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genomics and zoonotic infections: middle east respiratory syndrome.the emergence of middle east respiratory syndrome (mers) and the discovery of mers coronavirus (mers-cov) in 2012 suggests that another sars-like epidemic is occurring. unlike the severe acute respiratory syndrome (sars) epidemic, which rapidly disappeared in less than one year, mers has persisted for over three years. more than 1,600 cases of mers have been reported worldwide, and the disease carries a worryingly high fatality rate of >30%. a total of 182 mers-cov genomes have been sequenced, i ...201627217178
dystocia in dromedary camels: prevalence, forms, risks and hematobiochemical changes.the objectives of this study were to investigate the prevalence of dystocia in camel herds, its forms in primi- and multipara, the risks to fetus and dam, and the associated hematobiochemical changes. a total of 1890 calvings were surveyed for the prevalence of dystocia. cases with dystocia (n=107) were examined for causes and treated with traction, fetotomy or cesarean section. logistic regression was performed to identify risk factors. the dependent variables were the fetal and maternal mortal ...201627211280
ancient and modern dna reveal dynamics of domestication and cross-continental dispersal of the dromedary.dromedaries have been fundamental to the development of human societies in arid landscapes and for long-distance trade across hostile hot terrains for 3,000 y. today they continue to be an important livestock resource in marginal agro-ecological zones. however, the history of dromedary domestication and the influence of ancient trading networks on their genetic structure have remained elusive. we combined ancient dna sequences of wild and early-domesticated dromedary samples from arid regions wi ...201627162355
structural analysis of nested neutralizing and non-neutralizing b cell epitopes on ricin toxin's enzymatic subunit.in this report, we describe the x-ray crystal structures of two single domain camelid antibodies (vh h), f5 and f8, each in complex with ricin toxin's enzymatic subunit (rta). f5 has potent toxin-neutralizing activity, while f8 has weak neutralizing activity. f5 buried a total of 1760 å(2) in complex with rta and made contact with three prominent secondary structural elements: α-helix b (residues 98-106), β-strand h (residues 113-117), and the c-terminus of α-helix d (residues 154-156). f8 burie ...201627159829
papain and its inhibitor e-64 reduce camelid semen viscosity without impairing sperm function and improve post-thaw motility rates.in camelids, the development of assisted reproductive technologies is impaired by the viscous nature of the semen. the protease papain has shown promise in reducing viscosity, although its effect on sperm integrity is unknown. the present study determined the optimal papain concentration and exposure time to reduce seminal plasma viscosity and investigated the effect of papain and its inhibitor e-64 on sperm function and cryopreservation in alpacas. papain (0.1 mg ml-1, 20 min, 37°c) eliminated ...201627156102
cerebrospinal nematodiasis in 20 camelids.information about the clinical and clinicopathologic aspects of cerebrospinal nematodiasis (cn) in camelids is limited.201627155894
relationship between external and internal udder and teat measurements of machine milked dromedary camels.this study aims to determine the relationship between internal and external udder and teat measurements and evaluate their correlation with milk yield and milk partitioning in the udder of dromedary camels. six maghrebi camels reared under intensive conditions were monitored at early, middle, and late lactation. udder measurements included udder depth, udder horizontal circumference, fore and rear teat length and diameter. besides, scans of the left fore and rear quarters were taken in duplicate ...201627129886
structural mimicry of receptor interaction by antagonistic interleukin-6 (il-6) antibodies.interleukin 6 plays a key role in mediating inflammatory reactions in autoimmune diseases and cancer, where it is also involved in metastasis and tissue invasion. neutralizing antibodies against il-6 and its receptor have been approved for therapeutic intervention or are in advanced stages of clinical development. here we describe the crystal structures of the complexes of il-6 with two fabs derived from conventional camelid antibodies that antagonize the interaction between the cytokine and its ...201627129274
complete genome sequence of middle east respiratory syndrome coronavirus isolated from a dromedary camel in egypt.we generated the near-full genome sequence of middle east respiratory syndrome coronavirus (mers-cov) from a collected nasal sample of dromedary camel in egypt. the newly characterized egyptian strain has high similarity to the previously characterized egyptian virus and both of viruses fell into a cluster distinct from other mers-covs.201627125484
emerging site-specific bioconjugation strategies for radioimmunotracer development.radioimmunotracers are a promising class of companion diagnostics for precision medicine. they are composed of an antibody-based targeting agent and a radiolabeled imaging probe. together with the tendency towards the use of small antibody-derived fragments, the employed conjugation method is gaining increasing attention. conventional bioconjugation methods result in heterogeneous tracer populations of which the single elements can differ in immunoreactivity, pharmacokinetic behavior and stabili ...201627116898
prevalence and morphopathological characteristics of linguatulosis in one-humped camel (camelus dromedarius) in yazd, iran.linguatula serrata is a cosmopolitan zoonotic parasite. its adult form inhabit the nasal and respiratory passages of canids as the definitive hosts while its immature stages localize in the mesenteric lymph nodes or in other organs of herbivorous intermediate hosts. we examined the liver, mesenteric, and mediastinal lymph nodes of 272 camels slaughtered at the slaughterhouse of yazd, iran. forty-one out of 272 camels (15.1 %) were infected with nymphs of l. serrata. twenty-four out of 166 males ...201627106238
structural effects of two camelid nanobodies directed to distinct c-terminal epitopes on α-synuclein.α-synuclein is an intrinsically disordered protein whose aggregation is associated with parkinson's disease and other related neurodegenerative disorders. recently, two single-domain camelid antibodies (nanobodies) were shown to bind α-synuclein with high affinity. herein, we investigated how these two nanobodies (nbsyn2 and nbsyn87), which are directed to two distinct epitopes within the c-terminal domain of α-synuclein, affect the conformational properties of this protein. our results suggest ...201627096466
comparative chromosome map and heterochromatin features of the gray whale karyotype (cetacea).cetacean karyotypes possess exceptionally stable diploid numbers and highly conserved chromosomes. to date, only toothed whales (odontoceti) have been analyzed by comparative chromosome painting. here, we studied the karyotype of a representative of baleen whales, the gray whale (eschrichtius robustus, mysticeti), by zoo-fish with dromedary camel and human chromosome-specific probes. we confirmed a high degree of karyotype conservation and found an identical order of syntenic segments in both br ...201627088853
mers-cov antibodies in humans, africa, 2013-2014.dromedaries in africa and elsewhere carry the middle east respiratory syndrome coronavirus (mers-cov). to search for evidence of autochthonous mers-cov infection in humans, we tested archived serum from livestock handlers in kenya for mers-cov antibodies. serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.201627071076
mers-cov infection of alpaca in a region where mers-cov is endemic. 201627070501
infection, replication, and transmission of middle east respiratory syndrome coronavirus in alpacas.middle east respiratory syndrome coronavirus is a recently emerged pathogen associated with severe human disease. zoonotic spillover from camels appears to play a major role in transmission. because of logistic difficulties in working with dromedaries in containment, a more manageable animal model would be desirable. we report shedding and transmission of this virus in experimentally infected alpacas (n = 3) or those infected by contact (n = 3). infectious virus was detected in all infected anim ...201627070385
effect of dystocia on some hormonal and biochemical parameters in the one-humped camel (camelus dromedarius).the present study compared some of the hormonal and biochemical constituents of serum from eutocic and dystocic one-humped camels (camelus dromedarius). sera were harvested from eutocic (n = 9) and dystocic (n = 20) camels within the first 15 minutes after delivery. although there were no differences in the concentrations of estradiol-17β (e2) and prostaglandin f2α (pgf2α) between the eutocic and the dystocic animals, the level of progesterone (p4) and cortisol was significantly higher (p < 0.01 ...201627068358
development of synthetic light-chain antibodies as novel and potent hiv fusion inhibitors.to develop a novel and potent fusion inhibitor of hiv infection based on a rational strategy for synthetic antibody library construction.201627058352
a proposal of linear assessment scheme for the udder of dairy camels (camelus dromedarius l.).digital images from the left side of the mammary gland of 146 multiparous lactating dromedary camels in mid lactation and managed under intensive conditions were obtained immediately before milking and used to build up a reference scheme for the morphological evaluation of camel mammary glands. a 5-point linear scoring scheme (with 0.5-point accuracy) was subsequently generated based on five mammary traits (udder, depth and floor inclination, teats, shape, length, and width). results showed that ...201627038610
proprotein convertase subtilisin/kexin type 9 (pcsk9) single domain antibodies are potent inhibitors of low density lipoprotein receptor degradation.single domain antibodies (sdabs) correspond to the antigen-binding domains of camelid antibodies. they have the same antigen-binding properties and specificity as monoclonal antibodies (mabs) but are easier and cheaper to produce. we report here the development of sdabs targeting human pcsk9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-pcsk9 mabs. after immunizing a llama with human pcsk9, we selected four sdabs that bind pcsk9 with a high affinity and produced them ...201627284008
first complete mitochondrial genome data from ancient south american camelids - the mystery of the chilihueques from isla mocha (chile).in south american societies, domesticated camelids were of great cultural importance and subject to trade and translocation. south american camelids were even found on remote and hard to reach islands, emphasizing their importance to historic and pre-historic south american populations. isla mocha, a volcanic island 35 km offshore of central-south chile, is an example of such an island. when dutch and spanish explorers reached the island in the early 17th century, they found that domesticated ca ...201627929050
[gastrointestinal bezoars].gastrointestinal bezoars are a concretion of indigested material that can be found in the gastrointestinal tract of humans and some animals. this material forms an intraluminal mass, more commonly located in the stomach. during a large period of history animal bezoars were considered antidotes to poisons and diseases. we report a historical overview since bezoars stones were thought to have medicinal properties. this magic conception was introduced in south america by spanish conquerors. in chil ...201627905655
mers-cov recombination: implications about the reservoir and potential for adaptation.recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. if not properly accounted for, recombination can compromise many evolutionary analyses. in addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. since june 2012, middle east respiratory syndrome coronavirus (mers-cov) has caused 1,1 ...201627774293
ovulation-inducing factor (oif/ngf) in seminal plasma: a review and update.the ovulation-inducing effect of seminal plasma was first reported in bactrian camels over 30 years ago, and the entity responsible was dubbed 'ovulation-inducing factor' (oif). more recent studies, primarily in llamas and alpacas, characterized the biological and chemical properties of oif and ultimately identified it as βngf. this recent discovery has allowed a convergence of knowledge previously separated by discipline and by mechanism; that is, neurobiology and reproductive biology, and auto ...201627762054
mers-cov at the animal-human interface: inputs on exposure pathways from an expert-opinion elicitation.nearly 4 years after the first report of the emergence of middle-east respiratory syndrome coronavirus (mers-cov) and nearly 1800 human cases later, the ecology of mers-cov, its epidemiology, and more than risk factors of mers-cov transmission between camels are poorly understood. knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. moreover the divergent sanitary situations and exposures to animals ...201627761437
camelid single-domain antibodies: a versatile tool for in vivo imaging of extracellular and intracellular brain targets.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 ex ...201627671875
dromedary immune response and specific kv2.1 antibody generation using a specific immunization approach.voltage-gated potassium (kv) channels form cells repolarizing power and are commonly expressed in excitable cells. in non-excitable cells, kv channels such as kv2.1 are involved in cell differentiation and growth. due to the involvement of kv2.1 in several physiological processes, these channels are promising therapeutic targets. to develop kv2.1 specific antibody-based channel modulators, we applied a novel approach and immunized a dromedary with heterologous ltk- cells that overexpress the mou ...201627320844
evaluation of two platelet-rich plasma processing methods and two platelet-activation techniques for use in llamas and alpacas.objective to evaluate 2 processing methods (commercial kit vs conical tube centrifugation) for preparing platelet rich plasma (prp) for use in llamas and alpacas. samples blood samples (30 ml each) aseptically collected from 6 healthy llamas and 6 healthy alpacas. procedures prp was prepared from blood samples by use of a commercial kit and by double-step conical tube centrifugation. a cbc was performed for blood and prp samples. platelets in prp samples were activated by means of a freeze-thaw ...201627805447
epidemiological investigation of middle east respiratory syndrome coronavirus in dromedary camel farms linked with human infection in abu dhabi emirate, united arab emirates.the objective of this research was to investigate the prevalence of middle east respiratory syndrome coronavirus (mers-cov) infection primarily in dromedary camel farms and the relationship of those infections with infections in humans in the emirate of abu dhabi. nasal swabs from 1113 dromedary camels (39 farms) and 34 sheep (1 farm) and sputum samples from 2 mers-cov-infected camel farm owners and 1 mers-cov-infected sheep farm owner were collected. samples from camels and humans underwent rea ...201627357298
camelid and shark single domain antibodies: structural features and therapeutic potential.in addition to canonical antibodies composed of heavy and light chains, the adaptive immune systems of camelids and cartilaginous fish comprise heavy-chain only isotypes (hcab) devoid of light chains, where antigen-binding is mediated exclusively by one variable domain. due to their inherent favorable attributes, such as high affinity and specificity for their cognate antigen, extraordinary stability, small size and, most importantly, the possibility to complement classical antibodies in terms o ...201627865111
exposures among mers case-patients, saudi arabia, january-february 2016. 201627606432
sortase a-mediated site-specific labeling of camelid single-domain antibody-fragments: a versatile strategy for multiple molecular imaging modalities.a generic site-specific conjugation method that generates a homogeneous product is of utmost importance in tracer development for molecular imaging and therapy. we explored the protein-ligation capacity of the enzyme sortase a to label camelid single-domain antibody-fragments, also known as nanobodies. the versatility of the approach was demonstrated by conjugating independently three different imaging probes: the chelating agents chx-a"-dtpa and nota for single-photon emission computed tomograp ...201627147480
an outbreak of middle east respiratory syndrome (mers) due to coronavirus in al-ahssa region, saudi arabia, 2015.between 19 april and 23 june 2015, 52 laboratory-confirmed cases of middle east respiratory syndrome due to coronavirus (mers) were reported from al-ahssa region, eastern saudi arabia. the first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. the objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of ...201627714741
comparison of visual and electronic devices for individual identification of dromedary camels under different farming conditions.the camel industry uses traditional (i.e., iron brands and ear tags) and modern (i.e., microchips) identification (id) systems without having performance results of reference. previously iron-branded ( = 45; 1 yr) and microchipped ( = 59; 7 yr) camels showed problems of healing (8.6% of brands) and reading (only 42.9% of brands and 69.5% of microchips were readable), which made their use inadvisable. with the aim of proposing suitable id systems for different farming conditions, an on-field stud ...201627695805
the structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers.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 struc ...201627670069
identification of useful nanobodies by phage display of immune single domain libraries derived from camelid heavy chain antibodies.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 antigenbinding fragments, also known as nanobodies.201627669966
engineered autonomous human variable domains.the complex multi-chain architecture of antibodies has spurred interest in smaller derivatives that retain specificity but can be more easily produced in bacteria. domain antibodies consisting of single variable domains are the smallest antibody fragments and have been shown to possess enhanced ability to target epitopes that are difficult to access using multidomain antibodies. however, in contrast to natural camelid antibody domains, human variable domains typically suffer from low stability a ...201627655414
cumulus cell expansion and first polar body extrusion during in vitro oocyte maturation in relation to morphological and morphometric characteristics of the dromedary camel ovary.the morphological and morphometric characteristics of the ovary are fundamental properties for in vitro oocyte maturation. nuclear maturation, including first polar body (1pb) extrusion, cytoplasmic maturation and cumulus cell (cc) expansion are the criteria for in vitro maturation (ivm) of oocyte. this study was designed to determine the effect of morphological and morphometric features of the ovary on cc expansion and 1pb extrusion during ivm of oocyte in the adult female dromedary camel. the ...201627650260
main anatomical and histological features of the tonsils in the camel (camelus dromedarius).the tonsils, located around the pharyngeal cavity, constitute the first defence barrier against intruding microorganisms and antigens. the present work aimed to study the anatomical and histological aspects of camel tonsils in order to elucidate their role. the study was carried out on 12 camel heads fixed by infusion with 10 % neutral buffered formalin. a careful dissection of the oral cavity, the soft palate and the pharynx was conducted to explore the morphological aspect of different tonsils ...201627639878
a rational engineering strategy for designing protein a-binding camelid single-domain antibodies.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 mutagen ...201627631624
evaluation of cholesterol- treated dromedary camel sperm function by heterologous ivf and ai.cholesterol (cholesterol-loaded cyclodextrins: clc) treatment of dromedary camel sperm prior to freezing enhances cryosurvival. the present study first validated the efficacy of a heterologous zona-free goat oocyte assay (n=115 oocytes) to evaluate camel sperm function in vitro (experiment 1: n=6 bulls), then examined the effects of clc treatment (1.5mg/ml clc; clc+) versus no treatment (0 clc) of fresh (experiment 2: n=4 bulls) and frozen-thawed (experiment 3: n=5 bulls) camel sperm to penetrat ...201627622555
global analysis of vhhs framework regions with a structural alphabet.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 regio ...201627613403
phage display derived ignar v region binding domains for therapeutic development.phage display technology has revolutionized the science of drug discovery by transforming the generation and manipulation of ligands, such as antibody fragments, enzymes, and peptides. the basis of this technology is the expression of recombinant proteins or peptides fused to a phage coat protein, and subsequent isolation of ligands based on a variety of catalytic, physicochemical/binding kinetic and/or biological characteristics. an incredible number of diagnostic and therapeutic domains have b ...201627604606
inoculation of goats, sheep, and horses with mers-cov does not result in productive viral shedding.the middle east respiratory syndrome coronavirus (mers-cov) was first recognized in 2012 and can cause severe disease in infected humans. dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. in order to un ...201627548203
dual anti-idiotypic purification of a novel, native-format biparatopic anti-met antibody with improved in vitro and in vivo efficacy.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 o ...201627546726
seasonal immunohistochemical reactivity of s-100 and α-smooth muscle actin proteins in the epididymis of dromedary camel, camelus dromedarius.the s-100 and alpha smooth muscle actin (α-sma) proteins have been localised in epididymal tissue of several mammalian species, but there have been no data for a seasonal work in camel. the aim of this study was to investigate the immunoreactivities of s-100 and α-sma proteins in the epididymis of dromedary camel during breeding and nonbreeding seasons. the immunopositive signals for both proteins were observed in different regions of camel epididymis. s-100-immunopositive signals were noted in ...201627506493
reference values and repeatability of the schirmer tear tests i and ii in domesticated, clinically normal dromedary camels (camelus dromedarius).to determine the normal values and repeatability for schirmer tear test (stt) in clinically normal dromedary camels and to analyze the influence of the age and gender on these values.201627491827
middle east respiratory syndrome virus pathogenesis.coronaviruses (covs) are enveloped rna viruses that infect birds, mammals, and humans. infections caused by human coronaviruses (hcovs) are mostly associated with the respiratory, enteric, and nervous systems. the hcovs only occasionally induce lower respiratory tract disease, including bronchitis, bronchiolitis, and pneumonia. in 2002 to 2003, a global outbreak of severe acute respiratory syndrome (sars) was the seminal detection of a novel cov (sars-cov). a decade later (june 2012), another no ...201627486737
reply to marom et al.: mitochondrial panmixia in dromedaries predates ancient caravan trading. 201627486242
daily rhythms of physiological parameters in the dromedary camel under natural and laboratory conditions.camels are well adapted to hot arid environments and can contribute significantly to the economy of developing countries in arid regions of the world. full understanding of the physiology of camels requires understanding of the internal temporal order of the body, as reflected in daily or circadian rhythms. in the current study, we investigated the daily rhythmicity of 20 physiological variables in camels exposed to natural oscillations of ambient temperature in a desert environment and compared ...201627474007
toward developing a preventive mers-cov vaccine-report from a workshop organized by the saudi arabia ministry of health and the international vaccine institute, riyadh, saudi arabia, november 14-15, 2015.middle east respiratory syndrome (mers) remains a serious international public health threat. with the goal of accelerating the development of countermeasures against mers coronavirus (mers-cov), funding agencies, nongovernmental organizations, and researchers across the world assembled in riyadh, saudi arabia, on november 14-15, 2015, to discuss vaccine development challenges. the meeting was spearheaded by the saudi ministry of health and co-organized by the international vaccine institute, so ...201627439020
the therapeutic effects of camel milk: a systematic review of animal and human trials.the clinical effectiveness and value of camel milk as a therapeutic agent is currently unclear. medline (1946 to march 2016), embase (1974 to march 2016), and google scholar were searched using the following terms: milk, bodily secretions, camels, camelus, camelini, camelidae, dromedary, bactrian camel, body fluid, and bodily secretions. articles identified were reviewed if the study was investigating the use of camel milk for the potential treatment of diseases affecting humans. of 430 studies, ...201627432772
nanobodies as versatile tools to understand, diagnose, visualize and treat cancer.since their discovery, nanobodies have been used extensively in the fields of research, diagnostics and therapy. these antigen binding fragments, originating from camelid heavy-chain antibodies, possess unusual hallmarks in terms of (small) size, stability, solubility and specificity, hence allowing cost-effective production and sometimes outperforming monoclonal antibodies. in this review, we evaluate the current status of nanobodies to study, diagnose, visualize or inhibit cancer-specific prot ...201627428417
pregnancy-associated changes of igg and serum n-glycosylation in camel (camelus dromedarius).the dromedary camel (camelus dromedarius) is an agriculturally important species of high economic value but of low reproductive efficiency. serum and igg n-glycosylation are affected by physiological and pathogenic changes and might therefore be a useful diagnostic tool in camel livestock management. this study presents the first comprehensive annotation of the n-glycome from dromedary camel serum as well as their single-domain and conventional antibodies and its subsequent application for camel ...201627428249
allosteric nanobodies reveal the dynamic range and diverse mechanisms of g-protein-coupled receptor activation.g-protein-coupled receptors (gpcrs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signalling effectors such as g proteins and β-arrestins. it is well known that different agonists can share the same binding pocket but evoke unique receptor conformations leading t ...201627409812
data of rational process optimization for the production of a full igg and its fab fragment from hybridoma cells.this data article focuses on the production of monoclonal antibodies (mab) and their fragments fab and f(ab')2. here, we present the data of an optimization protocol to improve the product yield of a hybridoma cell process using a design of experiment (doe) strategy. furthermore, the data of the evaluated conditions were used to test feeding strategies in shake flasks. they were verified in controlled 2 l fed-batch bioreactor processes. supplementing the culture medium with human insulin-like gr ...201627366780
intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains.here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. by fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (vhhs) to the n-terminus of a human collagen xviii trimerization domain (tie(xviii)) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. the purified vhh-tie(xviii) trimerbodies were trimeric in solution and exhibited exce ...201627345490
sars and mers: recent insights into emerging coronaviruses.the emergence of middle east respiratory syndrome coronavirus (mers-cov) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. the continuing introductions of mers-cov from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. scientific advancements since the 2002-2003 severe acute ...201627344959
mers and the dromedary camel trade between africa and the middle east.dromedary camels are the most likely source for the coronavirus that sporadically causes middle east respiratory syndrome (mers) in humans. serological results from archived camel sera provide evidence for circulation of mers coronavirus (mers-cov) among dromedary camels in the greater horn of africa as far back as 1983 and in saudi arabia as far back as 1992. high seroprevalences of mers-cov antibodies and the high virus prevalence in saudi arabian dromedary camels indicate an endemicity of the ...201627324244
generation and characterization of cd1d-specific single-domain antibodies with distinct functional features.ligation of the cd1d antigen-presenting molecule by monoclonal antibodies (mabs) can trigger important biological functions. for therapeutic purposes camelid-derived variable domain of heavy-chain-only antibodies (vhh) have multiple advantages over mabs because they are small, stable and have low immunogenicity. here, we generated 21 human cd1d-specific vhh by immunizing lama glama and subsequent phage display. two clones induced maturation of dendritic cells, one clone induced early apoptosis i ...201627312006
a bispecific antibody promotes aggregation of ricin toxin on cell surfaces and alters dynamics of toxin internalization and trafficking.jjx12 is an engineered bispecific antibody against ricin, a member of the medically important a-b family of toxins that exploits retrograde transport as means to gain entry into the cytosol of target cells. jjx12 consists of rta-d10, a camelid single variable domain (vhh) antibody directed against an epitope on ricin's enzymatic subunit (rta), linked via a 15-mer peptide to rtb-b7, a vhh against ricin's bivalent galactose binding subunit (rtb). we previously reported that jjx12, but not an equim ...201627300140
corrigendum to "plasma leptin, glucose and non-esterified fatty acid variations in dromedary camels exposed to prolonged periods of underfeeding or dehydration" [comp. biochem. physiol., a 166 (2013) 177-185]. 201627292549
polyphyletic origin of mers coronaviruses and isolation of a novel clade a strain from dromedary camels in the united arab emirates.little is known regarding the molecular epidemiology of middle east respiratory syndrome coronavirus (mers-cov) circulating in dromedaries outside saudi arabia. to address this knowledge gap, we sequenced 10 complete genomes of mers-covs isolated from 2 live and 8 dead dromedaries from different regions in the united arab emirates (uae). phylogenetic analysis revealed one novel clade a strain, the first detected in the uae, and nine clade b strains. strain d998/15 had a distinct phylogenetic pos ...201627999424
cordão formation: loess deposits in the southern coastal plain of the state of rio grande do sul, brazil.loess consists of silt-dominated sediments that cover ~10% of the earth's surface. in southern south america it occurs in argentina, bolivia, paraguay and uruguay, and its presence in southern brazil was never studied in detail. here is proposed a new lithostratigraphic unit, cordão formation, consisting of loess deposits in the southern brazilian coastal plain. it consists of fine-very fine silt with subordinate sand and clay, found mostly in lowland areas between pleistocene coastal barriers. ...201627991956
active-site mmp-selective antibody inhibitors discovered from convex paratope synthetic libraries.proteases are frequent pharmacological targets, and their inhibitors are valuable drugs in multiple pathologies. the catalytic mechanism and the active-site fold, however, are largely conserved among the protease classes, making the development of the selective inhibitors exceedingly challenging. in our departure from the conventional strategies, we reviewed the structure of known camelid inhibitory antibodies, which block enzyme activities via their unusually long, convex-shaped paratopes. we s ...201627965386
developmental competence of dromedary camel oocytes fertilized in vitro by frozen-thawed ejaculated and epididymal spermatozoa.the present study aimed to compare the in vitro fertilizing capacity of frozen-thawed ejaculated and epididymal spermatozoa in order to standardize the semen preparation protocol for camel in vitro fertilization (ivf). semen samples were collected from 7 dromedary camels by means of artificial vagina (av). ten cauda epididymes were obtained from slaughtered adult camels, isolated, incised and rinsed for obtaining the sperm rich fluid. ejaculated and epididymal spermatozoa were processed for cryo ...201628224009
the history of old world camelids in the light of molecular genetics.old world camels have come into the focus as sustainable livestock species, unique in their morphological and physiological characteristics and capable of providing vital products even under extreme environmental conditions. the evolutionary history of dromedary and bactrian camels traces back to the middle eocene (around 40 million years ago, mya), when the ancestors of camelus emerged on the north american continent. while the genetic status of the two domestic species has long been establishe ...201627048619
the major histocompatibility complex in old world camelids and low polymorphism of its class ii genes.the major histocompatibility complex (mhc) is a genomic region containing genes with crucial roles in immune responses. mhc class i and class ii genes encode antigen-presenting molecules expressed on the cell surface. to counteract the high variability of pathogens, the mhc evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. studies of mhcs in different model species contribute to our understanding of mechanisms of immunity, diseases and th ...201626931144
middle east respiratory syndrome coronavirus: review of the current situation in the world.this article reviews the current epidemiology and clinical presentation of middle east respiratory syndrome coronavirus (mers-cov) infection and describes the preparedness plan of several countries. the mers-cov was first reported in 2012 and has since infected more than 1600 patients in 26 countries, mostly in saudi arabia and the middle east. the epidemiology of the infection is compatible with multiple introductions of the virus into humans from an animal reservoir, probably dromedary camels. ...201628265443
effects of gestational age on physical findings of immaturity, body weight, and survival in neonatal alpacas (2002-2010).gestational duration is highly variable in camelids (reference range 330-360 days), and a definition for prematurity has not been established. anecdotally, it is suggested that crias born outside of this have increased incidence of physical findings of immaturity (tendon laxity, floppy ears, and unerupted teeth) and need increased intensive support in the neonatal period.201623870011
evaluation of four point-of-care glucose meters in alpacas.hospitalized alpacas are often hyperglycemic requiring frequent blood glucose testing.201623734626
evaluation of methods to improve the diagnosis of systemic inflammation in alpacas.the stoic nature of alpacas and limitations of current diagnostic tests make early recognition of inflammatory diseases in this species challenging.201623662652
development and application of camelid molecular cytogenetic tools.cytogenetic chromosome maps offer molecular tools for genome analysis and clinical cytogenetics and are of particular importance for species with difficult karyotypes, such as camelids (2n = 74). building on the available human-camel zoo-fluorescence in situ hybridization (fish) data, we developed the first cytogenetic map for the alpaca (lama pacos, lpa) genome by isolating and identifying 151 alpaca bacterial artificial chromosome (bac) clones corresponding to 44 specific genes. the genes were ...201623109720
haematological and biochemical alterations caused by epidural and intramuscular administration of xylazine hydrochloride in dromedary camels (camelus dromedarius).this study was conducted in 16 healthy immature dromedary camels weighing 120-150 kg to evaluate and compare the effects of epidural and intramuscular injections of xylazine administered at 0.1 mg/kg and 0.2 mg/kg. haematological parameters included haemoglobin, packed cell volume, total erythrocyte count and total leukocyte count. biochemical parameters included alkaline phosphates, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine and glucose. parameters wer ...201623038078
adp-ribosylation of p2x7: a matter of life and death for regulatory t cells and natural killer t cells.adp-ribosyltransferases comprise a family of enzymes originally discovered as bacterial toxins and later characterised also in mammals. in mice, the adp-ribosyltransferase artc2.2 is expressed at the surface of t lymphocytes and has been studied extensively. in the presence of extracellular nad(+), artc2.2 adp-ribosylates several cell surface target proteins and thereby regulates their function. p2x7, an atp-gated cation channel, has been discovered as a prominent artc2.2 target at the surface o ...201525048544
retinal ganglion cell distribution and visual acuity in alpacas (vicugna pacos).to investigate the distribution of retinal ganglion cells (rgcs) and visual acuity in alpacas (vicugna pacos) through brn-3a immunofluorescent labeling.201524320877
sectional anatomic and computed tomography features of the nasal and oral cavities of the one-humped camel (camelus dromedarius).the purpose of the study was to provide a description of normal cross-sectional anatomy of the camel nasal and oral cavities using computed tomography (ct) and macroscopic cross-sections. transverse images of two isolated camel cadaver heads were obtained by an axial ct equipment. computed tomography scans were processed with a detailed algorithm using nasal and soft tissue windows settings and compared with the corresponding frozen cross-sections of the heads, to assist in the accurate identifi ...201524527752
presence and distribution of urocortin and its receptors in the epididymis of alpaca (vicugna pacos).urocortin 1 (ucn) is a 40-amino acid peptide belonging to the corticotrophin-releasing hormone (crh) family. the biological effects of this peptide are modulated by binding two g-coupled receptors named crh receptor 1 (crhr1) and crh receptor 2 (crhr2). crhr2 has high affinity for ucn. the aim of the present study was to investigate the presence and distribution of ucn, crhr1 and crhr2 in the epididymis of the south america camelid alpaca (vicugna pacos) by western blotting analysis and immunohi ...201524661003
absence of mers-cov antibodies in feral camels in australia: implications for the pathogen's origin and spread.middle east respiratory syndrome coronavirus (mers-cov) infections continue to be a serious emerging disease problem internationally with well over 1000 cases and a major outbreak outside of the middle east region. while the hypothesis that dromedary camels are the likely major source of mers-cov infection in humans is gaining acceptance, conjecture continues over the original natural reservoir host(s) and specifically the role of bats in the emergence of the virus. dromedary camels were importe ...201528616468
animal models of middle east respiratory syndrome coronavirus infection.the emergence of the middle east respiratory syndrome coronavirus (mers-cov) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. in this review, we discuss the current state of knowledge of animal models of mers-cov infection. commonly used laboratory animal species such as syrian hamsters, mice and ferrets are not susceptible to mers-cov, due to differences in the mers-cov receptor dipeptidyl peptidase 4 (dpp4). the i ...201526192750
genomic data from extinct north american camelops revise camel evolutionary history.recent advances in paleogenomic technologies have enabled an increasingly detailed understanding of the evolutionary relationships of now-extinct mammalian taxa. however, a number of enigmatic quaternary species have never been characterized with molecular data, often because available fossils are rare or are found in environments that are not optimal for dna preservation. here, we analyze paleogenomic data extracted from bones attributed to the late pleistocene western camel, camelops cf. heste ...201526037535
[new world camelid days 2014]. 201526753315
lymph node hemangioma in one-humped camel.hemangioma is a benign tumor of blood and lymphatic vessels. it is common in skin, mucosa and soft tissues, and its occurrence in lymph nodes is extremely rare. a 10 year-old she-camel was slaughtered at nyala slaughterhouse, south darfur state, sudan. grossly, the carcass was emaciated. the left ventral superficial cervical lymph node was enlarged, hard on palpation and protruded outside the body. its cut surface was dark red in color and measured (18 cm) in diameter. histopathologically, the s ...201526753134
middle east respiratory syndrome coronavirus (mers-cov): animal to human interaction.the middle east respiratory syndrome coronavirus (mers-cov) is a novel enzootic betacoronavirus that was first described in september 2012. the clinical spectrum of mers-cov infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. bats harbour several betacoronaviruses that are closely related to mers-cov but more research is needed to establish the relationship between bats and mers-cov. the serop ...201526924345
hydatidosis of camel (camelus dromedarius) at jijiga municipal abattoir, eastern ethiopia: prevalence, associated risk factors and financial implication.a cross-sectional study was conducted from november 2010 to may 2011 to estimate the prevalence of camel hydatidosis, associated risk factors and financial loss in jijiga municipal abattoir, somali regional state, eastern ethiopia. accordingly, of the total 400 inspected camel, 92 (23 %) camels and 109 organs were positive for hydatid cyst with the highest proportion recorded in lung (56 %) followed by liver (33.9 %), spleen (7.3 %) and kidneys (2.8 %). the prevalence of hydatidosis significantl ...201526688643
middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels in nigeria, 2015.evidence of current and past middle east respiratory syndrome coronavirus (mers-cov) infection in dromedary camels slaughtered at an abattoir in kano, nigeria in january 2015, was sought by reverse transcription-quantitative polymerase chain reaction (rt-qpcr) and serology. mers-cov rna was detected in 14 (11%) of 132 nasal swabs and antibody in 126 (96%) of 131 serum samples. phylogenetic analyses demonstrate that the viruses in nigeria are genetically distinct from those reported in the arabia ...201526676406
a phylogenetically distinct middle east respiratory syndrome coronavirus detected in a dromedary calf from a closed dairy herd in dubai with rising seroprevalence with age.middle east respiratory syndrome coronavirus (mers-cov) was detected by monoclonal antibody-based nucleocapsid protein-capture enzyme-linked immunosorbent assay (elisa), rna detection, and viral culture from the nasal sample of a 1-month-old dromedary calf in dubai with sudden death. whole genome phylogeny showed that this mers-cov strain did not cluster with the other mers-cov strains from dubai that we reported recently. instead, it formed a unique branch more closely related to other mers-cov ...201526632876
mers coronavirus: diagnostics, epidemiology and transmission.the first known cases of middle east respiratory syndrome (mers), associated with infection by a novel coronavirus (cov), occurred in 2012 in jordan but were reported retrospectively. the case first to be publicly reported was from jeddah, in the kingdom of saudi arabia (ksa). since then, mers-cov sequences have been found in a bat and in many dromedary camels (dc). mers-cov is enzootic in dc across the arabian peninsula and in parts of africa, causing mild upper respiratory tract illness in its ...201526695637
adenovirus vector expressing stx1/stx2-neutralizing agent protects piglets infected with escherichia coli o157:h7 against fatal systemic intoxication.hemolytic-uremic syndrome (hus), caused by shiga toxin (stx)-producing escherichia coli (stec), remains untreatable. production of human monoclonal antibodies against stx, which are highly effective in preventing stx sequelae in animal models, is languishing due to cost and logistics. we reported previously that the production and evaluation of a camelid heavy-chain-only vh domain (vhh)-based neutralizing agent (vna) targeting stx1 and stx2 (vna-stx) protected mice from stx1 and stx2 intoxicatio ...201525368111
effects of vacuum level and pulsation rate on milk ejection and milk flow traits in tunisian dairy camels (camelus dromedarius).this work aims to compare the effects of milking at two vacuum levels (38 and 48 kpa) and three pulsation rates (60, 90, and 120 cpm) on milk production and milk flow characteristics. six multiparous maghrebi camels in late lactation and once daily milked were used. the best combination of setting for camel's milking was high vacuum and low pulsation rate (48 kpa/60 cpm). milk yield and average and peak milk flow rate were the highest, while milking time was the shortest using this combination o ...201525348647
bioengineering of bacteria to assemble custom-made polyester affinity resins.proof of concept for the in vivo bacterial production of a polyester resin displaying various customizable affinity protein binding domains is provided. this was achieved by engineering various protein binding domains into a bacterial polyester-synthesizing enzyme. affinity binding domains based on various structural folds and derived from molecular libraries were used to demonstrate the potential of this technique. designed ankyrin repeat proteins (darpins), engineered ob-fold domains (obodies) ...201525344238
seminal plasma and serum fertility biomarkers in dromedary camels (camelus dromedarius).eight healthy fertile (control) and 11 infertile male dromedaries were used to investigate whether specific seminal plasma and serum fertility biomarkers could be related to their in vivo fertility. eight fertility biomarkers and testosterone were determined in both seminal plasma and serum of all studied camels during the rutting season using commercial kits. results revealed a significant (p < 0.01) difference in semen parameters between the control and infertile camels. there was a significan ...201525434775
effect of pregnancy and embryonic mortality on milk production in dromedary camels (camelus dromedarius).the main objective of the present study was to compare milk production in pregnant versus nonpregnant dromedary camels. in addition, we described the effect of embryonic mortality on lactation and measured serum progesterone levels until d 60 to 90 of gestation. twenty-five multiparous camels were selected in midlactation for 2 studies in consecutive years. camels were mated naturally when the size of the dominant follicle reached 1.2 to 1.5cm. pregnancy was diagnosed by ultrasonography and prog ...201525434338
spectroscopic and thermodynamic properties of recombinant heat shock protein a6 from camelus dromedarius.heat shock protein a6, also known as hsp70b', is a member of the hsp70 family of molecular chaperones. under stressed conditions, the level of hspa6 increases substantially, and the protein has been targeted as a biomarker of cellular stress in several studies. we report the spectroscopic and thermodynamic properties of arabian camel species chspa6, determined by measurement of intrinsic and extrinsic fluorescence emission, and use of far-uv circular dichroism and dynamic multimode spectroscopy. ...201525395330
optimization of storage and stability of camel liver glutathione s-transferase.glutathione s-transferases (gsts) are multifunctional enzymes and play an important role in cellular detoxification. besides this, gsts act as cytosolic carrier proteins that bind hydrophobic compounds such as heme, bilirubin, steroids, and polycyclic hydrocarbons. gst has great importance in biotechnology, as it is a target for vaccine and drug development and biosensors development for xenobiotics. moreover, the gst tag has been extensively used for protein expression and purification. until n ...201525036813
metrical analysis of dromedary digital bones.dromedary camels are large even-toed ungulates which are well adapted to life in large deserts. examinations of their feet have revealed many structural peculiarities. we have measured the digital bones of the dromedary in order to determine whether there are morphometric variations in the digital bones between the lateral and medial sides in individual limbs and/or in the right and left thoracic and pelvic limbs, with the aim to clarify whether there are anatomical differences in the digital bo ...201524908273
structural insights and biomedical potential of ignar scaffolds from sharks.in addition to antibodies with the classical composition of heavy and light chains, the adaptive immune repertoire of sharks also includes a heavy-chain only isotype, where antigen binding is mediated exclusively by a small and highly stable domain, referred to as vnar. in recent years, due to their high affinity and specificity combined with their small size, high physicochemical stability and low-cost of production, vnar fragments have evolved as promising target-binding scaffolds that can be ...201525523873
biochemical composition and protein profile of alpaca (vicugna pacos) oviductal fluid.knowledge and assessment of the constituents of the oviductal fluid (of) in camelids is necessary for a correct formulation of specific culture media for the development of reproductive biotechnology. this study is the first describing the biochemical composition and sds-page protein profile of alpaca oviductal fluid in non-pregnant animals and animals that have completed the first month and second month of gestation. samples were also classified into oviducts that were ipsilateral or contralate ...201525592861
histochemical structure and immunolocalisation of the hyaluronan system in the dromedary oviduct.we investigated the local modulation of some histochemical properties of oviducts of the dromedary (camelus dromedarius), focusing on the immnolocalisation of hyaluronic acid (ha) synthases (has2 and has3), hyaluronidases (hyal2 and hyal1) and the ha receptor cd44 in the ampulla and isthmus. abundant acidic mucopolysaccharides (glycosaminoglycans) were detected by alcian blue staining along the luminal surface of both ciliated and non-ciliated epithelial cells (le). staining for has2 was higher ...201525562384
a survey of rift valley fever and associated risk factors among the one-humped camel (camelus dromedaries) in sudan.rift valley fever (rvf) is a mosquito-borne viral disease of domestic livestock and wild ruminants. in camels rvf may cause abortion among pregnant camels, but is most often asymptomatic among other camels. in this study, a seroepidemiological survey was conducted to determine the prevalence of rvfv antibodies and to identify the potential risk factors associated with rvfv seropositivity among the sudanese one-humped camel (camelus dromedaries) in khartoum state, sudan. a cross sectional study w ...201527293548
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