Kavosh: a new algorithm for finding network motifs

Background  

Complex networks are studied across many fields of science and are particularly important to understand biological processes. Motifs in networks are small connected sub-graphs that occur significantly in higher frequencies than in random networks. They have recently gathered much attention as a useful concept to uncover structural design principles of complex networks. Existing algorithms for finding network motifs are extremely costly in CPU time and memory consumption and have practically restrictions on the size of motifs.     

Heterochrony and Cross-Species Intersensory Matching by Infant Vervet Monkeys

Background

Understanding the evolutionary origins of a phenotype requires understanding the relationship between ontogenetic and phylogenetic processes. Human infants have been shown to undergo a process of perceptual narrowing during their first year of life, whereby their intersensory ability to match the faces and voices of another species declines as they get older. We investigated the evolutionary origins of this behavioral phenotype by examining whether or not this developmental process occurs in non-human primates as well.

Methodology/Principal Findings

We tested the ability of infant vervet monkeys (Cercopithecus aethiops), ranging in age from 23 to 65 weeks, to match the faces and voices of another non-human primate species (the rhesus monkey, Macaca mulatta). Even though the vervets had no prior exposure to rhesus monkey faces and vocalizations, our findings show that infant vervets can, in fact, recognize the correspondence between rhesus monkey faces and voices (but indicate that they do so by looking at the non-matching face for a greater proportion of overall looking time), and can do so well beyond the age of perceptual narrowing in human infants. Our results further suggest that the pattern of matching by vervet monkeys is influenced by the emotional saliency of the Face+Voice combination. That is, although they looked at the non-matching screen for Face+Voice combinations, they switched to looking at the matching screen when the Voice was replaced with a complex tone of equal duration. Furthermore, an analysis of pupillary responses revealed that their pupils showed greater dilation when looking at the matching natural face/voice combination versus the face/tone combination.

Conclusions/Significance

Because the infant vervets in the current study exhibited cross-species intersensory matching far later in development than do human infants, our findings suggest either that intersensory perceptual narrowing does not occur in Old World monkeys or that it occurs later in development. We argue that these findings reflect the faster rate of neural development in monkeys relative to humans and the resulting differential interaction of this factor with the effects of early experience.     

Portable,Battery-Operated,Low-Cost,Bright Field and Fluorescence Microscope

This study describes the design and evaluation of a portable bright-field and fluorescence microscope that can be manufactured for $240 USD. The microscope uses a battery-operated LED-based flashlight as the light source and achieves a resolution of 0.8 µm at 1000× magnification in fluorescence mode. We tested the diagnostic capability of this new instrument to identify infections caused by the human pathogen, Mycobacterium tuberculosis. Sixty-four direct, decontaminated, and serially diluted smears were prepared from sputa obtained from 19 patients suspected to have M. tuberculosis infection. Slides were stained with auramine orange and evaluated as being positive or negative for M. tuberculosis with both the new portable fluorescence microscope and a laboratory grade fluorescence microscope. Concordant results were obtained in 98.4% of cases. This highly portable, low cost, fluorescence microscope may be a useful diagnostic tool to expand the availability of M. tuberculosis testing at the point-of-care in low resource settings.     

Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization

To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three-dimensional angiospheres reminiscent of alveolar-capillary sacs. After PNX, endothelial-specific inducible genetic ablation of Vegfr2 and Fgfr1 in mice inhibits production of MMP14, impairing alveolarization. MMP14 promotes expansion of epithelial progenitor cells by unmasking cryptic EGF-like ectodomains that activate the EGF receptor (EGFR). Consistent with this, neutralization of MMP14 impairs EGFR-mediated alveolar regeneration, whereas administration of EGF or intravascular transplantation of MMP14(+) PCECs into pneumonectomized Vegfr2/Fgfr1-deficient mice restores alveologenesis and lung inspiratory volume and compliance function. VEGFR2 and FGFR1 activation in PCECs therefore increases MMP14-dependent bioavailability of EGFR ligands to initiate and sustain alveologenesis.     

Seed and gland morphology in Euphorbia (Euphorbiaceae) with focus on their systematic and phylogenetic importance, a case study in Iranian highlands

A comprehensive study based on gland and seed micromorphology in Euphorbia (Euphorbiaceae) for species distributed in Iranian highlands is presented. A total of 86 species were studied. The gland structure was examined by direct field observations. Taxonomically important characters of glands were observed and measured: size, texture, shape, color, and horns. For species out of Iran herbarium materials were studied. Seed characteristics were examined using scanning electron microscopy (SEM) as well as dissecting light microscopy. Significant features are: seed size, seed shape, presence of caruncle, shape of caruncle, and seed surface ornamentation. A phylogenetic study using Maximum Parsimony (MP) and Bayesian Inference (BI) was performed based on sequences of nuclear DNA internal transcribed spacers (ITS) for selected species representing the main clades known in Euphorbia and with special focus on the species distributed in Iranian highlands. ITS sequences for 20 accessions representing 19 species are provided for the first time, and 48 accessions of 47 species were used from GenBank. The topologies of both analyses were congruent. The results indicate: (1) four main clades with high supports in subgen. Esula which are appropriate to be recognized at sectional rank. (2) E. larica is nested within clade A including few members of subgen. Rhizanthium and is closely related to sect. Balsamis, which is suggested here to be transferred from subgen. Esula into subgen. Rhizanthium. (3) E. osyridea of the monotypic subsect. Osyrideae is closely related to E. buhsei and to the members of sect. Esula. Tracing morphological characters on the phylogenetic tree shows that several morphological characters, such as seed ornamentation applied in previous subgeneric classification of the subgen. Esula, are homoplasious, but the gland structure and capsule surface characters are more reliable for classification purposes.     

Protein phosphatase 1-dependent dephosphorylation of Akt is the prime signaling event in sphingosine-induced apoptosis in Jurkat cells

Sphingosine (SPH) is an important bioactive lipid involved in mediating a variety of cell functions including apoptosis. However, the signaling mechanism of SPH-induced apoptosis remains unclear. We have investigated whether SPH inhibits survival signaling in cells by inhibiting Akt kinase activity. This study demonstrates that treatment of Jurkat cells with SPH leads to Akt dephosphorylation as early as 15 min, and the cells undergo apoptosis after 6 h. This Akt dephosphorylation is not mediated through deactivation of upstream kinases, since SPH does not inhibit the upstream phosphoinositide-dependent kinase 1 (PDK1) phosphorylation. Rather, sensitivity to the Ser/Thr protein phosphatase inhibitors (calyculin A, phosphatidic acid, tautomycin, and okadaic acid) indicates an important role for protein phosphatase 1 (PP1) in this process. In vitro phosphatase assay, using Akt immunoprecipitate following treatment with SPH, reveals an increase in Akt-PP1 association as determined by immunoprecipitation analysis. Moreover, SPH-induced dephosphorylation of Akt at Ser(473) subsequently leads to the activation of GSK-3β, caspase 3, PARP cleavage, and ultimately apoptosis. Pre-treatment with caspase 3 inhibitor z-VAD-fmk and Ser/Thr phosphatase inhibitor abrogates the effect of SPH on facilitating apoptosis. Altogether, these results demonstrate that PP1-mediated inhibition of the key anti-apoptotic protein, Akt, plays an important role in SPH-mediated apoptosis in Jurkat cells.     

Systematic implication of seed micromorphology in Arenaria (Caryophyllaceae) and allied genera

Variations in seed micromorphology of 64 taxa of Arenaria and allied genera were examined using scanning electron microscopy (SEM) in order to evaluate their diagnostic value for systematic studies in the genus and providing additional evidence on delimitation of natural groups. Significant diversity was found in seed coat morphology both among and within genera. Size, color, and shape of seeds appear to be of low importance at species level but provide useful evidence at generic rank. Cerastium and Stellaria are well distinguished from Arenaria by serrate seed margins and solid columellae on testa cells. The sculpturing pattern renders most characters potentially applicable in taxonomy and phylogeny assessment in Arenaria. The studied taxa show four basic types of sculpturing, viz. colliculate, rugose, papillate, and smooth. The colliculate type which is characteristic for the core group of Arenaria (A. subg. Arenaria) can be further divided into five subtypes. The smooth seed surface with indistinct cell boundaries represents a synapomorphy for A. subg. Leiosperma, whereas the winged seeds along with rugose surface characterize subg. Odontostemma. Otherwise seed micromorphology rarely provides adequate evidence for separation of natural groups, especially at sectional rank. We hypothesize that the seeds are highly polymorphic in certain groups of taxa showing recent adaptive radiation, such as the annual species of Arenaria, and do not provide strong support for natural groups within the genus.     

NMR structure of the Vibrio vulnificus ribosomal protein S1 domains D3 and D4 provides insights into molecular recognition of single-stranded RNAs

The ribosomal S1 protein (rS1) is indispensable for translation initiation in Gram-negative bacteria. rS1 is a multidomain protein that acts as an RNA chaperone and ensures that mRNAs can bind the ribosome in a single-stranded conformation, which could be related to fast recognition. Although many ribosome structures were solved in recent years, a high-resolution structure of a two-domain mRNA-binding competent rS1 construct is not yet available. Here, we present the NMR solution structure of the minimal mRNA-binding fragment of Vibrio Vulnificus rS1 containing the domains D3 and D4. Both domains are homologues and adapt an oligonucleotide-binding fold (OB fold) motif. NMR titration experiments reveal that recognition of miscellaneous mRNAs occurs via a continuous interaction surface to one side of these structurally linked domains. Using a novel paramagnetic relaxation enhancement (PRE) approach and exploring different spin-labeling positions within RNA, we were able to track the location and determine the orientation of the RNA in the rS1–D34 bound form. Our investigations show that paramagnetically labeled RNAs, spiked into unmodified RNA, can be used as a molecular ruler to provide structural information on protein-RNA complexes. The dynamic interaction occurs on a defined binding groove spanning both domains with identical β2-β3-β5 interfaces. Evidently, the 3′-ends of the cis-acting RNAs are positioned in the direction of the N-terminus of the rS1 protein, thus towards the 30S binding site and adopt a conformation required for translation initiation.