Type-specific radioimmunoassays for the gp70s of mink cell focus-inducing murine leukemia viruses: expression of a cross-reacting antigen in cells infected with the friend strain of the spleen focus-forming virus

We have isolated the gp70 of a helper-independent strain of a Friend mink cell focus-inducing (MCF) virus, Fr-MCF-1. This recombinant virus, like the previously described AKR-MCF viruses, has been shown by both biological and biochemical means to be an envelope gene recombinant between Friend murine leukemia virus (F-MuLV) and a mouse xenotropic virus. Utilizing (125)I- labeled Fr-MCF-1 gp70 and antiserum prepared against an MCF strain of Moloney type-C virus (Mol-MCF(83)), we have developed a radioimmunoassay which detects immunological determinant (s)contained in the gp70s of MCF viruses derived from F-MuLV, Mol-MuLV, and AKR-MuLV. This MCF determinant(s) is not detected in the ecotropic parents of each of these MCF viruses, nor in helper-independent murine xenotropic viruses derived from Swiss or BALB/c mice. A protein partially cross-reactive with the MCF gp70 determinant(s) is detected in a replicating xenotropic virus derived from NZB mice. Utilizing this MCF gp70 specific immunoassay, we can detect a cross-reacting gene product coded for by the Friend strain of the spleen focus-forming virus (SFFV) in rat fibroblasts nonproductively infected with SFFV. The results support earlier molecular hybridization studies which indicated that the genome of SFFV contains genetic information derived from both F-MuLV and xenotropic virus, and that the xenotropic-related sequences in SFFV are highly related to those found in MCF murine type-C viruses

The future of psychiatric research: Genomes and neural circuits

The burden of neuropsychiatric illnesses is enormous. These conditions, which include schizophrenia, mood disorders, and autism, affect thought, emotions, and a person's very sense of self. Together, they are the leading cause of disability in North America and Europe and constitute 40% of all years lost to disability. In the United States, the cost in lost earnings due to psychiatric disease is estimated conservatively to be $200 billion per year (1). The burden to individuals, families, and society is all the more tragic because these illnesses typically begin early in life, are life-long, and damage the affected individuals' self-perception, productivity, and ability to relate to others

Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder

Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case–control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 × 10−8). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD

The Anti-Proliferative Effects of the CHFR Depend on the Forkhead Associated Domain, but not E3 Ligase Activity Mediated by Ring Finger Domain

The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF) domain and is frequently downregulated in human colon and gastric cancers up to 50%. The loss of CHFR mRNA expression is a consequence of promoter methylation, suggesting a tumor suppressor role for this gene in gastrointestinal carcinogenesis. In terms of the biological functions of CHFR, it has been shown to activate cell cycle checkpoint when cells are treated with microtubule depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity and promote ubiquitination and degradation of oncogenic proteins such as Aurora A and polo-like kinase 1. However, molecular pathways involved in the tumor suppressive function of CHFR are not yet clear since the two established roles of this protein are likely to inhibit cell growth. In this study, we have identified that the FHA domain of CHFR protein is critical for growth suppressive properties, whereas the RF and cysteine rich domains (Cys) are not required for this function. In contrast, the RF and Cys domains are essential for E3 ligase activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed that the FHA domain of CHFR plays an important role in initiating a cell cycle arrest at G2/M, indicating a functional link exists between the anti-proliferative effects and checkpoint function of this tumor suppressor protein via this domain. Collectively, our data show that the checkpoint function of the FHA domain of CHFR is a core component of anti-proliferative properties against the gastrointestinal carcinogenesis

Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves

Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines

Copy number variation in schizophrenia in Sweden

Schizophrenia is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare CNVs in schizophrenia cases and identified multiple rare recurrent CNVs that increase risk of schizophrenia although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for schizophrenia CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with schizophrenia using a Swedish national sample (4,719 cases and 5,917 controls). High-confidence CNV calls were generated using genotyping array intensity data and their effect on risk of schizophrenia was measured. Our data confirm increased burden of large, rare CNVs in schizophrenia cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio=4.16, P=0.018), previously associated with autism and mental retardation but not schizophrenia. Intriguingly, gene set association analyses implicate biological pathways previously associated with schizophrenia through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500Kb) in genes present in the post-synaptic density, in genomic regions implicated via schizophrenia genome-wide association studies, and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry – genome-wide screens for CNVs, common variation, and exonic variation – are converging on similar sets of pathways and/or genes