17ß-estradiol regulates adenosine triphosphate-binding cassette transporters A1 expression via estrogen receptor A to increase macrophage cholesterol efflux.

The liver is the focus of research on the effects of estrogen on cholesterol metabolism. Few studies have investigated the effects of estrogen on macrophages despite the significance of cells in atherosclerosis. The purpose of this study is to examine the effect of estrogen on macrophage cholesterol efflux. Macrophage cholesterol efflux, oil red O staining, RT-qPCR, Western blotting analyses were used to determine cholesterol metabolize and the expressions of adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1) and ATP-binding cassette transporter A1 (ABCA1) in J774A.1 cells, and the effect of these treatments was compared to without adding 17ß-estradiol (E2). Gain and loss of estrogen receptor alpha (ERα), liver X receptor α (LXRα) were conducted to study interactions between E2, ERα, LXRα and ABCA. Finally, in mice, we validate the relationship between ERα and ABCA1. E2 increases cholesterol efflux from macrophages and decreases the formation of lipid droplets and positively regulates the expression of ABCA1. This suggests that estrogen receptors (ERs) directly regulate ABCA1 translation. We suppressed ERα, which decreased the mRNA and protein expression of ABCA1. At the mRNA level, E2 treatment could partially counteract these phenomena, but not at the protein level. ABCA1 expression decreased after LXRα was inhibited. This suggests that ABCA1 translation is directly regulated by ERα. In the ovariectomized mouse model of ABCA1 protein expression was significantly reduced in the peritoneal macrophages of the ovariectomy (OVX) group. ABCA1 protein expression was greater in the E2+OVX group than in the OVX group. E2 contributes to the positive regulation of ABCA1 expression and promotes cholesterol efflux in macrophages by binding to ERα. The effect is independent of ABCA1 transcription regulation by LXRα.

[Clinical value of prenatal MRI in the diagnosis of fetal simple expansion of lateral ventricle and follow-up after birth].

Objective: To explore the value of prenatal MRI in the diagnosis of fetal simple expansion of lateral ventricle (ventriculomegaly) , and follow up the nervous system development status after birth. Methods: Simple expansion of the lateral ventricle fetus by prenatal MRI examination were collected in Huzhou Maternal and Child Care Hospital from May 2013 to June 2015, 126 cases of live births in expansion group, 50 normal cases were recruited in the same period as the control group. In expansion group, fetal subgroup analysis was done: (1) unilateral or bilateral lateral ventricle expasion: one group was 98 cases was lateral ventricle expansion (77.8%, 98/126), expansion of bilateral ventricle group was 28 cases (22.2%, 28/126). (2) Prenatal MRI in the diagnosis of the lateral ventricle of expansion: expansion of the lateral ventricle width was greater than 10.0 mm, if both sides were expanding, the expand width was the heavier one side, divided into 3 subgroups: ①Expansion in group A (lateral ventricle width 10.0-12.0 mm) were 88 cases (69.8%, 88/126). ②Expansion in group B (lateral ventricle width 12.1-15.0 mm) were 29 cases (23.0%, 29/126). ③Expansion of group C (lateral ventricle width> 15.0 mm) were 9 cases (7.12%, 9/126). All 176 cases were followed up after birth at the 3rd, 6th, 12th, 18th month (corrected age was used for premature babies), and Gesell developmental schedules (GDS) were used to evaluate the neurobehavioral development. Results: (1) The MRI results after birth: 21 cases were followed up by MRI after birth. In group A, 11 cases had MRI and 9 were normal (the ventricular width <10.0 mm after birth), the other 2 cases were stable (the ventricular width measured first time after birth was ≥10.0 mm, but the difference was within 2.0 mm from the MRI before birth). In group B, 4 cases had MRI, 1 was normal, 1 was stable, and 2 cases were getting better (the ventricular width measured first time after birth was ≥10.0 mm, but the width decreased more than 2.0 mm from the MRI before birth). In group C, 6 cases had MRI. 3 cases were getting better and 3 cases were stable. (2) Overall GDS results: expansion group after the birth of the 3rd, 6th, 12th, 18th month GDS evaluation results compared with control group, respectively, the differences were not statistically significant (all P>0.05). (3) The GDS results among the subgroups: in each evaluation after birth, there were no statistically significant differences between group A and the control group (all P>0.05). The GDS results of group B at the 3rd and 6th month were lower than those of the control group (P<0.05); while there were no statistically significant differences between the 2 goups at the 12th and 18th month (P>0.05). And for group C, statistically significant differences were found compared to the control group at each follow-up time (all P<0.05). (4) GDS results at different times after birth in the expansion group: there was no statistically significant difference between the results at the 3rd and 6th month (P>0.05). But when the result at the 3rd month was compared to the results of the 12th or 18th month, the differences were statistically significant (P<0.05). GDS result of 6th months after birth compared with 12th and 18th months, respectively, there were no statistically significant differences (P>0.05). There was no statistically significant difference between the results at the 12th and 18th month (P>0.05). (5) The GDS results in unilateral and bilateral ventricle expansion: at the 18th month, among the 98 unilateral cases, 86 (87.8%, 86/98) had normal GDS results(>85 scores); 8 (8.2%, 8/98) had borderline results (75-85 scores); 4 (4.1%, 4/98) had delayed results (<75 scores). Among the 28 bilateral cases, 23 (82.1%, 23/28) had normal GDS results; 3 (10.7%, 3/28) had borderline results; 2 (7.1%, 2/28) had delayed results. There was no statistically significant difference (P>0.05). Conclusions: Among the simple expansion of lateral ventricle, those whose ventricular width are ≤12.0 mm may not need clinical treatment. If the width is between 12.1 to 15.0 mm, closely follow-up and targeted rehabilitation training after birth are recommended. When the width is more than 15.0 mm, the risk of the central nervous system function delay is significantly increased, and early intervention might improve the prognosis.

Association between -44G/A and +71A/G polymorphisms in the connexin 40 gene and atrial fibrillation in Uyghur and Han populations in Xinjiang, China.

We aimed to elucidate the association between connexin 40 (Cx40) genetic polymorphisms and atrial fibrillation (AF) in a Chinese population in Xinjiang comprising Uyghur and Han individuals. We enrolled 275 Uyghur and 305 age- and gender-matched Han subjects, and used polymerase chain reaction to detect single nucleotide polymorphisms (SNPs; -44G/A and +71A/G) in the gene encoding Cx40. A mutation screening was performed by direct sequencing and calculation of genotype and allele frequencies among AF patients and control subjects to determine the relationship between these variants and this condition in Uyghur and Han populations. The two SNPs examined were significantly associated with AF in both ethnic groups. Further analysis showed the SNPs to be in perfect linkage disequilibrium in both AF and control groups among Uyghur and Han individuals. In both populations -44AA genotype and A allele frequencies among AF patients were significantly higher than those in the control group. In addition, under the dominant model (GG vs GA+AA), a significant difference in the distribution of Cx40 -44G/A genotypes was detected between patients and controls. Logistic regression analysis revealed that Cx40 genetic polymorphisms increase AF risk in Uyghur and Han residents of Xinjiang. In conclusion, both the -44G/A and +71A/G variants of the gene encoding this protein are associated with AF in Uyghur and Han populations in northern China.

Relationship between the TaqI B polymorphism of the cholesterol ester transfer protein gene and atrial fibrillation in Han and Kazak populations.

The TaqI B polymorphism in the cholesterol ester transfer protein (CETP) (B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The B1 allele of the CETP gene is a known independent risk factor for genetic susceptibility to atrial fibrillation (AF); however, little is known about this polymorphism in the minority groups of Xinjiang, China. We examined the role of this polymorphism in AF using two independent case-control studies: the Han population (101 AF patients and 129 control subjects) and the Kazak population (103 AF patients and 101 control subjects). Carriers of the B1B1 genotype were more frequent among AF patients than among controls both in the Han population (34.7 versus 26.4%; χ(2) = 10.686, P = 0.001) and in the Kazak population (53.4 versus 24.8%; χ(2) = 27.802, P < 0.001). The odds ratio (OR) for carriers of the B1B1 genotype to AF susceptibility was 0.187 [95% confidence interval (CI) = 0.071- 0.491] in the Han group and 8.426 (95%CI = 2.295-30.933) in the Kazak population. After adjustment of confounding factors such as gender, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, and high-density lipoprotein, the difference remained significant in the Han group (P = 0.001; OR = 0.187, 95%CI = 0.071-0.491) and in the Kazak group (P = 0.001; OR = 8.426, 95%CI = 2.295-30.933). The presence of the B1B1 polymorphism of the Taq1B CETP genotype contributes to the development of AF in the Han and Kazak populations in western China (Xinjiang).

Effects of integrin-linked kinase on human corpus cavernosum smooth muscle cell cytoskeletal organisation.

We investigated the effects of integrin-linked kinase (ILK) on the in vitro attachment, spreading, migration and microfilament dynamics of human corpus cavernosum smooth muscle cells. ILK small interfering RNA (siRNA) was used to transfect human corpus cavernosum smooth muscle cells; and cell attachment, spreading and migration were assessed. Additionally, microfilament dynamics were evaluated using Alexa Fluor 488 and phalloidin staining. We found that ILK gene knock-down significantly inhibited human corpus cavernosum smooth muscle cell attachment, spreading and migration. Moreover, blocking the expression of ILK disturbed actin cytoskeleton reorganisation and morphology in human corpus cavernosum smooth muscle cells. These results show that the targeting of ILK with siRNA significantly inhibited cell attachment, spreading, migration and microfilament dynamics in human corpus cavernosum smooth muscle cells. These findings indicate that ILK might be a potential therapeutic molecular target for the treatment of erectile dysfunction.

Saccadic localization of eccentric forms.

Saccades made to outline drawings of eccentric forms were compared with saccades made to single-point targets. Saccades could be directed to designated locations within eccentric forms nearly as accurately and precisely as they could be directed to single points. Saccades directed to the form as a whole landed at consistent locations near the center of the form. These results show that contour information is sufficient for accurate computation of a saccadic command and that this computation is constrained by the internal coding of the shape. A serial two-stage process, voluntary selection followed by a weighted-averaging process, is proposed for computation of the saccadic command based on information provided by shape.

The role of location probability in the programming of saccades: implications for "center-of-gravity" tendencies.

Short-latency saccades to targets among nontarget backgrounds are often directed to the center of the entire (target + nontarget) stimulus configuration. This "averaging" or "center-of-gravity" tendency has been attributed to an automatic, reflexive saccadic response to a poorly-resolved visual signal. We investigated the role of high-level processes by varying the probability of the target appearing in one of two locations. Subjects were asked to make a saccade to a target "+" located above-right or above-left of a central fixation point. A nontarget ("x") was in the other location (directional separation = 30 deg). The mean latencies were short (180-230 msec) in accordance with instructions. Mean saccadic direction was shifted to the right by 24-52% of the directional separation of the stimulus pair as the probability of the target appearing on the right increased from 0.2 to 0.8. The difference in saccadic directions as a function of the actual target location was small and independent of probability, showing that probability introduced a bias without affecting the discriminability of the target from the nontarget. The effect of probability was reduced when the discrimination of the target from the nontarget was easier (square vs triangle), and abolished (saccadic accuracy near perfect with the same average latencies) when the target was presented alone. The results show that the direction of short-latency saccades, initiated before the target has been distinguished from a nearby nontarget, is based on the prior history of target locations and expectations about the future location of the target. High-level plans can account for effects of nontargets on saccades. To infer that a reflexive sensorimotor averaging mechanism exists solely on the basis of observed saccadic "centering" tendencies is unwarranted.