Intraocular pressure in inbred mouse strains

PURPOSE: To develop a protocol to measure the intraocular pressure (IOP) of living mice and to determine the IOP of genetically different mouse strains. METHODS: Eyes of anesthetized animals were cannulated with a very fine fluid-filled glass microneedle. The microneedle was connected to a pressure transducer, and the pressure signal was analyzed with a computer system. Intraocular pressures of male C3H/He iota, C57BL/ 6 iota, A/iota, and BALB/c iota mice were determined. RESULTS: Differences in IOP were detected between genetically distinct mouse strains maintained in virtually identical environments. C3H/He iota was the strain with the highest average IOP (13.7 +/- 0.8 mm Hg). This strain average was 1.4 mm Hg higher than that for C57BL/6 iota (12.3 +/- 0.5 mm Hg; P = 0.14), 4.3 mm Hg higher than that for A/iota (9.4 +/- 0.5 mm Hg; P < 0.001), and 6 mm Hg higher than that for BALB/c iota (7.7 +/- 0.5 mm Hg; P < 0.001). CONCLUSIONS: The authors have developed an accurate and reliable procedure for measuring intraocular pressure in living mice. This procedure can detect IOP differences between groups of mice that differ by genotype

Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6J genetic backgrounds

We investigated the relationships between hemodynamics and differential plaque development at the aortic arch of apolipoprotein E (apoE)-null mice on 129S6/SvEvTac (129) and C57BL/6J (B6) genetic backgrounds

Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds

There are well-known genetic background effects on atherosclerosis susceptibility in mice. To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and backcrossed to a C57BL/6 genetic background (B6-apoE). Plasma cholesterol and triglyceride levels in the apoE-129 mice are twice the levels in apoE-B6, and both VLDL/chylomicron remnants and HDL particles are increased. Regression analysis of plaque size relative to the age of mice suggests that the initiation of atherosclerotic plaque development at the aortic root is slower in 129-apoE mice (intercept at 3.9 mo in females and 4.1 mo in males) than in B6-apoE mice (1.3 mo in females and 2.8 mo in males). In contrast, 129-apoE mice develop extensive plaques in the aortic arches earlier than B6-apoE mice. Distinct differences in the geometry of the aortic arch between the two strains suggest that anatomical differences may contribute to the effects of genetic background on atherosclerosis. The 129-apoE/B6-apoE pair thus provides a tool to study factors governing the relation between arterial geometry and the location of plaque development

Maternal depression in rural Pakistan: the protective associations with cultural postpartum practices

Background Traditional postpartum practices are intended to provide care to mothers, but there is mixed evidence concerning their impact on postpartum depression (PPD). It remains unknown if there is a unique impact of postpartum practices on PPD separately from other types of social support, or if practices differentially affect those with existing prenatal depression. In Pakistan, chilla (چله) is a traditional postpartum practice in which women receive relief from household work, additional familial support, and supplemental food for up to 40 days postpartum. This study aims to understand if chilla protects against PPD independent of other support and whether this relationship varies by prenatal depression status. Methods Data come from the Bachpan cohort study in rural Pakistan. Chilla participation and social support (Multidimensional Scale of Perceived Social Support) were assessed at 3 months postpartum. Women were assessed for major depressive episodes (MDE) with the Structured Clinical Interview, DSM-IV and for depression symptom severity with the Patient Health Questionnaire (PHQ-9) in their third trimester and at 6 months postpartum. Adjusted linear mixed models were used to assess the relationship between chilla participation and PPD. Results Eighty-nine percent of women (N = 786) participated in chilla and almost 70% of those that participated took part in all of chilla’s aspects. In adjusted models, chilla participation was inversely related to MDE (OR = 0.56;95%CI = 0.31,1.03) and symptom severity (Mean Difference (MD) = − 1.54;95%CI: − 2.94,-0.14). Chilla participation was associated with lower odds of MDE (OR = 0.44;95%CI = 0.20,0.97) among those not prenatally depressed and with lower symptom severity among those prenatally depressed (MD = -2.05;95%CI:-3.81,-0.49). Conclusions Chilla is inversely associated with both MDE and symptom severity at 6 months postpartum above and beyond social support. Specifically, chilla is inversely associated with MDE among those not prenatally depressed and with lower symptom severity among those prenatally depressed. This relationship signals an opportunity for interventions aimed at preventing and treating PPD in this region to draw upon chilla and similar traditional postpartum practices in creating community-based, low-cost, sustainable interventions for maternal mental health

Reduction of \u3ci\u3eStabilin-2\u3c/i\u3e Contributes to a Protection Against Atherosclerosis

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele on a background of 129S6 confirmed the small reductions of atherosclerotic plaque development. To further determine whether Stab2 is an underlying gene for Aath5, we generated Stab2−/−Apoe−/− mice on a C57BL/6J background. When fed with a Western diet for 8 weeks, Stab2−/−Apoe−/− males developed approximately 30% smaller plaques than Stab2+/+Apoe−/− mice. HA was accumulated in circulation but not in major organs in the Stab2 deficient mice. STAB2-binding molecules that are involved in atherosclerosis, including acLDL, apoptotic cells, heparin and vWF were not likely the direct cause of the protection in the Stab2−/−Apoe−/− males. These data indicate that reduction of Stab2 is protective against atherosclerotic plaque development, and that Stab2 is a contributing gene underlying Aath5, although its effect is small. To test whether non-synonymous amino acid changes unique to DBA/2J affect the function of STAB2 protein, we made HEK293 cell lines expressing STAB2129 or STAB2DBA proteins, as well as STAB2129 proteins carrying each of five DBA-unique replacements that have been predicted to be deleterious. These mutant cells were capable of internalizing 125I -HA and DiI-acLDL similarly to the control cells. These results indicate that the amino acid changes unique to DBA/2J are not affecting the function of STAB2 protein, and support our previous observation that the reduced transcription of Stab2 in the liver sinusoid as a consequence of the insertion of a viral-derived sequence, intracisternal A particle, is the primary contributor to the athero-protection conferred by the DBA/2J allele

Reduction of Stabilin-2 Contributes to a Protection Against AtherosclerosisStabilin

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele on a background of 129S6 confirmed the small reductions of atherosclerotic plaque development. To further determine whether Stab2 is an underlying gene for Aath5, we generated Stab2−/−Apoe−/− mice on a C57BL/6J background. When fed with a Western diet for 8 weeks, Stab2−/−Apoe−/− males developed approximately 30% smaller plaques than Stab2+/+Apoe−/− mice. HA was accumulated in circulation but not in major organs in the Stab2 deficient mice. STAB2-binding molecules that are involved in atherosclerosis, including acLDL, apoptotic cells, heparin and vWF were not likely the direct cause of the protection in the Stab2−/−Apoe−/− males. These data indicate that reduction of Stab2 is protective against atherosclerotic plaque development, and that Stab2 is a contributing gene underlying Aath5, although its effect is small. To test whether non-synonymous amino acid changes unique to DBA/2J affect the function of STAB2 protein, we made HEK293 cell lines expressing STAB2129 or STAB2DBA proteins, as well as STAB2129 proteins carrying each of five DBA-unique replacements that have been predicted to be deleterious. These mutant cells were capable of internalizing 125I -HA and DiI-acLDL similarly to the control cells. These results indicate that the amino acid changes unique to DBA/2J are not affecting the function of STAB2 protein, and support our previous observation that the reduced transcription of Stab2 in the liver sinusoid as a consequence of the insertion of a viral-derived sequence, intracisternal A particle, is the primary contributor to the athero-protection conferred by the DBA/2J allele

A multinuclear solid state NMR, density functional theory and X-Ray diffraction study of hydrogen bonding in Group I hydrogen dibenzoates

An NMR crystallographic approach incorporating multinuclear solid state NMR (SSNMR), X-ray structure determinations and density functional theory (DFT) are used to characterise the H bonding arrangements in benzoic acid (BZA) and the corresponding Group I alkali metal hydrogen dibenzoates (HD) systems. Since the XRD data often cannot precisely confirm the proton position within the hydrogen bond, the relationship between the experimental SSNMR parameters and the ability of gauge included plane augmented wave (GIPAW) DFT to predict them becomes a powerful constraint that can assist with further structure refinement. Both the 1H and 13C MAS NMR methods provide primary descriptions of the H bonding via accurate measurements of the 1H and 13C isotropic chemical shifts, and the individual 13C chemical shift tensor elements; these are unequivocally corroborated by DFT calculations, which together accurately describe the trend of the H bonding strength as the size of the monovalent cation changes. In addition, 17O MAS and DOR NMR form a powerful combination to characterise the O environments, with the DOR technique providing highly resolved 17O NMR data which helps verify unequivocally the number of inequivalent O positions for the conventional 17O MAS NMR to process. Further multinuclear MAS and static NMR studies involving the quadrupolar 7Li, 39K, 87Rb and 133Cs nuclei, and the associated DFT calculations, provide trends and a corroboration of the H bond geometry which assist in the understanding of these arrangements. Even though the crystallographic H positions in each H bonding arrangement reported from the single crystal X-ray studies are prone to uncertainty, the good corroboration between the measured and DFT calculated chemical shift and quadrupole tensor parameters for the Group I alkali species suggest that these reported H positions are reliable

Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A–deficient mice

Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac response to hypertrophic stimuli. Here, we have followed the changes in cardiac function in response to altered mechanical load on the heart of NPRA-null mice (Npr1–/–). Chronic treatment with either enalapril, furosemide, hydralazine, or losartan were all effective in reducing and maintaining BP at normal levels without affecting heart weight/body weight. In the reverse direction, we used transverse aortic constriction (TAC) to induce pressure overload. In the Npr1–/– mice, TAC resulted in a 15-fold increase in atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular weight/body weight (LV/BW), dilatation of the LV, and significant decline in cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end diastolic dimension, and no change in fractional shortening. The activation of mitogen-activated protein kinases that occurs in response to TAC did not differ in the Npr1+/+ and Npr1–/– mice. Taken together, these results suggest that the NPRA system has direct antihypertrophic actions in the heart, independent of its role in BP control

Cohort Profile: Perinatal depression and child socioemotional development ; the Bachpan cohort study from rural Pakistan.

PURPOSE:This is a prospective pregnancy-birth cohort designed to investigate the effects of depression on socioemotional development of children. Perinatal depression is a risk factor for poor child development and for many it has a recurring chronic course. Thus, the exposure to depression can continue through the early years of the child with detrimental developmental outcomes. PARTICIPANTS:Between October 2014 and February 2016, we recruited 1154 pregnant women from a rural subdistrict of Pakistan. Data include longitudinal and repeated measures of maternal psychosocial measures and child growth, cognitive and socioemotional measures. Follow-up include mother-child dyad assessments at 3rd, 6th, 12th, 24th and 36th months of child age. All these follow-ups are community based at the household level. We have competed baseline assessment. FINDINGS TO DATE:Of the eligible dyads, we followed 885 (76.6%), 929 (91%) and 940 (93.3%) at 3, 6 and 12 months post-childbirth. We include a subsample mother-child dyad DNA and inflammatory biomarkers, 73 and 104, respectively. FUTURE PLANS:While we continue to do 24-month and 36-month follow-up assessments, we plan to follow these mother-child dyads up to the age of 7-8 years with some children being exposed to at least 1 year of school environment. Investigators interested in learning more about the study can contact ([email protected]) and ([email protected])

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia

Preeclampsia (PE), high blood pressure and protein in the urine in the last third of pregnancy, complicates about 1 in 20 human pregnancies, and it is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in premature babies. Blood pressure-lowering drugs help, but results in preventing preterm delivery and correcting the fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that feeding high doses of nicotinamide, a vitamin, improves the maternal condition, prolongs pregnancies, and prevents FGR in mice having PE-like conditions due to two contrasting causes. Because nicotinamide benefits both mothers and pups, it merits evaluation for preventing or treating PE in humans