Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue

Severe malaria due to Plasmodium falciparum infection remains a serious threat to health worldwide and new therapeutic targets are highly desirable. Small molecule inhibitors of prenyl transferases, enzymes that catalyze the post-translational isoprenyl modifications of proteins, exhibit potent antimalarial activity. The antimalarial actions of prenyltransferase inhibitors indicate that protein prenylation is required for malaria parasite development. In this study, we used a chemical biology strategy to experimentally characterize the entire complement of prenylated proteins in the human malaria parasite. In contrast to the expansive mammalian and fungal prenylomes, we find that P. falciparum possesses a restricted set of prenylated proteins. The prenylome of P. falciparum is dominated by Rab GTPases, in addition to a small number of prenylated proteins that also appear to function primarily in membrane trafficking. Overall, we found robust experimental evidence for a total of only thirteen prenylated proteins in P. falciparum, with suggestive evidence for an additional two probable prenyltransferase substrates. Our work contributes to an increasingly complete picture of essential, post-translational hydrophobic modifications in blood-stage P. falciparum

The Degenerate Parametric Oscillator and Ince's Equation

We construct Green's function for the quantum degenerate parametric oscillator in terms of standard solutions of Ince's equation in a framework of a general approach to harmonic oscillators. Exact time-dependent wave functions and their connections with dynamical invariants and SU(1,1) group are also discussed.Comment: 10 pages, no figure

The Minimum-Uncertainty Squeezed States for for Atoms and Photons in a Cavity

We describe a six-parameter family of the minimum-uncertainty squeezed states for the harmonic oscillator in nonrelativistic quantum mechanics. They are derived by the action of corresponding maximal kinematical invariance group on the standard ground state solution. We show that the product of the variances attains the required minimum value 1/4 only at the instances that one variance is a minimum and the other is a maximum, when the squeezing of one of the variances occurs. The generalized coherent states are explicitly constructed and their Wigner function is studied. The overlap coefficients between the squeezed, or generalized harmonic, and the Fock states are explicitly evaluated in terms of hypergeometric functions. The corresponding photons statistics are discussed and some applications to quantum optics, cavity quantum electrodynamics, and superfocusing in channeling scattering are mentioned. Explicit solutions of the Heisenberg equations for radiation field operators with squeezing are found.Comment: 27 pages, no figures, 174 references J. Phys. B: At. Mol. Opt. Phys., Special Issue celebrating the 20th anniversary of quantum state engineering (R. Blatt, A. Lvovsky, and G. Milburn, Guest Editors), May 201

Evolutionary factors affecting the cross-species utility of newly developed microsatellite markers in seabirds

Microsatellite loci are ideal for testing hypotheses relating to genetic segregation at fine spatio-temporal scales. They are also conserved among closely related species, making them potentially useful for clarifying interspecific relationships between recently diverged taxa. However, mutations at primer binding sites may lead to increased non-amplification, or disruptions that may lead to decreased polymorphism in non-target species. Furthermore, high mutation rates and constraints on allele size may also lead, with evolutionary time, to an increase in convergently evolved allele size classes, biasing measures of interspecific genetic differentiation. Here, we used next-generation sequencing to develop microsatellite markers from a shotgun genome sequence of the sub-Antarctic seabird, the thin-billed prion (Pachyptila belcheri), that we tested for cross-species amplification in other Pachyptila and related sub-Antarctic species. We found that heterozygosity decreased and the proportion of non-amplifying loci increased with phylogenetic distance from the target species. Surprisingly, we found that species trees estimated from interspecific FST provided better approximations of mtDNA relationships among the studied species than those estimated using DC, even though FST was more affected by null alleles. We observed a significantly non-linear second order polynomial relationship between microsatellite and mtDNA distances. We propose that the loss of linearity with increasing mtDNA distance stems from an increasing proportion of homoplastic allele size classes that are identical in state, but not identical by descent. Therefore, despite high cross-species amplification success and high polymorphism among the closely related Pachyptila species, we caution against the use of microsatellites in phylogenetic inference among distantly related taxa

Diagnóstico del posgrado en México. Región Centro Occidente

El estudio tiene como propósito analizar la estructura institucional de la oferta del Posgrado en la Región Centro Occidente, con la finalidad de identificar fortalezas y debilidades y con ello proponer políticas públicas para el impulso de la calidad de los estudios de posgrado en México. Con base en la información nacional se elaboraron seis diagnósticos regionales y un diagnóstico nacional del posgrado. En este volumen se presentan los resultados de la Región Centro Occidente que incluye los estados Jalisco, Colima, Guanajuato, Nayarit, Michoacán y Aguascalientes. Se analizan las características de las Instituciones de Educación Superior que impactan en los posgrados que imparten, tales como origen de financiamiento, grado de desarrollo de su normativa, así como las formas de evaluación, entre otras. Se revisan las características académicas, administrativas y financieras de los programas de posgrado como niveles, orientación, modalidades, formación de competencias. Se da cuenta de las características de los actores del posgrado: estudiantes, coordinadores, egresados. Se presentan las relaciones de los posgrados con el entorno y se ofrece una sistematización y análisis cualitativo respecto a lo que los coordinadores identifican como problemas y perspectivas a futuro y estrategias de fortalecimiento del posgrado.Consejo Mexicano de Estudios de PosgradoConsejo Nacional de Ciencia y Tecnologí

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

TAp73 is a central transcriptional regulator of airway multiciliogenesis.

Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation

CD8 Cells of Patients with Diffuse Cutaneous Leishmaniasis Display Functional Exhaustion: The Latter Is Reversed, In Vitro, by TLR2 Agonists

Leishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO) infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL+ cells in their lesions. These characteristics are similar to cellular “exhaustion” described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG) or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion) expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8 T lymphocytes in DCL patients and, additionally, that pre-stimulation with TLR2 ligands can restore the effector mechanisms of CD8 T lymphocytes from DCL patients against Leishmania mexicana-infected macrophages