Pore Mutations of the Escherichia coli MscS Channel Affect Desensitization but Not Ionic Preference

Mechanosensitive channels rescue bacterial cells from a fate of lysis when they transfer from a high- to low-osmolarity environment. Of three Escherichia coli mechanosensitive proteins studied to date, only MscS-Ec demonstrates a small anionic preference and a desensitized, nonconducting state under sustained pressure. Little is known about the mechanisms generating these distinctive properties. Eliminating the sole positive charge in the MscS-Ec pore region (Arg88) did not alter anionic preference. Adding positive charges at either end of the pore did not augment anionic preference, and placing negative charges within the pore did not diminish it. Thus, pore charges do not control this characteristic. However, from this analysis we identified mutations in the hinge region of the MscS-Ec pore helix (at Gly113) that profoundly affected ability of the channel to desensitize. Substitution with nonpolar (Ala, Pro) or polar (Asp, Arg, Ser) residues inhibited transition to the desensitized state. Interestingly, Gly113 replaced with Met did not impede desensitization. Thus, although Gly is not specifically required at position 113, MscS desensitization is strongly influenced by the residue situated here. Mutations at residues further into the pore also regulated desensitization. Transition to this unique mechanosensitive channel state is discussed in terms of existing data

Temperature Controlled Transport of Vaccines by Drone In Developing Countries

According to the World Health Organization, vaccines must be transported within a temperature window of 2C to 8C. Much of the world's population does not have access to all season roads. Mountainous regions and regions experiencing violent conflict present challenges to vaccine delivery. Delivering vaccines by drone circumvents many of these problems. The typical drone can carry a 2kg payload. The current method for cooling vaccines is by conditioned ice pack. However, conditioned ice packs are heavy and consume approximately 1/3 or more of the drone's limited payload capacity. This project focuses on developing a more efficient way to keep vaccines cool within a drone's small payload, during transport between facilities regional healthcare facilities and smaller local facilities. The container will need to be packed by a regional worker at the origination point and unpacked by a local worker at the other end. The container needs to be easy to open and close. It needs to be easy to load. It cannot exceed a specific weight and cannot exceed a specific temperature window. Methods researched include redeveloping the ice packs and using simple insulation to finally develop a container that maintains a specific temperature range during transport more efficiently than current conditioned ice packs

Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives.

To identify low penetrance susceptibility alleles for colorectal cancer (CRC), we genotyped 1467 non-synonymous SNPs mapping to 871 candidate cancer genes in 2575 cases and 2707 controls. nsSNP selection was biased towards those predicted to be functionally deleterious. One SNP AKAP9 M463I remained significantly associated with CRC risk after stringent adjustment for multiple testing. Further SNPs associated with CRC risk included several previously reported to be associated with cancer risk including ATM F858L [OR=1.48; 95% confidence interval (CI): 1.06-2.07] and P1054R (OR=1.42; 95% CI: 1.14-1.77) and MTHFR A222V (OR=0.82; 95% CI: 0.69-0.97). To validate associations, we performed a kin-cohort analysis on the 14 704 first-degree relatives of cases for each SNP associated at the 5% level in the case-control analysis employing the marginal maximum likelihood method to infer genotypes of relatives. Our observations support the hypothesis that inherited predisposition to CRC is in part mediated through polymorphic variation and identify a number of SNPs defining inter-individual susceptibility. We have made data from this analysis publicly available at http://www.icr.ac.uk/research/research_sections/cancer_genetics/cancer_genetics_teams/molecular_and_population_genetics/software_and_databases/index.shtml in order to facilitate the identification of low penetrance CRC susceptibility alleles through pooled analyses

Facilitating Interactions for Dogs with Occupations: Wearable Dog - Activated Interfaces

Presented at the 2013 International Symposium on Wearable Computers (ISWC’ 2013), 9-12 September 2013, Zurich, Switzerland.Copyright © 2013 ACMhttp://doi.acm.org/10.1145/2493988.2494334DOI: 10.1145/2493988.2494334Working dogs have improved the lives of thousands of people. However, communication between human and canine partners is currently limited. The main goal of the FIDO project is to research fundamental aspects of wearable technologies to support communication between working dogs and their handlers. In this pilot study, the FIDO team investigated on-body interfaces for assistance dogs in the form of wearable technology integrated into assistance dog vests. We created four different sensors that dogs could activate (based on biting, tugging, and nose gestures) and tested them on-body with three assistance-trained dogs. We were able to demonstrate that it is possible to create wearable sensors that dogs can reliably activate on command