Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production

One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation.     

Discovery of Novel Potent Small Natural Molecules Able to Enhance Attenuation of the Pathobiology of Gastric Cancer-Associated Helicobacter pylori by Molecular Modeling

CagA is an oncoprotein that plays a significant role in the advancement of gastric cancer by interacting with phosphatidylserine of host cell plasma membrane. This protein is a potential target for the cancer therapy. In the present study, the initial and dynamic binding interaction mechanisms between CagA and herbal compounds were investigated by molecular docking of the 38 compounds followed by an analysis combining molecular dynamics simulations and molecular mechanics–Poisson Boltzmann surface area binding free energy calculations of the top four hit compounds; spinasterol, luteoxanthin, 3′-prenylrubranine and neoxanthin. Energetic analyses disclosed binding free energies pointing out that neoxanthin and luteoxanthin were potential candidates as lead compounds in drug development towards the CagA–phosphatidylserine inhibitors. Ultimately, binding free energy decomposition gave detailed information regarding the essential amino acid residues stabilizing the complexes.

     

The gene for mitochondrial ribosomal protein S14 has been transferred to the nucleus in Arabidopsis thaliana

The transfer of genetic information from the mitochondrion to the nucleus is thought to be still underway in higher plants. The mitochondrial genome of Arabidopsis thaliana contains only one rps14 pseudogene. In this paper we show that the functional gene encoding mitochondrial ribosomal protein S14 has been translocated to the nucleus. This gene transfer is a recent evolutionary event, which occurred within Cruciferae, probably after the divergence of Arabidopsis and Brassica napus. A 5′ extension of the rps14 reading frame encodes a presequence which, in vitro, targets the polypeptide to isolated mitochondria and is cleaved off during or after import. No intron was found at the junction of the targeting presequence with the mitochondrially derived sequence, which are directly connected. By contrast, a 90-bp intron, which is removed by splicing to give a mature poly(A)⁺mRNA of 0.9 kb, is located in the 3′ non-coding region. To our knowledge, this is the first report of an intron in such a position in a functional transferred gene in higher plants, and suggests that exon shuffling may have been involved in the acquisition of elements necessary for expression in the nucleus. Putative roles of this intron in polyadenylation and enhancement of gene expression are discussed. Received: 11 January 1999 / Accepted: 27 April 1999     

Modulation of the Physical Properties of 3D Spheroids Derived from Human Scleral Stroma Fibroblasts (HSSFs) with Different Axial Lengths Obtained from Surgical Patients

In the current study, to elucidate the pathological characteristics of myopic scleral stroma, three-dimensional (3D) cultures of human scleral stroma fibroblasts (HSSFs) with several axial lengths (AL, 22.80–30.63 mm) that were obtained from patients (n = 7) were examined. Among the three groups of ALs, <25 mm (n = 2), 25–30 mm (n = 2), and >30 mm (n = 3), the physical properties of the 3D HSSFs spheroids with respect to size and stiffness, the expressions of extracellular matrix (ECM) molecules, including collagen (COL) 1, 4, and 6 and fibronectin (FN) by qPCR and immunohistochemistry (IHC), and the mRNA expression of ECM metabolism modulators including hypoxia-inducible factor 1A (HIF 1A), HIF 2A, lysyl oxidase (LOX), tissue inhibitor of metalloproteinase (TIMP) 1–4, and matrix metalloproteinase (MMP) 2, 9, and 14 as well as several endoplasmic reticulum (ER) stress-related factors were compared. In the largest AL group (>30 mm), the 3D HSSFs spheroids were (1) significantly down-sized and less stiff compared to the other groups, and (2) significant changes were detected in the expression of some ECMs (qPCR; the up-regulation of COL1 and COL4, and the down-regulation of FN, IHC; the up-regulation of COL1 and FN, and down-regulation of COL4). The mRNA expressions of ECM modulators and ER stress-related genes were also altered with increasing AL length (up-regulation of HIF2A, MMP2, XBP1, and MMP14, down-regulation of LOX, TIMP 2 and 3, GRP78, GRP94, IRE1, and ATF6). In addition, a substantial down-regulation of some ER stress-related genes (ATF4, sXPB1 and CHOP) was observed in the 25–30 mm AL group. The findings presented herein suggest that small and stiffer 3D HSSFs spheroids in the largest AL group may accurately replicate the pathological significance of scleral thinning and weakening in myopic eyes. In addition, the modulation of several related factors among the different AL groups may also provide significant insights into our understanding of the molecular mechanisms responsible for causing myopic changes in the sclera.     

A new species of Aeneator Finlay, 1926 (Mollusca,Gastropoda, Buccinidae) from northern Chile,with comments on the genus and a key to the Chilean species

A new species of the genus Aeneator Finlay, 1926 is described from off the coast of Caldera (27°S), northern Chile. Aeneator martae sp. n. has a small, broad, stout, angulated shell with more prominent axial ribs and a more obviously keeled periphery than all previously named Chilean species. Comparisons are provided with all other South American named species of Aeneator.     

Laboratory observation of siblicide with hatching asynchrony in an insect with parental provisioning

We report laboratory observation of siblicide with hatching asynchrony in the passalid beetle Cylindrocaulus patalis. Parents construct a breeding gallery in rotten logs and show complex care of offspring, including provisioning. Clutch sizes are extremely small, and only a single offspring is raised in a colony in each breeding season. We introduced field-collected colonies into an artificial gallery and recorded the behaviour of colony members. Eggs hatched at 2- to 10-day intervals in each colony. Fatal fighting invariably occurred among the larvae soon after hatching of the junior larva, and a single larva, usually the senior one, survived.