An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Dysgerminoma in three patients with Swyer syndrome

<p>Abstract</p> <p>Background</p> <p>Dysgerminoma is the most common malignant germ cell tumor of the ovary. This malignancy can be associated with pure gonadal dysgenesis or Swyer syndrome, mixed gonadal dysgenesis and partial gonadal dysgenesis.</p> <p>Case presentation</p> <p>Dysgerminoma developed in 3 phenotypic female patients with 46 XY pure gonadal dysgenesis. All patients presented first with abdominopelvic mass. Laparatomy was done. 46 XY karyotype was made by lymphocyte culture. Then these patients underwent gonadectomy that histopathology results were streak ovaries without evidence for malignancy. Two patients received postoperative adjuvant therapy.</p> <p>Conclusion</p> <p>In Patients with Swyer syndrome the risk of dysgerminoma is high and gonadectomy is recommended. Also 5% of dysgerminomas are discovered in phenotypic female and 46 XY karyotype, thus in adolescent with dysgerminoimas and amenorrhea, karyotype should be done.</p

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Ovarian carcinoma associated with pregnancy: A clinicopathologic analysis of 23 cases and review of the literature

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze and describe cases of ovarian cancer in pregnant women treated at our center and to review the literature concerned, and to discuss the rationale for therapy.</p> <p>Methods</p> <p>Twenty-Three patients of ovarian malignancies during pregnancy were treated at Vali- Asr Hospital between 1991 and 2002. Data on treatment and follow-up were evaluated.</p> <p>Results</p> <p>The incidence of ovarian carcinoma associated with pregnancy in our series was 0.083/1000 deliveries. Eleven (47.8%) were found with ovarian malignant germ cell tumors, five (21.7%) with low malignant potential tumors, four (17.4%) with invasive epithelial tumors, and three (13%) with sex cord stromal tumors. Seventeen (73.9%) of the patients were diagnosed in stage I and had complete remission. Five of the six in advanced stage died. The mean follow-up was 36.3 months. The prognosis was significantly related with stage and histological type (<it>P </it>< 0.05). Sixteen healthy live babies were recorded in this group, and two premature newborn died of respiratory distress syndrome. Chemotherapy was administered to 44% of the patients, in two cases during pregnancy. Overall survival at 5 years was 61%. In most of case conservative surgical treatment could be performed with adequate staging and debulking.</p> <p>Conclusion</p> <p>Early finding of ascitis by ultrasound and persistent large ovarian mass during pregnancy may be related to malignancy and advanced stage. Pregnant women in advanced stage of ovarian cancer seem to have poor prognosis.</p

Enzymatic hydrolysis of sorghum straw using native cellulase produced by T. reesei NCIM 992 under solid state fermentation using rice straw

Cellulose is a major constituent of renewable lignocellulosic waste available in large quantities and is considered the most important reservoir of carbon for the production of glucose, for alternative fuel and as a chemical feedstock. Over the past decade, the emphasis has been on the enzymatic hydrolysis of cellulose to glucose and the efficiency of which depends on source of cellulosic substrate, its composition, structure, pretreatment process, and reactor design. In the present study, efforts were made to produce cellulase enzyme using rice straw. The produced enzyme was used for the hydrolysis of selected lignocellulosic substrate, i.e., sorghum straw. When rice straw was used as a substrate for cellulase production under solid state fermentation, the highest enzyme activity obtained was 30.7 FPU/gds, using T. reesei NCIM 992. 25 FPU/g of cellulase was added to differently treated (native, alkali treated, alkali treated followed by 3% acid treated and alkali treated followed by 3 and 5% acid treated) sorghum straw and hydrolysis was carried out at 50 °C for 60 h. 42.5% hydrolysis was obtained after 36 h of incubation. Optimization of enzyme loading, substrate concentration, temperature, time and buffer yielded a maximum of 546.00 ± 0.55 mg/g sugars (54.60 ± 0.44 g/l) with an improved hydrolysis efficiency of 70 ± 0.45%. The enzymatic hydrolyzate can be used for fermentation of ethanol by yeasts

RMDAP: A Versatile, Ready-To-Use Toolbox for Multigene Genetic Transformation

Background: The use of transgenes to improve complex traits in crops has challenged current genetic transformation technology for multigene transfer. Therefore, a multigene transformation strategy for use in plant molecular biology and plant genetic breeding is thus needed. Methodology/Principal Findings: Here we describe a versatile, ready-to-use multigene genetic transformation method, named the Recombination-assisted Multifunctional DNA Assembly Platform (RMDAP), which combines many of the useful features of existing plant transformation systems. This platform incorporates three widely-used recombination systems, namely, Gateway technology, in vivo Cre/loxP and recombineering into a highly efficient and reliable approach for gene assembly. RMDAP proposes a strategy for gene stacking and contains a wide range of flexible, modular vectors offering a series of functionally validated genetic elements to manipulate transgene overexpression or gene silencing involved in a metabolic pathway. In particular, the ability to construct a multigene marker-free vector is another attractive feature. The built-in flexibility of original vectors has greatly increased the expansibility and applicability of the system. A proof-ofprinciple experiment was confirmed by successfully transferring several heterologous genes into the plant genome. Conclusions/Significance: This platform is a ready-to-use toolbox for full exploitation of the potential for coordinate regulation of metabolic pathways and molecular breeding, and will eventually achieve the aim of what we call ‘‘one-sto

Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

<p>Abstract</p> <p>Background</p> <p>Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds.</p> <p>Methods</p> <p>A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T), G6PD Chatham (1003 G→A), G6PD A- (202 G→A), G6PD Aures (143 T→C) and G6PD Cosenza (1376 G→C), as well as the silent 1311 (C→T) mutation.</p> <p>Results</p> <p>Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases.</p> <p>Conclusions</p> <p>The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.</p

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

<p>Abstract</p> <p>Background</p> <p>Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).</p> <p>Methods</p> <p>We isolated a breast cancer cell population (CD44⁺CD24^-cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44⁺CD24^-phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.</p> <p>Results</p> <p>Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.</p> <p>Conclusions</p> <p>Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.</p

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs