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https://www.readbyqxmd.com/read/28212731/hamlet-a-protein-lipid-complex-with-broad-tumoricidal-activity
#1
REVIEW
James C S Ho, Aftab Nadeem, Catharina Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28193539/dimeric-but-not-monomeric-%C3%AE-lactalbumin-potentiates-apoptosis-by-up-regulation-of-atf3-and-reduction-of-histone-deacetylase-activity-in-primary-and-immortalised-cells
#2
Julie A Sharp, Amelia J Brennan, Galina Polekhina, David B Ascher, Christophe Lefevre, Kevin R Nicholas
α-lactalbumin is a protein of dual function found in milk of most mammals. α-lactalbumin binds β-1,4-galactosyltransferase to form the regulatory subunit for lactose synthesis and has also been shown to cause cell death. This study shows, for the first time, that α-lactalbumin isolated in a rare 28kDa dimeric form induces cell death, while 14kDa monomeric α-lactalbumin is inactive. In contrast to the casein derived and chemically induced α-lactalbumin variants, MAL and HAMLET/BAMLET, the effects of 28kDa α-lactalbumin are calcium independent and, unlike MAL and HAMLET, 28kDa α-lactalbumin dimer causes cell death of primary mammary cells and a variety of immortalised cell lines, which are committed to cell death pathways within 1-4h of exposure...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28183170/physico-chemical-properties-of-late-incubation-egg-amniotic-fluid-and-a-potential-in-ovo-feed-supplement
#3
Apeh A Omede, Momenuzzaman M Bhuiyan, Fakrul A Islam, Paul A Iji
This study explored the physico-chemical properties of late-incubation egg amniotic fluid and a potential in ovo feed (IOF) supplement. Amniotic fluid was collected from broiler breeders (Ross 308, 51 weeks and Cobb 500, 35 weeks) on day 17 after incubation. A mixture of high-quality soy protein supplement - Hamlet Protein AviStart (HPA) was serially diluted in MilliQ water to obtain solutions ranging from 150 to 9.375 mg/ml. The mixtures were heat-treated (0, 30, 60 minutes) in a waterbath (80 oC) and then centrifuged to obtain supernatants...
January 26, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28066813/risks-posed-by-reston-the-forgotten-ebolavirus
#4
REVIEW
Diego Cantoni, Arran Hamlet, Martin Michaelis, Mark N Wass, Jeremy S Rossman
Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans...
November 2016: MSphere
https://www.readbyqxmd.com/read/28032906/3-dimensional-functionalized-polycaprolactone-hyaluronic-acid-hydrogel-constructs-for-bone-tissue-engineering
#5
Stephen M Hamlet, Cedryck Vaquette, Amit Shah, Dietmar W Hutmacher, Saso Ivanovski
AIM: Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts encapsulated in a hyaluronic acid (HA) hydrogel incorporating bone morphogenetic protein-7 (BMP-7). MATERIALS AND METHODS: HA-hydrogels containing human osteoblasts ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological / μ-CT examination and ELISA respectively...
December 29, 2016: Journal of Clinical Periodontology
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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