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Article: Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.

bioRxiv : the preprint server for biology

2024

Abstract: New therapeutics are a priority for preventing and ... ...

Abstract	New therapeutics are a priority for preventing and eliminating
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.07.579302
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Article ; Online: Adenine-(methoxy)-ethoxy-P

Nassir, Molhm / Mirza, Salahuddin / Arad, Uri / Lee, Sangyong / Rafehi, Muhammad / Yaw Attah, Isaac / Renn, Christian / Zimmermann, Herbert / Pelletier, Julie / Sévigny, Jean / Müller, Christa E / Fischer, Bilha

Organic & biomolecular chemistry

2019 Volume 17, Issue 46, Page(s) 9913–9923

Abstract: Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) inhibitors have been suggested as a potential treatment for calcium pyrophosphate dihydrate (CPPD) deposition disease. Here, we targeted the development of improved NPP1 inhibitors based on acyclic ... ...

Abstract	Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) inhibitors have been suggested as a potential treatment for calcium pyrophosphate dihydrate (CPPD) deposition disease. Here, we targeted the development of improved NPP1 inhibitors based on acyclic mimics of Pα,α-phosphorodithioate-substituted adenine nucleotides, 7-10. The latter were obtained in a facile two-step synthesis from adenine-(methoxy)ethanol. Among analogs 7-10, adenine-(methoxy)ethoxy-Pα,α-dithio-triphosphate, 8, was the most potent NPP1 inhibitor both with purified enzyme (IC50 0.645 μM) and in osteoarthritic human chondrocytes (IC50 0.033 μM). Furthermore, it efficaciously (10-fold vs. control) inhibited ATP-induced CPPD in human articular chondrocytes. Importantly, 8 was a highly selective NPP1 inhibitor which showed only minor inhibition of NPP3, CD39 and CD73, and did not inhibit TNAP (tissue nonspecific alkaline phosphatase) activity in human chondrocytes. Furthermore, 8 did not activate P2Y1,2,6 receptors. Analog 8 was not toxic to cultured chondrocytes at 100 μM. Therefore, 8 may be suitable for further development as a drug candidate for the treatment of CPPD arthritis and other NPP1-related diseases.
MeSH term(s)	Adenine/chemical synthesis ; Adenine/chemistry ; Adenine/pharmacology ; Calcium Pyrophosphate/antagonists & inhibitors ; Calcium Pyrophosphate/metabolism ; Cell Survival/drug effects ; Cells, Cultured ; Chondrocytes/drug effects ; Chondrocytes/metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; Molecular Structure ; Osteoarthritis, Knee/drug therapy ; Osteoarthritis, Knee/metabolism ; Osteoarthritis, Knee/pathology ; Phosphoric Diester Hydrolases/metabolism ; Polyphosphates/chemistry ; Polyphosphates/pharmacology ; Pyrophosphatases/antagonists & inhibitors ; Pyrophosphatases/metabolism ; Structure-Activity Relationship ; Sulfhydryl Compounds/chemistry ; Sulfhydryl Compounds/pharmacology
Chemical Substances	Enzyme Inhibitors ; Polyphosphates ; Sulfhydryl Compounds ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-) ; Adenine (JAC85A2161) ; triphosphoric acid (NU43IAG5BC) ; Calcium Pyrophosphate (X69NU20D19)
Language	English
Publishing date	2019-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2097583-1
ISSN	1477-0539 ; 1477-0520
ISSN (online)	1477-0539
ISSN	1477-0520
DOI	10.1039/c9ob02199j
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Article ; Online: Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice.

Science translational medicine

2021 Volume 13, Issue 596

Abstract: ... understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury ... but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients ... of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain ...

Abstract	Compelling evidence supports vascular contributions to cognitive impairment and dementia (VCID) including Alzheimer's disease (AD), but the underlying pathogenic mechanisms and treatments are not fully understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury, but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients with VCID and in mice modeling key aspects of clinical VCID, likely because of the inhibition of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain-specific Pin1 overexpression, or DAPK1 knockout effectively rescues VCID-like neurodegeneration and cognitive impairment in executive function. Cis mAb also prevents and ameliorates progression of AD-like neurodegeneration and memory loss in mice. Furthermore, single-cell RNA sequencing revealed that young VCID mice display diverse cortical cell type-specific transcriptomic changes resembling old patients with AD, and the vast majority of these global changes were recovered by cis-targeted immunotherapy. Moreover, purified soluble cis P-tau was sufficient to induce progressive neurodegeneration and brain dysfunction by causing axonopathy and conserved transcriptomic signature found in VCID mice and patients with AD with early pathology. Thus, cis P-tau might play a major role in mediating VCID and AD, and antibody targeting it may be useful for early diagnosis, prevention, and treatment of cognitive impairment and dementia after neurovascular insults and in AD.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/therapy ; Animals ; Brain/metabolism ; Cognitive Dysfunction/therapy ; Dementia, Vascular/therapy ; Humans ; Immunotherapy ; Mice ; NIMA-Interacting Peptidylprolyl Isomerase ; tau Proteins/metabolism
Chemical Substances	NIMA-Interacting Peptidylprolyl Isomerase ; tau Proteins ; PIN1 protein, human (EC 5.2.1.8)
Language	English
Publishing date	2021-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aaz7615
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Article ; Online: Elucidating the conformational change and electronic absorption spectrum of p-dimethylamino-cinnamaldehyde merocyanine across different solvent polarities.

Franco, Leandro R / Fonseca, Tertius L / Coutinho, Kaline / Georg, Herbert C

The Journal of chemical physics

2023 Volume 159, Issue 7

Abstract: We present a theoretical study on the structural and electronic properties of the p-dimethylamino ...

Abstract	We present a theoretical study on the structural and electronic properties of the p-dimethylamino-cinnamaldehyde (DMACA) merocyanine molecule in solvents of different polarities by combining the free energy gradient and the average solvent electrostatic configuration methods via an iterative procedure based on the sequential quantum mechanics/molecular mechanics hybrid methodology. Studying such a system in solution is a crucial step for understanding the solvent effects on its properties, which can have implications in fields such as optoelectronics and biophysics. We found that the DMACA molecule presents different geometries in nonpolar and polar solvents, changing from a polyene-like structure with a pyramidal dimethylamino group (in gas phase or nonpolar solvents) to a cyanine-like structure with a planar dimethylamino group in water due to the stabilizing effect of hydrogen bonds between DMACA and water. The molecular absorption spectrum showed a significant change, increasing solvent polarity with a large shift of the lower energy band, while the other two low lying bands did not shift significantly. The study accurately described the solvatochromic shift of the lowest-energy band and analyzed the structure of the excited states in terms of the one-electron transition density matrix, which showed that the dominant excited state (associated with the first lower energy band) is characterized by a local excitation on the benzene ring with charge transfer character to the carbon conjugated segment.
Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0158994
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Article ; Online: Gain of function p.E138A alteration in Card14 leads to psoriasiform skin inflammation and implicates genetic modifiers in disease severity.

Sundberg, John P / Pratt, C Herbert / Silva, Kathleen A / Kennedy, Victoria E / Qin, Wenning / Stearns, Timothy M / Frost, Jacqueline / Sundberg, Beth A / Bowcock, Anne M

Experimental and molecular pathology

2019 Volume 110, Page(s) 104286

Abstract: ... to the development of PS and psoriatic arthritis (PSA) (a familial p.G117S and de-novo p.E138A alteration ...

Abstract	Psoriasis (PS) is a common inflammatory and incurable skin disease affecting 2-3% of the human population. Although genome-wide association studies implicate more than 60 loci, the full complement of genetic factors leading to disease is not known. Rare, highly penetrant, gain-of-function, dominantly acting mutations within the human caspase recruitment domain family, member 14 (CARD14) gene lead to the development of PS and psoriatic arthritis (PSA) (a familial p.G117S and de-novo p.E138A alteration). These residues are conserved in mouse and orthologous Knock-In (KI) mutations within Card14 were created. The Card14
MeSH term(s)	Animals ; CARD Signaling Adaptor Proteins/genetics ; CARD Signaling Adaptor Proteins/physiology ; Female ; Gain of Function Mutation ; Gene Knock-In Techniques ; Genes, Modifier ; Guanylate Cyclase/genetics ; Guanylate Kinases/physiology ; Humans ; Inflammation/genetics ; Inflammation/pathology ; Membrane Proteins/genetics ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Knockout ; Psoriasis/genetics ; Psoriasis/pathology ; Severity of Illness Index ; Skin Diseases/genetics ; Skin Diseases/pathology ; Transcriptome
Chemical Substances	CARD Signaling Adaptor Proteins ; Membrane Proteins ; Card14 protein, mouse (EC 2.7.4.8) ; Guanylate Kinases (EC 2.7.4.8) ; CARD14 protein, human (EC 4.6.1.-) ; Guanylate Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2019-07-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2019.104286
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Article ; Online: Rational design of a hypoallergenic Phl p 7 variant for immunotherapy of polcalcin-sensitized patients.

Raith, Marianne / Zach, Doris / Sonnleitner, Linda / Woroszylo, Konrad / Focke-Tejkl, Margarete / Wank, Herbert / Graf, Thorsten / Kuehn, Annette / Pascal, Mariona / Muñoz-Cano, Rosa Maria / Wortmann, Judith / Aschauer, Philipp / Keller, Walter / Braeuer, Simone / Goessler, Walter / Swoboda, Ines

Scientific reports

2019 Volume 9, Issue 1, Page(s) 7802

Abstract: ... a hypoallergenic variant of the grass pollen polcalcin Phl p 7 by introducing specific point mutations ... performed with sera from Phl p 7-sensitized patients showed a drastically reduced IgE reactivity of the Phl ... p 7 mutant in comparison to wildtype Phl p 7, and basophil activation assays indicated ...

Abstract	Polcalcins are important respiratory panallergens, whose IgE-binding capacity depends on the presence of calcium. Since specific immunotherapy is not yet available for the treatment of polcalcin-sensitized patients, we aimed to develop a molecule for efficient and safe immunotherapy. We generated a hypoallergenic variant of the grass pollen polcalcin Phl p 7 by introducing specific point mutations into the allergen's calcium-binding regions. We thereby followed a mutation strategy that had previously resulted in a hypoallergenic mutant of a calcium-binding food allergen, the major fish allergen parvalbumin. Dot blot assays performed with sera from Phl p 7-sensitized patients showed a drastically reduced IgE reactivity of the Phl p 7 mutant in comparison to wildtype Phl p 7, and basophil activation assays indicated a significantly reduced allergenic activity. Rabbit IgG directed against mutant rPhl p 7 blocked patients' IgE binding to wildtype Phl p 7, indicating the mutant's potential applicability for immunotherapy. Mass spectrometry and circular dichroism experiments showed that the mutant had lost the calcium-binding capacity, but still represented a folded protein. In silico analyses revealed that the hypoallergenicity might be due to fewer negative charges on the molecule's surface and an increased molecular flexibility. We thus generated a hypoallergenic Phl p 7 variant that could be used for immunotherapy of polcalcin-sensitized individuals.
MeSH term(s)	Animals ; Antigens, Plant/genetics ; Antigens, Plant/immunology ; Antigens, Plant/therapeutic use ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/immunology ; Calcium-Binding Proteins/therapeutic use ; Female ; Humans ; Immunoglobulin E/immunology ; Immunotherapy ; Male ; Models, Molecular ; Poaceae/immunology ; Point Mutation ; Pollen/immunology ; Protein Engineering ; Rabbits ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Recombinant Proteins/therapeutic use ; Rhinitis, Allergic, Seasonal/immunology ; Rhinitis, Allergic, Seasonal/therapy
Chemical Substances	Antigens, Plant ; Calcium-Binding Proteins ; Phl p 7 allergen ; Recombinant Proteins ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2019-05-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-44208-0
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Article ; Online: High-purity cellulose production from birch wood by γ-valerolactone/water fractionation and IONCELL-P process.

Shokri, Shokoufeh / Hedjazi, Sahab / Lê, Huy Quang / Abdulkhani, Ali / Sixta, Herbert

Carbohydrate polymers

2022 Volume 288, Page(s) 119364

Abstract: ... of pulp, IONCELL-P (IP). A paper grade pulp was produced from optimal GVL cook with a similar composition ... the IONCELL-P process. The purity of the GVL-IP pulp significantly exceeded that of commercial prehydrolysis ... kraft (PHK) and prehydrolysis soda-anthraquinone (PH-Soda-AQ) pulps. IONCELL-P extraction removed more ...

Abstract	This study presents an environmentally friendly process to produce high-purity cellulose (dissolving pulp) from birch wood by combining γ-valerolactone (GVL)/water fractionation and ionic liquid treatment of pulp, IONCELL-P (IP). A paper grade pulp was produced from optimal GVL cook with a similar composition to birch kraft pulp and was bleached with ECF sequence before the hemicelluloses were removed using the IONCELL-P process. The purity of the GVL-IP pulp significantly exceeded that of commercial prehydrolysis kraft (PHK) and prehydrolysis soda-anthraquinone (PH-Soda-AQ) pulps. IONCELL-P extraction removed more than 90% of the hemicelluloses, resulting in a dissolving pulp with a purity of 96% and a high molecular mass fraction, 2.3 times higher than that of a conventional PHK pulp. GVL-IP pulps are suitable not only for regenerated cellulose fibers or films, but also for high-purity, high-viscosity cellulose acetate and ethers, which cannot be produced in an environmentally friendly way by conventional processes.
MeSH term(s)	Betula ; Cellulose ; Lactones ; Water ; Wood
Chemical Substances	Lactones ; Water (059QF0KO0R) ; Cellulose (9004-34-6) ; gamma-valerolactone (O7056XK37X)
Language	English
Publishing date	2022-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2022.119364
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Article ; Online: Victor P. Whittaker (1919-2016).

Zimmermann, Herbert / Fonnum, Frode

Journal of neurochemistry

2016 Volume 139, Issue 2, Page(s) 333–335

Abstract: This Obituary honors Victor P. Whittaker, one of the pioneers in the field of neurochemistry ...

Abstract	This Obituary honors Victor P. Whittaker, one of the pioneers in the field of neurochemistry. Victor Whittaker died on 5th July 2016 aged 97 in Cambridge (UK) after a short illness. Victor is best known for his landmark advances in the subcellular fractionation of brain tissue which led to the isolation of synaptosomes and subsequently synaptic vesicles at the beginning of the 1960s and for the cellular and molecular analysis of the cholinergic synapse.
MeSH term(s)	Brain Chemistry ; Cholinesterases/genetics ; England ; Germany ; History, 20th Century ; History, 21st Century ; Neurochemistry/history ; Synaptosomes
Chemical Substances	Cholinesterases (EC 3.1.1.8)
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Biography ; Historical Article ; Journal Article ; Portraits
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.13778
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Article ; Online: Oxygenation promotes vegetable growth by enhancing P nutrient availability and facilitating a stable soil bacterial community in compacted soil

Wang, Rui / Shi, Weiming / Kronzucker, Herbert J. / Li, Yilin

Soil & Tillage Research. 2023 June, v. 230 p.105686-

2023

Abstract: ... decreased malondialdehyde content. Oxygenation furthermore increased phosphorus (P) bioavailability ... Firmicutes and Proteobacteria), with an increase in DGT-P by 10.5–23.6 % compared to control. The soil ...

Abstract	Soil compaction is a widespread phenomenon in intensive agriculture and can severely hamper root growth and crop yield. Hydrogen peroxide urea (UHP) has been employed as an effective measure for oxygenation in dryland systems. However, whether oxygenation via UHP could alleviate negative effects on vegetable growth induced by soil compaction is unknown. A pot experiment involving different soil bulk densities (1.2, 1.5, and 1.7 g cm⁻³) with oxygenation at different stages of development (seedling stage, mid-growth stage) was conducted in amaranth (A. mangostanus), with non-oxygenation at different soil bulk densities as a control. Increased soil compaction affected vegetative growth of both the shoot and root system of amaranth and caused yield reduction. Oxygenation in topdressing significantly improved soil O₂ supply until the harvest period, imparted 17.9–20.4 % additional O₂ to soils. Increased O₂ supply alleviated soil compaction stress, and amaranth yield increased by 5.50–16.1 % at the same soil bulk density compared with control, respectively. Oxygenation during the mid-growth stage had a superior effect on vegetable growth compared to oxygenation at the seedling stage, coincident with the higher oxygen demand during mid-growth in amaranth. Oxygenation promoted root growth in compacted soil, and increased root length by 76.3 % at a soil bulk density of 1.5 g cm⁻³ and 74.7 % at a bulk density of 1.7 g cm⁻³ compared with control. The alleviatory effect on the root system can be linked to increased root catalase activity and decreased malondialdehyde content. Oxygenation furthermore increased phosphorus (P) bioavailability by increasing both phosphatase activity and the relative abundance of phosphate-solubilizing bacteria (Firmicutes and Proteobacteria), with an increase in DGT-P by 10.5–23.6 % compared to control. The soil bacterial co-occurrence network at a soil bulk density of 1.5 g cm⁻³ with oxygenation was more similar to 1.2 g cm⁻³ soil compaction with oxygenation, which possessed most complex and the proportion of connectors, but was dissimilar from 1.7 g cm⁻³ soil compaction with oxygenation, which was less stable microbial network structure. Improvement of O₂ content could build a healthy and stable rhizosphere bacterial community, and increased the proportion of important nodes in the network, which was conducive to the collaborative development of microorganisms to face compaction stress. And bacterial community structure with oxygenation in compacted soil could recovery to near normal microbiology community structure. The research provides a theoretical and technical framework for the development of strategies that can maximize crop yield in compacted soil.
Keywords	Firmicutes ; Proteobacteria ; arid lands ; bacterial communities ; bulk density ; catalase ; community structure ; compacted soils ; crop yield ; harvest date ; hydrogen peroxide ; intensive farming ; malondialdehyde ; nutrient availability ; oxygen ; phosphorus ; research ; rhizosphere ; root growth ; root systems ; seedlings ; soil bacteria ; soil compaction ; soil density ; tillage ; urea ; vegetables ; vegetative growth ; Oxygenation ; Vegetable crops ; Bacteria ; Microbial co-occurrence network
Language	English
Dates of publication	2023-06
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	406698-4
ISSN	0167-1987
ISSN	0167-1987
DOI	10.1016/j.still.2023.105686
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Article ; Online: Conceptualizing life via non-equilibrium physics; is it enough?: Comment on "Unified representation of life's basic properties by a 3-species stochastic cubic autocatalytic reaction-diffusion system of equations" by A.P. Muñuzuri and J. Pérez-Mercader.

Levine, Herbert

Physics of life reviews

2023 Volume 45, Page(s) 71–73

MeSH term(s)	Life ; Physics
Language	English
Publishing date	2023-04-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2148883-6
ISSN	1873-1457 ; 1571-0645
ISSN (online)	1873-1457
ISSN	1571-0645
DOI	10.1016/j.plrev.2023.04.007
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