Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation

Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in specific hypothalamic changes characterized by a precocious increase in the chemokine ligand 2 (CCL2) followed by an increase in pro‐inflammatory cytokines and a decrease in the orexigenic neuropeptide melanin‐concentrating hormone (MCH). We therefore hypothesized that CCL2 could be the central relay for the loss in body weight induced by the inflammatory signal LPS. We find that central delivery of CCL2 promotes neuroinflammation and the decrease in MCH and body weight. MCH neurons express CCL2 receptor and respond to CCL2 by decreasing both electrical activity and MCH release. Pharmacological or genetic inhibition of CCL2 signaling opposes the response to LPS at both molecular and physiologic levels. We conclude that CCL2 signaling onto MCH neurons represents a core mechanism that relays peripheral inflammation to sickness behavior.     

Identification of genetic and environmental factors stimulating excision from Streptomyces scabiei chromosome of the toxicogenic region responsible for pathogenicity

The genes conferring pathogenicity in Streptomyces turgidiscabies, a pathogen causing common scab of potato, are grouped together on a pathogenicity island (PAI), which has been found to be mobile and appears to transfer and disseminate like an integrative and conjugative element (ICE). However, in Streptomyces scabiei, another common scab‐inducing species, the pathogenicity genes are clustered in two regions: the toxicogenic region (TR) and the colonization region. The S. scabiei 87.22 genome was analysed to investigate the potential mobility of the TR. Attachment sites (att), short homologous sequences that delineate ICEs, were identified at both extremities of the TR. An internal att site was also found, suggesting that the TR has a composite structure (TR1 and TR2). Thaxtomin biosynthetic genes, essential for pathogenicity, were found in TR1, whereas candidate genes with known functions in recombination, replication and conjugal transfer were found in TR2. Excision of the TR1 or TR2 subregions alone, or of the entire TR region, was observed, although the excision frequency of TR was low. However, the excision frequency was considerably increased in the presence of either mitomycin C or Streptomyces coelicolor cells. A composite TR structure was not observed in all S. scabiei and Streptomyces acidiscabies strains tested. Of the ten strains analysed, seven lacked TR2 and no TR excision event could be detected in these strains, thus suggesting the implication of TR2 in the mobilization of S. scabiei TR.     

Muscle parameters estimation based on biplanar radiography

The evaluation of muscle and joint forces in vivo is still a challenge. Musculo-Skeletal (musculo-skeletal) models are used to compute forces based on movement analysis. Most of them are built from a scaled-generic model based on cadaver measurements, which provides a low level of personalization, or from Magnetic Resonance Images, which provide a personalized model in lying position. This study proposed an original two steps method to access a subject-specific musculo-skeletal model in 30 min, which is based solely on biplanar X-Rays. First, the subject-specific 3D geometry of bones and skin envelopes were reconstructed from biplanar X-Rays radiography. Then, 2200 corresponding control points were identified between a reference model and the subject-specific X-Rays model. Finally, the shape of 21 lower limb muscles was estimated using a non-linear transformation between the control points in order to fit the muscle shape of the reference model to the X-Rays model. Twelfth musculo-skeletal models were reconstructed and compared to their reference. The muscle volume was not accurately estimated with a standard deviation (SD) ranging from 10 to 68%. However, this method provided an accurate estimation the muscle line of action with a SD of the length difference lower than 2% and a positioning error lower than 20 mm. The moment arm was also well estimated with SD lower than 15% for most muscle, which was significantly better than scaled-generic model for most muscle. This method open the way to a quick modeling method for gait analysis based on biplanar radiography.     

Acquired and Transmitted Multidrug Resistant Tuberculosis: The Role of Social Determinants

Although risk factors for multi-drug resistant tuberculosis are known, few studies have differentiated between acquired and transmitted resistance. It is important to identify factors associated with these different mechanisms to optimize control measures. We conducted a prospective cohort study of index TB patients and their household contacts in Lima, Peru to identify risk factors associated with acquired and transmitted resistance, respectively. Patients with higher socioeconomic status (SES) had a 3-fold increased risk of transmitted resistance compared to those with lower SES when acquired resistance served as the baseline. Quality of housing mediated most of the impact of SES.     

Effect of Mild-to-Moderate Smoking on Viral Load,Cytokines, Oxidative Stress,and Cytochrome P450 Enzymes in HIV-Infected Individuals

Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.     

Mutation for Nonsyndromic Mental Retardation in the trans-2-Enoyl-CoA Reductase TER Gene Involved in Fatty Acid Elongation Impairs the Enzyme Activity and Stability,Leading to Change in Sphingolipid Profile

Very long-chain fatty acids (VLCFAs, chain length >C20) exist in tissues throughout the body and are synthesized by repetition of the fatty acid (FA) elongation cycle composed of four successive enzymatic reactions. In mammals, the TER gene is the only gene encoding trans-2-enoyl-CoA reductase, which catalyzes the fourth reaction in the FA elongation cycle. The TER P182L mutation is the pathogenic mutation for nonsyndromic mental retardation. This mutation substitutes a leucine for a proline residue at amino acid 182 in the TER enzyme. Currently, the mechanism by which the TER P182L mutation causes nonsyndromic mental retardation is unknown. To understand the effect of this mutation on the TER enzyme and VLCFA synthesis, we have biochemically characterized the TER P182L mutant enzyme using yeast and mammalian cells transfected with the TER P182L mutant gene and analyzed the FA elongation cycle in the B-lymphoblastoid cell line with the homozygous TER P182L mutation (TER^P182L/P182L B-lymphoblastoid cell line). We have found that TER P182L mutant enzyme exhibits reduced trans-2-enoyl-CoA reductase activity and protein stability, thereby impairing VLCFA synthesis and, in turn, altering the sphingolipid profile (i.e. decreased level of C24 sphingomyelin and C24 ceramide) in the TER^P182L/P182L B-lymphoblastoid cell line. We have also found that in addition to the TER enzyme-catalyzed fourth reaction, the third reaction in the FA elongation cycle is affected by the TER P182L mutation. These findings provide new insight into the biochemical defects associated with this genetic mutation.     

Host and Phenology Shifts in the Evolution of the Social Moth Genus Thaumetopoea

The genus Thaumetopoea contains the processionary moths, a group of lepidopteran associated with forest trees, well known for the social behaviour of the larvae and for carrying urticating setae. The taxonomy of the genus is partly unresolved and a phylogenetic approach is lacking. The goal of this work is to produce a phylogeny for Thaumetopoea and to identify the main traits driving the evolution of this group. Eighteen mitochondrial and three nuclear genes were fully/partly sequenced. Markers were aligned and analysed singularly or in various combinations. Phylogenetic analyses were performed according to maximum likelihood and Bayesian inference methods. Trees obtained from largest data sets provided identical topologies that received strong statistical support. Three main clades were identified within Thaumetopoea and were further supported by several signatures located in the mitochondrial tRNAs and intergenic spacers. The reference topology was used to investigate the evolution of life history traits related to biogeography, host plant, ecology, and morphology. A multigenic approach allowed to produce a robust phylogenetic analysis of the genus Thaumetopoea, with the identification of three major clades linked to different ecological and life history traits. The first clade is associated with Angiosperm host plants and has a fast spring development of larvae on young foliage. The other clades have originated by one event of host plant shift to Gymnosperm Pinaceae, which implied a longer larval developmental time due to the lower nutritional quality of leaves. These clades showed different adaptations to such a constraint, the first with a switch of larval feeding to cold season (winter pine processionary moths), and the second with a retraction to high altitude and latitude and a development cycle extended over two years (summer pine processionary moths). Recent global warming is affecting all species and seems able to further shape the evolution of the group.     

Connectivity across the Caribbean Sea: DNA Barcoding and Morphology Unite an Enigmatic Fish Larva from the Florida Straits with a New Species of Sea Bass from Deep Reefs off Cura?ao

Integrative taxonomy, in which multiple disciplines are combined to address questions related to biological species diversity, is a valuable tool for identifying pelagic marine fish larvae and recognizing the existence of new fish species. Here we combine data from DNA barcoding, comparative morphology, and analysis of color patterns to identify an unusual fish larva from the Florida Straits and demonstrate that it is the pelagic larval phase of a previously undescribed species of Liopropoma sea bass from deep reefs off Curaçao, southern Caribbean. The larva is unique among larvae of the teleost family Serranidae, Tribe Liopropomini, in having seven elongate dorsal-fin spines. Adults of the new species are similar to the golden bass, Liopropoma aberrans, with which they have been confused, but they are distinct genetically and morphologically. The new species differs from all other western Atlantic liopropomins in having IX, 11 dorsal-fin rays and in having a unique color pattern–most notably the predominance of yellow pigment on the dorsal portion of the trunk, a pale to white body ventrally, and yellow spots scattered across both the dorsal and ventral portions of the trunk. Exploration of deep reefs to 300 m using a manned submersible off Curaçao is resulting in the discovery of numerous new fish species, improving our genetic databases, and greatly enhancing our understanding of deep-reef fish diversity in the southern Caribbean. Oh the mother and child reunion is only a moment away. Paul Simon.