The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems

Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells

Study protocol for ELIXIR: an evaluation of learning and exposure to the undergraduate Interventional Radiology curriculum

Background: Despite the initiation of a suggested undergraduate curriculum for Interventional Radiology (IR) by the British Society of Interventional Radiology, there is still a lack of exposure to IR amongst medical students and junior doctors. It is unclear how much of the proposed curriculum is implemented in the undergraduate curricula of the respective medical schools in the UK. Methods and Materials: This is a cross-sectional study that aims to evaluate the level of awareness of IR as a subspecialty amongst medical students in the UK. All final year students from the 34 UK medical universities that award primary medical qualifications are eligible for the study. A student representative from each university will be recruited through a social media drive to distribute a survey. The online questionnaire is divided into five different sections; (i) Particulars, (ii) Basic knowledge on IR, (iii) Medical School Curriculum and Exposure, (iv) Career Prospects and (v) Satisfaction with Medical School Curriculum, with the intent of gauging their exposure and understanding of IR throughout the years of medical school and assessing their perceptions of IR as a potential career choice

A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma: Implications for the COVID19 pandemic and beyond

© 2022 Leow, Tan, Tan, Tan, Chan, Tikkinen, Kamat, Sengupta, Meng, Shariat, Roupret, Decaestecker, Vasdev, Chong, Enikeev, Giannarini, Ficarra and Teoh. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Purpose: The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC. Methods: We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed. Results: We identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09–1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96–1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19–2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50–4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery. Conclusions: A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.Peer reviewe

Generating chromosome geometries in a minimal cell from cryo-electron tomograms and chromosome conformation capture maps

Macromolecular Biochemistr

Bone Density and Hyperlipidemia: The T-lymphocyte Connection

Osteoporosis, which contributes to morbidity and mortality, often coexists with cardiovascular disease, especially atherosclerosis. We have reported recently that in vitro exposure of human T-lymphocytes to oxidized lipids induced expression of a key osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL). Our previous studies have shown that mice fed an atherogenic high-fat diet developed osteopenia and that bone marrow preosteoclasts from these hyperlipidemic mice have increased osteoclastic potential. To investigate the role of T-lymphocytes in the diet-induced bone loss, C57BL/6 mice were fed either chow or a high-fat diet, and bone parameters and T-lymphocyte activation were assessed at 6 and 11 months. Consistent with our previous findings, peripheral quantitative computed tomographic (pQCT) analysis showed that mice in the high-fat group had lower bone mineral content than mice in the chow group. Furthermore, histomorphometric analysis showed decreased structural parameters in the high-fat group. Coculture studies showed that bone marrow cells isolated from the high-fat group, which contained increased levels of activated memory T-lymphocytes compared with bone marrow cells from the chow mice, supported osteoclastic differentiation of RAW 264.7 cells. Additionally, RANKL expression was upregulated significantly in the T-lymphocytes isolated from the bone marrow of the high-fat group. Splenic T-lymphocytes isolated from the high-fat group also had increased expression of transcripts for the receptor for oxidized lipids (LOX-1) as well as for inflammatory and osteoclastogenic cytokines, including RANKL, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-1β, and interferon γ (IFN-γ). Together these findings suggest that T-lymphocytes play a key role in the osteoclastogenesis induced by a high-fat diet and may contribute to the bone loss associated with diet-induced osteopenia. © 2010 American Society for Bone and Mineral Research

A probabilistic approach for quantitative identification of multiple delaminations in laminated composite beams using guided waves

Available online 16 September 2016In this study a probabilistic approach is proposed to identify multiple delaminations in laminated composite beams using guided waves. The proposed method is a model-based approach, which provides a quantitative identification of the delaminations. This study puts forward a practical damage identification method, and hence, it can identify multiple delaminations using guided wave signal measured at a single measurement point on the laminated composite beams. The proposed method first determines the number of delaminations using Bayesian model class selection method. The Bayesian statistical framework is then employed to not only identify the delamination locations, lengths and through-thickness locations, but also quantify the associated uncertainties, which provides valuable information for engineers in making decision on necessary remedial work. In addition the proposed method employs the time-domain spectral finite element method and Bayesian updating with Subset simulation to further improve the computational efficiency. The proposed probabilistic approach is verified and demonstrated using data obtained from numerical simulations, which consider both measurement noise and modeling error, and experimental data. The results show that the proposed method can accurately determine the number of delaminations, and the identified delamination locations, lengths and through-thickness locations are closed to the true values.Shuai He, Ching-Tai N

When and How to Provide Feedback and Instructions to Athletes?—How Sport Psychology and Pedagogy Insights Can Improve Coaching Interventions to Enhance Self-Regulation in Training

In specialist sports coaching, the type and manner of augmented information that the coach chooses to use in communicating and training with individual athletes can have a significant impact on skill development and performance. Informed by insights from psychology, pedagogy, and sport science, this position paper presents a practitioner-based approach in response to the overarching question: When, why, and how could coaches provide information to athletes during coaching interventions? In an ecological dynamics rationale, practice is seen as a search for functional performance solutions, and augmented feedback is outlined as instructional constraints to guide athletes’ self-regulation of action in practice. Using the exemplar of team sports, we present a Skill Training Communication Model for practical application in the context of the role of a specialist coach, using a constraints-led approach (CLA). Further based on principles of a non-linear pedagogy and using the recently introduced Periodization of Skill Training (PoST) framework, the proposed model aims to support practitioners’ understanding of the pedagogical constraints of feedback and instruction during practice. In detail, the PoST framework’s three skill development and training stages work to (1) directly impact constraint manipulations in practice designs and (2) indirectly affect coaches’ choices of external (coach-induced) information. In turn, these guide practitioners on how and when to apply different verbal instruction methodologies and aim to support the design of effective skill learning environments. Finally, several practical guidelines in regard to sports coaches’ feedback and instruction processes are proposed

LEARN: a multicentre, cross‐sectional evaluation of Urology teaching in UK medical schools

Objective: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)‐mandated urological procedures, and the proportion of undergraduates considering urology as a career. Subjects and Methods: The uroLogical tEAching in bRitish medical schools Nationally (LEARN) study was a national multicentre cross‐sectional evaluation. Year 2 to Year 5 medical students and Foundation Year (FY) 1 doctors were invited to complete a survey between 3 October and 20 December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E‐Surveys (CHERRIES). Results: In all, 7063/8346 (84.6%) responses from all 39 UK medical schools were included; 1127/7063 (16.0%) were from FY1 doctors who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory‐based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. In all, 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. Conclusion: The LEARN Study is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated against the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Visualizing circadian cell biology in cyanobacteria

Circadian clocks are nearly ubiquitous throughout life, appearing in eukaryotes and prokaryotes alike. They are an adaptation that evolved to modify metabolism and behavior in anticipation of the daily fluctuation in light and other environmental conditions. One of the simplest organisms to posses a circadian clock is the photoautotrophic cyanobacterium Synechococcus elongatus PCC 7942. As an organism wholly dependent on the sun's energy, its biology is structured around the day-night cycle. Its metabolism, gene expression, and cellular organization are regulated in a circadian manner. Here, I investigate the potential role of circadian chromosome compaction in imparting rhythmicity to downstream gene expression. I used fluorescence microscopy to visualize chromosome compaction status and correlate it to rhythmic gene expression. I also investigated circadian changes in cellular organization using high-resolution cryo-electron tomography (CET) to visualize cells in a near-native state. I report interesting subcellular structures and features that have not been observed previously. In support of CET as a maturing tool for cell biology, I present data and considerations for sample preparation and downstream data analysis