CARMIL family proteins as multidomain regulators of actin-based motility

CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity. Vertebrates have three highly conserved genes and expressed isoforms of CARMIL with distinct and overlapping localizations and functions in cells. Various domains of these CARMIL isoforms interact with plasma membranes, vimentin intermediate filaments, SH3-containing class I myosins, the dual-GEF Trio, and other adaptors and signaling molecules. These biochemical properties suggest that CARMILs play a variety of membrane-associated functions related to actin assembly and signaling. CARMIL mutations and variants have been implicated in several human diseases. We focus on roles for CARMILs in signaling in addition to their function as regulators of CP and actin. </jats:p

B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells.

Dendritic cells comprise a system of highly efficient antigen-presenting cells involved in the initiation of T cell responses. Herein, we investigated the role of the CD28 pathway during alloreactive T cell proliferation induced by dendritic-Langerhans cells (D-Lc) generated by culturing human cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. In addition to expressing CD80 (B7/BB1), a subset of D-Lc expressed B70/B7-2. Binding of the CTLA4-Ig fusion protein was completely inhibited by a combination of monoclonal antibodies (mAbs) against CD80 and B70/B7-2, indicating the absence of expression of a third ligand for CD28/CTLA-4. It is interesting to note that mAbs against CD86 completely prevented the binding of CTLA4-Ig in the presence of mAbs against CD80 and bound to a B70/B7-2-transfected fibroblast cell line, demonstrating that the B70/B7-2 antigen is identical to CD86. CD28 triggering was essential during D-Lc-induced alloreaction as it was inhibited by mAbs against CD28 (9 out of 11 tested). However, none of six anti-CD80 mAbs demonstrated any activity on the D-Lc-induced alloreaction, though some were previously described as inhibitory in assays using CD80-transfected cell lines. In contrast, a mAb against CD86 (IT-2) was found to suppress the D-Lc-dependent alloreaction by 70%. This inhibitory effect was enhanced to &gt; or = 90% when a combination of anti-CD80 and anti-CD86 mAbs was used. The present results demonstrate that D-Lc express, in addition to CD80, the other ligand for CTLA-4, CD86 (B70/B7-2), which plays a primordial role during D-Lc-induced alloreaction

Resistive flow in a weakly interacting Bose-Einstein condensate

We report the direct observation of resistive flow through a weak link in a weakly interacting atomic Bose-Einstein condensate. Two weak links separate our ring-shaped superfluid atomtronic circuit into two distinct regions, a source and a drain. Motion of these weak links allows for creation of controlled flow between the source and the drain. At a critical value of the weak link velocity, we observe a transition from superfluid flow to superfluid plus resistive flow. Working in the hydrodynamic limit, we observe a conductivity that is 4 orders of magnitude larger than previously reported conductivities for a Bose-Einstein condensate with a tunnel junction. Good agreement with zero-temperature Gross-Pitaevskii simulations and a phenomenological model based on phase slips indicate that the creation of excitations plays an important role in the resulting conductivity. Our measurements of resistive flow elucidate the microscopic origin of the dissipation and pave the way for more complex atomtronic devices.Comment: Version published in PR

A Comparative Analysis of Human Trafficking: The United States of America (USA) and the Republic of South Africa (RSA)

Human trafficking is a serious global problem that transcends international borders and disciplinary boundaries. It presents a conglomeration of problems generally dealt with by public health, criminal justice, social service and immigration agencies. Victim advocates state that millions are victimized each year. The data suggest that law enforcement agencies perceive human trafficking to be of greater, or equal, concern for the myriad of social institutions and participants affected by human trafficking than for law enforcement, itself. Policy recommendations are to refocus the law enforcement response - which may include various approaches that can simultaneously benefit public health - by incorporating an Epidemiological Criminology framework to help to guide the development of more systematic and integrative insight into the world of human trafficking

Atomic-scale structure of the SrTiO3(001)-c(6x2) reconstruction: Experiments and first-principles calculations

The c(6x2) is a reconstruction of the SrTiO3(001) surface that is formed between 1050-1100oC in oxidizing annealing conditions. This work proposes a model for the atomic structure for the c(6x2) obtained through a combination of results from transmission electron diffraction, surface x-ray diffraction, direct methods analysis, computational combinational screening, and density functional theory. As it is formed at high temperatures, the surface is complex and can be described as a short-range ordered phase featuring microscopic domains composed of four main structural motifs. Additionally, non-periodic TiO2 units are present on the surface. Simulated scanning tunneling microscopy images based on the electronic structure calculations are consistent with experimental images

A Surface Reconstruction with a Fractional Hole: (5×5)R26.6∘(\sqrt{5}\times\sqrt{5}) R26.6^\circ LaAlO3_3 (001)

The structure of the $(\sqrt{5}\times\sqrt{5})R26.6^\circ$ reconstruction of LaAlO$_3$ (001) has been determined using transmission electron diffraction combined with direct methods. The structure is relatively simple, consisting of a lanthanum oxide termination with one lanthanum cation vacancy per surface unit cell. The electronic structure is unusual since a fractional number of holes or atomic occupancies per surface unit cell are required to achieve charge neutrality. Density functional calculations indicate that the charge compensation mechanism occurs by means of highly delocalized holes. The surface contains no oxygen vacancies and with a better than 99% confidence level, the holes are not filled with hydrogen. The reconstruction can be understood in terms of expulsion of the more electropositive cation from the surface followed by an increased covalency between the remaining surface lanthanum atoms and adjacent oxygen atoms.Comment: 4 Pages, 3 Figure