Current Understanding of the Gut Microflora in Subjects with Nutrition-Associated Metabolic Disorder Such as Obesity and/or Diabetes : Is There Any Relevance with Oral Microflora?

Purpose of review: The oral cavity is one of the main gateways to the whole body and leads to the gastrointestinal tract. Both oral cavity and gastrointestinal tract have complex ecosystems of microorganisms called microbiota. Recent studies have showed that altered local microbiome in human, such as gut microflora, is associated with various systemic diseases. This review focuses on the association between the microbiota at local sites, such as gut and oral cavity, and the systemic diseases, especially nutrition-associated metabolic disorder, such as obesity and/or diabetes. Recent findings: The gut microbiota has a potential for regulation in host immune system and metabolisms, such as energy, glucose and lipid, and is therefore an additional contributing environmental factor to the pathophysiology of obesity and diabetes as well as gut infectious inflammatory diseases. In addition, oral microorganisms play important roles as reservoirs for exacerbation of gut diseases and altered oral microbial profiles causing periodontal diseases, one of common oral infectious diseases, has been also associated with several systemic diseases including diabetes. Summary: It is necessary to consider that impaired oral microbiota, called oral dysbiosis, may affect the metabolic disorders leading to obesity and diabetes in addition to the gut inflammatory diseases via alteration of gut microflora. The relevance of oral microflora to gut dysbiosis leading to nutrition-associated metabolic disorder should be addressed as future investigations

CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme

AbstractDNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein. Immunoblot analysis after treatment of Jurkat cells with anti-Fas antibody demonstrated the cleavage of p460 concomitantly with an increase in CPP32/Yama/apopain activity. Recombinant CPP32/Yama/apopain specifically cleaved p460 in the DNA-PK preparation that had been purified from Raji cells into 230- and 160-kDa polypeptides, the latter of which was detected in anti-Fas-treated Jurkat cells. The regulatory component Ku protein was not significantly affected by CPP32/Yama/apopain. DNA-PK activity was decreased with the disappearance of p460 in the incubation of DNA-PK with CPP32/Yama/apopain. These results suggest that the catalytic component of DNA-PK is one of the target proteins for CPP32/Yama/apopain in Fas-mediated apoptosis

Chromosome analysis of a brain malignant lymphoma cell line.

Chromosome studies of a malignant lymphoma cell line derived from the brain were made by Q- and G-banding techniques. The modal number of chromosomes was 45. Complex structural rearrangements were present, but the 14q+ marker chromosome frequently seen in malignant lymphomas was not identified in the cell line. The main karyotype in cells analyzed was 45, X, -Y, del (2) (q21q23), t (3;?) (p25;?), t (p12;?), -8, 11q+, 18q+, +mar. Absence of the 14q+ may be explained by: firstly, clones which possessed 14q+ marker chromosome in brain tumor cells may have been selected out with increasing culture time and repeated passages; or secondly, the presence of the 14q+ marker chromosome depends on the type of lymphoma

Ictal Cardiorespiratory Arrest Associated with Status Epilepticus in Panayiotopoulos Syndrome

A healthy 10-year-old boy vomited during sleep and later complained of abdominal pain; he became drowsy and uncommunicative. At the nearby hospital E.R., he deteriorated rapidly, and his respiratory movements were absent with cardiac arrest. He was immediately resuscitated. Brain MRI showed no abnormalities. EEG revealed an abnormal pattern with recurrent multifocal epileptiform activity over the bilateral occipital and frontal regions during sleep. Based on the clinical/radiological findings we diagnosed Panayiotopoulos syndrome (PS), a benign form of early-onset pediatric epilepsy characterized by autonomic symptoms. Lifethreating cardiopulmonary arrest is rare in PS, but long seizure duration of PS may associate with apnea and bradycardia

Immune response of macrophages from young and aged mice to the oral pathogenic bacterium Porphyromonas gingivalis

Periodontal disease is a chronic inflammatory gum disease that in severe cases leads to tooth loss. Porphyromonas gingivalis (Pg) is a bacterium closely associated with generalized forms of periodontal disease. Clinical onset of generalized periodontal disease commonly presents in individuals over the age of 40. Little is known regarding the effect of aging on inflammation associated with periodontal disease. In the present study we examined the immune response of bone marrow derived macrophages (BMM) from young (2-months) and aged (1-year and 2-years) mice to Pg strain 381. Pg induced robust expression of cytokines; tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, chemokines; neutrophil chemoattractant protein (KC), macrophage colony stimulating factor (MCP)-1, macrophage inflammatory protein (MIP)-1α and regulated upon activation normal T cell expressed and secreted (RANTES), as well as nitric oxide (NO, measured as nitrite), and prostaglandin E2 (PGE2) from BMM of young mice. BMM from the 2-year age group produced significantly less TNF-α, IL-6 and NO in response to Pg as compared with BMM from 2-months and 1-year of age. We did not observe any difference in the levels of IL-1β, IL-10 and PGE2 produced by BMM in response to Pg. BMM from 2-months and 1-year of age produced similar levels of all chemokines measured with the exception of MCP-1, which was reduced in BMM from 1-year of age. BMM from the 2-year group produced significantly less MCP-1 and MIP-1α compared with 2-months and 1-year age groups. No difference in RANTES production was observed between age groups. Employing a Pg attenuated mutant, deficient in major fimbriae (Pg DPG3), we observed reduced ability of the mutant to stimulate inflammatory mediator expression from BMMs as compared to Pg 381, irrespective of age. Taken together these results support senescence as an important facet of the reduced immunological response observed by BMM of aged host to the periodontal pathogen Pg

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism