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hamlet protein

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https://www.readbyqxmd.com/read/27898907/apparent-total-tract-macronutrient-digestibility-fecal-characteristics-and-fecal-fermentative-end-product-concentrations-of-healthy-adult-dogs-fed-bioprocessed-soy-protein
#1
A N Beloshapka, M R C de Godoy, K B Detweiler, M Newcomb, K H Ellegård, G C Fahey, K S Swanson
Animal proteins are commonly used in extruded dog foods. Plant-based proteins have a more consistent nutrient profile than animal sources but may contain antinutritional factors, including trypsin inhibitors and oligosaccharides. Bioprocessed soy protein (SP; HP-300; Hamlet Protein, Inc., Findlay, OH) is a processed soy-based product with low antinutritional factor concentrations and high protein quality. The objective was to evaluate the effects of SP on apparent total tract macronutrient digestibility, fecal characteristics, and fecal fermentative end products...
September 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27109252/behaviour-of-oleic-acid-depleted-bovine-alpha-lactalbumin-made-lethal-to-tumor-cells-bamlet
#2
Mehboob Hoque, Jyoti Gupta, Gulam Rabbani, Rizwan Hasan Khan, M Saleemuddin
Oleic acid (OA) complexes of human alpha-lactalbumin (α-LA) and several other proteins are effective in the killing of a variety of tumor cells. While debate on whether the key component of the complexes is the OA or protein continues, studies probing the mechanism of action of the complexes at the tumor cell surface or in the cell interior assume the action of a molecule in the form of an undissociated complex. Recent evidence however suggests that OA complexes of protein are stripped of bound OA on interaction with artificial or natural membranes before entering the cell...
May 24, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/26964678/intrinsic-plasticity-induced-by-group-ii-metabotropic-glutamate-receptors-via-enhancement-of-high-threshold-kv-currents-in-sound-localizing-neurons
#3
W R Hamlet, Y Lu
Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization...
June 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/26626257/structure-and-potential-cellular-targets-of-hamlet-like-anti-cancer-compounds-made-from-milk-components
#4
REVIEW
Emma M Rath, Anthony P Duff, Anders P Håkansson, Catherine S Vacher, Guo Jun Liu, Robert B Knott, William Bret Church
The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis...
2015: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/26561036/protein-receptor-independent-plasma-membrane-remodeling-by-hamlet-a-tumoricidal-protein-lipid-complex
#5
Aftab Nadeem, Jeremy Sanborn, Douglas L Gettel, Ho C S James, Anna Rydström, Viviane N Ngassam, Thomas Kjær Klausen, Stine Falsig Pedersen, Matti Lam, Atul N Parikh, Catharina Svanborg
A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies...
November 12, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26300899/the-novel-and-taxonomically-restricted-ah24-gene-from-grain-amaranth-amaranthus-hypochondriacus-has-a-dual-role-in-development-and-defense
#6
Julio A Massange-Sanchez, Paola A Palmeros-Suarez, Norma A Martinez-Gallardo, Paula A Castrillon-Arbelaez, Hamlet Avilés-Arnaut, Fulgencio Alatorre-Cobos, Axel Tiessen, John P Délano-Frier
Grain amaranths tolerate stress and produce highly nutritious seeds. We have identified several (a)biotic stress-responsive genes of unknown function in Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed in young or developing tissues; it was also strongly induced by mechanical damage, insect herbivory and methyl jasmonate and in meristems and newly emerging leaves of severely defoliated plants. Interestingly, an in silico analysis of its 1304 bp promoter region showed a predominance of regulatory boxes involved in development, but not in defense...
2015: Frontiers in Plant Science
https://www.readbyqxmd.com/read/26297199/%C3%AE-lactalbumin-oleic-acid-complex-spontaneously-delivers-oleic-acid-to-artificial-and-erythrocyte-membranes
#7
Hanzhen Wen, Øyvind Strømland, Øyvind Halskau
Human α-lactalbumin made lethal to tumor cells (HAMLET) is a tumoricidal complex consisting of human α-lactalbumin and multiple oleic acids (OAs). OA has been shown to play a key role in the activity of HAMLET and its related complexes, generally known as protein-fatty acid (PFA) complexes. In contrast to what is known about the fate of the protein component of such complexes, information about what happens to OA during their action is still lacking. We monitored the membrane, OA and protein components of bovine α-lactalbumin complexed with OA (BLAOA; a HAMLET-like substance) and how they associate with each other...
September 25, 2015: Journal of Molecular Biology
https://www.readbyqxmd.com/read/26101738/the-cytotoxicity-of-bamlet-complexes-is-due-to-oleic-acid-and-independent-of-the-%C3%AE-lactalbumin-component
#8
Yamixa Delgado, Moraima Morales-Cruz, Cindy M Figueroa, José Hernández-Román, Glinda Hernández, Kai Griebenow
Lipid-protein complexes comprised of oleic acid (OA) non-covalently coupled to human/bovine α-lactalbumin, named HAMLET/BAMLET, display cytotoxic properties against cancer cells. However, there is still a substantial debate about the role of the protein in these complexes. To shed light into this, we obtained three different BAMLET complexes using varying synthesis conditions. Our data suggest that to form active BAMLET particles, OA has to reach critical micelle concentration with an approximate diameter of 250 nm...
2015: FEBS Open Bio
https://www.readbyqxmd.com/read/26028028/targeting-of-nucleotide-binding-proteins-by-hamlet-a-conserved-tumor-cell-death-mechanism
#9
J C S Ho, A Nadeem, A Rydström, M Puthia, C Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills tumor cells broadly suggesting that conserved survival pathways are perturbed. We now identify nucleotide-binding proteins as HAMLET binding partners, accounting for about 35% of all HAMLET targets in a protein microarray comprising 8000 human proteins. Target kinases were present in all branches of the Kinome tree, including 26 tyrosine kinases, 10 tyrosine kinase-like kinases, 13 homologs of yeast sterile kinases, 4 casein kinase 1 kinases, 15 containing PKA, PKG, PKC family kinases, 15 calcium/calmodulin-dependent protein kinase kinases and 13 kinases from CDK, MAPK, GSK3, CLK families...
February 18, 2016: Oncogene
https://www.readbyqxmd.com/read/25959494/tcr-itam-multiplicity-is-required-for-the-generation-of-follicular-helper-t-cells
#10
SuJin Hwang, Amy C Palin, LiQi Li, Ki-Duk Song, Jan Lee, Jasmin Herz, Noah Tubo, Hamlet Chu, Marion Pepper, Renaud Lesourne, Ekaterina Zvezdova, Julia Pinkhasov, Marc K Jenkins, Dorian McGavern, Paul E Love
The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire...
May 11, 2015: Nature Communications
https://www.readbyqxmd.com/read/25891934/the-evolutionarily-conserved-transcription-factor-prdm12-controls-sensory-neuron-development-and-pain-perception
#11
Vanja Nagy, Tiffany Cole, Claude Van Campenhout, Thang M Khoung, Calvin Leung, Simon Vermeiren, Maria Novatchkova, Daniel Wenzel, Domagoj Cikes, Anton A Polyansky, Ivona Kozieradzki, Arabella Meixner, Eric J Bellefroid, G Gregory Neely, Josef M Penninger
PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants...
2015: Cell Cycle
https://www.readbyqxmd.com/read/25755927/structure-determination-of-murine-norovirus-ns6-proteases-with-c-terminal-extensions-designed-to-probe-protease-substrate-interactions
#12
Humberto Fernandes, Eoin N Leen, Hamlet Cromwell, Marc-Philipp Pfeil, Stephen Curry
Noroviruses are positive-sense single-stranded RNA viruses. They encode an NS6 protease that cleaves a viral polyprotein at specific sites to produce mature viral proteins. In an earlier study we obtained crystals of murine norovirus (MNV) NS6 protease in which crystal contacts were mediated by specific insertion of the C-terminus of one protein (which contains residues P5-P1 of the NS6-7 cleavage junction) into the peptide binding site of an adjacent molecule, forming an adventitious protease-product complex...
2015: PeerJ
https://www.readbyqxmd.com/read/25681694/the-molecular-motor-f-atp-synthase-is-targeted-by-the-tumoricidal-protein-hamlet
#13
James Ho, Hendrik Sielaff, Aftab Nadeem, Catharina Svanborg, Gerhard Grüber
HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected...
May 22, 2015: Journal of Molecular Biology
https://www.readbyqxmd.com/read/25311339/titanium-surface-hydrophilicity-enhances-platelet-activation
#14
Mohammed A Alfarsi, Stephen M Hamlet, Saso Ivanovski
Titanium implant surface modification is a key strategy used to enhance osseointegration. Platelets are the first cells that interact with the implant surface whereupon they release a wide array of proteins that influence the subsequent healing process. This study therefore investigated the effect of titanium surface modification on the attachment and activation of human platelets. The surface characteristics of three titanium surfaces: smooth (SMO), micro-rough (SLA) and hydrophilic micro-rough (SLActive) and the subsequent attachment and activation of platelets following exposure to these surfaces were determined...
2014: Dental Materials Journal
https://www.readbyqxmd.com/read/24909201/the-effect-of-platelet-proteins-released-in-response-to-titanium-implant-surfaces-on-macrophage-pro-inflammatory-cytokine-gene-expression
#15
Mohammed A Alfarsi, Stephen M Hamlet, Saso Ivanovski
BACKGROUND AND PURPOSE: Platelets are one of the earliest cell types to interact with surgically inserted titanium implants. This in vitro study investigated the effect of titanium surface-induced platelet releasate on macrophage cytokine gene expression. MATERIALS AND METHODS: To mimic the in vivo temporal sequence of platelet arrival and protein production at the implant surface and the subsequent effect of these proteins on mediators of the immune response, the levels of platelet attachment and activation in response to culture on smooth polished, sandblasted and acid-etched (SLA), and hydrophilic-modified SLA (modSLA) titanium surfaces were first determined by microscopy and protein assay...
December 2015: Clinical Implant Dentistry and related Research
https://www.readbyqxmd.com/read/24857659/impact-of-regulated-secretion-on-antiparasitic-cd8-t-cell-responses
#16
Harshita Satija Grover, H Hamlet Chu, Felice D Kelly, Soo Jung Yang, Michael L Reese, Nicolas Blanchard, Federico Gonzalez, Shiao Wei Chan, John C Boothroyd, Nilabh Shastri, Ellen A Robey
CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma, but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen, ROP5, that elicits a CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense-granule antigen GRA6 is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses...
June 12, 2014: Cell Reports
https://www.readbyqxmd.com/read/24630726/swi-snf-complex-prevents-lineage-reversion-and-induces-temporal-patterning-in-neural-stem-cells
#17
Elif Eroglu, Thomas R Burkard, Yanrui Jiang, Nidhi Saini, Catarina C F Homem, Heinrich Reichert, Juergen A Knoblich
Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation...
March 13, 2014: Cell
https://www.readbyqxmd.com/read/24524762/potential-clinical-applications-of-multi-functional-milk-proteins-and-peptides-in-cancer-management
#18
REVIEW
H Y F Chen, O Mollstedt, Men-Hwei Tsai, R B Kreider
The progression of cancer involves multiple changes that alter intracellular signaling to promote cell proliferation. Subsequent remodeling of the tumor microenvironment enhances metastasis by manipulating the immune system. Research in the past decade has shown that milk proteins and peptides are often multi-functional, exerting activities such as anti-microbial, immunomodulatory, cancer cell apoptosis, anti-metastasis, and antioxidant effects. Several milk-derived biologics, such as HAMLET (human α-lactalbumin made lethal to tumor cells) and the human recombinant form of lactoferrin, already demonstrated promising results in clinical trials...
2014: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/24477824/benchmark-dose-of-cadmium-concentration-in-rice-for-renal-effects-in-a-cadmium-polluted-area-in-japan
#19
Kazuhiro Nogawa, Teruhiko Kido, Muneko Nishijo, Hideaki Nakagawa, Yasushi Suwazono
The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and β(2) -microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets...
January 2015: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/24408789/small-angle-x-ray-scattering-of-bamlet-at-ph-12-a-complex-of-%C3%AE-lactalbumin-and-oleic-acid
#20
Emma M Rath, Anthony P Duff, Anders P Håkansson, Robert B Knott, W Bret Church
BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration...
July 2014: Proteins
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