Convergence of developmental mutants into a single tomato model system: 'Micro-Tom' as an effective toolkit for plant development research

<p>Abstract</p> <p>Background</p> <p>The tomato (<it>Solanum lycopersicum </it>L.) plant is both an economically important food crop and an ideal dicot model to investigate various physiological phenomena not possible in <it>Arabidopsis thaliana</it>. Due to the great diversity of tomato cultivars used by the research community, it is often difficult to reliably compare phenotypes. The lack of tomato developmental mutants in a single genetic background prevents the stacking of mutations to facilitate analysis of double and multiple mutants, often required for elucidating developmental pathways.</p> <p>Results</p> <p>We took advantage of the small size and rapid life cycle of the tomato cultivar Micro-Tom (MT) to create near-isogenic lines (NILs) by introgressing a suite of hormonal and photomorphogenetic mutations (altered sensitivity or endogenous levels of auxin, ethylene, abscisic acid, gibberellin, brassinosteroid, and light response) into this genetic background. To demonstrate the usefulness of this collection, we compared developmental traits between the produced NILs. All expected mutant phenotypes were expressed in the NILs. We also created NILs harboring the wild type alleles for <it>dwarf</it>, <it>self-pruning </it>and <it>uniform fruit</it>, which are mutations characteristic of MT. This amplified both the applications of the mutant collection presented here and of MT as a genetic model system.</p> <p>Conclusions</p> <p>The community resource presented here is a useful toolkit for plant research, particularly for future studies in plant development, which will require the simultaneous observation of the effect of various hormones, signaling pathways and crosstalk.</p

Validation of <i>N</i>-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of <i>Trypanosoma cruzi</i>

BACKGROUND:Trypanosoma cruzi causes Chagas disease, an endemic and debilitating illness in Latin America. Lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. The two clinically available drugs for the chemotherapy of Chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. The development of new anti-T. cruzi agents is therefore imperative. The enzyme N-myristoyltransferase (NMT) has recently been biochemically characterized, shown to be essential in Leishmania major, Trypanosoma brucei, and T. cruzi¸ and proposed as promising chemotherapeutic target in these trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS:Here, using high-content imaging we assayed eight known trypanosomatid NMT inhibitors, against mammal-dwelling intracellular amastigote and trypomastigote stages and demonstrated that three of them (compounds 1, 5, and 8) have potent anti-proliferative effect at submicromolar concentrations against T. cruzi, with very low toxicity against human epithelial cells. Moreover, metabolic labeling using myristic acid, azide showed a considerable decrease in the myristoylation of proteins in parasites treated with NMT inhibitors, providing evidence of the on-target activity of the inhibitors. CONCLUSIONS/SIGNIFICANCE:Taken together, our data point out to the potential use of NMT inhibitors as anti-T. cruzi chemotherapy

"I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania

\ud Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG), the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition. A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS) version 15 for Microsoft windows. The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences. The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This knowledge will help to improve women's sense of self-worth and maintain their identity as women, wives, friends and community members. Educational programmes to empower women socially and economically and counselling of families of women living with obstetric fistula may help these women receive medical and social support that is necessary.\u

Determining the use of prophylactic antibiotics in breast cancer surgeries : a survey of practice

Q3Q2Background: Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. Methods: An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. Results: The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Conclusion: Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery