Genome Wide Conditional Mouse Knockout Resources.

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6,000 mutant mouse strains have been produced by the IKMC and mostly the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 inducible cre-driver mouse strains in a C57BL/6 background. Complementing the cre-driver resource, a collection of comprising 27 cre-driver rAAVs has also been produced. The resources can be easily accessed at the IKMC/IMPC web portal (www.mousephenotype.org). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds that enables the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research.

From molecular biology to anti-aging cognitive-behavioral practices: the pioneering research of Walter Pierpaoli on the pineal and bone marrow foreshadows the contemporary revolution in stem cell and regenerative biology.

Evidence is accruing that a cognitive-behavioral regimen integrating cognitive techniques (meditation-based anti-stress, anti-inflammatory techniques, others), dietary modification ("dietary restriction" or modified dietary restriction), and certain forms of aerobic exercise, may prolong the healthy life span in humans. Recent research has identified some of the likely molecular mediators of these potentially broad-ranging, health-enhancing and anti-aging effects; these include DHEA, interleukins -10 and -4 (IL-10, 1L-4), and especially melatonin. Relatedly, what some are calling a revolution in biology and medicine has been emerging from research on stem cells and regeneration processes more generally. Dogma regarding limitations on the regenerative capacities of adult vertebrates is being cautiously yet enthusiastically revised in the wake of rapidly accumulating discoveries of more types of adult stem cells in mammals, including humans. For example, a recent review by D. Krause of Yale concluded that "in the [adult] bone marrow, in addition to hematopoietic stem cells and supportive stromal cells, there are cells with the potential to differentiate into mature cells of the heart, liver, kidney, lungs, GI tract, skin, bone, muscle, cartilage, fat, endothelium and brain." In addition, very recent studies have shown that DHEA, ILs-10 and -4, and melatonin all possess potential regenerative, including stem cell-activating, properties. More than a quarter of a century ago, Walter Pierpaoli initiated a series of extraordinary studies that demonstrated in experimental animals the potential for dramatic regeneration associated with changes in the pineal gland and bone marrow. This appeared to be not only retardation of aging, but also its reversal. Furthermore, as Pierpaoli was attempting to understand both anti-aging regeneration and oncogenesis, he was focusing on both pro- and anti-mitotic mechanisms: recent research now suggests that there is a nonpathologic, "healthy" form of regeneration that is actually antagonistic to oncogenesis, and that melatonin may be important in this form of regeneration. This paper explores Pierpaoli's pioneering studies in light of recent developments in stem cell and regenerative biology, particularly as related to the regenerative potential associated with certain cognitive-behavioral practices, and includes evidence on this subject presented for the first time.

The heroin epidemic in New York City: current status and prognoses.

Since 1989, heroin production worldwide has risen; in New York City, as its purity rose and prices fell, street-level markets were restructured and offered heroin in addition to cocaine and crack (which had been popular during the 1980s). While officials estimate that there are between 500,000 and one million hard-core, chronic heroin users nationwide, evidence of supplemental users heralding another heroin era includes: more overdoses and overdose deaths, greater demand for treatment, larger seizures of heroin at all levels of distribution and related arrests, and broader media coverage. In this article, the authors describe the characteristics of populations in which there may have been a percentage increase of new users, such as young middle- or upper-class European-Americans, young Puerto Ricans and recent Haitian and Russian immigrants. The abstinence of young African-Americans is also noted. The article ends with a preliminary needs assessment of the new users in the areas of health (including AIDS), housing, employment, treatment, arrest and imprisonment.