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https://www.readbyqxmd.com/read/28718923/using-homology-modeling-to-interrogate-binding-affinity-in-neutralization-of-ricin-toxin-by-a-family-of-single-domain-antibodies
#1
Andrea Bazzoli, David J Vance, Michael J Rudolph, Yinghui Rong, Siva Krishna Angalakurthi, Ronald T Toth, C Russell Middaugh, David B Volkin, David D Weis, John Karanicolas, Nicholas J Mantis
In this report we investigated, within a group of closely related single domain camelid antibodies (VH Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like VH Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer...
July 18, 2017: Proteins
https://www.readbyqxmd.com/read/28713816/effect-of-the-camelid-s-seminal-plasma-ovulation-inducing-factor-%C3%AE-ngf-a-kisspeptin-target-hypothesis
#2
REVIEW
Khalid El Allali, Najlae El Bousmaki, Hassan Ainani, Valérie Simonneaux
Female mammals are classified into spontaneous and induced ovulators based on the mechanism eliciting ovulation. Ovulation in spontaneous species (e.g., human, sheep, cattle, horse, pigs, and most rodents) occurs at regular intervals and depends upon the circulating estradiol. However, in induced ovulators (e.g., rabbits, ferrets, cats, and camelids), ovulation is associated with coitus. In the later, various factors have been proposed to trigger ovulation, including auditory, visual, olfactory, and mechanic stimuli...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28704956/rapid-and-direct-vhh-and-target-identification-by-staphylococcal-surface-display-libraries
#3
Marco Cavallari
Unbiased and simultaneous identification of a specific antibody and its target antigen has been difficult without prior knowledge of at least one interaction partner. Immunization with complex mixtures of antigens such as whole organisms and tissue extracts including tumoral ones evokes a highly diverse immune response. During such a response, antibodies are generated against a variety of epitopes in the mixture. Here, we propose a surface display design that is suited to simultaneously identify camelid single domain antibodies and their targets...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28699276/y-chromosome-and-mtdna-variation-confirms-independent-domestications-and-directional-hybridization-in-south-american-camelids
#4
J C Marín, K Romero, R Rivera, W E Johnson, B A González
Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally-inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex-specific markers (male specific Y-chromosome and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns...
July 11, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28690185/selection-of-similar-single-domain-antibodies-from-two-immune-vhh-libraries-obtained-from-two-alpacas-by-using-different-selection-methods
#5
Tengfei Li, Matthias Vandesquille, Sylvie Bay, Marc Dhenain, Benoît Delatour, Pierre Lafaye
The two most used methods to select camelid single-domain antibody-fragments (VHHs) are: displaying their repertoires on the surface of filamentous bacteriophages (phage display) or linking them to ribosomes (ribosome display). In this study, we compared specific VHHs isolated from two different immune libraries coming from two different alpacas by using these two selection methods. Three anti-GFAP (glial fibrillary acidic protein) VHHs were derived from an immune library obtained by ribosome display after immunization of one alpaca with purified GFAP, a protein expressed by astroglial cells...
July 6, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28679457/new-parasitological-findings-for-pre-hispanic-camelids
#6
V Taglioretti, M H Fugassa, D Rindel, N H Sardella
Paleoparasitological examination provides information of parasite-host associations in the past, shedding light on the geographical origin of some parasites, on the possible dispersal routes and on some of the processes that modelled the parasitic communities. The aim of the present study was to examine parasite remains present in camelid coprolites collected from the archaeological site Alero Destacamento Guardaparque, Patagonia and to discuss the paleoparasitological findings in a biogeographical and paleoecological context...
July 6, 2017: Parasitology
https://www.readbyqxmd.com/read/28677403/septicemia-and-meningoencephalitis-caused-by-listeria-monocytogenes-in-two-neonatal-llamas
#7
Ian K Hawkins, Marcia Ilha, Eman Anis, Rebecca P Wilkes
Listeriosis is a disease of humans and domestic mammals (mainly ruminants) with variable manifestations, primarily encephalitis, septicemia, and abortion. Although Listeria monocytogenes readily causes illness in ruminants, the prevalence among domestic South American camelids (llamas and alpacas) is low and has not been documented in their wild counterparts, the vicuna and guanaco. We describe herein the clinical signs, autopsy findings, and histopathology of septicemia and suppurative meningoencephalitis caused by L...
July 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28659884/fungal-glucosylceramide-specific-camelid-single-domain-antibodies-are-characterized-by-broad-spectrum-antifungal-activity
#8
Barbara De Coninck, Peter Verheesen, Christine M Vos, Inge Van Daele, Miguel F De Bolle, Joao V Vieira, Marnix Peferoen, Bruno P A Cammue, Karin Thevissen
Chemical crop protection is widely used to control plant diseases. However, the adverse effects of pesticide use on human health and environment, resistance development and the impact of regulatory requirements on the crop protection market urges the agrochemical industry to explore innovative and alternative approaches. In that context, we demonstrate here the potential of camelid single domain antibodies (VHHs) generated against fungal glucosylceramides (fGlcCer), important pathogenicity factors. To this end, llamas were immunized with purified fGlcCer and a mixture of mycelium and spores of the fungus Botrytis cinerea, one of the most important plant pathogenic fungi...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28659409/prevalence-of-mycobacterium-avium-subspecies-paratuberculosis-and-hepatitis-e-in-new-world-camelids-in-austria
#9
A Stanitznig, J L Khol, B Lambacher, S Franz, P Kralik, I Slana, P Vasickova, T Wittek
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of paratuberculosis in domestic ruminants and New World Camelids (NWC). Hepatitis E virus (HEV) is an important public health concern worldwide. The virus has been identified in several species, some of them serving as a reservoir for zoonotic HEV strains. Husbandry and breeding of llamas and alpacas have increased in Austria in recent years. Therefore, the aim of the present study was to evaluate the prevalence of MAP and HEV in NWC in Austria...
June 28, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28657418/chemically-defined-camelid-antibody-bioconjugate-for-the-magnetic-resonance-imaging-of-alzheimer-s-disease
#10
Matthias Vandesquille, Tengfei Li, Chrystelle Po, Christelle Ganneau, Pascal Lenormand, Clémence Dudeffant, Christian Czech, Fiona Grueninger, Charles Duyckaerts, Benoît Delatour, Marc Dhenain, Pierre Lafaye, Sylvie Bay
Today, molecular imaging of neurodegenerative diseases is mainly based on small molecule probes. Alternatively, antibodies are versatile tools that may be developed as new imaging agents. Indeed, they can be readily obtained to specifically target any antigen of interest and their scaffold can be functionalized. One of the critical issues involved in translating antibody-based probes to the clinic is the design and synthesis of perfectly-defined conjugates. Camelid single-domain antibody-fragments (VHHs) are very small and stable antibodies that are able to diffuse in tissues and potentially cross the blood brain barrier (BBB)...
June 28, 2017: MAbs
https://www.readbyqxmd.com/read/28649245/camelid-single-domain-antibodies-as-an-alternative-to-overcome-challenges-related-to-the-prevention-detection-and-control-of-neglected-tropical-diseases
#11
REVIEW
Carla F C Fernandes, Soraya Dos S Pereira, Marcos B Luiz, Juliana P Zuliani, Gilvan P Furtado, Rodrigo G Stabeli
Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen-antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28646705/identification-and-in-vitro-characterization-of-novel-nanobodies-against-human-granulocyte-colony-stimulating-factor-receptor-to-provide-inhibition-of-g-csf-function
#12
Hamid Bakherad, Seyed Latif Mousavi Gargari, Zargham Sepehrizadeh, Hossein Aghamollaei, Ramezan Ali Taheri, Maryam Torshabi, Mojtaba Tabatabaei Yazdi, Walead Ebrahimizadeh, Neda Setayesh
It has been shown that Granulocyte colony-stimulating factor (G-CSF) has a higher expression in malignant tumors, and anti-G-CSF therapy considerably decreases tumor growth, tumor vascularization and metastasis. Thus, blocking the signaling pathway of G-CSF could be beneficial in cancer therapy. This study is aimed at designing and producing a monoclonal nanobody that could act as an antagonist of G-CSF receptor. Nanobodies are the antigen binding fragments of camelid single-chain antibodies, also known as VHH...
June 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28646058/semen-collection-methods-in-alpacas
#13
REVIEW
M C Abraham, K de Verdier, R Båge, J M Morrell
South American camelids, particularly alpacas, are gaining in popularity outside their native lands. Reproductive biotechnologies, such as artificial insemination or embryo transfer with cryopreserved embryos, are more complicated in these species than many others due to differences in their reproductive physiology compared to the more commonly encountered domestic livestock. This article reviews the methods currently available for obtaining semen or spermatozoa from alpacas and describes some of the problems associated with handling the viscous seminal plasma characteristic of camelids...
June 24, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28642127/exploiting-sequence-and-stability-information-for-directing-nanobody-stability-engineering
#14
Patrick Kunz, Tilman Flock, Nicolas Soler, Moritz Zaiss, Cécile Vincke, Yann Sterckx, Damjana Kastelic, Serge Muyldermans, Jörg D Hoheisel
BACKGROUND: Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view of their broad range of applications in research, diagnostics and therapy, engineering their stability is of particular interest. One important aspect is the improvement of thermostability, because it can have immediate effects on conformational stability, protease resistance and aggregation propensity of the protein. METHODS: We analyzed the sequences and thermostabilities of 78 purified nanobody binders...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28587791/evaluation-of-anti-botulinum-neurotoxin-single-domain-antibodies-with-additional-optimization-for-improved-production-and-stability
#15
Lisa C Shriver-Lake, Dan Zabetakis, Ellen R Goldman, George P Anderson
Botulinum neurotoxin (BoNT) is a highly potent and lethal toxin, which even in minute quantities can lead to death. BoNT occurs in seven well described serotypes, A-G, and it is critical to not only detect the presence of BoNT, but also to determine the serotype to which a person has been exposed, as the degree of toxicity and persistence of symptoms varies greatly between the various types. Recently, Conway et al. 2010 developed single domain antibodies (sdAb), the recombinant variable domains of heavy-chain-only antibodies derived from camelids, for the detection of all seven serotypes of BoNT; identifying pairs of sdAb for each serotype they demonstrated the sensitive detection of each toxin...
June 3, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28528176/production-and-preclinical-assessment-of-camelid-immunoglobulins-against-echis-sochureki-venom-from-desert-of-rajasthan-india
#16
P D Tanwar, S K Ghorui, S K Kochar, Raghvendar Singh, N V Patil
Snakebite is a significant cause of death and disability in subsistent farming populations of rural India. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses. Because of complex fiscal reasons, the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region has been questioned time to time. In this study, we report successful immunisation of dromedaries (Camelus dromedarius) against the venom of Indian saw-scaled Viper- Echis carinatus sochureki...
May 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28497227/seroprevalence-of-neospora-caninum-and-toxoplasma-gondii-in-exotic-ruminants-and-camelids-in-the-czech-republic
#17
Eva Bártová, Kateřina Kobédová, Jiří Lamka, Radim Kotrba, Roman Vodička, Kamil Sedlák
Neospora caninum and Toxoplasma gondii are the protozoan parasites with definitive hosts from order Carnivora. Due to vertical transmission, both parasites can cause abortions and neonatal mortality that lead to significant productive and economic losses in the domestic ruminants. The aim of this study was to describe N. caninum and T. gondii seroprevalence in the group of frequently farmed captive exotic ruminants (n = 184) including Bovidae (barbary sheep, bezoar goat, common eland, American bison, water buffalo, and yak) and Camelidae (bactrian camel, guanaco, llama, and alpaca)...
July 2017: Parasitology Research
https://www.readbyqxmd.com/read/28490657/targeting-endogenous-proteins-for-degradation-through-the-affinity-directed-protein-missile-system
#18
Luke J Fulcher, Luke D Hutchinson, Thomas J Macartney, Craig Turnbull, Gopal P Sapkota
Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28471361/camelid-nanobodies-used-as-crystallization-chaperones-for-different-constructs-of-porm-a-component-of-the-type-ix-secretion-system-from-porphyromonas-gingivalis
#19
Yoan Duhoo, Jennifer Roche, Thi Trang Nhung Trinh, Aline Desmyter, Anaïs Gaubert, Christine Kellenberger, Christian Cambillau, Alain Roussel, Philippe Leone
PorM is a membrane protein that is involved in the assembly of the type IX secretion system (T9SS) in Porphyromonas gingivalis, a major bacterial pathogen that is responsible for periodontal disease in humans. In the context of structural studies of PorM to better understand T9SS assembly, four camelid nanobodies were selected, produced and purified, and their specific interaction with the N-terminal or C-terminal part of the periplasmic domain of PorM was investigated. Diffracting crystals were also obtained, and the structures of the four nanobodies were solved by molecular replacement...
May 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28443097/large-diversity-of-functional-nanobodies-from-a-camelid-immune-library-revealed-by-an-alternative-analysis-of-next-generation-sequencing-data
#20
Pieter Deschaght, Ana Paula Vintém, Marc Logghe, Miguel Conde, David Felix, Rob Mensink, Juliana Gonçalves, Jorn Audiens, Yanik Bruynooghe, Rita Figueiredo, Diana Ramos, Robbe Tanghe, Daniela Teixeira, Liesbeth Van de Ven, Catelijne Stortelers, Bruno Dombrecht
Next-generation sequencing (NGS) has been applied successfully to the field of therapeutic antibody discovery, often outperforming conventional screening campaigns which tend to identify only the more abundant selective antibody sequences. We used NGS to mine the functional nanobody repertoire from a phage-displayed camelid immune library directed to the recepteur d'origine nantais (RON) receptor kinase. Challenges to this application of NGS include accurate removal of read errors, correct identification of related sequences, and establishing meaningful inclusion criteria for sequences-of-interest...
2017: Frontiers in Immunology
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