Shifting Patterns of Nitrogen Excretion and Amino Acid Catabolism Capacity during the Life Cycle of the Sea Lamprey (\u3cem\u3ePetromyzon mariunus\u3c/em\u3e)

The jawless fish, the sea lamprey (Petromyzon marinus), spends part of its life as a burrow-dwelling, suspension-feeding larva (ammocoete) before undergoing a metamorphosis into a free swimming, parasitic juvenile that feeds on the blood of fishes. We predicted that animals in this juvenile, parasitic stage have a great capacity for catabolizing amino acids when large quantities of protein-rich blood are ingested. The sixfold to 20-fold greater ammonia excretion rates (JAmm) in postmetamorphic (nonfeeding) and parasitic lampreys compared with ammocoetes suggested that basal rates of amino acid catabolism increased following metamorphosis. This was likely due to a greater basal amino acid catabolizing capacity in which there was a sixfold higher hepatic glutamate dehydrogenase (GDH) activity in parasitic lampreys compared with ammocoetes. Immunoblotting also revealed that GDH quantity was 10-fold and threefold greater in parasitic lampreys than in ammocoetes and upstream migrant lampreys, respectively. Higher hepatic alanine and aspartate aminotransferase activities in the parasitic lampreys also suggested an enhanced amino acid catabolizing capacity in this life stage. In contrast to parasitic lampreys, the twofold larger free amino acid pool in the muscle of upstream migrant lampreys confirmed that this period of natural starvation is accompanied by a prominent proteolysis. Carbamoyl phosphate synthetase III was detected at low levels in the liver of parasitic and upstream migrant lampreys, but there was no evidence of extrahepatic (muscle, intestine) urea production via the ornithine urea cycle. However, detection of arginase activity and high concentrations of arginine in the liver at all life stages examined infers that arginine hydrolysis is an important source of urea. We conclude that metamorphosis is accompanied by a metabolic reorganization that increases the capacity of parasitic sea lampreys to catabolize intermittently large amino acid loads arising from the ingestion of protein rich blood from their prey/hosts. The subsequent generation of energy-rich carbon skeletons can then be oxidized or retained for glycogen and fatty acid synthesis, which are essential fuels for the upstream migratory and spawning phases of the sea lamprey’s life cycle

Are We Training Our Detectives? A Survey of Large Law Enforcement Agencies Regarding Investigation Training and Training Needs

In this study, a mail survey was conducted of 146 of the largest local, sheriff, and state law enforcement agencies in the United States to assess the extent and type of investigation training they receive, and to identify needs. Twenty-nine agencies (20%) responded regarding extent and training for investigators that provided references for agency training programs. Many agencies reported similar courses, delivery systems, and needs. This indicated similar central investigation tasks across agency types, and suggested standardized training courses and delivery systems would likely fit their training needs. Two promising developments concerning online training were noted

Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity

BACKGROUND: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. METHODS: Human CNS cultures were derived from 16–18 week gestation post-mortem fetal brain. Cultures were incubated with 400 μM ascorbate-2-O-phosphate (Asc-p) or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2) and astrocytic (GFAP) structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM). RESULTS: Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. CONCLUSIONS: Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

High-Resolution Spectroscopic Study of Extremely Metal-Poor Star Candidates from the SkyMapper Survey

The SkyMapper Southern Sky Survey is carrying out a search for the most metal-poor stars in the Galaxy. It identifies candidates by way of its unique filter set that allows for estimation of stellar atmospheric parameters. The set includes a narrow filter centered on the Ca II K 3933A line, enabling a robust estimate of stellar metallicity. Promising candidates are then confirmed with spectroscopy. We present the analysis of Magellan-MIKE high-resolution spectroscopy of 122 metal-poor stars found by SkyMapper in the first two years of commissioning observations. 41 stars have [Fe/H] <= -3.0. Nine have [Fe/H] <= -3.5, with three at [Fe/H] ~ -4. A 1D LTE abundance analysis of the elements Li, C, Na, Mg, Al, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, Ba and Eu shows these stars have [X/Fe] ratios typical of other halo stars. One star with low [X/Fe] [X/Fe values appears to be "Fe-enhanced," while another star has an extremely large [Sr/Ba] ratio: >2. Only one other star is known to have a comparable value. Seven stars are "CEMP-no" stars ([C/Fe] > 0.7, [Ba/Fe] < 0). 21 stars exhibit mild r-process element enhancements (0.3 <=[Eu/Fe] < 1.0), while four stars have [Eu/Fe] >= 1.0. These results demonstrate the ability to identify extremely metal-poor stars from SkyMapper photometry, pointing to increased sample sizes and a better characterization of the metal-poor tail of the halo metallicity distribution function in the future.Comment: Minor corrections to text, missing data added to Tables 3 and 4; updated to match published version. Complete tables included in sourc

Offenders' Crime Narratives across Different Types of Crimes

The current study explores the roles offenders see themselves playing during an offence and their relationship to different crime types. One hundred and twenty incarcerated offenders indicated the narrative roles they acted out whilst committing a specific crime they remembered well. The data were subjected to Smallest Space Analysis (SSA) and four themes were identified: Hero, Professional, Revenger and Victim in line with the recent theoretical framework posited for Narrative Offence Roles (Youngs & Canter, 2012). Further analysis showed that different subsets of crimes were more like to be associated with different narrative offence roles. Hero and Professional were found to be associated with property offences (theft, burglary and shoplifting), drug offences and robbery and Revenger and Victim were found to be associated with violence, sexual offences and murder. The theoretical implications for understanding crime on the basis of offenders' narrative roles as well as practical implications are discussed

Kefir ameliorates specific microbiota-gut-brain axis impairments in a mouse model relevant to autism spectrum disorder.

Abstract Autism spectrum disorder (ASD) is one of the most severe developmental disorders, affecting on average 1 in 150 children worldwide. There is a great need for more effective strategies to improve quality of life in ASD subjects. The gut microbiome has emerged as a potential therapeutic target in ASD. A novel modulator of the gut microbiome, the traditionally fermented milk drink kefir, has recently been shown to modulate the microbiota and decrease repetitive behaviour, one of the hallmarks of ASD, in mice. As such, we hypothesized that kefir could ameliorate behavioural deficits in a mouse model relevant to ASD; the BTBR T+ Itpr3tf/J mouse strain. To this end, adult mice were administered either kefir (UK4) or a milk control for three weeks as treatment lead-in, after which they were assessed for their behavioural phenotype using a battery of tests. In addition, we assessed systemic immunity by flow cytometry and the gut microbiome using shotgun metagenomic sequencing. We found that indeed kefir decreased repetitive behaviour in this mouse model. Furthermore, kefir prolonged stress-induced increases in corticosterone 60 min post-stress, which was accompanied by an ameliorated innate immune response as measured by LY6Chi monocyte levels. In addition, kefir increased the levels of anti-inflammatory Treg cells in mesenteric lymph nodes (MLNs). Kefir also increased the relative abundance of Lachnospiraceae bacterium A2, which correlated with reduced repetitive behaviour and increased Treg cells in MLNs. Functionally, kefir modulated various predicted gut microbial pathways, including the gut-brain module S-Adenosylmethionine (SAM) synthesis, as well as L-valine biosynthesis and pyruvate fermentation to isobutanol, which all correlated with repetitive behaviour. Taken together our data show that kefir modulates peripheral immunoregulation, can ameliorate specific ASD behavioural dysfunctions and modulates selective aspects of the composition and function of the gut microbiome, indicating that kefir supplementation might prove a viable strategy in improving quality of life in ASD subjects