Laminar fMRI: Applications for cognitive neuroscience.

Neuroimage. 2017 Jul 04;:

Authors: Lawrence SJD, Formisano E, Muckli L, de Lange FP

Abstract
The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses.

PMID: 28687519 [PubMed - as supplied by publisher]

A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules.

Metab Eng. 2017 Jul 04;:

Authors: Reed J, Stephenson MJ, Miettinen K, Brouwer B, Leveau A, Brett P, Goss RJM, Goossens A, O'Connell MA, Osbourn A

Abstract
Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines.

PMID: 28687337 [PubMed - as supplied by publisher]

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MicroRNA Profiling and Target Genes Related to Metastasis of Salivary Adenoid Cystic Carcinoma.

Anticancer Res. 2017 Jul;37(7):3473-3481

Authors: Feng X, Matsuo K, Zhang T, Hu Y, Mays AC, Browne JD, Zhou X, Sullivan CA

Abstract
BACKGROUND/AIM: Perineural invasion and distant metastasis lead to a poor prognosis of adenoid cystic carcinoma and there is no effective therapy available. MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression, which can be biomarkers or therapeutic targets for certain cancer types. We aimed to identify miRNAs and their target genes possibly involved in metastasis of salivary gland adenoid cystic carcinoma (SACC).
MATERIALS AND METHODS: Using Nanostring nCounter analysis, we examined miRNA expression in two SACC cell lines: SACC-83 and SACC-LM, with low and high lung metastasis rates, respectively. We then verified the differentially expressed miRNAs with real-time polymerase chain reaction in the cell lines and in tumor samples from patients with SACC. miRNA target-gene expression was also analyzed.
RESULTS: SACC-83 showed higher gene expression of miR-130a, miR-342, and miR-205; SACC-LM showed higher gene expression of miR-99a and miR-155. In human tissue, miR-205 was highly expressed in the primary SACC, while miR-155 and miR-342 were highly expressed in recurrent SACC. Six predicted target genes of miRNA-155 and miR-99a linked to tumorigenesis were further analyzed and RNA expression of ubiquitin-like modifier activating enzyme 2 (UBA2) was higher in SACC than normal salivary gland tissue, and higher in primary compared to recurrent SACC (p<0.05). RNA expression of retinoic acid receptors (RARS) was higher in tissue from primary than recurrent SACC and normal salivary gland (p<0.05), but that in recurrent SACC was not significantly higher than normal salivary gland tissue. RNA expression of minichromosome maintenance 8 homologous recombination repair factor (MCM8) and 24-dehydrocholesterol reductase (DHCR24) was higher in primary SACC than normal salivary gland tissue (p<0.05).
CONCLUSION: miR-99a, miR-155, miR-130a, miR-342, and miR-205 may play a role in metastasis of SACC. MiR-155 may be involved in SACC metastasis through UBA2 pathways, and UBA2 may function as a biomarker/mediator of SACC metastasis.

PMID: 28668836 [PubMed - in process]

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening.

Sci Rep. 2017 Jun 30;7(1):4439

Authors: Wagner GP, Nnamani MC, Chavan AR, Maziarz J, Protopapas S, Condon J, Romero R

Abstract
The uterine cervix is the boundary structure between the uterus and the vagina and is key for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammals, mouse, guinea pig, rabbit and armadillo, and one marsupial, opossum. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our findings are: 1) The patterns of gene expression in eutherian (placental) mammals are consistent with the notion that an increase in the E/P4 signaling ratio is critical for cervical ripening. How the increased E/P4 ratio is achieved, however, is variable between species. 2) None of the genes related to steroid signaling, that are modulated in eutherian species, change expression during opossum gestation. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBBP) towards term is a shared derived feature of eutherians. This suggests that parturition is associated with broad scale histone de-acetylation. Western-blotting on mouse cervix confirmed large scale histone de-acetylation in labor. This finding may have important implications for the control of premature cervical ripening and prevention of preterm birth in humans.

PMID: 28667298 [PubMed - in process]

Tuberculosis infection in rural labor migrants in Shenzhen, China: Emerging challenge to tuberculosis control during urbanization.

Sci Rep. 2017 Jun 30;7(1):4457

Authors: Li X, Yang Q, Feng B, Xin H, Zhang M, Deng Q, Deng G, Shan W, Yue J, Zhang H, Li M, Li H, Jin Q, Chen X, Gao L

Abstract
During China's urbanization process, rural labor migrants have been suggested to be one important bridge population to change urban-rural distribution on tuberculosis (TB) burden. Aiming to estimate the prevalence of TB infection and to track the active disease development in rural labor migrants, a prospective study was conducted in Shenzhen city, southern China. TB infection was detected using interferon-γ release assay (IGRA). Here we mainly report the characteristics of TB infection in the study population based on the baseline survey. A total of 4,422 eligible participants completed baseline survey in July 2013. QuantiFERON (QFT) positivity rates 17.87% (790/4,422) and was found to be consistent with the local TB epidemic of the areas where the participants immigrated from. Age, smoking, residence registered place, and present of BCG scars were found to be independently associated with QFT positivity. Additionally, evidence for interaction between smoking and age was observed (p for likelihood ratio test < 0.001). Our results suggested that the development of TB control strategy including latent TB infection management should pay more attention to the rural flowing population due to their high mobility and higher prevalence of TB infection.

PMID: 28667275 [PubMed - in process]

Response of microbial community function to fluctuating geochemical conditions within a legacy radioactive waste trench environment.

Appl Environ Microbiol. 2017 Jun 30;:

Authors: Vázquez-Campos X, Kinsela AS, Bligh MW, Harrison JJ, Payne TE, Waite TD

Abstract
During the 1960s, small quantities of radioactive materials were co-disposed with chemical waste at the Little Forest Legacy Site (Sydney, Australia) in three-metre-deep, unlined trenches. Chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a six-week period immediately after a prolonged rainfall event to assess how changing water levels impact upon the microbial ecology and contaminant mobility. Collectively, results demonstrated that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse, to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the potentially important role that the taxonomically-diverse microbial community played in this transition. In particular, aerobes dominated in the first day followed by an increase of facultative anaerobes/denitrifiers at day four. Towards the mid-end of the sampling period, the functional and taxonomic profiles depicted an anaerobic community distinguished by a higher representation of dissimilatory sulfate reduction and methanogenesis pathways. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs.Importance The role of chemical and microbiological factors in mediating the biogeochemistry of groundwaters from trenches used to dispose of radioactive materials during the 1960s is examined in this study. Specifically, chemical and microbial analyses, including functional and taxonomic information derived from shotgun metagenomics, were collected across a six-week period immediately after a prolonged rainfall event to assess how changing water levels influence microbial ecology and contaminant mobility.Results demonstrate that oxygen-laden rainwater rapidly altered the redox balance in the trench water, strongly impacting microbial functioning as well as the radiochemistry. Two contaminants of concern, plutonium and americium, were shown to transition from solid-iron-associated species immediately after the initial rainwater pulse, to progressively more soluble moieties as reducing conditions were enhanced. Functional metagenomics revealed the important role that the taxonomically-diverse microbial community played in this transition. Our results have important implications to similar near-surface environmental systems in which redox cycling occurs.

PMID: 28667104 [PubMed - as supplied by publisher]

Control of serine integrase recombination directionality by fusion with the directionality factor.

Nucleic Acids Res. 2017 Jun 28;:

Authors: Olorunniji FJ, McPherson AL, Rosser SJ, Smith MCM, Colloms SD, Stark WM

Abstract
Bacteriophage serine integrases are extensively used in biotechnology and synthetic biology for assembly and rearrangement of DNA sequences. Serine integrases promote recombination between two different DNA sites, attP and attB, to form recombinant attL and attR sites. The 'reverse' reaction requires another phage-encoded protein called the recombination directionality factor (RDF) in addition to integrase; RDF activates attL × attR recombination and inhibits attP × attB recombination. We show here that serine integrases can be fused to their cognate RDFs to create single proteins that catalyse efficient attL × attR recombination in vivo and in vitro, whereas attP × attB recombination efficiency is reduced. We provide evidence that activation of attL × attR recombination involves intra-subunit contacts between the integrase and RDF moieties of the fusion protein. Minor changes in the length and sequence of the integrase-RDF linker peptide did not affect fusion protein recombination activity. The efficiency and single-protein convenience of integrase-RDF fusion proteins make them potentially very advantageous for biotechnology/synthetic biology applications. Here, we demonstrate efficient gene cassette replacement in a synthetic metabolic pathway gene array as a proof of principle.

PMID: 28666339 [PubMed - as supplied by publisher]

Inferring transcriptional logic from multiple dynamic experiments.

Bioinformatics. 2017 Jun 28;:

Authors: Minas G, Jenkins DJ, Rand DA, Finkenstädt B

Abstract
Motivation: The availability of more data of dynamic gene expression under multiple experimental conditions provides new information that makes the key goal of identifying not only the transcriptional regulators of a gene but also the underlying logical structure attainable.
Results: We propose a novel method for inferring transcriptional regulation using a simple, yet biologically interpretable, model to find the logic by which a set of candidate genes and their associated transcription factors (TFs) regulate the transcriptional process of a gene of interest. Our dynamic model links the mRNA transcription rate of the target gene to the activation states of the TFs assuming that these interactions are consistent across multiple experiments and over time. A trans-dimensional Markov Chain Monte Carlo (MCMC) algorithm is used to efficiently sample the regulatory logic under different combinations of parents and rank the estimated models by their posterior probabilities. We demonstrate and compare our methodology with other methods using simulation examples and apply it to a study of transcriptional regulation of selected target genes of Arabidopsis Thaliana from microarray time series data obtained under multiple biotic stresses. We show that our method is able to detect complex regulatory interactions that are consistent under multiple experimental conditions.
Availability: Programs are written in MATLAB and Statistics Toolbox Release 2016b, The MathWorks, Inc., Natick, Massachusetts, United States and are available on GitHub https://github.com/giorgosminas/TRS .
Contact: giorgos.minas@warwick.ac.uk , B.F.Finkenstadt@warwick.ac.uk.
Supplementary information: Supplementary data are available at Bioinformatics online.

PMID: 28666320 [PubMed - as supplied by publisher]

GPU-powered model analysis with PySB/cupSODA.

Bioinformatics. 2017 Jun 28;:

Authors: Harris LA, Nobile MS, Pino JC, Lubbock ALR, Besozzi D, Mauri G, Cazzaniga P, Lopez CF

Abstract
Summary: A major barrier to the practical utilization of large, complex models of biochemical systems is the lack of open-source computational tools to evaluate model behaviors over high-dimensional parameter spaces. This is due to the high computational expense of performing thousands to millions of model simulations required for statistical analysis. To address this need, we have implemented a user-friendly interface between cupSODA, a GPU-powered kinetic simulator, and PySB, a Python-based modeling and simulation framework. For three example models of varying size, we show that for large numbers of simulations PySB/cupSODA achieves order-of-magnitude speedups relative to a CPU-based ordinary differential equation integrator.
Availability and Implementation: The PySB/cupSODA interface has been integrated into the PySB modeling framework (version 1.4.0), which can be installed from the Python Package Index (PyPI) using a Python package manager such as pip . cupSODA source code and precompiled binaries (Linux, Mac OS/X, Windows) are available at github.com/aresio/cupSODA (requires an Nvidia GPU; developer.nvidia.com/cuda-gpus ). Additional information about PySB is available at pysb.org.
Contact: c.lopez@vanderbilt.edu ; paolo.cazzaniga@unibg.it.
Supplementary information: Supplementary data are available at Bioinformatics online.

PMID: 28666314 [PubMed - as supplied by publisher]

Multimodal nonlinear optical microscopy reveals critical role of kinesin-1 in cartilage development.

Biomed Opt Express. 2017 Mar 01;8(3):1771-1782

Authors: He S, Xue W, Duan Z, Sun Q, Li X, Gan H, Huang J, Qu JY

Abstract
We developed a multimodal nonlinear optical (NLO) microscope system by integrating stimulated Raman scattering (SRS), second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging. The system was used to study the morphological and biochemical characteristics of tibial cartilage in a kinesin-1 (Kif5b) knockout mouse model. The detailed structure of fibrillar collagen in the extracellular matrix of cartilage was visualized by the forward and backward SHG signals, while high resolution imaging of chondrocytes was achieved by capturing endogenous TPEF and SRS signals of the cells. The results demonstrate that collagen fibrils in the superficial surface of the articular cartilage decreased significantly in the absence of Kif5b. The distorted morphology along with accumulated intracellular collagen was observed in the Kif5b-deficient chondrocytes, indicating the critical roles of kinesin-1 in the chondrocyte morphogenesis and collagen secretion. The study shows that multimodal NLO imaging method is an effective approach to investigate early development of cartilage.

PMID: 28663865 [PubMed]

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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