Cloning and characterisation of genes encoding molecular recognition proteins from insects

Olfaction is one of the most important senses by which insects obtain information about their environment. In the early stages of olfactory perception in insects, odour molecules are carried across the sensillum lymph by small soluble Odorant Binding Proteins (OBPs). This is followed by activation of the appropriate olfactory receptor, resulting in an electrical impulse, and subsequent degradation of the initial signal. OBPs have been studied in a range of insect orders including Lepidoptera, Diptera and Orthoptera, and this study reports the cloning and characterisation of cDNAs with a potential olfactory role in the vetch aphid, Megoura viciae (Buckton, Homoptera: Aphididiae). Construction and sequencing of antennal cDNA libraries identified two cDNAs, MvicOBP1 and Mv164, which were approximately 0.8kb and 1kb respectively. The amino acid sequence of MvicOBP1 has the spacing pattern of six cysteine residues that is characteristic of insect OBPs, and Mv164 shows similarity to insect cytochrome P450 enzymes. RT-PCR showed that these cDNAs have specific or enhanced expression in the chemosensory tissues of M. viciae, and parallel expression patterns suggest a "linked" function. Related sequences are present and expressed in other aphid species, and sequencing of genomic fragments allowed the partial elucidation of the intron/exon organisation of these genes. Subtracted antennal cDNA libraries identified two cDNAs encoding proteins with significant similarity to insect chemosensory proteins (CSPs), cDNAs encoding Juvenile Hormone Binding Proteins (JHBPs), and a tissue-specific cDNA with a potential carrier role. These, coupled with the OBPs, add evidence to the suggestion that there is an insect superfamily of binding proteins. A PBP from Bombyx mori (BmorPBP1) was used as a model system for in vitro expression of an insect OBP and subsequent characterisation of the recombinant protein. Four forms of this protein, identified through their interaction with an anti-BmorPBP antibody, were resolved by isoelectric focusing

Sertoli–Leydig cell tumor of the ovary: A diagnostic dilemma

AbstractBackgroundSertoli–Leydig cell tumors are rare sex-cord stromal tumors of the ovary that can present with a variety of histological elements, which may complicate diagnosis and treatment.CaseA 40-year-old female presenting with pelvic pain is found to have a large complex right adnexal mass and elevated alpha-fetoprotein. The mass was diagnosed as a Sertoli–Leydig cell tumor with heterologous elements including carcinoid and hepatoid components. She was treated with surgical resection followed by adjuvant chemotherapy and remains clear of disease.ConclusionPrognostic indicators for Sertoli–Leydig cell tumors include degree and type of heterologous element differentiation. Thorough characterization of such elements is crucial for adequate diagnosis and treatment

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types

Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53–0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54–1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans

Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more aggressive clinical course than B-cell lymphomas, with the T-cell phenotype itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With notable exceptions such as ALK+ anaplastic large cell lymphoma (ALCL, ALK+), the molecular abnormalities in PTCL remain poorly characterised. We had previously identified circulating antibodies to ALK in patients with ALCL, ALK+. Thus, as a strategy to identify potential antigens associated with the pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis cDNA library with sera from four PTCL, NOS patients using the SEREX (serological analysis of recombinant cDNA expression libraries) technique. We identified nine PTCL, NOS-associated antigens whose immunological reactivity was further investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal controls. The centrosomal protein CEP250 was specifically recognised by patients sera and showed increased protein expression in cell lines derived from T-cell versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera. Transcripts for all nine genes were identified in 39 cancer cell lines and the five genes encoding preferentially lymphoma-recognised antigens were widely expressed in normal tissues and mononuclear cell subsets. In summary, this study identifies novel molecules that are immunologically recognised in vivo by patients with PTCL, NOS. Future studies are needed to determine whether these tumor antigens play a role in the pathogenesis of PTCL

Elimination of Pain and Improvement of Exercise Capacity in Camurati-Engelmann Disease With Losartan

Background: Camurati-Engelmann disease (CED) is a rare disorder, with approximately 250 described cases in the literature. Treatment options are limited and have been suboptimal so far

A need for “good eyes”: Experiences told by patients diagnosed with psychosis

This study highlights experiences of psychiatric care described by patients diagnosed with psychosis. The aim was to investigate how patients, based on earlier experiences, described their wishes and needs regarding the psychiatric care system. Data comprised material from four focus groups; analysis used an inductive thematic approach. Relationships with staff emerged as a recurring theme. During periods of psychosis, patients needed staff to act as “parental figures,” providing care, safety, and help in dealing with overwhelming stimulation from the outside word. In the ensuing struggle to devise a livable life, the need for relationships recurred. In this phase, staff needed to give their time, provide support through information, and mirror the patient's capacity and hope. The patient's trials were described as threatened by a lack of continuity and non-listening professionals. It was important for staff to listen and understand, and to see and respect the patients' viewpoints

The conceptual design of CLARA, a novel fel test facility for ultra-short pulse generation

CLARA will be a novel FEL test facility focussed on the generation of ultra-short photon pulses with extreme levels of stability and synchronisation. The principal aim is to experimentally demonstrate that sub-cooperation length pulse generation with FELs is viable, and to compare the various schemes being championed. The results will translate directly to existing and future X-ray FELs, enabling them to generate attosecond pulses, thereby extending their science capabilities. This paper gives an overview of the motivation for CLARA, describes the facility design (reported in detail in the recently published Conceptual Design Report [1]) and proposed operating modes and summarises the proposed areas of FEL research