Rockefeller University

About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.

Physiological response to long-term peripheral and central leptin infusion in lean and obese mice

Abstract: Recent data have identified leptin as an afferent signal in a negative-feedback loop regulating the mass of the adipose tissue. High leptin levels are observed in obese humans and rodents, suggesting that, in some cases, obesity is the result of leptin insensitivity. This hypothesis was tested by comparing the response to peripherally and centrally administered leptin among lean and three obese strains of mice: diet-induced obese AKR/J, New Zealand Obese (NZO), and Ay. Subcutaneous leptin infusion to lean mice resulted in a dose-dependent loss of body weight at physiologic plasma levels. Chronic infusions of leptin intracerebroventricularly (i.c.v.) at doses of 3 ng/hr or greater resulted in complete depletion of visible adipose tissue, which was maintained throughout 30 days of continuous i.c.v. infusion. Direct measurement of energy balance indicated that leptin treatment did not increase total energy expenditure but prevented the decrease that follows reduced food intake. Diet-induced obese mice lost weight in response to peripheral leptin but were less sensitive than lean mice. NZO mice were unresponsive to peripheral leptin but were responsive to i.c.v. leptin. Ay mice did not respond to subcutaneous leptin and were 1/100 as sensitive to i.c.v. leptin. The decreased response to leptin in diet-induced obese, NZO, and Ay mice suggests that obesity in these strains is the result of leptin resistance. In NZO mice, leptin resistance may be the result of decreased transport of leptin into the cerebrospinal fluid, whereas in Ay mice, leptin resistance probably results from defects downstream of the leptin receptor in the hypothalamus.

Origin of luteinizing hormone-releasing hormone neurons.

Abstract: Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour. LHRH-expressing neurons are also found in the nervus terminalis, a cranial nerve that is a part of the accessory olfactory system and which projects directly from the nose to the septal-preoptic nuclei in the brain. During development, LHRH-immunoreactivity is detected in the peripheral parts of the nervus terminalis before it is found in the brain. Using a combination of LHRH immunocytochemistry and tritiated thymidine autoradiography in fetal mice, we show that LHRH neurons originate in the medial olfactory placode of the developing nose, migrate across the nasal septum and enter the forebrain with the nervus terminalis, arching into the septal-preoptic area and hypothalamus. Clinically, this migratory route for LHRH-expressing neurons could explain the deficiency of gonadotropins seen in 'Kallmann's syndrome' (hypogonadotropic hypogonadism with anosmia).

Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres

Abstract: Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres. Tankyrase binds to the telomeric protein TRF1 (telomeric repeat binding factor-1), a negative regulator of telomere length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with TRF1. Recombinant tankyrase was found to have PARP activity in vitro, with both TRF1 and tankyrase functioning as acceptors for adenosine diphosphate (ADP)-ribosylation. ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation.

The molecular architecture of the nuclear pore complex

Abstract: Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC's 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of 'columns'. These findings provide clues to the evolutionary origins of the NPC.