Protein degradation-associated mechanisms that are affected in Alzheimer´s disease

Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is the most common type of dementia associated with age-related neurodegeneration. Alteration of several molecular mechanisms...     

Genetic variation among populations of the endangered fan mussel <Emphasis Type="Italic">Pinna nobilis</Emphasis> (Mollusca: Bivalvia) along the Tunisian coastline

The Mediterranean fan mussel Pinna nobilis is an endangered invertebrate due to overexploitation and habitat deterioration. In this species, two distinctive morphs, the “combed” and “straight and wide” forms, have been recorded and it is not known whether this morphometric variability is attributed to genetic or environmental factors. In this study, we used mitochondrial COI sequences to describe the genetic variability of five Pinna nobilis populations sampled along the northern, eastern, and southern Tunisian coastline, and to examine whether there is a genetic differentiation between the two forms of this species. DNA sequences of 675 bp from the mitochondrial COI gene have revealed 10 different haplotypes among 49 examined specimens. Haplotype diversity was high, ranging between 0.40441 and 0.80952, and showed a decreasing North-East gradient, which seems to be explained by the hydrogeography of the study area. The mitochondrial COI marker did not suggest a genetic distinctiveness between the two Pinna nobilis shell forms, “combed” and “straight and wide”. Although the morphometric plasticity of the fan mussel could be due to the influence of environmental factors, further genetic studies using nuclear markers are envisaged to investigate whether this differentiation is associated to gene flow restrictions.     

Effects of prenatal hypoxia on expression of amyloid precursor protein and metallopeptidases in the rat brain

Summary In the present study we have investigated the effect of prenatal hypoxia on expression of amyloid precursor protein (APP) and some metallopeptidases, which regulate β-amyloid peptide (Aβ) levels (neprilysin (NEP) and endothelin-converting enzyme (ECE-1)) in the cortex of rats during different periods of postnatal development. We have found that the level of APP in the sensorimotor cortex (SMC) of rats, analysed by Western blotting, increases from days 1 to 5 of postnatal development and then steadily decreases with age, with the most dramatic decline in the period from day 180 to 600. In the cortex of rats subjected to prenatal hypoxia on day 13.5 of embryogenesis, the postnatal levels of APP were higher than in the control. Secretion of the soluble form of APP (sAPP) by α-secretase was found to be the most active on day 30 of postnatal development and there was a significant decrease in the production of sAPP after prenatal hypoxia. NEP was found to be expressed in the cortex of rats only at the early stages of postnatal development and it was barely detectable in adult rats. The decline of NEP levels during ageing might contribute to accumulation of Aβ in later life in humans. Prenatal hypoxia resulted in a significant decrease of NEP expression on day 10, but its level was recovered when animals were preconditioned to mild hypoxia. A similar phenomenon was observed when the expression of ECE-1 was analysed. Overall, prenatal hypoxia leads to significant changes in the levels of APP and expression of metallopeptidases involved in amyloid metabolism during all postnatal life and preconditioning to hypoxia appeared to be neuroprotective.     

Omental adipose tissue gene expression,gene variants,branched-chain amino acids,and their relationship with metabolic syndrome and insulin resistance in humans

Obesity is a complex disorder caused by several factors. Thus, the aim of the present study was to assess whether the expression of genes in the omental white adipose tissue (AT) of subjects with insulin resistance (IR) or metabolic syndrome (MetS) is associated with an elevation in serum branched-chain amino acids (BCAAs) and whether this response depends on specific genetic variants. Serum BCAA concentration, the adipocyte area, and gene variants of PPARγ, ABCA1, FTO, TCF7L2, GFOD2,BCAT2, and BCKDH were determined in 115 Mexican subjects. The gene expression in the AT and adipocytes of BCAT, BCKDH E1α, C/EBPα, PPARγ2, SREBP-1, PPARα, UCP1, leptin receptor, leptin, adiponectin, and TNFα was measured in 51 subjects. Subjects with IR showed higher values for the BMI, HOMA-IR, and adipocyte area and higher levels of serum glucose, insulin, leptin, and C-reactive protein, as well as an elevation of the AT gene expression of SREBP-1, leptin, and TNFα and a significant reduction in the expression of adiponectin, BCAT2, and BCKDH E1α, compared with non-IR subjects. The presence of MetS was associated with higher HOMA-IR as well as higher serum BCAA concentrations. Subjects with the genetic variants for BCAT2 and BCKDH E1 α showed a lower serum BCAA concentration, and those with the ABCA1 and FTO gene variant showed higher levels of insulin and HOMA-IR than non-IR subjects. AT dysfunction is the result of a combination of the presence of some genetic variants, altered AT gene expression, the presence of MetS risk factors, IR, and serum BCAA concentrations.     

Synthesis and bioevaluation of some new isoniazid derivatives

The aim of the study was to synthesize some new compounds with potential anti-tuberculosis activity, containing isoniazid and α,β-unsaturated thiocinnamamide-like thioamides as precursors. The obtained derivatives were evaluated regarding their biological activity (antioxidant and antibacterial), as well as their influence on the eukaryotic cell cycle. The results suggested that the newly obtained derivatives of isoniazid exhibited different biological activities, depending on their structure; thus, the most active compound in terms of anti-oxidant and anti-Mycobacterium tuberculosis effects proved to be the isonicotinic acid N′-(1-amino-1-mercapto-3-phenyl-propen-1-yl)-hydrazide. This compound also increased the expression of NAT1 and NAT2 genes, which are implicated in the metabolism of the isoniazid, demonstrating that it could be rapidly metabolized, and thus well tolerated. The largest spectrum of antibacterial activity (excluding M. tuberculosis) was noticed for the isonicotinic acid N′-[1-amino-1-mercapto-3-(p-chloro-phenyl)-propen-1-yl]-hydrazide, which was also the most cytotoxic, especially at high concentrations, although not significantly affecting the cellular cycle phases. The obtained results showed that the new derivatives could represent potential candidates for the treatment of M. tuberculosis infections, but further research is needed in order to improve their pharmacological properties, by increasing their antimicrobial activity and reducing the risk of side-effects.     

Enhancement on the Europium emission band of Europium chlortetracycline complex in the presence of LDL

Low-density lipoprotein (LDL) particles are the major cholesterol-carrying lipoprotein in the human circulation from the liver to peripheral tissues. High levels of LDL-Cholesterol (LDL-C) are known risk factor for the development of coronary artery disease (CAD). The most common approach to determine the LDL-C in the clinical laboratory involves the Friedewald formula. However, in certain situations, this approach is inadequate. In this paper we report on the enhancement on the Europium emission band of Europium chlortetracycline complex (CTEu) in the presence of LDL. The emission intensity at 615 nm of the CTEu increases with increasing amounts of LDL. This phenomenon allowed us to propose a method to determine the LDL concentration in a sample composed by an aqueous solution of LDL. With this result we obtained LDL calibration curve, LOD (limit of detection) of 0.49 mg/mL and SD (standard deviation) of 0.003. We observed that CTEu complex provides a wider dynamic concentration-range for LDL determination than that from Eu-tetracycline previously. The averaged emission lifetimes of the CTEu and CTEu with LDL (1.5 mg/mL) complexes were measured as 15 and 46 μs, respectively. Study with some metallic interferents is presented.     

A new mechanism for reduced sensitivity to demethylation‐inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis

The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications, with a major contribution from sterol demethylation‐inhibitors (DMIs). The continued use of DMIs places considerable selection pressure on natural P. fijiensis populations, enabling the selection of novel genotypes with reduced sensitivity. The hitherto explanatory mechanism for this reduced sensitivity was the presence of non‐synonymous point mutations in the target gene Pfcyp51, encoding the sterol 14α‐demethylase enzyme. Here, we demonstrate a second mechanism involved in DMI sensitivity of P. fijiensis. We identified a 19‐bp element in the wild‐type (wt) Pfcyp51 promoter that concatenates in strains with reduced DMI sensitivity. A polymerase chain reaction (PCR) assay identified up to six Pfcyp51 promoter repeats in four field populations of P. fijiensis in Costa Rica. We used transformation experiments to swap the wt promoter of a sensitive field isolate with a promoter from a strain with reduced DMI sensitivity that comprised multiple insertions. Comparative in vivo phenotyping showed a functional and proportional up‐regulation of Pfcyp51, which consequently decreased DMI sensitivity. Our data demonstrate that point mutations in the Pfcyp51 coding domain, as well as promoter inserts, contribute to the reduced DMI sensitivity of P. fijiensis. These results provide new insights into the importance of the appropriate use of DMIs and the need for the discovery of new molecules for black Sigatoka management.     

Testosterone and intrasexual competition in men: is there any relation with digit ratio (2D:4D)?

Digit ratio 2D:4D is a sexually dimorphic characteristic and it is believed that this difference is related to high levels of prenatal testosterone and circulating testosterone in men. High levels of testosterone are also associated with traits related to competitiveness. Therefore, this study aimed to examine the relation between intrasexual competition and 2D:4D in men. One hundred thirteen college men answered a questionnaire to measure their scores of intrasexual competition and donated a saliva sample to measure their testosterone levels; finally, the finger length from both hands was measured. It was found a positive correlation between testosterone levels and intrasexual competition scores, and a negative correlation between testosterone levels and left 2D:4D. Finally, we did not find a significant association between digit ratios 2D:4D and intrasexual competition scores. Our study shows that men with higher testosterone levels also have higher intrasexual competition scores and lower values of left digit ratio 2D:4D. Further studies will have to take into account fluctuations in testosterone over the time to observe if the relation between competitiveness scores and digit ratios 2D:4D becomes significant.