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Studies on camel hemoglobin. 1. Physico-chemical properties and some structural aspects of camel hemoglobin (Camelus dromedarius).

Hemoglobin from an adult camel (Camelus dromedarius) was prepared from the red cell lysate by CM- and DEAE-cellulose chromatography. The purified hemoglobin showed a lesser mobility on starch gel electrophoresis at pH 8.5 than that of human hemoglobin C. Native camel hemoglobin contains 95-99% alkali-resistant hemoglobin and in soluble in 2.94 M K2HPO4/KH2PO4 buffer. Different forms of camel hemoglobin show similar ammonium sulfate precipitation curves. Indirect evidence for the stability of camel hemoglobin solutions was obtained from several sources. Spontaneous met-hemoglobin formation is extremely slow and minimal quantities of degradation products appear on starch gel electrophoresis and on chromatographic separation. The alpha and beta chains of camel hemoglobin A were separated on a CM-23 column by the use of a pyridine formate gradient. Large peptide fragments were obtained by tryptic digestion of maleylated alpha and beta chains. The N-terminal structure of the alpha and beta chains and of tryptic maleylated peptides derived from alpha and beta chains are presented. Between adult camel hemoglobin and adult human hemoglobin six amino acid differences in the N-terminal 20 amino acid residues of the alpha chain, at residues: 4, 5, 12, 14, 17, and 19; eight amino acid substitutions were found in the beta chain at positions: 4, 5, 6, 9, 12, 13, 16, and 19. Substitutions at alpha5 Ala leads to Lys, and beta19 Asn leads to Lys, increase the net positive charge of camel hemoglobin by two, while other substitutions result in no charge differences. The molecular basis of the stability of camel adult hemoglobin is discussed.

Amino Acid Sequence

Whole-Genome Sequencing Reveals Population Structure, Genetic Diversity, and Selection Signatures in Kazakh Dromedary and Bactrian Camels.

Understanding the genomic basis of environmental adaptation is essential for the conservation and genetic improvement of domestic camels. In this study, we investigated the population structure, genetic diversity, and genomic variation potentially associated with environmental adaptation of Kazakh dromedary and Bactrian camels using whole-genome sequencing. Whole-genome sequencing data were generated for Kazakh camels (15 dromedaries and 16 Bactrian camels) and integrated with 131 publicly available genomes representing camel populations from the Arabian Peninsula, Iran, Xinjiang, Inner Mongolia, and Mongolian wild camels. Population structure, genetic diversity, and genome-wide selection were evaluated using principal component analysis, ADMIXTURE, nucleotide diversity, linkage disequilibrium, runs of homozygosity, genomic inbreeding (FROH), and selection scans based on FST, θπ ratio, and XP-EHH. Population genomic analyses revealed clear differentiation between dromedary and Bactrian camels, whereas Kazakh camel populations exhibited higher nucleotide diversity (θπ = 1.307-1.551 × 10-3), and lower genomic inbreeding (median FROH: 0.037-0.056) than Arabian populations. Genome-wide selection analyses identified MC4R as the prominent candidate gene in Kazakh dromedaries and RYR1 as a prominent candidate gene in Kazakh Bactrian camels. Functional enrichment analyses highlighted pathways related to energy metabolism, thermogenesis, calcium signaling, skeletal muscle function, mitochondrial activity, and oxidative stress response. These findings provide new insights into genomic variation potentially associated with environmental adaptation in Kazakh camels and offer valuable genomic resources for future conservation, breeding, and evolutionary studies.

MC4R

Toxoplasma gondii IgG seroprevalence in Mauritanian dromedary camels: First multi-regional survey.

Toxoplasma gondii is a globally distributed zoonotic parasite, and dromedary camels are important intermediate hosts in arid and semi-arid regions. However, information on T. gondii exposure in camels is lacking in Mauritania, which harbors one of the largest camel populations in West Africa. This study reports the first multi-regional seroepidemiological survey to estimate T. gondii seroprevalence and identify associated risk factors in Mauritanian dromedaries. Between 2023 and 2024, serum samples were collected from 953 camels across eight climatically distinct regions. Anti-T. gondii IgG antibodies were detected using the Modified Agglutination Test (MAT; cutoff≥1:20). Risk factors investigated included geographical region, sex, age group, and season of sampling, using multivariable logistic regression and a mixed-effects linear probability model accounting for regional clustering. The overall seroprevalence was 15.0% (143/953). Exposure varied markedly across regions, ranging from 0% in the hyper-arid northern regions of Adrar and Tagant to 41.7% in the southern Sahelian region of Guidimakha. This pronounced spatial gradient is consistent with contrasting climatic and ecological conditions, as higher rainfall and humidity in the south are hypothesized to favor environmental oocyst survival compared to the extreme aridity of the north. Geographical region and age were independent predictors of seropositivity. Compared with camels from Nouakchott, those from Guidimakha had higher odds of exposure (aOR = 2.63), whereas camels from Trarza had a markedly lower risk (aOR = 0.09). Camels older than 6 years were more than twice as likely to be seropositive as those aged 3-5 years, whereas sex and season were not associated with seropositivity. These findings indicate that T. gondii exposure is widespread in Mauritanian dromedaries and that ecological conditions may influence exposure patterns. The marked spatial heterogeneity supports targeted surveillance and One Health interventions to reduce the potential zoonotic risk associated with camel-derived food products.

Animals

Revealing the cytokine-mediated embryo-maternal crosstalk during extended in vitro culture in the Arabian camel (Camelus dromedarius).

This study reports, for the first time, the establishment of endometrial organoids (EOs) from the Arabian camel (Camelus dromedarius) and evaluates their suitability as an in vitro model for embryo-maternal interactions during implantation. Endometrial tissues were collected from non-pregnant she-camels and cultured in Matrigel with a defined growth medium. By Day 7, organoids displayed a spherical morphology (200-250 µm), remained viable for up to 20 days, and expanded to approximately 1 mm. They exhibited epithelial characteristics and high proliferative activity, confirmed by expression of mucin-1, pan-cytokeratin, vimentin, and Ki67. Day 7 in vitro-produced embryos co-cultured with EOs showed significant improvements in development and trophoblast outgrowth. This was accompanied by upregulation of key developmental genes (OCT4, c-MYC, KLF4, CDX2). Cytokine profiling revealed enhanced bidirectional signaling: embryos increased secretion of CCL2, CCL4, IGF-1, IFNG, IL1α, IL12b, IL-8, LIF, IL-10, and NTF3, while EOs upregulated VEGFA, IL-8, CCL2, and TIMP1. Co-culture uniquely induced additional cytokines and amplified signaling intensity. Metabolomic analysis of embryo-conditioned medium identified 108 metabolites, including steroids associated with immunomodulation. Notably, embryos cultured in EO-conditioned medium developed up to Day 21 post-cleavage, reaching a mean diameter of 2.4 mm. Overall, camel EOs provide a physiologically relevant platform that supports embryo development and enables detailed investigation of cytokine-mediated embryo-maternal communication and implantation processes in the dromedary camel.

Camel

MERS-CoV in the Middle East and Africa: from surveillance gaps in humans and dromedary camels to One Health frameworks for spillover, prevention, research and response preparedness.

Middle East respiratory syndrome coronavirus (MERS-CoV) remains a low-incidence but high-consequence zoonotic coronavirus threat. Since its identification in Saudi Arabia in 2012, more than 2600 laboratory-confirmed cases have been reported from 27 countries, most from the Arabian Peninsula; the reported case fatality ratio is high but probably overestimates infection fatality because mild and asymptomatic infections are under-detected. Dromedary camels across the Middle East, North Africa, East Africa, the Horn of Africa, and parts of the Sahel show extensive evidence of MERS-CoV infection or exposure, yet PCR-confirmed human disease has rarely been reported from Africa. This "Africa paradox" is one of the most important unresolved issues in MERS-CoV epidemiology. We propose a dromedary camel-centered One Health framework for the connected Middle East-Africa dromedary belt. The framework is organized around two linked barriers: an upstream barrier that detects and reduces zoonotic spillover at the camel-human interface, and a downstream healthcare barrier that prevents amplification after human infection occurs. Preparedness should include sentinel surveillance for severe acute respiratory infection and atypical pneumonia in camel-exposed populations, linked animal-human genomic surveillance, culturally respectful and occupationally practical risk reduction, rapid diagnostic pathways, healthcare infection prevention and control, mass-gathering and travel preparedness, and preapproved research platforms. A Middle East-Africa preparedness compact aligned with the International Health Regulations, One Health governance, and equitable pathogen access and benefit sharing could transform fragmented surveillance into a standing transregional system for early detection, prevention, and research-ready response.

Africa paradox

Acid-base parameters in the dehydrated camel.

The effect of prolonged (10 days) dehydration on acid-base parameters of camel blood was examined. The pH and PCO2 levels rose significantly in the course of dehydration. This state was comparable with compensated non-respiratory alkalosis found in other animals. The plasma sodium, and magnesium levels rose significantly also. The plasma oxygen and calcium levels declined significantly. There were no significant changes in potassium and phosphate levels. It is concluded that the changes found in acid-base status following dehydration are further evidence of water preservation mechanisms in the dehydrated camel.

Acid-Base Equilibrium

Comparative studies on poxvirus strains isolated from camels.

Five poxvirus strains isolated from camels in Egypt, Iran and the U.S.S.R. were investigated. The morphology and size of the negatively stained virions of the investigated strains were identical. The strains produced minute white pock lesions localized mainly on the infected area of the chorioallantoic membrane, without generalization of lesions or death of embryos. The ceiling temperature and the haemagglutinating activity of the different strains were different. All the strains were apathogenic for rabbit skin and highly pathogenic for mice inoculated intracerebrally. Serologically, all the strains were related to vaccinia virus but with different degrees. The studied strains had the characteristics of members of the genus Orthopoxvirus.

Animals

Coronavirus Cryptic Landscape and Draft Genome of a Novel CoV Clade Related to MERS From Bats Circulating in Northeastern Brazil.

We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis. Notably, gaps in the spike-encoding gene led us to design new primers and perform Sanger sequencing, which revealed high similarities to MERS-related (MERSr) CoV strains found in humans and camels. Additionally, we identified key residues in the receptor-binding domain (RBD) of the spike protein, suggesting potential interactions with DPP4, the receptor for MERSr-CoV. Our analyses also revealed evidence of recombination involving our laboratory-produced sequences. These findings highlight the extensive genetic diversity of CoVs, the presence of novel viral lineages, and the occurrence of recombination events among bat CoVs circulating in Brazil, underscoring the critical role bats play as reservoirs for emerging viruses and emphasizing the necessity of ongoing surveillance to monitor the public health risks associated with CoV spillover events.

Chiroptera

Nanobodies: From High-Throughput Identification to Therapeutic Development.

The camelid single-domain antibody fragment, commonly referred to as a nanobody, achieves the targeting power of conventional monoclonal antibodies (mAbs) at only a fraction of their size. Isolated from camelid species (including llamas, alpacas, and camels), their small size at ∼15 kDa, low structural complexity, and high stability compared with conventional antibodies have propelled nanobody technology into the limelight of biologic development. Nanobodies are proving themselves to be a potent complement to traditional mAb therapies, showing success in the treatment of, for example, autoimmune diseases and cancer, and more recently as therapeutic options to treat infectious diseases caused by rapidly evolving biological targets such as the SARS-CoV-2 virus. This review highlights the benefits of applying a proteomic approach to identify diverse nanobody sequences against a single antigen. This proteomic approach coupled with conventional yeast/phage display methods enables the production of highly diverse repertoires of nanobodies able to bind the vast epitope landscape of an antigen, with epitope sampling surpassing that of mAbs. Additionally, we aim to highlight recent findings illuminating the structural attributes of nanobodies that make them particularly amenable to comprehensive antigen sampling and to synergistic activity-underscoring the powerful advantage of acquiring a large, diverse nanobody repertoire against a single antigen. Lastly, we highlight the efforts being made in the clinical development of nanobodies, which have great potential as powerful diagnostic reagents and treatment options, especially when targeting infectious disease agents.

Animals

Genotype-dependent DNA methylation patterns are negatively associated with allelic variation rather than heat-induced gene expression in two contrasting potato genotypes.

Potato (Solanum tuberosum L.) is an important food crop that is sensitive to high temperatures, which cause major changes in the transcriptome and a reduction in yield. In several plant species, DNA methylation has been reported to influence gene expression, particularly under abiotic stress conditions. However, the role of DNA methylation in regulating gene expression in heat-tolerant and heat-sensitive potato genotypes is still poorly understood. In this study, we conducted genome-wide DNA methylome and transcriptome analyses of leaves from two contrasting potato cultivars, Annabelle (moderately heat-tolerant) and Camel (heat-sensitive), before and after heat stress (HS). Genome-wide differential methylation analysis revealed that most identified differentially methylated regions (DMRs) were constitutive, reflecting variation between cultivars rather than being induced by HS. While thousands of heat-responsive differentially expressed genes (DEGs) were identified, only a small fraction coincided with heat-induced DMRs. Despite substantial constitutive DNA methylation and transcriptome differences between the cultivars, we found no consistent association between DMRs and DEGs, indicating that DNA methylation does not play a widespread direct regulatory role in gene expression. Surprisingly, hypermethylated genomic regions were associated with lower alternative allele frequencies, whereas hypomethylated regions showed the opposite trend. These findings indicate that the potato DNA methylome is largely stable under HS and that constitutive DNA methylation variation contributes rather to genetic diversity than to the direct regulation of gene expression.

DNA Methylation

Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity.

Coronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.IMPORTANCEEmerging coronaviruses like SARS-CoV, SARS-CoV-2, and MERS-CoV cause a range of disease outcomes in humans from an asymptomatic, moderate, and severe respiratory disease that can progress to death but the factors causing these disparate outcomes remain unclear. Understanding host responses to mild and life-threatening infections provides insight into virus-host networks within and across organ systems that contribute to disease outcomes. We used multi-omics approaches to comprehensively define the host response to moderate and severe MERS-CoV infection. Severe respiratory disease was associated with dysregulation of the immune response. Key lung epithelial cell populations that are essential for lung function get infected and die. Mice lacking key immune cell populations experienced greater virus replication but decreased disease severity implicating the immune system in both protective and pathogenic roles in response to MERS-CoV. These data could be utilized to design new therapeutic strategies targeting specific pathways that contribute to severe disease.

Animals

Discovery of a novel Betacoronavirus 1, cpCoV, in goats in China: The new risk of cross-species transmission.

Betacoronavirus is a causative agent of respiratory and enteric diseases in humans and animals. Several ruminants are recognized to be intermediate hosts in the transmission of emerging coronaviruses from reservoir hosts to humans. Here, we first report a novel Betacoronavirus isolated from goats suffering from diarrhea in China, putatively named caprine coronavirus (cpCoV). Full-genome characterization and nuclear acid comparisons demonstrated that this virus is an evolutionarily distinct Betacoronavirus belonging to the subgenus Embecovirus and is a Betacoronavirus 1 species. Notably, on phylogenetic trees based on complete genomes and RdRp, S, and N genes, the cpCoVs were grouped into a clade distinct from other Betacoronavirus strains and were closely related to the HKU23- and HKU23-associated coronaviruses. CpCoV possessed a unique genome organization with a truncated NS4a protein and an elongated NS4b protein that showed no significant matches in the GenBank database. The homology of the S and NS4a-4b genes between cpCoV and Embecovirus was less than 95%. Analysis revealed possible recombination events occurred during the evolution of cpCoV and HKU23, and there are striking similarities between the two viruses in evolutionary terms. In addition, cpCoV showed a narrow cell tropism, replicating in human- and bovine-origin cells in vitro, and caused diarrhea and enteric pathologic changes in goats and calves in vivo. We have provided epidemiological, virological, evolutionary, and experimental evidence that cpCoV is a novel etiological agent for enteric disease in goats. Evidently, a spilling-over event might have occurred between ruminants, including goats, camels, cattle, and wild animals. This study highlights the importance of identifying coronavirus diversity and inter-species transmission in ruminants worldwide, broadens our understanding of the ecology of coronaviruses, and aids in the prevention of animal-to-human transmission and outbreaks.

Animals