Cardiorenal fibrosis and dysfunction in aging: Imbalance in mediators and regulators of collagen

Cardiorenal fibrosis is a biological process that increases with age and contributes to dysfunction of the heart and kidney. While numerous circulating and tissue hormones, cytokines and enzymes have been identified in the development of cardiorenal fibrosis, several reports have suggested that the anti-fibrotic natriuretic peptide system (NPS), pro-fibrotic renin–angiotensin–aldosterone system (RAAS), transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are fundamental regulators and mediators of this process. However, the simultaneous assessment of these components in the development of age-mediated cardiorenal fibrotic remodeling is not completely understood. Thus, we assessed cardiorenal structure and function, the circulating NPS and RAAS and the cardiorenal tissue gene expression of collagen (Col) I, Col III, TGF-β1, MMP-9 and TIMP-1 in 2 and 20 month old Fischer rats. Our studies determined that aging was characterized by an increase in cardiorenal fibrosis that was accompanied with cardiorenal dysfunction. These alterations were associated with lower circulating atrial and C-type natriuretic peptides and higher angiotensin II and aldosterone levels in the aged rats. Moreover, we observed a decrease in Col I and III and an increase in TIMP- mRNA expressions in the aged heart and kidney, while TGF-β1 expression increased and MMP-9 decreased only in the aged kidney. We conclude that the age-mediated alterations in these fibrotic regulator and mediator profiles favors collagen accumulation due to an imbalance between the NPS and RAAS as well as a decline in the degradative pathway, thus suggesting a therapeutic opportunity to target these components.     

The Detection of Hamster Connexins: A Comparison of Expression Profiles with Wild-Type Mouse and the Cancer-Prone Min Mouse

The open reading frames of 17 connexins from Syrian hamster (using tissues) and 16 connexins from the Chinese hamster cell line V79, were fully (Cx30, Cx31, Cx37, Cx43 and Cx45) or partially sequenced. We have also detected, and partially sequenced, seven rat connexins that previously were unavailable. The expression of connexin genes was examined in some hamster organs and cultured hamster cells, and compared with wild-type mouse and the cancer-prone Min mouse. Although the expression patterns were similar for most organs and connexins in hamster and mouse, there were also some prominent differences (Cx29 and 30.3 in testis; Cx31.1 and 32 in eye; Cx46 in brain, kidney and testis; Cx47 in kidney). This suggests that some connexins have species-specific expression profiles. In contrast, there were minimal differences in expression profiles between wild type and Min mice. Species-specific expression profiles should be considered in attempts to make animal models of human connexin-associated diseases.     

Social cognitive impairment and autism: what are we trying to explain?

Early psychological theories of autism explained the clinical features of this condition in terms of perceptual and sensory processing impairments. The arrival of domain-specific social cognitive theories changed this focus, postulating a ‘primary’ and specific psychological impairment of social cognition. Across the years, evidence has been growing in support of social cognitive and social attention explanations in autism. However, there has also been evidence for general non-social cognitive impairments in representational understanding, attention allocation and sensory processing. Here, I review recent findings and consider the case for the specificity and primacy of the social cognitive impairment, proposing that we should focus more explicitly on clinically valid features for insights on the integration of ‘social’ and ‘non-social’ cognition.     

Genetic differentiation of Elysia timida (Risso, 1818) populations in the Southwest Mediterranean and Mar Menor coastal lagoon

Genetic variation at 10 enzyme loci was analysed in Elysia timida sacoglossan mollusc samples, originating from both coastal lagoon and marine sites. The observed heterozygosity ranged from 0.390 (Los Urrutias) to 0.277 (Tabarca). Marine and coastal lagoon populations were characterised by exclusive alleles.     

Yield stability of determinate and indeterminate dry bean cultivars

Summary Yield stability of determinate and indeterminate dry bean (Phaseolus vulgaris L.) cultivars was compared using regression of genotypic performance on environmental means. Yields of 28 dry bean cultivars differing in plant growth habit and commercial class designation were obtained from 42 Michigan performance nurseries over the 6 year period 1980 to 1985. The determinate type I large-seeded kidney and cranberry bean cultivars had below-average seed yield and large mean square deviations from regression. Lower yielding determinate small-seeded navy cultivars had low deviation mean square values, while higher yielding determinate navy cultivars had correspondingly higher mean square deviations from regression. Although seed yield of cultivars with an indeterminate growth habit was greater than determinate cultivars, prostrate type III indeterminate cultivars had deviation mean square values equivalent to those of large-seeded determinate cultivars. The erect, short vine type II indeterminate cultivars (architypes) had greater than average seed yields and minimum deviations from regression. Compared with other plant types, the architype group showed a greater yield response to more productive environments, with regression coefficient values significantly greater than unity. These results indicate that the type II growth habit offers the breeder the best opportunity of obtaining greater seed yield without incurring loss of yield stability as occurs with the type I and type III growth habits. Since the dry bean cultivars utilized in this study represent two distinct centers of domestication, the regression analysis suggests that cultivars from the predominant genetic center demonstrate more yield stability. A non-significant rank correlation coefficient between the combined and separate analyses for deviation mean square values of large-seeded cultivars implies that commercial dry bean classes should be compared separately based on center of domestication.Contributions from Michigan Bean Commission, Michigan Bean Shippers Assoc. and Michigan Agric. Exp. Sta., Michigan Agric. Exp. Sta. Journal Article No. 11986     

Characterization of human-dog social interaction using owner report

Dog owners were surveyed for observations of social behaviors in their dogs, using questions adapted from the human Autism Diagnostic Observation Schedule (ADOS) pre-verbal module. Using 939 responses for purebred and mixed-breed dogs, three factors were identified: initiation of reciprocal social behaviors (INIT), response to social interactions (RSPNS), and communication (COMM). There were small or no effects of sex, age, breed group or training. For six breeds with more than 35 responses (Border Collie, Rough Collie, German Shepherd, Golden Retriever, Labrador Retriever, Standard Poodle), the behaviors eye contact with humans, enjoyment in interactions with human interaction, and name recognition demonstrated little variability across breeds, while asking for objects, giving/showing objects to humans, and attempts to direct humans’ attention showed higher variability across these breeds. Breeds with genetically similar backgrounds had similar response distributions for owner reports of dog response to pointing. When considering these breeds according to the broad categories of “herders” and “retrievers,” owners reported that the “herders” used more eye contact and vocalization, while the “retrievers” used more body contact. Information regarding social cognitive abilities in dogs provided by owner report suggest that there is variability across many social cognitive abilities in dogs and offers direction for further experimental investigations.     

Molecular Characteristics and Peptide Specificity of Vasoactive Intestinal Peptide Receptors from Rat Cerebral Cortex

Vasoactive intestinal peptide (VIP) receptors have been identified in CNS by their chemical specificity and molecular size. Using synaptosomes isolated from rat cerebral cortex, it was shown that central VIP receptors discriminated among natural and synthetic VIP-related peptides, because half-maximal inhibition of [125I]VIP binding to synaptosomes was obtained for 0.6 nM VIP, 9 nM peptide histidine isoleucineamide (PHI), 50 nM VIP 2-28, 70 nM secretin, 100 nM rat growth hormone-releasing factor (GRF), and 350 nM human GRF. Other peptides of the VIP family, such as glucagon and gastric inhibitory polypeptide, did not interact with cortical VIP receptors. The molecular components of VIP receptors in rat cerebral cortex were identified after [125I]VIP cross-linking to synaptosomes using the cross-linker dithiobis(succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of synaptosomal proteins revealed two major [125I]VIP-protein complexes of Mr 49,000 and 18,000. The labeling of the Mr 49,000 component was specific, because it was abolished by native VIP, whereas the labeling of the Mr 18,000 component was not. Natural VIP agonists reduced the labeling of the Mr 49,000 component with the following order of potency: VIP greater than PHI greater than secretin approximately equal to rat GRF. In contrast, glucagon and octapeptide of cholecystokinin were without effect, a result indicating its peptide specificity. Densitometric scanning of autoradiographs showed that the labeling of the Mr 49,000 component was inhibited by low VIP concentrations between 10(-10) and 10(-6) M (IC50 = 0.8 nM), a result indicating the component's high affinity for VIP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression level of enzymes related to in situ estrogen synthesis and clinicopathological parameters in breast cancer patients

In order to evaluate the importance of estrogen production in tumor and surrounding tissues, we measured mRNA expression levels of 5 enzymes participating to estrogen synthesis in situ and 4 breast cancer-related proteins in 27 pairs of tumor and non-malignant tissues. Steroid sulfatase (STS) mRNA was more frequently detected in tumor tissues rather than in their non-malignant counterparts. Estrogen sulfotransferase (EST) was constantly expressed with high level not only in tumor tissues but also in their surrounding non-malignant counterparts. In contrast, mRNA expression levels of aromatase, and 17β-hydroxysteroid dehydrogenase type I and II were relatively low and detected only in small proportion of the patients. We also measured the mRNA expression levels of the same nine genes in tumor tissues of 197 breast cancer patients, and analyzed relationship between the mRNA expression level and the clinicopathological parameters. The mRNA expression levels of STS, aromatase and erbB2 in tumor tissues increased as breast cancer progressed. The tumoral mRNA expression levels of STS, estrogen receptor β, and erbB2 in patients with recurrence were higher than those in patients without recurrence. Upregulation of STS expression plays an important role in tumor progression of human breast cancer and is considered to be responsible for estrogen production in tumor and surrounding tissues.