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AbstractInfectious disease remains one of the major impediments to the growth and sustainability of shrimp farming worldwide. Despite extensive efforts, including surveillance and diagnostic testing, movement of infected broodstock and post-larvae across countries and continents has been a primary driver of disease introduction into new geographic locations. Often the etiology of a disease and diagnostic tools used to prevent its spread were developed only after the disease was detected somewhere new. From the 1970s to the mid-1990s, disease diagnosis in shrimp hatcheries and farms depended on clinical presentation, farm records, histopathology, and traditional microbial culture techniques for bacterial and fungal pathogens; followed by characterization of the isolated microbes. For viral pathogens, histopathology and electron microscopy were the primary tools for disease discovery and basic characterization since there was (and still is) no immortal cell line for crustaceans. In the late 1990s and early 2000s, molecular techniques supporting genomic characterization of pathogens and polymerase chain reaction (PCR)-based diagnostic tools started gaining momentum in the realm of pathogen discovery and disease diagnosis. The late 2000s saw rapid development of molecular diagnostic tools for a wide array of shrimp pathogens and today PCR-based assays have become the most widely relied upon methods of disease diagnosis and surveillance in the shrimp industry. Molecular diagnostics have a number of strengths, including high sensitivity, specificity, speed, and robustness, but like every modality, also have limitations. PCR-based diagnostics detect only those pathogens being targeted and fail to detect unknown pathogens or even newly emerged strains or genotypes of a known target pathogen. Beyond the presence or absence of a target pathogen, PCR-based diagnostics do not provide information about overall health status or disease state of an animal. Progressive over reliance on molecular diagnostics and concurrent neglect of histopathology is creating unforeseeable challenges for shrimp farming worldwide. In this commentary, we provide empirical evidence of how overreliance on PCR-based diagnostics can lead to erroneous diagnoses and failure to detect a new genotype of an existing World Organization for Animal Health (WOAH, Paris, France)-listed pathogen, and an emerging pathogen. These findings illustrate the risks of over reliance on a single methodological approach and emphasize the need to preserve the practice of pairing molecular diagnostics with conventional histopathology. Concurrent utilization of histopathology and molecular diagnostics are critical components of safeguarding the global shrimp farming industry by reducing detection failures of new or rapidly evolving pathogens, improving disease detection and identification, and improving animal health management practices. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified a genetic variant at a locus on chromosome 1p13 that is associated with reduced risk of myocardial infarction, reduced plasma levels of LDL cholesterol [...]

Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sorf7 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes., MI is the leading cause of death in the developed world. LDL-C is a causal risk factor for the disease, as demonstrated by the increased and early burden of MI [...]

Neurotrophin binding to the p75 neurotrophin receptor ([p75.sup.NTR]) activates neuronal apoptosis following adult central nervous system injury, but the underlying cellular mechanisms remain poorly defined. In this study, we show that the proform of nerve growth factor (proNGF) induces death of retinal ganglion cells in adult rodents via a [p75.sup.NTR]-dependent signaling mechanism. Expression of [p75.sup.NTR] in the adult retina is confined to Muller glial cells; therefore we tested the hypothesis that proNGF activates a non-cell-autonomous signaling pathway to induce retinal ganglion cell (RGC) death. Consistent with this, we show that proNGF induced robust expression of tumor necrosis factor alpha (TNF[alpha]) in Muller cells and that genetic or biochemical ablation of TNF[alpha] blocked proNGF-induced death of retinal neurons. Mice rendered null for [p75.sup.NTR], its coreceptor sortilin, or the adaptor protein NRAGE were defective in proNGF-induced glial TNF[alpha] production and did not undergo proNGF-induced retinal ganglion cell death. We conclude that proNGF activates a non-cell-autonomous signaling pathway that causes [TNF.sub.[alpha]]-dependent death of retinal neurons in vivo. doi/10.1073/pnas.0909276107

The testis brain RNA-binding protein (TB-RBP) functions as an RNA-binding protein in brain and testis, binding to conserved sequence elements present in specific mRNAs, such as protamine I and 2. We show here by RNA gel shift assays, immunoprecipitation, and by a novel in situ hybridization immunohistochemical technique that TB-RBP binds to AKAP4 mRNA in male mouse germ cells. AKAP4 is a component of the fibrous sheath and functions as a scaffolding protein in the sperm flagellum. AKAP4 is encoded by an X-linked gene, is expressed solely in postmeiotic (haploid) male germ cells, and is an essential protein in all spermatozoa, requiring its transport between spermatids as a protein or mRNA. AKAP4 mRNA forms a complex with TB-RBP and the Ter ATPase in nuclei and remains associated with these proteins as it exits nuclei into the cytoplasm and as it passes through intercellular bridges between spermatids. A similar mRNA-TB-RBP-Ter ATPase association is seen for protamine 2 mRNA, which is stored in the cytoplasm of postmeiotic germ cells about 7 days before translation. In contrast, no association is seen with PGK-2 mRNA which is initially transcribed early in meiosis with increased transcription in postmeiotic male germ cells. Although PGK-2 mRNA is subject to translational control, it lacks TB-RBP-binding sequences in its mRNA. The AKAP4 or protamine 2 mRNA-protein complexes dissociate in late-stage male germ cells when the mRNAs are translated. We propose that TB-RBP and the Ter ATPase are part of a complex that accompanies specific mRNAs in haploid mouse male germ cells in intracellular and intercellular movement. The temporal relationship of TB-RBP binding and mRNA inactivation in conjunction with the subsequent dissociation of the mRNA-protein complex at the time of mRNA translation suggests a role in translational suppression and/or mRNA stabilization. Key Words: testis; male germ cells; mRNA movement.

The genetically haploid spermatids are functionally diploid as a result of the sharing of gene products through their intercellular bridges. This movement of molecules among haploid cells is crucial for the production of spermatozoa since numerous essential proteins are encoded on sex chromosomes. Testis-brain RNA-binding protein (TB-RBP) is a single-stranded DNA- and RNA-binding protein prominent in the nuclei and cytoplasm of specific stages of differentiating male germ cells. Here we present evidence that TB-RBP moves from the nucleus to the cytoplasm and through intercellular bridges of male germ cells. based on its RNA-binding capabilities, we propose a role for TB-RBP in the distribution of equal amounts of mRNAs in haploid male germ cells. Key Words: spermatogenesis; RNA-binding proteins; haploid gene expression; mRNA movement.

In situ hybridization and Northern blot analysis of the sequence and functions of the rat perforatorium protein PERF 15 isolated from a testicular lambda-gt11 phage cDNA library reveals that PERF 15 is a member of the fatty acid binding protein family with 58%, 47% and 61% sequence identity with adipocyte and heart fatty acid binding proteins, and myelin P2, respectively. The protein associates with the acrosomal membrane to mediate the stability and structural modulation of acrosomes. The amino acid sequence homology between myelin P2 and PERF 15 indicates that both proteins contribute to experimental autoimmune neuritis.