Kinetochores associated with the nuclear envelope in the mitosis of a dinoflagellate

This is the publisher's version, also available electronically from "http://jcb.rupress.org".No abstract availabl

The spindle pole body of Schizosaccharomyces pombe enters and leaves the nuclear envelope as the cell cycle proceeds

This is the publisher's version, also available electronically from "http://www.molbiolcell.org".he cycle of spindle pole body (SPB) duplication, differentiation, and segregation in Schizosaccharomyces pombe is different from that in some other yeasts. Like the centrosome of vertebrate cells, the SPB of S. pombe spends most of interphase in the cytoplasm, immediately next to the nuclear envelope. Some gamma-tubulin is localized on the SPB, suggesting that it plays a role in the organization of interphase microtubules (MTs), and serial sections demonstrate that some interphase MTs end on or very near to the SPB. gamma-Tubulin is also found on osmiophilic material that lies near the inner surface of the nuclear envelope, immediately adjacent to the SPB, even though there are no MTs in the interphase nucleus. Apparently, the MT initiation activities of gamma-tubulin in S. pombe are regulated. The SPB duplicates in the cytoplasm during late G2 phase, and the two resulting structures are connected by a darkly staining bridge until the mitotic spindle forms. As the cell enters mitosis, the nuclear envelope invaginates beside the SPB, forming a pocket of cytoplasm that accumulates dark amorphous material. The nuclear envelope then opens to form a fenestra, and the duplicated SPB settles into it. Each part of the SPB initiates intranuclear MTs, and then the two structures separate to lie in distinct fenestrae as a bipolar spindle forms. Through metaphase, the SPBs remain in their fenestrae, bound to the polar ends of spindle MTs; at about this time, a small bundle of cytoplasmic MTs forms in association with each SPB. These MTs are situated with one end near to, but not on, the SPBs, and they project into the cytoplasm at an orientation that is oblique to the simple axis. As anaphase proceeds, the nuclear fenestrae close, and the SPBs are extruded back into the cytoplasm. These observations define new fields of enquiry about the control of SPB duplication and the dynamics of the nuclear envelope

Role of vasopressin in impaired water excretion in conscious rats with experimental cirrhosis

Role of vasopressin in impaired water excretion in conscious rats with experimental cirrhosis. The present study was undertaken to study the mechanism of impaired water excretion in experimental cirrhosis in the rat. Conscious rats in whom histologically proven cirrhosis was induced with carbon tetrachloride and phenobarbital were compared with control rats given phenobarbital alone. Impaired water excretion in experimental cirrhosis was verified by a basal hyponatremia (138 vs. 147 mEq/liter, P < 0.005) and an impaired excretion of water load (minimal urinary osmolality, 262 vs. 100 mOsm/kg; 58 vs. 102% of water load excreted, P < 0.001). To clarify the mechanism of this impaired water excretion, we measured glomerular filtration rate (GFR), renal blood flow (RBF), and vasopressin (VP) levels. In cirrhosis, GFR was normal but RBF was decreased (4.5 vs 6.8 ml/min/g, P < 0.01). VP levels were found to be higher in cirrhotic rats (1.61 vs. 0.71 pg/ml, P < 0.025). The significance of the impaired renal hemodynamics and the increase in VP was assessed by inducing cirrhosis in VP-free Brattle-boro (diabetes insipidus; DI) rats. Despite histologic, biochemical, and renal hemodynamic changes that were comparable to cirrhotic rats with an intact neurohypophysis, cirrhotic DI rats had no impairment in water excretion. To determine the cause of increased VP in experimental cirrhosis, we determined blood volume and systemic hemodynamics. Although plasma volume was greater in experimental cirrhosis (4.3 vs. 3.0 ml/100 g, P < 0.05), cirrhotic rats had a significantly lower peripheral resistance (0.37 vs. 0.42mm Hg/ml/min/kg, P < 0.05) and mean arterial pressure (104 vs. 120mm Hg, P < 0.001) than did control rats. These results document that experimental cirrhosis in the rat is associated with impaired renal water excretion in association with both abnormal renal hemodynamics and increased VP levels. The impaired water excretion, however, is solely VP mediated. The nonosmolar stimulus for VP release may be due to abnormal systemic hemodynamics.Rôle de la vasopressine dans l'altération de l'excrétion de l'eau par le rat conscient atteint de cirrhose expérimentale. Cette étude a été entreprise pour élucider le mécanisme de l'altération de l'excrétion de l'eau au cours de la cirrhose du rat. Des rats conscients chez lesquels une cirrhose prouvée histologiquement a été induite par le tétrachlorure et le phénobarbital ont été comparés à des rats contrôles recevant seulement le phénobarbital. L'altération de l'excrétion de l'eau dans la cirrhose expérimentale a été vérifiée par l'hyponatrémie basale (138 vs. 147 mEq/litre, P < 0,005) et le défaut d'excrétion d'une charge en eau (osmolalité urinaire minimale 262 vs. 100 mOsm/kg; 58 vs. 102% de la charge d'eau sont excrétés, P < 0,001). Pour élucider le mécanisme de cette altération de l'excrétion de l'eau le débit de filtration glomérulaire (GFR), le débit sanguin rénal (RBF) et les concentrations de vasopressine (VP) ont été mesurés. Dans la cirrhose GFR est normal alors que RBF est diminué (4,5 vs. 6,8 ml/min/gm, P < 0,01). VP est plus élevée chez les rats cirrhotiques (1,61 vs. 0,71 pg/ml, P < 0,025). La signification des modifications de l'hémodynamique rénale et de l'augmentation de VP a été évaluée en créant des cirrhoses chez des rats sans VP de la souche Brattleboro (DI). Malgré des modifications histologiques, biochimiques et hémodynamiques rénales qui sont comparables à celles des rats dont la neurohypophyse est intacte, les rats DI cirrhotiques n'ont pas d'altération de l'excrétion de l'eau. Pour connaître la cause de l'augmentation de VP dans la cirrhose expérimentale le volume sanguin et l'hémodynamique systémique ont été étudiés. Quoique le volume plasmatique soit augmenté dans la cirrhose expérimentale (4,3 vs. 3,0 ml/100 g, P < 0,05) les rats cirrhotiques ont des résistances périphériques inférieures (0,37 vs. 0,42mm Hg/ml/min/kg, P < 0,05) et une pression artérielle moyenne inférieure (104 vs. 120mm Hg, P < 0,001) à celles des rats contrôles. Ces résultats indiquent que la cirrhose expérimentale du rat comporte une altération de l'excrétion de l'eau associée à une hémodynamique rénale anormale et à des concentrations de VP augmentées. L'altération de l'excrétion de l'eau, cependant, a la vasopressione comme seul médiateur. Le stimulus non osmolaire de la libération de VP pourrait être l'anomalie de l'hémodynamique systémique

Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999

Conversion of Polyethylenes into Fungal Secondary Metabolites

Waste plastics represent major environmental and economic burdens due to their ubiquity, slow breakdown rates, and inadequacy of current recycling routes. Polyethylenes are particularly problematic, because they lack robust recycling approaches despite being the most abundant plastics in use today. We report a novel chemical and biological approach for the rapid conversion of polyethylenes into structurally complex and pharmacologically active compounds. We present conditions for aerobic, catalytic digestion of polyethylenes collected from post‐consumer and oceanic waste streams, creating carboxylic diacids that can then be used as a carbon source by the fungus Aspergillus nidulans. As a proof of principle, we have engineered strains of A. nidulans to synthesize the fungal secondary metabolites asperbenzaldehyde, citreoviridin, and mutilin when grown on these digestion products. This hybrid approach considerably expands the range of products to which polyethylenes can be upcycled

Self-assembly in solution of a reversible comb-shaped supramolecular polymer

We report a single step synthesis of a polyisobutene with a bis-urea moiety in the middle of the chain. In low polarity solvents, this polymer self-assembles by hydrogen bonding to form a combshaped polymer with a central hydrogen bonded backbone and polyisobutene arms. The comb backbone can be reversibly broken, and consequently, its length can be tuned by changing the solvent, the concentration or the temperature. Moreover, we have proved that the bulkiness of the side-chains have a strong influence on both the self-assembly pattern and the length of the backbone. Finally, the density of arms can be reduced, by simply mixing with a low molar mass bis-urea