Regulatory B cells in seasonal allergic rhinitis and the influence of grass pollen immunotherapy

Introduction: Interleukin (IL)-10-producing B cells (Bregs) regulate immune responses in autoimmune disease; however their role in allergy is unclear. Allergen exposure in predisposed atopic individuals results in the induction of IgE-secreting B cells, crucial in the immunopathophysiology of allergic rhinitis. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis. AIT results in long-term clinical and immunological tolerance; however, whether Bregs contribute towards AIT-induced tolerance remains unclear. Hypotheses: 1. In vitro induced IL-10-producing B cells regulate allergen-driven Th2 inflammation, 2. Bregs are present in fewer numbers in seasonal grass pollen allergic (SAR) individuals compared with healthy controls, which is restored during AIT. Methods: B cells were isolated and subjected to flow cytometry to detect surface markers and IL-10 capacity following CpG stimulation. FluoroSpot, ELISA or qPCR were used to confirm IL-10. Suppression of T cell proliferation (by CFSE) and cytokine production (by ELISA) were carried out in co-cultures. Regulatory B cells in SAR (n=14), AIT (n=18) and healthy (n=14) donors were compared. Nasal allergen challenge (NAC) was carried out, with blood taken pre and post challenge for flow cytometry. Results: CpG significantly enhanced proportions of Bregs, with enrichment particularly within CD24hiCD27+, CD5hi, PD-L1+ and CD24hiCD38hi populations. Bregs suppressed both polyclonally- and grass pollen allergen-stimulated T cells. Ex vivo, proportions of IL-10+ B cells from SAR and healthy donors matched, but were significantly greater amongst AIT donors (particularly sublingual immunotherapy - SLIT) compared to SAR. Following NAC, proportions of B cells within CD24hiCD38hi, CD5hi, CD24hiCD27hi and CD25+ subsets were significantly increased amongst non-allergic and AIT groups, but not amongst SAR donors. Conclusion: Bregs are capable of suppressing allergen induced, Th2-driven inflammation in vitro and may be involved in the induction of tolerance during allergen immunotherapy in vivo, particularly following SLIT.Open Acces

The Temple, purity and the Background to Jesus' Death

Alguns impressionants descobriments arqueològics han donat nova llum en alguns dels raonaments després de la mort de Jesús. El més important d’aquests descobriments és el dels recipients de pedra (per a les purificacions rituals), mikvaot (banys rituals jueus) i piscines fetes de fems (que no estan profanades ja que són d’una matèria natural i no han estat cuites, com els recipients de ceràmica). Moltes de les halakot jueves (regles legals jueves) vigents en època de Jesús estaven contra la legislació de la Torah (les que es troben a l’Antic Testament). Jesús apareix ara com contrari al desenvolupament de la nova legislació anti-Torah en alguns grups jueus. Molts d’aquests es varen desenvolupar I havien rebut el suport dels caps de les faccions jueves, inclús els sacerdots que controlaven el Temple. Per una banda, hem de reconèixer el retrat del judaisme del període del Segon Temple com a legalista o equiparar els fariseus com a hipòcrites. Per l’altra banda, hem de reconèixer que molts dels ensenyaments de Jesús eren considerats inacceptables per molts grups de jueus poderosos. Finalment, molts jueus, que formaven part del Temple, respectaven la postura de Jesús (Mc 12,32).Impressive archaeological discoveries have shed new light on some of the reasoning behind Jesus’ death. Most importantly among them are the discovery of stone vessels [for ritual purification], mikvaot [Jewish ritual baths], and dung vessels [which do not become defiled because they are natural and unbaked as are pottery vessels]. Some of the Jewish halakot (Jewish legal rules) developed during Jesus’ time are against the Torah legislations [those found in the “Old Testament”]. Jesus appears now to be against the newly developing anti-Torah legislation in some Jewish groups. Many of these were developed and endorsed by the ruling Jewish parties, including the priests who controlled the Temple. On the one hand, we must avoid the portrayal of Second Temple Judaism as “legalistic” or equate Pharisees with hypocrites. On the other hand, we must recognize that some of Jesus’ teachings were deemed unacceptable by some powerful Jewish groups. Finally, many Jews, including those in the Temple admired Jesus’ position (Mk 12:32)

Neuropsychological evaluation of blast-related concussion: Illustrating the challenges and complexities through OEF/OIF case studies

Background/objective: Soldiers of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) sustain blast-related mild traumatic brain injury (concussion) with alarming regularity. This study discusses factors in addition to concussion, such as co-morbid psychological difficulty (e.g. post-traumatic stress) and symptom validity concerns that may complicate neuropsychological evaluation in the late stage of concussive injury. Case report: The study presents the complexities that accompany neuropsychological evaluation of blast concussion through discussion of three case reports of OEF/OIF personnel. Discussion: The authors emphasize uniform assessment of blast concussion, the importance of determining concussion severity according to acute-injury characteristics and elaborate upon non-concussion-related factors that may impact course of cognitive limitation. The authors conclude with a discussion of the need for future research examining the impact of blast concussion (particularly recurrent concussion) and neuropsychological performance

Evaluation Context Impacts Neuropsychological Performance of OEF/OIF Veterans with Reported Combat-Related Concussion

Although soldiers of Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) encounter combat-related concussion at an unprecedented rate, relatively few studies have examined how evaluation context, insufficient effort, and concussion history impact neuropsychological performances in the years following injury. The current study explores these issues in a sample of 119 U.S. veterans (OEF/OIF forensic concussion, n = 24; non-OEF/OIF forensic concussion, n = 20; OEF/OIF research concussion, n = 38; OEF/OIF research without concussion, n = 37). The OEF/OIF forensic concussion group exhibited significantly higher rates of insufficient effort relative to the OEF/OIF research concussion group, but a comparable rate of insufficient effort relative to the non-OEF/OIF forensic concussion group. After controlling for effort, the research concussion and the research non-concussion groups demonstrated comparable neuropsychological performance. Results highlight the importance of effort assessment among OEF/OIF and other veterans with concussion history, particularly in forensic contexts

Kierkegaard and Optical Linguistics

Kierkegaard and Optical Linguistic

Untapped Resources: Biotechnological Potential of Peptides and Secondary Metabolites in Archaea

Archaea are an understudied domain of life often found in “extreme” environments in terms of temperature, salinity, and a range of other factors. Archaeal proteins, such as a wide range of enzymes, have adapted to function under these extreme conditions, providing biotechnology with interesting activities to exploit. In addition to producing structural and enzymatic proteins, archaea also produce a range of small peptide molecules (such as archaeocins) and other novel secondary metabolites such as those putatively involved in cell communication (acyl homoserine lactones), which can be exploited for biotechnological purposes. Due to the wide array of metabolites produced there is a great deal of biotechnological potential from antimicrobials such as diketopiperazines and archaeocins, as well as roles in the cosmetics and food industry. In this review we will discuss the diversity of small molecules, both peptide and nonpeptide, produced by archaea and their potential biotechnological applications

Neuropsychological Outcomes of U.S. Veterans with Report of Remote Blast-Related Concussion and Current Psychopathology

This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11

EVIDENCE FOR OVERDOMINANT SELECTION MAINTAINING X-LINKED FITNESS VARIATION IN DROSOPHILA MELANOGASTER

The role of balancing selection in maintaining genetic variation for fitness is largely unresolved. This reflects the inherent difficult in distinguishing between models of recurrent mutation versus selection, which produce similar patterns of inbreeding depression, as well as the limitations of testing such hypotheses when fitness variation is averaged across the genome. Signatures of X-linked overdominant selection are less likely to be obscured by mutational variation because X-linked mutations are rapidly eliminated by purifying selection in males. Although models maintaining genetic variation for fitness are not necessarily mutually exlusive, a series of predictins for identifying X-linked overdominant selection can be used to separate its contribution from other underlying processes. We consider the role of overdominant selection in maintaining fitness variation in a sample of 12 X chromosomes from a population of Drosophila melanogaster. Substantial variation was observed for male reproductive success and female fecundity, with heterozygous-X genotypes exhibiting the greatest gegree of variance, a finding that agress well with predictions of the overdominance model. The importance of X-linked overdominant selection is discussed along with models of recurrent mutation and sexually antagonistic selection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75442/1/j.0014-3820.2006.tb01223.x.pd