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41.
Nara F. Nascimento Jasmin A. Hicks Karen N. Carlson Aikaterini Hatzidis Danielle N. Amaral Ryan W. Logan 《Chronobiology international》2016,33(1):108-116
Studies have shown a relationship between circadian rhythm disruptions and type-2 diabetes. This investigation examined the effects of circadian disruption (6-h phase advances) on the progression of diabetes in a type-2 diabetic mouse model –TALLYHO/JngJ – and whether wheel-running can alleviate the effects of the phase advances. 6-h advances alter fasting glucose, glucose tolerance and insulin production. Wheel-running reduced body mass, improved glucose tolerance and reduced insulin in TALLYHO/JngJ and alleviated some of the changes in diabetic symptoms due to 6-h advances. These results indicate that individuals with type-2 diabetes can benefit from physical activity and exercise can be a countermeasure to offset the effects of an acute phase advance. 相似文献
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Trost E Blom J Soares Sde C Huang IH Al-Dilaimi A Schröder J Jaenicke S Dorella FA Rocha FS Miyoshi A Azevedo V Schneider MP Silva A Camello TC Sabbadini PS Santos CS Santos LS Hirata R Mattos-Guaraldi AL Efstratiou A Schmitt MP Ton-That H Tauch A 《Journal of bacteriology》2012,194(12):3199-3215
Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ω(tox)(+) phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox(+) corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions. 相似文献
45.
Jasmin Chekidhenkuzhiyil Abdulaziz Anas P.A. Thomas Balu Tharakan Shanta Nair 《Saudi Journal of Biological Sciences》2021,28(7):3783-3788
Sponges accommodate a diverse group of microorganisms with varied metabolic capabilities. The bacterial associates of sponges are widely studied while our understanding of archaeal counterparts is scanty. In the present study, we report the archaeal associates of two sponges, Pseudoceratina purpurea (NCBI barcode: KX454492) and Cinachyra sp. (NCBI barcode: KX454495), found in the coral reef ecosystems of Gulf of Mannar, India. Archaea in the water column was predominated by members of class Halobacteria of Phylum Euryarchaeota (97%) followed by a minor fraction (3%) of Nitrosopumilus sp. of phylum Thaumarchaeota. Interestingly, Thaumarchaeota was identified as the sole archaeal population associated with the two sponges studied, among which Nitrosopumilus sp. occuppied 80 and 100% of the sequences in the clone library of P. purpurea and Cinachyra sp. respectively. Other archaea found in the P. purpurea were Nitrososphaera (10%) and unclassified ones (10%). The study identified Nitrosopumilus sp. as a unique symbiotic archaeon of sponges, P. purpurea and Cinachyra sp. The existence of host driven factors in selecting specific associates from a diverse group of archaea in the environment may need further investigations. 相似文献
46.
Excitatory amino acid transporters (EAATs) terminate glutamatergic synaptic transmission by removing glutamate from the synaptic cleft into neuronal and glial cells. EAATs are not only secondary active glutamate transporters but also function as anion channels. Gating of EAAT anion channels is tightly coupled to transitions within the glutamate uptake cycle, resulting in Na(+)- and glutamate-dependent anion currents. A point mutation neutralizing a conserved aspartic acid within the intracellular loop close to the end of transmembrane domain 2 was recently shown to modify the substrate dependence of EAAT anion currents. To distinguish whether this mutation affects transitions within the uptake cycle or directly modifies the opening/closing of the anion channel, we used voltage clamp fluorometry. Using three different sites for fluorophore attachment, V120C, M205C, and A430C, we observed time-, voltage-, and substrate-dependent alterations of EAAT3 fluorescence intensities. The voltage and substrate dependence of fluorescence intensities can be described by a 15-state model of the transport cycle in which several states are connected to branching anion channel states. D83A-mediated changes of fluorescence intensities, anion currents, and secondary active transport can be explained by exclusive modifications of substrate translocation rates. In contrast, sole modification of anion channel opening and closing is insufficient to account for all experimental data. We conclude that D83A has direct effects on the glutamate transport cycle and that these effects result in changed anion channel function. 相似文献
47.
Birte Arlt Guido Mastrobuoni Jasmin Wuenschel Kathy Astrahantseff Angelika Eggert Stefan Kempa Hedwig E. Deubzer 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1282
The small-molecule inhibitor of phosphoglycerate dehydrogenase, NCT-503, reduces incorporation of glucose-derived carbons into serine in vitro. Here we describe an off-target effect of NCT-503 in neuroblastoma cell lines expressing divergent phosphoglycerate dehydrogenase (PHGDH) levels and single-cell clones with CRISPR-Cas9-directed PHGDH knockout or their respective wildtype controls. NCT-503 treatment strongly reduced synthesis of glucose-derived citrate in all cell models investigated compared to the inactive drug control and independent of PHGDH expression level. Incorporation of glucose-derived carbons entering the TCA cycle via pyruvate carboxylase was enhanced by NCT-503 treatment. The activity of citrate synthase was not altered by NCT-503 treatment. We also detected no change in the thermal stabilisation of citrate synthase in cellular thermal shift assays from NCT-503-treated cells. Thus, the direct cause of the observed off-target effect remains enigmatic. Our findings highlight off-target potential within a metabolic assessment of carbon usage in cells treated with the small-molecule inhibitor, NCT-503. 相似文献
48.
Mala Isrie Martin Breuss Guoling Tian Andi?Harley Hansen Francesca Cristofoli Jasmin Morandell Zachari?A. Kupchinsky Alejandro Sifrim Celia?Maria Rodriguez-Rodriguez Elena?Porta Dapena Kurston Doonanco Norma Leonard Faten Tinsa Stéphanie Moortgat Hakan Ulucan Erkan Koparir Ender Karaca Nicholas Katsanis Valeria Marton Joris?Robert Vermeesch Erica?E. Davis Nicholas?J. Cowan David?Anthony Keays Hilde Van?Esch 《American journal of human genetics》2015,97(6):790-800
Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect. 相似文献
49.
Ferdinand Bohlmann Maniruddin Ahmed Jasmin Jakupovic Robert M. King Harold Robinson 《Phytochemistry》1982,21(3):691-694
An investigation of Brickellia diffusa afforded three new dehydronerolidol derivatives and five new labdane derivatives, all highly oxygenated. The structures were elucidated by spectroscopic methods and a few chemical transformations. The compounds isolated showed close relationships to those isolated from Brickellia sp. 相似文献
50.
Schmidt-Bleek K Schell H Schulz N Hoff P Perka C Buttgereit F Volk HD Lienau J Duda GN 《Cell and tissue research》2012,347(3):567-573
Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to
reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the
healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition
and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced
impaired/delayed bone healing group. In the impaired/delayed healing group, significantly higher T cell percentages were present
in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group. This was
mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory
processes. The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell
markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor. This indicates a deferred revascularization
of the injured area due to ongoing pro-inflammatory processes in the delayed healing group. Results from this study suggest
that there are unfavorable immune cells and factors participating in the initial healing phase. In conclusion, identifying
beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable
factors. 相似文献