RIAM-VASP module relays integrin complement receptors in outside-in signaling driving particle engulfment

The phagocytic integrins and complement receptors M 2/CR3 and X 2/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-RIAM-Talin-1 pathway. Here, we analyze the implication of RIAM and its binding partner VASP in the signaling events occurring downstream of 2 integrins (outside-in) during complement-mediated phagocytosis. To this end, we used HL-60 promyelocytic cell lines deficient in RIAM or VASP or overexpressing EGFP-tagged VASP to determine VASP dynamics at phagocytic cups. Our results indicate that RIAM-deficient HL-60 cells presented impaired particle internalization and altered integrin downstream signaling during complement-dependent phagocytosis. Similarly, VASP deficiency completely blocked phagocytosis, while VASP overexpression increased the random movement of phagocytic particles at the cell surface, with reduced internalization. Moreover, the recruitment of VASP to particle contact sites, amount of pSer157-VASP and formation of actin-rich phagocytic cups were dependent on RIAM expression. Our results suggested that RIAM worked as a relay for integrin complement receptors in outside-in signaling, coordinating integrin activation and cytoskeletal rearrangements via its interaction with VASPThis work has been supported by Ministerio Español de Economía y Competitividad (MINECO) grants: SAF2016-77096-R (ELD and CC), BIO2014:54164-R (PAR), BIO2017-86500-R (MY-M), EI/MICIU EXPLORA BIO2017-91272-EXP & FEDER (PI17/02303) (S.R.-P). AT-G is supported by a predoctoral fellowship from MINECO, JLS-T is supported by a predoctoral fellowship from Universidad Complutense de Madrid, RT-R is supported by a postdoctoral fellowship from Asociación Española Contra el Cáncer (AECC

Bulletin of the California Polytechnic School 1933-34

Identification of peptides that can bind to major histocompatibility complex (MHC) molecules is important for anticipation of T-cell epitopes and for the design of epitope-based vaccines. Population coverage of epitope vaccines is, however, compromised by the extreme polymorphism of MHC molecules, which is in fact the basis for their differential peptide binding. Therefore, grouping of MHC molecules into supertypes according to peptide-binding specificity is relevant for optimizing the composition of epitope-based vaccines. Despite the fact that the peptide-binding specificity of MHC molecules is linked to their specific amino acid sequences, it is unclear how amino sequence differences correlate with peptide-binding specificities. In this chapter, we detail a method for defining MHC supertypes based on the analysis and subsequent clustering of their peptide-binding repertoires

Moving Towards Self-Reliance: Living Conditions of Refugee Camps in Lebanon and Opportunities for Development

Refugee camps in Lebanon are harsh, continuously and rapidly deteriorating environments. In addition to poverty, numerous wars and the restrictions of civil rights, refugee camps that were not designed as a long-term settlement were made to accommodate their residents in addition to their descendents for a period that has lasted over 59 years. Since the establishment of the camps in 1948 the Palestinian refugees in Lebanon have fallen victim to multiple wars and as a result most camps have witnessed major destruction of homes and infrastructure, and a few were entirely destroyed. Today, the planning and development of the camps are highly restricted by the local government, building material is banned from entering the camps and horizontal as well as vertical expansion is prohibited by Lebanese law. According to the United Nations Relief and Work Agency (UNRWA) the hundreds of thousands of Palestinian refugees in Lebanon have the highest rate of people living in abject poverty in the Middle East. Meanwhile, the refugee community and the international aid agencies working in the camps are caught in the dilemma of investing in the development of a sustainable environment in a settlement with a temporary purpose and an uncertain future. This thesis explores the problems facing the built-environment in the camps within the political and socio-economic context, and takes the camp of Burj El Barajneh as a case study for deeper investigation. It then suggests three possible solution approaches that address the environmental problems within different future scenarios. The thesis also looks at the feasibility and requirements of an energy generation plant to provide part of the energy needs of the camp of Burj El Barjneh. Finally, a set of conclusions and recommendations are derived that address the refugee community, the international aid agencies and the host country. The significance of this study is to mitigate a possible humanitarian and environmental crisis in the most dire of refugee situations in the Middle East, with the hope that conclusions drawn from this study can be applied to refugee communities elsewhere in the region

Strongly zero-dimensional bispaces

Let Cb be the admissible functorial quasi-uniformity on the completely regular bispaces which is spanned by the upper quasi-uniformity on the real line. Answering a question posed by B. Banaschewski and G. C. L. Brümmer in the affirmative we show that CbX is transitive for every strongly zero-dimensional bispace

Definition of MHC Supertypes Through Clustering of MHC Peptide Binding Repertoires

§To whom correspondence should be addresse

Molecular basis of quinolone resistance in Escherichia coli from wild birds

Nine quinolone resistant (minimal inhibitory concentration [MIC] was > 32 μg/mL for nalidixic acid, > 1 μg/mL for ciprofloxacin) isolates of Escherichia coli have been found in wild birds with septicemia. All of the isolates were aerobactin positive. The mechanisms of resistance were characterised by sequencing the quinolone resistance-determining region (QRDR) of the gyrA, gyrB, parC, and parE genes. Sequence analysis of the gyrA gene in all isolates identified only 1 nucleotide substitution at codon Serine-83 for Leucine-83. Sequence analysis of the gyrB, parC, and parE QRDR genes revealed no mutations in any of the isolates. This study was conducted to determine the importance of these genes in the susceptibility of E. coli strains isolated from wild birds to quinolones