40 Works

Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI

Pashtun Shahim, Adam Politis, Andre Van Der Merwe, Brian Moore, Vindhya Ekanayake, Sara Lippa, Yi-Yu Chou, Dzung Pham, John Butman, Ramon Diaz-Arrastia, Henrik Zetterberg, Kaj Blennow, Jessica Gill, David Brody & Leighton Chan
Objective: To determine if neurofilament light (NfL), glial fibrillary acidic protein (GFAp), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury in patients with TBI. Methods:Patients with TBI (n=162) and controls (n=68) were prospectively enrolled between 2009–2018. Of the 162 patients, 102 underwent repeated serum, functional outcome, brain MRI volumetry, and DTI assessments at...

Barn-Raising on the Digital Frontier

Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie McComsey, Alexandra Hubenko, Bin Huang, Corey Baker & Don Norman
A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches—or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond...

An animal without a mitochondrial genome: the salmon parasite Henneguya salminicola (Cnidaria: Myxozoa)

Dorothée Huchon, Dayana Yahalomi, Stephen D. Atkinson, Moran Neuhof, E. Sally Chang, Hervé Philippe, Paulyn Cartwright & Jerri L. Bartholomew
Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no...

Computerized analysis of brain MRI parameters dynamics in young patients with Cushing Syndrome – a case-control study

Amit Tirosh, Harish RaviPrakash, Georgios Z Papadakis, Christina Tatsi, Elena Belyavskaya, Lyssikatos Charalampos, Maya B. Lodish, Ulas Bagci & Constantine A Stratakis
Background – Young patients with Cushing Syndrome (CS) may develop cognitive and behavioral alterations during disease course. Methods - To define the implications of CS on the brain, we analyzed consecutive MRI scans of patients with (n=29) vs. without CS (n=8). Multiple brain compartments were processed for total and gray/white matter (GM/WM) volumes and intensities; and cortical volume, thickness and surface-area. Dynamics (last/baseline scans ratio per parameter) were analyzed vs. cortisol levels and CS status...

Data from: Quantifying hummingbird preference for floral trait combinations: the role of selection on trait interactions in the evolution of pollination syndromes

Charles B. Fenster, Richard J. Reynolds, Christopher W. Williams, Robert Makowsky & Michele R. Dudash
Darwin recognized the flower's importance for the study of adaptation and emphasized that the flower's functionality reflects the coordinated action of multiple traits. Here we use a multi-trait manipulative approach to quantify the potential role of selection acting on floral trait combinations underlying the divergence and maintenance of three related North American species of Silene (Caryophyllaceae). We artificially generated 48 plant phenotypes corresponding to all combinations of key attractive traits differing among the three Silene...

Data from: Identification of migratory bird flyways in North America using community detection on biological networks

Michael G. Buhnerkempe, Colleen T. Webb, Andrew A. Merton, John E. Buhnerkempe, Geof H. Givens, Ryan S. Miller & Jennifer A. Hoeting
Migratory behavior of waterfowl populations in North America has traditionally been broadly characterized by four north-south flyways, and these flyways have been central to the management of waterfowl populations for more than 80 years. However, previous flyway characterizations are not easily updated with current bird movement data and fail to provide assessments of the importance of specific geographical regions to the identification of flyways. Here, we developed a network model of migratory movement for four...

Data from: Adaptive evolution and environmental durability jointly structure phylodynamic patterns in avian influenza viruses

Benjamin Roche, John M. Drake, Justin Brown, David E. Stallknecht, Trevor Bedford & Pejman Rohani
Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker...

Data from: Global distribution maps of the Leishmaniases

David M. Pigott, Samir Bhatt, Nick Golding, Kirsten A. Duda, Katherine E. Battle, Oliver J. Brady, Jane P. Messina, Yves Balard, Patrick Bastien, Francine Pratlong, John S. Brownstein, Clark Freifeld, Sumiko R. Mekaru, Peter W. Gething, Dylan B. George, Monica F. Myers, Richard Reithinger, Simon I. Hay, John S Brownstein, Clark C Freifeld, Sumiko R Mekaru, Dylan B George, Simon I Hay, David M Pigott, Kirsten A Duda … & Monica F Myers
The leishmaniases are vector-borne diseases that have a broad global distribution throughout much of the Americas, Africa and Asia. Despite representing a significant public health burden, our understanding of the global distribution of the leishmaniases remains vague, reliant upon expert opinion and limited to poor spatial resolution. A global assessment of the consensus of evidence for leishmaniasis was performed at a sub-national level by aggregating information from a variety of sources. A database of records...

Data from: Inferring heterogeneous evolutionary processes through time: from sequence substitution to phylogeography

Filip Bielejec, Philippe Lemey, Guy Baele, Andrew Rambaut & Marc A. Suchard
Molecular phylogenetic and phylogeographic reconstructions generally assume time-homogeneous substitution processes. Motivated by computational convenience, this assumption sacrifices biological realism and offers little opportunity to uncover the temporal dynamics in evolutionary histories. Here, we propose an evolutionary approach that explicitly relaxes the time-homogeneity assumption by allowing the specification of different infinitesimal substitution rate matrices across different time intervals, called epochs, along the evolutionary history. We focus on an epoch model implementation in a Bayesian inference framework...

Data from: From cellular characteristics to disease diagnosis: uncovering phenotypes with supercells

Julián Candia, Ryan Maunu, Meghan Driscoll, Angélique Biancotto, Pradeep Dagur, McCoy Jr., J. Philip, H. Nida Sen, Lai Wei, Amos Maritan, Kan Cao, Robert B. Nussenblatt, Jayanth R. Banavar, Wolfgang Losert & J. Philip McCoy
Cell heterogeneity and the inherent complexity due to the interplay of multiple molecular processes within the cell pose difficult challenges for current single-cell biology. We introduce an approach that identifies a disease phenotype from multiparameter single-cell measurements, which is based on the concept of “supercell statistics”, a single-cell-based averaging procedure followed by a machine learning classification scheme. We are able to assess the optimal tradeoff between the number of single cells averaged and the number...

Data from: High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging in vivo

Guanghan Meng, Yajie Liang, Sarah Sarsfield, Wan-Chen Jiang, Rongwen Lu, Joshua Tate Dudman, Yeka Aponte & Na Ji
Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain structures. Incorporating a Bessel focus scanning module into two-photon fluorescence microendoscopy, we extended the excitation focus axially and improved its lateral resolution. Scanning...

Data from: Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa

Lin Li, Xiaodong Jiao, Ilaria D’Atri, Fumihito Ono, Ralph Nelson, Chi-Chao Chan, Naoki Nakaya, Zhiwei Ma, Yan Ma, Xiaoying Cai, Longhua Zhang, Siying Lin, Abdul Hameed, Barry A. Chioza, Holly Hardy, Gavin Arno, Sarah Hull, Muhammad Imran Khan, James Fasham, V. Gaurav Harlalka, Michel Michaelides, Anthony T. Moore, Zeynep Hande Coban Akdemir, Shalini Jhangiani, James R. Lupski … & S. Amer Riazuddin
We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p.D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE-19 cells. TALEN KO in zebrafish was lethal 11 days post...

Data from: Emergence and evolution of novel reassortant influenza A viruses in canines in southern China

Ying Chen, Nídia S. Trovão, Guojun Wang, Weifeng Zhao, Ping He, Huabo Zhou, Yanning Mo, Zuzhang Wei, Kang Ouyang, Weijiang Huang, Adolfo García-Sastre, Martha I. Nelson & Weijian Huang
The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to...

Data from: Dietary challenges differentially affect activity and sleep/wake behavior in mus musculus: isolating independent associations with diet/energy balance and body weight

Isaac J. Perron, Brendan T. Keenan, Karthikeyani Chellappa, Nicholas F. Lahens, Nicole Y. Yohn, Keith R. Shockley, Allan I. Pack, Sigrid C. Veasey & Nicole L. Yohn
Background and Aims: Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities. Here, we use dietary challenges to parse apart the relative influence of diet and/or energy balance from body weight on various metabolic and behavioral outcomes. Materials and Methods: Seventy male mice (mus musculus) were subjected...

Data from: Genome-wide evolutionary dynamics of influenza B viruses on a global scale

Pinky Langat, Jayna Raghwani, Gytis Dudas, Thomas A. Bowden, Stephanie Edwards, Astrid Gall, Trevor Bedford, Andrew Rambaut, Rodney S. Daniels, Colin A. Russell, Oliver G. Pybus, John McCauley, Paul Kellam & Simon J. Watson
The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study...

Data from: High throughput functional genomics identifies modulators of TCE metabolite genotoxicity and candidate susceptibility genes

Vanessa Y. De La Rosa, Jonathan Asfaha, Michael Fasullo, Alex Loguinov, Peng Li, Lee E. Moore, Nathaniel Rothman, Jun Nakamura, James A. Swenberg, Ghislaine Scelo, Luoping Zhang, Martyn T. Smith & Chris D. Vulpe
Trichloroethylene (TCE), an industrial chemical and environmental contaminant, is a human carcinogen. Reactive metabolites are implicated in renal carcinogenesis associated with TCE exposure, yet the toxicity mechanisms of these metabolites and their contribution to cancer and other adverse effects remain unclear. We employed an integrated functional genomics approach that combined functional profiling studies in yeast and avian DT40 cell models to provide new insights into the specific mechanisms contributing to toxicity associated with TCE metabolites....

Data from: Multiple sequence alignment averaging improves phylogeny reconstruction

Haim Ashkenazy, Itamar Sela, Eli Levy Karin, Giddy Landan & Tal Pupko
The classic methodology of inferring a phylogenetic tree from sequence data is composed of two steps. First, a multiple sequence alignment (MSA) is computed. Then, a tree is reconstructed assuming the MSA is correct. Yet, inferred MSAs were shown to be inaccurate and alignment errors reduce tree inference accuracy. It was previously proposed that filtering unreliable alignment regions can increase the accuracy of tree inference. However, it was also demonstrated that the benefit of this...

Data from: NK-CD11c+ cell crosstalk in diabetes enhances IL-6-mediated inflammation during mycobacterium tuberculosis infection

Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan K. Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R. Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati & Pavan Kumar Nathella
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in...

Data from: Origins of the 2009 H1N1 influenza pandemic in swine in Mexico

Ignacio Mena, Martha I. Nelson, Francisco Quezada-Monroy, Jayeeta Dutta, Refugio Cortes-Fernández, J. Horacio Lara-Puente, Felipa Castro-Peralta, Luis F. Cunha, Nídia Sequeira-Trovão, Bernardo Lozano-Dubernard, Andrew Rambaut, Harm Van Bakel & Adolfo García-Sastre
Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of...

Data from: Persistent chaos of measles epidemics in the prevaccination United States caused by a small change in seasonal transmission patterns

Benjamin D. Dalziel, Ottar N. Bjornstad, Willem G. Van Panhuis, Donald S. Burke, C Jessica E. Metcalf, Bryan T. Grenfell, Ottar N. Bjørnstad & C. Jessica E. Metcalf
Epidemics of infectious diseases often occur in predictable limit cycles. Theory suggests these cycles can be disrupted by high amplitude seasonal fluctuations in transmission rates, resulting in deterministic chaos. However, persistent deterministic chaos has never been observed, in part because sufficiently large oscillations in transmission rates are uncommon. Where they do occur, the resulting deep epidemic troughs break the chain of transmission, leading to epidemic extinction, even in large cities. Here we demonstrate a new...

Data from: Extracellular space preservation aids the connectomic analysis of neural circuits

Marta Pallotto, Paul V. Watkins, Boma Fubara, Joshua H. Singer, Kevin L. Briggman, Joshua H Singer, Kevin L Briggman & Paul V Watkins
Dense connectomic mapping of neuronal circuits is limited by the time and effort required to analyze 3D electron microscopy (EM) datasets. Algorithms designed to automate image segmentation suffer from substantial error rates and require significant manual error correction. Any improvement in segmentation error rates would therefore directly reduce the time required to analyze 3D EM data. We explored preserving extracellular space (ECS) during chemical tissue fixation to improve the ability to segment neurites and to...

Data from: Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring

Laura C. Pollitt, Derek Sim, Rahel Salathé & Andrew F. Read
Artemisinin-based drugs are the front-line weapon in the treatment of human malaria cases, but there is concern that recent reports of slow clearing infections may signal developing resistance to treatment. In the absence of molecular markers for resistance, current efforts to monitor drug efficacy are based on the rate at which parasites are cleared from infections. However, some knowledge of the standing variation in parasite susceptibility is needed to identify a meaningful increase in infection...

Data from: Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions

Michael G. Buhnerkempe, Katherine C. Prager, Christopher C. Strelioff, Denise J. Greig, Jeff L. Laake, Sharon R. Melin, Robert L. DeLong, Frances M. D. Gulland & James O. Lloyd-Smith
Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection but demonstrations of the importance of chronic shedding to pathogen persistence at the population level remain scarce. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding...

Data from: Cough frequency during treatment associated with baseline cavitary volume and proximity to the airway in pulmonary TB

Alvaro Proaño, David P. Bui, José W. López, Nancy M. Vu, Marjory A. Bravard, Gwenyth O. Lee, Brian H. Tracey, Ziyue Xu, Germán Comina, Eduardo Ticona, Daniel J. Mollura, Jon S. Friedland, David A. J. Moore, Carlton A. Evans, Philip Caligiuri, Robert H. Gilman & Tuberculosis Working Group In Peru
Background: Cough frequency, and its duration, is a lab-free biomarker that can be used in low-resource settings and has been associated with transmission and treatment response. Radiological characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has never been studied. Methods: We analyzed 41 human immunodeficiency virus-negative adults with culture-confirmed, drug-susceptible pulmonary tuberculosis throughout treatment. Cough recordings were based on the Cayetano Cough...

Data from: Does high-dose antimicrobial chemotherapy prevent the evolution of resistance?

Troy Day & Andrew F. Read
High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the...

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