The locust frontal ganglion: a central pattern generator network controlling foregut rhythmic motor patterns

The frontal ganglion (FG) is part of the insect stomatogastric nervous system and is found in most insect orders. Previous work has shown that in the desert locust, Schistocerca gregaria, the FG constitutes a major source of innervation to the foregut. In an in vitro preparation, isolated from all descending and sensory inputs, the FG spontaneously generated rhythmic multi-unit bursts of action potentials that could be recorded from all its efferent nerves. The consistent endogenous FG rhythmic pattern indicates the presence of a central pattern generator network. We found the appearance of in vitro rhythmic activity to be strongly correlated with the physiological state of the donor locust. A robust pattern emerged only after a period of saline superfusion, if the locust had a very full foregut and crop, or if the animal was close to ecdysis. Accordingly, haemolymph collected at these stages inhibited an ongoing rhythmic pattern when applied onto the ganglion. We present this novel central pattern generating system as a basis for future work on the neural network characterisation and its role in generating and controlling behaviour

ОСНОВЫ УПРАВЛЕНИЯ СОЦИАЛЬНЫМИ ПРОЕКТАМИ БИЗНЕСА

In article on wide material the author opens basic approaches to formation of the theoretical base of management of social projects of business.The purpose of work is generalization of theoretical bases of project management of business which have social character. The logic of a statement of material is under construction as follows. In water part of article authors do the assumption that at the heart of an object of research three basic elements are put: project management, social management and management of social projects. Proceeding from this assumption in work further reasonings are under construction. The main part of article contains three subsections. In the fi rst subsection of article defi nition of the concept «project management» is formulated and methodological approaches to project management (PRINCE2, PERT, the Model Agile, Lean Management, BRM) are generalized. In the second subsection the author's understanding of entity of social management is presented and the main techniques of social management are considered, and also the characteristic of methodology of management of social projects is given. In the third subsection the author's concept of entity of management of social projects of business is formulated. In fi nal part of article authors draw a conclusion about the importance of management of social projects of business. This article, fi rst of all, has theoretical and methodological value for formation of eff ective methods and instruments of management of social projects of business, and also for development of the theory and practice of corporate social responsibility.В статье авторы раскрывают основные подходы к формированию теоретического фундамента управления социальными проектами бизнеса. Целью работы является обобщение теоретических основ управления проектами бизнеса, которые носят социальный характер. Логика изложения материала строится следующим образом. В водной части статьи авторы делают предположение о том, что в основе предмета исследования заложены три основных элемента: управление проектами, социальное управление и управление социальными проектами. Исходя из этого предположения в работе строятся дальнейшие рассуждения. Основная часть статьи содержит три подраздела. В первом подразделе статьи сформулировано определение понятия «управление проектами» и обобщены методологические подходы к управлению проектами (PRINCE2, PERT, Модель Agile, Лин-менеджмент, BRM). Во втором подразделе представлено авторское понимание сущности социального управления и рассмотрены основные методики социального управления, а также дана характеристика методологии управления социальными проектами. В третьем подразделе сформулирована авторская концепция сущности управления социальными проектами бизнеса. В заключительной части статьи авторы делают вывод о значимости управления социальными проектами бизнеса. Данная статья, в первую очередь, имеет теоретическое и методологическое значение для формирования эффективных методов и инструментов управления социальными проектами бизнеса, а также для развития теории и практики корпоративной социальной ответственности

A Translation Initiation Element Specific to mRNAs with Very Short 5′UTR that Also Regulates Transcription

Transcription is controlled by cis regulatory elements, which if localized downstream to the transcriptional start site (TSS), in the 5′UTR, could influence translation as well. However presently there is little evidence for such composite regulatory elements. We have identified by computational analysis an abundant element located downstream to the TSS up to position +30, which controls both transcription and translation. This element has an invariable ATG sequence, which serves as the translation initiation codon in 64% of the genes bearing it. In these genes the initiating AUG is preceded by an extremely short 5′UTR. We show that translation in vitro and in vivo is initiated exclusively from the AUG of this motif, and that the AUG flanking sequences create a strong translation initiation context. This motif is distinguished from the well-known Kozak in its unique ability to direct efficient and accurate translation initiation from mRNAs with a very short 5′UTR. We therefore named it TISU for Translation Initiator of Short 5′UTR. Interestingly, this translation initiation element is also an essential transcription regulatory element of Yin Yang 1. Our characterization of a common transcription and translation element points to a link between mammalian transcription and translation initiation

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

Detection of Light Images by Simple Tissues as Visualized by Photosensitized Magnetic Resonance Imaging

In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI). We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD)-MRI protocol, termed photosensitized (ps)MRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold) were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1). This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind

Finding microRNA regulatory modules in human genome using rule induction

Background: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules (20-24 nt), which are believed to participate in repression of gene expression. They play important roles in several biological processes (e.g. cell death and cell growth). Both experimental and computational approaches have been used to determine the function of miRNAs in cellular processes. Most efforts have concentrated on identification of miRNAs and their target genes. However, understanding the regulatory mechanism of miRNAs in the gene regulatory network is also essential to the discovery of functions of miRNAs in complex cellular systems. To understand the regulatory mechanism of miRNAs in complex cellular systems, we need to identify the functional modules involved in complex interactions between miRNAs and their target genes. Results: We propose a rule-based learning method to identify groups of miRNAs and target genes that are believed to participate cooperatively in the post-transcriptional gene regulation, so-called miRNA regulatory modules (MRMs). Applying our method to human genes and miRNAs, we found 79 MRMs. The MRMs are produced from multiple information sources, including miRNA-target binding information, gene expression and miRNA expression profiles. Analysis of two first MRMs shows that these MRMs consist of highly-related miRNAs and their target genes with respect to biological processes. Conclusion: The MRMs found by our method have high correlation in expression patterns of miRNAs as well as mRNAs. The mRNAs included in the same module shared similar biological functions, indicating the ability of our method to detect functionality-related genes. Moreover, review of the literature reveals that miRNAs in a module are involved in several types of human cancer

SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters

Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis

Induced production of antifungal naphthoquinones in the pitchers of the carnivorous plant Nepenthes khasiana

Nepenthes spp. are carnivorous plants that have developed insect capturing traps, evolved by specific modification of the leaf tips, and are able to utilize insect degradation products as nutritional precursors. A chitin-induced antifungal ability, based on the production and secretion to the trap liquid of droserone and 5-O-methyldroserone, is described here. Such specific secretion uniquely occurred when chitin injection was used as the eliciting agent and probably reflects a certain kind of defence mechanism that has been evolved for protecting the carnivory-based provision of nutritional precursors. The pitcher liquid containing droserone and 5-O-methyldroserone at 3:1 or 4:1 molar ratio, as well as the purified naphthoquinones, exerted an antifungal effect on a wide range of plant and human fungal pathogens. When tested against Candida and Aspergillus spp., the concentrations required for achieving inhibitory and fungicidal effects were significantly lower than those causing cytotoxicity in cells of the human embryonic kidney cell line, 293T. These naturally secreted 1,4-naphthoquinone derivatives, that are assumed to act via semiquinone enhancement of free radical production, may offer a new lead to develop alternative antifungal drugs with reduced selectable pressure for potentially evolved resistance