Diffuse Lipomatosis of Thyroid Gland

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Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation

This is the final version. Available from eLife Sciences Publications via the DOI in this record.Several studies have shown that RNAi-mediated depletion of splicing factors (SFs) results in mitotic abnormalities. However, it is currently unclear whether these abnormalities reflect defective splicing of specific pre-mRNAs or a direct role of the SFs in mitosis. Here, we show that two highly conserved SFs, Sf3A2 and Prp31, are required for chromosome segregation in both Drosophila and human cells. Injections of anti-Sf3A2 and anti-Prp31 antibodies into Drosophila embryos disrupt mitotic division within 1 min, arguing strongly against a splicing-related mitotic function of these factors. We demonstrate that both SFs bind spindle microtubules (MTs) and the Ndc80 complex, which in Sf3A2- and Prp31-depleted cells is not tightly associated with the kinetochores; in HeLa cells the Ndc80/HEC1-SF interaction is restricted to the M phase. These results indicate that Sf3A2 and Prp31 directly regulate interactions among kinetochores, spindle microtubules and the Ndc80 complex in both Drosophila and human cells.Italian Association for Cancer ResearchItalian Association for Cancer Researc

Stem cells and cancer immunotherapy: Arrowhead’s 2nd annual cancer immunotherapy conference

Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead’s 2nd Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer “stem cells” as targets and therapeutic platforms based on stem cells

High rate of unintended pregnancy among pregnant women in a maternity hospital in Córdoba, Argentina: a pilot study

<p>Abstract</p> <p>Background</p> <p>Although Argentina has a new law on Reproductive Health, many barriers continue to exist regarding provision of contraceptive methods at public healthcare facilities.</p> <p>Methods</p> <p>We asked 212 pregnant women selected at random at the Maternity and Neonatal Hospital, Córdoba, Argentina, to participate in our descriptive study. Women were asked to complete a structured questionnaire. The objectives were to determine the rate of unintended pregnancies, reasons for not using contraception, past history of contraceptive use, and intended future use.</p> <p>Results</p> <p>Two hundred women responded to the questionnaire. Forty percent of the women stated that they had never used contraception and pregnancy was declared unintended by 65%. In the unintended pregnancy group, almost 50% of women said that they had not been using a contraceptive method because they were "unaware about contraception", and 25% stated that their contraceptive method had failed. Almost 85% of women stated that they intended to use contraception after delivery.</p> <p>Conclusion</p> <p>Approximately two-thirds of all pregnancies in this sample were unintended. Although the data is limited by the small sample size, our findings suggest that our government needs to invest in counseling and in improving the availability and access to contraceptive methods.</p

Duplication of a well-conserved homeodomain-leucine zipper transcription factor gene in barley generates a copy with more specific functions

Three spikelets are formed at each rachis node of the cultivated barley (Hordeum vulgare ssp. vulgare) spike. In two-rowed barley, the central one is fertile and the two lateral ones are sterile, whereas in the six-rowed type, all three are fertile. This characteristic is determined by the allelic constitution at the six-rowed spike 1 (vrs1) locus on the long arm of chromosome 2H, with the recessive allele (vrs1) being responsible for the six-rowed phenotype. The Vrs1 (HvHox1) gene encodes a homeodomain-leucine zipper (HD-Zip) transcription factor. Here, we show that the Vrs1 gene evolved in the Poaceae via a duplication, with a second copy of the gene, HvHox2, present on the short arm of chromosome 2H. Micro-collinearity and polypeptide sequences were both well conserved between HvHox2 and its Poaceae orthologs, but Vrs1 is unique to the barley tribe. The Vrs1 gene product lacks a motif which is conserved among the HvHox2 orthologs. A phylogenetic analysis demonstrated that Vrs1 and HvHox2 must have diverged after the separation of Brachypodium distachyon from the Pooideae and suggests that Vrs1 arose following the duplication of HvHox2, and acquired its new function during the evolution of the barley tribe. HvHox2 was expressed in all organs examined but Vrs1 was predominantly expressed in immature inflorescence

Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to clarify the prognostic significance of peritumoral lymphocyte infiltration in the capsule of soft tissue sarcomas (STS). Multiple observations in preclinical and clinical studies have shown that the immune system has a role in controlling tumor growth and progression. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of peritumoral lymphocytes is unknown.</p> <p>Methods</p> <p>Tissue microarrays from 80 patients with STS were constructed from duplicate cores of tissue from the tumor and the peritumoral capsule. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+ and CD20+ lymphocytes in the tumor and the peritumoral capsule.</p> <p>Results</p> <p>In univariate analyses, increasing numbers of CD20+ (<it>P </it>= 0.032) peritumoral lymphocytes were associated with a reduced disease free survival (DSS). In multivariate analyses, a high number of CD20+ peritumoral lymphocytes (<it>P </it>= 0.030) in the capsule was an independent negative prognostic factor for DSS. There were no such associations of lymphocyte infiltration in the tumor.</p> <p>Conclusions</p> <p>A high density of CD20+ peritumoral lymphocytes is an independent negative prognostic indicator for patients with STS. Further research is needed to determine whether CD20 cells in the peritumoral capsule of STS may promote tumor invasion in the surrounding tissue and increase the metastatic potential.</p

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines : a case report

Abstract Background Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Methods Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. Results A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Conclusions Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial

Data from an International Multi-Centre Study of Statistics and Mathematics Anxieties and Related Variables in University Students (the SMARVUS Dataset)

This large, international dataset contains survey responses from N = 12,570 students from 100 universities in 35 countries, collected in 21 languages. We measured anxieties (statistics, mathematics, test, trait, social interaction, performance, creativity, intolerance of uncertainty, and fear of negative evaluation), self-efficacy, persistence, and the cognitive reflection test, and collected demographics, previous mathematics grades, self-reported and official statistics grades, and statistics module details. Data reuse potential is broad, including testing links between anxieties and statistics/mathematics education factors, and examining instruments’ psychometric properties across different languages and contexts. Data and metadata are stored on the Open Science Framework website [https://osf.io/mhg94/]