BACL is a novel brain-associated, non-NKC-encoded mammalian C-type lectin-like receptor of the CLEC2 family

Natural Killer Gene Complex (NKC)–encoded C-type lectin-like receptors (CTLRs) are expressed on various immune cells including T cells, NK cells and myeloid cells and thereby contribute to the orchestration of cellular immune responses. Some NKC-encoded CTLRs are grouped into the C-type lectin family 2 (CLEC2 family) and interact with genetically linked CTLRs of the NKRP1 family. While many CLEC2 family members are expressed by hematopoietic cells (e.g. CD69 (CLEC2C)), others such as the keratinocyte-associated KACL (CLEC2A) are specifically expressed by other tissues. Here we provide the first characterization of the orphan gene CLEC2L. In contrast to other CLEC2 family members, CLEC2L is conserved among mammals and located outside of the NKC. We show that CLEC2L-encoded CTLRs are expressed as non-glycosylated, disulfide-linked homodimers at the cell surface. CLEC2L expression is fairly tissue-restricted with a predominant expression in the brain. Thus CLEC2L-encoded CTLRs were designated BACL (brain-associated C-type lectin). Combining in situ hybridization and immunohistochemistry, we show that BACL is expressed by neurons in the CNS, with a pronounced expression by Purkinje cells. Notably, the CLEC2L locus is adjacent to another orphan CTLR gene (KLRG2), but reporter cell assays did neither indicate interaction of BACL with the KLRG2 ectodomain nor with human NK cell lines or lymphocytes. Along these lines, growth of BACL-expressing tumor cell lines in immunocompetent mice did not provide evidence for an immune-related function of BACL. Altogether, the CLEC2L gene encodes a homodimeric cell surface CTLR that stands out among CLEC2 family members by its conservation in mammals, its biochemical properties and the predominant expression in the brain. Future studies will have to reveal insights into the functional relevance of BACL in the context of its neuronal expression

Оценка эффективности комбинированной терапии у больных артериальной гипертензией

Представлены результаты исследования воздействия комбинации антигипертензивного препарата аккупро и психотропного препарата золофта на клинические показатели больных артериальной гипертензией и их психологическое состояние и качество жизни. Показана высокая эффективность комбинированной терапии.The findings of the research of the effect of combination of an antihypertensive drug Accupro and a psychotropic drug Zoloft on clinical parameters in patients with arterial hypertension as well as their mental state and quality of life are presented. A high efficacy of the combined therapy is shown

Combined Aluminum Roll-Formed Profiles

Aluminum roll-formed profiles in various shapes can act as various straight or bent hollow vehicle body structures, include but not limited to front bumpers, rear bumpers, roof rails, upper A-pillars, front and/or rear longitudinals, and/or seat cross-members, among others, and may be use for various vehicles, including but not limited to commercial vehicles, trucks, busses, vans, and/or railway cars, among others. Aluminum roll-formed profiles may provide strength and/or energy absorption in case of crash events, and may be particularly useful for structures with high crash load requirements. In addition, relatively small bending radii (depending on alloy choice, temper during forming and sheet thickness) may allow for the manufacture of efficient sections with tailored properties. Aluminum roll-formed profiles may be significantly lighter than steel roll-formed profiles at the same performance while also providing significant cost saving potential compared to aluminum extrusions at similar or lower weights

A novel fluorescent pH probe for expression in plants

BACKGROUND: The pH is an important parameter controlling many metabolic and signalling pathways in living cells. Recombinant fluorescent pH indicators (pHluorins) have come into vogue for monitoring cellular pH. They are derived from the most popular Aequorea victoria GFP (Av-GFP). Here, we present a novel fluorescent pH reporter protein from the orange seapen Ptilosarcus gurneyi (Pt-GFP) and compare its properties with pHluorins for expression and use in plants. RESULTS: pHluorins have a higher pH-sensitivity. However, Pt-GFP has a broader pH-responsiveness, an excellent dynamic ratio range and a better acid stability. We demonstrate how Pt-GFP expressing Arabidopsis thaliana report cytosolic pH-clamp and changes of cytosolic pH in the response to anoxia and salt-stress. CONCLUSION: Pt-GFP appears to be the better choice when used for in vivo-recording of cellular pH in plants

Sensitivity to cdk1-inhibition is modulated by p53 status in preclinical models of embryonal tumors

Dysregulation of the cell cycle and cyclin-dependent kinases (cdks) is a hallmark of cancer cells. Intervention with cdk function is currently evaluated as a therapeutic option in many cancer types including neuroblastoma (NB), a common solid tumor of childhood. Re-analyses of mRNA profiling data from primary NB revealed that high level mRNA expression of both cdk1 and its corresponding cyclin, CCNB1, were significantly associated with worse patient outcome independent of MYCN amplification, a strong indicator of adverse NB prognosis. Cdk1 as well as CCNB1 expression were readily detectable in all embryonal tumor cell lines investigated. Pharmacological inhibition or siRNA-mediated knockdown of cdk1/CCNB1 induced proliferation arrest independent of MYCN status in NB cells. Sensitivity to cdk1 inhibition was modulated by TP53, which was demonstrated using isogenic cells with wild-type TP53 expressing either dominant-negative p53 or a short hairpin RNA directed against TP53. Apoptosis induced by cdk1 inhibition was dependent on caspase activation and was concomitant with upregulation of transcriptional targets of TP53. Our results confirm an essential role for the cdk1/CCNB1 complex in tumor cell survival. As relapsing embryonal tumors often present with p53 pathway alterations, these findings have potential implications for therapy approaches targeting cdks

The cancer stem cell in hepatocellular carcinoma

The recognition of intra-tumoral cellular heterogeneity has given way to the concept of the cancer stem cell (CSC). According to this concept, CSCs are able to self-renew and differentiate into all of the cancer cell lineages present within the tumor, placing the CSC at the top of a hierarchical tree. The observation that these cells—in contrast to bulk tumor cells—are able to exclusively initiate new tumors, initiate metastatic spread and resist chemotherapy implies that CSCs are solely responsible for tumor recurrence and should be therapeutically targeted. Toward this end, dissecting and understanding the biology of CSCs should translate into new clinical therapeutic approaches. In this article, we review the CSC concept in cancer, with a special focus on hepatocellular carcinoma.Work in the laboratory of P.C.H. is supported by a Max Eder Fellowship of the German Cancer Aid (111746), by a Collaborative Research Centre grant of the German Research Foundation (316249678–SFB 1279) and by a Hector Foundation Cancer Research grant (M65.1). Work in the laboratory of B.S.J. is supported by a Rámon y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economía y Competitividad, Spain. L.-A.S. is supported by the clinician scientist program of Ulm Universit