The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across the Human Genome

Chromatin structure plays an important role in modulating the accessibility of genomic DNA to regulatory proteins in eukaryotic cells. We performed an integrative analysis on dozens of recent datasets generated by deep-sequencing and high-density tiling arrays, and we discovered an array of well-positioned nucleosomes flanking sites occupied by the insulator binding protein CTCF across the human genome. These nucleosomes are highly enriched for the histone variant H2A.Z and 11 histone modifications. The distances between the center positions of the neighboring nucleosomes are largely invariant, and we estimate them to be 185 bp on average. Surprisingly, subsets of nucleosomes that are enriched in different histone modifications vary greatly in the lengths of DNA protected from micrococcal nuclease cleavage (106–164 bp). The nucleosomes enriched in those histone modifications previously implicated to be correlated with active transcription tend to contain less protected DNA, indicating that these modifications are correlated with greater DNA accessibility. Another striking result obtained from our analysis is that nucleosomes flanking CTCF sites are much better positioned than those downstream of transcription start sites, the only genomic feature previously known to position nucleosomes genome-wide. This nucleosome-positioning phenomenon is not observed for other transcriptional factors for which we had genome-wide binding data. We suggest that binding of CTCF provides an anchor point for positioning nucleosomes, and chromatin remodeling is an important component of CTCF function

Development and Disease: How Susceptibility to an Emerging Pathogen Changes through Anuran Development

Ranaviruses have caused die-offs of amphibians across the globe. In North America, these pathogens cause more amphibian mortality events than any other pathogen. Field observations suggest that ranavirus epizootics in amphibian communities are common during metamorphosis, presumably due to changes in immune function. However, few controlled studies have compared the relative susceptibility of amphibians to ranaviruses across life stages. Our objectives were to measure differences in mortality and infection prevalence following exposure to ranavirus at four developmental stages and determine whether the differences were consistent among seven anuran species. Based on previous studies, we hypothesized that susceptibility to ranavirus would be greatest at metamorphosis. Our results did not support this hypothesis, as four of the species were most susceptible to ranavirus during the larval or hatchling stages. The embryo stage had the lowest susceptibility among species probably due to the protective membranous layers of the egg. Our results indicate that generalizations should be made cautiously about patterns of susceptibility to ranaviruses among amphibian developmental stages and species. Further, if early developmental stages of amphibians are susceptible to ranaviruses, the impact of ranavirus epizootic events may be greater than realized due to the greater difficulty of detecting morbid hatchlings and larvae compared to metamorphs

Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies

International audienceAbstractGastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host–pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host–pathogen interactions may help to identify novel prevention and control strategies

EFFECTS OF GUARANA COMPARED TO MATCHED DOSE CAFFEINE: EXERCISE PERFORMANCE BENEFITS?

Alec Harp1, Eduardo Marcedo Penna2, Brian Hack1, Tyler Talik1, Mindy Millard-Stafford, FACSM1. 1Georgia Institute of Technology, Atlanta, GA. 2Federal University of Pará, Belem. BACKGROUND: Effects of guarana (Paullinia cupana) seed extract, a Brazilian plant containing caffeine but with additional bioactive compounds, has been observed to positively affect cognitive tasks but evidence on exercise performance is limited. The purpose of this study was to assess acute effects of guarana (GUA) compared to a matched dose of caffeine (CAF) on exercise performance. METHODS: Eleven endurance athletes (age: 20 ± 4.7 y, ht: 180.2 ± 7.2 cm, body mass: 73.9 ± 8.8 kg, V̇O2max: 54.6 ± 7.8 ml/kg/min) participated in a randomized, double-blind, crossover experiment. All subjects completed three trials ingesting capsules containing: 1) 100 mg CAF; 2) 100 mg GUA, or 3) placebo (P) 60-min prior to a 75-min cycling trial (fixed load 60-min steady state [SS] + self-paced 15-min time trial [TT]). Maximal isometric quadriceps strength was assessed before and after cycling. RESULTS: During SS, no differences (p \u3e0.05) in oxygen consumption (15 min blocks averaging ~70-75% V̇O2max), heart rate (HR), or respiratory exchange ratio (RER) were observed among trials. During SS, blood glucose tended to be higher (p=0.13) with CAF (4.6 ± 0.5 mmol) versus P (4.4 ± 0.4 mmol), and lactate higher (p=0.054) with GUA (2.7 ± 1.0 mmol) versus P (2.2 ± 0.9 mmol). During the TT, %HRpeak, (96.3 ± 2.3 vs. 94.1± 2.2 bt/min) and %V̇O2max (93.3 ± 8.6 vs. 89.1 ± 7.6%) tended to be higher (p=0.053, p= 0.11) with GUA versus P, respectively. Mean power was 6% higher (p=0.012) (269.4 ± 47.1 vs. 253.8 ± 51.5 W) averaged over the TT and 4% more work accumulated (241.3 ± 39.9 vs. 232.1 ± 46.6 kJ) with GUA vs. P, respectively. Post-exercise strength loss was not attenuated with GUA (-5.6% ± 8.5) or CAF (-8.3% ± 9.4) compared to P (-10.3% ± 5.1). An order effect was not found (p=0.88) for total work across trial 1 (236.2 ± 42.4 kJ), trial 2 (233.6 ± 46.2 kJ), and trial 3 (235.9 ± 41.1 kJ). CONCLUSION: High intensity cycling performance following ingestion of GUA is improved compared to P but not different from CAF. The potential ergogenicity of GUA does not appear related to changes in substrate oxidation or the maintenance of muscle strength related to fatigue and merits further investigation. Supported in part by the Fulbright Scholar Fellowship Program

ACUTE EFFECTS OF GUARANA INGESTION COMPARED TO MATCHED DOSE CAFFEINE: MENTAL PERFORMANCE BENEFITS?

Tyler N. Talik1, Mindy Millard-Stafford, FACSM1, Brian Hack1, Alec Harp1, Eduardo Macedo Penna2. 1Georgia Institute of Technology, Atlanta, GA. 2Federal University of Pará, Belem. BACKGROUND: Effects of guarana (Paullinia cupana) seed extract, a Brazilian plant containing caffeine but with additional bioactive compounds, has been observed to potentially improve cognitive performance and mood, particularly under fatiguing conditions. Our purpose was to assess the effects of acute ingestion of guarana (GUA) compared to a matched dose of caffeine (CAF) on cognitive function and mood in endurance athletes before and after high-intensity exercise. METHODS: Eleven endurance-trained athletes (age: 20 ± 4.7 y, height: 180.2 ± 7.2 cm, body mass: 73.9 ± 8.8 kg, V̇O2max: 54.6 ± 7.8 ml/kg/min) participated in a randomized, double-blind, crossover experiment. All subjects completed three trials ingesting capsules containing: 1) 100 mg CAF, 2) 100 mg GUA or 3) placebo (P). Cognitive and mood tests were performed at baseline (pre-ingestion), 60 min post-ingestion of capsules, then again after cycling (60-min steady state at ~70% V̇O2max [SS] + 15-min maximal effort time trial). Accuracy (% correct responses) and reaction time (RT) were recorded on Simon Task (interference/conflict resolution) and N-Back Task (working memory) followed by NASA Task Load (mental workload) and Brunel Mood Scales (fatigue and other subscales). RESULTS: Accuracy was not affected (p \u3e 0.05) by capsule treatment or time (pre-versus post-ingestion or post-exercise) for both cognitive tests. RT was only affected (p = 0.03) by time: faster post-exercise compared to pre-ingestion on the N-Back test. Neither capsule treatment nor time of measurement influenced (p \u3e 0.05) mental workload or mood subscales. During the last 10 min of SS, there was a significant interaction effect (p = 0.042) for ratings of perceived exertion (Borg Scale): ratings were lower for GUA (14.0 ± 1.0) versus CAF (15.0 ± 1.0) and tended to be lower than P (14.8 ± 1.4). CONCLUSION: Neither guarana nor a matched dose of caffeine influenced cognitive performance or mood before or after fatiguing exercise. However, guarana appeared to reduce the perceived effort for endurance-trained athletes toward the late stage of moderate-to-vigorous intensity exercise. These findings merit additional investigation to determine whether acute guarana ingestion can attenuate fatigue in different populations (clinical, sedentary, athletic individuals). Supported in part by the Fulbright Scholar Fellowship Progra