scholarly journals Wnt11/Fzd7 signaling compartmentalizes AKAP2/PKA to regulate L-type Ca2+ channel

2019 ◽  
Author(s):  
Kitti D. Csályi ◽  
Tareck Rharass ◽  
Maike Schulz ◽  
Mai H.Q. Phan ◽  
Paulina Wakula ◽  
...  
Keyword(s):  
Heart Development ◽  
Calcium Influx ◽  
Electrical Coupling ◽  
Proteolytic Processing ◽  
Adrenergic Stimulation ◽  
Systematic Analysis ◽  
Physiological Processes ◽  
C Terminus ◽  
Anchoring Proteins ◽  
Wide Range

AbstractCalcium influx through the voltage-gated L-type calcium channels (LTCC) mediates a wide range of physiological processes from contraction to secretion. Despite extensive research on regulation of LTCC conductance by PKA phosphorylation in response to β-adrenergic stimulation, the science remains incomplete. Here, we show that Wnt11, a non-canonical Wnt ligand, through its G protein-coupled receptor (GPCR) Fzd7 attenuates the LTCC conductance by preventing the proteolytic processing of its C terminus. This is mediated across species by protein kinase A (PKA), which is compartmentalized by A-kinase anchoring proteins (AKAP). Systematic analysis of all AKAP family members revealed AKAP2 anchoring of PKA is central to the Wnt11-dependent regulation of the channel. The identified Wnt11/AKAP2/PKA signalosome is required for heart development, controlling the intercellular electrical coupling in the developing zebrafish heart. Altogether, our data revealed Wnt11/Fzd7 signaling via AKAP2/PKA as a conserved alternative GPCR system regulating Ca2+ homeostasis.

scholarly journals Recent Advances in Unmanned Aerial Vehicle Forest Remote Sensing—A Systematic Review. Part I: A General Framework

Forests ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 327 ◽  
Author(s):  
Riccardo Dainelli ◽  
Piero Toscano ◽  
Salvatore Filippo Di Gennaro ◽  
Alessandro Matese
Keyword(s):  
Remote Sensing ◽  
Unmanned Aerial Vehicle ◽  
Relevant Information ◽  
Forest Monitoring ◽  
Machine Learning Techniques ◽  
Planted Forests ◽  
Systematic Analysis ◽  
Aerial Photogrammetry ◽  
Wide Range ◽  
Aerial Vehicle

Natural, semi-natural, and planted forests are a key asset worldwide, providing a broad range of positive externalities. For sustainable forest planning and management, remote sensing (RS) platforms are rapidly going mainstream. In a framework where scientific production is growing exponentially, a systematic analysis of unmanned aerial vehicle (UAV)-based forestry research papers is of paramount importance to understand trends, overlaps and gaps. The present review is organized into two parts (Part I and Part II). Part II inspects specific technical issues regarding the application of UAV-RS in forestry, together with the pros and cons of different UAV solutions and activities where additional effort is needed, such as the technology transfer. Part I systematically analyzes and discusses general aspects of applying UAV in natural, semi-natural and artificial forestry ecosystems in the recent peer-reviewed literature (2018–mid-2020). The specific goals are threefold: (i) create a carefully selected bibliographic dataset that other researchers can draw on for their scientific works; (ii) analyze general and recent trends in RS forest monitoring (iii) reveal gaps in the general research framework where an additional activity is needed. Through double-step filtering of research items found in the Web of Science search engine, the study gathers and analyzes a comprehensive dataset (226 articles). Papers have been categorized into six main topics, and the relevant information has been subsequently extracted. The strong points emerging from this study concern the wide range of topics in the forestry sector and in particular the retrieval of tree inventory parameters often through Digital Aerial Photogrammetry (DAP), RGB sensors, and machine learning techniques. Nevertheless, challenges still exist regarding the promotion of UAV-RS in specific parts of the world, mostly in the tropical and equatorial forests. Much additional research is required for the full exploitation of hyperspectral sensors and for planning long-term monitoring.

scholarly journals Glucocorticoid resistance conferring mutation in the C-terminus of GR alters the receptor conformational dynamics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Kaziales ◽  
Florian Rührnößl ◽  
Klaus Richter
Keyword(s):  
Glucocorticoid Receptor ◽  
Steroid Hormones ◽  
In Silico ◽  
Conformational Dynamics ◽  
Glucocorticoid Resistance ◽  
Physiological Processes ◽  
C Terminus ◽  
Hsp90 Chaperone ◽  
In Silico Methods

AbstractThe glucocorticoid receptor is a key regulator of essential physiological processes, which under the control of the Hsp90 chaperone machinery, binds to steroid hormones and steroid-like molecules and in a rather complicated and elusive response, regulates a set of glucocorticoid responsive genes. We here examine a human glucocorticoid receptor variant, harboring a point mutation in the last C-terminal residues, L773P, that was associated to Primary Generalized Glucocorticoid Resistance, a condition originating from decreased affinity to hormone, impairing one or multiple aspects of GR action. Using in vitro and in silico methods, we assign the conformational consequences of this mutation to particular GR elements and report on the altered receptor properties regarding its binding to dexamethasone, a NCOA-2 coactivator-derived peptide, DNA, and importantly, its interaction with the chaperone machinery of Hsp90.

scholarly journals Human Plasma and Recombinant Hemopexins: Heme Binding Revisited

2021 ◽  
Vol 22 (3) ◽  
pp. 1199
Author(s):  
Elena Karnaukhova ◽  
Catherine Owczarek ◽  
Peter Schmidt ◽  
Dominik J. Schaer ◽  
Paul W. Buehler
Keyword(s):  
Protein S ◽  
Soret Band ◽  
Cell System ◽  
Size Exclusion ◽  
Heme Binding ◽  
Systematic Analysis ◽  
Molar Ratios ◽  
Recombinant Production ◽  
Wide Range ◽  
Exclusion Chromatography

Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin (the term “heme” is used in this article to denote both the ferrous and ferric forms). During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), size-exclusion chromatography (SEC)-HPLC, and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX–heme interactions to approximate physiological conditions (from extremely low to more than two-fold heme molar excess over the protein). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggest more than one binding site in both plasma and rhHPX. Furthermore, our study provides a useful analytical platform for the detailed characterization of HPX–heme interactions and potentially novel HPX fusion constructs.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

EXPRESS: On the Limit of Detection in Infrared Spectroscopic Imaging

2021 ◽  
pp. 000370282110509
Author(s):  
Laurin Lux ◽  
Yamuna Dilip Phal ◽  
Pei-Hsuan Hsieh ◽  
Rohit Bhargava
Keyword(s):  
Limit Of Detection ◽  
Protein Microarray ◽  
Spectroscopic Imaging ◽  
Single Frequency ◽  
Systematic Analysis ◽  
Protein Mass ◽  
Ir Imaging ◽  
Wide Range ◽  
Ft Ir ◽  
Processing Techniques

Infrared (IR) spectroscopic imaging instruments’ performance can be characterized and optimized by an analysis of their limit of detection (LoD). Here we report a systematic analysis of the LoD for Fourier transform IR (FT-IR) and discrete frequency IR (DFIR) imaging spectrometers. In addition to traditional measurements of sample and blank data, we propose a decision theory perspective to pose the determination of LoD as a binary classification problem under different assumptions of noise uniformity and correlation. We also examine three spectral analysis approaches, namely absorbance at a single frequency, sum of absorbance over selected frequencies and total spectral distance – to suit instruments that acquire discrete or contiguous spectral bandwidths. The analysis is validated by refining the fabrication of a bovine serum albumin protein microarray to provide eight uniform spots from 2.8 nL of solution for each concentration over a wide range (0.05 -10 mg/mL). Using scanning parameters that are typical for each instrument, we estimate a LoD of 0.16 mg/mL and 0.12 mg/mL for widefield and line scanning FT-IR imaging systems, respectively, usingthespectraldistanceapproach,and0.22mg/mLand0.15mg/mL using an optimal set of discrete frequencies. As expected, averaging and the use of post-processing techniques such as minimum noise fraction (MNF) transformation results in LoDs as low as 0.075 mg/mL that correspond to a spotted protein mass of 112 fg/pixel. We emphasize that these measurements were conducted at typical imaging parameters for each instrument and can be improved using the usual trading rules of IR spectroscopy. This systematic analysis and methodology for determining the LoD can allow for quantitative measures of confidence in imaging an analyte’s concentration and a basis for further improving IR imaging technology.

scholarly journals Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

2014 ◽  
Vol 10 ◽  
pp. 1354-1364 ◽  
Author(s):  
Melanie Rauschenberg ◽  
Eva-Corrina Fritz ◽  
Christian Schulz ◽  
Tobias Kaufmann ◽  
Bart Jan Ravoo
Keyword(s):  
Molecular Recognition ◽  
Self Assembled Monolayers ◽  
Carbohydrate Binding ◽  
Air Oxidation ◽  
Acetylneuraminic Acid ◽  
Physiological Processes ◽  
Wide Range ◽  
Assembled Monolayers ◽  
Synthetic Carbohydrate ◽  
Derivatives Of

The molecular recognition of carbohydrates and proteins mediates a wide range of physiological processes and the development of synthetic carbohydrate receptors (“synthetic lectins”) constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by our previous work, we prepared a fluorescently labeled synthetic lectin consisting of a cyclic dimer of the tripeptide Cys-His-Cys, which forms spontaneously by air oxidation of the monomer. Amine-tethered derivatives of N-acetylneuraminic acid (NANA), β-D-galactose, β-D-glucose and α-D-mannose were microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut agglutinin. It was found that the printed carbohydrates retain their characteristic selectivity towards the synthetic and natural lectins and that the recognition of synthetic and natural lectins is strictly orthogonal.

SHELL DEFORMATION AND SPIN EFFECTS IN NUCLEON SEPARATION ENERGIES

1993 ◽  
Vol 02 (04) ◽  
pp. 789-807
Author(s):  
D. CALEB CHANTHI RAJ ◽  
M. RAJASEKARAN ◽  
R. PREMANAND
Keyword(s):  
Structural Changes ◽  
Shell Correction ◽  
Separation Energy ◽  
Systematic Analysis ◽  
Spin Effects ◽  
Wide Range ◽  
Type Calculation ◽  
Nucleon Separation Energy ◽  
New Formula ◽  
Good Agreement

A new formula to obtain shell correction to separation energy is derived from a Strutinsky type calculation. A systematic analysis of shell and deformation effects on nucleon separation energy is made. Spin induced structural changes are also evident in shape changes along the spin coordinate. Calculations are performed for a wide range of nuclei from Zr to Cm. The results are generally in very good agreement with experimental analysis.

Behavior as a window on physiology: a simple apparatus for recording caterpillar feeding.

1992 ◽  
Vol 262 (6) ◽  
pp. S9 ◽  
Author(s):  
E Bowdan
Keyword(s):  
Feeding Behavior ◽  
Control Mechanisms ◽  
Inexpensive Method ◽  
Simple Apparatus ◽  
Physiological Processes ◽  
Wide Range ◽  
Relationship Of ◽  
The Relationship

Regulation of feeding is a fundamental element of homeostasis. This is reflected in the similarity of control mechanisms in a wide range of animals, including insects and humans. A close examination of feeding behavior can illuminate the physiological processes driving regulation. A simple, inexpensive method for recording fine details of feeding by caterpillars is described. Possible experiments, interpretation of the data, and the relationship of observations to the underlying physiology, are outlined.

scholarly journals Proteolytic processing of the L-type Ca2+ channel alpha11.2 subunit in neurons

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1166 ◽  
Author(s):  
Olivia R. Buonarati ◽  
Peter B. Henderson ◽  
Geoffrey G. Murphy ◽  
Mary C. Horne ◽  
Johannes W. Hell
Keyword(s):  
Gene Expression ◽  
Brain Tissue ◽  
Neuronal Excitability ◽  
Central Element ◽  
Proteolytic Processing ◽  
Full Length ◽  
Hek293 Cells ◽  
Specific Antibodies ◽  
C Terminus ◽  
Molecular Masses

Background: The L-type Ca2+ channel Cav1.2 is a prominent regulator of neuronal excitability, synaptic plasticity, and gene expression. The central element of Cav1.2 is the pore-forming α11.2 subunit. It exists in two major size forms, whose molecular masses have proven difficult to precisely determine. Recent work suggests that α11.2 is proteolytically cleaved between the second and third of its four pore-forming domains (Michailidis et al,. 2014). Methods: To better determine the apparent molecular masses (MR)of the α11.2 size forms, extensive systematic immunoblotting of brain tissue as well as full length and C-terminally truncated α11.2 expressed in HEK293 cells was conducted using six different region–specific antibodies against α11.2. Results: The full length form of α11.2 migrated, as expected, with an apparent MR of ~250 kDa. A shorter form of comparable prevalence with an apparent MR of ~210 kDa could only be detected in immunoblots probed with antibodies recognizing α11.2 at an epitope 400 or more residues upstream of the C-terminus. Conclusions: The main two size forms of α11.2 are the full length form and a shorter form, which lacks ~350 distal C-terminal residues. Midchannel cleavage as suggested by Michailidis et al. (2014) is at best minimal in brain tissue.

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