Effects of elevated [CO2 ] on maize defence against mycotoxigenic Fusarium verticillioides.

Maize is by quantity the most important C4 cereal crop; however, future climate changes are expected to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce productivity. While rising atmospheric [CO2 ] is a driving force behind the warmer temperatures and drought, which aggravate fungal disease and mycotoxin accumulation, our understanding of how elevated [CO2 ] will effect maize defences against such pathogens is limited. Here we report that elevated [CO2 ] increases maize susceptibility to Fusarium verticillioides proliferation, while mycotoxin levels are unaltered. Fumonisin production is not proportional to the increase in F. verticillioides biomass, and the amount of fumonisin produced per unit pathogen is reduced at elevated [CO2 ]. Following F. verticillioides stalk inoculation, the accumulation of sugars, free fatty acids, lipoxygenase (LOX) transcripts, phytohormones and downstream phytoalexins is dampened in maize grown at elevated [CO2 ]. The attenuation of maize 13-LOXs and jasmonic acid production correlates with reduced terpenoid phytoalexins and increased susceptibility. Furthermore, the attenuated induction of 9-LOXs, which have been suggested to stimulate mycotoxin biosynthesis, is consistent with reduced fumonisin per unit fungal biomass at elevated [CO2 ]. Our findings suggest that elevated [CO2 ] will compromise maize LOX-dependent signalling, which will influence the interactions between maize and mycotoxigenic fungi

Circulating miRNA Biomarkers in Early Breast Cancer Detection following Mammography

The currently accepted stepwise model of breast tumorigenesis assumes a gradual transition from normal breast epithelial cells to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Percutaneous core needle biopsy (CNB) is the standard technique following an abnormal mammographic finding. However, CNB is less reliable in differentiating simple ADH (sADH) from ADH component coexisted with advanced lesions such as DCIS and/or IDC (cADH). Therefore, to identify and validate novel reliable molecular biomarkers is essential in order to improve the efficiency of therapeutic recommendations, as well as to minimize anxiety and unnecessary procedures. miRNAs function as tumor suppressors or oncogenes and play a critical role in cancer initiation and progression by regulating their target genes. Unlike messenger RNAs (mRNAs), which could be easily degraded, miRNAs are found to be stable not only in body fluid, but also in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues. The stability of miRNAs in FFPE and blood samples suggests that they may be the ideal biomarkers for the early diagnosis and prognosis of cancer, including breast cancer. The goal of this research is to use FFPE and blood samples from the two different groups of patients, analyze the candidate miRNAs to differentiating simple sADH from cADH. In our published studies, we identified a series of miRNAs that are differentially expressed during stepwise transition of breast carcinogenesis, including miR-671-5p. In this study, we showed that the expression of miR-671-5p and miR-638 decreases in ADH, DCIS, and IDC compared with the matched adjacent normal tissues. In addition, we examined the candidate miRNA expression in two groups of ADH blood samples: 28 sADHs and 32 cADHs by qRT-PCR. We found that miR-671-5p expression was decreased in cADHs, but not in sADHs, compared with their matched normal controls. Our recent publication demonstrated that miR-671-5p functions as a tumor suppressor miRNA during breast cancer progression by regulating FOXM1 expression. Using NanoString technology, we found another miRNA, miR-545-3p to be significantly overexpressed in cADHs compared with sADH. miR-545-3p is related to Snai2, which is a member of Snail family transcription factor, encoding a transcription repressor involving in epithelial-mesenchymal transitions (EMT). Our data suggest that miRNAs, such as miR-671-5p and miR-545-3p may be potential circulating biomarkers for early breast cancer detection following mammography and CNB

Characterizations of how species mediate ecosystem properties require more comprehensive functional effect descriptors

The importance of individual species in mediating ecosystem process and functioning is generally accepted, but categorical descriptors that summarize species-specific contributions to ecosystems tend to reference a limited number of biological traits and underestimate the importance of how organisms interact with their environment. Here, we show how three functionally contrasting sediment-dwelling marine invertebrates affect fluid and particle transport - important processes in mediating nutrient cycling - and use high-resolution reconstructions of burrow geometry to determine the extent and nature of biogenic modification. We find that individual functional effect descriptors fall short of being able to adequately characterize how species mediate the stocks and flows of important ecosystem properties and that, in contrary to common practice and understanding, they are not substitutable with one another because they emphasize different aspects of species activity and behavior. When information derived from these metrics is combined with knowledge of how species behave and modify their environment, however, detailed mechanistic information emerges that increases the likelihood that a species functional standing will be appropriately summarized. Our study provides evidence that more comprehensive functional effect descriptors are required if they are to be of value to those tasked with projecting how altered biodiversity will influence future ecosystems

Validity of self-reported history of Chlamydia trachomatis infection

BACKGROUND: Chlamydia trachomatis infection is common and largely asymptomatic in women. If untreated, it can lead to sequelae such as pelvic inflammatory disease and infertility. It is unknown whether a patient's self-reported history of Chlamydia trachomatis infection is a valid marker of past infection. OBJECTIVE: Our objective was to evaluate the validity of women's self-reported history of Chlamydia trachomatis infection compared with Chlamydia trachomatis serology, a marker for previous infection. STUDY DESIGN: We analyzed data from the Fertility After Contraception Termination study. We compared participants' survey responses with the question, "Have you ever been told by a health care provider that you had Chlamydia?" to serological test results indicating the presence or absence of antibodies to Chlamydia trachomatis as assessed by a microimmunofluorescence assay. Prevalence of past infection, sensitivity, specificity, predictive values, and likelihood ratios were calculated. The Cohen's kappa statistic was computed to assess agreement between self-report and serology. RESULTS: Among 409 participants, 108 (26%) reported having a history of Chlamydia trachomatis infection, whereas 146 (36%) had positive serological test results. Relative to positive microimmunofluorescence assay, the sensitivity and specificity of self-reported history of Chlamydia trachomatis infection were 52.1% (95% confidence interval, 43.6-60.4%) and 87.8% (95% confidence interval, 83.3-91.5%), respectively. The positive predictive value of the self-report was 70.4% (95% confidence interval, 60.8-78.8%), and the negative predictive value was 76.7% (95% confidence interval, 71.6-81.4%). The likelihood ratio was found to be 4.28. Agreement between self-report and serology was found to be moderate (kappa = 0.42, P < .001). CONCLUSION: Self-reported history of Chlamydia trachomatis infection commonly yields false-negative and false-positive results. When definitive status of past Chlamydia trachomatis infection is needed, serology should be obtained

Invasive cutaneous rhizopus infections in an immunocompromised patient population associated with hospital laundry carts

Mucormycosis is an invasive fungal infection with high morbidity and mortality that most commonly occurs in immunocompromised hosts.1–5 Cutaneous mucormycosis is rare and can be acquired through direct contact of the fungi with non-intact skin or mucous membranes.3,4,7–9 Outbreaks of mucormycosis associated with contaminated adhesive bandages, ostomy supplies, wooden tongue depressors, and linen have been published.1,6–9 This is a report of a cluster of cutaneous mucormycosis with Rhizopus that occurred in 4 immunocompromised inpatients housed primarily in the same intensive care unit (ICU) prior to infection

miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple negative breast cancer

Introduction Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment. Methods Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays. Results The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression. Conclusions Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer

Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography

BACKGROUND: Among physicians who perform endoscopic retrograde cholangiopancreatography (ERCP), the relationship between procedure volume and outcome is unknown. OBJECTIVE: Quantify the ERCP volume-outcome relationship by measuring provider-specific failure rates, hospitalization rates, and other quality measures. RESEARCH DESIGN: Retrospective cohort. SUBJECTS: A total of 16,968 ERCPs performed by 130 physicians between 2001 and 2011, identified in the Indiana Network for Patient Care. MEASURES: Physicians were classified by their average annual Indiana Network for Patient Care volume and stratified into low (<25/y) and high (≥25/y). Outcomes included failed procedures, defined as repeat ERCP, percutaneous transhepatic cholangiography or surgical exploration of the bile duct≤7 days after the index procedure, hospitalization rates, and 30-day mortality. RESULTS: Among 15,514 index ERCPs, there were 1163 (7.5%) failures; the failure rate was higher among low (9.5%) compared with high volume (5.7%) providers (P<0.001). A second ERCP within 7 days (a subgroup of failure rate) occurred more frequently when the original ERCP was performed by a low-volume (4.1%) versus a high-volume physician (2.3%, P=0.013). Patients were more frequently hospitalized within 24 hours when the ERCP was performed by a low-volume (28.3%) versus high-volume physician (14.8%, P=0.002). Mortality within 30 days was similar (low=1.9%, high=1.9%). Among low-volume physicians and after adjusting, the odds of having a failed procedure decreased 3.3% (95% confidence interval, 1.6%-5.0%, P<0.001) with each additional ERCP performed per year. CONCLUSIONS: Lower provider volume is associated with higher failure rate for ERCP, and greater need for postprocedure hospitalization

Norms and trust-shaping relationships among food-exporting SMEs in Ghana

There is a marked paucity of empirically rigorous research that focuses on the impact that indigenous institutional influences can have on the internationalization strategies of entrepreneurs operating in developing countries. This study therefore explores the complex processes through which owner-managers of food-exporting SMEs in Ghana draw on cultural norms to build networks that enable internationalization, in the absence of formal institutional support. The results facilitate a better understanding of the hybridization of indigenous and global norms that underpin SME internationalization in Ghana and other developing economies, particularly in Africa. The study contributes to the theory and practice of interorganizational relationships and to international entrepreneurship in an African context

Subduktion muokkaamaa merellistä kuorta sekoittuneena köyhtyneeseen vaippalähteeseen Karoon laakiobasalttiprovinssin alkulähteillä

The great majority of continental flood basalts (CFBs) have a marked lithospheric geochemical signature, suggesting derivation from the continental lithosphere, or contamination by it. Here we present new Pb and Os isotopic data and review previously published major element, trace element, mineral chemical, and Sr and Nd isotopic data for geochemically unusual mafic and ultramafic dikes located in the Antarctic segment (Ahlmannryggen, western Dronning Maud Land) of the Karoo CFB province. Some of the dikes show evidence of minor contamination with continental crust, but the least contaminated dikes exhibit depleted mantle –like initial εNd (+9) and 187Os/188Os (0.1244–0.1251) at 180 Ma. In contrast, their initial Sr and Pb isotopic compositions (87Sr/86Sr = 0.7035–0.7062, 206Pb/204Pb = 18.2–18.4, 207Pb/204Pb = 15.49–15.52, 208Pb/204Pb = 37.7–37.9 at 180 Ma) are more enriched than expected for depleted mantle, and the major element and mineral chemical evidence indicate contribution from (recycled) pyroxenite sources. Our Sr, Nd, Pb, and Os isotopic and trace element modeling indicate mixed peridotite-pyroxenite sources that contain ~10–30 % of seawater-altered and subduction-modified MORB with a recycling age of less than 1.0 Ga entrained in a depleted Os-rich peridotite matrix. Such a source would explain the unusual combination of elevated initial 87Sr/86Sr and Pb isotopic ratios and relative depletion in LILE, U, Th, Pb and LREE, high initial εNd, and low initial 187Os/188Os. Although the sources of the dikes probably did not play a major part in the generation of the Karoo CFBs in general, different kind of recycled source components (e.g., sediment-influenced) would be more difficult to distinguish from lithospheric CFB geochemical signatures. In addition to underlying continental lithosphere, the involvement of recycled sources in causing the apparent lithospheric geochemical affinity of CFBs should thus be carefully assessed in every case.The great majority of continental flood basalts (CFBs) have a marked lithospheric geochemical signature, suggesting derivation from the continental lithosphere, or contamination by it. Here we present new Pb and Os isotopic data and review previously published major element, trace element, mineral chemical, and Sr and Nd isotopic data for geochemically unusual mafic and ultramafic dikes located in the Antarctic segment (Ahlmannryggen, western Dronning Maud Land) of the Karoo CFB province. Some of the dikes show evidence of minor contamination with continental crust, but the least contaminated dikes exhibit depleted mantle –like initial εNd (+9) and 187Os/188Os (0.1244–0.1251) at 180 Ma. In contrast, their initial Sr and Pb isotopic compositions (87Sr/86Sr = 0.7035–0.7062, 206Pb/204Pb = 18.2–18.4, 207Pb/204Pb = 15.49–15.52, 208Pb/204Pb = 37.7–37.9 at 180 Ma) are more enriched than expected for depleted mantle, and the major element and mineral chemical evidence indicate contribution from (recycled) pyroxenite sources. Our Sr, Nd, Pb, and Os isotopic and trace element modeling indicate mixed peridotite-pyroxenite sources that contain ~10–30 % of seawater-altered and subduction-modified MORB with a recycling age of less than 1.0 Ga entrained in a depleted Os-rich peridotite matrix. Such a source would explain the unusual combination of elevated initial 87Sr/86Sr and Pb isotopic ratios and relative depletion in LILE, U, Th, Pb and LREE, high initial εNd, and low initial 187Os/188Os. Although the sources of the dikes probably did not play a major part in the generation of the Karoo CFBs in general, different kind of recycled source components (e.g., sediment-influenced) would be more difficult to distinguish from lithospheric CFB geochemical signatures. In addition to underlying continental lithosphere, the involvement of recycled sources in causing the apparent lithospheric geochemical affinity of CFBs should thus be carefully assessed in every case.Peer reviewe