Copper Supplementation at 8 mg Neither Affects Circulating Lipids nor Liver Function in Apparently Healthy Chilean Men

There is a close relationship between selenium deficiency and Kaschin–Beck disease (KBD). Although the etiology of KBD is not known and selenium deficiency is not its actual cause, it is an important environmental risk factor. In particular, in the Qing-Tibet Plateau, a selenium-deficient region, the prevalence of KBD is serious and still increasing and continues to damage public health. By providing selenium to the population in appropriate amounts, and especially to children, KBD can be effectively controlled and prevented.     

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Alzheimer′s disease (AD) is the most common form of dementia in the elderly. Memory loss in AD is increasingly attributed to soluble oligomers of the amyloid‐β peptide (AβOs), toxins that accumulate in AD brains and target particular synapses. Glutamate receptors appear to be centrally involved in synaptic targeting by AβOs. Once bound to neurons, AβOs dysregulate the activity and reduce the surface expression of both N‐methyl‐d ‐aspartate (NMDA) and 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid (AMPA) types of glutamate receptors, impairing signaling pathways involved in synaptic plasticity. In the extracellular milieu, AβOs promote accumulation of the excitatory amino acids, glutamate and d ‐serine. This leads to overactivation of glutamate receptors, triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking AβOs to deregulated glutamate neurotransmission and implicating this as a primary mechanism of synapse failure in AD. We also discuss strategies to counteract the impact of AβOs on excitatory neurotransmission. In particular, we review evidence showing that inducing neuronal hyperpolarization via activation of inhibitory GABA_A receptors prevents AβO‐induced excitotoxicity, suggesting that this could comprise a possible therapeutic approach in AD.     

Identification and Characterization of a High-Affinity Choline Uptake System of Brucella abortus

Phosphatidylcholine (PC), a common phospholipid of the eukaryotic cell membrane, is present in the cell envelope of the intracellular pathogen Brucella abortus, the etiological agent of bovine brucellosis. In this pathogen, the biosynthesis of PC proceeds mainly through the phosphatidylcholine synthase pathway; hence, it relies on the presence of choline in the milieu. These observations imply that B. abortus encodes an as-yet-unknown choline uptake system. Taking advantage of the requirement of choline uptake for PC synthesis, we devised a method that allowed us to identify a homologue of ChoX, the high-affinity periplasmic binding protein of the ABC transporter ChoXWV. Disruption of the choX gene completely abrogated PC synthesis at low choline concentrations in the medium, thus indicating that it is a high-affinity transporter needed for PC synthesis via the PC synthase (PCS) pathway. However, the synthesis of PC was restored when the mutant was incubated in media with higher choline concentrations, suggesting the presence of an alternative low-affinity choline uptake activity. By means of a fluorescence-based equilibrium-binding assay and using the kinetics of radiolabeled choline uptake, we show that ChoX binds choline with an extremely high affinity, and we also demonstrate that its activity is inhibited by increasing choline concentrations. Cell infection assays indicate that ChoX activity is required during the first phase of B. abortus intracellular traffic, suggesting that choline concentrations in the early and intermediate Brucella-containing vacuoles are limited. Altogether, these results suggest that choline transport and PC synthesis are strictly regulated in B. abortus.     

A Ruler Protein in a Complex for Antiviral Defense Determines the Length of Small Interfering CRISPR RNAs

Small RNAs undergo maturation events that precisely determine the length and structure required for their function. CRISPRs (clustered regularly interspaced short palindromic repeats) encode small RNAs (crRNAs) that together with CRISPR-associated (cas) genes constitute a sequence-specific prokaryotic immune system for anti-viral and anti-plasmid defense. crRNAs are subject to multiple processing events during their biogenesis, and little is known about the mechanism of the final maturation step. We show that in the Staphylococcus epidermidis type III CRISPR-Cas system, mature crRNAs are measured in a Cas10·Csm ribonucleoprotein complex to yield discrete lengths that differ by 6-nucleotide increments. We looked for mutants that impact this crRNA size pattern and found that an alanine substitution of a conserved aspartate residue of Csm3 eliminates the 6-nucleotide increments in the length of crRNAs. In vitro, recombinant Csm3 binds RNA molecules at multiple sites, producing gel-shift patterns that suggest that each protein binds 6 nucleotides of substrate. In vivo, changes in the levels of Csm3 modulate the crRNA size distribution without disrupting the 6-nucleotide periodicity. Our data support a model in which multiple Csm3 molecules within the Cas10·Csm complex bind the crRNA with a 6-nucleotide periodicity to function as a ruler that measures the extent of crRNA maturation.     

Crystal structure of head-to-head dimers of cholic and deoxycholic acid derivatives with different symmetric bridges

The crystal structure of three head-to-head dimers (having two cholic acid or deoxycholic acid units) linked at carbon atoms C3 by aromatic or alkyl bridges is studied. An internal coordinates system is necessary for describing the relative orientation in the space of the two bile acid residues. Five angles (three torsion and two common ones) are necessary for defining the relative position of both steroid residues in space. Carbon atoms C3 (which always carries a α-hydroxy group in natural bile acids), and C10 and C13 (which always carry β-methyl groups) of each steroid residue are suitable for this purpose. Furthermore, the distance between each C3 carbon atoms of both steroid residues will allow one to locate the steroids in space. The three dimers selected provide a large range of values for these angles. The packing, hydrogen bond network, and location of guest in the three crystals are discussed.     

Detection of Leishmania infantum in animals and their ectoparasites by conventional PCR and real time PCR

Visceral leishmaniosis (VL) is a parasitic disease caused by Leishmania infantum, which is primarily transmitted by phlebotomine sandflies. However, there has been much speculation on the role of other arthropods in the transmission of VL. Thus, the aim of this study was to assess the presence of L. infantum in cats, dogs and their ectoparasites in a VL-endemic area in northeastern Brazil. DNA was extracted from blood samples and ectoparasites, tested by conventional PCR (cPCR) and quantitative real time PCR (qPCR) targeting the L. infantum kinetoplast DNA. A total of 280 blood samples (from five cats and 275 dogs) and 117 ectoparasites from dogs were collected. Animals were apparently healthy and not previously tested by serological or molecular diagnostic methods. Overall, 213 (76.1 %) animals and 51 (43.6 %) ectoparasites were positive to L. infantum, with mean parasite loads of 795.2, 31.9 and 9.1 fg in dogs, cats and ectoparasites, respectively. Concerning the positivity between dogs and their ectoparasites, 32 (15.3 %) positive dogs were parasitized by positive ectoparasites. The overall concordance between the PCR protocols used was 59.2 %, with qPCR being more efficient than cPCR; 34.1 % of all positive samples were exclusively positive by qPCR. The high number of positive animals and ectoparasites also indicates that they could serve as sentinels or indicators of the circulation of L. infantum in risk areas.     

Microstructural morphology in early dermal denticles of hammerhead sharks (Elasmobranchii: Sphyrnidae) and related taxa

Mello, W.C., de Carvalho, J.J., Brito, P.M.M. 2011. Microstructural morphology in early dermal denticles of hammerhead sharks (Elasmobranchii: Sphyrnidae) and related taxa. —Acta Zoologica (Stockholm) 00 : 1–7. This study uses scanning electron microscopies to investigate and describe the microstructural diversity of dermal denticles in the family Sphyrnidae, which comprises all living hammerhead shark species, comparing them to other related taxa (i.e. Carcharhinus dussumieri, Carcharhinus plumbeus, Carcharhinus acronotus, Rhizoprionodon acutus, Negaprion brevirostris and Hemigaleus microstoma). The results reveal that sphyrnids present noticeable microstructures in the dermal denticles, distinguishing them from the other related species investigated. Additionally, scale patterns are the same in three distinct body regions (i.e. cephalic, branchial and dorsal fin). Species of Sphyrnidae that reach bigger total lengths and that are widely distributed (i.e. Sphyrna lewini and Sphyrna mokarran) presented more, smaller and nearly hexagonal microstructures that do not cover the entire scale surface, unlike species reaching smaller sizes and restricted to coastal habits (i.e. Sphyrna tiburo, Sphyrna tudes, Sphyrna media and Eusphyra blochii). The sphyrnid scales are similar to R. acutus and C. dussumieri rather than to the other species, but it is not possible to identify the sphyrnid species only by scale features. It is clear that a similar morphology of scales is not necessarily related to similar life habits, and that they are candidates to provide new characters in phylogenetical studies among sphyrnids.     

Evaluating marine diets through radiocarbon dating and stable isotope analysis of victims of the AD79 eruption of vesuvius

The stable carbon (δ¹³C) and nitrogen (δ¹⁵N) isotope values of bone collagen are frequently used in paleodietary studies to assess the marine contribution to an individual's diet. Surprisingly, the relationship between stable isotope these values characteristics and the percentage of marine foods in diet has never been effectively demonstrated. To clarify this relationship, the stable isotope values and radiocarbon dates of nine humans and one sheep from Herculaneum, all who perished simultaneously during the AD 79 eruption of Vesuvius, were determined. Significant differences were found in the radiocarbon dates which are attributable to the incorporation of “old” carbon from the marine reservoir. The magnitude of the observed differences was linearly correlated with both δ¹³C and δ¹⁵N values allowing the response of each isotope to increasing marine carbon in collagen to be independently verified. Regression analyses showed that for every 1‰ enrichment in δ¹³C and δ¹⁵N, 56 years and 34 years were added to the radiocarbon age, respectively. Predictions of the maximum marine reservoir age differed considerably depending on which stable isotope was considered. This discrepancy is attributed to some degree of macronutrient scrambling whereby nitrogen from marine protein is preferentially incorporated in collagen over marine carbon. It is suggested that the macronutrient scrambling explains the observed relationship between δ¹³C and δ¹⁵N from Roman coastal sites and should be considered when interpreting any diet which is not dominated by protein. Nevertheless, without knowing the degree of macronutrient scrambling in different dietary scenarios, the accuracy of dietary reconstructions is severely compromised. Am J Phys Anthropol 152:345–352, 2013. © 2013 Wiley Periodicals, Inc.