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Carlos Raúl Belotti López de Medina, Lautaro López Geronazzo, Clarisa Otero
This paper reports the results of a zooarchaeological analysis conducted on the occupation layer of a compound structure (Residential Unit 1) of the Pucara de Tilcara archaeological site (Jujuy Province, northwestern Argentina). Its occupation span extends between the 13th and 15th centuries AD, but evidence diagnostic of the Inka Period (AD 1430-1536) is predominant. Residential Unit 1 was a house-workshop that hosted specialized crafts like metallurgy and lapidary during the Inka Period. It was proposed in previous works that artisans living at Pucara de Tilcara were provisioned with agropastoral products by the Inka administration...
2016: PloS One
Miguel A Soler, Ario de Marco, Sara Fortuna
Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features...
October 10, 2016: Scientific Reports
Natalie Krahn, Maureen Spearman, Markus Meier, July Dorion-Thibaudeau, Matthew McDougall, Trushar R Patel, Gregory De Crescenzo, Yves Durocher, Jörg Stetefeld, Michael Butler
Glycoengineering of mAbs has become common practice in attempts to generate the ideal mAb candidate for a wide range of therapeutic applications. The effects of these glycan modifications on the binding affinity of IgG mAbs for FcγRIIIa and their cytotoxicity is well known. However, little is understood about the effect that these modifications have on binding to the high affinity FcγRI receptor. This study analysed the effect of variable N-glycosylation on a human-llama hybrid mAb (EG2-hFc, 80 kDa) binding to FcγRI including a comparison to a full-sized IgG1 (DP-12, 150 kDa)...
October 6, 2016: European Journal of Pharmaceutical Sciences
Parameswaran Hariharan, Magnus Andersson, Xiaoxu Jiang, Els Pardon, Jan Steyaert, H Ronald Kaback, Lan Guan
Camelid nanobodies (Nbs) raised against the outward-facing conformer of a double-Trp mutant of the lactose permease of Escherichia coli (LacY) stabilize the permease in outward-facing conformations. Isothermal titration calorimetry is applied herein to dissect the binding thermodynamics of two Nbs, one that markedly improves access to the sugar-binding site and another that dramatically increases the affinity for galactoside. The findings presented here show that both enthalpy and entropy contribute favorably to binding of the Nbs to wild-type (WT) LacY and that binding of Nb to double-Trp mutant G46W/G262W is driven by a greater enthalpy at an entropic penalty...
October 12, 2016: Biochemistry
Timothy M Pabst, Michaela Wendeler, Xiangyang Wang, Sandra Bezemer, Pim Hermans, Alan K Hunter
Interest in new and diverse classes of molecules such as recombinant toxins, enzymes, and blood factors continues to grow for use a biotherapeutics. Compared to monoclonal antibodies, these novel drugs typically lack a commercially available affinity chromatography option, which leads to greater process complexity, longer development timelines, and poor platformability. To date, for both monoclonal antibodies and novel molecules, affinity chromatography has been mostly reserved for separation of process-related impurities such as host cell proteins and DNA...
September 27, 2016: Biotechnology Journal
Tengfei Li, Matthias Vandesquille, Fani Koukouli, Clémence Dudeffant, Ihsen Youssef, Pascal Lenormand, Christelle Ganneau, Uwe Maskos, Christian Czech, Fiona Grueninger, Charles Duyckaerts, Marc Dhenain, Sylvie Bay, Benoît Delatour, Pierre Lafaye
Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer's disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles...
October 5, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Sven O Dahms, John W M Creemers, Yvonne Schaub, Gleb P Bourenkov, Thomas Zögg, Hans Brandstetter, Manuel E Than
Proprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2...
September 27, 2016: Scientific Reports
Ema Romão, Francisco Morales-Yánez, Yaozhong Hu, Maxine Crauwels, Pieter De Pauw, Gholamreza Ghassanzadeh Hassanzadeh, Nick Devoogdt, Chloé Ackaert, Cécile Vincke, Serge Muyldermans
BACKGROUND: The discovery of functional heavy chain-only antibodies devoid of light chains in sera of camelids and sharks in the early nineties provided access to the generation of minimal-sized, single-domain, in vivo affinity-matured, recombinant antigen-binding fragments, also known as Nanobodies. METHODS: Recombinant DNA technology and adaptation of phage display vectors form the basis to construct large naïve, synthetic or medium sized immune libraries from where multiple Nanobodies have been retrieved...
September 23, 2016: Current Pharmaceutical Design
Zhengfei Wang, Shixia Xu, Kexing Du, Fang Huang, Zhuo Chen, Kaiya Zhou, Wenhua Ren, Guang Yang
Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i...
September 20, 2016: Molecular Biology and Evolution
Fereniki Perperopoulou, Farid S Ataya, Dalia Fouad, Ajamaluddin Malik, Hesham Mahmoud Saeed, Nikolaos E Labrou
Glutathione transferase (GST, EC is a primary line of defense against toxicities of electrophile compounds and oxidative stress and therefore is involved in stress-response and cell detoxification. In the present study, we investigated the catalytic and structural properties of the glutathione transferase (GST) isoenzyme P1-1 from Camelus dromedarius (CdGSTP1-1). Recombinant CdGSTP1-1 was produced in Escherichia coli BL21(DE3) and purified to electrophoretic homogeneity. Kinetic analysis revealed that CdGSTP1-1 displays broad substrate specificity and shows high activity towards halogenated aryl-compounds, isothiocyanates and hydroperoxides...
September 17, 2016: Cell Biochemistry and Biophysics
Kevin A Henry, Traian Sulea, Henk van Faassen, Greg Hussack, Enrico O Purisima, C Roger MacKenzie, Mehdi Arbabi-Ghahroudi
Staphylococcal protein A (SpA) and streptococcal protein G (SpG) affinity chromatography are the gold standards for purifying monoclonal antibodies (mAbs) in therapeutic applications. However, camelid VHH single-domain Abs (sdAbs or VHHs) are not bound by SpG and only sporadically bound by SpA. Currently, VHHs require affinity tag-based purification, which limits their therapeutic potential and adds considerable complexity and cost to their production. Here we describe a simple and rapid mutagenesis-based approach designed to confer SpA binding upon a priori non-SpA-binding VHHs...
2016: PloS One
Mara Martin, Cecilia Decker Franco, Sandra Romero, Tamara Carletti, Leonhard Schnittger, Monica Florin-Christensen
Sarcocystis aucheniae are apicomplexan protozoa that infect South American camelids (SACs), giving rise to macroscopic cysts similar to rice grains in skeletal muscles. Visual detection of macrocysts in slaughtered animals hampers commercialization of SAC meat, a highly relevant economic exploitation for Andean rural families. Importantly, the consumption of undercooked S. aucheniae-infested meat causes gastroenteritis. A carnivore definitive host, possibly the dog, acquires the parasite when feeding on infected SAC meat, and later eliminates infective oocysts in its feces...
July 2016: Revista Argentina de Microbiología
Floriane Noel, Alain Malpertuy, Alexandre G de Brevern
The VHHs are antigen-binding region/domain of camelid heavy chain antibodies (HCAb). They have many interesting biotechnological and biomedical properties due to their small size, high solubility and stability, and high affinity and specificity for their antigens. HCAb and classical IgGs are evolutionary related and share a common fold. VHHs are composed of regions considered as constant, called the frameworks (FRs) connected by Complementarity Determining Regions (CDRs), a highly variable region that provide interaction with the epitope...
September 6, 2016: Biochimie
Ryan M Wallace, Michael Niezgoda, Emily A Waggoner, Jesse Dean Blanton, Rachel A Radcliffe
CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression. CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection. TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results...
September 15, 2016: Journal of the American Veterinary Medical Association
Florian I Schmidt, Leo Hanke, Benjamin Morin, Rebeccah Brewer, Vesna Brusic, Sean P J Whelan, Hidde L Ploegh
Manipulation of proteins is key in assessing their in vivo function. Although genetic ablation is straightforward, reversible and specific perturbation of protein function remains a challenge. Single domain antibody fragments, such as camelid-derived VHHs, can serve as inhibitors or activators of intracellular protein function, but functional testing of identified VHHs is laborious. To address this challenge, we have developed a lentiviral screening approach to identify VHHs that elicit a phenotype when expressed intracellularly...
2016: Nature Microbiology
M I Carretero, S M Giuliano, C C Arraztoa, R C Santa Cruz, F G Fumuso, D M Neild
Seminal plasma (SP) of South American Camelids could interfere with the interaction of spermatozoa with the extenders; therefore it becomes necessary to improve semen management using enzymatic treatment. Our objective was to compare two cooling protocols for llama semen. Twelve ejaculates were incubated in 0.1% collagenase and then were divided into two aliquots. One was extended in lactose and egg yolk (LEY) (Protocol A: collagenase and SP present). The other aliquot was centrifuged, and the pellet was resuspended in LEY (Protocol B: collagenase and SP absent)...
August 25, 2016: Andrologia
Marie Godar, Virginia Morello, Ava Sadi, Anna Hultberg, Natalie De Jonge, Cristina Basilico, Valérie Hanssens, Michael Saunders, Bart N Lambrecht, Mohamed El Khattabi, Hans de Haard, Paolo Michieli, Christophe Blanchetot
Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm...
2016: Scientific Reports
Esayas Gelaye, Jenna Elizabeth Achenbach, Gelagay Ayelet, Shiferaw Jenberie, Martha Yami, Reingard Grabherr, Angelika Loitsch, Adama Diallo, Charles Euloge Lamien
Camelpox and camel contagious ecthyma are infectious viral diseases of camelids caused by camelpox virus (CMLV) and camel contagious ecthyma virus (CCEV), respectively. Even though, in Ethiopia, pox disease has been creating significant economic losses in camel production, little is known on the responsible pathogens and their genetic diversity. Thus, the present study aimed at isolation, identification and genetic characterization of the causative viruses. Accordingly, clinical case observations, infectious virus isolation, and molecular and phylogenetic analysis of poxviruses infecting camels in three regions and six districts in the country, Afar (Chifra), Oromia (Arero, Miyu and Yabello) and Somali (Gursum and Jijiga) between 2011 and 2014 were undertaken...
October 2016: Antiviral Research
Rodrigo Carrasco, Jaswant Singh, Gregg P Adams
BACKGROUND: Ovulation-inducing factor in semen (OIF/NGF) influences ovulation and CL form and function in camelids and, remarkably, in cows. To test the hypothesis that the luteotrophic effect of OIF/NGF is mediated by an increase in trkA receptors in the ovulatory follicle and early CL, a study was designed to characterize the spatial and temporal distribution of trkA in ovarian follicles and CL at known stages of the bovine estrous cycle. METHODS: Sexually mature cattle (n = 14) were examined daily by transrectal ultrasonography to determine the day of ovulation (Day 0), and assigned randomly to be unilaterally ovariectomized on Day 2, 4, 6 or in the pre-ovulatory period just before or after exogenous LH treatment...
2016: Reproductive Biology and Endocrinology: RB&E
Sonja Franz, Joachim Spergser, Ilse Schwendenwein, Anna Stanitznig, Bianca Lambacher, Alexander Tichy, Thomas Wittek
Reports of CMhl infections in South American Camelids in Europe are only available from the United Kingdom and Switzerland. Knowing that CMhl infections can lead to severe disease resulting in death if combined with other diseases or stress, it was the aim of this study to assess prevalence data from camelids in Austria. In comparison to the previous studies a representative number of camelids was investigated nationwide. Data were assessed due to differences in geographical region, age, sex, species, and origin...
July 2016: Berliner und Münchener Tierärztliche Wochenschrift
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