Tension-induced organelle stress: an emerging target in fibrosis.

Fibrosis accounts for approximately one-third of disease-related deaths globally. Current therapies fail to cure fibrosis, emphasizing the need to identify new antifibrotic approaches. Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and resultant stiffening of tissue stroma.

Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk.

Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression, but tissue-specific factors linking these associations remain ill-defined. We observed that stiff breast tissue from women with high mammographic density, who exhibit increased lifetime risk for breast cancer, associates with abundant stem-progenitor epithelial cells. Using genetically engineered mouse models of elevated integrin mechanosignaling and collagen density, syngeneic manipulations, and spheroid models, we determined that a stiff matrix and high mechanosignaling increase mammary epithelial stem-progenitor cell frequency and enhance tumor initiation in vivo.

Novel cryo-tomography workflow reveals nanometer-scale responses of epithelial cells to matrix stiffness and dimensionality.

Matrix stiffness and dimensionality have been shown to be major determinants of cell behavior. However, a workflow for examining nanometer-scale responses of the associated molecular machinery is not available. Here, we describe a comprehensive, quantitative workflow that permits the analysis of cells responding to mechanical and dimensionality cues in their native state at nanometer scale by cryogenic electron tomography.

ECM dimensionality tunes actin tension to modulate endoplasmic reticulum function and spheroid phenotypes of mammary epithelial cells.

Patient-derived organoids and cellular spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a reconstituted basement membrane in three dimensions (3D) supports the polarized, stress resilient tissue phenotype of mammary epithelial spheroids. Cells interacting with reconstituted basement membrane in 3D had reduced levels of total and actin-associated filamin and decreased cortical actin tension that increased plasma membrane protrusions to promote negative plasma membrane curvature and plasma membrane protein associations linked to protein secretion.

Survival of Lung Cancer Patients Dependent on the LOH Status for , , and .

Lung cancer is the leading cause of cancer deaths in the world, and accounts for more solid tumor deaths than any other carcinomas. The prognostic values of , , and p53-loss are unknown in lung cancer. We have conducted survival analyses of non-small cell lung cancer (NSCLC) patients from the University of Minnesota VA hospital and those from the Wake Forest University Hospital.

The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles.

Traditionally viewed as an autodigestive pathway, autophagy also facilitates cellular secretion; however, the mechanisms underlying these processes remain unclear. Here, we demonstrate that components of the autophagy machinery specify secretion within extracellular vesicles (EVs). Using a proximity-dependent biotinylation proteomics strategy, we identify 200 putative targets of LC3-dependent secretion.

CO emissions from an undrained tropical peatland: Interacting influences of temperature, shading and water table depth.

Emission of CO from tropical peatlands is an important component of the global carbon budget. Over days to months, these fluxes are largely controlled by water table depth. However, the diurnal cycle is less well understood, in part, because most measurements have been collected daily at midday.

The Extracellular Matrix Modulates the Metastatic Journey.

The extracellular matrix is perturbed in tumors. The tumor matrix promotes the growth, survival, and invasion of the cancer and modifies fibroblast and immune cell behavior to drive metastasis and impair treatment. Here, we discuss how the tumor matrix regulates metastasis by fostering tumor cell invasion into the stroma and migration toward the vasculature.

Smoke radiocarbon measurements from Indonesian fires provide evidence for burning of millennia-aged peat.

In response to a strong El Niño, fires in Indonesia during September and October 2015 released a large amount of carbon dioxide and created a massive regional smoke cloud that severely degraded air quality in many urban centers across Southeast Asia. Although several lines of evidence indicate that peat burning was a dominant contributor to emissions in the region, El Niñ-induced drought is also known to increase deforestation fires and agricultural waste burning in plantations. As a result, uncertainties remain with respect to partitioning emissions among different ecosystem and fire types.

A tension-mediated glycocalyx-integrin feedback loop promotes mesenchymal-like glioblastoma.

Glioblastoma multiforme (GBMs) are recurrent lethal brain tumours. Recurrent GBMs often exhibit mesenchymal, stem-like phenotypes that could explain their resistance to therapy. Analyses revealed that recurrent GBMs have increased tension and express high levels of glycoproteins that increase the bulkiness of the glycocalyx.

Genetically Encoded Toolbox for Glycocalyx Engineering: Tunable Control of Cell Adhesion, Survival, and Cancer Cell Behaviors.

The glycocalyx is a coating of protein and sugar on the surface of all living cells. Dramatic perturbations to the composition and structure of the glycocalyx are frequently observed in aggressive cancers. However, tools to experimentally mimic and model the cancer-specific glycocalyx remain limited.

A Prototype Sensor for In Situ Sensing of Fine Particulate Matter and Volatile Organic Compounds.

Air pollution exposure causes seven million deaths per year, according to the World Health Organization. Possessing knowledge of air quality and sources of air pollution is crucial for managing air pollution and providing early warning so that a swift counteractive response can be carried out. An optical prototype sensor (AtmOptic) capable of scattering and absorbance measurements has been developed to target in situ sensing of fine particulate matter (PM2.

A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression.

Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression.

How temporal patterns in rainfall determine the geomorphology and carbon fluxes of tropical peatlands.

Tropical peatlands now emit hundreds of megatons of carbon dioxide per year because of human disruption of the feedbacks that link peat accumulation and groundwater hydrology. However, no quantitative theory has existed for how patterns of carbon storage and release accompanying growth and subsidence of tropical peatlands are affected by climate and disturbance. Using comprehensive data from a pristine peatland in Brunei Darussalam, we show how rainfall and groundwater flow determine a shape parameter (the Laplacian of the peat surface elevation) that specifies, under a given rainfall regime, the ultimate, stable morphology, and hence carbon storage, of a tropical peatland within a network of rivers or canals.

Stabilization of the p53-DNA Complex by the Nuclear Protein Dmp1α.

We recently reported the existence of a physical interaction between the Myb-like transcription factor Dmp1 (Dmtf1) and p53 in which Dmp1 antagonized polyubiquitination of p53 by Mdm2 and promoted its nuclear localization. Dmp1 significantly stabilized p53-DNA complexes on promoters that contained p53-consensus sequences, which were either supershifted or disrupted with antibodies to Dmp1. Lysates from mice injected with doxorubicin showed that Dmp1 bound to p21, Bbc3, and Thbs1 gene regulatory regions in a p53-dependent fashion.

Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype.

Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein.

Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced.

[The significance of a 4,183 Da peptide of dermcidin protein in the early diagnosis and differential diagnosis of acute coronary syndrome].

Objective: To investigate the predictive value of 4,183 Da peptide of dermcidin protein in the early diagnosis and differential diagnosis of ischemic heart disease.

Methods: A prospective controlled study was conducted. Serum samples were drawn from 161 patients with acute coronary'syndrome [ACS, including 46 patients with unstable angina (UA), 23 with acute non-ST elevation myocardial infarction, and 92 with acute ST segment elevation myocardial infarction], 111 subjects for routine physical examination, including 45 patients with hypertension history, 42 with coronary heart disease, 22 with diabetes, and 54 patients with non-ACS (including pulmonary embolism, aortic dissection, aneurysm, arrhythmia, myocarditis, coronary myocardial bridge, pleurisy, pneumothorax pneumomediastinum, rib fracture, reflux esophagitis, peptic ulcer, and pancreatitis) to serve as controls.

Force Matters: Biomechanical Regulation of Cell Invasion and Migration in Disease.

Atherosclerosis, cancer, and various chronic fibrotic conditions are characterized by an increase in the migratory behavior of resident cells and the enhanced invasion of assorted exogenous cells across a stiffened extracellular matrix (ECM). This stiffened scaffold aberrantly engages cellular mechanosignaling networks in cells, which promotes the assembly of invadosomes and lamellae for cell invasion and migration. Accordingly, deciphering the conserved molecular mechanisms whereby matrix stiffness fosters invadosome and lamella formation could identify therapeutic targets to treat fibrotic conditions, and reducing ECM stiffness could ameliorate disease progression.

Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration.

Synaptopodin-2 (Synpo2), an actin-binding protein and invasive cancer biomarker, induces formation of complex stress fiber networks in the cell body and promotes PC3 prostate cancer cell migration in response to serum stimulation. The role of these actin networks in enhanced cancer cell migration is unknown. Using time-course analysis and live cell imaging of mock- and Synpo2-transduced PC3 cells, we now show that Synpo2 induces assembly of actin fibers near the cell periphery and Arp2/3-dependent lamellipodia formation.

Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study.

Background: Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis.

Methods: Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition.

Carbon fluxes from an urban tropical grassland.

Turfgrass covers a large fraction of the urbanized landscape, but the carbon exchange of urban lawns is poorly understood. We used eddy covariance and flux chambers in a grassland field manipulative experiment to quantify the carbon mass balance in a Singapore tropical turfgrass. We also assessed how management and variations in environmental factors influenced CO2 respiration.

[Incomplete self-castration by the patient with gender identify disorder: a case report].

A 29-year-old man with gender identify disorder presented to our hospital complaining of scrotal pain. Two hours before the consultation, he tried to do self-castration by himself, but he stopped due to bleeding and scrotal pain. His testes were not removed, and his scrotal wound was closed at the emergency operation under spinal anesthesia.

[Salvage therapy for castration-refractory prostate cancer resistant to docetaxel].

Objectives: To evaluate the treatment for castration-refractory prostate cancer (CRPC) resistant to docetaxel

Materials And Methods: Among 45 patients with CRPC treated with docetaxel (70-75 mg/m2) every 3 to 4 weeks at Hamamatsu University Hospital from January 2004 to July 2012, 19 patients underwent salvage treatments. We retrospectively analyzed the medical records of 14 patients except for 5 patients who were enrolled in clinical trials.

Results: The median age and serum prostate-specific antigen (PSA) level at starting salvage treatments was 71 years (range 45 to 79) and 241.

Golgi complex-plasma membrane trafficking directed by an autonomous, tribasic Golgi export signal.

Although numerous linear motifs that direct protein trafficking within cells have been identified, there are few examples of linear sorting signals mediating directed export of membrane proteins from the Golgi complex to the plasma membrane. The reovirus fusion-associated small transmembrane proteins are simple, single-pass transmembrane proteins that traffic through the endoplasmic reticulum-Golgi pathway to the plasma membrane, where they induce cell-cell membrane fusion. Here we show that a membrane-proximal, polybasic motif (PBM) in the cytosolic tail of p14 is essential for efficient export of p14 from the Golgi complex to the plasma membrane.