Irreversible inhibition of sodium transport by the toad urinary bladder following photolysis of amiloride analogs

Summary Active sodium transport was completely and irreversibly inhibited in toad urinary bladders photolyzed in the presence of iodeam loride.     

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.     

El Niño/Southern Oscillation and tropical Pacific climate during the last millennium

Any assessment of future climate change requires knowledge of the full range of natural variability in the El Ni?o/Southern Oscillation (ENSO) phenomenon. Here we splice together fossil-coral oxygen isotopic records from Palmyra Island in the tropical Pacific Ocean to provide 30-150-year windows of tropical Pacific climate variability within the last 1,100 years. The records indicate mean climate conditions in the central tropical Pacific ranging from relatively cool and dry during the tenth century to increasingly warmer and wetter climate in the twentieth century. But the corals also document a broad range of ENSO behaviour that correlates poorly with these estimates of mean climate. The most intense ENSO activity within the reconstruction occurred during the mid-seventeenth century. Taken together, the coral data imply that the majority of ENSO variability over the last millennium may have arisen from dynamics internal to the ENSO system itself.     

Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160

The development of a vaccine to provide protective immunity to human immunodeficiency virus type 1 (HIV-1), the virus causing AIDS, would be the most practical method to control its spread. Subunit vaccines consisting of virus envelope glycoproteins, produced by recombinant DNA technology, are effective in preventing viral infections. We have now used this approach in the development of a candidate AIDS vaccine. Chimpanzees were immunized with recombinant forms of the HIV-1 glycoproteins gp120 and gp160 produced in Chinese hamster ovary cells, and then challenged with HIV-1. The control and the two animals immunized with the gp160 variant became infected within 7 weeks of challenge. The two animals immunized with the gp120 variant have shown no signs of infection after more than 6 months. These studies demonstrate that recombinant gp120, formulated in an adjuvant approved for human use, can elicit protective immunity against a homologous strain of HIV-1.     

History and scientific practice in the construction of an adequate philosophy of science: revisiting a Whewell/Mill debate

William Whewell raised a series of objections concerning John Stuart Mill’s philosophy of science which suggested that Mill’s views were not properly informed by the history of science or by adequate reflection on scientific practices. The aim of this paper is to revisit and evaluate this incisive Whewellian criticism of Mill’s views by assessing Mill’s account of Michael Faraday’s discovery of electrical induction. The historical evidence demonstrates that Mill’s reconstruction is an inadequate reconstruction of this historical episode and the scientific practices Faraday employed. But a study of Faraday’s research also raises some questions about Whewell’s characterization of this discovery. Thus, this example provides an opportunity to reconsider the debate between Whewell and Mill concerning the role of the sciences in the development of an adequate philosophy of scientific methodology.     

Millennial-scale trends in west Pacific warm pool hydrology since the Last Glacial Maximum

Models and palaeoclimate data suggest that the tropical Pacific climate system plays a key part in the mechanisms underlying orbital-scale and abrupt climate change. Atmospheric convection over the western tropical Pacific is a major source of heat and moisture to extratropical regions, and may therefore influence the global climate response to a variety of forcing factors. The response of tropical Pacific convection to changes in global climate boundary conditions, abrupt climate changes and radiative forcing remains uncertain, however. Here we present three absolutely dated oxygen isotope records from stalagmites in northern Borneo that reflect changes in west Pacific warm pool hydrology over the past 27,000 years. Our results suggest that convection over the western tropical Pacific weakened 18,000-20,000 years ago, as tropical Pacific and Antarctic temperatures began to rise during the early stages of deglaciation. Convective activity, as inferred from oxygen isotopes, reached a minimum during Heinrich event 1 (ref. 10), when the Atlantic meridional overturning circulation was weak, pointing to feedbacks between the strength of the overturning circulation and tropical Pacific hydrology. There is no evidence of the Younger Dryas event in the stalagmite records, however, suggesting that different mechanisms operated during these two abrupt deglacial climate events. During the Holocene epoch, convective activity appears to track changes in spring and autumn insolation, highlighting the sensitivity of tropical Pacific convection to external radiative forcing. Together, these findings demonstrate that the tropical Pacific hydrological cycle is sensitive to high-latitude climate processes in both hemispheres, as well as to external radiative forcing, and that it may have a central role in abrupt climate change events.     

Do zebra stripes influence thermoregulation?

The temperatures of black and white stripes on two zebras and a zebra hide were measured, throughout separate sunny days in Kenya. There is a 12–15^oC difference between living zebras’ stripe temperatures throughout the middle seven daytime hours. The hide temperatures reach 16^oC higher than the living zebras. Like all equids, zebras sweat to keep cool. Movement of sweat away from the skin is accelerated by the recently discovered surfactant equid protein latherin, a vital component of cooling in racehorses. Latherin decreases the surface tension of the sweat, facilitating evaporative cooling at the hair tips. We suggest that the abrupt temperature difference between the stripes causes chaotic air movement above the hair surface, thus enhancing evaporative heat dissipation. This cooling mechanism explains the lower temperatures of living zebra stripes than those of the inanimate hide. We observed that the black stripes can be separately erected, while the white remain flat. This may further refine the mechanism. There is an ongoing debate about the function of zebra stripes, recently focussed on the fact that stripes deter biting flies. The data and observations in this paper suggest that the primary function of the stripes may be thermoregulation and a secondary benefit, fly-deterrence.     

上海市百岁老人的谱系及其分析

本文调查了上海市百岁老人的性别、职业和谱系,并绘制了57个完整的寿命谱系图,其中男性10名(占总数的17.5%),女性47名(占82.5%).男性中脑力劳动者4名(占男性总数的40%),体力劳动者6名(占60%);女性中脑力劳动者1人(占女性总数的2.1%),体力劳动者3人(占6.4%),操持家务者43人(占91.5%).有长寿家族史者40人(占寿命家族史清楚者的70.2%),无长寿家族史者17人(占29.8%).百岁老人配偶寿长≥70岁者,其已故子女的平均寿命高于配偶<70岁的.作者认为长寿是遗传的,并着重从遗传和环境两方面分析了女寿星数明显多于男寿星数的原因.