Clust&See: A Cytoscape plugin for the identification,visualization and manipulation of network clusters

Background and scope

Large networks, such as protein interaction networks, are extremely difficult to analyze as a whole. We developed Clust&See, a Cytoscape plugin dedicated to the identification, visualization and analysis of clusters extracted from such networks.

Implementation and performance

Clust&See provides the ability to apply three different, recently developed graph clustering algorithms to networks and to visualize: (i) the obtained partition as a quotient graph in which nodes correspond to clusters and (ii) the obtained clusters as their corresponding subnetworks. Importantly, tools for investigating the relationships between clusters and vertices as well as their organization within the whole graph are supplied.     

Complexities in Research on Fathering: Illustrations from the Tufts Study of Young Fathers

Theory and research suggest that the transition to parenthood is a major life transition, and that adaptation to the parenting role is influenced by a complex set of factors, including the relationship with the child's mother, family of origin, and how the father is situated within sociocultural contexts. The father–]mother relationship is particularly important for men making the transition to fatherhood. This study examined patterns of fathering among young fathers (15–24 years) and investigated how fathers' relationships with the mothers of their young children (infants and toddlers) were related to fathering. In general, higher quality father–mother relationships were related to greater father involvement with children; when mothers were perceived as barriers to involved fathering fathers also had less accurate and adaptive parenting knowledge, attitudes, and behavior. Person-centered analyses revealed quite complex relations between father–mother relationships and father–child interaction. One pattern showed strong positive father–mother relationships associated with a disengaged pattern of father–child interaction, while another pattern showed sensitive and positive father–child engagement in the context of negative or distant father–mother relationships. Four patterns of association between fathering and mother–father relationships were demonstrated. Results highlight the complexity of understanding fathering and family relationships among young fathers.     

A one-pot enzymatic approach to the O-fluoroglucoside of N-methylanthranilate

In connection with prospective ¹⁸F-PET imaging studies, the potential for enzymatic synthesis of fluorine-labelled glycosides of small molecules was investigated. Approaches to the enzymatic synthesis of anomeric phosphates of d-gluco-configured fluorosugars proved ineffective. In contrast, starting in the d-galacto series and relying on the consecutive action of Escherichia coli galactokinase (GalK), galactose-1-phosphate uridylyltransferase (GalPUT), uridine-5′-diphosphogalactose 4-epimerase (GalE) and oat root glucosyltransferase (SAD10), a quick and effective synthesis of 6-deoxy-6-fluoro-d-glucosyl N-methylanthranilate ester was achieved.     

A Compact Viral Processing Proteinase/Ubiquitin Hydrolase from the OTU Family

Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule''s C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO''s DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.     

Nanosilicon‐Based Thick Negative Composite Electrodes for Lithium Batteries with Graphene as Conductive Additive

Reduced graphene oxide (rGO) is used as a conductive additive for nanosilicon‐based lithium battery anodes with the high active‐mass loading typically required for industrial applications. In contrast to conventional Si electrodes that use acetylene black (AcB) as an additive, the rGO system shows pronounced improvement of electrochemical performance, irrespective of the cycling conditions. With capacity limitation, the rGO system results in improved coulombic efficiency (99.9%) and longer cycle life than conventional electrodes. Upon cycling without capacity limitation, much higher discharge capacity is maintained (2000 mAh g^?1 after 100 cycles for 2.5 mg of Si cm^?2). Used in conjunction with the bridging carboxymethyl cellulose binder, the crumpled and resilient rGO allows highly reversible functioning of the electrode in which the Si particles repeatedly inflate and deflate upon alloying and dealloying with lithium.     

Luminal lipid regulates CD36 levels and downstream signaling to stimulate chylomicron synthesis

The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.     

Fluid and condensed ApoA-I/phospholipid monolayers provide insights into ApoA-I membrane insertion

Apolipoprotein A-I (ApoA-I) is a protein implicated in the solubilization of lipids and cholesterol from cellular membranes. The study of ApoA-I in phospholipid (PL) monolayers brings relevant information about ApoA-I/PL interactions. We investigated the influence of PL charge and acyl chain organization on the interaction with ApoA-I using dipalmitoyl-phosphatidylcholine, dioleoyl-phosphatidylcholine and dipalmitoyl-phosphatidylglycerol monolayers coupled to ellipsometric, surface pressure, atomic force microscopy and infrared (polarization modulation infrared reflection-absorption spectroscopy) measurements. We show that monolayer compressibility is the major factor controlling protein insertion into PL monolayers and show evidence of the requirement of a minimal distance between lipid headgroups for insertion to occur, Moreover, we demonstrate that ApoA-I inserts deepest at the highest compressibility of the protein monolayer and that the presence of an anionic headgroup increases the amount of protein inserted in the PL monolayer and prevents the steric constrains imposed by the spacing of the headgroup. We also defined the geometry of protein clusters into the lipid monolayer by atomic force microscopy and show evidence of the geometry dependence upon the lipid charge and the distance between headgroups. Finally, we show that ApoA-I helices have a specific orientation when associated to form clusters and that this is influenced by the character of PL charges. Taken together, our results suggest that the interaction of ApoA-I with the cellular membrane may be driven by a mechanism that resembles that of antimicrobial peptide/lipid interaction.