The CXCL12γ Chemokine Displays Unprecedented Structural and Functional Properties that Make It a Paradigm of Chemoattractant Proteins

The CXCL12γ chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12γ is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12γ through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12γ both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12γ strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12γ one of the higher affinity for HS (K_d = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12γ to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12α. In good agreement, mutant CXCL12γ chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12γ features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12γ the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells.     

Morpho-physiological investigations in transgenic tomato (Solanum lycopersicum L.) over expressing OsRGLP1 gene

In Vitro Cellular & Developmental Biology - Plant - The OsRGLP1 gene was overexpressed under the control of CaMV 35S promoter in tomato (Solanum lycopersicum L.) plants using...     

Regulation of autophagy by polyphenols: Paving the road for treatment of neurodegeneration

In the present paper, we will discuss on the importance of autophagy in the central nervous system, and outline the relation between autophagic pathways and the pathogenesis of neurodegenerative disorders. The potential therapeutic benefits of naturally occurring phytochemicals as pharmacological modulators of autophagy will also be addressed. Our findings provide renewed insight on the molecular modes of protection by polyphenols, which is likely to be at least in part mediated not only by their potent antioxidant and anti-inflammatory effects, but also through modulation of autophagic processes to remove the aberrant protein aggregates.     

Assessment of Titanium Dioxide Nanoparticles (TiO<Subscript>2</Subscript>-NPs) Induced Hepatotoxicity and Ameliorative Effects of <Emphasis Type="Italic">Cinnamomum cassia</Emphasis> in Sprague-Dawley Rats

This study assessed the protective effects of Cinnamomum cassia (cinnamon) bark extract in rats exposed to titanium dioxide nanoparticles or titanium dioxide bulk salt. For in vivo evaluation of the ameliorative role of the cinnamon extract, the experimental groups were orally administered with the cinnamon extract at different dose levels (50 or 100 or 150 mg/kg bodyweight) along with the subcutaneous injections of 150 mg/kg bodyweight titanium dioxide nanoparticles or titanium dioxide bulk salt. The extract showed significant ameliorative role on the antioxidant system in response to elevated levels of titanium dioxide nanoparticles or titanium dioxide bulk salt-induced oxidative stress. It aided in the recovery of the antioxidant system as well as protective role in histological damages and some haematological parameters in the rat liver treated with titanium dioxide nanoparticles or titanium dioxide bulk salt.     

Secondary metabolism of pharmaceuticals in the plant in vitro cultures: strategies,approaches, and limitations to achieving higher yield

Biotechnology is playing a vital alternative role in the production of pharmaceutical plant secondary metabolites to support industrial production and mitigate over-exploitation of natural sources. High-value pharmaceuticals that include alkaloids, flavonoids, terpenes, steroids, among others, are biosynthesized as a defensive strategy by plants in response to perturbations under natural environmental conditions. However, they can also be produced using plant cell, tissue, and organ culture techniques through the application of various in vitro approaches and strategies. In the past decades, efforts were on the clonal propagation, biomass and secondary metabolites production in the in vitro cultures of medicinally important plants that produce these molecules. In recent years, the effort has shifted towards optimizing culture conditions for their production through the application of cell line selection, elicitation, precursor feeding, two-phase co-culture among cell, tissue, and organ culture approaches. The efforts are made with the possibility to scale-up the production, meet pharmaceutical industry demand and conserve natural sources of the molecules. Applications of metabolic engineering and production from endophytes are also getting increasing attention but, the approaches are far from practical application in their industrial production.     

Sugar beet extract acts as a natural bio-stimulant for physio-biochemical attributes in water stressed wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

The present study investigated the role of sugar beet extract (SBE) as a bio-stimulant to ameliorate the adverse effects of drought on seed germination and growth of wheat (Triticum aestivum L.). Different concentrations of SBE (0, 10, 20, 30, 40 and 50%) were used for priming the wheat seeds. The experiment was conducted in laboratory (PEG-8000 was used to create water stress) as well as under natural environmental conditions (using soil with 100 and 60% field capacity). Significant ameliorating effects of seed priming with SBE were recorded on different germination attributes, i.e., time to 50% emergence (E₅₀), germination index (GI), mean emergence time (MET), germination percentage (G%), coefficient of uniformity of emergence (CUE) and germination energy (GE) under water stress. Without priming, the plants exhibited symptoms of water stress like decreased biomass, reduction in photosynthetic pigments, e.g., chlorophyll, carotenoids. Seed pre-conditioning with SBE improved the plant growth, photosynthetic pigments, antioxidants’ activities and nutrient homeostasis of plants facing water deficit and grown under well-watered conditions. The maximum increase in biomass, content of chlorophyll, carotenoids and activities of superoxide dismutase (SOD) and peroxidase (POD) was 13.4, 8.5, 11.9, 7.6, 13.6, 42.0, 19.8%, respectively, with SBE seed priming under water stress. In conclusion, SBE seed priming effectively reduced the negativities of water stress on seed germination which resulted in better plant growth in terms of enhanced biomass, photosynthetic pigments, antioxidant defense mechanism and better nutrient homeostasis. Overall, the findings suggest that seed pre-conditioning with SBE as a bio-stimulant will be helpful for better crop stand establishment under low field capacity, especially in semi-arid and arid agricultural fields.