Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause

Estrogen is thought to protect against the development of chronic kidney disease, and menopause increases the development and severity of diabetic kidney disease. In this study, we used streptozotocin (STZ) to induce diabetes in the 4-vinylcyclohexene diepoxide (VCD)-treated mouse model of menopause. DNA microarrays were used to identify gene expression changes in the diabetic kidney postmenopause. An ANOVA model, CARMA, was used to isolate the menopause effect between two groups of diabetic mice, diabetic menopausal (STZ/VCD) and diabetic cycling (STZ). In this diabetic study, 8,864 genes of the possible 15,600 genes on the array were included in the ANOVA; 99 genes were identified as demonstrating a >1.5-fold up- or downregulation between the STZ/VCD and STZ groups. We randomly selected genes for confirmation by real-time PCR; midkine (Mdk), immediate early response gene 3 (IEX-1), mitogen-inducible gene 6 (Mig6), and ubiquitin-specific protease 2 (USP2) were significantly increased in the kidneys of STZ/VCD compared with STZ mice. Western blot analysis confirmed that Mdk and IEX-1 protein abundance was significantly increased in the kidney cortex of STZ/VCD compared with STZ mice. In a separate study, DNA microarrays and CARMA analysis were used to identify the effect of menopause on the nondiabetic kidney; VCD-treated mice were compared with cycling mice. Of the possible 15,600 genes on the array, 9,142 genes were included in the ANOVA; 20 genes were identified as demonstrating a >1.5-fold up- or downregulation; histidine decarboxylase and vanin 1 were among the genes identified as differentially expressed in the postmenopausal nondiabetic kidney. These data expand our understanding of how hormone status correlates with the development of diabetic kidney disease and identify several target genes for further studies.     

Carbon dioxide supersaturation in Florida lakes

We examined data on CO₂ and related limnological and geographic information from a sample of 948 Florida freshwater lakes. The objectives for this study were (1) to determine the partial pressures of carbon dioxide (ρCO₂) in the surface waters of a large sample of Florida lakes, (2) to determine if several limnological or geographic factors are related to levels of ρCO₂ in Florida lakes, and (3) to estimate the net annual rate of loss of CO₂ to the atmosphere from the freshwater lakes of Florida. The calculated ρCO₂ for the lakes in our sample range from 0 to 81,000 μatm, with a mean of 3,550 μatm, a median of 1,030 μatm, and a geometric mean of 1,270 μatm. About 87% of the Florida lakes were supersaturated with CO₂. There were statistically significant correlations between values for ρCO₂ and several water chemistry variables; however, the R ² values were small and accounted for only a small portion of the variance. In general the ρCO₂ values were higher in the lakes with low alkalinities and low contents of dissolved salts. The best predictor of ρCO₂ is pH, with an R ² of 0.82 for a polynomial relationship. The ρCO₂ values tend to decrease from northwest to southeast across the state of Florida, which corresponds to the gradients we found for pH, alkalinity, and specific conductance. The average areal rate of carbon emission from the Florida lakes was 328 g C m⁻² y⁻¹, and the total carbon loss for the lakes and ponds of Florida was 2.0 Tg y⁻¹. This amounts to about 2% of the total carbon emissions from all the lakes of the world as estimated by previous studies. Handling editors: Darren Bade     

African manatee (Trichechus senegalensis) habitat suitability at Lake Ossa,Cameroon, using trophic state models and predictions of submerged aquatic vegetation

The present study aims at investigating the past and current trophic status of Lake Ossa and evaluating its potential impact on African manatee health. Lake Ossa is known as a refuge for the threatened African manatees in Cameroon. Little information exists on the water quality and health of the ecosystem as reflected by its chemical and biological characteristics. Aquatic biotic and abiotic parameters including water clarity, nitrogen, phosphorous, and chlorophyll concentrations were measured monthly during four months at each of 18 water sampling stations evenly distributed across the lake. These parameters were then compared with historical values obtained from the literature to examine the dynamic trophic state of Lake Ossa. Results indicate that Lake Ossa''s trophic state parameters doubled in only three decades (from 1985 to 2016), moving from a mesotrophic to a eutrophic state. The decreasing nutrient gradient moving from the mouth of the lake (in the south) to the north indicates that the flow of the adjacent Sanaga River is the primary source of nutrient input. Further analysis suggests that the poor transparency of the lake is not associated with chlorophyll concentrations but rather with the suspended sediments brought‐in by the Sanaga River. Consequently, our model demonstrated that despite nutrient enrichment, less than 5% of the lake bottom surface sustained submerged aquatic vegetation. Thus, shoreline emergent vegetation is the primary food available for the local manatee population. During the dry season, water recedes drastically and disconnects from the dominant shoreline emergent vegetation, decreasing accessibility for manatees. The current study revealed major environmental concerns (eutrophication and sedimentation) that may negatively impact habitat quality for manatees. The information from the results will be key for the development of the management plan of the lake and its manatee population. Efficient land use and water management across the entire watershed may be necessary to mitigate such issues.     

Anxiety and increased 5‐HT1A receptor response in NCAM null mutant mice

Mice deficient in the neural cell adhesion molecule (NCAM) show behavioral abnormalities as adults, including altered exploratory behavior, deficits in spatial learning, and increased intermale aggression. Here, we report increased anxiety‐like behavior of homozygous (NCAM^−/−) and heterozygous (NCAM^+/−) mutant mice in a light/dark avoidance test, independent of genetic background and gender. Anxiety‐like behavior was reduced in both NCAM^+/+ and NCAM^−/− mice by systemic administration of the benzodiazepine agonist diazepam and the 5‐HT_1A receptor agonists buspirone and 8‐OH‐DPAT. However, NCAM^−/− mice showed anxiolytic‐like effects at lower doses of buspirone and 8‐OH‐DPAT than NCAM^+/+ mice. Such increased response to 5‐HT_1A receptor stimulation suggests a functional change in the serotonergic system of NCAM^−/− mice, likely involved in the control of anxiety and aggression. However, 5‐HT_1A receptor binding and tissue content of serotonin and its metabolite 5‐hydroxyindolacetic acid were found unaltered in every brain area of NCAM^−/− mice investigated, indicating that expression of 5‐HT_1A receptors as well as synthesis and release of serotonin are largely unchanged in NCAM^−/− mice. We hypothesize a critical involvement of endogenous NCAM in serotonergic transmission via 5‐HT_1A receptors and inwardly rectifying K⁺ channels as the respective effector systems. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 343–355, 1999     

Inhibition of an IUD-induced precocious luteolysis by prostaglandin E1 (PGE1) in sheep

Fifteen ewes were assigned as they came into estrus to one of three randomized treatment groups: 1. Sham IUD + Vehicle, 2. IUD + Vehicle or 3. IUD + PGE₁ in vehicle. An IUD was inserted adjacent to the luteal-bearing ovary on day 3 postestrus. Prostaglandin E₁ (500 μg) in vehicle (Na₂CO₃) or vehicle was given intrauterine through an indwelling uterine cannula every four hours from day 3 postestrus until ewes returned to estrus. Precocious estrus was induced in both the sham IUD groups receiving vehicle. Prostaglandin E₁ prevented an IUD-induced premature luteolysis based on daily concentrations of progesterone in peripheral blood and the interestrous interval. It is concluded that an IUD-induced premature luteolysis is not necessarily via physical distention by the IUD. It is also concluded that chronic intrauterine infusions of PGE₁ can prevent an IUD-induced premature luteolysis.     

Rare Copy Number Variants Are a Common Cause of Short Stature

Human growth has an estimated heritability of about 80%–90%. Nevertheless, the underlying cause of shortness of stature remains unknown in the majority of individuals. Genome-wide association studies (GWAS) showed that both common single nucleotide polymorphisms and copy number variants (CNVs) contribute to height variation under a polygenic model, although explaining only a small fraction of overall genetic variability in the general population. Under the hypothesis that severe forms of growth retardation might also be caused by major gene effects, we searched for rare CNVs in 200 families, 92 sporadic and 108 familial, with idiopathic short stature compared to 820 control individuals. Although similar in number, patients had overall significantly larger CNVs (p-value<1×10⁻⁷). In a gene-based analysis of all non-polymorphic CNVs>50 kb for gene function, tissue expression, and murine knock-out phenotypes, we identified 10 duplications and 10 deletions ranging in size from 109 kb to 14 Mb, of which 7 were de novo (p<0.03) and 13 inherited from the likewise affected parent but absent in controls. Patients with these likely disease causing 20 CNVs were smaller than the remaining group (p<0.01). Eleven (55%) of these CNVs either overlapped with known microaberration syndromes associated with short stature or contained GWAS loci for height. Haploinsufficiency (HI) score and further expression profiling suggested dosage sensitivity of major growth-related genes at these loci. Overall 10% of patients carried a disease-causing CNV indicating that, like in neurodevelopmental disorders, rare CNVs are a frequent cause of severe growth retardation.