Glycobiology of cell death: when glycans and lectins govern cell fate

Although one typically thinks of carbohydrates as associated with cell growth and viability, glycosylation also has an integral role in many processes leading to cell death. Glycans, either alone or complexed with glycan-binding proteins, can deliver intracellular signals or control extracellular processes that promote initiation, execution and resolution of cell death programs. Herein, we review the role of glycans and glycan-binding proteins as essential components of the cell death machinery during physiologic and pathologic settings.Fil: Lichtenstein, Rachel. Ben-Gurion University of the Negev. Faculty of Engineering. Department of Biotechnology Engineering; IsraelFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica; Argentin

Cross-tolerance to abiotic stresses in halophytes: Application for phytoremediation of organic pollutants

International audienceHalopytes are plants able to tolerate high salt concentrations but no clear definition was retained for them. In literature, there are more studies that showed salt-enhanced tolerance to other abiotic stresses compared to investigations that found enhanced salt tolerance by other abiotic stresses in halophytes. The phenomenon by which a plant resistance to a stress induces resistance to another is referred to as cross-tolerance. In this work, we reviewed cross-tolerance in halophytes at the physiological, biochemical, and molecular levels. A special attention was accorded to the cross-tolerance between salinity and organic pollutants that could allow halophytes a higher potential of xenobiotic phytoremediation in comparison with glycophytes

Noninjection Synthesis of CdS and Alloyed CdSxSe1−xNanocrystals Without Nucleation Initiators

CdS and alloyed CdSxSe1−x nanocrystals were prepared by a simple noninjection method without nucleation initiators. Oleic acid (OA) was used to stabilize the growth of the CdS nanocrystals. The size of the CdS nanocrystals can be tuned by changing the OA/Cd molar ratios. On the basis of the successful synthesis of CdS nanocrystals, alloyed CdSxSe1−x nanocrystals can also be prepared by simply replacing certain amount of S precursor with equal amount of Se precursor, verified by TEM, XRD, EDX as well as UV–Vis absorption analysis. The optical properties of the alloyed CdSxSe1−x nanocrystals can be tuned by adjusting the S/Se feed molar ratios. This synthetic approach developed is highly reproducible and can be readily scaled up for potential industrial production

HiNO: An Approach for Inferring Hierarchical Organization from Regulatory Networks

BACKGROUND: Gene expression as governed by the interplay of the components of regulatory networks is indeed one of the most complex fundamental processes in biological systems. Although several methods have been published to unravel the hierarchical structure of regulatory networks, weaknesses such as the incorrect or inconsistent assignment of elements to their hierarchical levels, the incapability to cope with cyclic dependencies within the networks or the need for a manual curation to retrieve non-overlapping levels remain unsolved. METHODOLOGY/RESULTS: We developed HiNO as a significant improvement of the so-called breadth-first-search (BFS) method. While BFS is capable of determining the overall hierarchical structures from gene regulatory networks, it especially has problems solving feed-forward type of loops leading to conflicts within the level assignments. We resolved these problems by adding a recursive correction approach consisting of two steps. First each vertex is placed on the lowest level that this vertex and its regulating vertices are assigned to (downgrade procedure). Second, vertices are assigned to the next higher level (upgrade procedure) if they have successors with the same level assignment and have themselves no regulators. We evaluated HiNO by comparing it with the BFS method by applying them to the regulatory networks from Saccharomyces cerevisiae and Escherichia coli, respectively. The comparison shows clearly how conflicts in level assignment are resolved in HiNO in order to produce correct hierarchical structures even on the local levels in an automated fashion. CONCLUSIONS: We showed that the resolution of conflicting assignments clearly improves the BFS-method. While we restricted our analysis to gene regulatory networks, our approach is suitable to deal with any directed hierarchical networks structure such as the interaction of microRNAs or the action of non-coding RNAs in general. Furthermore we provide a user-friendly web-interface for HiNO that enables the extraction of the hierarchical structure of any directed regulatory network. AVAILABILITY: HiNO is freely accessible at http://mips.helmholtz-muenchen.de/hino/

TLR9 Agonist Protects Mice from Radiation-Induced Gastrointestinal Syndrome

Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption of mucosal barrier, bacterial invasion, inflammation and sepsis. Intestinal macrophages could recognize invading bacterial DNA via TLR9 receptors and transmit regenerative signals to the neighboring crypt. We therefore investigated whether systemic administration of designer TLR9 agonist could ameliorate RIGS by activating TLR9.Male C57Bl6 mice were distributed in four experimental cohorts, whole body irradiation (WBI) (8.4-10.4 Gy), TLR9 agonist (1 mg/kg s.c.), 1 h pre- or post-WBI and TLR9 agonist+WBI+iMyd88 (pretreatment with inhibitory peptide against Myd88). Animals were observed for survival and intestine was harvested for histological analysis. BALB/c mice with CT26 colon tumors in abdominal wall were irradiated with 14 Gy single dose of whole abdominal irradiation (AIR) for tumor growth study.Mice receiving pre-WBI TLR9 agonist demonstrated improvement of survival after 10.4 Gy (p<0.03), 9.4 Gy (p<0.008) and 8.4 Gy (p<0.002) of WBI, compared to untreated or iMyd88-treated controls. Post-WBI TLR9 agonist mitigates up to 8.4 Gy WBI (p<0.01). Histological analysis and xylose absorption test demonstrated significant structural and functional restitution of the intestine in WBI+TLR9 agonist cohorts. Although, AIR reduced tumor growth, all animals died within 12 days from RIGS. TLR9 agonist improved the survival of mice beyond 28 days post-AIR (p<0.008) with significant reduction of tumor growth (p<0.0001).TLR9 agonist treatment could serve both as a prophylactic or mitigating agent against acute radiation syndrome and also as an adjuvant therapy to increase the therapeutic ratio of abdominal Radiation Therapy for Gastro Intestinal malignancies

Semaphorin-1a Is Required for Aedes aegypti Embryonic Nerve Cord Development

Although mosquito genome projects have uncovered orthologues of many known developmental regulatory genes, extremely little is known about mosquito development. In this study, the role of semaphorin-1a (sema1a) was investigated during vector mosquito embryonic ventral nerve cord development. Expression of sema1a and the plexin A (plexA) receptor are detected in the embryonic ventral nerve cords of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector), suggesting that Sema1a signaling may regulate mosquito nervous system development. Analysis of sema1a function was investigated through siRNA-mediated knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti development results in a number of nerve cord phenotypes, including thinning, breakage, and occasional fusion of the longitudinal connectives, thin or absent commissures, and general distortion of the nerve cord. Although analysis of Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar phenotypes, aspects of the longitudinal phenotypes differed between D. melanogaster and A. aegypti. The results of this investigation suggest that Sema1a is required for development of the insect ventral nerve cord, but that the developmental roles of this guidance molecule have diverged in dipteran insects