• Globular proteins are only marginally stable because the free energy released when the protein folded into its native conformation is relatively small. (wikipedia.org)
  • As the free energy difference in a globular protein that results from folding into its native conformation is small, it is marginally stable, thus providing a rapid turnover rate and effective control of protein degradation and synthesis. (wikipedia.org)
  • In addition to the native conformation, a protein sequence populates small fluctuations around the native state, partially unfolded forms and even the globally unfolded conformation. (berkeley.edu)
  • The term globular protein is quite old (dating probably from the 19th century) and is now somewhat archaic given the hundreds of thousands of proteins and more elegant and descriptive structural motif vocabulary. (wikipedia.org)
  • Unlike fibrous proteins which only play a structural function, globular proteins can act as: Enzymes, by catalyzing organic reactions taking place in the organism in mild conditions and with a great specificity. (wikipedia.org)
  • Structural proteins, e.g., actin and tubulin, which are globular and soluble as monomers, but polymerize to form long, stiff fibers Among the most known globular proteins is hemoglobin, a member of the globin protein family. (wikipedia.org)
  • Other projects in the lab focus on the mechanism of protein misfolding, the structural and energetic mechanism of signaling, computational identification of folding modules, and the role of ligand binding. (berkeley.edu)
  • Due to the ability to heavily label analyte proteins in a benchtop setup, FPOP has been used to examine therapeutic proteins and compare conformations between biosimilars and originator biotherapeutics (22), map antibody-antigen interaction interfaces (23C26), and examine structural consequences of gaps in the cold chain for therapeutic protein handling (22). (ibs-italy.info)
  • They are characterized by extraordinary structural flexibility and plasticity, which enable them to adopt different conformations in response to different stimuli or different interactions. (bvsalud.org)
  • MARV assembles and buds from the host cell plasma where MARV matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane inner leaflet and undergo a dynamic and extensive self-oligomerization into the structural matrix layer. (uci.edu)
  • Large polypeptides that form a-helix or ß-sheet structures are currently beyond the reach of rotational spectroscopists, but the recent ion-drift experiments [13-15] on acetyl-(alanine)7-lysine suggest that the first direct observations of the structural motifs found in protein and peptide secondary structure using high resolution spectroscopy may not be far off. (kent.edu)
  • 1991), none of the the structural details of the heterogeneous protein surface and experimental studies mentioned so far could provide un- takes into account a variety of short-range interactions, direct ambiguous information about oligomer structure. (lu.se)
  • In a first couple of examples, I will show how distance and shape restraints from SANS have helped to improve the uniqueness of structural models for two multi-protein-RNA complexes, in combination with NMR restraints and building blocks from crystallography [1, 2]. (lu.se)
  • Surfactant recovered by alveolar wash from most mammals contains 70-80% phospholipids, 8-10% protein, and 10% neutral lipids, primarily cholesterol. (medscape.com)
  • its primary translation product, 22 kd, is processed to an extremely hydrophobic 4-kd protein that is associated with lipids in lamellar bodies. (medscape.com)
  • Small angle neutron scattering (SANS) provides unique insight into biomacromolecular complexes by combining solvent contrast variation (H2O:D2O exchange) with either natural contrast between different classes of biomolecules (proteins, RNA/DNA, lipids/detergents) and/or by applying artificial contrast, i.e. deuteration of specific biomolecules. (lu.se)
  • Utilizing a triazine core, side groups are readily introduced, and polymers formed by solid phase synthesis. (pnnl.gov)
  • Such non-native states on the energy landscape are thought to play a determining function in many cellular processes such as translocation, protein synthesis, degradation, signaling and allostery. (berkeley.edu)
  • We highlight the importance of protein degradation and/or conformational inactivation for buffering to appear. (biomedcentral.com)
  • The extraordinary stability against proteolytic degradation in presence of proteases and ability to generate stable helical secondary structures, such as, 14- 12- and alternate 10/12-helices, with as few as 4-6 amino acids are the two main reasons behind the booming entry of β-peptides into peptidomimetics. (uni-goettingen.de)
  • These covalent bonds are found in almost all classes of extracellular peptides and proteins. (lifetein.com)
  • The consequential perturbations provide a useful tool for chemical biologists to reveal new structure-function relationships, and to endow peptides and proteins with desirable attributes. (pdffox.com)
  • Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. (springeropen.com)
  • Despite the complexity of causative factors that can lead to these disease states, the tools of modern drug discovery have the power to cover millions of compounds or fragments and determine their potential association with a target before specific chemical synthesis and biological testing is done. (springeropen.com)
  • In chemical synthesis, the folding and disulfide formation of the fully unprotected amino acids in an aqueous solution by a mild oxidization to form the target product with the correct disulfide bonds. (lifetein.com)
  • There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a roughly spherical shape. (wikipedia.org)
  • Globular proteins seem to have two mechanisms for protein folding, either the diffusion-collision model or nucleation condensation model, although recent findings have shown globular proteins, such as PTP-BL PDZ2, that fold with characteristic features of both models. (wikipedia.org)
  • The folding of globular proteins has also recently been connected to treatment of diseases, and anti-cancer ligands have been developed which bind to the folded but not the natural protein. (wikipedia.org)
  • These studies have shown that the folding of globular proteins affects its function. (wikipedia.org)
  • Albumins are also globular proteins, although, unlike all of the other globular proteins, they are completely soluble in water. (wikipedia.org)
  • Nonetheless, and as noted by Hofmeister,[2] peptide bonds can be much less stable in vivo, due to the action of proteases. (pdffox.com)
  • Part of the protein folding problem is that several non-covalent, weak interactions are formed, such as hydrogen bonds and Van der Waals interactions. (wikipedia.org)
  • The simulations show conformational order due to hydrogen bonding and other interactions illustrative of protein secondary structure. (pnnl.gov)
  • RNA catalytic and binding interactions with proteins and small molecules are fundamental elements of cellular life processes as well as the basis for RNA therapeutics and molecular engineering. (nature.com)
  • Some conserved cysteines within proteins are critical for protein-protein interactions. (lifetein.com)
  • Protein conformation is critically linked to function and often controlled by interactions with regulatory factors. (cipsm.de)
  • Ca2 + -Glutamic residue interactions altered E protein conformation and favored ion channel opening and the flow of ions into and through the channels. (medicalwritersnewshubb.com)
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
  • Moreover, iron interactions with N-terminally acetylated α S, the physiologically relevant form of the human protein, will be addressed to shed light on the current understanding of protein dynamics and the physiological environment in the disease state. (hindawi.com)
  • The magnetic relaxation dispersion method sensitively detects stable oligomers without being affected by other interactions. (lu.se)
  • Protein complexes perform a diversity of functions in natural biological systems. (mdpi.com)
  • While computational protein design has enabled the development of symmetric protein complexes with spherical shapes and hollow interiors, the individual subunits often comprise large proteins. (mdpi.com)
  • From Protein Complexes to Subunit Backbone Fragments: a Novel Approach to Native Mass Spectrometry. (chicagobiomedicalconsortium.org)
  • The voltage experiments showed that the E protein was most likely a voltage-gated pore regulated by electrowetting and a hydrophobic gating motif (comprising Phe20, 23, and 26 residues) located in the pore's center. (medicalwritersnewshubb.com)
  • Among the four surfactant apoproteins identified, surfactant protein B (SP-B) and SP-C are two small hydrophobic proteins that make up 2-4% of the surfactant mass and are present in commercially available surfactant preparations. (medscape.com)
  • We have found that although protein stability can be altered by single amino acid substitution, evolution for optimal function requires more subtle and delocalized mechanisms.Recent results implicate structure in the unfolded state as playing an important and novel role for the thermostability of these proteins. (berkeley.edu)
  • The most promising Ags were submitted to a more in-depth biophysical investigation of their structure and conformation stability, and for their capacity to interact with neutralising antibodies (Abs) and peptides. (europa.eu)
  • Disulfides in proteins play an important role in the maintenance of biological activity and conformational stability. (lifetein.com)
  • Both studies suggest that defects in rhodopsin glycosylation are associated with impairment of protein folding or stability. (jneurosci.org)
  • The larger Rep proteins, Rep78 and Rep68, assemble into stable, hexameric oligomers on specific secondary structures on the 3' and 5' termini of the single stranded viral DNA. (utoledo.edu)
  • N-linked glycosylation is the most prevalent posttranslational modification of plasma membrane and secretory proteins and participates in many important biological roles such as protein folding, intracellular targeting, immune response, cell adhesion, and protease resistance. (jneurosci.org)
  • Understanding the sequence determinants of the energy landscape is therefore fundamental to the biological process that proteins carry out as well as protein folding itself. (berkeley.edu)
  • TSPO is a ubiquitous mitochondrial protein and is involved in numerous biological functions. (uni-regensburg.de)
  • The biological function of the differentially expressed circRNAs was determined by protein interaction network, Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment. (biomedcentral.com)
  • We found 1100 differentially expressed circRNAs (675 downregulated and 425 upregulated) which were involved in various biological processes such as protein ubiquitination modification, cell cycle regulation, RNA transport, and autophagy. (biomedcentral.com)
  • Here we report the selection of camelid-derived single-domain antibodies (nanobodies) that modulate the conformation and spectral properties of the green fluorescent protein (GFP). (cipsm.de)
  • This vulnerability, along with a desire to modulate the structure and function of proteins, has motivated chemical biologists to develop surrogates of the peptide bond. (pdffox.com)
  • Preexisting antivector immunity can severely compromise the ability of Salmonella enterica serovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. (cipsm.de)
  • Our use of different hydrogen exchange methods to study three different types of intermediates of E. coli ribonuclease H (the acid molten globule, the higher energy conformations of the native state and a kinetic folding intermediate) has been particularly powerful. (berkeley.edu)
  • Our studies on the mechanism of folding include investigating the role of topological complexity using permuted proteins, the nature and function of folding intermediates, and studies on the role of mechanical unfolding using single molecule measurements. (berkeley.edu)
  • these have included dihydroxylation of the coumarin double bond, and the synthesis of 4- benzylaminocoumarin derivatives as potential intermediates. (ru.ac.za)
  • The isotope synthesis projects provide practical experience in peptide synthesis, purification, and analysis of intermediates using NMR, IR, and MS. Other students have tackled the rotational spectroscopy of these species. (kent.edu)
  • It reminds me of the Morrison & Mosher text, Asymmetric Synthesis, that was published more than three decades ago. (fieldofscience.com)
  • The 414K-MDI conjugation appears to covalently cross- link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric ( S , N -linked) bis(GSH)-MDI conjugates. (cdc.gov)
  • In conclusion, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains. (osti.gov)
  • We find that the addition of polysorbate-80 does not alter the conformation of the biosimilar in either buffer, but it does provide substantial protection from protein conformational perturbation during short periods of exposure to high temperature. (ibs-italy.info)
  • The research of my laboratory is focused on nucleic acid enzymology, nucleic acid protein interaction and more recently on the development of modified human albumin for the treatment of shock. (utoledo.edu)
  • A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. (osti.gov)
  • Actin and myosin are the basic proteins involved in contractile machinery of our body to which type of proteins do they belong? (r4r.in)
  • Furthermore, the mAb D6F10 rescues inhibition of protein synthesis by abrin in HeLa cells by internalizing in cells along with abrin and possibly occluding the active site cleft of ABA. (iisc.ac.in)
  • The rationale behind using polyethylene glycol-modified albumin is that this modified protein has a sufficiently large hydrodynamic radius that precludes its passing through defects in capillaries that occur in shock and is thus retained within blood vessels to maintain the oncotic gradient. (utoledo.edu)
  • The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position 414K, a preferred site of MDI reactivity on human albumin. (cdc.gov)
  • Functional proteins that do not have unique, stable, folded, three-dimensional native structures or that possess non-ordered regions under physiological conditions. (bvsalud.org)
  • Here we demonstrate that PSRP1 is not a bona fide ribosomal protein, but rather a functional homologue of the Escherichia coli cold-shock protein pY. (cipsm.de)
  • The team investigated if the transmembrane (TM) site formed EFL functional substructures, for which ETM was produced comprising viral E protein residues 8 to 38, by solid-phase peptide synthesis and assessed ETM functionality in-vitro . (medicalwritersnewshubb.com)
  • The TM domain, individually, did not form physiologically functional substructures of the viral E protein. (medicalwritersnewshubb.com)
  • In our present view, these areas are found for systems where several types of macromolecules (proteins, polysaccharides or polyelectrolytes) and/or amphiphiles interact to form a functional or destructive unit. (lu.se)
  • This is because protein folding requires entropic cost. (wikipedia.org)
  • Via several techniques, the mechanism of protein folding is currently being studied. (wikipedia.org)
  • This hypothesis unites a lot of work in the field of and has also provided insight and experimental tests for current theoretical work on protein folding. (berkeley.edu)
  • Understanding the molecular forces and other physico-chemical processes behind the folding conformation and transmembrane dynamics of these protein domains are an integral part in the process of developing updated synthetic transmembrane protein domains. (uni-goettingen.de)
  • This delocalization is primarily responsible for the rotational barrier between the cis and trans isomers of the peptide bond, which can limit the rate of protein folding. (pdffox.com)
  • Lipid-specific oligomerization of the Marburg virus matrix protein VP40 is regulated by two distinct interfaces for virion assembly. (uci.edu)
  • Compensated HRPF measurements are validated and contextualized by dynamic light scattering (DLS), which suggests that changes in adalimumab biosimilar aggregation is a major driver in measured changes in protein topography. (ibs-italy.info)
  • The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. (cipsm.de)
  • A tetrameric form of α S has also been identified in human tissues that has been postulated as the inactive storage form of this structurally dynamic protein due to its aggregation resistance [ 6 , 7 ]. (hindawi.com)
  • For instance, many proteins share the same native structure yet their cellular dynamics and function, in other words their energy landscapes, are different. (berkeley.edu)
  • We focus on the dynamics of the pseudorotation process, in particular, the lifetime of the THF conformations and their mutual rearrangements. (researchgate.net)
  • A disulfide bridge is created when a sulfur atom from one cysteine forms a single covalent bond with another sulfur atom from a second cysteine residue located in a different part of the protein. (lifetein.com)
  • Palmitoylation of ≥1 cysteine residue promoted the formation of open and stable E protein pores. (medicalwritersnewshubb.com)
  • This 58-residue (6.5 kDa) basic (pI ¼ 10.5) isoelectric point of BPTI, with phosphate as the salting-out protein has long been thought to undergo self-association. (lu.se)
  • A more recent NMR pulsed-gradient, spin-echo misfolded proteins (Kelly, 1998), and the nucleation, growth, (PGSE) self-diffusion study concluded that BPTI is pre- and polymorphism of protein crystals (Rosenberger et al. (lu.se)
  • Tetrahydrofuran (THF) is a widely used chemical compound, in particular as a solvent in organic and inorganic synthesis. (researchgate.net)
  • Rarely used strained molecules step up for organic synthesis. (qmul.ac.uk)
  • Furthermore, different conformations of phage tail fibers correlated with the aforementioned orientations of the tails. (stanford.edu)
  • Our studies are aimed at understanding how these proteins assemble on DNA structures and the specificity of their interaction with DNA. (utoledo.edu)
  • These methods dramatically increase the likelihood of producing proteins that cannot fold or assemble appropriately. (cipsm.de)
  • We have shown that FadR Mt (Rv0494) directly binds to long-chain fatty acyl-CoA and that binding quenches the intrinsic fluorescence of the purified protein. (microbiologyresearch.org)
  • Overexpression of Rv0494 in Mycobacterium bovis BCG reduced the basal level expression of kas operon genes, thereby suggesting the repressor nature of this protein in fatty acid synthase II regulation. (microbiologyresearch.org)
  • This is the first report, to the best of our knowledge, of a GntR/FadR family protein acting as a fatty acid-responsive transcriptional regulator in M. tuberculosis , suggesting a possible role for this protein in mycolic acid biosynthesis. (microbiologyresearch.org)
  • Escherichia coli unsaturated fatty acid synthesis: complex transcription of the fabA gene and in vivo identification of the essential reaction catalyzed by FabB. (microbiologyresearch.org)
  • The major constituent of LBs is aggregated α -synuclein ( α S), an intrinsically unfolded protein predominantly localized in the presynaptic regions of dopaminergic neurons. (hindawi.com)
  • The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. (cipsm.de)
  • The enhancement of immune responsiveness observed in mice fed the 28% L diet was moderately reduced by the addition of phenylalanine to the diet, indicating that the lower level of this amino acid in the L protein may be of some significance. (immunehealthscience.com)
  • The principal factor responsible for the observed immune effect does not appear to be the availability or concentration of single essential amino acids but rather the composite effect of the specific amino acid distribution in the protein. (immunehealthscience.com)
  • Studies of the thermodynamics of binding of ligands to glycyl tRNAs suggest that the formation of glycyl adenylate, an obligate intermediate on the reaction pathway, is accompanied by a significant conformation change in the protein that alters the affinity of the enzyme for tRNA. (utoledo.edu)
  • High-throughput sequencing-RNA affinity profiling (HiTS-RAP) 22 is conceptually similar to RNA-MaP, but uses the E. coli replication terminator protein Tus to stall the RNA polymerase after transcribing the variable section of the DNA library. (nature.com)
  • Low energy difference between the envelope (Cs symmetry) and twisted (C2 symmetry) conformations of the THF molecule leads to the interconversion between the two conformers. (researchgate.net)
  • The smaller replication proteins, Rep40 and Rep52, require ATP to bind DNA, show no sequence specificity in DNA binding and lack the N-terminal nuclease domains. (utoledo.edu)
  • In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. (frontiersin.org)
  • The hydrophobically gated ion channel activity of the viral E protein and viroporins were regulated by elevated luminal Ca2 + concentrations (0.1 mM to 1.0 mM), electrochemical gradients, pH, PTMs, ERGIC phospholipids with negative charges, and voltage applied to the membranes. (medicalwritersnewshubb.com)
  • BTK, a TEC-family tyrosine kinase activated by the B-cell antigen receptor, contains a variety of regulatory domains and it is subject to complex regulation by membrane phospholipids, protein ligands, phosphorylation, and dimerization. (elifesciences.org)
  • The SP-B gene is on human chromosome 2, and its primary translation product is 40 kd, which is clipped to become an 8-kd protein in the type II cells before entering lamellar bodies to be cosecreted with phospholipids. (medscape.com)
  • Proteins undergo an incredible transformation from one-dimensional sequence information into complex three-dimensional shapes that carry out intricate cellular functions. (berkeley.edu)
  • Much has been learned regarding nuclear entry, but the cellular proteins involved are still unknown and the exact role of each viral component remains controversial [ 7 ]. (biomedcentral.com)
  • The etiology of Parkinson's disease (PD) is linked with cellular inclusions in the substantia nigra pars compacta region of the brain that are enriched in the misfolded presynaptic protein α -synuclein ( α S) and death of the dopaminergic neurons. (hindawi.com)
  • 1997) at higher how proteins interact with themselves in solution. (lu.se)
  • Due to the Arbutin (Uva, p-Arbutin) short timescale of the reaction, proteins can be heavily modified by FPOP without labeling artifactual conformations induced by the FPOP process itself (8, 21). (ibs-italy.info)
  • Proteins from thermophilic organisms must retain their native structures under extreme conditions, where their homologues from mesophilic organisms denature. (berkeley.edu)
  • Tau is a protein that is important in neuronal function, but can misfold and aggregate into pathological structures that accumulate in neurodegenerative disorders such as Alzheimer's disease. (utsa.edu)
  • Our proof-of-concept benchmark revealed the 3D distribution of organelles and subcellular structures in whole heat-shocked yeast cells, including the ultrastructure of protein inclusions that recruit fluorescently-labeled chaperone Hsp104. (stanford.edu)
  • Plastid-specific ribosomal proteins (PSRPs) have been proposed to play roles in the light-dependent regulation of chloroplast translation. (cipsm.de)
  • Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
  • Disulfide bonds are an integral component of the three-dimensional structure of many proteins. (lifetein.com)
  • As a primary sequence of a polypeptide chain can form numerous conformations, native globular structure restricts its conformation to a few only. (wikipedia.org)
  • E protein construct comprising the full-length E sequence or residues 1 to 75 (EFL) was produced, purified from E. coli inclusion bodies, and reconstituted into phosphatidylethanolamine (PE) membranes under voltage-clamp conditions. (medicalwritersnewshubb.com)
  • Therefore, different types of β-peptides including 14-, 12- and alternate 10/12-helical peptides with comparable transmembrane length and sequence are planned to be synthesized by mixing different synthetic strategies, such as, microwave-assisted manual SPPS, non-microwave-assisted manual SPPS, and fluorous-tag-attached liquid phase peptide synthesis. (uni-goettingen.de)
  • DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
  • Several mutations in the N terminus of the G-protein-coupled receptor rhodopsin disrupt NXS/T consensus sequences for N-linked glycosylation (located at N2 and N15) and cause sector retinitis pigmentosa in which the inferior retina preferentially degenerates. (jneurosci.org)
  • Mutations affecting glycosylation of the heptahelical G-protein-coupled receptor rhodopsin are associated with retinitis pigmentosa (RP), a disease characterized by progressive degeneration of photoreceptors. (jneurosci.org)
  • Modification of the cysteine using Acm blocks disulfide bond formation, but retains the cysteine and preserves the primary structure of the protein. (lifetein.com)
  • Detailed knowledge of protein structure aids in explaining why one bioisostere works and another one does not. (fieldofscience.com)
  • The synthesis of the peptides may provide sufficient material to enable further studies and to determine the structure-activity relationships or may provide discovery of new analogues with improved properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. (intechopen.com)
  • An Evaluation of Peptide-Bond Isosteres Amit Choudhary[c] and Ronald T. Raines*[a, b] Peptide-bond isosteres can enable a deep interrogation of the structure and function of a peptide or protein by amplifying or attenuating particular chemical properties. (pdffox.com)
  • Analysis of the crystal structure of abrin A chain revealed that a helix spanning the amino acids 148-167 was present at the core of the protein structure and truncation in this region of the protein possibly results in loss of conformation leading to abrogation of antibody binding. (iisc.ac.in)
  • Here we describe the 3.2 Å cryo-EM structure of human DEC-205, thereby illuminating the structure of the mannose receptor protein family. (uci.edu)
  • We have taken a proteomic and biophysical approach to understand how a protein fine-tunes its landscape to control this feature. (berkeley.edu)
  • We observe a different ratio between envelope (Cs) and twisted (C2) conformations with respect to a change of the temperature. (researchgate.net)
  • In a recent study posted to the bioRxiv * preprint server, researchers investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein activity in terms of calcium cations (Ca2 + ) cations. (medicalwritersnewshubb.com)
  • The SARS-CoV-2 envelope (E) protein forms a calcium- and voltage-activated calcium channel. (medicalwritersnewshubb.com)