The rockefeller university

Background: Psoriasis is a chronic, inflammatory disease affecting 2-3% of the worldwide population, and it may worsen with HIV or be detected as HIV cutaneous manifestation. HIV-related psoriasis shows a severe and prolonged clinical course with more frequent exacerbations. The management of this condition is challenging because immunomodulating and immunosuppressant agents may have variable and partial efficacy, and therefore, antiretroviral treatment represents a potential adjunctive therapeutic option. Results: In the case we report, the HIV test was shown to be crucial for driving the therapeutic approach. Indeed, antiretroviral agents have been proven to be effective in the treatment of HIV+ psoriasis as first-line therapy. Conclusion: The HIV test should be considered in high-risk patients affected by severe psoriasis and resistant to conventional and biological treatments. Copyright (c) 2012 S. Karger AG, Basel

A major barrier to complex experimental design in mouse genetics is the allele problem: combining three or more alleles is time-consuming and inefficient. Here, we solve this problem for transgenic animals with a simple modification of existing BAC transgenesis protocols, and generate triple-colored 'prism' mice in which the major cell types of the brain: neurons, astrocytes, and oligodendrocytes, are each labeled with a distinct fluorophore. All three fluorophores are expressed from the same locus, yet each fluorophore is expressed in an independent temporal and spatial pattern. All three transgenes are generally co-inherited across multiple generations with stable genomic copy number and expression patterns. This generic solution should permit more sophisticated experimental manipulations to assess functional interactions amongst populations of cell types in vivo in a more rapid and efficient manner.

From personality to neuropsychiatric disorders, individual differences in brain function are known to have a strong heritable component. Here we report that between close relatives, a variety of neuropsychiatric disorders covary strongly with intellectual interests. We surveyed an entire class of high-functioning young adults at an elite university for prospective major, familial incidence of neuropsychiatric disorders, and demographic and attitudinal questions. Students aspiring to technical majors (science/mathematics/engineering) were more likely than other students to report a sibling with an autism spectrum disorder (p = 0.037). Conversely, students interested in the humanities were more likely to report a family member with major depressive disorder (p = 8.8 x 10(-4)), bipolar disorder (p = 0.027), or substance abuse problems (p = 1.9 x 10(-6)). A combined PREdisposition for Subject MattEr (PRESUME) score based on these disorders was strongly predictive of subject matter interests (p = 9.6 x 10(-8)). Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests.

Background: The major cell cycle control acting at the G2 to mitosis transition is triggered in all eukaryotes by cyclin-dependent kinases (CDKs). In the fission yeast Schizosaccharomyces pombe the activation of the G2/M CDK is regulated primarily by dephosphorylation of the conserved residue Tyr15 in response to the stress-nutritional response and cell geometry sensing pathways. To obtain a more complete view of the G2/M control we have screened systematically for gene deletions that advance cells prematurely into mitosis. Results: A screen of 82% of fission yeast non-essential genes, comprising approximately 3,000 gene deletion mutants, identified 18 genes that act negatively at mitotic entry, 7 of which have not been previously described as cell cycle regulators. Eleven of the 18 genes function through the stress response and cell geometry sensing pathways, both of which act through CDK Tyr15 phosphorylation, and 4 of the remaining genes regulate the G2/M transition by inputs from hitherto unknown pathways. Three genes act independently of CDK Tyr15 phosphorylation and define additional uncharacterized molecular control mechanisms. Conclusions: Despite extensive investigation of the G2/M control, our work has revealed new components of characterized pathways that regulate CDK Tyr15 phosphorylation and new components of novel mechanisms controlling mitotic entry.

The aim of this pilot study was to assess the effectiveness of buprenorphine/naloxone (BUP/NX) among marginalized, opioid-dependent individuals in terms of retention in and cycling into and out of a harm-reduction program. This pilot study enrolled 100 participants and followed them from November 2005 to July 2008. The overall proportion of patients retained in the program at the end of 3, 6, 9, and 12 months was 68%, 63%, 56%, and 42%, respectively. This pilot study demonstrated that BUP/NX could be successfully used to treat marginalized heroin users.

The existence of extraterrestrial life was heralded by controversial claims made in 1996 that the Martian meteorite ALH84001 harbored relics of ancient microorganisms. We review here the accumulated evidence for and against past extraterrestrial life in this Martian meteorite. The main pro-life arguments-the presence of polycyclic aromatic hydrocarbons, magnetite crystals, carbonate globules, and structures resembling terrestrial life-forms known as nanobacteria-can be deemed ambiguous at best. Although these criteria are compatible with living processes, each one of them can be explained by nonliving chemical processes. By undergoing amorphous-tocrystalline transformations and binding to multiple substrates, including other ions and simple organic compounds, minerals-especially those containing carbonate-have been shown to display biomimetic properties, producing forms that resemble bacteria. This simple and down-to-earth explanation can account fully for the existence of mineral entities resembling putative nano-and microorganisms that have been described not only in the ALH84001 meteorite but also in the human body.

BACKGROUND: : The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function. METHODS: : We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and simian immunodeficiency (SIV)-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239. RESULTS: : There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T-cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal, and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells. CONCLUSION: : Early initiation of ART prevented virus-induced damage and did not impede mucosal or systemic immune functions.

A study of forward energy flow and central charged-particle multiplicity in events with W and Z bosons decaying into leptons is presented. The analysis uses a sample of 7 TeV pp collisions, corresponding to an integrated luminosity of 36 pb(-1), recorded by the CMS experiment at the LHC. The observed forward energy depositions, their correlations, and the central charged-particle multiplicities are not well described by the available non-diffractive soft-hadron production models. A study of about 300 events with no significant energy deposited in one of the forward calorimeters, corresponding to a pseudorapidity gap of at least 1.9 units, is also presented. An indication for a diffractive component in these events comes from the observation that the majority of the charged leptons from the W(Z) decays are found in the hemisphere opposite to the gap. When fitting the signed lepton pseudorapidity distribution of these events with predicted distributions from an admixture of diffractive (POMPYT) and non-diffractive (PYTHIA) Monte Carlo simulations, the diffractive component is determined to be (50.0 +/- 9.3 (stat.) +/- 5.2 (syst.))%.

Ohkuni H, Nagamune H, Ozaki N, Tabata A, Todome Y, Watanabe Y, Takahashi H, Ohkura K, Kourai H, Ohtsuka H, Fischetti VA, Zabriskie JB. Characterization of recombinant Streptococcus mitis-derived human platelet aggregation factor. APMIS 2012; 120: 5671.