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https://www.readbyqxmd.com/read/28934684/scientific-evidence-for-the-identification-of-an-aboriginal-massacre-at-the-sturt-creek-sites-on-the-kimberley-frontier-of-north-western-australia
#1
Pamela A Smith, Mark D Raven, Keryn Walshe, Robert W Fitzpatrick, F Donald Pate
Archival research into episodes of frontier violence in the Kimberley region of Western Australia indicate that the bodies of Aboriginal victims of massacres were frequently incinerated following the event. This paper presents the results of a scientific investigation of a reported massacre at Sturt Creek where burnt bone fragments were identified in two adjacent sites and documents the archaeological signatures associated with the sites. The methodology used to undertake the project brought together three systems of knowledge: the oral testimonies of the descent group originating from a sole adult survivor of the massacre; archival, historical and scientific research...
August 31, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#2
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28933623/the-defining-dna-methylation-signature-of-kabuki-syndrome-enables-functional-assessment-of-genetic-variants-of-unknown-clinical-significance
#3
Erfan Aref-Eshghi, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, David Rodenhiser, Charles Schwartz, Bekim Sadikovic
Kabuki syndrome (KS) is caused by mutations in KMT2D, which is a histone methyltransferase involved in methylation of H3K4, a histone marker associated with DNA methylation. Analysis of >450,000 CpGs in 24 KS patients with pathogenic mutations in KMT2D and 216 controls, identified several genomic regions, along with 1,504 CpG sites with significant DNA methylation changes including a number of Hox genes and the MYO1F gene. Using the most differentiating and significant probes and regions we developed a "methylation variant pathogenicity (MVP) score," which enables 100% sensitive and specific identification of individuals with KS, which was confirmed using multiple public and internal patient DNA methylation databases...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933035/expression-profiling-of-micrornas-in-human-bone-tissue-from-postmenopausal-women
#4
Laura De-Ugarte, Jenny Serra-Vinardell, Lara Nonell, Susana Balcells, Magdalena Arnal, Xavier Nogues, Leonardo Mellibovsky, Daniel Grinberg, Adolfo Diez-Perez, Natalia Garcia-Giralt
Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5)...
September 20, 2017: Human Cell
https://www.readbyqxmd.com/read/28932682/stroke-associated-pattern-of-gene-expression-previously-identified-by-machine-learning-is-diagnostically-robust-in-an-independent-patient-population
#5
Grant C O'Connell, Paul D Chantler, Taura L Barr
Our group recently employed genome-wide transcriptional profiling in tandem with machine-learning based analysis to identify a ten-gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population. Publicly available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 h post-symptom onset, as well from 23 cardiovascular disease controls, were obtained via the National Center for Biotechnology Information Gene Expression Omnibus...
December 2017: Genomics Data
https://www.readbyqxmd.com/read/28931758/molecular-characterization-of-the-transition-from-acute-to-chronic-kidney-injury-following-ischemia-reperfusion
#6
Jing Liu, Sanjeev Kumar, Egor Dolzhenko, Gregory F Alvarado, Jinjin Guo, Can Lu, Yibu Chen, Meng Li, Mark C Dessing, Riana K Parvez, Pietro E Cippà, A Michaela Krautzberger, Gohar Saribekyan, Andrew D Smith, Andrew P McMahon
Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931754/activated-signature-of-antiphospholipid-syndrome-neutrophils-reveals-potential-therapeutic-target
#7
Jason S Knight, He Meng, Patrick Coit, Srilakshmi Yalavarthi, Gautam Sule, Alex A Gandhi, Robert C Grenn, Levi F Mazza, Ramadan A Ali, Paul Renauer, Jonathan D Wren, Paula L Bockenstedt, Hui Wang, Daniel T Eitzman, Amr H Sawalha
Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils - neutrophil extracellular traps (NETs), in particular - in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931706/diabetes-research-and-care-through-the-ages
#8
Bernard Zinman, Jay S Skyler, Matthew C Riddle, Ele Ferrannini
As has been well established, the Diabetes Care journal's most visible signature event is the Diabetes Care Symposium held each year during the American Diabetes Association's Scientific Sessions. Held this past year on 10 June 2017 in San Diego, California, at the 77th Scientific Sessions, this event has become one of the most attended sessions during the Scientific Sessions. Each year, in order to continue to have the symposium generate interest, we revise the format and content of this event. For this past year, our 6th annual symposium, I felt it was time to provide a comprehensive overview of our efforts in diabetes care to determine, first and foremost, how we arrived at our current state of management...
October 2017: Diabetes Care
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#9
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28931525/ectopic-ilt3-controls-bcr-dependent-activation-of-akt-in-b-cell-chronic-lymphocytic-leukemia
#10
Vanessa Zurli, Giuliana Wimmer, Francesca Cattaneo, Veronica Candi, Emanuele Cencini, Alessandro Gozzetti, Donatella Raspadori, Giuseppe Campoccia, Francesca Sanseviero, Monica Bocchia, Cosima Tatiana Baldari, Anna Kabanova
The high proportion of long-term non-progressors among chronic lymphocytic leukemia (CLL) patients suggests the existence of a regulatory network which restrains the proliferation of tumor B cells. The identification of molecular determinants composing such network is hence fundamental for our understanding of CLL pathogenesis. Based on our previous finding establishing a deficiency in the signaling adaptor p66Shc in CLL cells, we undertook to identify unique phenotypic traits caused by this defect. Here we show that a lack of p66Shc shapes the transcriptional profile of CLL cells and leads to an upregulation of the surface receptor ILT3, the immunoglobulin-like transcript 3 which is normally found on myeloid cells...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28930977/fourier-based-diffraction-analysis-of-live-caenorhabditis-elegans
#11
Jenny Magnes, Harold M Hastings, Kathleen M Raley-Susman, Clara Alivisatos, Adam Warner, Miranda Hulsey-Vincent
This manuscript describes how to classify nematodes using temporal far-field diffraction signatures. A single C. elegans is suspended in a water column inside an optical cuvette. A 632 nm continuous wave HeNe laser is directed through the cuvette using front surface mirrors. A significant distance of at least 20-30 cm traveled after the light passes through the cuvette ensures a useful far-field (Fraunhofer) diffraction pattern. The diffraction pattern changes in real time as the nematode swims within the laser beam...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#12
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28930697/overexpression-of-muc1-and-genomic-alterations-in-its-network-associate-with-prostate-cancer-progression
#13
Xiaozeng Lin, Yan Gu, Anil Kapoor, Fengxiang Wei, Tariq Aziz, Diane Ojo, Yanzhi Jiang, Michael Bonert, Bobby Shayegan, Huixiang Yang, Khalid Al-Nedawi, Pierre Major, Damu Tang
We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN(-/-) mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n=300), testing (n=185), and validation (n=194) cohort...
September 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28930691/dna-methylome-analysis-identifies-transcription-factor-based-epigenomic-signatures-of-multilineage-competence-in-neural-stem-progenitor-cells
#14
Tsukasa Sanosaka, Takuya Imamura, Nobuhiko Hamazaki, MuhChyi Chai, Katsuhide Igarashi, Maky Ideta-Otsuka, Fumihito Miura, Takashi Ito, Nobuyuki Fujii, Kazuho Ikeo, Kinichi Nakashima
Regulation of the epigenome during in vivo specification of brain stem cells is still poorly understood. Here, we report DNA methylome analyses of directly sampled cortical neural stem and progenitor cells (NS/PCs) at different development stages, as well as those of terminally differentiated cortical neurons, astrocytes, and oligodendrocytes. We found that sequential specification of cortical NS/PCs is regulated by two successive waves of demethylation at early and late development stages, which are responsible for the establishment of neuron- and glia-specific low-methylated regions (LMRs), respectively...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930685/human-tissue-resident-memory-t-cells-are-defined-by-core-transcriptional-and-functional-signatures-in-lymphoid-and-mucosal-sites
#15
Brahma V Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L Friedman, Yufeng Shen, Donna L Farber
Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#16
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#17
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930544/neural-signatures-of-attention-insights-from-decoding-population-activity-patterns
#18
Panagiotis Sapountzis, Georgia G Gregoriou
Understanding brain function and the computations that individual neurons and neuronal ensembles carry out during cognitive functions is one of the biggest challenges in neuroscientific research. To this end, invasive electrophysiological studies have provided important insights by recording the activity of single neurons in behaving animals. To average out noise, responses are typically averaged across repetitions and across neurons that are usually recorded on different days. However, the brain makes decisions on short time scales based on limited exposure to sensory stimulation by interpreting responses of populations of neurons on a moment to moment basis...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930289/genetic-signatures-of-variation-in-population-size-in-a-native-fungal-pathogen-after-the-recent-massive-plantation-of-its-host-tree
#19
F Labbé, M C Fontaine, C Robin, C Dutech
Historical fluctuations in forests' distribution driven by past climate changes and anthropogenic activities can have large impacts on the demographic history of pathogens that have a long co-evolution history with these host trees. Using a population genetic approach, we investigated that hypothesis by reconstructing the demographic history of Armillaria ostoyae, one of the major pathogens of the maritime pine (Pinus pinaster), in the largest monospecific pine planted forest in Europe (south-western France)...
September 20, 2017: Heredity
https://www.readbyqxmd.com/read/28930286/molecular-and-cellular-signatures-underlying-superior-immunity-against-bordetella-pertussis-upon-pulmonary-vaccination
#20
R Hm Raeven, J Brummelman, J LA Pennings, L van der Maas, K Helm, W Tilstra, A van der Ark, A Sloots, P van der Ley, W van Eden, W Jiskoot, E van Riet, C Acm van Els, G Fa Kersten, W Gh Han, B Metz
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells...
September 20, 2017: Mucosal Immunology
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