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.

Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α/β

Abstract: To understand how virulent mycobacteria subvert host immunity and establish disease, we examined the differential response of mice to infection with various human outbreak Mycobacterium tuberculosis clinical isolates. One clinical isolate, HN878, was found to be hypervirulent, as demonstrated by unusually early death of infected immune-competent mice, compared with infection with other clinical isolates. The differential effect on survival required lymphocyte function because severe combined immunodeficiency (SCID) mice infected with HN878 or other clinical isolates all died at the same rate. The hypervirulence of HN878 was associated with failure to induce M. tuberculosis-specific proliferation and IFN-gamma production by spleen and lymph node cells from infected mice. In addition, 2- to 4-fold lower levels of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-12, and IFN-gamma mRNAs were observed in lungs of HN878-infected mice. IL-10, IL-4, and IL-5 mRNA levels were not significantly elevated in lungs of HN878 infected mice. In contrast, IFN-alpha mRNA levels were significantly higher in lungs of these mice. To further investigate the role of Type 1 IFNs, mice infected with HN878 were treated intranasally with purified IFN-alpha/beta. The treatment resulted in increased lung bacillary loads and even further reduced survival. These results suggest that the hypervirulence of HN878 may be due to failure of this strain to stimulate Th1 type immunity. In addition, the lack of development of Th1 immunity in response to HN878 appears to be associated with increased induction of Type 1 IFNs.

Permanganate—A New Fixative for Electron Microscopy

Abstract: During the early phases of tissue sectioning for electron microscopy, virtually all of the standard cytological fixatives were tried. Of these, osmium tetroxide appeared to give the best preservation, and this was further improved by buffering the fixative solution at a slightly alkaline pH (Palade (1)). A variant developed by Dalton (2) contains Os04 in a chromate-dichromate system. Formalin has been used for special purposes for electron microscopy, and a fixative without OsO4 has been described by Low (3), consisting of a chromic acid-formaldehyde mixture. Potassium permanganate, or more specifically the permanganate ion, has occasionally been used as a fixative or stain in light microscopy (4). I t provides remarkable preservation of many cell components at the electron microscope level, as the following plates illustrate. The tissue fine structure looks similar to that following osmium treatment, thus rendering less likely the criticism that electron microscopists are merely seeing artifacts of osmium fixation. Besides preserving fine structure, permanganate fixation enhances tissue density

The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity.

Abstract: Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity.

Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement

Abstract: Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development.

Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala

Abstract: It has long been hypothesized that morphological and numerical alterations in dendritic spines underlie long-term structural encoding of experiences. Here we investigate the efficacy of aversive experience in the form of acute immobilization stress (AIS) and chronic immobilization stress (CIS) in modulating spine density in the basolateral amygdala (BLA) of male rats. We find that CIS elicits a robust increase in spine density across primary and secondary branches of BLA spiny neurons. We observed this CIS-induced spinogenesis in the BLA 1 d after the termination of CIS. In contrast, AIS fails to affect spine density or dendritic arborization when measured 1 d later. Strikingly, the same AIS causes a gradual increase in spine density 10 d later but without any effect on dendritic arbors. Thus, by modulating the duration of immobilization stress, it is possible to induce the formation of new spines without remodeling dendrites. However, unlike CIS-induced spine formation, the gradual increase in spine density 10 d after a single exposure to AIS is localized on primary dendrites. Finally, this delayed induction of BLA spinogenesis is paralleled by a gradual development of anxiety-like behavior on the elevated plus-maze 10 d after AIS. These findings demonstrate that stressful experiences can lead to the formation of new dendritic spines in the BLA, which is believed to be a locus of storage for fear memories. Our results also suggest that stress may facilitate symptoms of chronic anxiety disorders like post-traumatic stress disorder by enhancing synaptic connectivity in the BLA.