Bradykinin, but not muscarinic, inhibition of M-current in rat sympathetic ganglion neurons involves phospholipase C-β4

Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (I-K(M)), which can be inhibited by activation of M-1 muscarinic receptors (M-1 mAChR) and bradykinin (BK) B-2 receptors. Inhibition by the M1 mAChR agonist oxotremorine methiodide (Oxo-M) is mediated, at least in part, by the pertussis toxin-insensitive G-protein G alpha (q) (Caulfield et al., 1994; Haley et al., 1998a), whereas BK inhibition involves G alpha (q) and/or G alpha (11) (Jones et al., 1995). G alpha (q) and G alpha (11) can stimulate phospholipase C-beta (PLC-beta), raising the possibility that PLC is involved in I-K(M) inhibition by Oxo-M and BK. RT-PCR and antibody staining confirmed the presence of PLC-beta1, - beta2, - beta3, and - beta4 in rat SCG. We have tested the role of two PLC isoforms (PLC-beta1 and PLC-beta4) using antisense-expression constructs. Antisense constructs, consisting of the cytomegalovirus promoter driving antisense cRNA corresponding to the 3'-untranslated regions of PLC-beta1 and PLC-beta4, were injected into the nucleus of dissociated SCG neurons. Injected cells showed reduced antibody staining for the relevant PLC-beta isoform when compared to uninjected cells 48 hr later. BK inhibition of I-K(M) was significantly reduced 48 hr after injection of the PLC-beta4, but not the PLC-beta1, antisense-encoding plasmid. Neither PLC-beta antisense altered M-1 mAChR inhibition by Oxo-M. These data support the conclusion of Cruzblanca et al. (1998) that BK, but not M-1 mAChR, inhibition of I-K(M) involves PLC and extends this finding by indicating that PLC-beta4 is involved.

CUBN is a gene locus for albuminuria.

Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2±6.6 fmol/mL (mean±SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14±3) and submaxillary gland (521±315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89±9) was not different from right renal BK (75±23). Similarly, KA was comparable in the two kidneys (left 18.0±1.5, right 15.8±1.4μkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.

Upper Guinea Creole Evidence in favor of a Santiago birth

This paper addresses the debate on the place of origin of the Upper Guinea branch of Portuguese Creole (UGPC) as spoken in Guinea-Bissau and Casamance (GBC)1 and on the Santiago Island of Cape Verde (SCV). The hypothesis that UGPC emerged on Santiago rather than on the mainland is underpinned both historically and linguistically. First, a historical framework is presented that accounts for the linguistic transfer from Santiago to Cacheu. Secondly, Parkvall’s (2000) lexical evidence in favor of a Santiago birth will be analyzed and corroborated. Thirdly, a phonological trait that separates GBC from SCV is highlighted and shown to favor a Santiago origin. Finally, lexical and phonological features typical of 15th–16th century Portuguese shared by GBC and SCV are combined with historical data to further strengthen the Santiago birth hypothesis.

Higher education and national identity : Polish student activism in Russia 1832-1863

Doctoral dissertation, University of Helsinki

Suomen valkoinen sotilasarkkitehtuuri 1926-1939

Summary: "White" military architecture in Finland, 1926-1939

Keskustajääkäri Aarne Sihvo : näkökulma aseellisen voiman ja yhteiskunnan vuorovaikutukseen itsenäistymisen murroksesta paasikiviläiseen toiseen tasavaltaan

Summary: Middle-of-the-roader : General Aarne Sihvo (1889-1963) and the interaction between the Finnish armed forces and democracy

Yksissä leivissä : ruokolahtelainen perhelaitos ja yhteisöllinen toiminta 1750-1850

Summary: Together as one : extended families and collective labour in Ruokolahti, 1750-1850

Vanhan Suomen lahjoitusmaat 1710-1826

English summary: Noble Land-Holding and Serfdom in "Old Finland"

Kaikki irti metsästä : metsän käyttö ja muutos taigan reunalla itäisimmässä Suomessa erätaloudesta vuoteen 2000

Summary: Capitalizing on the forest : use, users and change in the forest in the wilderness economy on the edge of the taiga in Eastern Finland through the year 2000

Arkkitehdit, sota ja yhdyskuntasuhteiden hallinta : Alvar Aallon Kokemäenjokilaakson aluesuunnitelma tilansäätelyprojektina

Summary: Architects, war, and the governance of socio-spatial relationships in localities : a study of Alvar Aalto's Kokemäenjoki River Valley regional plan as a project of the regulation of space

Talonpoikainen etiikka ja kulutuksen henki : kotitalousneuvonnasta kuluttajapolitiikkaan 1900-luvun Suomessa

Summary: Peasant ethic and the spirit of consumption : from household advising to consumer policy in the 20th century Finland

Korkeakoulutuksen kasvu, lohkoutuminen ja eriarvoisuus Suomessa

Summary: Growth, fragmentation and inequality in higher education in Finland

The discourse on political pluralism in early eighteenth-century England : a conceptual study with special reference to terminology of religious origin

Doctoral dissertation, University of Jyväskylä