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https://www.readbyqxmd.com/read/28445786/metallo-%C3%AE-lactamase-inhibitors-by-bioisosteric-replacement-preparation-activity-and-binding
#1
Susann Skagseth, Sundus Akhter, Marianne H Paulsen, Zeeshan Muhammad, Silje Lauksund, Ørjan Samuelsen, Hanna-Kirsti S Leiros, Annette Bayer
Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent scaffolds reported as MBL inhibitors. In this study, the carboxylate group of mercaptocarboxylic acids was replaced with bioisosteric groups like phosphonate esters, phosphonic acids and NH-tetrazoles...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28445753/pyroglutamate-modified-amyloid-%C3%AE-3-42-shows-%C3%AE-helical-intermediates-before-amyloid-formation
#2
Christina Dammers, Kerstin Reiss, Lothar Gremer, Justin Lecher, Tamar Ziehm, Matthias Stoldt, Melanie Schwarten, Dieter Willbold
Pyroglutamate-modified amyloid-β (pEAβ) has been described as a relevant Aβ species in Alzheimer's-disease-affected brains, with pEAβ (3-42) as a dominant isoform. Aβ (1-40) and Aβ (1-42) have been well characterized under various solution conditions, including aqueous solutions containing trifluoroethanol (TFE). To characterize structural properties of pEAβ (3-42) possibly underlying its drastically increased aggregation propensity compared to Aβ (1-42), we started our studies in various TFE-water mixtures and found striking differences between the two Aβ species...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445751/curcumin-dictates-divergent-fates-for-the-central-salt-bridges-in-amyloid-%C3%AE-40-and-amyloid-%C3%AE-42
#3
Bappaditya Chandra, Venus Singh Mithu, Debanjan Bhowmik, Anand Kant Das, Bankanidhi Sahoo, Sudipta Maiti, Perunthiruthy K Madhu
There are three specific regions in the Amyloid beta (Aβ) peptide sequence where variations cause enhanced toxicity in Alzheimer's disease: the N-terminus, the central salt bridge, and the C-terminus. Here, we investigate if there is a close conformational connection between these three regions, which may suggest a concerted mechanism of toxicity. We measure the effects of Zn(2+) and curcumin on Aβ40, and compare these with their previously reported effects on Aβ42. Aβ42 and Aβ40 differ only near the C-terminus, where curcumin interacts, while Zn(2+) interacts near the N-terminus...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445646/spinning-hierarchical-gold-nanowire-microfibers-by-shear-alignment-and-intermolecular-self-assembly
#4
Beate Reiser, Dominik Gerstner, Lola Gonzalez-Garcia, Johannes H M Maurer, Ioannis Kanelidis, Tobias Kraus
Hierarchical structures lend strength to natural fibers made of soft nanoscale building blocks. Intermolecular interactions connect the components at different levels of hierarchy, distribute stresses, and guarantee structural integrity under load. Here, we show that synthetic ultrathin gold nanowires with interacting ligand shells can be spun into biomimetic, free-standing microfibers. A solution spinning process first aligns the wires, then lets their ligand shells interact, and finally converts them into a hierarchical superstructure...
April 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28445499/fine-scale-population-genetic-structure-of-the-bengal-tiger-panthera-tigris-tigris-in-a-human-dominated-western-terai-arc-landscape-india
#5
Sujeet Kumar Singh, Jouni Aspi, Laura Kvist, Reeta Sharma, Puneet Pandey, Sudhanshu Mishra, Randeep Singh, Manoj Agrawal, Surendra Prakash Goyal
Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals...
2017: PloS One
https://www.readbyqxmd.com/read/28445056/superior-plasticity-and-tabletability-of-theophylline-monohydrate
#6
Shao-Yu Chang, Changquan Calvin Sun
A theophylline monohydrate (THm) powder, with particle size and shape substantially similar to a theophylline anhydrate powder, was prepared by vapor mediated phase conversion. The elimination of possible contributions by particle size and shape to tableting properties made it possible to unambiguously identify the role of bonding area and bonding strength on powder tableting performance. It was also shown that accurate true density is essential for correct analysis and understanding of tableting behavior of THm...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28445041/verbeekite-the-long-unknown-crystal-structure-of-monoclinic-pdse2
#7
Elisabeth Selb, Martina Tribus, Gunter Heymann
Verbeekite, a monoclinic polymorph of PdSe2, was reported for the first time in 2002 by Roberts et al. The mineral has been discovered in the Musonoi Cu-Co-Mn-U mine, Democratic Republic of Congo, and was named after Dr. Théodore Verbeek, the first geoscientist who studied the palladium mineralization there (1955-1967). Until today, the crystal structure of this very rare mineral has been unknown. By syntheses via multianvil high-pressure/high-temperature methods at 11.5 GPa and 1300 °C, synthetic verbeekite could be obtained in a high degree of purity and comparatively good crystal quality, which made it possible to determine the full crystal structure for PdSe2 verbeekite from single-crystal X-ray diffractometer data: I2/a, a = 671...
April 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28444823/dissociable-corticostriatal-circuits-underlie-goal-directed-versus-cue-elicited-habitual-food-seeking-after-satiation-evidence-from-a-multimodal-mri-study
#8
Henk van Steenbergen, Poppy Watson, Reinout W Wiers, Bernhard Hommel, Sanne de Wit
The present multimodal MRI study advances our understanding of the corticostriatal circuits underlying goal-directed versus cue-driven, habitual food seeking. To this end, we employed a computerized Pavlovian-instrumental transfer (PIT) paradigm. During the test phase, participants were free to perform learnt instrumental responses (left and right key presses) for popcorn and Smarties outcomes. Importantly, prior to this test half of the participants had been sated on popcorn and the other half on Smarties - resulting in a reduced desirability of those outcomes...
April 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28444556/thalamo-cortical-functional-connectivity-in-schizophrenia-and-bipolar-disorder
#9
Kristina C Skåtun, Tobias Kaufmann, Christine L Brandt, Nhat Trung Doan, Dag Alnæs, Siren Tønnesen, Guido Biele, Anja Vaskinn, Ingrid Melle, Ingrid Agartz, Ole A Andreassen, Lars T Westlye
The thalamus is a highly connected subcortical structure that relays and integrates sensory and cortical information, which is critical for coherent and accurate perceptual awareness and cognition. Thalamic dysfunction is a classical finding in schizophrenia (SZ), and resting-state functional MRI has implicated somatomotor and frontal lobe thalamic dysconnectivity. However, it remains unclear whether these findings generalize to different psychotic disorders, are confined to specific thalamic sub-regions, and how they relate to structural thalamic alterations...
April 25, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28444386/coevolution-with-pollinating-resin-midges-led-to-resin-filled-nurseries-in-the-androecia-gynoecia-and-tepals-of-kadsura-schisandraceae
#10
Shi-Xiao Luo, Ting-Ting Liu, Fei Cui, Zi-Yin Yang, Xiao-Ying Hu, Susanne S Renner
Background and Aims: Resin is a defence against herbivores and a floral reward in a few African and South American species whose bee pollinators collect it for nest construction. Here we describe a new role for floral resin from the Asian genus Kadsura (Schisandraceae). Kadsura tepals tightly cover a globe formed by carpels (in females) or near-fused stamens with fleshy connectives (in male flowers of most, but not all species). Methods: We carried out field observations at four sites in China and used pollinator behavioural assays, chemical analyses and time-calibrated insect and plant phylogenies to investigate the specificity of the interactions and their relationship to floral structure...
April 21, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28444137/effects-of-serotonin-transporter-gene-variation-on-impulsivity-mediated-by-default-mode-network-a-family-study-of-depression
#11
Jiook Cha, Guia Guffanti, Jay Gingrich, Ardesheer Talati, Priya Wickramaratne, Myrna Weissman, Jonathan Posner
Serotonergic neurotransmission, potentially through effects on the brain's default mode network (DMN), may regulate aspects of attention including impulse control. Indeed, genetic variants of the serotonin transporter (5-HTT) have been implicated in impulsivity and related psychopathology. Yet it remains unclear the mechanism by which the 5-HTT genetic variants contribute to individual variability in impulse control. Here, we tested whether DMN connectivity mediates an association between the 5-HTT genetic variants and impulsivity...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28443805/-a-population-targeted-approach-to-connect-prevention-care-and-welfare-visualising-the-trend
#12
L C Lemmens, H W Drewes, M Lette, C A Baan
OBJECTIVE: To map initiatives in the Netherlands using a population-targeted approach to link prevention, care and welfare. DESIGN: Descriptive investigation, based on conversations and structured interviews. METHOD: We searched for initiatives in which providers in the areas of prevention, care and welfare together with health insurers and/or local authorities attempted to provide the 'triple aim': improving the health of the population and the quality of care, and managing costs...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28443655/new-insights-on-electro-optical-response-of-pedot-pss-film-to-humidity
#13
Eric S Muckley, Christopher B Jacobs, Keith Vidal, Jyoti P Mahalik, Rajeev Kumar, Bobby G Sumpter, Ilia Ivanov
Understanding the relative humidity (RH) response of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is critical for improving the stability of organic electronic devices and developing selective sensors. In this work combined gravimetric sensing, nanoscale surface probing, and mesoscale optoelectronic characterization are used to directly compare the RH dependence of electrical and optical conductivities and unfold connections between the rate of water adsorption and changes in functional properties of PEDOT:PSS film...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28442501/chlorokb-a-web-application-for-the-integration-of-knowledge-related-to-chloroplast-metabolic-network
#14
Pauline Gloaguen, Sylvain Bournais, Claude Alban, Stephane Ravanel, Daphne Seigneurin-Berny, Michel Matringe, Marianne Tardif, Marcel Kuntz, Myriam Ferro, Christophe Bruley, Norbert Rolland, Yves Vandenbrouck, Gilles Curien
CONTEXT: Higher plants, as autotrophic organisms, are effective sources of molecules. They hold great promise for metabolic engineering, but the behavior of plant metabolism at the network level is still incompletely described. Although structural models (stoichiometry matrices) and pathway databases are extremely useful, they cannot describe the complexity of the metabolic context and new tools are required to visually represent integrated biocurated knowledge for use by both humans and computers...
April 25, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#15
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28441420/mapping-of-the-brain-hemodynamic-responses-to-sensorimotor-stimulation-in-a-rodent-model-a-bold-fmri-study
#16
Salem Boussida, Amidou S Traoré, Franck Durif
Blood Oxygenation Level Dependent functional MRI (BOLD fMRI) during electrical paw stimulation has been widely used in studies aimed at the understanding of the somatosensory network in rats. However, despite the well-established anatomical connections between cortical and subcortical structures of the sensorimotor system, most of these functional studies have been concentrated on the cortical effects of sensory electrical stimulation. BOLD fMRI study of the integration of a sensorimotor input across the sensorimotor network requires an appropriate methodology to elicit functional activation in cortical and subcortical areas owing to the regional differences in both neuronal and vascular architectures between these brain regions...
2017: PloS One
https://www.readbyqxmd.com/read/28441344/collagenous-extracellular-matrix-biomaterials-for-tissue-engineering-lessons-from-the-common-sea-urchin-tissue
#17
REVIEW
Kheng Lim Goh, David F Holmes
Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441246/x-ray-imaging-analysis-of-intrathecal-baclofen-pumps-for-pediatric-emergency-medicine
#18
Brianna Nicole Carr, Thomas Sernas, Catherine A Mazzola
Intrathecal baclofen therapy has become increasingly popular because of its effectiveness in treating spasticity in pediatric patients. The device implanted into each patient is structurally similar. However, x-ray imaging can give the appearance of missing or extraneous objects on or near the intrathecal baclofen device. The composition of the material used in making the catheters is transparent on x-ray images. In addition, the connection port between the pump and catheter resembles the shape of a needle...
April 24, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28439662/the-angular-gyrus-is-a-supramodal-comparator-area-in-action-outcome-monitoring
#19
Bianca M van Kemenade, B Ezgi Arikan, Tilo Kircher, Benjamin Straube
Predicting and processing the sensory consequences of one's own actions is essential to enable successful interactions with the environment. Previous studies have suggested that the angular gyrus detects discrepancies between predicted and actual action consequences, at least for unimodal feedback. However, most actions lead to multisensory consequences, raising the question whether previous models can sufficiently explain action-outcome processing. Here, we investigated neural comparator processes during detection of delays between action and unimodal or bimodal consequences in human subjects with fMRI, using parametric and connectivity analyses...
April 24, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28439519/structured-illumination-diffuse-optical-tomography-for-noninvasive-functional-neuroimaging-in-mice
#20
Matthew D Reisman, Zachary E Markow, Adam Q Bauer, Joseph P Culver
Optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to superficial cortical tissues. Diffuse optical tomography (DOT) techniques provide noninvasive imaging, but previous DOT systems for rodent neuroimaging have been limited either by sparse spatial sampling or by slow speed...
April 2017: Neurophotonics
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