Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs

Memory is a hallmark of immunity. Memory carried by antibodies is largely responsible for protection against reinfection with most known acutely lethal infectious agents and is the basis for most clinically successful vaccines. However, the nature of long-term B cell and antibody memory is still unclear. B cell memory was studied here after infection of mice with the rabies-like cytopathic vesicular stomatitis virus, the noncytopathic lymphocytic choriomeningitis virus (Armstrong and WE), and after immunization with various inert viral antigens inducing naive B cells to differentiate either to plasma cells or memory B cells in germinal centers of secondary lymphoid organs. The results show that in contrast to very low background levels against internal viral antigens, no significant neutralizing antibody memory was observed in the absence of antigen and suggest that memory B cells (i) are long-lived in the absence of antigen, nondividing, and relatively resistant to irradiation, and (ii) must be stimulated by antigen to differentiate to short-lived antibody-secreting plasma cells, a process that is also efficient in the bone marrow and always depends on radiosensitive, specific T help. Therefore, for vaccines to induce long-term protective antibody titers, they need to repeatedly provide, or continuously maintain, antigen in minimal quantities over a prolonged time period in secondary lymphoid organs or the bone marrow for sufficient numbers of long-lived memory B cells to mature to short-lived plasma cells.

Loss of HMW1 and HMW3 in noncytadhering mutants of Mycoplasma pneumoniae occurs post-translationally

The genomic sequence of Mycoplasma pneumoniae establish this cell-wall-less prokaryote as among the smallest known microorganisms capable of self-replication. However, this genomic simplicity and corresponding biosynthetic austerity are sharply contrasted by the complex terminal structure found in this species. This tip structure (attachment organelle) directs colonization of the human respiratory mucosa, leading to bronchitis and atypical pneumonia. Furthermore, formation of a second tip structure appears to precede cell division, implying temporal regulation. However, the organization, regulation, and assembly of the attachment organelle in M. pneumoniae are poorly understood, and no counterparts have been identified among the walled bacteria. M. pneumoniae possesses a cytoskeleton-like structure required to localize adhesin proteins to the attachment organelle. The cytadherence-associated proteins HMW1, HMW2, and HMW3 are components of the mycoplasma cytoskeleton, with HMW1 localizing strictly along the filamentous extensions from the cell body and HMW3 being a key structural element of the terminal organelle. Disruptions in hmw2 result in the loss of HMW1 and HMW3. However, the hmw1 and hmw3 genes were transcribed and translated at wild-type levels in hmw2 mutants. HMW1 and HMW3 were relatively stable in the wild-type background over 8 h but disappeared in the mutants over this time period. Evaluation of recombinant HMW1 levels in mycoplasma mutants suggested a requirement for the C-terminal domain of HMW1 for turnover. Finally, an apparent defect in the processing of the precursor for the adhesin protein P1 was noted in the HMW− mutants.

A molecular analysis of dietary diversity for three archaic Native Americans

DNA was extracted from three fecal samples, more than 2,000 years old, from Hinds Cave, Texas. Amplification of human mtDNA sequences showed their affiliation with contemporary Native Americans, while sequences from pronghorn antelope, bighorn sheep, and cottontail rabbit allowed these animals to be identified as part of the diet of these individuals. Furthermore, amplification of chloroplast DNA sequences identified eight different plants as dietary elements. These archaic humans consumed 2–4 different animal species and 4–8 different plant species during a short time period. The success rate for retrieval of DNA from paleofeces is in strong contrast to that from skeletal remains where the success rate is generally low. Thus, human paleofecal remains represent a source of ancient DNA that significantly complements and may in some cases be superior to that from skeletal tissue.

Studies of retrograde memory: A long-term view

Studies of retrograde amnesia are reviewed. First, the issues of temporal gradients of retrograde amnesia are discussed. Second, the question of the anatomical substrates of this syndrome are considered. Finally, some evidence for fractionation of different classes of memoranda within the retrograde time period are presented.

A developmental timer regulates degradation of cyclin E1 at the midblastula transition during Xenopus embryogenesis.

We have analyzed cyclin E1, a protein that is essential for the G1/S transition, during early development in Xenopus embryos. Cyclin E1 was found to be abundant in eggs, and after fertilization, until the midblastula transition (MBT) when levels of cyclin E1 protein, and associated kinase activity, were found to decline precipitously. Our results suggest that the reduced level of the cyclin E1 protein detected after the MBT does not occur indirectly as a result of degradation of the maternally encoded cyclin E1 mRNA. Instead, the stability of cyclin E1 protein appears to play a major role in reduction of cyclin E1 levels at this time. Cyclin E1 protein was found to be stable during the cleavage divisions but degraded with a much shorter half-life after the MBT. Activation of cyclin E1 protein turnover occurs independent of cell cycle progression, does not require ongoing protein synthesis, and is not triggered as a result of the ratio of nuclei to cytoplasm in embryonic cells that initiates the MBT. We therefore propose that a developmental timing mechanism measures an approximately 5-hr time period, from the time of fertilization, and then allows activation of a protein degradative pathway that regulates cyclin E1. Characterization of the timer suggests that it might be held inactive in eggs by a mitogen-activated protein kinase signal transduction pathway.

Effects of TH1 and TH2 cytokines on CD8+ cell response against human immunodeficiency virus: implications for long-term survival.

CD8+ cells from long-term survivors [LTS; infected with human immunodeficiency virus (HIV) for 10 or more years and having CD4+ cell counts of > or = 500 cells per microliters] have a 3-fold greater ability to suppress HIV replication than do CD8+ cells from patients who have progressed to disease (progressors) during the same time period. A change in the pattern of cytokines produced in the host from those that typically favor cell-mediated immunity (T helper 1, TH1 or type 1) to those that down-regulate it (T helper 2, TH2 or type 2) was investigated as a cause of this reduced CD8+ cell anti-HIV function. Treatment of CD8+ cells from LTS with the TH1 cytokine interleukin (IL)-2 enhanced their anti-HIV activity, whereas exposure of these cells to TH2 cytokines IL-4 or IL-10 reduced their ability to suppress HIV replication and to produce IL-2. IL-2 could prevent and reverse the inhibitory effects of IL-4 and IL-10. Moreover, prolonged exposure of CD8+ cells from some progressors to IL-2 improved the ability of these cells to suppress HIV replication. These observations support previous findings suggesting that strong CD8+ cell responses play an important role in maintaining an asymptomatic state in HIV infection. The data suggest that the loss of CD8+ cell suppression of HIV replication associated with disease progression results from a shift in cytokine production within the infected host from a TH1 to a TH2 pattern. Modulation of these cytokines could provide benefit to HIV-infected individuals by improving their CD8+ cell anti-HIV activity.

Temperatures at the last interglacial simulated by a coupled ocean-atmosphere climate model

The last interglacial (Eemian, 125,000 years ago) has generally been considered the warmest time period in the last 200,000 years and thus sometimes been used as a reference for greenhouse projections. Herein we report results from a coupled ocean-atmosphere climate model of the surface temperature response to changes in the radiative forcing at the last interglacial. Although the model generates the expected summer warming in the northern hemisphere, winter cooling of a comparable magnitude occurs over North Africa and tropical Asia. The global annual mean temperature for the Eemian run is 0.3 degrees C cooler than the control run. Validation of simulated sea surface temperatures (SSTs) against reconstructed SSTs supports this conclusion and also the assumption that the flux correction, fitted for the present state, operates satisfactorily for modest perturbations. Our results imply that contrary to conventional expectations, Eemian global temperatures may already have been reached by the mid 20th century.

Effects of Institutional Factors on the Retention of Graduate Students of Color in Schools of Library and Information Science

The intent of the study was to understand the changes that have occurred over the last 25 years in library programs as far as enrollment and diversity of students, number and ethnicity of the faculty, program income and expenses, cost of attendance, and scholarship and fellowship aid, in an effort to better understand library programs granting the MLIS degree. The study also endeavored to identify institutional factors associated with the retention and productivity rates of White students and students of color in schools of library and information science. During the period studied, the proportional representation of White students decreased. For students of color, proportional representation was stable during the same time period. Results revealed a medium effect size of time with productivity rates for both groups declining over time. Retention rate differed significantly by time, with a small effect size with retention rate that initially increased over time, but is now decreasing. The final analyses were meta-regressions to determine if retention and productivity rates can be predicted by cost of attendance, scholarship and fellow aid, and program size. Results indicated that for students of color, program size in 2000 was significantly predictive of retention, cost of attendance was predictive in 2002, and scholarship and fellowship aid was predictive of retention in 2004. No variables were significantly predictive for retention of White students. The last analysis was to determine if productivity rate can be predicted by cost of attendance, scholarship and fellow aid, and program size. Results indicate that for White students in 2002, the cost of attendance was predictive of productivity rating. In 2003, scholarship and fellowship aid was predictive of productivity rate and in 2004, scholarship and fellowship aid was predictive of productivity rating. For students of color, results indicate that only scholarship and fellowship aid in 2005 was predictive of productivity rate. No other variables in any of the years studied showed any significant prediction of productivity rating for students of color.

Ciliary muscle in avian is derived from mesenchymal and epithelial cells

It has long been maintained that the ciliary muscle derives from mesenchymal cells. The embryonic development of the avian ciliary muscle was studied in chick embryos from stage 25 HH to the time of hatching. Serial sections of the eye were stained routinely or immunocytochemically using the monoclonal antibody 13F4, which recognizes a cytoplasmic antigen specific for all types of muscle cells. We found that the mesenchymal immunoreactive cells, at stage 37 HH, are arranged in two distinct orientations forming the anterior and posterior portions of the ciliary muscle. At stages 38 and 39 HH the pigmented epithelium contained 13F4 positive cells, which detach from the epithelium and apparently migrate into stroma. These epithelial cells may differentiate into muscle cells. Within this same time period a progressive accumulation of myoblasts was detected between the pigmented epithelium and the ciliary muscle. Some myoblasts containing melanin were also observed. At stage 40 HH the internal portion of the ciliary muscle was visible. These findings indicate that the immunopositive epithelial cells participate in the formation of the internal portion of the muscle. We conclude that the ciliary muscle derives not only from the mesenchymal cells but also from the pigmented epithelium.

EAST by Northeast

The Eastern Academic Scholars’ Trust (EAST) is a shared print initiative involving 48 libraries across the Northeast. Initiated in 2012 with a planning grant from the Andrew W. Mellon Foundation, EAST addresses directly the growing need for academic libraries to ensure that monographs and journals of scholarly value are not inadvertently discarded as they undertake weeding and deselection programs to free up space for other library services. EAST is currently completing a large-scale analysis of collections across 40 of the participating libraries. This analysis will provide insight into both uniqueness and overlap across the libraries’ holdings and will result in agreements by the libraries to retain circulating monographs in their local collections for an agreed upon time period and to make those materials available to researchers and scholars from other EAST libraries. In parallel to this collection analysis, EAST is implementing validation sampling across the libraries to better understand volume availability and condition and the role they may plan in retention decisions. The project team has developed an innovative sampling methodology and tools to support the study. As the largest shared print initiative to date, this project will secure a substantial portion of the scholarly record that is held in the Northeast and positions EAST as an important component of the growing network of shared print initiatives nationally.

Portrait of Josephine Evans: 1887-1969

The genre of historical women's biography has a moderately short history, and has evolved into the twenty-first century as women's studies. Simultaneously, biography has become a multifaceted genre that keeps a close relationship between biography, history, women's studies, and cultural studies. The biography of Josephine Evans embraces the genre as a vehicle to enlighten broader historical issues, as the life of an ordinary woman and her position in an historic Colorado family is revealed. Her story contributes to the history of women's roles and rights in the late nineteenth and twentieth century as her life story is representative of the time period. This biography of Josephine Evans is an illustration of a biography written from personal letters, diaries, and recollections.

Trends in socioeconomic inequalities in amenable mortality in urban areas of Spanish cities, 1996-2007

Background: While research continues into indicators such as preventable and amenable mortality in order to evaluate quality, access, and equity in the healthcare, it is also necessary to continue identifying the areas of greatest risk owing to these causes of death in urban areas of large cities, where a large part of the population is concentrated, in order to carry out specific actions and reduce inequalities in mortality. This study describes inequalities in amenable mortality in relation to socioeconomic status in small urban areas, and analyses their evolution over the course of the periods 1996–99, 2000–2003 and 2004–2007 in three major cities in the Spanish Mediterranean coast (Alicante, Castellón, and Valencia). Methods: All deaths attributed to amenable causes were analysed among non-institutionalised residents in the three cities studied over the course of the study periods. Census tracts for the cities were grouped into 3 socioeconomic status levels, from higher to lower levels of deprivation, using 5 indicators obtained from the 2001 Spanish Population Census. For each city, the relative risks of death were estimated between socioeconomic status levels using Poisson’s Regression models, adjusted for age and study period, and distinguishing between genders. Results: Amenable mortality contributes significantly to general mortality (around 10%, higher among men), having decreased over time in the three cities studied for men and women. In the three cities studied, with a high degree of consistency, it has been seen that the risks of mortality are greater in areas of higher deprivation, and that these excesses have not significantly modified over time. Conclusions: Although amenable mortality decreases over the time period studied, the socioeconomic inequalities observed are maintained in the three cities. Areas have been identified that display excesses in amenable mortality, potentially attributable to differences in the healthcare system, associated with areas of greater deprivation. Action must be taken in these areas of greater inequality in order to reduce the health inequalities detected. The causes behind socioeconomic inequalities in amenable mortality must be studied in depth.

Familia y discapacidad intelectual: un estudio bibliométrico de 2000-2011 a través del Social Science Citation Index

El objetivo de este estudio fue realizar un análisis bibliométrico de la producción científica publicada entre el año 2000 y 2011 sobre familia y discapacidad intelectual, con la finalidad de ofrecer una descripción global del estado actual de la investigación en dicho ámbito. La base de datos empleada ha sido Social Science Citation lndex extrayendo una muestra de 952 artículos. Fueron analizados el año de publicación, las revistas, el índice de autoría, las temáticas, el tipo de investigación, las citas y el idioma. A por1ir de los resultados, se observó una periodicidad estable en cuanto a los indicadores de producción y una identificación de temáticas que mantienen una relación con la realidad social y las necesidades que envuelve este campo de conocimiento. El presente trabajo permite conocer la evolución que ha seguido el estudio de la familia y la discapacidad intelectual en el periodo temporal indicado y ofrece un amplio conocimiento sobre las investigaciones realizadas al respecto.

Research gaps in accessibility and MOOCs: A systematic literature review 2008-2016 (dataset)

This study presents the results of a systematic literature review on the combined field of Accessibility and Massive Open Online Courses (MOOCs), covering the time period from 2008 to 2016.

Mycophenolatemofetil in non-renal systemiclupuserythematosusmanifestations

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014