178,909 results match your criteria Cambridge Review Of International Affairs[Journal]


The Reference Genome Sequence of Scutellaria baicalensis Provides Insights into the Evolution of Wogonin Biosynthesis.

Mol Plant 2019 Apr 15. Epub 2019 Apr 15.

Shanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai, China; John Innes Centre, Norwich, NR4 7UH UK. Electronic address:

Scutellaria baicalensis Georgi is important in Chinese Traditional Medicine where preparations of dried roots, 'Huang Qin', are used for liver and lung complaints including complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S16742052193013
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http://dx.doi.org/10.1016/j.molp.2019.04.002DOI Listing
April 2019
12 Reads

High-fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett's Esophagus via IL8 and Alterations to the Gut Microbiome.

Gastroenterology 2019 Apr 15. Epub 2019 Apr 15.

Department of Internal Medicine, Technical University of Munich, Germany. Electronic address:

Background & Aims: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Progression from BE to cancer is associated with obesity, possibly due to increased abdominal pressure and gastroesophageal reflux disease, although this pathogenic mechanism has not been proven. We investigated whether environmental or dietary factors associated with obesity contribute to progression of BE to EAC in mice. Read More

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http://dx.doi.org/10.1053/j.gastro.2019.04.013DOI Listing
April 2019
1 Read

Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.

Neuron 2019 Apr;102(2):294-320

Department of Neurology, The Sean M. Healey and AMG Center for ALS at Mass General, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA. Electronic address:

RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA splicing, transport, and stability. Disruption of RNA binding proteins and widespread RNA processing defects are increasingly recognized as critical determinants of neurological diseases. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08966273193027
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http://dx.doi.org/10.1016/j.neuron.2019.03.014DOI Listing
April 2019
1 Read

Use of Crowd Innovation to Develop an Artificial Intelligence-Based Solution for Radiation Therapy Targeting.

JAMA Oncol 2019 Apr 18. Epub 2019 Apr 18.

Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts.

Importance: Radiation therapy (RT) is a critical cancer treatment, but the existing radiation oncologist work force does not meet growing global demand. One key physician task in RT planning involves tumor segmentation for targeting, which requires substantial training and is subject to significant interobserver variation.

Objective: To determine whether crowd innovation could be used to rapidly produce artificial intelligence (AI) solutions that replicate the accuracy of an expert radiation oncologist in segmenting lung tumors for RT targeting. Read More

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http://dx.doi.org/10.1001/jamaoncol.2019.0159DOI Listing

Wanting without enjoying: The social value of sharing experiences.

PLoS One 2019 18;14(4):e0215318. Epub 2019 Apr 18.

Harvard University, Department of Psychology, Cambridge, MA, United States of America.

Social connection can be a rich source of happiness. Humans routinely go out of their way to seek out social connection and avoid social isolation. What are the proximal forces that motivate people to share experiences with others? Here we used a novel experience-sharing and decision-making paradigm to understand the value of shared experiences. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215318PLOS

Psychometric assessments of Persian translations of three measures of conspiracist beliefs.

PLoS One 2019 18;14(4):e0215202. Epub 2019 Apr 18.

School of Psychology and Sport Science, Anglia Ruskin University, Cambridge, United Kingdom.

Several self-report measures of conspiracist beliefs have been developed in Western populations, but examination of their psychometric properties outside Europe and North America is limited. This study aimed to examine the psychometric properties of three widely-used measures of conspiracist beliefs in Iran. We translated the Belief in Conspiracy Theory Inventory (BCTI), Conspiracy Mentality Questionnaire (CMQ), and Generic Conspiracist Belief Scale (GCBS) into Persian. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215202PLOS
April 2019
1 Read

A theory of discrete hierarchies as optimal cost-adjusted productivity organisations.

PLoS One 2019 18;14(4):e0214911. Epub 2019 Apr 18.

ETH Zurich, Department of Management, Technology, and Economics, Zurich, Switzerland.

Hierarchical structures are ubiquitous in human and animal societies, but a fundamental understanding of their raison d'être has been lacking. Here, we present a general theory in which hierarchies are obtained as the optimal design that strikes a balance between the benefits of group productivity and the costs of communication for coordination. By maximising a generic representation of the output of a hierarchical organization with respect to its design, the optimal configuration of group sizes at different levels can be determined. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214911PLOS

Transplantation of Hearts Donated After Circulatory-Determined Death.

Circ Heart Fail 2019 Apr;12(4):e005991

Scottish National Advanced Heart Failure Service, Golden Jubilee National Hospital, Glasgow, United Kingdom (M.C.P.).

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.005991DOI Listing

Heart Transplantation With Donation After Circulatory Death.

Circ Heart Fail 2019 Apr;12(4):e005517

Department of Cardiovascular Surgery, Inselspital, Bern University Hospital and Department for BioMedical Research, University of Bern, Switzerland (P.N., E.F., M.D., T.P.C., H.T.T.S., S.L.L.).

Heart transplantation remains the preferred option for improving quality of life and survival for patients suffering from end-stage heart failure. Unfortunately, insufficient supply of cardiac grafts has become an obstacle. Increasing organ availability with donation after circulatory death (DCD) may be a promising option to overcome the organ shortage. Read More

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https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.118
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.118.005517DOI Listing
April 2019
1 Read

Chipping in on Diagnostics.

CRISPR J 2019 Apr;2:69-71

McGovern Institute for Brain Research, Massachusetts Institute of Technology , Cambridge Massachusetts.

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http://dx.doi.org/10.1089/crispr.2019.29053.omaDOI Listing

Perspectives on gender parity in bioanalysis: an interview with Lauren Stevenson.

Bioanalysis 2019 Apr 18. Epub 2019 Apr 18.

Development Biomarkers and Bioanalytical Sciences, Biogen, Cambridge, MA 02142, USA.

Biography Lauren is Senior Director, Development Biomarkers & Bioanalytical Sciences at Biogen, Cambridge, MA, USA where she leads a team of talented scientists, setting bioanalytical and biomarker strategies and developing pharmacokinetics (PK), immunogenicity and biomarker assays in support of programs at all stages of development, from discovery to post-marketing. Lauren's team currently supports over 40 therapeutic programs, delivering PK and immunogenicity strategy and execution for Biogen's large molecule, antisense oligonucleotide (ASO0 and gene therapy portfolio as well as developing biomarkers in support of multiple sclerosis, immunology, fibrosis, rare and neurodegenerative disease indications. Externally, Lauren engages the broader industry and regulatory agencies as an invited speaker and course instructor at multiple conferences and workshops each year. Read More

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https://www.future-science.com/doi/10.4155/bio-2019-0060
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http://dx.doi.org/10.4155/bio-2019-0060DOI Listing
April 2019
1 Read

Bioanalysis - but not as we knew it: an AstraZeneca perspective of the last 10 years evolution to meet a diversifying portfolio.

Bioanalysis 2019 Apr 18. Epub 2019 Apr 18.

Translational Biomarkers & Bioanalysis, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK.

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http://dx.doi.org/10.4155/bio-2019-0037DOI Listing

Pilot evaluation of the circadian rhythm of tear production in a population of healthy adult cats.

Vet Ophthalmol 2019 Apr 17. Epub 2019 Apr 17.

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Objectives: The purpose of this study was to determine if a circadian rhythm exists in Schirmer's tear test (STT-1) values in a group of healthy adult cats.

Animals Studied: Twenty adult neutered Domestic Short-haired cats (DSH) were used in the study.

Procedures: Tear production was measured with the Schirmer tear test (STT-1) at 12 different time points over a 48-hour period. Read More

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http://dx.doi.org/10.1111/vop.12673DOI Listing

Correction to: DNA Damage In situ Ligation followed by Proximity Ligation Assay (DI-PLA).

Methods Mol Biol 2019 ;1896:C3

IFOM-Foundation, The FIRC Institute of Molecular Oncology Foundation, Milan, Italy.

Work in Fabrizio d'Adda di Fagagna's laboratory is supported by the Associazione Italiana per la Ricerca sul Cancro, AIRC (application 12971), Cariplo Foundation (grant 2010.0818 and 2014-0812), Fondazione Telethon (GGP12059 and GGP17111), Association for International Cancer Research (AICR-Worldwide Cancer Research Rif. N. Read More

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http://dx.doi.org/10.1007/978-1-4939-8931-7_20DOI Listing
January 2019

Report of the AAPS Guidance Forum on the FDA Draft Guidance for Industry: "Drug Products, Including Biological Products, that Contain Nanomaterials".

AAPS J 2019 Apr 17;21(4):56. Epub 2019 Apr 17.

VPS Consulting LLC, North Potomac, Maryland, USA.

To guide developers of innovative and generic drug products that contain nanomaterials, the U.S. Food and Drug Administration issued the draft guidance for industry titled: "Drug Products, Including Biological Products, that Contain Nanomaterials" in December 2017. Read More

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http://dx.doi.org/10.1208/s12248-019-0329-7DOI Listing

'Why genes in pieces?'-revisited.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Department of Computer Science, University of Bristol, Bristol BS8 1UB, UK.

The alignment between the boundaries of protein domains and the boundaries of exons could provide evidence for the evolution of proteins via domain shuffling, but literature in the field has so far struggled to conclusively show this. Here, on larger data sets than previously possible, we do finally show that this phenomenon is indisputably found widely across the eukaryotic tree. In contrast, the alignment between exons and the boundaries of intrinsically disordered regions of proteins is not a general property of eukaryotes. Read More

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http://dx.doi.org/10.1093/nar/gkz284DOI Listing
April 2019
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Changes in plasma phospholipid fatty acid profiles over 13 years and correlates of change: European Prospective Investigation into Cancer and Nutrition-Norfolk Study.

Am J Clin Nutr 2019 Apr 17. Epub 2019 Apr 17.

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.

Objective: The aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes.

Methods: Plasma phospholipid fatty acids were profiled at 3 time-points (1993-1997, 1998-2000, 2004-2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Read More

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http://dx.doi.org/10.1093/ajcn/nqz030DOI Listing

Using lean thinking to improve hypertension in a community health centre: a quality improvement report.

BMJ Open Qual 2019 8;8(1):e000373. Epub 2019 Feb 8.

Lynn Community Health Center, Lynn, Massachusetts, USA.

Background: Achieving better care at lower cost in the US healthcare safety net will require federally qualified health centres (FQHC) to implement new models of team-based population healthcare. Lean thinking may offer a way to reduce the financial risk of practice transformation while increasing the likelihood of sustained improvement.

Objective: To demonstrate system-level improvement in hypertension control in a large FQHC through the situational use of lean thinking and statistical process control. Read More

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http://dx.doi.org/10.1136/bmjoq-2018-000373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440610PMC
February 2019

Solar electricity and fuel production with perylene monoimide dye-sensitised TiO in water.

Chem Sci 2019 Mar 21;10(9):2758-2766. Epub 2018 Dec 21.

Christian Doppler Laboratory for Sustainable SynGas Chemistry , Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , UK . Email:

Dye-sensitisation of TiO and other metal oxides is an established strategy to couple solar light harvesting with efficient charge separation for the production of electricity in dye-sensitised solar cells (DSCs) or fuels in dye-sensitised semiconductor photocatalysis (DSP). Perylene monoimide (PMI) dyes have emerged as promising organic dyes, but they have not previously been used in a functional assembly with TiO in aqueous solution. Here, five novel PMI dyes bearing carboxylic acid, phosphonic acid, acetylacetone, hydroxyquinoline or dipicolinic acid anchoring groups for attachment onto TiO are reported. Read More

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http://xlink.rsc.org/?DOI=C8SC05693E
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http://dx.doi.org/10.1039/c8sc05693eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419928PMC
March 2019
1 Read

A universal method for sensitive and cell-free detection of CRISPR-associated nucleases.

Chem Sci 2019 Mar 16;10(9):2653-2662. Epub 2019 Jan 16.

Chemical Biology and Therapeutics Science , Broad Institute of MIT and Harvard , 415 Main Street, Rm 3012 , Cambridge , MA 02142 , USA . Email: ; ; Tel: +1 617 714 7445.

A multitude of biological applications for CRISPR-associated (Cas) nucleases have propelled the development of robust cell-based methods for quantitation of on- and off-target activities of these nucleases. However, emerging applications of these nucleases require cell-free methods that are simple, sensitive, cost effective, high throughput, multiplexable, and generalizable to all classes of Cas nucleases. Current methods for cell-free detection are cumbersome, expensive, or require sophisticated sequencing technologies, hindering their widespread application beyond the field of life sciences. Read More

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http://xlink.rsc.org/?DOI=C8SC03426E
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http://dx.doi.org/10.1039/c8sc03426eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419926PMC
March 2019
1 Read

Synthesis of acyl(chloro)phosphines enabled by phosphinidene transfer.

Chem Sci 2019 Mar 7;10(12):3627-3631. Epub 2019 Feb 7.

Department of Chemistry , Massachusetts Institute of Technology , 77 Massachusetts Avenue , Cambridge , MA 02139-4307 , USA . Email: ; Tel: +1 617 253 5332.

Acyl(chloro)phosphines RC(O)P(Cl)(-Bu) have been prepared by formal insertion of -butyl phosphinidene (-Bu-P) from -BuP ( = CH or anthracene) into the C-Cl bond of acyl chlorides. We show that the under-explored acyl(chloro)phosphine functional group provides an efficient method to prepare bis(acyl)phosphines, which are important precursors to compounds used industrially as radical polymerization initiators. Experimental and computational investigations into the mechanism of formation of acyl(chloro)phosphines by our synthetic method reveal a pathway in which chloride attacks a phosphonium intermediate and leads to the reductive loss of anthracene from the phosphorus center in a P(v) to P(iii) process. Read More

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http://xlink.rsc.org/?DOI=C8SC05657A
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http://dx.doi.org/10.1039/c8sc05657aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432624PMC
March 2019
1 Read

Flux melting of metal-organic frameworks.

Chem Sci 2019 Mar 12;10(12):3592-3601. Epub 2019 Feb 12.

Department of Materials Science and Metallurgy , University of Cambridge , Charles Babbage Road , Cambridge , CB3 0FS , UK . Email:

Recent demonstrations of melting in the metal-organic framework (MOF) family have created interest in the interfacial domain between inorganic glasses and amorphous organic polymers. The chemical and physical behaviour of porous hybrid liquids and glasses is of particular interest, though opportunities are limited by the inaccessible melting temperatures of many MOFs. Here, we show that the processing technique of flux melting, 'borrowed' from the inorganic domain, may be applied in order to melt ZIF-8, a material which does not possess an accessible liquid state in the pure form. Read More

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http://xlink.rsc.org/?DOI=C8SC04044C
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http://dx.doi.org/10.1039/c8sc04044cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430010PMC
March 2019
1 Read

ppm Pd-catalyzed, Cu-free Sonogashira couplings in water using commercially available catalyst precursors.

Chem Sci 2019 Mar 31;10(12):3481-3485. Epub 2019 Jan 31.

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93106 , USA . Email:

A new catalyst that derives from commercially available precursors for copper-free, Pd-catalyzed Sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Both the palladium pre-catalyst and ligand are commercially available, bench stable, and highly cost-effective. The catalyst is applicable to both aryl- and heteroaryl-bromides as educts. Read More

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http://dx.doi.org/10.1039/c8sc05618hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438147PMC

A new route for the efficient metalation of unfunctionalized aromatics.

Chem Sci 2019 Mar 5;10(11):3385-3400. Epub 2019 Feb 5.

Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge , CB2 1EW , UK . Email:

The synthesis and isolation of a novel bimetallic species formed by reacting two equivalents of TMPLi with CuCl in the presence of EtO are reported. X-ray crystallography reveals the EtO-free tetranuclear aggregate (TMPCu)(TMPLi), which formally results from the catenation of dimers of TMPLi and TMPCu. NMR spectroscopy confirms that, upon dissolution in hydrocarbon media, the crystals fail to form a conventional Gilman cuprate dimer. Read More

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http://xlink.rsc.org/?DOI=C8SC04325F
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http://dx.doi.org/10.1039/c8sc04325fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429619PMC
March 2019
1 Read

Real-time mechanistic study of carbon nanotube anion functionalisation through open circuit voltammetry.

Chem Sci 2019 Mar 7;10(11):3300-3306. Epub 2019 Feb 7.

Department of Chemistry , Imperial College London , SW7 2AZ , UK . Email:

The mechanism of the functionalisation of reduced single walled carbon nanotubes with organobromides was monitored by open circuit voltammetry throughout the reaction and further elucidated through a series of comparative reactions. The degree of functionalisation was mapped against the reagent reduction potential, degree of electron donation of substituents (Hammett parameter), and energies calculated, , for dissociation and heterolytic cleavage of the C-Br bond. In contrast to the previously assumed reduction/homolytic cleavage mechanism, the reaction was shown to consist of a rapid association of carbon-halide bond to the reduced nanotube as a complex, displacing surface-condensed countercations, leading to an initial increase in the net nanotube surface negative charge. Read More

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http://dx.doi.org/10.1039/c8sc04970jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428032PMC

Synthesis of F-difluoromethylarenes using aryl boronic acids, ethyl bromofluoroacetate and [F]fluoride.

Chem Sci 2019 Mar 29;10(11):3237-3241. Epub 2019 Jan 29.

Chemistry Research Laboratory , Department of Chemistry , Oxford University , OX1 3TA Oxford , UK . Email: ; Tel: +44 (0)1865 285002.

Herein, we report the radiosynthesis of F-difluoromethylarenes the assembly of three components, a boron reagent, ethyl bromofluoroacetate, and cyclotron-produced non-carrier added [F]fluoride. The two key steps are a copper-catalysed cross-coupling reaction, and a Mn-mediated F-fluorodecarboxylation. Read More

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http://dx.doi.org/10.1039/c8sc05096aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429591PMC
March 2019
9.211 Impact Factor

Outcome of total hip and knee arthroplasty in HIV-infected patients: A systematic review.

Orthop Rev (Pavia) 2019 Feb 22;11(1):8020. Epub 2019 Mar 22.

Cappagh National Orthopaedic Hospital, Dublin, Ireland.

Significant advances in the treatment of Human Immunodeficiency Virus (HIV) have occurred in recent times, with life expectancy now approaching the normal population. Therefore, patients with HIV will increasingly be undergoing joint replacement in the future, however concerns remain regarding the complications and outcome in this patient cohort. The aim was to assess the outcome of total hip and knee arthroplasty in HIV-infected patients. Read More

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http://dx.doi.org/10.4081/or.2019.8020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452098PMC
February 2019

Prediction of UGT-mediated Metabolism Using the Manually Curated MetaQSAR Database.

ACS Med Chem Lett 2019 Apr 12;10(4):633-638. Epub 2019 Feb 12.

Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, U.K.

Even though glucuronidations are the most frequent metabolic reactions of conjugation, both in quantitative and qualitative terms, they have rather seldom been investigated using computational approaches. To fill this gap, we have used the manually collected MetaQSAR metabolic reaction database to generate two models for the prediction of UGT-mediated metabolism, both based on molecular descriptors and implementing the Random Forest algorithm. The first model predicts the occurrence of the reaction and was internally validated with a Matthew correlation coefficient (MCC) of 0. Read More

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http://dx.doi.org/10.1021/acsmedchemlett.8b00603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466832PMC

Discovering New Casein Kinase 1d Inhibitors with an Innovative Molecular Dynamics Enabled Virtual Screening Workflow.

ACS Med Chem Lett 2019 Apr 13;10(4):487-492. Epub 2018 Dec 13.

Department of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Torino, Italy.

The value of including protein flexibility in structure-based drug design (SBDD) is widely documented, and currently, molecular dynamics (MD) simulations represent a powerful tool to investigate protein dynamics. Yet, the inclusion of MD-derived information in pre-existing SBDD workflows is still far from trivial. We recently published an integrated MD-FLAP (Fingerprints for Ligands and Proteins) approach combining MD, clustering and Linear Discriminant Analysis (LDA) for enhancing accuracy, efficacy, and for protein conformational selection in virtual screening (VS) campaigns. Read More

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http://dx.doi.org/10.1021/acsmedchemlett.8b00523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466522PMC

Predicting disruptive instabilities in controlled fusion plasmas through deep learning.

Nature 2019 Apr 17. Epub 2019 Apr 17.

Princeton Plasma Physics Laboratory, Princeton, NJ, USA.

Nuclear fusion power delivered by magnetic-confinement tokamak reactors holds the promise of sustainable and clean energy. The avoidance of large-scale plasma instabilities called disruptions within these reactors is one of the most pressing challenges, because disruptions can halt power production and damage key components. Disruptions are particularly harmful for large burning-plasma systems such as the multibillion-dollar International Thermonuclear Experimental Reactor (ITER) project currently under construction, which aims to be the first reactor that produces more power from fusion than is injected to heat the plasma. Read More

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http://dx.doi.org/10.1038/s41586-019-1116-4DOI Listing

A new strategy for vascular complications in young people with type 1 diabetes mellitus.

Nat Rev Endocrinol 2019 Apr 17. Epub 2019 Apr 17.

Department of Paediatrics, University of Cambridge, Cambridge, UK.

Diabetes vascular complications, including cardiovascular disease, diabetic nephropathy and retinopathy, have a negative effect on the long-term prognosis of young people with type 1 diabetes mellitus (T1DM). Poor glycaemic control and consequent increased HbA levels are major risk factors for the development of vascular complications. HbA levels are the main focus of current management strategies; however, the recommended target is rarely achieved in adolescents. Read More

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http://www.nature.com/articles/s41574-019-0198-2
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http://dx.doi.org/10.1038/s41574-019-0198-2DOI Listing
April 2019
1 Read

Self-organization of swimmers drives long-range fluid transport in bacterial colonies.

Nat Commun 2019 Apr 17;10(1):1792. Epub 2019 Apr 17.

Department of Physics and Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.

Motile subpopulations in microbial communities are believed to be important for dispersal, quest for food, and material transport. Here, we show that motile cells in sessile colonies of peritrichously flagellated bacteria can self-organize into two adjacent, centimeter-scale motile rings surrounding the entire colony. The motile rings arise from spontaneous segregation of a homogeneous swimmer suspension that mimics a phase separation; the process is mediated by intercellular interactions and shear-induced depletion. Read More

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http://www.nature.com/articles/s41467-019-09818-2
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http://dx.doi.org/10.1038/s41467-019-09818-2DOI Listing
April 2019
1 Read

An additive Gaussian process regression model for interpretable non-parametric analysis of longitudinal data.

Nat Commun 2019 Apr 17;10(1):1798. Epub 2019 Apr 17.

Department of Computer Science, Aalto University School of Science, FI-00076, Aalto, Finland.

Biomedical research typically involves longitudinal study designs where samples from individuals are measured repeatedly over time and the goal is to identify risk factors (covariates) that are associated with an outcome value. General linear mixed effect models are the standard workhorse for statistical analysis of longitudinal data. However, analysis of longitudinal data can be complicated for reasons such as difficulties in modelling correlated outcome values, functional (time-varying) covariates, nonlinear and non-stationary effects, and model inference. Read More

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http://www.nature.com/articles/s41467-019-09785-8
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http://dx.doi.org/10.1038/s41467-019-09785-8DOI Listing
April 2019
1 Read

Author Correction: Crizotinib-induced immunogenic cell death in non-small cell lung cancer.

Nat Commun 2019 Apr 17;10(1):1883. Epub 2019 Apr 17.

Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus, Villejuif, 94805, France.

The original version of this Article contained an error in the spelling of the author Lin Xia, which was incorrectly given as Xia Lin. This has now been corrected in both the PDF and HTML versions of the Article. Read More

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http://www.nature.com/articles/s41467-019-09838-y
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http://dx.doi.org/10.1038/s41467-019-09838-yDOI Listing
April 2019
3 Reads

Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction.

Nat Commun 2019 Apr 17;10(1):1802. Epub 2019 Apr 17.

Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.

The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. Read More

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http://dx.doi.org/10.1038/s41467-019-09530-1DOI Listing

Organoid culture media formulated with growth factors of defined cellular activity.

Sci Rep 2019 Apr 17;9(1):6193. Epub 2019 Apr 17.

Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.

The media formulations necessary for deriving and sustaining organoids from epithelial tissues such as prostate, colon, gastric, liver, pancreas, and others have been established. Critical components of organoid media are a set of growth factors that include R-spondins and BMP signalling antagonists such as Noggin or Gremlin 1. Currently, the practical limitations for formulating organoid media of reproducible potency and larger-scale media production that have hampered further technological applications of organoid technology include: the cost of growth factors such as R-spondins and Gremlin 1/Noggin and their production as defined specific activities free of contaminants that may affect organoid growth. Read More

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http://dx.doi.org/10.1038/s41598-019-42604-0DOI Listing

Small molecule electro-optical binding assay using nanopores.

Nat Commun 2019 Apr 17;10(1):1797. Epub 2019 Apr 17.

Department of Chemistry, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.

The identification of short nucleic acids and proteins at the single molecule level is a major driving force for the development of novel detection strategies. Nanopore sensing has been gaining in prominence due to its label-free operation and single molecule sensitivity. However, it remains challenging to detect small molecules selectively. Read More

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http://www.nature.com/articles/s41467-019-09476-4
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http://dx.doi.org/10.1038/s41467-019-09476-4DOI Listing
April 2019
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Modular, stereocontrolled C-H/C-C activation of alkyl carboxylic acids.

Proc Natl Acad Sci U S A 2019 Apr 17. Epub 2019 Apr 17.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;

The union of two powerful transformations, directed C-H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus, amenable to rapid diversity incorporation. Read More

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http://dx.doi.org/10.1073/pnas.1903048116DOI Listing

Temperature-responsive biometamaterials for gastrointestinal applications.

Sci Transl Med 2019 Apr;11(488)

Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

We hypothesized that ingested warm fluids could act as triggers for biomedical devices. We investigated heat dissipation throughout the upper gastrointestinal (GI) tract by administering warm (55°C) water to pigs and identified two zones in which thermal actuation could be applied: esophageal (actuation through warm water ingestion) and extra-esophageal (protected from ingestion of warm liquids and actuatable by endoscopically administered warm fluids). Inspired by a blooming flower, we developed a capsule-sized esophageal system that deploys using elastomeric elements and then recovers its original shape in response to thermal triggering of shape-memory nitinol springs by ingestion of warm water. Read More

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http://dx.doi.org/10.1126/scitranslmed.aau8581DOI Listing

UK government's sugar reduction programme on test.

BMJ 2019 04 17;365:l1705. Epub 2019 Apr 17.

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada

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http://dx.doi.org/10.1136/bmj.l1705DOI Listing

Primary biliary cirrhosis: Family, genes, and bugs.

Authors:
George F Mells

Clin Liver Dis (Hoboken) 2014 Apr 28;3(4):69-73. Epub 2014 Apr 28.

Academic Department of Medical Genetics University of Cambridge Box 238 Addenbrooke's Hospital, Hills Road Cambridge CB2 0QQ United Kingdom.

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http://dx.doi.org/10.1002/cld.308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448703PMC

Therapeutic Approaches To Enhance PINK1/Parkin Mediated Mitophagy For The Treatment Of Parkinson's Disease.

Neurosci Lett 2019 Apr 14. Epub 2019 Apr 14.

MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dow St, Dundee, DD1 5EH, Scotland.

The discovery of rare familial monogenic forms of early-onset Parkinson's disease has led to the identification of a mitochondrial quality control process as a key player in this disease. Loss-of-function mutations in the genes encoding PINK1 or Parkin result in insufficient removal of dysfunctional mitochondria through autophagy, a process termed mitophagy. Understanding the mechanism of this process and the function of its two key players, PINK1 and Parkin, has led to the discovery of new therapeutic approaches. Read More

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http://dx.doi.org/10.1016/j.neulet.2019.04.029DOI Listing
April 2019
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Immune Signaling in Neurodegeneration.

Immunity 2019 Apr;50(4):955-974

Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:

Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.016DOI Listing

GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation.

Immunity 2019 Apr;50(4):796-811

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address:

The β common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193013
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http://dx.doi.org/10.1016/j.immuni.2019.03.022DOI Listing
April 2019
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A Comprehensive Drosophila melanogaster Transcription Factor Interactome.

Cell Rep 2019 Apr;27(3):955-970.e7

Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.071DOI Listing

Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.

Cell Rep 2019 Apr;27(3):806-819.e5

Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.066DOI Listing

The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.

Cell Rep 2019 Apr;27(3):776-792.e7

Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address:

Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.063DOI Listing

Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.

Cell Rep 2019 Apr;27(3):750-761.e7

Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil. Electronic address:

Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.054DOI Listing

lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

Cell Rep 2019 Apr;27(3):719-729.e6

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; New York Genome Center, New York, NY 10013, USA. Electronic address:

Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs may play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.080DOI Listing
April 2019
7.207 Impact Factor