Kappa Gene Research Articles

Epigenetic Regulation of the Kappa Opioid Receptor by Child Abuse

BackgroundExperiences of abuse and neglect during childhood are major predictors of the emergence of depressive and suicidal behaviors throughout life. The underlying biological mechanisms, however, remain poorly understood. Here, we focused on the opioid system as a potential brain substrate mediating these effects. MethodsPostmortem samples from three brain structures regulating social bonds and emotions were analyzed. Groups were constituted of depressed individuals who died by suicide, with or without a history of severe child abuse, and of psychiatrically healthy control subjects. Expression of opioid peptides and receptors was measured using real-time polymerase chain reaction. DNA methylation, a major epigenetic mark, was investigated using targeted bisulfite sequencing and characterized at functional level using in vitro reporter assays. Finally, oxidative bisulfite sequencing was used to differentiate methylation and hydroxymethylation of DNA. ResultsA history of child abuse specifically associated in the anterior insula with a downregulation of the kappa opioid receptor (Kappa), as well as decreased DNA methylation in the second intron of the Kappa gene. In vitro assays further showed that this intron functions as a genomic enhancer where glucocorticoid receptor binding regulates Kappa expression, unraveling a new mechanism mediating the well-established interactions between endogenous opioids and stress. Finally, results showed that child abuse is associated in the Kappa intron with a selective reduction in levels of DNA hydroxymethylation, likely mediating the observed downregulation of the receptor. ConclusionsAltogether, our findings uncover new facets of Kappa physiology, whereby this receptor may be epigenetically regulated by stressful experiences, in particular as a function of early social life.

Association between diacylglycerol kinase kappa variants and hypospadias susceptibility in a Han Chinese population.

Previous genome-wide association studies have identified variants in the diacylglycerol kinase kappa (DGKK) gene associated with hypospadias in populations of European descent. However, no variants of DGKK were confirmed to be associated with hypospadias in a recent Han Chinese study population, likely due to the limited number of single-nucleotide polymorphisms (SNPs) included in the analysis. In this study, we aimed to address the inconsistent results and evaluate the association between DGKK and hypospadias in the Han Chinese population through a more comprehensive analysis of DGKK variants. We conducted association analyses for 17 SNPs in or downstream of DGKK with hypospadias among 322 cases (58 mild, 113 moderate, 128 severe, and 23 unknown) and 1008 controls. Five SNPs (rs2211122, rs4554617, rs7058226, rs7063116, and rs5915254) in DGKK were significantly associated with hypospadias (P < 0.05), with odds ratios (ORs) of 1.64–1.76. When only mild and moderate cases were compared to controls, 10 SNPs in DGKK were significant (P < 0.05), with ORs of 1.56–2.13. No significant SNP was observed when only severe cases were compared to controls. This study successfully implicated DGKK variants in hypospadias risk among a Han Chinese population, especially for mild/moderate cases. Severe forms of hypospadias are likely due to other genetic factors.

The Sea Star Ig Kappa Gene and Cancerology

The Sea Star Ig Kappa Gene and Cancerology

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

Selection of therapeutic H5N1 monoclonal antibodies following IgVH repertoire analysis in mice

The rapid rate of influenza virus mutation drives the emergence of new strains that inflict serious seasonal epidemics and less frequent, but more deadly, pandemics. While vaccination provides the best protection against influenza, its utility is often diminished by the unpredictability of new pathogenic strains. Consequently, efforts are underway to identify new antiviral drugs and monoclonal antibodies that can be used to treat recently infected individuals and prevent disease in vulnerable populations. Next Generation Sequencing (NGS) and the analysis of antibody gene repertoires is a valuable tool for Ab discovery. Here, we describe a technology platform for isolating therapeutic monoclonal antibodies (MAbs) by analyzing the IgVH repertoires of mice immunized with recombinant H5N1 hemagglutinin (rH5). As an initial proof of concept, 35 IgVH genes were selected using a CDRH3 search algorithm and co-expressed in a murine IgG2a expression vector with a panel of germline murine kappa genes. Culture supernatants were then screened for antigen binding. Seventeen of the 35 IgVH MAbs (49%) bound rH5VN1203 in preliminary screens and 8 of 9 purified MAbs inhibited 3 heterosubtypic strains of H5N1 virus when assayed by HI. Two of these MAbs demonstrated prophylactic and therapeutic activity in virus-challenged mice. This is the first example in which an NGS discovery platform has been used to isolate anti-influenza MAbs with relevant therapeutic activity.

Association Between Single Nucleotide Polymorphisms in DNA Polymerase Kappa Gene and Breast Cancer Risk in Chinese Han Population: A STROBE-Compliant Observational Study.

DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk.We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses.We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC.Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women.

In Pursuit of Genes of Glucose Metabolism

If you don't know where you're going, you might wind up someplace else—Yogi Berra My professional journey, once I accepted the fact that I would not play first base for the Chicago Cubs, was not accomplished in a straight line. I entered medical school intending to become a family physician but soon became interested in research. I took an internal medicine residency at the University of California, San Francisco (UCSF), then a long research fellowship in the nascent field of molecular biology at the National Institutes of Health (NIH), and followed that with training in clinical endocrinology at the University of Wisconsin. I spent the next fifteen years dividing my time between the clinic and laboratory at the University of Iowa. Finally, I decided to concentrate on research and spent the next twenty-three years at Vanderbilt University. For the past eleven years, I have been at the University of Iowa, where I helped establish a new diabetes research center. My research journey also had several different directions. Upon reflection, I guess I ended up “someplace else” by choice, and it certainly has been an interesting trip. It is one I unreservedly recommend.

Diagnostic value of endoscopic ultrasonography combined with detection of immunoglobulin and T-cell receptor gene rearrangements in primary gastrointestinal lymphoma

Objective To evaluate the diagnostic value of endoscopic ultrasonography (EUS) combined with detection of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in primary gastrointestinal lymphoma (PGIL). Methods From 12nd January, 2012 to 23rd May, 2014, the clinical data of 24 patients with suspicious PGIL under endoscopy (regular biopsy negative and without treatment) and underwent further EUS examination was retrospectively analyzed. All patients received EUS-guided biopsy or EUS-guided fine needle aspiration (FNA) and the tissue specimens were detected for Ig and TCR gene rearrangements. Considering biopsy result, surgical pathological diagnosis and follow-up result as gold standard, the clinical significance of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of EUS combined with Ig/TCR gene rearrangements in PGIL were explored. Results Among 24 patients, 19 patients were finally diagnosed as PGIL, which were all non-Hodgkin's lymphoma (NHL); monoclonal gene rearrangement was found in 13 cases of the 19 cases. The left five cases were not lymphoma lesions (three cases of gastritis, one case of leather stomach and one case of malignant melanoma) with no monoclonal gene rearrangement. In cases diagnosed as PGIL, 14 were B cell NHL, which included eight cases of muscosa-associated lymphoid tissue (MALT) lymphoma and six cases of diffuse large B cell lymphoma. Of which, immunoglobulin heavy chain (IgH)/immunoglobulin kappa (IgK) gene rearrangement was found in 11 cases. A total of five cases were T cell NHL including one case of anaplastic large cell lymphoma, one case of NK/T cell lymphoma and three cases of enteropathy-associated T-cell lymphomas. TCR gene rearrangement was found in two cases. Because theoretically, there was no gene rearrangement in natural killer (NK)/T cell lymphoma, so NK/T cell lymphoma was excluded from statistical analysis. The sensitivity, specificity, PPV, NPV and accuracy of EUS combined with Ig/TCR gene rearrangements detection in PGIL were 72.2%, 100.0%, 100.0%, 50.0% and 78.3%, respectively. Conclusion The detection of monoclonal gene rearrangement in tissues from EUS-guided biopsy or EUS-guided FNA had better diagnostic value in PGIL, which improved the objectivity and accuracy of lymphoma diagnosis. Key words: Gastrointestinal neoplasms; Lymphoma; Gene rearrangement; Endoscopy

Construction and bacterial expression of a recombinant single-chain antibody fragment against Wuchereria bancrofti SXP-1 antigen for the diagnosis of lymphatic filariasis.

Global programmes to eliminate lymphatic filariasis (GPELF) require mapping, monitoring and evaluation using filarial antigen diagnostic kits. To meet this objective, a functional single-chain fragment variable (ScFv) specific for filarial Wuchereria bancrofti SXP-1 (Wb-SXP-1) antigen was constructed for the diagnosis of active filarial infection, an alternative to the production of complete antibodies using hybridomas. The variable heavy chain (VH) and the variable light chain (kappa) (Vκ) genes were amplified from the mouse hybridoma cell line and were linked together with a flexible linker by overlap extension polymerase chain reaction (PCR). The ScFv construct (Vκ-Linker-VH) was expressed as a fusion protein with N-terminal His tag in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC) without the addition of reducing agents. Immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA) were used to analyse the antigen binding affinity of purified ScFv. The purified ScFv was found to recognize recombinant and native Wb-SXP-1 antigen in microfilariae (Mf)-positive patient sera. The affinity of ScFv was comparable with that of the monoclonal antibody. The development of recombinant ScFv to replace monoclonal antibody for detection of filarial antigen was achieved. The recombinant ScFv was purified, on-column refolded and its detection ability validated using field samples.

Use of Enzyme-digested Virus-like Particles as Probes for Flow Cytometric Sorting of HIV-specific Neutralizing Ab-producing B-cells

OA06.04 Background: Isolating new broadly neutralizing antibodies (bnAbs) provides fresh insights for rational HIV-1 vaccine design. Several sites of vulnerability to bnAbs are now well defined, and it is likely that additional targets exist. Virus-like particles (VLPs) that express Env trimers display all of the natural epitopes and are therefore attractive candidates for use as probes. However, VLP surfaces are also decorated with nonfunctional forms of HIV Env. Exposing VLPs to proteases clears nonfunctional Env, leaving native trimeric Env intact. The resulting “trimer-VLPs” preferentially bind to nAbs compared to non-neutralizing antibodies and therefore may have gained sufficient selective power for use as B cell probes to identify new bnAbs. Methods: PBMC from HIV-infected patients were stained with the enzyme-digested trimer-VLPs, and VLP-positive memory B cells were sorted by flow cytometry. Multiplex RT-PCR was performed on cell lysates to amplify kappa, lambda, and heavy chain genes. Cloned antibodies were assessed for neutralization breadth and potency against a panel of Env-pseudoviruses using the TZM-bl neutralization assay. Results: VLPs were used to sort B cells from the donor of the broad CD4bs antibody VRC13. The sort yielded relatives of VRC13, as well as unrelated sequences that exhibited high sequence divergence from germline VH genes and/or long CDR3 regions, which are characteristics of known bnAbs. Cloning and characterization of these Abs is ongoing. Conclusions: Unlike many previously used B cell probes, VLPs express multiple epitopes including those for trimer specific antibodies which allows for simultaneous sorting of B-cells of different specificities. Additionally, these probes are devoid of non-functional forms of Env and therefore preferentially bind to neutralizing Ab-producing B cells. VLPs therefore hold great promise for isolating novel HIV-specific bnAbs that can better inform vaccine design.

Abstract 2383: Translesion DNA synthesis by DNA polymerase kappa somatic variants found in prostate cancer

Abstract Prostate cancer is one of the most prevalent malignancies affecting men worldwide, and is the most frequent cancer among men in the USA, with an estimated 238,590 new cases and 29720 deaths in 2013 (NCI). DNA damage found in prostate cancer promotes tumor progression. Repair of DNA lesions that occur endogenously or in response to diverse genotoxic stresses is indispensable for genome integrity. DNA lesions activate checkpoint pathways that regulate specific DNA-repair mechanisms. During replication, DNA polymerases frequently encounter unrepaired DNA lesions and posses 3′→5′ exonuclease proofreading activities. Such polymerases tend to stall at sites of damage, which can lead to replication fork collapse and which, unless rescued, can eventually cause large-scale genomic rearrangements and cell death. As a preventative measure, most organisms have alternative polymerases that are capable of ‘damage tolerance’ and can synthesize past DNA lesions by a mechanism called translesion synthesis (TLS). Polymerase kappa (Polκ) a Y-family polymerase participates in the process of TLS. Current study was designed to investigate the TLS of somatic missense mutations of Polκ such as p.F155S, p.L442F, p.G154E, p.E29K, p.E449K and p.E430G found after sequence analysis of prostate tumor DNA from 30 prostate cancer patients. We studied these variants to identify the nucleotide incorporated opposite to the apurinic (AP) site template, in vitro using site-specific tetrahydrofuran (AP site analog). We report that missense somatic mutations of Polκ at p.F155S, p.L442F, p.G154E, p.E29K, p.E449K mutants significantly decreases catalytic efficiency (k(cat)/Km). The biological consequence of an unrepaired DNA lesion is determined by whether it is bypassed or not, bypassed error prone. Our results provide evidence that mutations in the polymerase kappa gene can causes interference in Translesion DNA synthesis, this interference in pol κ function may play a role in prostate tumor progression. We acknowledge to Prof. Dr. Guengerich, for providing Polκ construct. This work was supported by DOD grant PC094628, and NIH grant 8 P20 GM103518. Citation Format: Santosh Yadav, Sudurika Mukhopadhyay, Nick Makridakis. Translesion DNA synthesis by DNA polymerase kappa somatic variants found in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2383. doi:10.1158/1538-7445.AM2014-2383

A new gene in A. rubens: A sea star Ig kappa gene

The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish peroxydase) and produces an antibody anti-HRP. We previously identified a candidate Ig kappa gene corresponding to this manuscript. We show now the gene referred to as: “sea star Ig kappa gene in its specificity”.

Genomics, phylogeny and in silico analysis of mitochondrial glutathione S-transferase-kappa from the camel Camelus dromedarius

The domesticated one-humped camel, Camelus dromedarius, is one of the most important animals in the Arabian Peninsula. For most of its life, this species is exposed to both intrinsic and extrinsic genotoxic factors that cause gross DNA alterations in many organisms. GST enzymes constitute an important supergene family involved in protection against the deleterious effects of oxidative stress and xenobiotics. Cloning the camel mitochondrial GST kappa (GSTK) gene and comparing its structural similarities with different species may aid in understanding its evolutionary relics. We cloned the camel GSTK using RT-PCR. This yielded an open reading frame of 678 nucleotides, encoding a protein of 226 amino acid residues. In a comparative analysis, the cloned GSTK was used to screen orthologues from different organisms. Phylogenetic analysis demonstrated that the camel GSTK apparently evolved from an ancestral GSTK gene that predated the appearance of vertebrates, and it grouped with pig, cattle, dog, horse, human and monkey GSTKs. The calculated molecular weight of the translated ORF was 25.52 kDa and the isoelectric point was 8.4. The deduced cGSTK sequence exhibited high identity with many mammals, such as Bactrian camel (99.55%), pig, cattle and human (>74%), and lower identity with other unrelated organisms, such as frog (Xenopus tropicalis, 61%), chicken (Gallus gallus, 57%), salmon (Salmo salar, 49%), sponge (Amphimedon queenslandica, 46%), tick (Amblyomma maculatum, 45%) and roundworm (Caenorhabditis elegans, 33%). A 3D structure was built based on the crystal structure of the human and rat enzymes. The levels of cGSTK expression in five camel tissues were examined via real-time PCR. The highest level of cGSTK transcripts was found in the camel liver, followed by the testis, spleen, kidney and lung.

ANOTHER CANDIDATE IG KAPPA-LIKE GENE IN THE SEA STAR &lt;i&gt;A. RUBENS&lt;/i&gt;

In a recent paper we have shown that Ig Kappa genes (region MOPC 63, region K2), of 250 nucleotides each, were present in the sea star Asterias rubens. Two years later, a 697 nucleotide Ig Kappa chain V-V region K2 gene was accentuated.

Two Hematological Pre-Malignancies In a Pair Of Homozygous Twins Revealing Differences In Their Pre- and Postnatal Development

Prior studies have established that ALL can be present at birth. However, such inborn hematological malignancies are rare and contrast to the far more frequent hematological (pre-) malignancies, which are typically found in patients in their sixties or later. Thus, the point mutation V617F in the JAK2 gene in myeloid cells has been found to be a significant player for many chronic myeloproliferations, e.g. polycythemia vera (PCV). In fact, its prevalence in the elderly population is as high as 0.1%. In addition, studies in B-cell derived chronic lymphocytic leukemia (B-CLL) has found that this malignancy is preceded by a clinically silent phase of monoclonal B-cell lymphocytosis (MBL) in the majority of patients. In contrast to leukemic childhood twins, where a high (10-15%) concordance is thought to reflect the inborn initiating mutations, much less is known about the balance between genetics and environment for the pre-leukemic conditions mentioned above.This report relates to a pair of homozygous twins, who came to our attention when they were 73 years old in 2009. Twin A presented at a hematological department for the first time in 2005 at the age of 70 years. He had experienced a 1 h episode of amaurosis fugax and during a neurological workup mild thrombocytopenia (126x109/L), increased hematocrit (0.52) and lymphocytosis (7.95x109/L) without abnormalities in other leukocyte subsets. Immunophenotyping at this time revealed CD5/CD19/CD23+ monoclonal B-cells at the 7-8 109/L levels, but no lymphadenopathy or organomegaly. While no therapy for the latter cells has been instituted, venesectio 3-4 times /year has been deemed necessary to keep the hematocrit below 0.45. Twin B went for a checkup at his GP subsequent to the brother experiencing the above episode. He, too, was diagnosed with lymphocytosis, but his hematocrit was only slightly increased levels. No intervention has been instituted in this twin. While the extent of lymphocytosis in twin A is consistently between 5 and 10 bill/L, that of twin B remains below 5 bill/L. Remarkably, the B-cell light chain expression differed between these identical twins, with twin A being kappa- and twin B lambda positive. High-resolution arrayCGH on blood sample revealed that twin A had microdeletions on chromosome 2p11.2 involving the Ig kappa gene cluster, on chromosome 7p11.2 involving the processed pseudogene ENST00000448242, chromosome 13 involving the RB gene, and on chromosome 17 involving the azacytidine induced gene. In contrast, twin B exhibited no clear aberrations by arrayCGH. For both twins, we have performed whole exome sequencing using FACS purified T-lymphocytes as surrogate germline cells and compared to whole the BM MNC exome in order to identify mutated genes. This analysis revealed (Figure) that twin A predominantly displayed mutations, which have been related to myeloid cells in the literature, while twin B mainly exhibited alterations in genes linked to lymphoid cells. In fact, only the three genes, NTSR2, ATP2C2 and ACOX3, were altered in the BM cells and present on both twins, neither of these readily explaining the shared monoclonal B-cell disorders. Interestingly, mutations in the genes TET2 and RUNX1, which have been closely related to myeloid cells, were solely found in twin A. [Display omitted] In conclusion, we have described a pair of homozygous twins who in their seventies were diagnosed with benign monoclonal B-cell lymphocytosis (MBL) with different B-cell light chain expression. Additionally, one twin, but not the other, was found to be JAK2+ with clear polycythemia vera (PCV) features requiring frequent phlebotomies. Extensive molecular analyses including whole exome sequencing have revealed that while both twins harbored point mutation in NTSR2, ATP2C2 and ACOX3, the mutations displayed in twin A with PCV were predominantly genetic abnormalities that have been associated with the myeloid cells underlining that extensive alterations in myelopoiesis have taken place postnatally in this twin. Thus, for these two pre-leukemic conditions, while predisposition to MBL seems to be prenatal, that related to JAK2 is postnatal. Ongoing studies are aimed at discovering a link between the 3 shared genes and B-cell development in an effort to link them to BML development. Disclosures:No relevant conflicts of interest to declare.

Tumor Derived Mutations of Protein Tyrosine Phosphatase Receptor Type K Affect Its Function and Alter Sensitivity to Chemotherapeutics in Glioma

Poor prognosis and resistance to therapy in malignant gliomas is mainly due to the highly dispersive nature of glioma cells. This dispersive characteristic results from genetic alterations in key regulators of cell migration and diffusion. A better understanding of these regulatory signals holds promise to improve overall survival and response to therapy. Using mapping arrays to screen for genomic alterations in gliomas, we recently identified alterations of the protein tyrosine phosphatase receptor type kappa gene (PTPRK) that correlate to patient outcomes. These PTPRK alterations are very relevant to glioma biology as PTPRK can directly sense cell–cell contact and is a dephosphorylation regulator of tyrosine phosphorylation signaling, which is a major driving force behind tumor development and progression. Subsequent sequencing of the full length PTPRK transcripts revealed novel PTPRK gene deletion and missense mutations in numerous glioma biopsies. PTPRK mutations were cloned and expressed in PTPRK-null malignant glioma cells. The effect of these mutations on PTPRK anti-oncogenic function and their association with response to anti-glioma therapeutics, such as temozolomide and tyrosine kinase inhibitors, was subsequently analyzed using in vitro cell-based assays. These genetic variations altered PTPRK activity and its post-translational processing. Reconstitution of wild-type PTPRK in malignant glioma cell lines suppressed cell growth and migration by inhibiting EGFR and β-catenin signaling and improved the effect of conventional therapies for glioma. However, PTPRK mutations abrogated tumor suppressive effects of wild-type PTPRK and altered sensitivity of glioma cells to chemotherapy.

A TRUE “CANDIDATE IG KAPPA GENE” IN THE SEA-STAR: &lt;i&gt;ASTERIAS RUBENS&lt;/i&gt; (ECHINODERMA)

The axial organ of the sea-star Asterias rubens is a primitive immune organ. The B-like cells, when stimulated by various antigens, produce antibody substances correlated with Ig Kappa gene. A candidate Ig kappa gene (IgK chain V-IV region S107B precursor) more convincing in term of genome was shown.

Evidence of complement genes in the sea-star Asterias rubens. Comparisons with the sea urchin

The axial organ of the sea star Asterias rubens is a primitive immune organ. The B-like cells, when stimulated by various antigens, produce antibody substances correlating with Ig kappa genes, .On the other hand,component complement genes were found. For each component, one or several contigs were analyzed.It is said that Asterias forbesi, another sea-star, in earlier results, showed complement-like activity.A brief comparison with the complement system in sea urchin was performed, especially about the C3 component.

COMPLEMENT GENES IN THE ASTERIDS COMPARISONS WITH THE ECHINIDS (ECHINODERMA)

The axial organ of the sea star Asterias rubens (Asterid) is a primitive immune organ. The B-like cells, when stimulated by various antigens, produce antibody substances correlating with ig kappa genes. On the other hand, component complement genes were found. For each component, one or several contigs were analysed. It is said that Asterias forbesi, another sea-star, in earlier results, showed complement-like activity. A brief comparison with the complement system in sea urchin (Echinid) was performed, especially about the C3 component.

Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol

Naltrexone, one of four FDA-approved pharmacotherapies for alcohol dependence, has shown moderate efficacy in clinical trials. Pharmacogenetic effects have been reported such that allelic variation at the gene encoding the mu-opioid receptor (OPRM1, rs1799971) predicts naltrexone-induced blunting of the positively reinforcing effects of alcohol. However, naltrexone also binds, albeit to a lesser degree, to kappa and delta opioid receptors in the brain. This alternate binding presents the possibility that single nucleotide polymorphisms (SNPs) in the kappa and delta opioid receptor (OPRK1 and OPRD1) genes may contribute to naltrexone pharmacogenetics. Therefore, the goal of this exploratory study was to re-examine data from a double-blind placebo controlled laboratory trial of naltrexone for pharmacogenetic effects at kappa and delta opioid receptor tag SNPs. Participants were 40 heavy drinkers (12 female) who underwent an intravenous alcohol challenge paradigm after receiving naltrexone (50mg) or placebo in randomized and crossover fashion. Dependent variables were self-reported alcohol-induced stimulation, sedation, and craving. Multilevel models revealed a significant Naltrexone×OPRK1 Genotype (rs997917) interaction predicting alcohol-induced sedation, such that TT homozygotes reported lower naltrexone-induced alcohol sedation as compared to carriers of the C allele. Moreover, there was a significant Naltrexone×OPRD1 Genotype (rs4654327) interaction predicting alcohol-induced stimulation and craving, such that carriers of the A allele at this locus reported greater naltrexone-induced blunting of alcohol stimulation and alcohol craving compared to GG homozygotes. These findings suggest that additional pharmacogenetic effects in the opioid receptor system may account for individual differences in response to naltrexone in the human laboratory.