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1.
mBio ; 13(3): e0026722, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35446127

ABSTRACT

Gliding motility using cell surface adhesins, and export of proteins by the type IX secretion system (T9SS) are two phylum-specific features of the Bacteroidetes. Both of these processes are energized by the GldLM motor complex, which transduces the proton motive force at the inner membrane into mechanical work at the outer membrane. We previously used cryo-electron microscopy to solve the structure of the GldLM motor core from Flavobacterium johnsoniae at 3.9-Å resolution (R. Hennell James, J. C. Deme, A. Kjaer, F. Alcock, et al., Nat Microbiol 6:221-233, 2021, https://dx.doi.org/10.1038/s41564-020-00823-6). Here, we present structures of homologous complexes from a range of pathogenic and environmental Bacteroidetes species at up to 3.0-Å resolution. These structures show that the architecture of the GldLM motor core is conserved across the Bacteroidetes phylum, although there are species-specific differences at the N terminus of GldL. The resolution improvements reveal a cage-like structure that ties together the membrane-proximal cytoplasmic region of GldL and influences gliding function. These findings add detail to our structural understanding of bacterial ion-driven motors that drive the T9SS and gliding motility. IMPORTANCE Many bacteria in the Bacteroidetes phylum use the type IX secretion system to secrete proteins across their outer membrane. Most of these bacteria can also glide across surfaces using adhesin proteins that are propelled across the cell surface. Both secretion and gliding motility are driven by the GldLM protein complex, which forms a nanoscale electrochemical motor. We used cryo-electron microscopy to study the structure of the GldLM protein complex from different species, including the human pathogens Porphyromonas gingivalis and Capnocytophaga canimorsus. The organization of the motor is conserved across species, but we find species-specific structural differences and resolve motor features at higher resolution. This work improves our understanding of the type IX secretion system, which is a virulence determinant in human and animal diseases.


Subject(s)
Bacterial Proteins , Bacterial Secretion Systems , Bacteroidetes , Adhesins, Bacterial/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Secretion Systems/metabolism , Bacteroidetes/metabolism , Cryoelectron Microscopy
2.
BMJ Case Rep ; 14(4)2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33837033

ABSTRACT

Ovarian tumours harbouring foci of anaplastic carcinoma are extremely rare. With just a handful of cases reported in the literature, understanding of the disease and optimal management remains limited. A 38-year-old woman was referred to the gynaeoncologists with a multiloculated complex ovarian mass. High-grade mucinous ovarian carcinoma with mural nodules of anaplastic carcinoma was found on biopsy. Furthermore, an umbilical Sister Mary Joseph nodule signalled advanced metastatic disease. The patient underwent primary debulking surgery and was referred for adjuvant chemotherapy. High-quality radiological and surgical images are included to illustrate the approach taken to preoperative diagnosis and described surgical technique. Our case demonstrates the aggressive and rapidly progressive nature of mucinous ovarian carcinoma bearing anaplastic components. Sharing experience of such cases generates awareness and highlights the need for early detection and thorough investigations to guide subsequent management.


Subject(s)
Adenocarcinoma, Mucinous , Ovarian Neoplasms , Sister Mary Joseph's Nodule , Adult , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Female , Humans , Ovarian Neoplasms/diagnostic imaging
3.
Eur J Haematol ; 105(4): 476-483, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32544294

ABSTRACT

OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , COVID-19/mortality , COVID-19/prevention & control , Cytotoxins/adverse effects , Female , Hematologic Neoplasms/therapy , Hospitalization , Humans , Immunosuppression Therapy/adverse effects , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , United Kingdom/epidemiology
7.
Milbank Q ; 87(1): 215-27, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19298421

ABSTRACT

CONTEXT: Obesity constitutes a major public health challenge in the United States. Obesogenic environments have increased owing to the consumption of calorie-dense foods of low nutritional value and the reduction of daily physical activity (e.g., increased portion sizes of meals eaten in and out of the home and fewer physical activity requirements in schools). Policymakers and public health practitioners need to know the best practices and have the competencies to use laws and legal authorities to reverse the obesity epidemic. For instance, statutes and regulations at the federal, state, and local levels of government have been implemented to improve nutritional choices and access to healthy foods, encourage physical activity, and educate consumers about adopting healthy lifestyles. METHODS: In an effort to understand the application of laws and legal authorities for obesity prevention and control, in June 2008 the Centers for Disease Control and Prevention convened the National Summit on Legal Preparedness for Obesity Prevention and Control. An outcome of this summit will be the publication of the proceeding's white papers written by eight law and subject-matter experts with substantive contributions from summit participants, which will identify actionable options that sectors and organizations at various jurisdictional levels can consider adopting. FINDINGS: Law has played a critical role in the control of chronic diseases and the behaviors that lead to them. The use of a systematic legal framework--the use of legislation, regulation, and policy to address the multiple factors that contribute to obesogenic environments--can assist in the development, implementation, and evaluation of a variety of legal approaches for obesity prevention and control. CONCLUSIONS: Although public health-focused legal interventions are in an early stage and the direct and indirect impact they may have on the obesity epidemic is not yet understood, efforts such as the summit and white papers should help determine potentially viable legal interventions and assess their impact on population-level change.


Subject(s)
Obesity/prevention & control , Public Health/legislation & jurisprudence , Feeding Behavior , Health Knowledge, Attitudes, Practice , Health Promotion , Humans , Nutrition Policy , Obesity/epidemiology , United States/epidemiology
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