Activation with (±)N-n-propyl-nor-apomorphine (NPA) of the male rat copulatory behavior

Summary I.p. (±)N-n-propyl-nor-apomorphine HCl (NPA) influences copulatory behavior of vigorous adult male rats in the same ways as apomorphine, i.e., it reduces the latency to ejaculation as well as mount and intromission frequency. Furthermore, NPA administered to impotent male rats restores normal mating behavior in some of them.     

In vitro Polio virus inhibition by two guanidino-pyrimidines

Riassunto La 2-guanidino-pirimidina solfato e la 4-guanidino-2,6-dimetilpirimidina solfato inibisconoin vitro la moltiplicazione del poliovirus e del Coxsackie B₃ ma non quella del virus vaccinico e dell'adenovirus 5. L'analogia di comportamento con la guanidina è documentata oltre che da ciò, dalla esistenza di una resistenza e di una dipendenza crociata. Si dimostra cioè che non tutte le sostituzioni nella molecola della guanidina comportano una perdita dell'attività antivirale, come ritenuto in precedenza.     

Template-imprinted nanostructured surfaces for protein recognition

Synthetic materials capable of selectively recognizing proteins are important in separations, biosensors and the development of biomedical materials. The technique of molecular imprinting creates specific recognition sites in polymers by using template molecules. Molecular recognition is attributed to binding sites that complement molecules in size, shape and chemical functionality. But attempts to imprint proteins have met with only limited success. Here we report a method for imprinting surfaces with protein-recognition sites. We use radio-frequency glow-discharge plasma deposition to form polymeric thin films around proteins coated with disaccharide molecules. The disaccharides become covalently attached to the polymer film, creating polysaccharide-like cavities that exhibit highly selective recognition for a variety of template proteins, including albumin, immunoglobulin G, lysozyme, ribonuclease and streptavidin. Direct imaging of template recognition is achieved by patterning a surface at the micrometre scale with imprinted regions.     

Insolation-driven changes in atmospheric circulation over the past 116,000 years in subtropical Brazil

During the last glacial period, large millennial-scale temperature oscillations--the 'Dansgaard/Oeschger' cycles--were the primary climate signal in Northern Hemisphere climate archives from the high latitudes to the tropics. But whether the influence of these abrupt climate changes extended to the tropical and subtropical Southern Hemisphere, where changes in insolation are thought to be the main direct forcing of climate, has remained unclear. Here we present a high-resolution oxygen isotope record of a U/Th-dated stalagmite from subtropical southern Brazil, covering the past 116,200 years. The oxygen isotope signature varies with shifts in the source region and amount of rainfall in the area, and hence records changes in atmospheric circulation and convective intensity over South America. We find that these variations in rainfall source and amount are primarily driven by summer solar radiation, which is controlled by the Earth's precessional cycle. The Dansgaard/Oeschger cycles can be detected in our record and therefore we confirm that they also affect the tropical hydrological cycle, but that in southern subtropical Brazil, millennial-scale climate changes are not as dominant as they are in the Northern Hemisphere.     

Circulatory and respiratory consequences of massive hemorrhage are reversed by protoveratrines

In a rat model of severe hypotension and respiratory depression induced by step-wise bleeding, protoveratrines cause a prompt and sustained improvement of cardiovascular and respiratory functions, both in anesthetized and in conscious animals, seemingly through a magnification of the reflex response originated by the chemoreceptors of aortic and carotid bodies. The restoration of cardiovascular function is attributable to an increase both in total peripheral resistance and cardiac output. The finding could provide the basis for a new approach to the first-aid management of massive blood losses.     

Multifunctional to multistage delivery systems: The evolution of nanoparticles for biomedical applications

Nanomaterials are advancing in several directions with significant progress being achieved with respect to their synthesis, functionalization and biomedical application. In this review, we will describe several classes of prototypical nanocarriers, such as liposomes, silicon particles, and gold nanoshells, in terms of their individual function as well as their synergistic use. Active and passive targeting, photothermal ablation, and drug controlled release constitute some of the crucial functions identified to achieve a medical purpose. Current limitations in targeting, slow clearance, and systemic as well as local toxicity are addressed in reference to the recent studies that attempted to comprehend and solve these issues. The demand for a more sophisticated understanding of the impact of nanomaterials on the body and of their potential immune response underlies this discussion. Combined components are then discussed in the setting of multifunctional nanocarriers, a class of drug delivery systems we envisioned, proposed, and evolved in the last 5 years. In particular, our third generation of nanocarriers, the multistage vectors, usher in the new field of nanomedicine by combining several components onto multifunctional nanocarriers characterized by emerging properties and able to achieve synergistic effects.     

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.     

The structure of a new phytoecdysone kaladasterone: An application of13C magnetic resonance spectroscopy to structural problems

Zusammenfassung Isolierung und Strukturaufklärung von Kaladasteron (C₂₇H₄₂O₇), eines neuen Phytoecdysons, werden beschrieben.

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Acknowledgement: We would like to express our gratitude to Dr.P. Beynon and Dr.S. Murakami (Jeol Co., London and Milan) for running the CMR-spectra on the PS 100 PFT Spectrometer. We are also greatly indebted to Dr.S. Maroni for letting us have the high resolution mass spectrum on the Varian Mat 311 instrument.