Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.

[Expression of B7-H1 on peripheral myeloid dendritic cells in patients with HIV infection and its correlation with diseases progression].

OBJECTIVE: To investigate the features of B7-H1 expression on peripheral myeloid dendritic cells (mDCs) in patients with HIV infection and evaluate the correlations between B7-H1 expression and disease progression. METHODS: Peripheral blood samples from 82 treatment-naïve patients with HIV infection, 28 viral complete responders (CRs) under antiretroviral therapy (ART) and 14 healthy controls (HCs) were collected. Flow cytometry was applied to investigate the expression of B7-H1 on mDCs and CD4 cell counts. Plasma HIV-1 viral load was detected by bDNA. RESULTS: The frequency of B7-H1 expression on mDCs were 14.15% +/- 2.63%, 3.31% +/- 0.51% and 0.52% +/- 0.10% in AIDS patients, asymptomatic HIV infected individuals and HCs respectively. As compared with HCs, B7-H1 was significantly up-regulated on mDCs in HIV/AIDS patients. The order was as follows: AIDS patients > asymptomatic HIV infected individuals > HCs (all P < 0.05). Interestingly, the expression of B7-H1 on mDCs in long-term nonprogressors (LTNPs) was 3.12% +/- 1.14%. And it was lower than that in typical progressors (TPs) [8.12% +/- 1.37% (P = 0.001)]. Moreover, the expression of B7-H1 was negatively correlated with CD4 cell counts and positively correlated with plasma viral load in these patients (r = -0.631, P < 0.01 and r = 0.482, P < 0.01 respectively). The expression of B7-H1 on mDCs was significantly lower in ART complete responders than that in AIDS patients (6.59% +/- 1.43% vs 14.15% +/- 2.63%) (P < 0.01). Expression of B7-H1 on mDCs decreased markedly in patients whose CD4 cell counts greatly elevated after a successful antiretroviral treatment. CONCLUSION: The expression of B7-H1 on mDCs is significantly up-regulated in HIV/AIDS patients. With a close correlation with disease status, it acts as a marker of disease progression.

[A cross-sectional case study of human immunodeficiency virus and tuberculosis co-infection in mainland China].

OBJECTIVE: In order to take an insight into the profile of HIV/AIDS and tuberculosis (TB) co-infection, we made a statistic survey in 9 hospitals in mainland China. With the purpose of guiding the prevention and treatment, 241 cases with such co-infection were enrolled and the data with respect to clinical manifestations, laboratory tests, therapy and prognosis were analysed. METHODS: All indices were collected with unified questionary. RESULTS: Young men (75.9%) took constituted the majority. HIV was transmitted mainly by intravenous drug use (IDU) in Xinjiang and Yunnan provinces, by blood transfusion or blood products in Shanghai, Henan and Wenxi county of Shanxi, and by sexual transmission in Fuzhou, Shanghai, Shenzhen and Dehong prefecture of Yunnan province. In this survey, pulmonary TB accounted for 59.3%, extra-pulmonary TB for 21.2%, and both for 19.5% of the patients. As for laboratory tests, only 9.5% was positive in sputum for acid-fast bacillus (AFB) and 2.9% in culture, 10.8% of the patients had AFB in pleural fluid or cerebrospinal fluid. Besides, PPD was negative or weakly positive in most of the cases. Overall, 76.8% of the 241 cases had a CD(4) cell count < 200/microl, and 58.5% < 100/microl. 80.5% of the patients was treated with anti-tuberculous medications and 69.7% with highly active antiretroviral therapy (HAART). 203 (84.2%) were still alive and 38 (15.8%) died. CONCLUSIONS: (1) The clinical manifestations of the 241 cases were varied because of prevailing pulmonary TB. (2) The immune function was depressed with reducing CD(4) counts in most of the patients. (3) Positivity rate of examination relevant to TB was too low to help the diagnosis. (4) The mortality (15.8%) was high even with HAART and/or chemotherapy.

Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators.

Intracellular Ca(2+) homeostasis is a prerequisite for a healthy cell life. While cells from some mammals may suffer dysregulation of intracellular Ca(2+) levels under certain deleterious and stressful conditions, including hypothermia and ischemia, cells from mammalian hibernators exhibit a remarkable ability to maintain a homeostatic intracellular Ca(2+) environment. Compared with cells from non-hibernators, hibernator cells are characterized by downregulation of the activity of Ca(2+) channels in the cell membrane, which helps to prevent excessive Ca(2+) entry. Concomitantly, sequestration of Ca(2+) by intracellular Ca(2+) stores, especially the sarcoplasmic/endoplasmic reticulum, is enhanced to keep the resting levels of intracellular Ca(2+) stable. An increase in stored Ca(2+) in heart cells during hibernation ensures that the levels of Ca(2+) messenger are sufficient for forceful cell contraction under conditions of hypothermia. Maintenance of Na(+) gradients, via Na(+)-Ca(2+) exchangers, is also important in the Ca(2+) homeostasis of hibernator cells. Understanding the adaptive mechanisms of Ca(2+) regulation in hibernating mammals may suggest new strategies to protect nonhibernator cells, including those of humans, from Ca(2+)-induced dysfunction.