CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies

<p>Abstract</p> <p>Background</p> <p>Immunoglobulin (IG or antibody) and the T-cell receptor (TR) are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]).</p> <p>Description</p> <p>This database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I) and 1,470 on hematological tumors (Group II). Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration at <url>http://www.scchr-cigdb.jp/</url>, and the search results are freely downloadable.</p> <p>Conclusions</p> <p>The CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting annotation on IG, TR, and their epitopes. This database contains IG and TR data classified into two cancer-related groups and is able to automatically classify accumulating entries into these groups. The entries in Group I are particularly crucial for cancer immunotherapy, providing supportive information for genetic engineering of novel antibody medicines, tumor-specific TR, and peptide vaccines.</p

Effects of Genetic Mutation Sites in ADR Genes on Modern Chickens Produced and Domesticated by Artificial Selection

Associations between neurotransmitters, adrenergic receptor (ADR) mutations, and behaviors in chickens produced and domesticated by artificial selection remain unclear. This study investigates the association of neurotransmitters and ADR mutations with egg laying and cockfighting—behaviors associated with significantly different breeding backgrounds—in Shaver Brown and Shamo chickens. Accordingly, the whole sequences of nine ADR genes were determined, and nine amino acid-specific mutation sites from five genes (ADRα1A: S365G, ADRα1D: T440N, ADRα2A: D273E, ADRβ1: N443S, S445N, ADRβ3: R342C, Q404L, and P406S) were extracted. Evolutionary analysis showed that these mutations were not ancestrally derived. These results confirm that the mutations at these sites were artificially selected for domestication and are breed specific. NST population analysis confirmed a difference in the degree of genetic differentiation between the two populations in seven genes. The results further confirm differences in the degree of genetic differentiation between the two populations in Shaver Brown (ADRA1B and ADRA1D) and Shamo (ADRA1A and ADRA2B) chickens, indicating that the ADR gene differs between the two breeds. The effects of artificial selection, guided by the human-driven selection of desirable traits, are reflected in adrenaline gene mutations. Furthermore, certain gene mutations may affect domestication, while others may affect other traits in populations or individuals

Effects of Genetic Mutation Sites in ADR Genes on Modern Chickens Produced and Domesticated by Artificial Selection

Associations between neurotransmitters, adrenergic receptor (ADR) mutations, and behaviors in chickens produced and domesticated by artificial selection remain unclear. This study investigates the association of neurotransmitters and ADR mutations with egg laying and cockfighting&mdash;behaviors associated with significantly different breeding backgrounds&mdash;in Shaver Brown and Shamo chickens. Accordingly, the whole sequences of nine ADR genes were determined, and nine amino acid-specific mutation sites from five genes (ADR&alpha;1A: S365G, ADR&alpha;1D: T440N, ADR&alpha;2A: D273E, ADR&beta;1: N443S, S445N, ADR&beta;3: R342C, Q404L, and P406S) were extracted. Evolutionary analysis showed that these mutations were not ancestrally derived. These results confirm that the mutations at these sites were artificially selected for domestication and are breed specific. NST population analysis confirmed a difference in the degree of genetic differentiation between the two populations in seven genes. The results further confirm differences in the degree of genetic differentiation between the two populations in Shaver Brown (ADRA1B and ADRA1D) and Shamo (ADRA1A and ADRA2B) chickens, indicating that the ADR gene differs between the two breeds. The effects of artificial selection, guided by the human-driven selection of desirable traits, are reflected in adrenaline gene mutations. Furthermore, certain gene mutations may affect domestication, while others may affect other traits in populations or individuals

aCGH Analysis to Estimate Genetic Variations among Domesticated Chickens

Chickens have been familiar to humans since ancient times and have been used not only for culinary purposes but also for cultural purposes including ritual ceremonies and traditional entertainment. The various chicken breeds developed for these purposes often display distinct morphological and/or behavioural traits. For example, the Japanese Shamo is larger and more aggressive than other domesticated chickens, reflecting its role as a fighting cock breed, whereas Japanese Naganakidori breeds, which have long-crowing behaviour, were bred instead for their entertaining and aesthetic qualities. However, the genetic backgrounds of these distinct morphological and behavioural traits remain unclear. Therefore, the question arises as to which genomic regions in these chickens were acted upon by selective pressures through breeding. We compared the entire genomes of six chicken breeds domesticated for various cultural purposes by utilizing array comparative genomic hybridization. From these analyses, we identified 782 regions that underwent insertions, deletions, or mutations, representing man-made selection pressure in these chickens. Furthermore, we found that a number of genes diversified in domesticated chickens bred for cultural or entertainment purposes were different from those diversified in chickens bred for food, such as broilers and layers

Gender Differences in Takotsubo Syndrome

Most patients with Takotsubo Syndrome (TTS) are postmenopausal females. TTS in males is rare and gender differences have not been sufficiently investigated. Therefore, we investigated gender differences in TTS. TTS in males and females is often triggered by physical and emotional stress, respectively. Heart failure, a severe in-hospital complication, requires greater mechanical respiratory support in males. Fatal arrhythmias such as ventricular tachycardia and ventricular fibrillation and in-hospital mortality rates are higher in males. The white blood cell (WBC) count has been shown to be higher in males than in females with cardiovascular death compared with non-cardiovascular death. Therefore, the WBC count, a simple marker, may reflect severe TTS. Decreased estrogen levels, common in postmenopausal females, are a pathogenic mechanism of TTS. Females have a more significant increase in the extracellular matrix-receptor interaction than males. Moreover, the pathological findings after hematoxylin–eosin staining were different in males and females. Males had more severe complications than females in the acute phase of TTS; thus, more careful observations and interventions are likely required. From these results, it can be considered that the mechanism of the onset of TTS may be different between males and females. Therefore, it is necessary to fully understand the gender differences in order to more effectively manage TTS

The mitochondrial DNA sequence analysis of domesticated chickens and its implication to the evolutionary origin of fighting cocks

　　　This study gives clarity to the origin and evolution of domesticated chickens in Asia in view of molecular evolution. For domesticated chickens, evolution is tightly related to many aspects of human nature and culture. Because of the interest in the evolutionary process involved with such human factors, domesticated chickens have been chosen for study because of their evolutionary origin and process that has been deeply influenced by human factors.　　　Man has domesticated and bred chickens for various purposes for a long time. For example, a fighting cocks, Shamo, and long-crowing chickens, Naganakidori, are typical examples that must have been bred for the purposes of entertainment and appreciation that are part of human culture. For this reason, these two varieties of domesticated chickens are excellent materials for the study of how human culture has influenced the domestication and breeding process of animals.　　　A variey of cultural aspects of raising and keeping Shamo and Naganakidori have been observed not only in Japan but also in other Asian countries such as Thailand and China. Therefore, the understanding of the geographical origin and domestication process of Shamo and Naganakidori is one of the key issues for elucidating the relationships between human culture and its reflective breeding efforts. However, it is of prime importance to study their evolutionary origin and phylogenetic relationships using DNA sequence data, because their molecular phylogenetic relationships will be so objective and reliable as to form the bases of the discussion about domestication and breeding of chickens.　　　Chapter 1 explained the background of the studies of domesticated chickens from the viewpoint of evolutionary biology and cultural intervention. It also described the purpose and biological significance of the present study.　　　Chapter 2 focused upon the evolutionary origin of Japanese fighting cocks. A total of 42 blood samples were collected and measured three morphological traits (height, weight, and shank length) of fighting cocks, Shamo, in nine places in Japan. Moreover, in collaboration with colleagues in Myanmar and Southeast China, blood samples of domesticated chickens in their respective regions were also examined. Extracting the mitochondrial DNAs from the blood samples and sequencing their D-loop regions, phylogenetic trees of the domesticated chickens were constructed. The phylogenetic analysis has shown that the Japanese Shamo was separated into two groups: One group contained exclusively individuals from the island of Okinawa, and the other was composed of the individuals from Kyushu and Honshu islands of Japan.　　　The results of the phylogenetic analysis are consistent with that of the morphological analysis of the three traits. In particular, the Okinawa Shamo showed consistently larger values of height, weight, and shank length than the other Shamo groups studied. This observation supports that the Japanese Shamo has come frorn two separate origins. It is also known that different names are used for calling Shamo in Japan. In Okinawa, Shamo is pronounced as "taut∫i:" which is quite similar to its Chinese pronunciation. In the other parts of Japan, it is pronounced as "shamo" which is very similar to the pronunciation of the old name of "Thailand." This cultural aspect also supports the separate origins of Japanese Shamo.　　　In Chapter 3, to elucidate the evolutionary origin and the domestication process of Naganakidori, nine blood samples of this variety were collected from five places in Japan. In Japan, three varieties of Naganakidori; Koeyoshi, Totenko, Tomaru, have been bred to develop an exceptionally long crow of over 15 seconds. the mitochondrial DNA was then extracted and its D-loop region sequenced. When a molecular phylogenetic tree was constructed, it was found that all three varieties were monophyletically related. This finding is surprisingly interesting, because the three varieties are remarkably different to each other in morphological characters. Moreover, Naganakidori\u27s group is located between the group of Okinawa Shamo and the other Shamo group. It strongly suggests that Naganakidori originated from Shamo.　　　Chapters 4, on the basis of the results of Chapters 2 and 3, 34 samples from 12 varieties of the ornamental chickens were examined to understand their evolutionary origin. Then, it was found that all the ornamental chickens examined have been derived from Shamo. It strongly suggested that all Japanese domesticated chickens including the ornamental chickens and Naganakidori might have been originated from Shamo, particularly the ancestor of Okinawa Shamo. The conclusion is that the intensive pressure of artificial selection was imposed on the Shamo population that had been already established for the tradition of cockfighting in order to create novel variation of ornamental chickens, resulting in profound differentiation of Japanese varieties of domesticated chickens.　　　Chapter 5 considered the background that the original Shamo has produced Japanese domesticated chickens, from both historical and biological approaches. The conclusion is that the ancestral Shamo was brought first into Okinawa and then distributed over Japan through driving forces such as appreciation, entertainment, and competition that are certainly part of human nature and culture. 　　　Finally, it should be emphasized that this study would eventually provide basic and useful information related not only to the evolutionary process but also the important issues such as the animal protection, nature conservation, and global environments