Age, growth, mortality, and radiometric age validation of gray snapper (Lutjanus griseus) from Louisiana

The gray snapper (Lutjanus griseus) is a temperate and tropical reef fish that is found along the Gulf of Mexico and Atlantic coasts of the southeastern United States. The recreational fishery for gray snapper has developed rapidly in south Louisiana with the advent of harvest and seasonal restrictions on the established red snapper (L. campechanus) fishery. We examined the age and growth of gray snapper in Louisiana with the use of cross-sectioned sagittae. A total of 833 specimens, (441 males, 387 females, and 5 of unknown sex) were opportunistically sampled from the recreational fishery from August 1998 to August 2002. Males ranged in size from 222 to 732 mm total length (TL) and from 280 g to 5700 g total weight (TW) and females ranged from 254 to 756 mm TL and from 340 g to 5800 g TW. Both edge analysis and bomb radiocarbon analyses were used to validate otolith-based age estimates. Ages were estimated for 718 individuals; both males and females ranged from 1 to 28 years. The von Bertalanffy growth models derived from TL at age were Lt = 655.4{1–e[–0.23(t)]} for males, Lt = 657.3{1–e[– 0.21(t)]} for females, and L t = 656.4{1–e[– 0.22 (t)]} for all specimens of known sex. Catch curves were used to produce a total mortality (Z) estimate of 0.17. Estimates of M calculated with various methods ranged from 0.15 to 0.50; however we felt that M= 0.15 was the most appropriate estimate based on our estimate of Z. Full recruitment to the gray snapper recreational fishery began at age 4, was completed by age 8, and there was no discernible peak in the catch curve dome

Relativistic quasipotential equations with u-channel exchange interactions

Various quasipotential two-body scattering equations are studied at the one-loop level for the case of $t$- and $u$-channel exchange potentials. We find that the quasipotential equations devised to satisfy the one-body limit for the $t$-channel exchange potential can be in large disagreement with the field-theoretical prediction in the case of $u$-channel exchange interactions. Within the spectator model, the description of the $u$-channel case improves if another choice of the spectator particle is made. Since the appropriate choice of the spectator depends strongly on the type of interaction used, one faces a problem when both types of interaction are contained in the potential. Equal-time formulations are presented, which, in the light-heavy particle system corresponding to the mass situation of the $\pi N$ system, approximate in a reasonable way the field-theoretical result for both types of interactions.Comment: Revtex, 20 pages, 12 PostScript figures, to appear in Phys. Rev.

Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut

Solution of the Bethe-Salpeter equation for pion-nucleon scattering

A relativistic description of pion-nucleon scattering based on the four-dimensional Bethe-Salpeter equation is presented. The kernel of the equation consists of s- and u-channel nucleon and delta pole diagrams, as well as rho and sigma exchange in the t-channel. The Bethe-Salpeter equation is solved by means of a Wick rotation, and good fits are obtained to the s- and p-wave phase shifts up to 360 MeV pion laboratory energy. The coupling constants determined by the fits are consistent with the commonly accepted values in the literature.Comment: 34 pages, RevTeX; 7 figures. Several references added, a few typos corrected. Accepted for publication in Physical Review

An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription

Aire induces the expression of a large set of autoantigen genes in the thymus, driving immunological tolerance in maturing T cells. To determine the full spectrum of molecular mechanisms underlying the Aire transactivation function, we screened an AIRE-dependent gene-expression system with a genome-scale lentiviral shRNA library, targeting factors associated with chromatin architecture/function, transcription, and mRNA processing. Fifty-one functional allies were identified, with a preponderance of factors that impact transcriptional elongation compared with initiation, in particular members of the positive transcription elongation factor b (P-TEFb) involved in the release of "paused" RNA polymerases (CCNT2 and HEXIM1); mRNA processing and polyadenylation factors were also highlighted (HNRNPL/F, SFRS1, SFRS3, and CLP1). Aire's functional allies were validated on transfected and endogenous target genes, including the generation of lentigenic knockdown (KD) mice. We uncovered the effect of the splicing factor Hnrnpl on Aire-induced transcription. Transcripts sensitive to the P-TEFb inhibitor flavopiridol were reduced by Hnrnpl knockdown in thymic epithelial cells, independently of their dependence on Aire, therefore indicating a general effect of Hnrnpl on RNA elongation. This conclusion was substantiated by demonstration of HNRNPL interactions with P-TEFb components (CDK9, CCNT2, HEXIM1, and the small 7SK RNA). Aire-containing complexes include 7SK RNA, the latter interaction disrupted by HNRNPL knockdown, suggesting that HNRNPL may partake in delivering inactive P-TEFb to Aire. Thus, these results indicate that mRNA processing factors cooperate with Aire to release stalled polymerases and to activate ectopic expression of autoantigen genes in the thymu

Sex-Specific Growth and Reproductive Dynamics of Red Drum in the Northern Gulf of Mexico

The Red Drum Sciaenops ocellatus stock is heavily targeted in the Gulf of Mexico (GOM) by recreational fishers and supports a small commercial fishery in Mississippi. Despite their popularity, little recent work has been done to describe their life history. In this work, we describe sex‐specific growth and reproductive dynamics of Red Drum collected from the northern GOM from September 2016 through October 2017. We evaluated seven candidate growth models and found that the three‐parameter von Bertalanffy growth function (VBGF) was the best candidate length‐at‐age model. No significant difference in growth between sexes was observed with the three‐parameter VBGF, despite the female‐specific curve having a larger mean asymptotic length than the male‐specific curve. All seven candidate growth models predicted similar mean length‐at‐age estimates, and four of them exhibited significant differences in sex‐specific mean length at age, with females reaching a larger length at age than males after age 5. There was no significant difference between the sex‐specific weight‐at‐length relationships. Red Drum are batch spawners that spawn in northern GOM coastal waters during August and September. We estimated 3.7 d between spawns and 10.5 spawning events per female in 2017. Nearly 20% of fish collected during the spawning season were sexually mature but reproductively inactive, indicating the possibility of skipped spawning. The age at 50% maturity was around 3 years (length at 50% maturity = 670 mm TL) in both sexes, but fish were not spawning capable until age 4.5 (703 mm TL) in males and age 5.8 (840 mm TL) in females. Furthermore, elevated gonadosomatic indices were not observed until around age 5–6. The updated life history information presented in this work helps to address current data limitations and provides critical information for future assessments of Red Drum stocks in the northern GOM

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

An Epigenetic Blockade of Cognitive Functions in the Neurodegenerating Brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade

Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection