The rockefeller university

Measurements of primary charged hadron multiplicity distributions are presented for non-single-diffractive events in proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36, and 7 TeV, in five pseudorapidity ranges from vertical bar eta vertical bar < 0.5 to vertical bar eta vertical bar < 2.4. The data were collected with the minimum-bias trigger of the CMS experiment during the LHC commissioning runs in 2009 and the 7 TeV run in 2010. The multiplicity distribution at root s - 0.9 TeV is in agreement with previous measurements. At higher energies the increase of the mean multiplicity with root s is underestimated by most event generators. The average transverse momentum as a function of the multiplicity is also presented. The measurement of higher-order moments of the multiplicity distribution con firms the violation of Koba-Nielsen-Olesen scaling that has been observed at lower energies.

In an effort to enhance patient safety in opioid treatment programs, the Substance Abuse and Mental Health Saervices Administration convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members (Appendix A) reviewed the literature, regulatory actions, professional guidances, and opioid treatment program experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every opioid treatment program should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, electrocardiogram assessment, risk stratification, and prevention of drug interactions) for all patients and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining electrocardiograms as indicated by a particular patient's risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events. The Panel also suggested specific modifications to informed consent documents, patient education, staff education, and methadone protocols.

There is no clear consensus about the definition of the term primary immunodeficiency in 2011. Although there is general agreement that defects in both adaptive and innate immunity should be included, issues related to the frequency of primary immunodeficiencies, the modes of inheritance, the other types of cells involved, and the required clinical phenotype are more contentious. Three friends with an interest in both the clinical and scientific aspects of primary immunodeficiency carried out a discussion or trialogue to address some of these issues.

RNA editing deaminases act on a variety of targets in different organisms. A number of such enzymes have been shown to act on mRNA, with the resultant nucleotide changes modifying a transcript's information content. Though the deaminase activity of mRNA editing enzymes is readily demonstrated in vitro, identifying their physiological targets has proved challenging. Recent advances in ultra high-throughput sequencing technologies have allowed for whole transcriptome sequencing and expression profiling (RNA-Seq). We have developed a system to identify novel mRNA editing deamination targets based on comparative analysis of RNA-Seq data. The efficacy and utility of this approach is demonstrated for APOBEC1, a cytidine deaminase with a known and well-characterized mRNA editing target in the mammalian small intestine.

Immune responses to hepatitis C virus (HCV) fail to clear the virus in most individuals Why patients who are less likely to clear HCV infection have high plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells to sites of infection, has long been unclear In this issue of the JCI, Casrouge and colleagues shed light on this paradox by showing that CXCL10 in the plasma of many HCV patients is enzymatically processed to produce a CXCL10 receptor antagonist These findings introduce a role for chemokine antagonism during HCV infection and unveil new avenues for improved HCV diagnosis and therapy

Here, we exploit the hair follicle to define the point at which stem cells (SCs) become irreversibly committed along a differentiation lineage. Employing histone and nucleotide double-pulse-chase and lineage tracing, we show that the early SC descendents en route to becoming transit-amplifying cells retain stemness and slow-cycling properties and home back to the bulge niche when hair growth stops. These become the primary SCs for the next hair cycle, whereas initial bulge SCs become reserves for injury. Proliferating descendents further en route irreversibly lose their stemness, although they retain many SC markers and survive, unlike their transit-amplifying progeny. Remarkably, these progeny also home back to the bulge. Combining purification and gene expression analysis with differential ablation and functional experiments, we define critical functions for these non-SC niche residents and unveil the intriguing concept that an irreversibly committed cell in an SC lineage can become an essential contributor to the niche microenvironment.

The mechanosensory hair cells of many auditory receptor organs are tuned by an electrical resonance that increases their responses to stimulation over a narrow band of frequencies. The small oscillations of membrane potential characteristic of this phenomenon have previously been detectable only through intracellular electrode measurements, which are laborious and preclude analysis at the level of an entire sensory organ. We used a voltage-sensitive dye to image hair-cell electrical resonance in an intact preparation of the bullfrog's sacculus, a receptor organ sensitive to low-frequency seismic and auditory stimuli. Imaging revealed distinct populations of hair cells whose resonant response varied with the frequency of transepithelial electrical stimulation. Most of the hair cells in the saccular epithelium in vitro were electrically tuned to stimulation at 25-50 Hz. The frequency dependence of the fluorescence signal was sensitive to pharmacological blockade of large-conductance Ca2+-sensitive K+ channels and to enzymatic digestion. At an elevated concentration of Ca2+, we observed transient fluorescence signals that probably represented action potentials. The stroboscopic imaging and analysis techniques described here present a general approach for studying subthreshold oscillations in electrically excitable cells.

Hepatitis C virus is a major medical problem. Novel small-animal models are likely to accelerate the development of more effective therapeutics and a vaccine.

Studies m hum ins and rodents indicate that a minimum amount of stored energy is required for normal pubertal development The adipocyte-derived hormone leptin is a key metabolic signal to the neuroendocrine reproductive axis Humans and mice lacking leptin or the leptin receptor (LepR) (ob/ob and db/db mice, respectively) are infertile and fail to enter puberty Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility, but the exact site or sites of leptin action are unclear Here, we found that genetic deletion of LepR selectively from hypothalamic Kiss1 neurons m mice had no effect on puberty or fertility, indicating that direct leptin signaling m Kiss1 neurons is not required for these processes However, bilateral lesions of the ventral premammillary nucleus (PMV) of ob/ob mice blunted the ability of exogenous leptin to induce sexual maturation Moreover, unilateral reexpression of endogenous LepR m PMV neurons was sufficient to induce puberty and improve fertility m female LepR-null mice This LepR reexpression also normalized the increased hypothalamic GnRH content characteristic of leptin-signaling deficiency These data suggest that the PMV is a key site for leptin's permissive action at the onset of puberty and support the hypothesis that the multiple actions of leptin to control metabolism and reproduction at e anatomically dissociated