Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant

The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat

Evidence for Restriction of Ancient Primate Gammaretroviruses by APOBEC3 but Not TRIM5α Proteins

Because of evolutionary pressures imposed through episodic colonization by retroviruses, many mammals express factors, such as TRIM5α and APOBEC3 proteins, that directly restrict retroviral replication. TRIM5 and APOBEC restriction factors are most often studied in the context of modern primate lentiviruses, but it is likely that ancient retroviruses imposed the selective pressure that is evident in primate TRIM5 and APOBEC3 genes. Moreover, these antiretroviral factors have been shown to act against a variety of retroviruses, including gammaretroviruses. Endogenous retroviruses can provide a ‘fossil record’ of extinct retroviruses and perhaps evidence of ancient TRIM5 and APOBEC3 antiviral activity. Here, we investigate whether TRIM5 and APOBEC3 proteins restricted the replication of two groups of gammaretroviruses that were endogenized in the past few million years. These endogenous retroviruses appear quite widespread in the genomes of old world primates but failed to colonize the human germline. Our analyses suggest that TRIM5α proteins did not pose a major barrier to the cross-species transmission of these two families of gammaretroviruses, and did not contribute to their extinction. However, we uncovered extensive evidence for inactivation of ancient gammaretroviruses through the action of APOBEC3 cytidine deaminases. Interestingly, the identities of the cytidine deaminases responsible for inactivation appear to have varied in both a virus and host species–dependent manner. Overall, sequence analyses and reconstitution of ancient retroviruses from remnants that have been preserved in the genomes of modern organisms offer the opportunity to probe and potentially explain the evolutionary history of host defenses against retroviruses

Channel Assignment with Separation for Interference Avoidance in Wireless Networks

Given an integer $\sigma > 1$, a vector $(\delta_1, \delta_2, \ldots, \delta_{\sigma-1})$ of nonnegative integers, and an undirected graph $G=(V,E)$, an $L(\delta_1, \delta_2, \ldots,\delta_{\sigma-1})$-coloring of $G$ is a function $f$ from the vertex set $V$ to a set of nonnegative integers such that $| f(u) -f(v) | \ge \delta_i$, if $d(u,v) = i, \ 1 \le i \le \sigma-1, \$ where $d(u,v)$ is the distance (i.e. the minimum number of edges) between the vertices $u$ and $v$. An optimal $L(\delta_1, \delta_2, \ldots,\delta_{\sigma-1})$-coloring for $G$ is one using the smallest range $\lambda$ of integers over all such colorings. This problem has relevant application in channel assignment for interference avoidance in wireless networks, where channels (i.e. colors) assigned to interfering stations (i.e. vertices) at distance $i$ must be at least $\delta_i$ apart, while the same channel can be reused in vertices whose distance is at least $\sigma$. In particular, two versions of the coloring problem -- $L(2,1,1)$, and $L(\delta_1, 1, \ldots,1)$ -- are considered. Since these versions of the problem are $NP$-hard for general graphs, efficient algorithms for finding optimal colorings are provided for specific graphs modeling realistic wireless networks including rings, bidimensional grids, and cellular grids

Identification des besoins en mécanisation des agricultures des pays en développement, le cas du lac Alaotra à Madagascar

The authors describe farmer's reactions to the innovations proposed for 70 years as regards agricultural mechanization in the region. The analysis is a help to understand current farming practices and take higher account of producers' implicit or explicit demands for assistance when defining action programs in which mechanization is supposed to promote the intensification and diversification of agricultural commodities.Les auteurs décrivent les réactions paysannes face aux innovations proposées depuis 70 ans pour la mécanisation de l'agriculture dans cette région. La diffusion de la culture attelée apparaît nettement corrélée aux dynamiques foncières et aux sollicitations des marchés de produits agricoles, dans un contexte favorable à l'extension des surfaces mais peu propice à l'intensification. Cette analyse aide à comprendre les pratiques culturales actuelles et à mieux intégrer les demandes d'appui implicites ou explicites des producteurs dans la définition d'un programme d'actions où la mécanisation doit favoriser l'intensification et la diversification des productions agricoles et d'élevage

Dynamic combinatorial mass spectrometry leads to metallo-beta-lactamase inhibitors.

The use of protein ESI mass spectrometry under non-denaturing conditions to analyze a dynamic combinatorial library of thiols/disulfides with the BcII metallo-beta-lactamase enabled the rapid identification of an inhibitor with a K(i) of < 1 microM. The study exemplifies the utility of protein-MS for screening dynamic mixtures of potential enzyme-inhibitors

Infection with Burkholderia pseudomallei - immune correlates of survival in acute melioidosis

Melioidosis, caused by Burkholderia pseudomallei, is a potentially lethal infection with no licensed vaccine. There is little understanding of why some exposed individuals have no symptoms, while others rapidly progress to sepsis and death, or why diabetes confers increased susceptibility. We prospectively recruited a cohort of 183 acute melioidosis patients and 21 control subjects from Northeast Thailand and studied immune parameters in the context of survival status and the presence or absence of diabetes. HLA-B*46 (one of the commonest HLA class I alleles in SE Asia) and HLA-C*01 were associated with an increased risk of death (odds ratio 2.8 and 3.1 respectively). Transcriptomic analysis during acute infection in diabetics indicated the importance of interplay between immune pathways including those involved in antigen presentation, chemotaxis, innate and adaptive immunity and their regulation. Survival was associated with enhanced T cell immunity to nine of fifteen immunodominant antigens analysed including AhpC (BPSL2096), BopE (BPSS1525), PilO (BPSS1599), ATP binding protein (BPSS1385) and an uncharacterised protein (BPSL2520). T cell immunity to GroEL (BPSL2697) was specifically impaired in diabetic individuals. This characterization of immunity associated with survival during acute infection offers insights into correlates of protection and a foundation for design of an effective multivalent vaccine