A new family of bacterial ribosome hibernation factors.

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery3-6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon-EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.

The induction of p53 correlates with defects in the production, but not the levels, of the small ribosomal subunit and stalled large ribosomal subunit biogenesis.

Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and 60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.

The Misinformation Susceptibility Test (MIST): A psychometrically validated measure of news veracity discernment.

Interest in the psychology of misinformation has exploded in recent years. Despite ample research, to date there is no validated framework to measure misinformation susceptibility. Therefore, we introduce Verification done, a nuanced interpretation schema and assessment tool that simultaneously considers Veracity discernment, and its distinct, measurable abilities (real/fake news detection), and biases (distrust/naïvité-negative/positive judgment bias). We then conduct three studies with seven independent samples (Ntotal = 8504) to show how to develop, validate, and apply the Misinformation Susceptibility Test (MIST). In Study 1 (N = 409) we use a neural network language model to generate items, and use three psychometric methods-factor analysis, item response theory, and exploratory graph analysis-to create the MIST-20 (20 items; completion time < 2 minutes), the MIST-16 (16 items; < 2 minutes), and the MIST-8 (8 items; < 1 minute). In Study 2 (N = 7674) we confirm the internal and predictive validity of the MIST in five national quota samples (US, UK), across 2 years, from three different sampling platforms-Respondi, CloudResearch, and Prolific. We also explore the MIST's nomological net and generate age-, region-, and country-specific norm tables. In Study 3 (N = 421) we demonstrate how the MIST-in conjunction with Verification done-can provide novel insights on existing psychological interventions, thereby advancing theory development. Finally, we outline the versatile implementations of the MIST as a screening tool, covariate, and intervention evaluation framework. As all methods are transparently reported and detailed, this work will allow other researchers to create similar scales or adapt them for any population of interest.

Weight loss associated with low-energy diets with different glycaemic loads does not improve arterial stiffness: a randomised clinical trial.

We evaluated the effects of two low-energy diets with different glycaemic loads on arterial stiffness in adults with excess weight. This was a 45-day parallel-group, randomised clinical trial including seventy-five participants (20-59 years; BMI 32 kg/m2). They were assigned to two similar low-energy diets (reduction of ∼750 kcal.d-1) with macronutrient composition (55 % carbohydrates, 20 % proteins and 25 % lipids) but different glycaemic loads: high-glycaemic load (HGL 171 g.d-1; n 36) or low-glycaemic load (LGL 67 g.d-1; n 39). We evaluated: arterial stiffness (pulse wave velocity, PWV); augmentation index (AIx@75); reflection coefficient; fasting blood glucose; fasting lipid profile; blood pressure and body composition. We found no improvements in PWV (P = 0·690) and AIx@75 (P = 0·083) in both diet groups, but there was a decrease in the reflection coefficient in the LGL group (P = 0·003) compared with baseline. The LGL diet group showed reductions in body weight (Δ -4·9 kg; P = 0·001), BMI (Δ -1·6 kg/m2; P = 0·001), waist circumference (Δ -3·1 cm; P = 0·001), body fat (Δ -1·8 %; P = 0·034), as well as TAG (Δ -14·7 mg/dl; P = 0·016) and VLDL (Δ -2·8 mg/dl; P = 0·020). The HGL diet group showed a reduction in total cholesterol (Δ -14·6 mg/dl; P = 0·001), LDL (Δ -9·3 mg/dl; P = 0·029) but a reduction in HDL (Δ -3·7 mg/dl; P = 0·002). In conclusion, a 45-day intervention with low-energy HGL or LGL diets in adults with excess weight was not effective to improve arterial stiffness. However, the LGL diet intervention was associated with a reduction of reflection coefficient and improvements in body composition, TAG and VLDL levels.

RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2'-O-methylation.

RNA helicases play important roles in diverse aspects of RNA metabolism through their functions in remodelling ribonucleoprotein complexes (RNPs), such as pre-ribosomes. Here, we show that the DEAD box helicase Dbp3 is required for efficient processing of the U18 and U24 intron-encoded snoRNAs and 2'-O-methylation of various sites within the 25S ribosomal RNA (rRNA) sequence. Furthermore, numerous box C/D snoRNPs accumulate on pre-ribosomes in the absence of Dbp3. Many snoRNAs guiding Dbp3-dependent rRNA modifications have overlapping pre-rRNA basepairing sites and therefore form mutually exclusive interactions with pre-ribosomes. Analysis of the distribution of these snoRNAs between pre-ribosome-associated and 'free' pools demonstrated that many are almost exclusively associated with pre-ribosomal complexes. Our data suggest that retention of such snoRNPs on pre-ribosomes when Dbp3 is lacking may impede rRNA 2'-O-methylation by reducing the recycling efficiency of snoRNPs and by inhibiting snoRNP access to proximal target sites. The observation of substoichiometric rRNA modification at adjacent sites suggests that the snoRNPs guiding such modifications likely interact stochastically rather than hierarchically with their pre-rRNA target sites. Together, our data provide new insights into the dynamics of snoRNPs on pre-ribosomal complexes and the remodelling events occurring during the early stages of ribosome assembly.

Relationship Between Dual-Energy X-Ray Absorptiometry, Ultrasonography, and Anthropometry Methods to Estimate Muscle Mass and Muscle Quality in Older Adults.

Decreased muscle quality (MQ) may explain functional capacity impairments during aging. Thus, it is essential to verify the interaction between MQ and functional capacity in older adults. We investigated the relationship between MQ and functional capacity in older adults (n = 34; 66.3 ± 4.6 year). MQ was estimated by maximum strength of knee extensors normalized to thigh muscle mass. Maximum strength was assessed on an isokinetic dynamometer (peak torque), while dual-energy X-ray absorptiometry (DXA), ultrasonography, and anthropometry were used to determine thigh muscle mass. Functional capacity was verified by 30-s sit to stand and timed up and go tests. Significant correlations were found between MQ assessed by DXA with 30-s sit to stand (r = .35; p < .05) and timed up and go (r = -.47; p < .05), and MQ assessed by anthropometry with timed up and go (r = -.41; p < .05), but not between MQ assessed by ultrasonography with functional capacity (p > .05). No significant relationship between muscle mass with functional capacity was observed. Thus, MQ assessed by DXA and MQ assessed by anthropometry may partially explain functional capacity in older adults. Interestingly, muscle mass alone did not explain performance in functional tests in this population.

Effects of omega-3 supplementation on muscle damage after resistance exercise in young women: a randomized placebo-controlled trial.

BACKGROUND: Omega-3 is a nutritional strategie that have been used to recover muscles from exercise-induced muscle damage in a preventive perspective. AIM: To verify whether omega-3 (ω-3) supplementation after a session of resistance exercise facilitates muscle recovery in women undergoing a balanced diet. METHODS: This clinical trial was registered under the number NCT02839525. Thirty healthy women (22.2 ± 3.3 years) participated in this double-blinded, placebo-controlled trial. They were randomly distributed into ω-3 (n=15) and placebo (n=15) groups. They ingested ω-3 fish oil (3200 mg/day) or placebo (olive oil) at the dinner after the exercise bout (10 sets of 10 unilateral eccentric contractions in a knee extension chair), as well as at lunch for the three subsequent days. In addition, both groups followed a balanced diet along the four days. Muscle soreness and maximal isometric and isokinetic voluntary contractions were assessed immediately before, and 24, 48, and 72 hours after the resistance exercise. MAIN FINDINGS: There was no significant group-time interaction for any outcome. Participants presented increased levels of muscle soreness and reduced muscle strength capacity along the three days after exercise. There was no difference between placebo and ω-3 groups. CONCLUSION: Supplementation of ω-3 fish oil for three days after resistance exercise provided no additional benefits compared to placebo supplementation on recovery of healthy young women following a balanced diet.

Challenging diagnosis of chronic cerebral fungal infection: Value of (1→3)-ß-D-glucan and mannan antigen testing in cerebrospinal fluid and of cerebral ventricle puncture.

Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture.

Grazing resistance and poor food quality of a widespread mixotroph impair zooplankton secondary production.

Growing evidence suggests that global climate change promotes the dominance of mixotrophic algae especially in oligotrophic aquatic ecosystems. While theory predicts that mixotrophy increases trophic transfer efficiency in aquatic food webs, deleterious effects of some mixotrophs on consumers have also been reported. Here, using a widespread mixotrophic algal genus Dinobryon, we aimed to quantify how colonial taxa contribute to secondary production in lakes. We, therefore, studied the dietary effects of Dinobryon divergens on Cladocera (Daphnia longispina) and Copepoda (Eudiaptomus gracilis), representing two main taxonomic and functional groups of zooplankton. In feeding experiments, we showed that Dinobryon was largely grazing resistant and even inhibited the uptake of the high-quality reference food in Daphnia. Eudiaptomus could to some extent compensate with selective feeding, but a negative long-term food quality effect was also evident. Besides, Eudiaptomus was more sensitive to the pure diet of Dinobryon than Daphnia. Low lipid content and high C:P elemental ratio further supported the low nutritional value of the mixotroph. In a stable isotope approach analysing a natural plankton community, we found further evidence that carbon of Dinobryon was not conveyed efficiently to zooplankton. Our results show that the increasing dominance of colonial mixotrophs can result in reduced dietary energy transfer to consumers at higher trophic levels. In a wider perspective, global climate change favours the dominance of some detrimental mixotrophic algae which may constrain pelagic trophic transfer efficiency in oligotrophic systems, similarly to cyanobacteria in eutrophic lakes.

Transcriptome-wide analysis of exosome targets.

The exosome plays major roles in RNA processing and surveillance but the in vivo target range and substrate acquisition mechanisms remain unclear. Here we apply in vivo RNA crosslinking (CRAC) to the nucleases (Rrp44, Rrp6), two structural subunits (Rrp41, Csl4) and a cofactor (Trf4) of the yeast exosome. Analysis of wild-type Rrp44 and catalytic mutants showed that both the CUT and SUT classes of non-coding RNA, snoRNAs and, most prominently, pre-tRNAs and other Pol III transcripts are targeted for oligoadenylation and exosome degradation. Unspliced pre-mRNAs were also identified as targets for Rrp44 and Rrp6. CRAC performed using cleavable proteins (split-CRAC) revealed that Rrp44 endonuclease and exonuclease activities cooperate on most substrates. Mapping oligoadenylated reads suggests that the endonuclease activity may release stalled exosome substrates. Rrp6 was preferentially associated with structured targets, which frequently did not associate with the core exosome indicating that substrates follow multiple pathways to the nucleases.

Turnover of aberrant pre-40S pre-ribosomal particles is initiated by a novel endonucleolytic decay pathway.

Ribosome biogenesis requires more than 200 trans-acting factors to achieve the correct production of the two mature ribosomal subunits. Here, we have identified Efg1 as a novel, nucleolar ribosome biogenesis factor in Saccharomyces cerevisiae that is directly linked to the surveillance of pre-40S particles. Depletion of Efg1 impairs early pre-rRNA processing, leading to a strong decrease in 18S rRNA and 40S subunit levels and an accumulation of the aberrant 23S rRNA. Using Efg1 as bait, we revealed a novel degradation pathway of the 23S rRNA. Co-immunoprecipitation experiments showed that Efg1 is a component of 90S pre-ribosomes, as it is associated with the 35S pre-rRNA and U3 snoRNA, but has stronger affinity for 23S pre-rRNA and its novel degradation intermediate 11S rRNA. 23S is cleaved at a new site, Q1, within the 18S sequence by the endonuclease Utp24, generating 11S and 17S' rRNA. Both of these cleavage products are targeted for degradation by the TRAMP/exosome complexes. Therefore, the Q1 site defines a novel endonucleolytic cleavage site of ribosomal RNA exclusively dedicated to surveillance of pre-ribosomal particles.

Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex.

The RNA exosome complex functions in both the accurate processing and rapid degradation of many classes of RNA. Functional and structural analyses indicate that RNA can either be threaded through the central channel of the exosome or more directly access the active sites of the ribonucleases Rrp44 and Rrp6, but it was unclear how many substrates follow each pathway in vivo. We used CRAC (UV crosslinking and analysis of cDNA) in growing cells to identify transcriptome-wide interactions of RNAs with the major nuclear exosome-cofactor Mtr4 and with individual exosome subunits (Rrp6, Csl4, Rrp41 and Rrp44) along the threaded RNA path. We compared exosome complexes lacking Rrp44 exonuclease activity, carrying a mutation in the Rrp44 S1 RNA-binding domain predicted to disfavor direct access, or with multiple mutations in Rrp41 reported to impede RNA access to the central channel in vitro. Preferential use of channel-threading was seen for mRNAs, 5S rRNA, scR1 (SRP) and aborted tRNAs transcripts. Conversely, pre-tRNAs preferentially accessed Rrp44 directly. Both routes participated in degradation and maturation of RNAPI transcripts, with hand-over during processing. Rrp41 mutations blocked substrate passage through the channel to Rrp44 only for cytoplasmic mRNAs, supporting the predicted widening of the lumen in the Rrp6-associated, nuclear complex. Many exosome substrates exhibited clear preferences for a specific path to Rrp44. Other targets showed redundancy, possibly allowing the efficient handling of highly diverse RNA-protein complexes and RNA structures. Both threading and direct access routes involve the RNA helicase Mtr4. mRNAs that are predominately nuclear or cytoplasmic exosome substrates can be distinguished in vivo.

Effects of grape juice consumption on muscle fatigue and oxidative stress in judo athletes: a randomized clinical trial.

Physiological levels of reactive oxygen species (ROS) are important for intracellular and extracellular redox regulation in signaling and defense processes. Strenuous exercise can also contribute to this imbalance, and the muscle fatigue, evidenced by impaired strength or power generation, can be caused by various reasons, including oxidative stress. Antioxidants can prevent the formation of ROS by intercepting free radicals. Twenty judo athletes were included in this randomized, double-blind clinical trial into grape juice and placebo groups, and they consumed grape juice or placebo daily for 14 days in a crossover model. The outcomes were analyzed before and after combat simulations. The upper limb strength was higher in the grape juice group than in the placebo (p [group] = 0.003). The lipid damage levels were 10% higher in the placebo group (p [interaction] = 0.048). During the pre-exercise, the placebo group showed 19% more DNA damage than the grape juice group. The superoxide dismutase activity was 80% lower in the grape juice group (p [interaction] < 0.001). The consumption of grape juice can improve parameters of oxidative stress by reducing the lipid and DNA damage.

Interactions and activities of factors involved in the late stages of human 18S rRNA maturation.

Ribosome production is an essential cellular process involving a plethora of trans-acting factors, such as nucleases, methyltransferases, RNA helicases and kinases that catalyse key maturation steps. Precise temporal and spatial regulation of such enzymes is essential to ensure accurate and efficient subunit assembly. Here, we focus on the maturation of the 3' end of the 18S rRNA in human cells. We reveal that human RIO2 is an active kinase that phosphorylates both itself and the rRNA methyltransferase DIM1 in vitro. In contrast to yeast, our data confirm that human DIM1 predominantly acts in the nucleus and we further demonstrate that the 21S pre-rRNA is the main target for DIM1-catalysed methylation. We show that the PIN domain of the endonuclease NOB1 is required for site 3 cleavage, while the zinc ribbon domain is essential for pre-40S recruitment. Furthermore, we also demonstrate that NOB1, PNO1 and DIM1 bind to a region of the pre-rRNA encompassing the 3' end of 18S and the start of ITS1, in vitro. Interestingly, NOB1 is present in the cell at higher levels than other pre-40S factors. We provide evidence that NOB1 is multimeric within the cell and show that NOB1 multimerisation is lost when ribosome biogenesis is blocked. Taken together, our data indicate a dynamic interplay of key factors associated with the 3' end of the 18S rRNA during human pre-40S biogenesis and highlight potential mechanisms by which this process can be regulated.

The ribosome biogenesis factor yUtp23/hUTP23 coordinates key interactions in the yeast and human pre-40S particle and hUTP23 contains an essential PIN domain.

Two proteins with PIN endonuclease domains, yUtp24(Fcf1)/hUTP24 and yUtp23/hUTP23 are essential for early pre-ribosomal (r)RNA cleavages at sites A0, A1/1 and A2/2a in yeast and humans. The yUtp24/hUTP24 PIN endonuclease is proposed to cleave at sites A1/1 and A2/2a, but the enzyme cleaving at site A0 is not known. Yeast yUtp23 contains a degenerate, non-essential PIN domain and functions together with the snR30 snoRNA, while human hUTP23 is associated with U17, the human snR30 counterpart. Using in vivo RNA-protein crosslinking and gel shift experiments, we reveal that yUtp23/hUTP23 makes direct contacts with expansion sequence 6 (ES6) in the 18S rRNA sequence and that yUtp23 interacts with the 3΄ half of the snR30 snoRNA. Protein-protein interaction studies further demonstrated that yeast yUtp23 and human hUTP23 directly interact with the H/ACA snoRNP protein yNhp2/hNHP2, the RNA helicase yRok1/hROK1(DDX52), the ribosome biogenesis factor yRrp7/hRRP7 and yUtp24/hUTP24. yUtp23/hUTP23 could therefore be central to the coordinated integration and release of ES6 binding factors and likely plays a pivotal role in remodeling this pre-rRNA region in both yeast and humans. Finally, studies using RNAi-rescue systems in human cells revealed that intact PIN domain and Zinc finger motifs in human hUTP23 are essential for 18S rRNA maturation.

Supplementation of Probiotics and Its Effects on Physically Active Individuals and Athletes: Systematic Review.

The aim of this study was to conduct a systematic review of the effects of probiotic supplementation on physically active individuals. The participants, interventions, comparisons, outcome and study design inclusion criteria were (a) studies involving healthy adults or older subjects of both sexes who did physical exercise (including athletes and physically active individuals), (b) interventions with probiotics, (c) inclusion of a control group, (d) outcomes not previously defined, and (e) clinical trials and randomized clinical trials, with no language or date restrictions. The search was conducted in the following scientific databases: MEDLINE, Embase, SciELO, Scopus, and Lilacs. Search terms were "Probiotics" OR "Prebiotics" OR "Microbiota" AND "Exercise" OR "Athletes." The articles were first screened by title and abstract by two independent reviewers and disagreements resolved by a third reviewer. Data were extracted independently by the same two reviewers; results were extracted in duplicate and then compared to avoid errors. A total of 544 articles were retrieved and 24 were included. A total of 1,680 patients were included, most of them being male (n = 1,134, 67.5%), with a mean age of 30.9 ± 6.1 years. Following probiotic supplementation, positive effects have been reported for several outcomes including respiratory tract infection, immunologic markers, and gastrointestinal symptoms in both athletes and nonathletes. However, published studies have distinct protocols and measured outcomes, and some of them have small sample size and failed to prove beneficial effect on probiotic supplementation, leading to inconclusive results for standardized supplementation protocols.

The PIN domain endonuclease Utp24 cleaves pre-ribosomal RNA at two coupled sites in yeast and humans.

During ribosomal RNA (rRNA) maturation, cleavages at defined sites separate the mature rRNAs from spacer regions, but the identities of several enzymes required for 18S rRNA release remain unknown. PilT N-terminus (PIN) domain proteins are frequently endonucleases and the PIN domain protein Utp24 is essential for early cleavages at three pre-rRNA sites in yeast (A0, A1 and A2) and humans (A0, 1 and 2a). In yeast, A1 is cleaved prior to A2 and both cleavages require base-pairing by the U3 snoRNA to the central pseudoknot elements of the 18S rRNA. We found that yeast Utp24 UV-crosslinked in vivo to U3 and the pseudoknot, placing Utp24 close to cleavage at site A1. Yeast and human Utp24 proteins exhibited in vitro endonuclease activity on an RNA substrate containing yeast site A2. Moreover, an intact PIN domain in human UTP24 was required for accurate cleavages at sites 1 and 2a in vivo, whereas mutation of another potential site 2a endonuclease, RCL1, did not affect 18S production. We propose that Utp24 cleaves sites A1/1 and A2/2a in yeast and human cells.

Comparison of the effects of two antioxidant diets on oxidative stress markers in triathletes.

Intense exercise generates an imbalance in the redox system. However, chronic exercise can yield antioxidant adaptations. A few studies with humans have investigated the effects of antioxidant diets on athletes. Therefore we compared the effects of two dietary interventions on oxidative stress in competitive triathletes. Thirteen male triathletes were selected and divided into 2 groups: one that had a regular antioxidant diet (RE-diet) and the other that had a high antioxidant diet (AO-diet). The diet period was 14 days and blood samples were collected before and after this period. The AO-diet provided twice the dietary reference intake (DRI) of α-tocopherol (30 mg), five times the DRI of ascorbic acid (450 mg), and twice the DRI of vitamin A (1800 g), while the RE-diet provided the DRI of α-tocopherol (15 mg), twice the DRI of ascorbic acid (180 mg) and the DRI of vitamin A (900 µg). The oxidative stress parameters evaluated were: thiobarbituric acid reactive substances (TBARS), total reactive antioxidant potential (TRAP), total sulfhydryl, carbonyl, superoxide dismutase (SOD) activity, hydrogen peroxide consumption and glutathione peroxidase (GPx) activity. We observed, after the diet period, an increase in sulfhydryl, TRAP, TBARS and SOD activity, and a decrease in carbonyl levels. However, no changes were found in hydrogen peroxide consumption or GPx activity. We concluded that antioxidant-enriched diets can improve the redox status of triathletes.

Threading the barrel of the RNA exosome.

In eukaryotes, the exosome complex degrades RNA backbones and plays key roles in RNA processing and surveillance. It was predicted that RNA substrates are threaded through a central channel. This pathway is conserved between eukaryotic and archaeal complexes, even though nuclease activity was lost from the nine-subunit eukaryotic core (EXO-9) and transferred to associated proteins. The exosome cooperates with nuclear and cytoplasmic cofactors, including RNA helicases Mtr4 and Ski2, respectively. Structures of an RNA-bound exosome and both helicases revealed how substrates are channeled through EXO-9 to the associated nuclease Rrp44. Recent high-throughput analyses provided fresh insights relating exosome structure to its diverse in vivo functions. They also revealed surprisingly high degradation rates for newly synthesized RNAs, particularly RNA polymerase III transcripts.

Reproducibility of the effects of homeopathically potentised Argentum nitricum on the growth of Lemna gibba L. in a randomised and blinded bioassay.

BACKGROUND: A previous study reported a significant statistical interaction between experiment date and treatment effect of Argentum nitricum 14x-30x on the growth rate of duckweed (Lemna gibba L.). The aim of the present study was to investigate the stability of the test system and intra-laboratory reproducibility of the effects found. METHODS: Duckweed was treated with A. nitricum potencies (14x-30x) as well as succussed and unsuccussed water controls. The outcome parameter area-related growth rate for day 0-7 was determined by a computerised image analysis system in two series of independent randomised and blinded experiments. Systematic negative control (SNC) experiments were carried out to investigate test system stability. Statistical analysis was performed with full two-way analysis of variance (ANOVA) and protected Fisher's Least Significant Difference (LSD) test. RESULTS: In the first repetition series we found a significant treatment effect (p = 0.016), while in the second series no effect was observed. The negative control experiments showed that the experimental system was stable. An a posteriori subgroup analysis concerning gibbosity revealed the importance of this growth state of L. gibba for successful reproduction of the statistically significant interaction in the original study; flat: no interaction (p = 0.762); slight gibbosity: no interaction (p = 0.356); medium gibbosity: significant interaction (p = 0.031), high gibbosity: highly significant interaction (p = 0.005). CONCLUSIONS: With the original study design (disregarding gibbosity status of L. gibba) results of the original study could not be reproduced sensu stricto. We conclude that the growth state gibbosity is crucial for successful reproduction of the original study. Different physiological states of the test organisms used for bioassays for homeopathic basic research must carefully be considered.