Systemic scleroderma (SSc) is an autoimmune disease that affects over 2.5 million people globally. SSc results in dysfunctional connective tissues with excessive profibrotic signaling, affecting skin, cardiovascular, and particularly lung tissue. Over three-quarters of individuals with SSc develop pulmonary fibrosis within 5 years, the main cause of SSc mortality. No approved medicines to manage lung SSc currently exist. Recent research suggests that profibrotic signaling by transforming growth factor...
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ORPphilins are bioactive natural products that strongly and selectively inhibit the growth of some cancer cell lines and are proposed to target intracellular lipid-transfer proteins of the oxysterol-binding protein (OSBP) family. These conserved proteins exchange key lipids, such as cholesterol and phosphatidylinositol 4-phosphate (PI(4)P), between organelle membranes. Among ORPphilins, molecules of the schweinfurthin family interfere with intracellular lipid distribution and metabolism, but their...
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Strigolactones (SLs) are terpenoid-derived plant hormones that regulate various developmental processes, particularly shoot branching, root development, and leaf senescence. The SL receptor has an unusual mode of action. Upon binding SL, it hydrolyzes the hormone, and then covalently binds one of the hydrolytic products. These initial events enable the SL receptor DAD2 (in petunia) to interact with the F-box protein PhMAX2A of the Skp-Cullin-F-box (SCF) complex and/or a repressor of SL signaling,...
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The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding...
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Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein phosphatase 2A (CIP2A), protein phosphatase methylesterase 1 (PME-1), and SET nuclear proto-oncogene (SET) that often are deregulated in cancers. However, how they impact cellular phosphorylation and how redundant they are in cellular regulation is poorly understood. Here, we conducted a systematic phosphoproteomics screen...
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Chemical biology is an emerging field that enables the study and manipulation of biological systems with probes whose reactivities provide structural insights. The opportunistic fungal pathogen Cryptococcus neoformans possesses a polysaccharide capsule that is a major virulence factor, but is challenging to study. We report here the synthesis of a hydroxylamine-armed fluorescent probe that reacts with reducing glycans and its application to study the architecture of the C. neoformans capsule under...
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In up to 15% of acute myeloid leukemias (AMLs), a recurring chromosomal translocation, termed t(8;21), generates the AML1–eight–twenty-one (ETO) leukemia fusion protein, which contains the DNA-binding domain of Runt-related transcription factor 1 (RUNX1) and almost all of ETO. RUNX1 and the AML1–ETO fusion protein are coexpressed in t(8;21) AML cells and antagonize each other's gene-regulatory functions. AML1–ETO represses transcription of RUNX1 target genes by competitively displacing RUNX1 and...
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The metalloprotease ADAM17 (a disintegrin and metalloprotease 17) is a key regulator of tumor necrosis factor α (TNFα), interleukin 6 receptor (IL-6R), and epidermal growth factor receptor (EGFR) signaling. ADAM17 maturation and function depend on the seven-membrane–spanning inactive rhomboid-like proteins 1 and 2 (iRhom1/2 or Rhbdf1/2). Most studies to date have focused on overexpressed iRhom1 and -2, so only little is known about the properties of the endogenous proteins. Here, we show that endogenous...
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In the extremophile bacterium Deinococcus radiodurans, the outermost surface layer is tightly connected with the rest of the cell wall. This integrated organization provides a compact structure that shields the bacterium against environmental stresses. The fundamental unit of this surface layer (S-layer) is the S-layer deinoxanthin-binding complex (SDBC), which binds the carotenoid deinoxanthin and provides both, thermostability and UV radiation resistance. However, the structural organization of...
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VOLUME 286 (2011) PAGES 16082–16090This article has been withdrawn by the authors. Part of the AKT immunoblot in Fig. 3A was used as actin in Fig. 1A (right, HCT116 wt). The actin immunoblots in Figs. 1B, 3A, and 4E have overlapping lanes. The actin immunoblots in Figs. 4 (A, C, and D) and 5C have overlapping lanes. Figs. 1B, 3A, and 5 (A and C) have undeclared gel splices.
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Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved...
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VOLUME 294 (2019) PAGES 8046–8063Due to publisher error, Figs. 4 and 5 were duplicated. This error has been corrected online.
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SAM and HD domain-containing protein 1 (SAMHD1) is a host factor that restricts reverse transcription of lentiviruses such as HIV in myeloid cells and resting T cells through its dNTP triphosphohydrolase (dNTPase) activity. Lentiviruses counteract this restriction by expressing the accessory protein Vpx or Vpr, which targets SAMHD1 for proteasomal degradation. SAMHD1 is conserved among mammals, and the feline and bovine SAMHD1 proteins (fSAM and bSAM) restrict lentiviruses by reducing cellular dNTP...
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Science relies on data acquisition via well-described, rigorous, reproducible procedures; statistically defensible interpretation of these data; and transparent reporting of the interpretations and conclusions reached based on these data. Each of these steps must be communicated to the broader scientific community in such a way that others can critically evaluate the studies, draw conclusions based on the reported findings, design subsequent experiments, and replicate and extend those observations....
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Introduction: Saccular aneurysms are thought to have a worse prognosis than fusiform aneurysms in humans, due to hemodynamic reasons. However, data comparing hemodynamic and biology in saccular and fusiform aneurysms are lacking. The main objective was to evaluate the impact of aneurysm morphology on intra-luminal thrombus (ILT) formation and activity. Methods: Forty Lewis rats were randomly divided into 2 groups of 20: “saccular” (Group A) and “fusiform” (Group B) aneurysms. Decellularized thoracic...
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Background:Brain metastases (BM) are one of the strongest negative prognostic factors in patients with non-small cell lung cancer (NSCLC). Molecularly targeted agents are standard of care for NSCLC patients with a driver mutation; however, their efficacy in patients with BM is not fully understood because patients with BM are usually excluded from clinical studies. This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice,...
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Abstract Introduction Immunotherapy has improved outcomes for patients with non-small cell lung cancer (NSCLC), yet durable clinical benefit (DCB) is experienced in only a fraction of patients. Here, we test the hypothesis that radiomics features from baseline pretreatment 18F-FDG PET/CT scans can predict clinical outcomes of NSCLC patients treated with checkpoint blockade immunotherapy. ...
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Abstract Purpose The aim of this case series is to illustrate the 18F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China. Methods We describe the 18F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January...
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Abstract Purpose Correct diagnosis and prognostic assessment of cardiac masses are crucial before therapy. We evaluated the diagnostic and prognostic value of 18F-FDG PET/CT in patients with cardiac masses. Methods 18F-FDG PET/CT images of 64 patients with 65 cardiac masses were retrospectively analysed (34 men, 30 women; average age,...
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Abstract Background Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment....
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Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error....
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Abstract Purpose The aim of this prospective study is to analyze the global tumor blood flow (BF) and its heterogeneity in newly diagnosed breast cancer (BC) according to tumor biological characteristics and molecular subtypes. These perfusion parameters were compared to those classically derived from metabolic studies to investigate links between perfusion and metabolism. ...
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Abstract Background The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed. Methods SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks...
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Abstract Purpose Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is commonly accepted as the gold standard to assess outcome after NAC in breast cancer patients. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has unique value in tumor staging, predicting prognosis, and evaluating treatment response. Our aim was to determine if we could identify radiomic predictors from PET/CT...
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Abstract Purpose Primary tumor (PT) and metastatic lymph node (MLN) status have a great influence on diagnosis and treatment of lung cancer. Our main purpose was to investigate the imaging characteristics of PT or MLN by applying the 18F-FDG PET dynamic modeling approach for non-small cell lung cancer (NSCLC). Methods Dynamic 18F-FDG...
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ObjectivesRegorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. DesignOpen-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. Setting11 tertiary centres in Turkey. ParticipantsEligible patients were adults with mCRC...
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ObjectivesTo examine the associations of parental social and economic position with health-seeking behaviour for diarrhoea and acute respiratory infection (ARI) among under-5 children in Myanmar and explore potential underlying mechanisms. DesignA cross-sectional study. SettingA secondary dataset from the nationwide 2015–2016 Myanmar Demographic and Health Survey (MDHS). ParticipantsAll under-5 children in the sampled households with reported symptoms of diarrhoea and ARI during the 2-week...
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ObjectivesTo investigate the rates and influencing factors of transient ischaemic attack (TIA) inpatient admissions and outpatient visits in China. SettingA door-to-door survey of 178 059 families from 155 urban and rural areas in 31 provinces in China, 2013. ParticipantsTotal 596 536 people were assessed in the annual rate analysis, and 829 TIA patients were assessed in the influencing factor analysis. Main outcome measuresThe weighted annual rates of TIA inpatient admissions and outpatient...
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ObjectiveIn 2001, Chinese guidelines for the care of acute myocardial infarction (AMI) included a new recommendation against the routine use of magnesium. We studied temporal trends and institutional variation in the use of intravenous magnesium sulfate in nationally representative samples of individuals hospitalised with AMI in China between 2001 and 2015. MethodsIn an observational study (China PEACE—Retrospective Study) of AMI care, we used a two-stage, random sampling strategy to create a nationally...
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ObjectivesTo compare the quality of communication in out-of-hours (OOH) telephone triage conducted by general practitioners (GPs), nurses using a computerised decision support system and physicians with different medical specialities, and to explore the association between communication quality and efficiency, length of call and the accuracy of telephone triage. DesignNatural quasi-experimental cross-sectional study. SettingTwo Danish OOH services using different telephone triage models: a GP...
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ObjectivesWe investigated whether a moderate-to-vigorous physical activity (MVPA) level and walking time were associated with a hilly environment in rural Japanese older adults. DesignCross-sectional study. SettingUnnan city, Ohnan and Okinoshima towns in Shimane, Japan. ParticipantsData were collected from 1115 adults from the Shimane CoHRE study, who were aged 60 years and older and living in rural Japan in 2012. MeasuresWe measured the total time spent on MVPA and walking using a Japanese...
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IntroductionPerson-centred care (PCC) has become a global movement in healthcare. Despite this, the level of PCC is not routinely assessed in clinical practice. This protocol describes the adaptation and validation of the Person-Centred Practice Inventory-Staff (PCPI-S) tool that will be used to assess person-centred practices of primary healthcare providers in Malaysia. Methods and analysisTo ensure conceptual and item equivalence, the original version of the PCPI-S will be reviewed and adapted...
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