Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat

Summary Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were measured in individual nuclei of rat hypothalamus and other brain areas using HPLC with electrochemical detection. 5-HIAA levels were first demonstrated in hypothalamic and some discrete brain areas. The 5-HIAA/5-HT ratio was highest in the n. caudatus putamen, high in the n. ventromedialis and lowest in the n. suprachiasmaticus.     

The occurrence and function of the sphragis in the zerynthiine genera Zerynthia,Allancastria and Bhutanitis (Lepidoptera: Papilionoidea: Papilionidae)

In some butterfly species males attach a large external mating plug termed a sphragis to the female abdomen during mating. This is derived from male accessory secretions and covers the female ostium bursae and surrounding areas, thus preventing or delaying remating. Specimens of all 12 species of the genera Zerynthia, Allancastria and Bhutanitis (Lepidoptera: papilionidae), which form a natural clade within the Zerynthiini, were examined for presence or absence of a sphragis and their male and female genitalia were studied. In all three genera female genitalia lack a typical sinus vaginalis and the sterigma is modified to form an exposed, shiny, well-sclerotized genital plate, derived from the fusion and expansion of the lamellae ante- and postvaginales. The exposed ostium bursae is situated near the posterior end of the genital plate in Zerynthia, whereas in Allancastria and Bhutanitis it is near the anterior end. A crude irregularly formed sphragis was found at least facultatively in all species. The sphragides of Zerynthia and Bhutanitis were generally poorly developed, in most cases only partially covering the female genital plate. In Allancastria the sphragis mostly covered the genital plate entirely, and generally incorporated numerous long scales derived from the male’s 8th abdominal segment; scales were sometimes sparse or absent, probably due to depletion from repeated matings by males. In Zerynthia, males lacked the dense terminal abdominal tuft of elongated scales found in Allancastria, and their sphragis lacked scales. The sphragis of Bhutanitis thaidina incorporated scales from the male valves, whereas in the B. lidderdalii sphragis (and probably B. ludlowi) the scales derived from the male’s 8th abdominal segment. The role of the scales and possible reasons for the difference in the development of the sphragis among these genera are discussed.     

Haploinsufficiency of NSD1 causes Sotos syndrome

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.     

Reduction of Pt Usage in Fuel Cell Electrocatalysts Using Carbon Nanotubes and Non-Pt Metals

The high-priced and limited Pt constitutes a high barrier to commercialization of fuel cells. Pt is essential for the electrode catalyst of polymer electrolyte fuel cells （PEFCs）. A reduction in Pt usage is one of the key requirements for the commercialization of fuel cells for use in everyday life, because of its high price and limited availability, and the difficulty of finding suitable substitutes. Non-Pt fuel cell catalysts will decrease the demand for Pt by PEFCs, enabling more Pt to be available for use in other essential products, and make fuel cells more popular. The cheaper Mo2C is known to possess similar catalytic activities and electronic structures to Pt. Carbon black （CB） is widely used as the support for Pt nanoparticles. However,     

Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration

The neuropathological hallmarks of Alzheimer's disease and other tauopathies include senile plaques and/or neurofibrillary tangles. Although mouse models have been created by overexpressing specific proteins including beta-amyloid precursor protein, presenilin and tau, no model has been generated by gene knockout. Phosphorylation of tau and other proteins on serine or threonine residues preceding proline seems to precede tangle formation and neurodegeneration in Alzheimer's disease. Notably, these phospho(Ser/Thr)-Pro motifs exist in two distinct conformations, whose conversion in some proteins is catalysed by the Pin1 prolyl isomerase. Pin1 activity can directly restore the conformation and function of phosphorylated tau or it can do so indirectly by promoting its dephosphorylation, which suggests that Pin1 is involved in neurodegeneration; however, genetic evidence is lacking. Here we show that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer's disease. Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioural deficits, tau hyperphosphorylation, tau filament formation and neuronal degeneration. Thus, Pin1 is pivotal in protecting against age-dependent neurodegeneration, providing insight into the pathogenesis and treatment of Alzheimer's disease and other tauopathies.     

Crystal structures of a multidrug transporter reveal a functionally rotating mechanism

AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change.     

IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9

The Toll-like receptor (TLR) family has important roles in microbial recognition and dendritic cell activation. TLRs 7 and 9 can recognize nucleic acids and trigger signalling cascades that activate plasmacytoid dendritic cells to produce interferon-alpha (IFN-alpha) (refs 7, 8). TLR7/9-mediated dendritic cell activation is critical for antiviral immunity but also contributes to the pathogenesis of systemic lupus erythematosus, a disease in which serum IFN-alpha levels are elevated owing to plasmacytoid dendritic cell activation. TLR7/9-induced IFN-alpha induction depends on a molecular complex that contains a TLR adaptor, MyD88, and IFN regulatory factor 7 (IRF-7) (refs 10-14), but the underlying molecular mechanisms are as yet unknown. Here we show that IkappaB kinase-alpha (IKK-alpha) is critically involved in TLR7/9-induced IFN-alpha production. TLR7/9-induced IFN-alpha production was severely impaired in IKK-alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine induction was decreased but still occurred. Kinase-deficient IKK-alpha inhibited the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7. Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a potential target for manipulating TLR-induced IFN-alpha production.