RXRα acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells

Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid receptors and other hormone receptors including the orphan receptor TR3, forming different heterodimers that transduce diverse steroid/thyroid hormone signaling. Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRalpha, shuttling is energy-dependent through a nuclear pore complex (NPC)mediated pathway for its import and an intact DNA binding domain-mediated pathway for its export. In the presence of its ligand 9-cis retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More importantly, we also show that RXRalpha. acts as a carrier to assist translocation of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3 colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depends on RXRalpha as in living cells GFP-TR3 alone did not result in export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP-TR3 cotransfected with RXRalpha was exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti-sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid. In addition, mitochondrial TR3, but not RXRalpha was critical for apoptosis, as TR3 mutants that were distributed in the mitochondria induced apoptosis in the presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of RXRalpha function, in which it acts as a carrier for nucleocytoplasmic translocation of orphan receptors

Maternal care in rural China: a case study from Anhui province

<p>Abstract</p> <p>Background</p> <p>Studies on prenatal care in China have focused on the timing and frequency of prenatal care and relatively little information can be found on how maternal care has been organized and funded or on the actual content of the visits, especially in the less developed rural areas. This study explored maternal care in a rural county from Anhui province in terms of care organization, provision and utilization.</p> <p>Methods</p> <p>A total of 699 mothers of infants under one year of age were interviewed with structured questionnaires; the county health bureau officials and managers of township hospitals (n = 10) and county level hospitals (n = 2) were interviewed; the process of the maternal care services was observed by the researchers. In addition, statistics from the local government were used.</p> <p>Results</p> <p>The county level hospitals were well staffed and equipped and served as a referral centre for women with a high-risk pregnancy. Township hospitals had, on average, 1.7 midwives serving an average population of 15,000 people. Only 10–20% of the current costs in county level hospitals and township hospitals were funded by the local government, and women paid for delivery care. There was no systematic organized prenatal care and referrals were not mandatory. About half of the women had their first prenatal visit before the 13th gestational week, 36% had fewer than 5 prenatal visits, and about 9% had no prenatal visits. A major reason for not having prenatal care visits was that women considered it unnecessary. Most women (87%) gave birth in public health facilities, and the rest in a private clinic or at home. A total of 8% of births were delivered by caesarean section. Very few women had any postnatal visits. About half of the women received the recommended number of prenatal blood pressure and haemoglobin measurements.</p> <p>Conclusion</p> <p>Delivery care was better provided than both prenatal and postnatal care in the study area. Reliance on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care.</p

A resource-based view and dynamic capabilities approach in the context of a region’s international attractiveness: The recent case of Western Australia

This exploratory study proposes a framework based on the resource view theory and the dynamic capabilities approach to further the understanding of a region’s attractiveness, particularly from an international perspective. The case of Western Australia is examined through in-depth, face-to-face interviews with nine country consuls experienced in international trade. The findings revealed significant ways in which Western Australia could enhance its future commercial appeal. The findings revealed the value of synergies between this state and other countries, particularly exchanging expertise, transferring knowledge, or exporting know-how, education, both university and industry-focused, research and development and expertise. These forms of regional attractiveness emphasise the strategic role of industry resources and dynamic capabilities, thus, underscoring the usefulness and applicability of the proposed framework. While the state’s mineral exports will continue to drive its economy, harnessing its potential in other areas is crucial to adapt to changing business environments and to build sustained competitive advantage. © 2018, The Author(s) 2018

An operative case of hepatic pseudolymphoma difficult to differentiate from primary hepatic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Hepatic pseudolymphoma (HPL) and primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are rare diseases and the differential diagnosis between these two entities is sometimes difficult. We herein report a 56-year-old Japanese woman who was pointed out to have a space occupying lesion in the left lateral segment of the liver. Hepatitis viral-associated antigen/antibody was negative and liver function tests including lactic dehydrogenase, peripheral blood count, tumor markers and soluble interleukin-2 receptor were all within normal limit. Imaging study using computed tomography and magnetic resonance imaging were not typical for hepatocellular carcinoma, cholangiocarcinoma, or other metastatic cancer. Fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning showed high standardized uptake value in the solitary lesion in the liver. Under a diagnosis of primary liver neoplasm, laparoscopic-assisted lateral segmentectomy was performed. Liver tumor of maximal 1.0 cm in diameter was consisted of aggregation of lymphocytes of predominantly B-cell, containing multiple lymphocyte follicles positive for CD10 and bcl-2, consistent with a diagnosis of HPL rather than MALT lymphoma, although a definitive differentiation was pending. The background liver showed non-alcoholic fatty liver disease/early non-alcoholic steatohepatitis. The patient is currently doing well with no sign of relapse 13 months after the surgery. Since the accurate diagnosis is difficult, laparoscopic approach would provide a reasonable procedure of diagnostic and therapeutic advantage with minimal invasiveness for patients. Considering that the real nature of this entity remains unclear, vigilant follow-up of patient is essential

Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells

Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3−/− and Pglyrp4−/− mice (but not Pglyrp2−/− mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3−/− and Pglyrp4−/− mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3−/− and Pglyrp4−/− mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3−/− mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1−/− mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin

Cytosporone B is an agonist for nuclear orphan receptor Nur77

Nuclear orphan receptor Nur77 has important roles in many biological processes. However, a physiological ligand for Nur77 has not been identified. Here, we report that the octaketide cytosporone B (Csn-B) is a naturally occurring agonist for Nur77. Csn-B specifically binds to the ligand-binding domain of Nur77 and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B-dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. These biological effects were not observed in Nur77-null (Nr4a1(-/-)) mice, which indicates that Csn-B regulates gluconeogenesis through Nur77. Moreover, Csn-B induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release. Thus, Csn-B may represent a promising therapeutic drug for cancers and hypoglycemia, and it may also be useful as a reagent to increase understanding of Nur77 biological function.National Natural Science Fund of China Ministry of Science and Technology Ministry of Educatio

Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian yaks

The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak’s hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ~1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding

Update on HHV-8-Associated Malignancies

The human herpesvirus 8 (HHV-8) is the oncogenic virus associated with Kaposi’s sarcoma (KS) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric Castleman’s disease. KS is among the most common malignancies seen in HIV-infected patients despite the decreased incidence of KS in the era of highly active antiretroviral therapy. Advances in molecular pathology reveal HHV-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activate several cellular signaling cascades while evading immune surveillance. This knowledge has led to the evolution of multiple therapeutic strategies against specific molecular targets. Many such therapeutic modalities have shown activity, but none have proven to be curative. Identifying possible prognostic factors is another active area of research. This review summarizes the recent developments in the fields of virus transmission, molecular biology, and treatment of HHV-8-related neoplasms

Etiological factors in primary hepatic B-cell lymphoma

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren’s syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells