Complete genome sequence and description of Salinispira pacifica gen. nov., sp. nov., a novel spirochaete isolated form a hypersaline microbial mat

During a study of the anaerobic microbial community of a lithifying hypersaline microbial mat of Lake 21 on the Kiritimati atoll (Kiribati Republic, Central Pacific) strain L21-RPul-D2(T) was isolated. The closest phylogenetic neighbor was Spirochaeta africana Z-7692(T) that shared a 16S rRNA gene sequence identity value of 90% with the novel strain and thus was only distantly related. A comprehensive polyphasic study including determination of the complete genome sequence was initiated to characterize the novel isolate. Cells of strain L21-RPul-D2(T) had a size of 0.2 - 0.25 x 8-9 mu m, were helical, motile, stained Gram-negative and produced an orange carotenoid-like pigment. Optimal conditions for growth were 35 degrees C, a salinity of 50 g/l NaCl and a pH around 7.0. Preferred substrates for growth were carbohydrates and a few carboxylic acids. The novel strain had an obligate fermentative metabolism and produced ethanol, acetate, lactate, hydrogen and carbon dioxide during growth on glucose. Strain L21-RPul-D2(T) was aerotolerant, but oxygen did not stimulate growth. Major cellular fatty acids were C-14:0, iso-C-15:0, C-16:0 and C-18:0. The major polar lipids were an unidentified aminolipid, phosphatidylglycerol, an unidentified phospholipid and two unidentified glycolipids. Whole cell hydrolysates contained L-ornithine as diagnostic diamino acid of the cell wall peptidoglycan. The complete genome sequence was determined and annotated. The genome comprised one circular chromosome with a size of 3.78 Mbp that contained 3450 protein-coding genes and 50 RNA genes, including 2 operons of ribosomal RNA genes. The DNA G + C content was determined from the genome sequence as 51.9 mol%. There were no predicted genes encoding cytochromes or enzymes responsible for the biosynthesis of respiratory lipoquinones. Based on significant differences to the uncultured type species of the genus Spirochaeta, S. plicatilis, as well as to any other phylogenetically related cultured species it is suggested to place strain L21-RPul-D2(T) (=DSM 27196(T) = JCM 18663(T)) in a novel species and genus, for which the name Salinispira pacifica gen. nov., sp. nov. is proposed

Ring closing reaction in diarylethene captured by femtosecond electron crystallography

The photoinduced ring-closing reaction in diarylethene, which serves as a model system for understanding reactive crossings through conical intersections, was directly observed with atomic resolution using femtosecond electron diffraction. Complementary ab initio calculations were also performed. Immediately following photoexcitation, subpicosecond structural changes associated with the formation of an open-ring excited-state intermediate were resolved. The key motion is the rotation of the thiophene rings, which significantly decreases the distance between the reactive carbon atoms prior to ring closing. Subsequently, on the few picosecond time scale, localized torsional motions of the carbon atoms lead to the formation of the closed-ring photoproduct. These direct observations of the molecular motions driving an organic chemical reaction were only made possible through the development of an ultrabright electron source to capture the atomic motions within the limited number of sampling frames and the low data acquisition rate dictated by the intrinsically poor thermal conductivity and limited photoreversibility of organic materials

Proposal for a new classification of a deep branching bacterial phylogenetic lineage: Transfer of Coprothermobacter proteolyticus and Coprothermobacter platensis to Coprothermobacteraceae fam. nov., within Coprothermobacterales ord. nov., Coprothermobacteria classis nov. and Coprothermobacterota phyl. nov. and emended description of the family Thermodesulfobiaceae

The genus Coprothermobacter (initially named Thermobacteroides) is currently placed within the phylum Firmicutes. Early 16S rRNA gene based phylogenetic studies pointed out the great differences between Coprothermobacter and other members of the Firmicutes, revealing that it constitutes a new deep branching lineage. Over the years, several studies based on 16S rRNA gene and whole genome sequences have indicated that Coprothermobacter is very distant phylogenetically to all other bacteria, supporting its placement in a distinct deeply rooted novel phylum. In view of this, we propose its allocation to the new family Coprothermobacteraceae within the novel order Coprothermobacterales, the new class Coprothermobacteria, and the new phylum Coprothermobacterota, and an emended description of the family Thermodesulfobiaceae.Fil: Pavan, Maria Elisa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Pavan, Esteban E.. Politecnico di Milano; ItaliaFil: Glaeser, Stefanie P.. Universitat Giessen; AlemaniaFil: Etchebehere, Claudia. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Kämpfer, Peter. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pettinari, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: López, Nancy Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Potential of doubled-haploid lines and localization of quantitative trait loci (QTL) for partial resistance to bacterial leaf streak (Xanthomonas campestris pv. hordei) in barley

Genetic variability for partial resistance to bacterial leaf streak in barley, caused by Xanthomonas campestris pv. hordei, was investigated in 119 doubled-haploid lines (DH) developed by the Hordeum bulbosum method from the F1 progeny of the cross between two cultivars, ‘Morex’ (resistant) and ‘Steptoe’ (susceptible). Two experiments were undertaken in a randomized complete block design with three replicates, in a controlled growth chamber. Twenty seeds per replicate were planted in plastic containers (60×40×8 cm) containing moistened vermiculite. At the two-leaf stage seedlings were inoculated with an Iranian strain of the pathogen. Genetic variability was observed among the 119 DH lines for partial resistance to the disease. Some DH lines were significantly more resistant than ‘Morex’ (resistant parent) to bacterial leaf streak. Genetic gain in percentage of resistant parent for 5% of the selected DH lines was significant (47.70% and 33.72% in the first and the second experiment, respectively). A QTL analysis of bacterial leaf streak resistance showed that three QTLs were detected on chromosomes 3 and 7. Multilocus allelic effects of the three QTLs account for almost 54% of the mean difference between the parents and nearly 30% of the phenotypic variation of the trait in the mean experiment. The resistance locus on chromosome 3, near ABG377, apprears to be a major gene

Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis subsp. lactis CNCM I-3446.

Non-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double-blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'- and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium-dominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum)

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

<p>Abstract</p> <p>Background</p> <p>Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week.</p> <p>Methods/design</p> <p>It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing <it>Bifidobacterium lactis </it>DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated.</p> <p>Conclusion</p> <p>This study is aimed to show that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week.</p

SMARCB1 regulates the hypoxic stress response in sickle cell trait during the pathogenesis of renal medullary carcinoma.

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SMARCB1 Regulates the Hypoxic Stress Response in Sickle Cell Trait

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies

PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS/DESIGN PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE