Efficacy of intra-lesional injections of meglumine antimoniate once a week vs. twice a week in the treatment of cutaneous leishmaniasis caused by L. tropica in Iran: A randomized controlled clinical trial

Treatment of Cutaneous leishmaniasis (CL) is based on using antimoniate derivatives; patients’ compliance for systemic injections is low due to the pain and systemic complications. In this randomized open trial, the efficacy of intra-lesional (IL) injections of meglumine antimoniate (MA) once a week vs. twice a week in the treatment of Anthrpoponothic CL caused by L. tropica was studied. Eligible volunteer patients were selected according to inclusion/exclusion criteria. The included patients were randomly allocated to receive IL-MA injections once a week or twice a week. The primary outcome was set as complete healing of the lesion(s), and defined as complete re-epithelialization and absence of induration in the lesions. A total of 180 parasitologicaly proven CL patients caused by L. tropica were recruited, 90 patients were treated with weekly IL-MA and 90 patients received IL-MA twice a week. The complete cure was 87.9% vs. 89.2% in the group received weekly and twice a week IL-MA injections, respectively (P = 0.808). Patients’ compliance was acceptable and side effects were limited to a few local allergic reactions to MA. Median time to healing was significantly shorter in patients who received IL-MA twice a week (median ± SE) 37±3.8, (CI: 29.6–44.4) days compared to whom received IL-MA once a week 60±2.3, (CI: 55.6–64.5) days (P< 0.001), however the number of injections was higher in group who received IL-MA twice a week (12 vs. 9 injections). In conclusion, the rate of cure in the group of CL patients with IL-MA twice a week was not significantly different from the group who received IL-MA once a week shorten, but the duration of healing was shorter in the group who received IL-MA twice a week while the group received more injections so is recommended to use IL-MA once a week due to the fact the compliance is acceptable with limited side effects.Clinical Trial Registration: IRCT20081130001475N13; https://en.irct.ir/.     

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons.

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.     

Diets of giants: the nutritional value of sauropod diet during the Mesozoic

A major uncertainty in estimating energy budgets and population densities of extinct animals is the carrying capacity of their ecosystems, constrained by net primary productivity (NPP) and its digestible energy content. The hypothesis that increases in NPP due to elevated atmospheric CO₂ contributed to the unparalleled size of the sauropods has recently been rejected, based on modern studies on herbivorous insects that imply a general, negative correlation of diet quality and increasing CO₂. However, the nutritional value of plants grown under elevated CO₂ levels might be very different for vertebrate megaherbivores than for insects. Here we show plant species‐specific responses in metabolizable energy and nitrogen content, equivalent to a two‐fold variation in daily food intake estimates for a typical sauropod, for dinosaur food plant analogues grown under CO₂ concentrations spanning estimates for Mesozoic atmospheric concentrations. Our results potentially rebut the hypothesis that constraints on sauropod diet quality were driven by Mesozoic CO₂ concentration.     

Enhanced Thermal Stability and Biocompatibility of Gold Nanorods by Graphene Oxide

In the present study, the effect of nanosized graphene oxide layer on thermal stability and biocompatibility of gold nanorods has been examined. The graphene oxide-wrapped gold nanorods were prepared by electrostatic interaction between negatively charged graphene oxide and positively charged nanorods. The resulting nanohybrids were then heated at different time intervals to 95 °C in a water bath to assess the effect of heat on the rods morphology. The structural changes in gold nanorods were monitored via UV-Vis spectroscopy measurements and transmission electron microscopy images. In similar experiments, the graphene oxide used to wrap gold nanorods was reduced by ascorbic acid in a 95 °C water bath. Our results indicate that while bare gold nanorods are highly vulnerable to elevated temperatures, graphene oxide and reduced graphene oxide-coated gold nanorods remain thermally stable with no structural changes. We also confirmed that the enhanced thermal stability is highly dependent on the concentration of deposited graphene oxide available on the surface of the gold nanorods. In addition, we performed an MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazoliumbromide) assay to make a comparison between the cytotoxicity of the nanohybrids and their primary building blocks on human dermal fibroblast cells as a normal cell line. We found evidence that graphene oxide can enhance the biocompatibility of the rods through covering toxic chemicals on the surface of them.

Open image in new window

Graphical Abstract ?

     

Sublethal effects of hexaflumuron on development and reproduction of the diamondback moth,Plutella xylostella (Lepidoptera: Yponomeutidae)

Abstract Effects of hexaflumuron at 10% lethal concentration (LC₁₀) and LC₂₅ on development and reproduction parameters of the diamondback moth, Plutella xylostella (Linnaeus, 1753) (Lep.: Yponomeutidae) were investigated. Estimated LC₅₀, LC₁₀ and LC₂₅ values of leaf dip bioassay of hexaflumuron on the third instar larvae of the P. xylostella were 1.48, 0.59 and 0.91 mg/L, respectively. Hexaflumuron decreased pupal weight in the parent generation at sublethal concentrations but in the offspring generation, this effect was not observed. Sublethal concentrations increased egg, first and second larval instar and pupa developmental time and shortened life span of adults, but did not change the third and fourth larval instars and pre‐pupa developmental period. Also fecundity of females reduced significantly but hatchability of treatments and control were similar. Survival rate of pre‐adult stages declined significantly at LC₂₅ concentration. Reproduction parameters such as reproductive rate (R₀) and intrinsic rate of increase in sublethal concentrations were significantly lower compared with control, but gross reproduction rate (GRR) at the LC₁₀ concentration was increased and it could be hormoligosis. Also hexaflumuron significantly increased doubling time (Dt). We conclude that the sublethal effects of hexaflumuron might exhibit significant effects on the population dynamics of P. xylostella.     

Plant–Microbe Symbiosis: What Has Proteomics Taught Us?

Beneficial microbes have a positive impact on the productivity and fitness of the host plant. A better understanding of the biological impacts and underlying mechanisms by which the host derives these benefits will help to address concerns around global food production and security. The recent development of omics‐based technologies has broadened our understanding of the molecular aspects of beneficial plant–microbe symbiosis. Specifically, proteomics has led to the identification and characterization of several novel symbiosis‐specific and symbiosis‐related proteins and post‐translational modifications that play a critical role in mediating symbiotic plant–microbe interactions and have helped assess the underlying molecular aspects of the symbiotic relationship. Integration of proteomic data with other “omics” data can provide valuable information to assess hypotheses regarding the underlying mechanism of symbiosis and help define the factors affecting the outcome of symbiosis. Herein, an update is provided on the current and potential applications of symbiosis‐based “omic” approaches to dissect different aspects of symbiotic plant interactions. The application of proteomics, metaproteomics, and secretomics as enabling approaches for the functional analysis of plant‐associated microbial communities is also discussed.     

In vivo evidence for two active nuclease motifs in the double-strand break repair enzyme RexAB of Lactococcus lactis

In bacteria, double-strand DNA break (DSB) repair involves an exonuclease/helicase (exo/hel) and a short regulatory DNA sequence (Chi) that attenuates exonuclease activity and stimulates DNA repair. Despite their key role in cell survival, these DSB repair components show surprisingly little conservation. The best-studied exo/hel, RecBCD of Escherichia coli, is composed of three subunits. In contrast, RexAB of Lactococcus lactis and exo/hel enzymes of other low-guanine-plus-cytosine branch gram-positive bacteria contain two subunits. We report that RexAB functions via a novel mechanism compared to that of the RecBCD model. Two potential nuclease motifs are present in RexAB compared with a single nuclease in RecBCD. Site-specific mutagenesis of the RexA nuclease motif abolished all nuclease activity. In contrast, the RexB nuclease motif mutants displayed strongly reduced nuclease activity but maintained Chi recognition and had a Chi-stimulated hyperrecombination phenotype. The distinct phenotypes resulting from RexA or RexB nuclease inactivation lead us to suggest that each of the identified active nuclease sites in RexAB is involved in the degradation of one DNA strand. In RecBCD, the single RecB nuclease degrades both DNA strands and is presumably positioned by RecD. The presence of two nucleases would suggest that this RecD function is dispensable in RexAB.     

Biofabrication with chitosan

The traditional motivation for integrating biological components into microfabricated devices has been to create biosensors that meld the molecular recognition capabilities of biology with the signal processing capabilities of electronic devices. However, a different motivation is emerging; biological components are being explored to radically change how fabrication is achieved at the micro- and nanoscales. Here we review biofabrication, the use of biological materials for fabrication, and focus on three specific biofabrication approaches: directed assembly, where localized external stimuli are employed to guide assembly; enzymatic assembly, where selective biocatalysts are enlisted to build macromolecular structure; and self-assembly, where information internal to the biological material guides its own assembly. Also reviewed are recent results with the aminopolysaccharide chitosan, a material that offers a combination of properties uniquely suited for biofabrication. In particular, chitosan can be directed to assemble in response to locally applied electrical signals, and the chitosan backbone provides sites that can be employed for the assembly of proteins, nucleic acids, and virus particles.     

Unconscious orientation processing

Recent findings have shown that certain attributes of visual stimuli, like orientation, are registered in cortical areas when the stimulus is unresolvable or perceptually invisible; however, there is no evidence to show that complex forms of orientation processing (e.g., modulatory effects of orientation on the processing of other features) could occur in the absence of awareness. To address these questions, different psychophysical paradigms were designed in six experiments to probe unconscious orientation processing. First we demonstrated orientation-selective adaptation and color-contingent orientation adaptation for peripheral unresolvable Gabor patches. The next experiments showed the modulatory effects of perceptually indiscriminable orientations on apparent motion processing and attentional mechanisms. Finally we investigated disappearance patterns of unresolvable Gabor stimuli during motion-induced blindness (MIB). Abrupt changes in local unresolvable orientations truncated MIB; however, orientation-based grouping failed to affect the MIB pattern when the orientations were unresolvable. Overall results revealed that unresolvable orientations substantially influence perception at multiple levels.     

Reproducibility of swallow-induced cortical BOLD positive and negative fMRI activity

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies (r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined "default-mode" network, and positive BOLD activity had noticeable overlap with the previously described "task-positive" network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.