Synthesis and in vitro activity of 2-thiazolylhydrazone derivatives compared with the activity of clotrimazole against clinical isolates of Candida spp

In this paper, we report on the synthesis of a novel series of 2-thiazolylhydrazone derivatives and the influence of the substituents on the thiazole ring on antifungal activity. All synthesized compounds were screened for their in vitro activities against 22 clinical isolates of Candida spp., representing six different species, compared to clotrimazole as a reference compound. Some of the tested compounds were found to possess significant antifungal activity when compared to clotrimazole, in particular compound 14 which exhibited higher potency against most of the Candida spp. considered. The compounds that were most active as anti-Candida agents were also submitted to cytotoxic screening by the Trypan Blue dye exclusion assay and in general they were shown to induce low cytotoxic effects.     

Infection of bovine oviduct cell cultures with Chlamydophila abortus

Bovine infertility is a major cause of loss in the livestock industry. In the present study bovine oviduct cell cultures were infected with a Chlamydophila abortus strain. A direct evaluation of infection was performed by means of May Grünwald-Giemsa and immunocytochemistry for chlamydial LPS, which revealed inclusion bodies and vacuolisation. SEM and TEM analysis of infected cells showed various degrees of cell damage and conglutination of microvilli. This finding suggests that cattle infertility may result from an alteration of oviduct environment caused by multiplication of C. abortus. This microorganism, among other infectious agents, could be considered a potential causative agent of bovine infertility.     

GATA elements control repression of cardiac troponin I promoter activity in skeletal muscle cells

Background  

We reported previously that the cardiac troponin I (cTnI) promoter drives cardiac-specific expression of reporter genes in cardiac muscle cells and in transgenic mice, and that disruption of GATA elements inactivates the cTnI promoter in cultured cardiomyocytes. We have now examined the role of cTnI promoter GATA elements in skeletal muscle cells.     

Chlorophyta microalgae as dietary protein supplement: a comparative analysis of productivity related to photosynthesis

Journal of Applied Phycology - Microalgae are studied as innovative sources of a wide range of highly valuable products, including proteins for the food/feed sectors. However, protein content...     

Analysis of the rpn11-m1 proteasomal mutant reveals connection between cell cycle and mitochondrial biogenesis

The proteasomal lid subunit Rpn11 is essential for maintaining a correct cell cycle and mitochondrial morphology in Saccharomyces cerevisiae. In this paper, we show that the rpn11-m1 mutant has a peculiar cell cycle defect reminiscent of mutants defective in the FEAR pathway that delay the release of the Cdc14 protein phosphatase from the nucleolus. We analyzed the rpn11-m1 phenotypes and found that overexpression of Cdc14 suppresses all the rpn11-m1 defects, including the mitochondrial ones. Suppression by Cdc14 of the rpn11-m1 mitochondrial morphology defect reveals an uncharacterized connection between mitochondrial and cell cycle events. Interestingly, the overexpression of Cdc14 also partially restores the tubular network in an Δmmm2 strain, which lacks a mitochondrial protein belonging to the complex necessary to anchor the mitochondrion to the actin cytoskeleton. Altogether our findings indicate, for the first time, a cross-talk between the cell cycle and mitochondrial morphology.     

Early defect of transforming growth factor β1 formation in Huntington’s disease

A defective expression or activity of neurotrophic factors, such as brain‐ and glial‐derived neurotrophic factors, contributes to neuronal damage in Huntington’s disease (HD). Here, we focused on transforming growth factor‐β (TGF‐β₁), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF‐β₁ levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post‐mortem brain tissues showed that TGF‐β₁ was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF‐β₁ in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF‐β₁ formation in asymptomatic R6/2 mice, where blood TGF‐β₁ levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF‐β₁ formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF‐β₁ production is associated with HD. Accordingly, reduced TGF‐β₁ mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock‐in cell lines expressing full‐length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF‐β₁ levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF‐β₁ levels in the brain may influence the progression of HD.     

Phylogeny and evolution of the Archaea: one hundred genomes later

Little more than 30 years since the discovery of the Archaea, over one hundred archaeal genome sequences are now publicly available, of which ～40% have been released in the last two years. Their analysis provides an increasingly complex picture of archaeal phylogeny and evolution with the proposal of new major phyla, such as the Thaumarchaeota, and important information on the evolution of key central cellular features such as cell division. Insights have been gained into the events and processes in archaeal evolution, with a number of additional and unexpected links to the Eukaryotes revealed. Taken together, these results predict that many more surprises will be found as new archaeal genomes are sequenced.     

A computational model of the LGI1 protein suggests a common binding site for ADAM proteins

Mutations of human leucine-rich glioma inactivated (LGI1) gene encoding the epitempin protein cause autosomal dominant temporal lateral epilepsy (ADTLE), a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate protein-protein interactions.A three dimensional in silico model of the two epitempin domains was built to predict the structure-function relationship and propose a functional model integrating previous experimental findings. Conserved and electrostatic charged regions of the model surface suggest a possible arrangement between the two domains and identifies a possible ADAM protein binding site in the β-propeller domain and another protein binding site in the leucine-rich repeat domain. The functional model indicates that epitempin could mediate the interaction between proteins localized to different synaptic sides in a static way, by forming a dimer, or in a dynamic way, by binding proteins at different times.The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process.