Bioengineers and dentists from the UCLA School of Dentistry have developed a new hydrogel that is more porous and effective in promoting tissue repair and regeneration compared to hydrogels that are currently available. Once injected in a mouse model, the new hydrogel is shown to induce migration of naturally occurring stem cells to better promote bone healing. Current experimental applications using hydrogels and stem cells introduced into the body or expensive biological agents can come with negative...
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CONCLUSIONS: Findings have important implications for the way in which psychosocial support for CL/P and related conditions is delivered and evaluated. A framework for the standardized assessment of holistic individual and familial well-being is proposed. Suggestions for increasing the evidence base for specific psychosocial interventions are made, including enhanced family functioning; social, emotional, and appearance concerns; treatment decision-making; and screening for psychosocial and developmental...
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Abstract Background Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer’s disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers. Methods KLK levels in cerebrospinal fluid (CSF),...
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Gross Chromosomal Rearrangements (GCRs) play an important role in human diseases, including cancer. Although most of the nonessential Genome Instability Suppressing (GIS) genes in Saccharomyces cerevisiae are known, the essential genes in which mutations can cause increased GCR rates are not well understood. Here 2 S. cerevisiae GCR assays were...
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Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early...
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Abstract Purpose The aim of this retrospective clinical quality assessment was to evaluate the efficacy of low-dose radiotherapy (RT) for painful benign skeletal disorders. Methods Patients with different painful benign skeletal disorders (arthrosis and enthesopathies) were recruited for this retrospective clinical quality assessment between January 2014...
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Keith A. Josephs, Ian Mackenzie, Matthew P. Frosch, Eileen H. Bigio, Manuela Neumann, Tetsuaki Arai, Brittany N. Dugger, Bernardino Ghetti, Murray Grossman, Masato Hasegawa, Karl Herrup, Janice Holton, Kurt Jellinger, Tammaryn Lashley, Kirsty E. McAleese, Joseph E. Parisi, Tamas Revesz, Yuko Saito, Jean Paul Vonsattel, Jennifer L. Whitwell, Thomas Wisniewski and William Hu. LATE to the PART-y. Brain 2019; 142: doi:10.1093/brain/awz224.
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AbstractThe loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson’s disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson’s disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7−/− and PARK7+/+ mice, we found that (i) PARK7−/−...
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Abstract Nonmotor symptoms (NMS) have been increasingly recognized in a number of neurodegenerative diseases with a burden of disability that parallels or even surpasses that induced by motor symptoms. As NMS have often been poorly recognized and inadequately treated, much of the most recent developments in the investigation of these disorders has focused on the recognition and quantification of NMS, which will form the basis of improved clinical care for these complex cases....
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Therapeutic Hypothermia and Temperature Management, Ahead of Print.
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Abstract Automated treatment planning may decrease the effort required in planning and promote increased routine clinical use of intensity-modulated radiation therapy (IMRT) for many breast cancer patients. The aim of this study was to evaluate a new commercial automated planning software for tangential breast IMRT by comparing it with clinical plans from whole-breast irradiation. We prospectively enrolled 150 patients with Stage 0–1 breast cancer who underwent breast-conserving...
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Abstract In this study, we aimed to develop a hybrid method for automated detection of high-uptake regions in the breast and axilla using dedicated breast positron-emission tomography (db PET) and whole-body PET/computed tomography (CT) images. In our proposed method, high-uptake regions in the breast and axilla were detected using db PET images and whole-body PET/CT images. In db PET images, high-uptake regions in the breast were detected using adaptive thresholding technique...
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ObjectiveTo estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer—CRC—or advanced adenoma).DesignProspective cohort of subjects aged 50–69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy.MethodsAll programmes adopted the same analytical procedure (OC...
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EVOLUTION Correction for “Deep evolutionary conservation of autism-related genes,” by Hagai Y. Shpigler, Michael C. Saul, Frida Corona, Lindsey Block, Amy Cash Ahmed, Sihai D. Zhao, and Gene E. Robinson, which was first published July 31, 2017; 10.1073/pnas.1708127114 (Proc. Natl. Acad. Sci. U.S.A. 114, 9653–9658). The authors note that on...
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ENGINEERING Correction for “Wettability effect on nanoconfined water flow,” by Keliu Wu, Zhangxin Chen, Jing Li, Xiangfang Li, Jinze Xu, and Xiaohu Dong, which was first published March 13, 2017; 10.1073/pnas.1612608114 (Proc. Natl. Acad. Sci. U.S.A. 114, 3358–3363). The authors note that the reference to a previously published version of...
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PLANT BIOLOGY Correction for “Leveraging abscisic acid receptors for efficient water use in Arabidopsis,” by Zhenyu Yang, Jinghui Liu, Stefanie V. Tischer, Alexander Christmann, Wilhelm Windisch, Hans Schnyder, and Erwin Grill, which was first published May 31, 2016; 10.1073/pnas.1601954113 (Proc. Natl. Acad. Sci. U.S.A. 113, 6791–6796). The authors wish to...
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Transposable elements (TEs) are extremely abundant in complex plant genomes. siRNAs of 24 nucleotides in length control transposon activity in a process that involves de novo methylation of targeted loci. Usually, these epigenetic modifications trigger nucleosome condensation and a permanent silencing of the affected loci. Here, we show that a...
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Environmental conditions are key factors in the progression of plant disease epidemics. Light affects the outbreak of plant diseases, but the underlying molecular mechanisms are not well understood. Here, we report that the light-harvesting complex II protein, LHCB5, from rice is subject to light-induced phosphorylation during infection by the rice...
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The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it...
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Photosynthetic organisms use nonphotochemical quenching (NPQ) mechanisms to dissipate excess absorbed light energy and protect themselves from photooxidation. In the model green alga Chlamydomonas reinhardtii, the capacity for rapidly reversible NPQ (qE) is induced by high light, blue light, and UV light via increased expression of LHCSR and PSBS genes...
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Ghrelin plays a central role in controlling major biological processes. As for other G protein-coupled receptor (GPCR) peptide agonists, the structure and dynamics of ghrelin bound to its receptor remain obscure. Using a combination of solution-state NMR and molecular modeling, we demonstrate that binding to the growth hormone secretagogue receptor...
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Diverse organisms, from insects to humans, actively seek out sensory information that best informs goal-directed actions. Efficient active sensing requires congruity between sensor properties and motor strategies, as typically honed through evolution. However, it has been difficult to study whether active sensing strategies are also modified with experience. Here, we...
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Nitric oxide (NO) is a major inhibitory neurotransmitter that mediates nonadrenergic noncholinergic (NANC) signaling. Neuronal NO synthase (nNOS) is activated by Ca2+/calmodulin to produce NO, which causes smooth muscle relaxation to regulate physiologic tone. nNOS serine1412 (S1412) phosphorylation may reduce the activating Ca2+ requirement and sustain NO production. We developed...
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Organisms need to balance sufficient uptake of iron (Fe) with possible toxicity. In plant roots, a regulon of uptake genes is transcriptionally activated under Fe deficiency, but it is unknown how this response is inactivated when Fe becomes available. Here we describe the function of 2 partially redundant E3 ubiquitin...
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In contrast to the importance of type II interferon-γ (IFN-γ) in control of toxoplasmosis, the role of type I IFN is less clear. We demonstrate here that TgIST, a secreted effector previously implicated in blocking type II IFN-γ signaling, also blocked IFN-β responses by inhibiting STAT1/STAT2-mediated transcription in infected cells....
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Tactile information is detected by thermoreceptors and mechanoreceptors in the skin and integrated by the central nervous system to produce the perception of somatosensation. Here we investigate the mechanism by which thermal and mechanical stimuli begin to interact and report that it is achieved by the mechanotransduction apparatus in cutaneous...
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Folates are critical for central nervous system function. Folate transport is mediated by 3 major pathways, reduced folate carrier (RFC), proton-coupled folate transporter (PCFT), and folate receptor alpha (FRα/Folr1), known to be regulated by ligand-activated nuclear receptors. Cerebral folate delivery primarily occurs at the choroid plexus through FRα and PCFT;...
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Stuttering is a common neurodevelopmental disorder that has been associated with mutations in genes involved in intracellular trafficking. However, the cellular mechanisms leading to stuttering remain unknown. Engineering a mutation in N-acetylglucosamine-1-phosphate transferase subunits α and β (GNPTAB) found in humans who stutter into the mouse Gnptab gene resulted in...
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Transmission of Plasmodium falciparum involves a complex process that starts with the ingestion of gametocytes by female Anopheles mosquitoes during a blood meal. Activation of gametocytes in the mosquito midgut triggers “rounding up” followed by egress of both male and female gametes. Egress requires secretion of a perforin-like protein, PfPLP2,...
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APPLIED PHYSICAL SCIENCES Correction for “Radio frequency transmitter based on a laser frequency comb,” by Marco Piccardo, Michele Tamagnone, Benedikt Schwarz, Paul Chevalier, Noah A. Rubin, Yongrui Wang, Christine A. Wang, Michael K. Connors, Daniel McNulty, Alexey Belyanin, and Federico Capasso, which was first published April 24, 2019; 10.1073/pnas.1903534116 (Proc....
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Cells require energy for growth and maintenance and have evolved to have multiple pathways to produce energy in response to varying conditions. A basic question in this context is how cells organize energy metabolism, which is, however, challenging to elucidate due to its complexity, i.e., the energy-producing pathways overlap with...
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Reactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP has poor...
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Global changes in the state of spatially distributed systems can often be traced back to perturbations that arise locally. Whether such local perturbations grow into global changes depends on the system geometry and the spatial spreading of these perturbations. Here, we investigate how different spreading behaviors of local perturbations determine...
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Dynamic small ubiquitin-like modifier (SUMO) linkages to diverse cellular protein groups are critical to orchestrate resolution of stresses such as genome damage, hypoxia, or proteotoxicity. Defense against pathogen insult (often reliant upon host recognition of “non-self” nucleic acids) is also modulated by SUMO, but the underlying mechanisms are incompletely understood....
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Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity...
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Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested,...
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Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expression of viperin regulates adipose tissue thermogenesis, which is known to counter...
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Although KRAS and TP53 mutations are major drivers of pancreatic ductal adenocarcinoma (PDAC), the incurable nature of this cancer still remains largely elusive. ARF6 and its effector AMAP1 are often overexpressed in different cancers and regulate the intracellular dynamics of integrins and E-cadherin, thus promoting tumor invasion and metastasis when...
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