A novel mechanism of modulation of 5-HT₃A receptors by hydrocortisone

Modulation of Cys-loop receptors by steroids is of physiological and therapeutical relevance. Nonetheless, its molecular mechanism has not been elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents from the high-conductance form (∼4.7 pA, −70 mV) appear as a series of long opening events forming bursts, which group into long clusters. Although they are very infrequent, subconductance events (∼2.4 pA) are detected within clusters. HC produces a significant concentration-dependent reduction in open and burst durations, demonstrating open-channel block. In addition, it increases the appearance of subconductance levels in a concentration- and slightly voltage-dependent manner. The amplitude of the subconductance level does not change with HC concentration and its open duration is briefer than that of full amplitude events, indicating lower open-channel stability. Dual effects are distinguished from macroscopic responses: HC reduces amplitude by acting from either open or closed states, and it increases decay rates from the open state. Thus, HC acts as a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts as an open-channel blocker and it favors opening to a preexisting subconductance level. The latter constitutes a novel, to our knowledge, mechanism of channel modulation, which might be applicable to other steroids and channels.     

A study of the nature of the immediate precursor of the extracellular α-amylase of Bacillus amyloliquefaciens. A reappraisal

1. A defined medium was devised for use in washed-cell experiments with post-exponential-phase cultures of Bacillus amyloliquefaciens. The medium allowed alpha-amylase to be secreted, bacterial concentration to increase and l-[U-(14)C]valine to be incorporated into protein at a linear rate, which was the same as in a post-exponential-phase culture, for up to 6h. 2. Determination of the specific radioactivity of l-[U-(14)C]valine in the medium, the intracellular amino acid pool, the cellular protein and the isolated alpha-amylase, after a 3h incubation of washed cells in the defined medium, showed that at least 76% of the alpha-amylase secreted was synthesized de novo. 3. By isolating the alpha-amylase formed during a 6h incubation in the presence of l-[U-(14)C]valine it was shown that the specific radioactivity of the N-terminal valine, within the limits of experimental error, was the same as that of the total valine residues from the complete alpha-amylase molecule. 4. A consideration of these results in relation to the whole literature on the subject strongly supports the idea that there is no reason to suppose that extracellular alpha-amylase is formed from a high-molecular-weight precursor in B. amyloliquefaciens and closely related organisms with identical characteristics of exoenzyme secretion.     

Effect of Huperzine A on Aβ-induced p65 of astrocyte in vitro

Alzheimer’s disease (AD) is the most common cause of dementia. Its pathology often accompanies inflammatory action, and astrocytes play important roles in such procedure. Rela(p65) is one of significant message factors in NF-κB pathway which has been reported high expression in astrocyte treated by Aβ. HupA, an alkaloid isolated from Chinese herb Huperzia serrata, has been widely used to treat AD and observations reflected that it improves memory and cognitive capacity of AD patients. To reveal its molecular mechanisms on p65, we cultured astrocytes, built Aβ-induced AD model, treated astrocytes with HupA at different concentrations, assayed cell viability with MTT, and detected p65 expression by immunohistochemistry and PCR. Our results revealed that treatment with 10 μM Aβ1–42 for 24 h induced a significant increase of NF-κB in astrocytes; HupA significantly down-regulated p65 expression induced by Aβ in astrocytes. This study infers that HupA can regulate NF-κB pathway to treat AD.     

Islands of Fertility: A Byproduct of Grazing?

Empirical work in arid shrubland systems has documented a distinct spatial pattern of soil nutrient distribution, with higher concentrations of nutrients under shrub canopies compared to bare ground interspaces between shrubs. This “fertile island” pattern is considered characteristic of arid ecosystems. However, recent work at a desertified shrubland site reported no island of fertility pattern for nitrogen inside a long-term grazing exclosure despite a strong fertile island pattern outside the exclosure, leading to a hypothesis that the pattern may be associated with grazing. In this paper we examine this hypothesis in two ways. First, we collected soil nitrogen data inside and outside two long-term livestock exclosures. Second, we examined published work on the fertile island pattern for nitrogen, phosphorus and carbon, and its association with livestock grazing. At the field sites, there was a strong fertile island pattern for soil nitrogen in the grazed area outside each exclosure but no fertile island pattern in the ungrazed area inside the fence. From the literature, we identified 49 studies, which represent 99 cases that examine differences in soil nutrients under and between shrubs (that is, tests of the fertile island pattern). In 92 cases, fertile islands were present for at least one of the nutrients. All cases where livestock grazing was present exhibited fertile island patterns for nitrogen and most did so for carbon and phosphorus. In contrast, fertile islands were less consistent where livestock grazing was absent; all nine cases that had been ungrazed for more than 30 years did not exhibit fertile islands for nitrogen. Our empirical data and literature review suggest that the fertile island pattern may be an artifact of grazing rather than an inherent property of arid shrublands. Further, we suggest that the grazing history of a site needs to be explicitly considered when documenting spatial patterns of soil nutrients in arid systems. This has significant implications for our understanding of soil nutrient dynamics in arid systems, the management of rangelands, and the potential for reversal of desertification.     

A survey of medicinal plants of Curaçao

Autopsy records (1936–66) show esophageal cancer to be the most common tumor for both men and women among the locally-born negroid population of Curaçao. Crude incidence rate of 20.9 per 100,000, virtually constant over 30 years, is exceeded only by that of certain parts of Russia and the Transkei region of South Africa. The island of Aruba (42 miles distant) has a very low incidence. Drought conditions and food and water supply are virtually identical in both islands, also reverse smoking by women only. But there are striking contrasts in the use of plants for remedies. In Curaçao, more than 100 species of local plants are employed for self-medication and for “tea.” Interrogation of living esophageal cancer victims and survivors of deceased has revealed consistent use of these plants. Species cited most frequently in interviews are being collected, lyophilized, and supplied to the Laboratory of Pathology, National Cancer Institute, for animal-testing.     

Immunoglobulin A: A next generation of therapeutic antibodies?

Although immunoglobulin (Ig) A is commonly recognized as the most prevalent antibody subclass at mucosal sites with an important role in mucosal defense, its potential as a therapeutic monoclonal antibody is less well known. However, IgA has multifaceted anti-, non- and pro-inflammatory functions that can be exploited for different immunotherapeutical strategies, which will be the focus of this review.Key words: IgA, SIgA, dIgA, CD89, FcαRI, therapy, pro-inflammatory, mucosal defence, tumor, ITAM     

Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer’s disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.     

A Review of: “A White Man's Foot”

While conducting research among the Aran Islanders of Ireland between 1958 and 1968, the author and his wife became aware that their interpretation of Aran culture and personality was at variance with those of filmmakers and writers of fame who had portrayed the Aran milieu in film, books, and plays. This article examines the several reasons why his and his wife's interpretation differs from those, in particular, of Robert Flaherty, John M. Synge, Pat Mullen, and P. A. Ó Síocháin, with special emphasis on the influence of nativism and primitivism on their portrayals. The setting of the article is Ireland of four decades ago and mirrors conditions much different from those of today.     

A Brief Introduction of Cell Research

General InformationCell Research is a peer-reviewed, bimomthly journal in English dedicated to providing worldwide significant original achievements in all areas of Cell Biology. It publishes variety and high-quality complete articles of Original research papers, Reviews/Minireviews, Short communications and Commentaries as well express reports in print and electronic version, full text of the journal since 1999 can be freely accessed on line at the web site: http://www.cell-research.com. In recent years, Cell Research is well-cited in the world with impact factor around 2.0.     

A New Synthesis of α-Methylspermidine

A five-step synthesis of -methylspermidine (1,8-diamino-5-azanonane), the first polyamine analogue preventing pathological consequences of spermidine depletion in transgenic rats overproducing spermine/spermidine N ¹-acetyltransferase, from ethyl 3-aminobutyrate was achieved in a high overall yield.     

A Review of: “Images: A Reader”

Photographs are a ubiquitous feature of Aboriginal life in Northeastern Australia, with images of relatives being prominently displayed in most Aboriginal houses. This display of photographs is tied to a form of distributed personhood that draws on photographs to create a sense of social immediacy in the absence of close kin. This sense of immediacy also occurs in relation to photographs of the dead, giving these images a particular force for Aboriginal viewers. But further consideration of this force of photographic images suggests that they should be treated neither as things nor as aspects of persons, despite their seeming ability to manifest agency in Aboriginal life-worlds.     

A Facile Synthesis of ε-Pyridoxinyl-L-Iysines

The intracellular cadmium (Cd) content was measured with early stationary phase cells of a highly Cd-tolerant moderately halophilic bacterium Pseudomonas sp. No. 40 cultivated in 1M and 3M NaCl medium containing 0 to 2500 μg of CdCl₂/ml. It was found that the Cd contents were greatly affected by the NaCl concentration of the medium. When the bacterium was cultivated in the 1, 2, 3, and 4M NaCl medium containing 1500 μg of CdCl₂/ml, the intracellular Cd content was 25.0, 4.1, 3.1, and 2.0 mg Cd per g of dry cells, respectively. The intracellular Cd content decreased with increases of NaCl concentration of the medium. The fact seems to reflect Cd-tolerance of the bacterium towards the growth in the medium of different NaCl concentration. It is worthwhile to note that the bacterium showed the highest Cd-tolerance (in 3M NaCl) and the lowest Cd content among the bacteria so far known. The bacterial cells grown in the 1M NaNO₃ and 1M Na₂SO₄ medium accumulated 1.8–1.3 times as much Cd²⁺ as those in the 1M NaCl medium in the presence of 50–200 μg of CdCl₂/ml. It would also explain the difference in the Cd toxicity in the medium of NaNO₃, Na₂SO₄, or NaCl.