Inferring adaptive codon preference to understand sources of selection shaping codon usage bias.

Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed

THERMODYNAMIC PROPERTIES OF γ\gamma--FLUIDS AND THE QUANTUM VACCUM

The thermodynamic behaviour of a relativistic perfect simple fluid obeying the equation of state $p=(\gamma-1)\rho$, where $0 \le \gamma \le 2$ is a constant, has been investigated. Particular cases include: vacuum($p=-\rho$, $\gamma=0$), a randomly oriented distribution of cosmic strings ($p=-{1 \over 3} \rho$, $\gamma =2/3$), blackbody radiation ($p={1\over 3} \rho$, $\gamma =4/3$) and stiff matter ($p=\rho$, $\gamma=2$). Fluids with $\gamma <1$ become hotter when they expand adiabatically ($T\propto V^{1- \gamma}$). By assuming that such fluids may be regarded as a kind of generalized radiation, the general Planck's type form of the spectrum is deduced. As a limiting case, a new Lorentz invariant spectrum of the vacuum which is compatible with the equation of state and other thermodynamic constraints is proposed. Some possible consequences to the early universe physics are also discussed.Comment: 20 pages, uses LATE

L,L-Diaminopimelate Aminotransferase from Chlamydomonas reinhardtii: A Target for Algaecide Development

In some bacterial species and photosynthetic cohorts, including algae, the enzyme l,l-diaminopimelate aminotransferase (DapL) (E.C. 2.6.1.83) is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA) to l,l-diaminopimelate (l,l-DAP), in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL). The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and l,l-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid l-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides

Along the Indian Ocean coast : genomic variation in Mozambique provides new insights into the Bantu expansion

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Sexuality throughout all the stages of pregnancy: experiences of expectant mothers

Objective: To explore and understand the sexual experiences of expectant mothers during their pregnancy. Methods: The study was carried out in two healthcare centers in the Almería Health District, in southern Spain. The participants included pregnant women who received prenatal care and/or maternity education. The inclusion criteria were being pregnant, maintaining sexual activity and agreeing to participate in the study. The exclusion criteria were having limitations on sexual activity by medical prescription. The sample consisted of 15 expectant women selected using a convenience sample, of which 5 took part in a focus group (FG) and 10 in in-depth interviews (IDI). Data was collected between the months of June and December 2016. Participants were contacted by the main researcher and an appointment was made to carry out the FGs or the IDIs. Results: Three main categories emerged: False beliefs and a holistic approach to sexuality during pregnancy, which is related to the concept of sexuality, false beliefs, and limited sexual counseling during pregnancy. Limitations: From fear at the beginning to physical diffi culty at the end, referring to the fluctuations in sexual desire as well as the physical changes that limit sexual activity. Adapting to changes: safe practices and satisfaction with one’s body image, which encompasses concerns about the risks and the relationship between body image and self-esteem. Conclusion: A lack of sexual counseling during pregnancy leads to the creation of false beliefs, which, together with physical changes, concerns about the risk, and fl uctuations in sexual desire and interest, bring about a decrease in sexual activity. But sexuality remains an important aspect of pregnancy, toward which the participants must adopt a broader approach, not limited to intercourse, and adopt sexual practices that are adapted to the physical and emotional changes that happen during this time