Individual Pause-and-Go Motion Is Instrumental to the Formation and Maintenance of Swarms of Marching Locust Nymphs

The principal interactions leading to the emergence of order in swarms of marching locust nymphs was studied both experimentally, using small groups of marching locusts in the lab, and using computer simulations. We utilized a custom tracking algorithm to reveal fundamental animal-animal interactions leading to collective motion. Uncovering this behavior introduced a new agent-based modeling approach in which pause-and-go motion is pivotal. The behavioral and modeling findings are largely based on motion-related visual sensory inputs obtained by the individual locust. Results suggest a generic principle, in which intermittent animal motion can be considered as a sequence of individual decisions as animals repeatedly reassess their situation and decide whether or not to swarm. This interpretation implies, among other things, some generic characteristics regarding the build-up and emergence of collective order in swarms: in particular, that order and disorder are generic meta-stable states of the system, suggesting that the emergence of order is kinetic and does not necessarily require external environmental changes. This work calls for further experimental as well as theoretical investigation of the neural mechanisms underlying locust coordinative behavior.     

Neural Control of Gas Exchange Patterns in Insects: Locust Density-Dependent Phases as a Test Case

The adaptive significance of discontinuous gas exchange cycles (DGC) in insects is contentious. Based on observations of DGC occurrence in insects of typically large brain size and often socially-complex life history, and spontaneous DGC in decapitated insects, the neural hypothesis for the evolution of DGC was recently proposed. It posits that DGC is a non-adaptive consequence of adaptive down-regulation of brain activity at rest, reverting ventilatory control to pattern-generating circuits in the thoracic ganglia. In line with the predictions of this new hypothesis, we expected a higher likelihood of DGC in the gregarious phase of the desert locust (Schistocerca gregaria, Orthoptera), which is characterized by a larger brain size and increased sensory sensitivity compared with the solitary phase. Furthermore, surgical severing of the neural connections between head and thoracic ganglia was expected to increase DGC prevalence in both phases, and to eliminate phase-dependent variation in gas exchange patterns. Using flow-through respirometry, we measured metabolic rates and gas exchange patterns in locusts at 30°C. In contrast to the predictions of the neural hypothesis, we found no phase-dependent differences in DGC expression. Likewise, surgically severing the descending regulation of thoracic ventilatory control did not increase DGC prevalence in either phase. Moreover, connective-cut solitary locusts abandoned DGC altogether, and employed a typical continuous gas exchange pattern despite maintaining metabolic rate levels of controls. These results are not consistent with the predictions of the neural hypothesis for the evolution of DGC in insects, and instead suggest neural plasticity of ventilatory control.     

Endothelins and their receptors in embryo implantation

As a critical stage of pregnancy, the implantation of blastocysts into the endometrium is a progressive, excessively regulated local tissue remodeling step involving a complex sequence of genetic and cellular interplay executed within an optimal time frame. For better understanding the causes of infertility and, more importantly, for developing powerful strategies for successful implantations and combating infertility, an increasing number of recent studies have been focused on the identification and study of newly described substances in the reproductive tree. The endothelins (ET), a 21-aminoacidic family of genes, have been reported to be responsible for the contraction of vascular and nonvascular smooth muscles, including the smooth muscles of the uterus. Therefore, this review aims to comprehensively discuss the physiological role of endothelins and signaling through their receptors, as well as their probable involvement in the implantation process.     

SWEETLEAD: an In Silico Database of Approved Drugs,Regulated Chemicals,and Herbal Isolates for Computer-Aided Drug Discovery

In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database. The motivation for SWEETLEAD stems from the observance of conflicting information in publicly available chemical databases and the lack of a highly curated database of chemical structures for the globally approved drugs. A consensus building scheme surveying information from several publicly accessible databases was employed to identify the correct structure for each chemical. Resulting structures are filtered for the active pharmaceutical ingredient, standardized, and differing formulations of the same drug were combined in the final database. The publically available release of SWEETLEAD (https://simtk.org/home/sweetlead) provides an important tool to enable the successful completion of computer-aided repurposing and drug discovery campaigns.     

Damped oscillations in the adaptive response of the iron homeostasis network of E. coli

Living organisms often have to adapt to sudden environmental changes and reach homeostasis. To achieve adaptation, cells deploy motifs such as feedback in their genetic networks, endowing the cellular response with desirable properties. We studied the iron homeostasis network of E. coli, which employs feedback loops to regulate iron usage and uptake, while maintaining intracellular iron at non‐toxic levels. Using fluorescence reporters for iron‐dependent promoters in bulk and microfluidics‐based, single‐cell experiments, we show that E. coli cells exhibit damped oscillations in gene expression, following sudden reductions in external iron levels. The oscillations, lasting for several generations, are independent of position along the cell cycle. Experiments with mutants in network components demonstrate the involvement of iron uptake in the oscillations. Our findings suggest that the response is driven by intracellular iron oscillations large enough to induce nearly full network activation/deactivation. We propose a mathematical model based on a negative feedback loop closed by rapid iron uptake, and including iron usage and storage, which captures the main features of the observed behaviour. Taken together, our results shed light on the control of iron metabolism in bacteria and suggest that the oscillations represent a compromise between the requirements of stability and speed of response.     

Mice with Alopecia,Osteoporosis, and Systemic Amyloidosis Due to Mutation in Zdhhc13, a Gene Coding for Palmitoyl Acyltransferase

Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein–protein interactions; however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea–mediated mutagenesis screen, we identified mice with failure to thrive, shortened life span, skin and hair abnormalities including alopecia, severe osteoporosis, and systemic amyloidosis (both AA and AL amyloids depositions). Whole-genome homozygosity mapping with 295 SNP markers and fine mapping with an additional 50 SNPs localized the disease gene to chromosome 7 between 53.9 and 56.3 Mb. A nonsense mutation (c.1273A>T) was located in exon 12 of the Zdhhc13 gene (Zinc finger, DHHC domain containing 13), a gene coding for palmitoyl transferase. The mutation predicted a truncated protein (R425X), and real-time PCR showed markedly reduced Zdhhc13 mRNA. A second gene trap allele of Zdhhc13 has the same phenotypes, suggesting that this is a loss of function allele. This is the first report that palmitoyl transferase deficiency causes a severe phenotype, and it establishes a direct link between protein palmitoylation and regulation of diverse physiologic functions where its absence can result in profound disease pathology. This mouse model can be used to investigate mechanisms where improper palmitoylation leads to disease processes and to understand molecular mechanisms underlying human alopecia, osteoporosis, and amyloidosis and many other neurodegenerative diseases caused by protein misfolding and amyloidosis.     

Lecithin soybean phospholipid nano-transfersomes as potential carriers for transdermal delivery of the human growth hormone

Pharmaceutical molecules such as peptides and proteins are usually injected into the body. Numerous efforts have been made to find new noninvasive ways to administer these peptides. In this study, highly flexible vesicles (transfersomes [TFs]) were designed as a new modern transdermal drug delivery system for systemic drug administration through the skin, which had also been evaluated in vitro. In this study, two growth hormone-loaded TF formulations were prepared, using soybean lecithin and two different surfactants; F₁_sodium deoxycholate and F ₂_sodium lauryl sulfate. Thereafter, the amount of skin penetration by the two formulas was assessed using the Franz diffusion cell system. TF formulations were evaluated for size, zeta potential and in vitro skin penetration across the rat skin. Results indicated that vesicle formulations were stable for 4 weeks and their mean sizes were 241.33 ± 17 and 171 ± 12.12 nm in the F ₁ and F ₂ formulation, respectively. After application to rat skin, transport of the human growth hormone (hGH) released from the TF formulations was found to be higher than that of the hGH alone. Maximum amounts of transdermal hormone delivery were estimated to be 489.54 ± 8.301 and 248.46 ± 4.019 ng·cm−2 , for F ₁ and F ₂, respectively. The results demonstrate the capability of the TF-containing growth hormone in transdermal delivery and superiority of the F ₁ to F ₂ TFs.     

Gastrin''s trophic effect in the colon: Identification of a signaling pathway mediated by protein kinase C

In previous studies we have reported that gastrin exerts a trophic effect on rat colonic epithelial cells in vitro. The effect of gastrin appeared to be mediated through a protein kinase C mechanism. In this study, we have characterized the role of protein kinase C in the gastrin-induced stimulation. Gastrin, in a time- and dose-dependent manner, increased protein kinase C translocation from the cytosol to the membrane, an index of enzyme activation. Maximum translocation occurred in 1 to 2 min following exposure to gastrin (10⁻⁸ M), before declining back to baseline level within 5 min. Gastrin did not change total protein kinase C activity in the colonic cells. Staurosporine, an inhibitor of protein kinase C, totally abolished the basal as well as the gastrin-stimulated activity of protein kinase C. The tumor promoter phorbol 12-myristate 13-acetate also stimulated colonic epithelial protein kinase C. However, prolonged treatment of cells with phorbol inhibited their subsequent response to gastrin stimulation. The response to gastrin was also prevented by the gastrin receptor antagonist proglumide. These observations suggest that protein kinase C mediates the stimulatory effect of gastrin on colonic epithelial cells, possibly through a receptor mechanism.