Miocene bristlemouths (Teleostei: Stomiiformes: Gonostomatidae) from the Makrilia Formation,Ierapetra, Crete

Bristlemouths of the genus Cyclothone are currently regarded as the most abundant vertebrates on Earth. The fossil record seems to suggest that these fishes diversified during the Miocene in the Pacific Ocean, but there is no evidence of their presence in the Miocene of the Atlantic Ocean and Mediterranean basin. A new bristlemouth, Cyclothone gaudanti sp. nov. (Teleostei, Stomiiformes, Gonostomatidae), is described herein based on 16 specimens from the Upper Miocene Makrilia Formation (late Tortonian of Crete, Greece). The small sized species is characterized by light pigmentation, 30–31 (14–15 + 15–16) vertebrae, dorsal fin with 10–13 rays, anal fin with 10–14 rays, premaxilla bearing seven closely spaced teeth, maxilla with 42–55 teeth, epipleurals, and autogenous parhypural. The presence of epipleurals appears to be unique of this Miocene species, and the re-establishment of this ancestral character state may be possibly interpreted as related to a phylogenetic character reversal. Morphological and paleoecological considerations suggest that this species possibly inhabited the upper mesopelagic layer, at depths ranging from 2–300 and 500 meters.     

Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma

BACKGROUND: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear. METHODS: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: We found PD-L1 positive expression in 31.11% (28/90) of peritumoral tissues. Peritumoral PD-L1 expression was associated with a significantly worse overall survival (OS) (P = .000) and disease-free survival (DFS) (P = .001) compared to the negative expression group. Additionally, peritumoral PD-L1 positivity significantly correlated with vascular invasion and a lower albumin level (≤35 g/L). Univariate and multivariate Cox regression models both revealed peritumoral PD-L1 as an independent prognostic factor for OS (HR = 2.853, P = .002) and DFS (HR = 2.362, P = .003). The prognostic value of PD-L1 positivity was validated in the independent data set. CONCLUSIONS: Our data suggest PD-L1 expression in peritumoral hepatocytes is an independent prognostic factor for OS and DFS. This implies that future anti-cancer therapy should target not only residual tumor cells but also the “soil” for promoting tumor growth. Peritumoral PD-L1 could be a good target for adjuvant therapy after hepatectomy.     

The Functional Roles of the MDM2 Splice Variants P2-MDM2-10 and MDM2-∆5 in Breast Cancer Cells

BACKGROUND: MDM2 is a negative regulator of p53 and is upregulated in numerous human cancers. While different MDM2 splice variants have been observed in both normal tissues and malignant cells, their functions are poorly understood. METHODS: We evaluated the effect of MDM2 splice variants by overexpression in MCF-7 cells and analyses of expression of downstream genes (qPCR and Western blot), subcellular localization (immunofluorescence), cell cycle assays (Nucleocounter3000), apoptosis analysis (Annexin V detection), and induction of senescence (β-galactosidase analysis). RESULTS: In a screen for MDM2 splice variants in MCF-7 breast cancer cells, extended with data from healthy leukocytes, we found P2-MDM2-10 and MDM2-Δ5 to be the splice variants expressed at highest levels. Contrasting MDM2 full-length protein, we found normal tissue expression levels of P2-MDM2-10 and MDM2-Δ5 to be highest in individuals harboring the promoter SNP309TT genotype. While we detected no protein product coded for by MDM2-Δ5, the P2-MDM2-10 variant generated a protein markedly more stable than MDM2-FL. Both splice variants were significantly upregulated in stressed cells (P = 4.3 × 10^?4 and P = 7.1 × 10^?4, respectively). Notably, chemotherapy treatment and overexpression of P2-MDM2-10 or MDM2-Δ5 both lead to increased mRNA levels of the endogenous MDM2-FL (P = .039 and P = .070, respectively) but also the proapoptotic gene PUMA (P = .010 and P = .033, respectively), accompanied by induction of apoptosis and repression of senescence. CONCLUSION: We found P2-MDM2-10 and MDM2-Δ5 to have distinct biological functions in breast cancer cells. GENERAL SIGNIFICANCE: Alternative splicing may influence the oncogenic effects of the MDM2 gene.     

ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib

The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor.     

Immune responses to Neospora caninum and prospects for vaccination

Developing an effective vaccine against neosporosis presents several interesting challenges. The parasite is spread efficiently from mother to foetus over several generations, and naturally infected cattle do not appear to develop adequate protective immunity. Modulation of the immune response during pregnancy favours parasite survival and multiplication. However, induction of pro-inflammatory responses that are thought to be protective against Neospora caninum would be detrimental to the pregnancy. So, is vaccination a feasible option to control the disease? This article discusses some of these issues and reports on the progress towards a vaccine for neosporosis.     

Pioneering Interdisciplinary Research Initiatives for Oceans and Human Health

Following the release of the report From Monsoons to Microbes by the National Research Council in 1999, efforts began to promote federal sponsorship of research and education in a new scientific discipline focusing on how the ocean affects human health. The National Institute of Environmental Health Sciences (NIEHS) and the National Science Foundation (NSF) initiated a joint program to establish and sustain several research Centers for Oceans and Human Health (COHH) at nonfederal institutions. Shortly thereafter, the National Oceanic and Atmospheric Administration (NOAA) mounted a similar initiative to establish intramural centers at existing NOAA facilities as well as an extramural grants program. This profile reviews the history and current state of these developments. The statements and opinions in this report are those of the authors only and do not necessarily represent the position of, or imply commitments by, any agency of the United States Government.     

Heterogeneities in anti-schistosome humoral responses following chemotherapy

Schistosomiasis is a major public health problem in Africa, the Middle East, Asia and South America. The main control strategy is to treat infected people with anthelmintic drugs, principally the safe and relatively cheap drug praziquantel. Several treatment re-infection studies in humans have shown that praziquantel can have long-term effects beyond a transient reduction of infection intensity. These long-term effects include the altering of schistosome-specific immune responses in humans, which is associated with resistance to re-infection. Differences have been observed in treatment-induced immunological changes between individuals and between populations. This article discusses the contributions of host- and parasite-related heterogeneities to post-treatment humoral responses in humans infected with Schistosoma mansoni and Schistosoma haematobium and considers the practical implications of such heterogeneity for schistosome immuno-epidemiology studies.     

1988～2011年国家自然科学基金真菌病学资助项目分析及文献复习

目的通过分析1988～2011年国家自然科学基金对真菌病学的资助情况和复习相关文献总结国内真菌病学领域1988～2011年的热点问题及研究现状。方法访问国家自然科学基金ISIS系统C0107、H1104、H1903,检索1988～2011年真菌病学获得国家自然基金资助的项目总数,并对其进行统计分析。结果 1988～2011年真菌病学获得国家自然科学基金资助项目共计95项,每年的资助项目数逐步上升,面上项目和青年基金项目为资助主体。1988～2011年国家自然科学基金对真菌病学的各个研究方向都有项目资助。排在前3位的分别是:隐球菌、念珠菌、曲霉,发表了很多有价值的文章。结论 1988～2011年真菌病学在国家自然科学基金的引领下取得了长足的进步与发展。