Antiplasmodial activity of extracts of 25 cyanobacterial species from coastal regions of Tamil Nadu

Context: Marine cyanobacteria offer considerable potential to isolate new antimalarials to meet a pressing need of our times.

Objective: To explore the antiplasmodial properties of marine cyanobacteria.

Materials and methods: Cyanobacterial samples collected from the coastal regions of Tamil Nadu were identified using light microscopy, and the strains were cultivated in ASN-III medium. Organic extracts (0–100?µg?mL^?1) of 25 in vitro mass-cultivated cyanobacteria, prepared using methanol: chloroform mixture (1:1?v/v) were evaluated for their antiplasmodial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum by fluorescence-based SYBR Green I assay where chloroquine was used as a control. To detect the toxic effects of cyanobacterial extracts against red blood cells, the invasion, maturation, and growth rate of malarial parasites in cyanobacterial extracts pre-treated versus untreated erythrocytes were quantified microscopically. Mammalian cell line (HeLa) was used to determine cyanobacterial extract toxicity using the MTT assay.

Results: The extracts of Lyngbya aestuarii Liebm. ex Gomont CNP 1005 (C12) Oscillatoria boryana BDU 91451 (C22) and Oscillatoria boryana Bory ex Gomont BDU 141071 (C18) showed promising antiplasmodial activity (IC₅₀?=?18, 18, and 51?μg?mL^?1 respectively) against Pf3D7. Pretreatment of red blood cells with IC₁₀₀ of C12, C18, and C22 (40, 100, and 40?µgmL^?1, respectively) did not significantly influence the invasion, maturation, and growth rate of malarial parasites in comparison with untreated RBC controls suggesting a lack of toxicity to host cells. MTT assay based IC₅₀ (>200?μg?mL^?1) of these extracts against HeLa cell line also indicates their high selectivity against the malaria parasite.

Discussion and conclusion: These exploratory studies suggest the possibilities of development of new antimalarial compounds from marine cyanobacteria.     

Yohimbine administration and cue-reactivity in cocaine-dependent individuals

Rationale

Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations.

Objectives

The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women.

Methods

In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n?=?32), cocaine-dependent women (n?=?30), control men (n?=?32), and control women (n?=?25) received either yohimbine or placebo prior to two cocaine cue exposure sessions.

Results

Yohimbine increased ratings of anxiety both before (p?p?=?0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p?=?0.001). Yohimbine also significantly increased craving, compared with placebo (p?p?=?0.006). Yohimbine also increased salivary cortisol (p?p?=?0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p?Conclusions Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions.     

Organic semiconductor/graphene oxide composites as a photo-anode for photo-electrochemical applications

An intimate physical mixture of graphene oxide (GO) and semiconducting organic molecules like bromophenathrene (BrPh) and bromopyrene (BrPy) was prepared by using a ball milling technique. The structural, microstructural, physical and chemical properties of the mixtures (20 wt% of GO) were analyzed by X-ray diffraction, SEM, FT-IR, TGA and TCSPC studies. Furthermore, the electrochemical properties like AC electrical conductivity, transient photocurrent response (PCTR) and open circuit voltage (OCVD) of the samples were analyzed. It has been observed from TCSPC and OCVD measurements that 20 wt% of GO in the semiconductor composite leads to an enhanced life-time of photo-generated charge carriers. The physical mixture composites exhibit a higher photocurrent than pure BrPh and BrPy.

New organic materials with longer life-times of the charge carrier and enhancement of photocurrent generation were developed.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity

The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore.Discovery and engineering of the microbial opsin genes not only has stimulated basic science investigation into the structure–function relationships of proteins involved in light-triggered ion flow but also has opened up opportunities for biological investigation (reviewed in ref. 1) via the technique of optogenetics, which involves targeting these genes and corresponding optical stimuli to control activity within specified types of cells within intact and functioning biological systems. For example, optogenetics has been used to identify causally the brain cells and projections involved in behaviors relevant to memory formation, affective states, and motor function, among many other discoveries (2–4). For the channelrhodopsins, an important member of this protein family widely used in optogenetics (5, 6), the light-activated cation-conducting channel pore has been the subject of structural investigation, both because of curiosity regarding the physical properties of its ion conduction and because the creation of inhibitory channels had been sought for optogenetic applications. Converging lines of work recently achieved the latter goal; resolving the high-resolution structure of channelrhodopsin (7) allowed a principled structure-guided approach to engineering for chloride selectivity by testing an electrostatic model for pore function (8, 9). Subsequently, by screening the genome of the Guillardia theta microbe, two naturally occurring light-gated chloride-conducting channelrhodopsins (10) were identified.Because optogenetic control of behavior has not yet been demonstrated with chloride channelrhodopsins, and to test further integrative ideas regarding pore function from structural considerations as shown here, we sought to design and test the next generation of enhanced chloride channels (iC++ and SwiChR++). Along the way, we provide the initial test of the hypothesis that light-activated channels will be more efficient tools than pumps for optogenetic neuronal inhibition at the cellular level, demonstrate the initial utility of light-gated chloride channels in controlling behavior in freely moving animals, and reveal key principles regarding the functional selectivity of light-gated ion channel pores.     

Chromatin higher-order structure studied by neutron scattering and scanning transmission electron microscopy.

Neutron scattering in solution and scanning transmission electron microscopy were simultaneously done on chicken erythrocyte chromatin at various salt and magnesium concentrations. We show that chromatin is organized into a higher-order structure even at low ionic strength and that the mass per unit length increases continuously as a function of salt concentration, reaching a limiting value of between six and seven nucleosomes per 11 nm. There is no evidence of a transition from a 10-nm to a 30-nm fiber. Fiber diameter is correlated with mass per unit length, showing that both increase during condensation. We also find that there is no essential difference between the mass per unit length measured by scanning transmission electron microscopy and neutron scattering in solution, showing that the ordered regions seen in micrographs are representative of chromatin in solution.