Increase in carbon dioxide accelerates the performance of endurance exercise in rats

Abstract

Endurance exercise generates CO₂ via aerobic metabolism; however, its role remains unclear. Exogenous CO₂ by transcutaneous delivery promotes muscle fibre-type switching to increase endurance power in skeletal muscles. Here we determined the performance of rats running in activity wheels with/without transcutaneous CO₂ exposure to clarify its effect on endurance exercise and recovery from muscle fatigue. Rats were randomised to control, training and CO₂ groups. Endurance exercise included activity-wheel running with/without transcutaneous CO₂ delivery. Running performance was measured after exercise initiation. We also analysed changes in muscle weight and muscle fibres in the tibialis anterior muscle. Running performance improved over the treatment period in the CO₂ group, with a concomitant switch in muscle fibres to slow-type. The mitochondrial DNA content and capillary density in the CO₂ group increased. CO₂ was beneficial for performance and muscle development during endurance exercise: it may enhance recovery from fatigue and support anabolic metabolism in skeletal muscles.

http://ift.tt/2t4Yvnc

Disease modeling in genetic kidney diseases: mice

Abstract

The mouse still represents arguably the most important mammal organism in research for modeling human genetic kidney diseases in vivo. Compared with many other mammal species, the breeding and maintenance of mice in the laboratory is relatively simple and cheap and reproduction cycles are short. In addition to classic gene knockout mouse lines, new molecular biological technologies have led to the development of a plethora of other, more sophisticated, mouse models, allowing the targeting of genes or gene function in a cell-specific, tissue-specific and time-dependent fashion. With the refinement of more recently developed genome-editing technologies, including the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system and other engineered nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), our "tool set" of mouse models is expected to rapidly expand. These technological advances hold great promise and should enable us to study and hence understand the biology of inherited kidney diseases in greater detail. By analogy, we may be able to answer questions regarding the impact of individual proteins on the development of human kidney disorders, the underlying mechanisms governing the evolution of the disease and the predicted responsiveness to therapeutic interventions. Moreover, knockout and transgenic mouse models can be highly informative with respect to the effects of genetic variations on renal phenotypes. This review focuses on mouse models that have been devised primarily to study monogenic human kidney diseases, which are typically caused by a single abnormal gene and passed on in a Mendelian pattern. Despite the large number of human hereditary kidney disorders and the multitude of mouse models described in the literature, we attempt to give a balanced overview of several well-known renal pathologies, a few of which are addressed in some detail.

http://ift.tt/2so70gr

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer

Summary

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient's immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.

http://ift.tt/2rfYaN1

Bradyrhizobium sacchari sp. nov., a legume nodulating bacterium isolated from sugarcane roots

Abstract

Members of the genus Bradyrhizobium are well-known as nitrogen-fixing microsymbionts of a wide variety of leguminous species, but they have also been found in different environments, notably as endophytes in non-legumes such as sugarcane. This study presents a detailed polyphasic characterization of four Bradyrhizobium strains (type strain BR 10280^T), previously isolated from roots of sugarcane in Brazil. 16S rRNA sequence analysis, multilocus sequence analysis (MLSA) and analysis of the 16S-23S rRNA internal transcribed spacer showed that these strains form a novel clade close to, but different from B. huanghuaihaiense strain CCBAU 23303^T. Average nucleotide identity (ANI) analyses confirmed that BR 10280^T represents a novel species. Phylogenetic analysis based on nodC gene sequences also placed the strains close to CCBAU 23303^T, but different from this latter strain, the sugarcane strains did not nodulate soybean, although they effectively nodulated Vigna unguiculata, Cajanus cajan and Macroptilium atropurpureum. Physiological traits are in agreement with the placement of the strains in the genus Bradyrhizobium as a novel species for which the name Bradyrhizobium sacchari sp. nov. is proposed.

http://ift.tt/2t5bwNo

Resurrection and emendation of the Hypoxylaceae, recognised from a multigene phylogeny of the Xylariales

Abstract

A multigene phylogeny was constructed, including a significant number of representative species of the main lineages in the Xylariaceae and four DNA loci the internal transcribed spacer region (ITS), the large subunit (LSU) of the nuclear rDNA, the second largest subunit of the RNA polymerase II (RPB2), and beta-tubulin (TUB2). Specimens were selected based on more than a decade of intensive morphological and chemotaxonomic work, and cautious taxon sampling was performed to cover the major lineages of the Xylariaceae; however, with emphasis on hypoxyloid species. The comprehensive phylogenetic analysis revealed a clear-cut segregation of the Xylariaceae into several major clades, which was well in accordance with previously established morphological and chemotaxonomic concepts. One of these clades contained Annulohypoxylon, Hypoxylon, Daldinia, and other related genera that have stromatal pigments and a nodulisporium-like anamorph. They are accommodated in the family Hypoxylaceae, which is resurrected and emended. Representatives of genera with a nodulisporium-like anamorph and bipartite stromata, lacking stromatal pigments (i.e. Biscogniauxia, Camillea, and Obolarina) appeared in a clade basal to the xylarioid taxa. As they clustered with Graphostroma platystomum, they are accommodated in the Graphostromataceae. The new genus Jackrogersella with J. multiformis as type species is segregated from Annulohypoxylon. The genus Pyrenopolyporus is resurrected for Hypoxylon polyporus and allied species. The genus Daldinia and its allies Entonaema, Rhopalostroma, Ruwenzoria, and Thamnomyces appeared in two separate subclades, which may warrant further splitting of Daldinia in the future, and even Hypoxylon was divided in several clades. However, more species of these genera need to be studied before a conclusive taxonomic rearrangement can be envisaged. Epitypes were designated for several important species in which living cultures and molecular data are available, in order to stabilise the taxonomy of the Xylariales.

http://ift.tt/2sdhlft

Knockout of pprM Decreases Resistance to Desiccation and Oxidation in Deinococcus radiodurans

Abstract

Deinococcus radiodurans has attracted a great interest in the past decades due to its extraordinary resistance to ionizing radiation and highly efficient DNA repair system. Recent studies indicated that pprM is a putative pleiotropic gene in D. radiodurans and plays an important role in radioresistance and antioxidation, but its underlying mechanisms are poorly elucidated. In this study, pprM mutation was generated to investigate resistance to desiccation and oxidative stress. The result showed that the survival of pprM mutant under desiccation was markedly retarded compared to the wild strain from day 7–28. Furthermore, knockout of pprM increases the intercellular accumulation of ROS and the sensibility to H₂O₂ stress in the bacterial growth inhibition assay. The absorbance spectrum experiment for detecting the carotenoid showed that deinoxanthin, a carotenoid that peculiarly exists in Deinococcus, was reduced in the pprM mutant in the pprM mutant. Quantitative real time PCR showed decreased expression of three genes viz. CrtI (DR0861, 50%),CrtB (DR0862, 40%) and CrtO (DR0093, 50%), which are involved in deinoxanthin synthesis, and of Dps (DNA protection during starving) gene (DRB0092) relevant to ion combining and DNA protection in cells. Our results suggest that pprM may affect antioxidative ability of D. radiodurans by regulating the synthesis of deinoxanthin and the concentration of metal ions. This may provide new clues for the treatment of antioxidants.

http://ift.tt/2sMQ00R

Diagnostic and prognostic efficacy of Von Willebrand factor and Clara cell in traumatic lung injury

Abstract

Background

Chest injury is one of the most frequent causes of death and complications in different societies. The search for a marker of lung injury is desirable for diagnosis and prognosis. This study was conducted to assess the serum level of Von Willebrand factor (VWF) and Clara cell secretory protein (CC16) as biomarker in traumatic lung injuries for diagnostic and prognostic significance.

Methods

We evaluated the demographic data of all patients of chest injury presenting to the department. Mode of injury, any intervention, and outcome were evaluated. The level of the VWF and CC16 was assessed as per protocol.

Results

The duration of this study was 1 year. The total number of patients was 96. The mean age of patients was 40.84 ± 9.89 (range 14–70 years). Male to female ratio was 5.4:1. There was a statistically significant association of VWF with diagnosis of patient. Markedly elevated levels of VWF were associated with high mortality rates (p = 0.002). The level of VWF was markedly raised in patient having duration of hospital stay more than 2 weeks (p = 0.001). There was a statistically significant association of CC16 with diagnosis of patient. Markedly elevated level of CC16 was associated with high mortality rates (p = 0.001). The level of CCI6 was markedly raised in patients having duration of hospital stay more than 2 weeks (p = 0.001).

Conclusion

VWF and CC16 appear to be useful markers for thoracic trauma. They may also be helpful for the prognosis of the patient. Further studies evaluating their role may substantiate our efforts.

http://ift.tt/2t4Bocs