Search

PIEZOs are mechanosensitive ion channels that convert force into chemoelectric signals1,2and have essential roles in diverse physiological settings3. In vitro studies have proposed that PIEZO channels transduce mechanical force through the deformation of extensive blades of transmembrane domains emanating from a central ion-conducting pore4–8. However, little is known about how these channels interact with their native environment and which molecular movements underlie activation. Here we directly observe the conformational dynamics of the blades of individual PIEZO1 molecules in a cell using nanoscopic fluorescence imaging. Compared with previous structural models of PIEZO1, we show that the blades are significantly expanded at rest by the bending stress exerted by the plasma membrane. The degree of expansion varies dramatically along the length of the blade, where decreased binding strength between subdomains can explain increased flexibility of the distal blade. Using chemical and mechanical modulators of PIEZO1, we show that blade expansion and channel activation are correlated. Our findings begin to uncover how PIEZO1 is activated in a native environment. More generally, as we reliably detect conformational shifts of single nanometres from populations of channels, we expect that this approach will serve as a framework for the structural analysis of membrane proteins through nanoscopic imaging.

Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC.

Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS).

Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA).

Two cell types with different migratory behaviors both exhibit guided actin polymerization along nanoscale ridge textures. Optical flow, a tool used in autonomous vehicles and facial recognition, is adapted for fluorescence imaging. The power of optical flow as a tool for future studies of intracellular dynamics is demonstrated.

Background Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC.Methods All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into “safety net” and “academic” based on where they received their care. The primary outcome was the OS.Results 1479 patients were included. The average age was 60 years and 78% (n = 1156) were male. 56% (n = 649) received care at academic and 44% (n = 649) at safety net hospitals. The median model for end-stage liver disease (MELD) was 10 (IQR 8-16). Median OS was 23 months. Etiology of cirrhosis was viral hepatitis 56% (n = 612), alcohol abuse 14% (n = 152), alcohol and hepatitis 23% (n = 251), and other 7% (n = 85). Patients with alcohol-related cirrhosis (alcohol alone or with hepatitis) were younger (59 vs 62 years), more likely to be male (86% vs 75%), treated at a safety net facility (45% vs 35%), uninsured (17% vs 13%), and had a higher MELD (median 12 vs 10) (all P< .003). They were less likely to have been screened for HCC within 1 year of diagnosis (20% vs 29%) and to receive treatment (69% vs 81%), and more likely to present with stage IV disease (21% vs 15%) (all P< .001). Patients with alcohol-related cirrhosis had decreased OS (5-year OS 24% vs 40%, P< .001), which persisted in a subset analysis of both academic and safety net populations.Conclusion Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes.

Distal cholangiocarcinoma is a rare malignancy with a dismal prognosis. Because of its location and aggressive nature, patients often present with locally advanced or metastatic disease, and effective treatment options are limited. For patients with resectable disease, surgery is the only chance for cure, but achieving an R0 resection is paramount. Optimal adjuvant therapy in resectable disease remains under investigation. Randomized controlled trials investigating neoadjuvant therapy and its impact on resectability and long-term outcomes are needed to continue to improve the outcomes of patients with distal cholangiocarcinoma.

Ergonomic challenges resulting in work-related injuries are highly prevalent, and women surgeons encounter more ergonomic difficulties and resultant injuries than men. Cardiothoracic (CT) surgery requires intense physical demands, and it is unknown how surgeon's sex may impact these challenges. Therefore, we sought to explore the impact of sex on ergonomic-related issues faced by CT surgeons.

Here, we present a protocol for electrotaxis of large epithelial cell sheets without compromising the integrity of cell epithelia in a high-throughput customized directed current electrotaxis chamber. We describe the fabrication and use of polydimethylsiloxane stencils to control the size and shape of human keratinocyte cell sheets. We detail cell tracking, cell sheet contour assay, and particle image velocimetry to reveal the spatial and temporal motility dynamics of cell sheets. This approach is applicable to other collective cell migration studies.

Hepatocellular carcinoma occurs primarily in patients with cirrhosis and is an important cause of cancer death. Screening for hepatocellular carcinoma every 6 months with ultrasound with or without alpha fetoprotein measurement is recommended by multiple professional societies. There are no randomized controlled trials in patients with cirrhosis documenting the effectiveness of screening in improving survival, however, making screening controversial. There are multiple retrospective and cohort studies, as well as pooled analyses that do show an association of screening with earlier stage at diagnosis, increased receipt of curative intent treatment, and improved overall survival. Though these studies are limited by lead and length time biases, they make compelling arguments in favor of screening. Additional research into barriers to receiving screening, barriers to receiving treatment, and the optimal screening modalities given the shift of cirrhosis etiology in the United States are needed to further improve patient outcomes.

The article reports that the Wisconsin Department of Natural Resources (WDNR) has adopted total phosphorus (TP) criteria for all surface waters in the state and mentions that the City of Fond du Lac and the City of Waukesha conducted four pilot studies from 2013 to 2015. It focuses on the Fond du Lac water resource recovery facility (WRRF) designed to treat the daily flow and discharges.

Cell migration plays an important role in a wide variety of biological processes and can incorporate both individual cell motion and collective behaviour. The emergent properties of collective migration are receiving increasing attention as collective motion's role in diseases such as metastatic cancer becomes clear. Yet, how individual cell behaviour influences large-scale, multi-cell collective motion remains unclear. In this study, we provide insight into the mechanisms behind collective migration by studying cell migration in a spreading monolayer of epithelial MCF10A cells. We quantify migration using particle image velocimetry and find that cell groups have features of motion that span multiple length scales. Comparing our experimental results to a model of collective cell migration, we find that cell migration within the monolayer can be affected in qualitatively different ways by cell motion at the boundary, yet it is not necessary to introduce leader cells at the boundary or specify other large-scale features to recapitulate this large-scale phenotype in simulations. Instead, in our model, collective motion can be enhanced by increasing the overall activity of the cells or by giving the cells a stronger coupling between their motion and polarity. This suggests that investigating the activity and polarity persistence of individual cells will add insight into the collective migration phenotypes observed during development and disease.