc IEEE 92(2):198–218Jiang M, Hanzo L (2007) Multiuser MIMO-OFDM for next-generation wireless systems. Proc IEEE 95(7):1430–14693GPP TS 36.201, V10.0.0, Evolved Universal Terrestrial Radio Access (E-UTRA); Physical layer—general description, December 2010Lin Y, Lee H, Woh M, Harel Y, Mahlke S, Mudge T, Chakrabarti C, Flautner K (2007) SODA: a high-performance DSP architecture for software-defined radio. IEEE MICRO 27(1):114–123Yang C-H, Markovic D (2008) A multi-core sphere decoder VLSI architecture for MIMO communications. In: Global telecommunications conference, November, pp 1–6Wu D, Eilert J, Liu D (2011) Implementation of a high-speed MIMO soft-output symbol detector for software defined radio. J Signal Process Syst 63(1):27–37Tan K, Liu H, Zhang J, Zhang Y, Fang J, Voelker GM (2011) Sora: high-performance software radio using general-purpose multi-core processors. Communun ACM 54(1):99–107Roger S, Ramiro C, Gonzalez A, Almenar V, Vidal AM (2012) An efficient GPU implementation of fixed-complexity sphere decoders for MIMO wireless systems. Integr Comput-Aided Eng 19(4):341–350Chen Y-K et al (2009) Signal processing on platforms with multiple cores: Part 1-Overview and methodologies. IEEE Signal Proc Mag 6:24–25Karam LJ, AlKamal I, Gatherer A, Frantz GA, Anderson DV, Evans BL (2009) Trends in multicore DSP platforms. IEEE Signal Process Mag 26(6):38–49Barbero LG, Thompson JS (2008) Fixing the complexity of the sphere decoder for MIMO detection. IEEE Trans Wirel Commun 7(6):2131–2142Hassibi B, Vikalo H (2005) On sphere decoding algorithm. Part I, The expected complexity. IEEE Trans Signal Process 54(5):2806–2818Agrell E, Eriksson T, Vardy A, Zeger K (2002) Closest point search in lattices. IEEE Trans Inf Theory 48(8):2201–2214OpenMP v3.0, http://www.openmp.org/mp-documents/spec30.pdf , May 200

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Effects of acute fatigue on the volitional and magnetically-evoked electromechanical delay of the knee flexors in males and females

Neuromuscular performance capabilities, including those measured by evoked responses, may be adversely affected by fatigue; however, the capability of the neuromuscular system to initiate muscle force rapidly under these circumstances is yet to be established. Sex-differences in the acute responses of neuromuscular performance to exercise stress may be linked to evidence that females are much more vulnerable to ACL injury than males. Optimal functioning of the knee flexors is paramount to the dynamic stabilisation of the knee joint, therefore the aim of this investigation was to examine the effects of acute maximal intensity fatiguing exercise on the voluntary and magnetically-evoked electromechanical delay in the knee flexors of males and females. Knee flexor volitional and magnetically-evoked neuromuscular performance was assessed in seven male and nine females prior to and immediately after: (i) an intervention condition comprising a fatigue trial of 30-seconds maximal static exercise of the knee flexors, (ii) a control condition consisting of no exercise. The results showed that the fatigue intervention was associated with a substantive reduction in volitional peak force (PFV) that was greater in males compared to females (15.0%, 10.2%, respectively, p < 0.01) and impairment to volitional electromechanical delay (EMDV) in females exclusively (19.3%, p < 0.05). Similar improvements in magnetically-evoked electromechanical delay in males and females following fatigue (21%, p < 0.001), however, may suggest a vital facilitatory mechanism to overcome the effects of impaired voluntary capabilities, and a faster neuromuscular response that can be deployed during critical times to protect the joint system

Structure-Function Relationships of the Mycobacterium tuberculosis Transcription Factor WhiB1

Background Members of the WhiB-like (Wbl) protein family possess iron-sulfur clusters and are implicated in the regulation of developmental processes in Actinomycetes. Mycobacterium tuberculosis possesses seven Wbl proteins. The [4Fe-4S] cluster of M. tuberculosis WhiB1 is relatively insensitive to O2 but very sensitive to nitric oxide (NO). Nitric oxide nitrosylates the WhiB1 iron-sulfur cluster and promotes DNA-binding; the apo-forms of WhiB1 also bind DNA. However, the molecular requirements for iron-sulfur cluster acquisition and for DNA-binding by WhiB1 are poorly characterized. Methods and Findings WhiB1 variants were created by site-directed mutagenesis and the abilities of the corresponding proteins to acquire an iron-sulfur cluster and/or bind to whiB1 promoter DNA were assessed. All four Cys residues (Cys9, 37, 40, and 46) in the N-terminal region of WhiB1 were required for incorporation of a [4Fe-4S] cluster, whereas a possible alternative cluster ligand Asp13 (by analogy with M. smegmatis WhiB2) was not. The C-terminal region of WhiB1 is predicted to house the DNA-binding domain of the protein consisting of a predicted β-turn (58GVWGG62) followed by two amino acid motifs (72KRRN75 and 78TKAR81) that are conserved in WhiB1 proteins. Gly residues (Gly58, 61 and 62) in the β-turn and positively-charged residues (Lys72, Arg73, Arg74, Lys79 and Arg81) in the downstream conserved regions were required for binding of WhiB1 DNA. Conclusions Site-directed mutagenesis of M. tuberculosis whiB1 and characterization of the corresponding proteins has been used to explore structure-function relationships of the NO-responsive transcription factor WhiB1. This showed that all four conserved Cys residues in the N-terminal region are required for incorporation of iron-sulfur clusters but not for DNA-binding. Analysis of variants with amino acid substitutions in the C-terminal region revealed the crucial roles played by a predicted β-turn and two conserved positively-charged motifs in facilitating DNA-binding, but not iron-sulfur cluster acquisition, by WhiB1

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Postoperative IMRT in head and neck cancer

BACKGROUND: Aim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres. Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2–48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60–70), delivered with doses per fraction of 2–2.3 Gy, respectively. RESULTS: 2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup. CONCLUSION: Surgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials

The Prostate Care Questionnaire for Carers (PCQ-C): reliability, validity and acceptability

<p>Abstract</p> <p>Background</p> <p>Patient experience is commonly monitored in evaluating and improving health care, but the experience of carers (partners/relatives/friends) is rarely monitored even though the role of carers can often be substantial. For carers to fulfil their role it is necessary to address their needs. This paper describes an evaluation of the reliability, validity and acceptability of the PCQ-C, a newly developed instrument designed to measure the experiences of carers of men with prostate cancer.</p> <p>Methods</p> <p>The reliability, acceptability and validity of the PCQ-C were tested through a postal survey and interviews with carers. The PCQ-C was posted to 1087 prostate cancer patients and patients were asked to pass the questionnaire on to their carer. Non-responders received one reminder. To assess test-retest reliability, 210 carers who had responded to the questionnaire were resent it a second time three weeks later. A subsample of nine carers from patients attending one hospital took part in qualitative interviews to assess validity and acceptability of the PCQ-C. Acceptability to service providers was evaluated based on four hospitals' experiences of running a survey using the PCQ-C.</p> <p>Results</p> <p>Questionnaires were returned by 514 carers (47.3%), and the majority of questions showed less than 10% missing data. Across the sections of the questionnaire internal consistency was high (Cronbach's alpha ranging from 0.80 to 0.89), and test-retest stability showed moderate to high stability (intraclass correlation coefficients ranging from 0.52 to 0.83). Interviews of carers indicated that the PCQ-C was valid and acceptable. Feedback from hospitals indicated that they found the questionnaire useful, and highlighted important considerations for its future use as part of quality improvement initiatives.</p> <p>Conclusions</p> <p>The PCQ-C has been found to be acceptable to carers and service providers having been used successfully in hospitals in England. It is ready for use to measure the aspects of care that need to be addressed to improve the quality of prostate cancer care, and for research.</p

Increasing response to a postal survey of sedentary patients – a randomised controlled trial [ISRCTN45665423]

BACKGROUND: A systematic review identified a range of methods, which can influence response rates. However, analysis specific to a healthcare setting, and in particular, involving people expected to be poor responders, was missing, We examined the effect of pre-warning letters on response rates to a postal survey of sedentary patients whom we expected a low rate of response. METHODS: Participants were randomised to receive a pre-warning letter or no pre-warning letter, seven days before sending the main questionnaire. The main questionnaire included a covering letter and pre-paid return envelope. After seven days, non-responders were sent a reminder letter and seven days later, another reminder letter with a further copy of the questionnaire and return envelope. RESULTS: 627 adults, with a mean age of 48 years (SD 13, range 18 to 78) of whom 69.2% (434/627) were women, were randomised. 49.0% (307/627) of patients were allocated to receive a pre-warning letter and 51.0% (320/627) no pre-warning letter, seven days in advance of posting the main questionnaire. The final response rate to the main questionnaire was 30.0% (92/307) amongst those sent a pre-warning letter and 20.9% (67/320) not sent a pre-warning letter, with an adjusted odds ratio of 1.60 (95% CI 1.1, 2.30). CONCLUSIONS: The relatively low cost method of sending a pre-warning letter had a modest impact on increasing response rates to a postal questionnaire sent to a group of patients for whom a low response rate was anticipated. Investigators should consider incorporating this simple intervention when conducting postal surveys, to reduce the potential for nonresponse bias and to increase the study power. Methods other than postal surveys may be needed however when a low response rate to postal surveys is likely