mab-31 and the TGF-β pathway act in the ray lineage to pattern C. elegans male sensory rays

<p>Abstract</p> <p>Background</p> <p><it>C. elegans </it>TGF-β-like Sma/Mab signaling pathway regulates both body size and sensory ray patterning. Most of the components in this pathway were initially identified by genetic screens based on the small body phenotype, and many of these mutants display sensory ray patterning defect. At the cellular level, little is known about how and where these components work although ray structural cell has been implicated as one of the targets. Based on the specific ray patterning abnormality, we aim to identify by RNAi approach additional components that function specifically in the ray lineage to elucidate the regulatory role of TGF-β signaling in ray differentiation.</p> <p>Result</p> <p>We report here the characterization of a new member of the Sma/Mab pathway, <it>mab-31</it>, recovered from a genome-wide RNAi screen. <it>mab-31 </it>mutants showed ray cell cluster patterning defect and mis-specification of the ray identity. <it>mab-31 </it>encodes a nuclear protein expressed in descendants of ray precursor cells impacting on the ray cell's clustering properties, orientation of cell division plane, and fusion of structural cells. Genetic experiments also establish its relationship with other Sma/Mab pathway components and transcription factors acting upstream and downstream of the signaling event.</p> <p>Conclusion</p> <p><it>mab-31 </it>function is indispensable in Sma/Mab signal recipient cells during sensory rays specification. Both <it>mab-31 </it>and <it>sma-6 </it>are required in ray lineage at the late larval stages. They act upstream of <it>C. elegans Pax-6 </it>homolog and repress its function. These findings suggested <it>mab-31 </it>is a key factor that can integrate TFG-β signals in male sensory ray lineage to define organ identity.</p

Negative Group Velocity from Quadrupole Resonance of Plasmonic Spheres

We study the dispersions of plasmonic bands that arise from the coupling of electric quadrupole resonances in three dimensional photonic crystals (PCs) consisting of plasmonic spheres. Through analytical derivation, we show that two branches of quadrupole bands in simple cubic PCs with a small lattice constant possess negative group velocities. Distinct from double negative media in which the negative responses originates from the coupling of electric and magnetic responses (P and M), the negative dispersion induced by quadrupole resonance is an intrinsic property of quadrupole that does not require coupling to another degree of freedom. In addition, there is no simple effective medium description. In plasmonic systems composed of metallic nanoparticle clusters, the coupled quadrupole resonance may be tuned to lower optical frequencies, and the coupling strength between this quadrupole resonance and external electromagnetic (EM) waves are in the same order of the magnetic dipole M.Comment: 21 pages, 4 figure

Formation of Super-Earths

Super-Earths are the most abundant planets known to date and are characterized by having sizes between that of Earth and Neptune, typical orbital periods of less than 100 days and gaseous envelopes that are often massive enough to significantly contribute to the planet's overall radius. Furthermore, super-Earths regularly appear in tightly-packed multiple-planet systems, but resonant configurations in such systems are rare. This chapters summarizes current super-Earth formation theories. It starts from the formation of rocky cores and subsequent accretion of gaseous envelopes. We follow the thermal evolution of newly formed super-Earths and discuss their atmospheric mass loss due to disk dispersal, photoevaporation, core-cooling and collisions. We conclude with a comparison of observations and theoretical predictions, highlighting that even super-Earths that appear as barren rocky cores today likely formed with primordial hydrogen and helium envelopes and discuss some paths forward for the future.Comment: Invited review accepted for publication in the 'Handbook of Exoplanets,' Planet Formation section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Ed

The bactericidal effect of dendritic copper microparticles, contained in an alginate matrix, on Escherichia coli.

Although the bactericidal effect of copper has been known for centuries, there is a current resurgence of interest in the use of this element as an antimicrobial agent. During this study the use of dendritic copper microparticles embedded in an alginate matrix as a rapid method for the deactivation of Escherichia coli ATCC 11775 was investigated. The copper/alginate produced a decrease in the minimum inhibitory concentration from free copper powder dispersed in the media from 0.25 to 0.065 mg/ml. Beads loaded with 4% Cu deactivated 99.97% of bacteria after 90 minutes, compared to a 44.2% reduction in viability in the equivalent free copper powder treatment. There was no observed loss in the efficacy of this method with increasing bacterial loading up to 10(6) cells/ml, however only 88.2% of E. coli were deactivated after 90 minutes at a loading of 10(8) cells/ml. The efficacy of this method was highly dependent on the oxygen content of the media, with a 4.01% increase in viable bacteria observed under anoxic conditions compared to a >99% reduction in bacterial viability in oxygen tensions above 50% of saturation. Scanning electron micrographs (SEM) of the beads indicated that the dendritic copper particles sit as discrete clusters within a layered alginate matrix, and that the external surface of the beads has a scale-like appearance with dendritic copper particles extruding. E. coli cells visualised using SEM indicated a loss of cellular integrity upon Cu bead treatment with obvious visible blebbing. This study indicates the use of microscale dendritic particles of Cu embedded in an alginate matrix to effectively deactivate E. coli cells and opens the possibility of their application within effective water treatment processes, especially in high particulate waste streams where conventional methods, such as UV treatment or chlorination, are ineffective or inappropriate

Methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii on computer interface surfaces of hospital wards and association with clinical isolates

<p>Abstract</p> <p>Background</p> <p>Computer keyboards and mice are potential reservoirs of nosocomial pathogens, but routine disinfection for non-water-proof computer devices is a problem. With better hand hygiene compliance of health-care workers (HCWs), the impact of these potential sources of contamination on clinical infection needs to be clarified.</p> <p>Methods</p> <p>This study was conducted in a 1600-bed medical center of southern Taiwan with 47 wards and 282 computers. With education and monitoring program of hand hygiene for HCWs, the average compliance rate was 74% before our surveillance. We investigated the association of methicillin-resistant <it>Staphylococcus aureus </it>(MRSA), <it>Pseudomonas aeruginosa </it>and <it>Acinetobacter baumannii</it>, three leading hospital-acquired pathogens, from ward computer keyboards, mice and from clinical isolates in non-outbreak period by pulsed field gel electrophoresis and antibiogram.</p> <p>Results</p> <p>Our results revealed a 17.4% (49/282) contamination rate of these computer devices by <it>S. aureus</it>, <it>Acinetobacter </it>spp. or <it>Pseudomonas </it>spp. The contamination rates of MRSA and <it>A. baumannii </it>in the ward computers were 1.1% and 4.3%, respectively. No <it>P. aeruginosa </it>was isolated. All isolates from computers and clinical specimens at the same ward showed different pulsotypes. However, <it>A. baumannii </it>isolates on two ward computers had the same pulsotype.</p> <p>Conclusion</p> <p>With good hand hygiene compliance, we found relatively low contamination rates of MRSA, <it>P. aeruginosa </it>and <it>A. baumannii </it>on ward computer interface, and without further contribution to nosocomial infection. Our results suggested no necessity of routine culture surveillance in non-outbreak situation.</p

A Brain-Computer Interface Based Attention Training Program for Treating Attention Deficit Hyperactivity Disorder

10.1371/journal.pone.0046692PLoS ONE710

Keratin 8/18 Regulation of Cell Stiffness-Extracellular Matrix Interplay through Modulation of Rho-Mediated Actin Cytoskeleton Dynamics

Cell mechanical activity generated from the interplay between the extracellular matrix (ECM) and the actin cytoskeleton is essential for the regulation of cell adhesion, spreading and migration during normal and cancer development. Keratins are the intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatic epithelial cell IFs are made solely of keratins 8/18 (K8/K18), hallmarks of all simple epithelia. Notably, our recent work on these epithelial cells has revealed a key regulatory function for K8/K18 IFs in adhesion/migration, through modulation of integrin interactions with ECM, actin adaptors and signaling molecules at focal adhesions. Here, using K8-knockdown rat H4 hepatoma cells and their K8/K18-containing counterparts seeded on fibronectin-coated substrata of different rigidities, we show that the K8/K18 IF-lacking cells lose their ability to spread and exhibit an altered actin fiber organization, upon seeding on a low-rigidity substratum. We also demonstrate a concomitant reduction in local cell stiffness at focal adhesions generated by fibronectin-coated microbeads attached to the dorsal cell surface. In addition, we find that this K8/K18 IF modulation of cell stiffness and actin fiber organization occurs through RhoA-ROCK signaling. Together, the results uncover a K8/K18 IF contribution to the cell stiffness-ECM rigidity interplay through a modulation of Rho-dependent actin organization and dynamics in simple epithelial cells

Characterizing Dynamic Changes in the Human Blood Transcriptional Network

Gene expression data generated systematically in a given system over multiple time points provides a source of perturbation that can be leveraged to infer causal relationships among genes explaining network changes. Previously, we showed that food intake has a large impact on blood gene expression patterns and that these responses, either in terms of gene expression level or gene-gene connectivity, are strongly associated with metabolic diseases. In this study, we explored which genes drive the changes of gene expression patterns in response to time and food intake. We applied the Granger causality test and the dynamic Bayesian network to gene expression data generated from blood samples collected at multiple time points during the course of a day. The simulation result shows that combining many short time series together is as powerful to infer Granger causality as using a single long time series. Using the Granger causality test, we identified genes that were supported as the most likely causal candidates for the coordinated temporal changes in the network. These results show that PER1 is a key regulator of the blood transcriptional network, in which multiple biological processes are under circadian rhythm regulation. The fasted and fed dynamic Bayesian networks showed that over 72% of dynamic connections are self links. Finally, we show that different processes such as inflammation and lipid metabolism, which are disconnected in the static network, become dynamically linked in response to food intake, which would suggest that increasing nutritional load leads to coordinate regulation of these biological processes. In conclusion, our results suggest that food intake has a profound impact on the dynamic co-regulation of multiple biological processes, such as metabolism, immune response, apoptosis and circadian rhythm. The results could have broader implications for the design of studies of disease association and drug response in clinical trials

Induction of Cellular Senescence by Doxorubicin Is Associated with Upregulated miR-375 and Induction of Autophagy in K562 Cells

BACKGROUND: Cellular senescence is a specialized form of growth arrest that is generally irreversible. Upregulated p16, p53, and p21 expression and silencing of E2F target genes have been characterized to promote the establishment of senescence. It can be further aided by the transcriptional repression of proliferation-associated genes by the action of HP1γ, HMGA, and DNMT proteins to produce a repressive chromatin environment. Therefore, senescence has been suggested to functions as a natural brake for tumor development and plays a critical role in tumor suppression and aging. METHODOLOGY/PRINCIPAL FINDINGS: An in vitro senescence model has been established by using K562 cells treated with 50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562 cells, the DOX-induced senescence in K562 cells ought to be independent of p53 and p16-pRb pathways. Indeed, no change in the expression of the typical senescence-associated premalignant cell markers in the DOX-induced senescent K562 cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the proliferation ability suppressed by DOX (p<0.05) and overexpression of miR-375 suppressed the normal proliferation of K562 cells. Upregulated miR-375 expression was associated with downregulated expression of 14-3-3zeta and SP1 genes. Autophagy was also investigated since DOX treatment was able to induce cells entering senescence and eventually lead to cell death. Among the 24 human autophagy-related genes examined, a 12-fold increase of ATG9B at day 4 and a 20-fold increase of ATG18 at day 2 after DOX treatment were noted. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

LRRK2 plays an important role in Parkinson's disease (PD), but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2) protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it caused Parkinsonism-like phenotypes, including loss of dopaminergic neurons in diencephalon and locomotion defects. These neurodegenerative and locomotion defects could be rescued by over-expressing zLRRK2 or hLRRK2 mRNA. The administration of L-dopa could also rescue the locomotion defects, but not the neurodegeneration. Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD