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https://www.readbyqxmd.com/read/28646659/analysis-of-recombinant-monoclonal-antibodies-in-hydrophilic-interaction-chromatography-a-generic-method-development-approach
#1
Balázs Bobály, Valentina D'Atri, Alain Beck, Davy Guillarme, Szabolcs Fekete
Hydrophilic interaction liquid chromatography (HILIC) is a well-established technique for the separation and analysis of small polar compounds. A recently introduced widepore stationary phase expanded HILIC applications to larger molecules, such as therapeutic proteins. In this paper, we present some generic HILIC conditions adapted for a wide range of FDA and EMA approved recombinant monoclonal antibody (mAb) species and for an antibody-drug conjugate (ADC). Seven approved mAbs possessing various isoelectric point (pI) and hydrophobicity as well as a cysteine conjugated ADC were used in this study...
June 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28646574/a-novel-habitat-based-approach-to-predict-impacts-of-marine-protected-areas-on-fishers
#2
João B Teixeira, Rodrigo L Moura, Morena Mills, Carissa Klein, Christopher J Brown, Vanessa M Adams, Hedley Grantham, Matthew Watts, Deborah Faria, Gilberto M Amado-Filho, Alex C Bastos, Reinaldo Lourival, Hugh P Possingham
While marine protected areas (MPAs) can simultaneously contribute to biodiversity conservation and fisheries management, the global network is biased towards particular ecosystem types, as it was largely established in an ad hoc fashion. The optimization of trade-offs between biodiversity benefits and socio-economic values increases implementation success and minimizes enforcement costs in the long run, but is often neglected in marine spatial planning (MSP). Although the acquisition of spatially explicit socioeconomic data is often perceived as a costly/secondary step in MSP, it is critical to account for lost opportunities by people whose activities will be restricted, especially fishers...
June 24, 2017: Conservation Biology: the Journal of the Society for Conservation Biology
https://www.readbyqxmd.com/read/28646543/hepatic-bile-acid-uptake-in-humans-and-mice-multiple-pathways-and-expanding-potential-role-for-gut-liver-signaling
#3
EDITORIAL
Paul A Dawson
No abstract text is available yet for this article.
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646400/a-brief-assessment-tool-for-investigating-facets-of-moral-judgment-from-realistic-vignettes
#4
Michael Kruepke, Erin K Molloy, Konrad Bresin, Aron K Barbey, Edelyn Verona
Humans make moral judgments every day, and research demonstrates that these evaluations are based on a host of related event features (e.g., harm, legality). In order to acquire systematic data on how moral judgments are made, our assessments need to be expanded to include real-life, ecologically valid stimuli that take into account the numerous event features that are known to influence moral judgment. To facilitate this, Knutson et al. (in Social Cognitive and Affective Neuroscience, 5(4), 378-384, 2010) developed vignettes based on real-life episodic memories rated concurrently on key moral features; however, the method is time intensive (~1...
June 23, 2017: Behavior Research Methods
https://www.readbyqxmd.com/read/28646371/objective-assessment-of-reconstructed-breast-hardness-using-a-durometer
#5
Hiroki Mori, Noriko Uemura, Haruka Koga, Mutsumi Okazaki
BACKGROUND: Whether a durometer was suitable for objectively measuring reconstructed breast hardness was evaluated. METHODS: Subjects were 81 women who underwent expander-implant reconstructions following breast cancer ablation. Capsular contracture was evaluated with Baker grading. Capsular thickness was measured with T1-weighted MRI at the upper areola area. The durometer was placed on the upper areola. Multiple logistic regression analysis was performed to compare variables...
June 23, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28646219/efficient-and-unbiased-metagenomic-recovery-of-rna-virus-genomes-from-human-plasma-samples
#6
Carmen F Manso, David F Bibby, Jean L Mbisa
RNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses - HIV, HCV and HEV...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646204/optogenetic-protein-clustering-through-fluorescent-protein-tagging-and-extension-of-cry2
#7
Hyerim Park, Na Yeon Kim, Sangkyu Lee, Nury Kim, Jihoon Kim, Won Do Heo
Protein homo-oligomerization is an important molecular mechanism in many biological processes. Therefore, the ability to control protein homo-oligomerization allows the manipulation and interrogation of numerous cellular events. To achieve this, cryptochrome 2 (CRY2) from Arabidopsis thaliana has been recently utilized for blue light-dependent spatiotemporal control of protein homo-oligomerization. However, limited knowledge on molecular characteristics of CRY2 obscures its widespread applications. Here, we identify important determinants for efficient cryptochrome 2 clustering and introduce a new CRY2 module, named ''CRY2clust'', to induce rapid and efficient homo-oligomerization of target proteins by employing diverse fluorescent proteins and an extremely short peptide...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28646160/loss-of-g%C3%AE-i-proteins-impairs-thymocyte-development-disrupts-t-cell-trafficking-and-leads-to-an-expanded-population-of-splenic-cd4-pd-1-cxcr5-t-cells
#8
Il-Young Hwang, Kathleen Harrison, Chung Park, John H Kehrl
Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in thymocyte and T cell function, we developed several mouse models. Gαi2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646145/the-calmodulin-fused-kinase-novel-gene-family-is-the-major-system-in-plants-converting-ca-2-signals-to-protein-phosphorylation-responses
#9
Fei Chen, Liangsheng Zhang, Zong-Ming Max Cheng
Eukaryotes utilize Ca(2+) as a universal second messenger to convert and multiply environmental and developmental signals to downstream protein phosphorylation responses. However, the phylogenetic relationships of the genes that convert Ca(2+) signal (CS) to protein phosphorylation responses (PPRs) remain highly controversial, and their origin and evolutionary trajectory are unclear, which greatly hinders functional studies. Here we examined the deep phylogeny of eukaryotic CS converter gene families and identified a phylogenetically and structurally distinctive monophyly in Archaeplastida...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#10
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645942/mutational-heterogeneity-in-apc-and-kras-arises-at-the-crypt-level-and%C3%A2-leads-to-polyclonality-in-early-colorectal-tumorigenesis
#11
Mireia Gausachs, Ester Borras, Kyle Chang, Sara González, Daniel Azuara, Axel Delgado Amador, Adriana Lopez-Doriga, F Anthony San Lucas, Xavier Sanjuan, Maria jOSE Paules, Melissa Taggart, Gareth Davies, Erik A Ehli, Jerry Fowler, Victor Moreno, Marta Pineda, Y Nancy You, Patrick M Lynch, Conxi Lazaro, Nicholas E Navin, Paul Scheet, Ernest T Hawk, Gabriel Capella, Eduardo Vilar
Purpose:  The majority of genomic alterations causing intratumoral heterogeneity (ITH) in colorectal cancer (CRC) are thought to arise during early stages of carcinogenesis as a burst but only after truncal mutations in APC have expanded a single founder clone. We have investigated if the initial source of ITH is consequent to multiple independent lineages derived from different crypts harboring distinct truncal APC and driver KRAS mutations, thus challenging the prevailing monoclonal monocryptal model. <p>Experimental design: High-depth next-generation sequencing and SNP arrays were performed in whole lesion extracts of 37 FAP colorectal adenomas...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#12
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645928/molecular-mechanisms-in-cardiomyopathy
#13
REVIEW
Keith Dadson, Ludger Hauck, Filio Billia
Cardiomyopathies represent a heterogeneous group of diseases that negatively affect heart function. Primary cardiomyopathies specifically target the myocardium, and may arise from genetic [hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), mitochondrial cardiomyopathy] or genetic and acquired [dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM)] etiology. Modern genomics has identified mutations that are common in these populations, while in vitro and in vivo experimentation with these mutations have provided invaluable insight into the molecular mechanisms native to these diseases...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645806/brugada-syndrome-a-general-cardiologist-s-perspective
#14
REVIEW
Marija M Polovina, Milica Vukicevic, Bojan Banko, Gregory Y H Lip, Tatjana S Potpara
Brugada syndrome (BrS) is one of the commonest inherited primary arrhythmia syndromes typically presenting with arrhythmic syncope or sudden cardiac death (SCD) due to polymorphic ventricular tachycardia and ventricular fibrillation precipitated by vagotonia or fever in apparently healthy adults, less frequently in children. The prevalence of the syndrome (0.01%-0.3%) varies among regions and ethnicities, being the highest in Southeast Asia. BrS is diagnosed by the "coved type" ST-segment elevation≥2mm followed by a negative T-wave in ≥1 of the right precordial leads V1-V2...
June 20, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#15
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28645766/phylogenomic-analysis-supports-multiple-instances-of-polyphyly-in-the-oomycete-peronosporalean-lineage
#16
Marina S Ascunce, Jose C Huguet-Tapia, Almudena Ortiz-Urquiza, Nemat O Keyhani, Edward L Braun, Erica M Goss
The study of biological diversification of oomycetes has been a difficult task for more than a century. Pioneer researchers used morphological characters to describe this heterogeneous group, and physiological and genetic tools expanded knowledge of these microorganisms. However, research on oomycete diversification is limited by conflicting phylogenies. Using whole genomic data from 17 oomycete taxa, we obtained a dataset of 277 core orthologous genes shared among these genomes. Analyses of this dataset resulted in highly congruent and strongly supported estimates of oomycete phylogeny when we used concatenated maximum likelihood and coalescent-based methods; the one important exception was the position of Albugo...
June 20, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28645375/current-and-emerging-assays-for-studying-the-primer-synthesis-activities-of-dna-primases
#17
Thomas A Guilliam, Aidan J Doherty
Primases play a crucial role in the initiation of DNA synthesis during replication by de novo synthesis of short RNA or DNA "primers." In recent years, evidence has accumulated which expands the essential roles of primases to include, not only the initiation of replication but also other critical roles in DNA metabolism, including damage tolerance and repair. Despite the broadening roles for these enzymes, the methods used to identify and characterize primase activities are limited. Historically, biochemical analysis of primases has been based on the synthesis of radioactively labeled primers and their detection on denaturing polyacrylamide gels...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645259/adapted-yoga-to-improve-physical-function-and-health-related-quality-of-life-in-physically-inactive-older-adults-a-randomised-controlled-pilot-trial
#18
Garry A Tew, Jenny Howsam, Matthew Hardy, Laura Bissell
BACKGROUND: Yoga is a holistic therapy of expanding popularity, which has the potential to produce a range of physical, mental and social benefits. This trial evaluated the feasibility and effects of an adapted yoga programme on physical function and health-related quality of life in physically-inactive older adults. METHODS: In this randomised controlled pilot trial, 52 older adults (90% female; mean age 74.8 years, SD 7.2) were randomised 1:1 to a yoga programme or wait-list control...
June 23, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28645099/harnessing-the-natural-diversity-and-in-vitro-evolution-of-cas9-to-expand-the-genome-editing-toolbox
#19
REVIEW
Tautvydas Karvelis, Giedrius Gasiunas, Virginijus Siksnys
In the past few years, the Cas9 endonuclease from the type II CRISPR-Cas bacterial antiviral defense system has revolutionized the genome editing field. Guided by an RNA molecule, Cas9 can be reprogrammed to target almost any DNA sequence: the only limitation being the short nucleotide sequence in the vicinity of the target, termed the PAM, which is characteristic for each Cas9 protein. Streptococcus pyogenes Cas9 which recognizes the NGG PAM is currently most widely used for genome manipulation. However, Cas9 orthologues and engineered Cas9 variants offer expanded genome targeting capabilities, improved specificity and biochemical properties...
June 20, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28645041/behavioral-and-neural-concordance-in-parent-child-dyadic-sleep-patterns
#20
Tae-Ho Lee, Michelle E Miernicki, Eva H Telzer
Sleep habits developed in adolescence shape long-term trajectories of psychological, educational, and physiological well-being. Adolescents' sleep behaviors are shaped by their parents' sleep at both the behavioral and biological levels. In the current study, we sought to examine how neural concordance in resting-state functional connectivity between parent-child dyads is associated with dyadic concordance in sleep duration and adolescents' sleep quality. To this end, we scanned both parents and their child (N=28 parent-child dyads; parent Mage=42...
June 15, 2017: Developmental Cognitive Neuroscience
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