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Vaccines are critical tools to treat and prevent diseases. For an effective conjugate vaccine, the carrier is crucial, but few carriers are available for clinical applications. In addition, a drawback of current protein carriers is that high levels of antibodies against the carrier are induced by the conjugate vaccine, which are known to interfere with the immune responses against the target antigen. To overcome these challenges, we obtained the near atomic resolution crystal structure of an emerging protein carrier, i.e., the bacteriophage Qβ virus like particle. On the basis of the detailed structural information, novel mutants of bacteriophage Qβ (mQβ) have been designed, which upon conjugation with tumor associated carbohydrate antigens (TACAs), a class of important tumor antigens, elicited powerful anti-TACA IgG responses and yet produced lower levels of anticarrier antibodies as compared to those from the wild type Qβ-TACA conjugates. In a therapeutic model against an aggressive breast cancer in mice, 100% unimmunized mice succumbed to tumors in just 12 days even with chemotherapy. In contrast, 80% of mice immunized with the mQβ-TACA conjugate were completely free from tumors. Besides TACAs, to aid in the development of vaccines to protect against COVID-19, the mQβ based conjugate vaccine has been shown to induce high levels of IgG antibodies against peptide antigens from the SARS-CoV-2 virus, demonstrating its generality. Thus, mQβ is a promising next-generation carrier platform for conjugate vaccines, and structure-based rational design is a powerful strategy to develop new vaccine carriers.

Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number of HS oligosaccharides. To overcome the obstacles and expedite the synthesis, a divergent approach was designed, where 64 HS tetrasaccharides covering all possible structures of 2-O-, 6-O- and N-sulfation with the glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from a single strategically protected tetrasaccharide intermediate. This extensive library helped identify the structural requirements for HS sequences to have strong fibroblast growth factor-2 binding but a weak affinity for platelet factor-4. Such a strategy to separate out these two interactions could lead to new HS-based potential therapeutics without the dangerous adverse effect of heparin-induced thrombocytopenia.

More than two years into the global pandemic, SARS-CoV-2 remains a significant threat to public health. Immunities acquired from infection or current vaccines fail to provide long term protection against subsequent infections, mainly due to their fast-waning nature and the emergence of variants of concerns (VOCs) such as Omicron. To overcome these limitations, SARS-CoV-2 Spike protein receptor binding domain (RBD)-based epitopes were investigated as conjugates with a powerful carrier, the mutant bacteriophage Qβ (mQβ). The epitope design was critical to eliciting potent antibody responses with the full length RBD being superior to peptide and glycopeptide antigens. The full length RBD with orientation-controlled conjugation with mQβ activated both humoral and cellular immune systems in vivo, inducing broad spectrum, persistent and comprehensive immune responses effective against multiple VOCs including Delta and Omicron variants, rendering it a promising vaccine candidate.

This study was performed on productive data collected from private farm of Holstein Friesian cows. The objective of this study was to evaluate the effect of days in milk (DIM), peak milk yield (PMY), dry period (DP), calving interval (CI), parity, and season of calving on 305-day milk yield (305-DMY). And the effect of 305- day milk yield (305-DMY), peak milk yield (PMY), days in milk (DIM), parity, and season of calving on lactation persistency. We found that DIM, parity, and PMY had significant effect on 305-DMY, the highest milk production was obtained when DIM more than 357 days and in the 1st lactation. Moreover, PMY, 305-DMY, and season of calving had significant effect on lactation persistency. In addition, average estimated breeding value (EBV) for 305-DMY, PMY and CI was higher in sire than in cow and dam. Also, Average estimated breeding values for lactation persistency, DP, and DIM were higher in dam than in cow and sire.

This study was performed on 1480 productive records collected from private farm of Holstein Friesian cows. In addition, collection of 70 milk samples for the measurement of somatic cell count (SCC). This study aims to evaluate the effect of some non-genetic factors (days in milk (DIM), peak milk yield (PMY), dry period (DP), calving interval (CI), parity, and season of calving) on total milk yield (TMY). And studying the effect of 305-day milk yield (305-DMY), peak milk yield (PMY), days in milk (DIM), parity and season of calving on mastitis in Holstein Friesian cows. All data were analyzed by general linear model (GLM) using SAS software ver.9.1.3. The current results revealed that DIM and parity had a significant effect on TMY, where the highest milk yield was obtained when DIM were more than 357 days and in the 3rd lactation season. Season of calving showed a significant effect on mastitis disease, where the highest incidence of mastitis was recorded for spring calvers.

[EN] Although growth hormone (GH) gene mutations are described in several species, the studies concerning their variabilities and associations with economic traits in rabbits are scarce, particularly associations with semen traits. A total of 149 rabbit bucks from five populations (V-line=36, Moshtohor line=28, APRI line=42, cross ½A½M=23, and Gabali=20) were used in the present study to identify polymorphism of c.-78 C>T single nucleotide polymorphism (SNP) of GH gene among these populations and to investigate the association of GH gene polymorphism with body weight (BW), daily weight gain (DG) and semen traits. DNA was extracted from blood samples for genotyping of c.-78 C>T SNP of GH gene based on polymerase chain reaction with the restriction fragment length polymorphism (PCR-RFLP) technique. The genetic diversity of SNP C>T of GH gene was assessed in terms of genotypic and allelic frequencies, effective number of alleles (Ne), observed (Ho) and expected (He) heterozygosity, Hardy-Weinberg equilibrium (HWE), reduction in heterozygosity due to inbreeding (FIS) and polymorphism information content (PIC). Three genotypes of TT, CC and TC of PCR product of 231 bp of GH gene were detected and all the populations were in HWE in terms of GH gene. The highest Ne was obtained for the Moshtohor line (1.978), while the lowest allelic numbers were obtained for V-line (1.715) and Gabali breed (1.800). The highest genotype frequency of GH gene was 0.48 in TT genotype of V-line, 0.21 in CC genotype of Moshtohor line, 0.67 and 0.56 in TC genotype of ½A½M and Gabali rabbits (P, The authors are very grateful to the Central Laboratory of the Faculty of Veterinary Medicine, Benha University, Egypt for the help and support in molecular genetic analyses. This work was financially supported by the research project entitled “Genetic improvement of local rabbit breeds by using molecular genetic techniques” from the Scientific Research Fund (SRF), Benha University, Egypt.

Pertussis is a highly contagious respiratory disease caused by the Gram-negative bacterial pathogen, Bordetella pertussis. Despite high global vaccination rates, pertussis is resurging worldwide. Here we discuss the development of current pertussis vaccines and their limitations, which highlight the need for new vaccines that can protect against the disease and prevent development of the carrier state, thereby reducing transmission. The lipo-oligosaccharide of Bp is an attractive antigen for vaccine development as the anti-glycan antibodies could have bactericidal activities. The structure of the lipo-oligosaccharide has been determined and its immunological properties analyzed. Strategies enabling the expression, isolation, and bioconjugation have been presented. However, obtaining the saccharide on a large scale with high purity remains one of the main obstacles. Chemical synthesis provides a complementary approach to accessing the carbohydrate epitopes in a pure and structurally well-defined form. The first total synthesis of the non-reducing end pertussis pentasaccharide is discussed. The conjugate of the synthetic glycan with a powerful immunogenic carrier, bacteriophage Qβ, results in high levels and long-lasting anti-glycan IgG antibodies, paving the way for the development of a new generation of anti-pertussis vaccines with high bactericidal activities and biocompatibilities.

Heparan sulfate (HS) plays important roles in many biological processes. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of their structure-activity relationship. To facilitate biological studies, a new strategy has been developed to synthesize a HS-like pseudo-hexasaccharide library, where HS disaccharides were linked in a “head-to-tail” fashion from the reducing end of a disaccharide module to the non-reducing end of a neighboring module. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved. This new class of compounds bound with fibroblast growth factor 2 (FGF-2) with similar structure-activity trends as HS oligosaccharides bearing native glycosyl linkages. The ease of synthesis and the ability to mirror natural HS activity trends suggest that the new head-to-tail linked pseudo-oligosaccharides could be an exciting tool to facilitate the understanding of HS biology.

MUC1 glycopeptides are attractive antigens for anti-cancer vaccine development. One potential drawback in using the native MUC1 glycopeptide for vaccine design is the instability of the O-glycosyl linkage between the glycan and the peptide backbone to glycosidase. To overcome this challenge, a MUC1 glycopeptide mimic has been synthesized with the galactose-galactosamine disaccharide linked with threonine (Thomsen-Friedenreich or Tf antigen) through an unnatural β-glycosyl bond. The resulting MUC1-β-Tf had a much-enhanced stability toward a glycosidase capable of cleaving the glycan from the corresponding MUC1 glycopeptide with the natural α-Tf linkage. The MUC1-β-Tf was subsequently conjugated with a powerful carrier bacteriophage Qβ. The conjugate induced high levels of IgG antibodies in clinically relevant human MUC1 transgenic mice, which cross-recognized not only the natural MUC1-α-Tf glycopeptide but also MUC1 expressing tumor cells, supporting the notion that a simple switch of the stereochemistry of the glycan/peptide linkage can be a strategy for anti-cancer vaccine epitope design for glycopeptides.

Background: Fosfomycin is a bactericidal drug that inhibits bacterial cell wall and also reduces the adherence ability of bacteria to uro-epithelial cells with a broad anti-bacterial activity against both Gram-negative and Gram-positive. Objective: To compare the efficacy and safety of fosfomycin compared to nitrofurantoin and cephalosporin in pregnant women presented with lower urinary tract infection. Patients and Methods: This was a double blinded, randomized controlled trial conducted at Shebin El-Kom Teaching Hospital from Aug 2019 to Aug 2020. Patients experienced uncomplicated lower urinary tract infection either asymptomatic bacteriuria or cystitis were recruited. Patients were randomly allocated via a random table number into three groups, each group comprised 35 patients. Group I received 3 g oral fosfomycin weekly, group II received 100 mg oral nitrofurantoin three times daily, and group III received 500 mg oral cephalosporin three times daily. After 7 days of treatment, all studied groups were subjected to urine sampling and culture analysis and were examined for occurrence of side effects. Results: All patients enrolled in our study had uncomplicated lower urinary tract infection either cystitis (n=85 cases) or asymptomatic bacteriuria (n=20 cases). There was clinical difference in urine pus cells and urine culture in fosfomycin after treatment compared to other groups. The side effects were reported in 7 cases with fosfomycin compared to 14 in other two groups with significant difference. Conclusion: Fosfomycin tromethamine was proved to be more effective, safe, and fewer side effects were reported, which makes fosfomycin the drug of choice for uncomplicated lower urinary tract infection during pregnancy.

The objectives of this study were to detect the polymorphism of 2126A∕G SNP in the β-casein (CSN2) gene among Egyptian Maghrebi camels and to investigate the association of 2126A∕G SNP genotypes, parity, lactation stage, and temperature–humidity index (THI) with the milk composition traits of Maghrebi camels. Sixty-eight hair samples were collected from three different populations of Maghrebi camels for DNA extraction. Fat, protein, total solids, solids-not-fat, and lactose percentages were determined in Maghrebi camel milk using an automatic milk analyzer device. Three different genotypes – A/A, A/G, and G/G – were identified in the 5′ flanking region of β-casein gene by using PCR-RFLP method with the A/G genotype showing the highest frequency. Association among these three genotypes with milk composition traits suggests a positive effect of A/A genotype on acidity and protein percentage. Higher protein and acidity values were observed in the milk of individuals carrying the A/A genotype. The protein percentage of this study significantly increased from the first till the fourth parity and then decreased. Fat and total solid percentages were significantly higher in the late stage of lactation, while lactose showed a decreasing trend from the early till the late stages of lactation. Fat and protein percentages were highest in the low THI class. Our results encourage the utilization of Maghrebi camel milk for cheese and butter processing at the late lactation stages of the middle parities of their productive life. Moreover, the A/G SNP of the CSN2 gene may be used as a DNA marker in selection programs for the improvement of camel milk composition. Further studies are needed in order to fully explore the variation in the chemical composition of camel milk due to the effect of CSN2 gene, parity, lactation stage, and THI factors.

The objectives of this study were to detect genetic polymorphism in exon 10 of Follicle Stimulating Hormone Receptor gene (FSHR) by using RFLP and direct sequence methods, also to investigate their possible association with infertility traits in Egyptian buffaloes. A total number of 50 female Egyptian buffaloes at Mahallet Mousa experimental farms in Kafr El-sheikh province were investigated. Animals were divided into three groups: normal fertile (20 animals), infertile due to anestrum (15 animals) and infertile due to repeat breeding (15 animals). Genomic DNA was extracted from blood samples, then PCR was performed with annealing temperatures of 57oC to amplify 231 bp of FSHR exon 10 gene. The amplicons were digested with Hin1II (NlaIII) restriction enzyme. The results showed that all the investigated buffaloes were monomorphic and genotyped as A/A genotype. Moreover, the monomorphism of buffaloes FSHR exon 10 gene was confirmed by sequencing three samples from each buffaloes’ group. It seems that FSHR gene are highly conserved in the investigated buffalo’s population.

A successful synthesis of O-sulfated syndecan-1-like (Q23-E120) glyco-polypeptide was accomplished. The synthesis features the integration of an O-sulfated carbohydrate-bearing glycopeptide cassette with efficient protein ligation strategies, overcoming the acid lability of carbohydrate sulfates as a major hurdle in solid-phase peptide synthesis. Crucial to the synthesis is the microwave-assisted Ag(I) ligation, which afforded the ligation product in improved overall yield. This O-sulfated syndecan-1 (Q23-E120) is the longest O-sulfated glyco-polypeptide prepared to date.

There is increasing interest in using stereotactic body radiation therapy (SBRT) in areas of oligoprogressive metastatic disease (OPD). Our main objective was to investigate the impact of SBRT on overall survival (OS) and the incidence of systemic therapy treatment switches in this population.A retrospective institutional review of patients treated with SBRT for OPD was performed. Patients were included if they received SBRT for 1-3 discrete progressing metastases, using a dose of at least 5 Gy per fraction. The study aimed to calculate progression-free survival (PFS), overall survival (OS), local control (LC), and incidence of treatment switch (TS). PFS and OS were calculated using the Kaplan-Meier methodology, while LC and TS were determined using cumulative incidence.Eighty-one patients with a total of 118 lesions were treated with SBRT from July 2014 to November 2020. The Median SBRT dose was 40 (18-60) Gy in 5 (2-8) fractions. Patients had primarily kidney, lung, or breast cancer. Most patients were treated with a tyrosine kinase inhibitor (TKI) (30.9%) or chemotherapy (29.6%) before OPD. The median follow-up post-SBRT was 14 months. Median OS and PFS were 25.1 (95% CI 11.2-39.1) months and 7.8 (95% CI 4.6-10.9) months, respectively. The cumulative incidence of local progression of treated lesions was 5% at 1 year and 7.3% at 2 years. Sixty patients progressed after SBRT and 17 underwent additional SBRT. Thirty-eight patients (47%) changed systemic therapy following SBRT; the cumulative incidence of TS was 28.5% at 6 months, 37.4% at 1 year, and 43.9% at 2 years.SBRT effectively controls locally progressing lesions but distant progression still occurs frequently. A sizeable number of patients can be salvaged by further SBRT or have minimally progressing diseases that may not warrant an immediate initiation/switch in systemic therapy. Further prospective studies are needed to validate this benefit.

Heparan sulfate (HS) regulates a wide range of biological events, including blood coagulation, cancer development, cell differentiation, and viral infections. It is generally recognized that structures of HS can critically impact its biological functions. However, with complex structures of naturally existing HS, systematic investigations into the structure-activity relationship (SAR) of HS and efforts to unlock their "sulfation code" have been largely limited due to the challenges in preparing diverse HS oligosaccharide sequences. Herein, we report an automated machine-aided solid-phase strategy that significantly expedited the assembly of HS disaccharides. The key strategically protected advanced disaccharide intermediates were immobilized onto Synphase lanterns. Divergent deprotections and sulfations of the disaccharides were achieved on the lanterns in high yields. In addition, the full synthetic process was automated, enabling the reproducible production of HS disaccharides. A library of 16 HS disaccharides with diverse sulfation patterns was prepared via this method. Compared to the traditional HS synthesis, this new strategy led to a reduction of 50% of the number of synthetic steps and over 80% of the number of column purification steps needed from the disaccharide intermediates, significantly improving the overall synthetic efficiency. The potential utility of the method was highlighted in a microarray study using the synthetic HS disaccharide library with fibroblast growth factor-2 (FGF-2), which yielded insights into the SAR of HS/FGF-2 interactions.

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qβ-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

Proteoglycans are a family of complex glycoproteins with glycosaminoglycan chains such as heparan sulfate (HS) attached to the core protein backbone. Due to the high structural heterogeneity of HS in nature, it is challenging to decipher the respective roles of the HS chain and the core protein on proteoglycan functions. While the sulfation patterns of HS dictate many activities, the core protein can potentially impact HS functions. In order to decipher this, homogeneous proteoglycan glycopeptides are needed. Herein, we report the first successful synthesis of proteoglycan glycopeptides bearing multiple aspartic acids in the core peptide and O- and N-sulfations in the glycan chain, as exemplified by the syndecan-4 glycopeptides. To overcome the high acid sensitivities of sulfates and base sensitivities of the glycopeptide during synthesis, a new synthetic approach has been developed to produce a sulfated glycan chain on a peptide sequence prone to the formation of aspartimide side products. The availability of the structurally well-defined synthetic glycopeptide enabled the investigation of their biological functions including cytokine, growth factor binding and heparanase inhibition. Interestingly, the glycopeptide exhibited context dependent enhancement or decrease of biological activities compared to the peptide or the glycan alone. The results presented herein suggest that besides varying the sulfation patterns of HS, linking the HS chain to core proteins as in proteoglycans may be an additional approach to modulate biological functions of HS in nature., Attaching heparan sulfate glycan on a peptide backbone can modulate biological functions of the glycan.

The objectives of this study were to identify polymorphisms in the lactoferrin gene among three Egyptian goat breeds (Barki, Zaraibi, and Damascus) and to investigate the effect of LF genotype, parity, and lactation stage on milk composition traits of Zaraibi goats. One hundred and thirty-two blood samples were collected for DNA extraction, with 53 from Zaraibi, 40 from Damascus, and 39 from Barki breeds. Fat, protein, total solids, solids-not-fat, and lactose percentages were determined in Zaraibi goat milk using an automatic milk analyzer. Two genotypes, GG and GA, in the lactoferrin gene were identified using single-strand conformation polymorphism and were confirmed by direct sequencing technique. The Zaraibi breed recorded the highest heterozygosity (0.272) and effective number of alleles (1.369), while the Damascus breed recorded the lowest values. The G/A SNP showed a significant association with protein, solids-not-fat, and total solid content of Zaraibi goat milk. Protein, solids-not-fat, and total solid content in our study were significantly higher at early and late parities. Lactose percentage decreased significantly from early to late parity. Fat, protein, solids-not-fat, and total solid content were significantly higher at early and late stages of lactation, and our results encourage the utilization of Zaraibi goat milk in cheese and butter processing at these stages. Moreover, the G/A SNP of the LF gene may be a useful marker for assisted selection programs to improve goat milk composition.

The objectives of this study were, firstly, to conduct genetic characterization of Egyptian Arabian horses based on 14 TKY microsatellite markers, secondly, to investigate the powerfulness of these 14 TKY markers for parentage assignment of Arabian horses. A total of 101 horse samples including (Arabian = 71, Thoroughbred = 19 and Nooitgedacht = 11) were analysed by 14 TKY microsatellite markers. The PCR products were electrophoresed on Genetic analyzer 3500 with the aid of Liz standard. The basic measures of the allele’s size and genetic diversity were computed using bioinformatics software. The polymorphism of the TKY markers across the Arabian population showed moderate values for genetic diversity parameters; number of allele ( N A ) =8.143, effective number of allele ( N e ) = 3.694, observed heterozygosity ( H O ) = 0.599, expected heterozygosity ( H E ) = 0.691, polymorphic Information Content ( PIC ) = 0.636 and Inbreeding coefficient ( F IS ) = 0.128 . The combined probability of exclusion (CPE) value of the 14 TKY microsatellite loci of our Arabian horses was 0.9999. The results from current study confirm the applicability and efficiency of TKY microsatellite panel for evaluating the genetic diversity and parentage assignment of Egyptian Arabian horses. Key words: Arabian horses; genetic diversity; microsatellite; TKY markers GENSKA RAZNOVRSTNOST EGIPCANSKIH KONJ ARABSKE PASME IZ KOBILARNE EL-ZAHRAA NA PODLAGI 14 MIKROSATELITSKIH OZNAK TKY Izvlecek: Nameni raziskave so bili genetska karakterizacija egipcanskih konj arabske pasme na podlagi 14 mikrosatelitskih oznacevalecv TKY ter raziskava moci 14 oznacevalcev TKY za dodelitev starsev arabskih konj. S pomocjo 14 mikrosatelitskih oznacevalcev TKY je bilo analiziranih 101 vzorcev konj (arabski = 71, cistokrvni = 19 in konji Nooitgedacht = 11). Produkte PCR so analizirali s pomocjo elektroforeze na genskem analizatorju 3500 s pomocjo Liz standarda. Osnovne mere velikosti alela in genske raznovrstnosti so bile izracunane s pomocjo programske opreme za bioinformatiko. Polimorfizem oznacevalcev TKY v arabski populaciji je pokazal zmerne vrednosti za parametre genske raznolikosti; stevilo alelov (NA) = 8,143, efektivno stevilo alelov (Ne) = 3,694, opazovana heterozigotnost (HO) = 0,599, pricakovana heterozigotnost (HE) = 0,691, polimorfna informacijska vsebina (PIC) = 0,636 in Inbriding koeficient (FIS) = 0,128. Skupna vrednost verjetnosti izkljucitve (CPE) 14 mikrosatelitskih lokusov TKY njihovih arabskih konj je bila 0,9999. Rezultati te raziskave potrjujejo uporabnost in ucinkovitost mikrosatelitske plosce TKY za oceno genetske raznovrstnosti in starsevske pripadnosti egipcanskih arabskih konj. Kljucne besede: arabski konji; genska raznolikost; mikrosatelit; markerji TKY

[EN] The objectives of the present study were 1) to evaluate the polymorphism of growth hormone(GH), insulin-like growth factor 2 (IGF2) and progesterone receptor (PGR) genes in Sinai Gabali rabbits, and 2) to assess their associations with growth, litter size and milk production traits in Sinai Gabali rabbits. The C>T, A>Del and A>G single nucleotide polymorphisms of GH, IGF2 and PGR genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism using BstUI, HpyF31 and BsaI restriction enzymes, respectively. The C/T genotype of GH gene recorded the heaviest body weights for body weight (BW) at 8 wk (1190.22±19.29 g) and 12 wk of age (1842.46±30.19 g) and recorded the largest litter size at birth (LSB: 7.37±0.12 kits) traits. The Del/Del genotype of IGF2 gene showed the superiority over the other genotypes for BW at 4 wk (507.17±8.87 g), 8 wk (1239.39±14.0 g), and 12 wk of age (1950.15±18.1 g), as well as for daily weight gain from 4 to 8 wk (26.05±0.37 g/d), and from 8 to 12 wk of age (25.48±0.56 g/d) traits. The G/G genotype of the PGR gene showed superiority for LSB (7.51±0.13 kits) and litter size at weaning (6.53±0.14 kits) traits over the other genotypes. Regarding milk yield traits; the C/C, A/A and A/A genotypes of GH, IGF2 and PGR genes yielded more milk compared to the other genotypes. The means of total milk yield in 28 d for these genotypes were 2936±29 g, 2921±43 g and 2930±35 g, respectively. Thus, GH, IGF2 and PGR genes might be useful for marker-assisted selection programmes for improvement of rabbit growth, litter size and milk yield traits., This work was supported by the research project “Genetic improvement of local rabbit breeds using molecular genetic techniques” from the Scientific Research Fund (SRF), Benha University, Egypt. The English revision of the manuscript conducted by Mr. Roderick Cantlay-Hollis is also acknowledged.

Please see the Author Video associated with this article. BACKGROUND. The use of synthetic 2D mammography (SM) with digital breast tomosynthesis (DBT) in place of standard 2D digital mammography (D...

A successful synthesis of O-sulfated syndecan-1-like (Q23–E120) glyco-polypeptide was accomplished. The synthesis features the integration of an O-sulfated carbohydrate-bearing glycopeptide cassette with efficient protein ligation strategies, overcoming the acid lability of carbohydrate sulfates as a major hurdle in solid-phase peptide synthesis. Crucial to the synthesis is the microwave-assisted Ag(I) ligation, which afforded the ligation product in improved overall yield. This O-sulfated syndecan-1 (Q23–E120) is the longest O-sulfated glyco-polypeptide prepared to date.

Atherosclerosis is associated with inflammation in the arteries, which is a major cause of heart attacks and strokes. Reducing the extent of local inflammation at atherosclerotic plaques can be an attractive strategy to combat atherosclerosis. While statins can exhibit direct anti-inflammatory activities, the high dose required for such a therapy renders it unrealistic due to their low systemic bioavailabilities and potential side effects. To overcome this, a new hyaluronan (HA) - atorvastatin (ATV) conjugate was designed with the hydrophobic statin ATV forming the core of the nanoparticle (HA-ATV-NP). The HA on the NPs can selectively bind with CD44, a cell surface receptor overexpressed on cells residing in atherosclerotic plaques and known to play important roles in plaque development. HA-ATV-NPs exhibited significantly higher anti-inflammatory effects on macrophages compared to ATV alone in vitro. Furthermore, when administered in an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis following a 1-week treatment regimen, HA-ATV-NPs markedly decreased inflammation in advanced atherosclerotic plaques, which were monitored through contrast agent aided magnetic resonance imaging. These results suggest CD44 targeting with HA-ATV-NPs is an attractive strategy to reduce harmful inflammation in atherosclerotic plaques.

Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUCl antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20–22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.

Aim: Native rabbits in smallholder system are considered as important genetic resources, and the present study was aimed to study the genetic and phenotypic characterization and detection of the maternal origin of the native rabbit populations located at the Middle of Egypt. Materials and Methods: A survey of native rabbit populations was conducted in three governorates (Fayum [FY], Beni Suef [BN], and El Menia [MN]). The phenotypic characterization of rabbits included the profile body of the head, ears, eyes, neck, and legs and the coat colors. The blood samples were collected for genetic characterization based on mitochondrial (cytochrome b) and the microsatellite markers. Results: The phenotypic characterization of the body parts in the three populations was almost similar. The body weight of the mature rabbits in MN government was significantly heaviest, and the measurements for the main body parts (body length, chest circumference, and abdominal girth) were the highest compared to the two populations. The results of mitochondrial (cytochrome b) analysis revealed that the rabbits from the three governments belonged to lineage A except one animal was recorded as lineage G from MN's rabbit population. The results of the microsatellite markers revealed that the genetic diversity between the three populations showed genetic interferences; however, a closer genetic relationship was observed between BN and MN than FY. The majority of the genetic diversity was the individual variability. Conclusion: The mitochondrial lineage A is the major lineage in rabbit populations in the area of the Middle Egypt understudy. The genetic populations' structure is the interferences among the three populations. A large-scale survey should be done on native rabbit populations for the sustainable management and conservation of the local breeds' genetic resources.

Objective: The objectives of our study were to estimate the effect of some non-genetic factors on production and reproduction traits of Egyptian buffaloes and to estimate the breeding values for these traits. Materials and Methods: Data from 965 lactation records of 305 Egyptian buffalo cows mated by 73 sires that were raised at Mahallet Mousa Experimental farms of Animal Production Research Institute were collected. Dairy records covered the period from 2001 to 2015. The data were arranged and statistically analyzed using SAS version 9.1.3 to study the effect of non-genetic factors and the MTDFREMAL program was included in estimating the expected breeding values. Results: Our results showed that buffalo cows that calved in winter season recorded the highest and significant total milk yield (TMY) and daily milk yield (DMY) traits and the best reproductive performance was indicated by the lower number of services per conception and the shortest calving interval (CI) period. Moreover, age at first calving and dry period (DP) showed a highly significant effect on the TMY and DMY. A significant effect for the level of milk production on days open (DO) period was recorded in our study. The range of sires EBV was 540 kg, 295.2 days, 113.9 days, 2.8 months, and 71.1 days for TMY, LL, DO, CI, and DP, respectively. Conclusion: Buffalos breeders must consider the season of calving, parity, and DP in management program because they greatly affect the farm productivity and profitability and they must select animals with higher breeding values to be the parent of the next generation. [J Adv Vet Anim Res 2018; 5(4.000): 374-380]

Aim: This study aimed to analyze the genetic diversity and relationships of 10 Egyptian pigeon populations belonging to Columba livia domestica species using 11 microsatellite markers and to investigate the success of these markers amplification across another eight pigeon species. Methods: Genomic DNA was isolated from feather samples of 179 pigeon samples from 10 Egyptian breeds: Asfer Weraq (n=14), Austoraly (n=20), Reehani (n=21), Messawed (n=17), Nemssawy (n=27), Otatti (n=12), Morasla (n=17), Tumbler (n=22), Halaby Asfer (n=10), and Karakandy (n=19) in addition to Japanese feral pigeons (n=30). Genotyping was done using 11 specific polymorphic microsatellite makers. Moreover, 37 samples not belonging to C. livia domestica but belonging to another eight pigeon species were genotyped. The polymerase chain reaction (PCR) products were electrophoresed on an ABI 3130xl DNA Sequencer. The basic measures of genetic diversity and phylogenetic trees were computed using bioinformatics software. Results: Across the 10 studied Egyptian populations, the number of alleles per locus ranged from 3 to 19 and the average number of alleles observed was 9.091. The lowest value of expected heterozygosity (0.373) was obtained for the Reehani breed, and the highest value (0.706) was found for Morasla breed. The overall expected heterozygosity of Egyptian pigeons was 0.548. The FST coefficient which indicates fixation coefficients of subpopulations within the total population for the 11 loci varied from 0.318 to 0.114 with a relatively high mean (0.226). In our study, the FIS showed a relatively high average (0.037). The pairwise Reynolds's genetic distance between the 11 studied pigeon populations recorded lower values between Otatti and Austoraly (0.025) and between Morasla and Japanese feral pigeons (0.054). These results are supported by clustering pattern either by the neighbor-joining phylogenetic tree or by a Bayesian clustering of STRUCTURE with the admixture method. Conclusion: We confirm the applicability of the CliμD17, CliμT17, CliμD16, CliμD32, CliμT13, CliμD01, PG1, PG2, PG4, PG6, and PG7 microsatellite markers among Egyptian domestic pigeons and across other pigeon species using cross-species amplification method. The information from this study should be useful for genetic characterization and for developing conservation programs of this important species.

IMPORTANCE: The use of ultrasonography (US) vs cross-sectional imaging for preoperative evaluation of papillary thyroid cancer is debated. OBJECTIVE: To compare thyroid US and computed tomography (CT) in the preoperative evaluation of papillary thyroid cancer for cervical lymph node metastasis (CLNM), as well as extrathyroidal disease extension. DATA SOURCES: MEDLINE and Embase were searched from January 1, 2000, to July 18, 2020. STUDY SELECTION: Studies reporting on the diagnostic accuracy of US and/or CT in individuals with treatment-naive papillary thyroid cancer for CLNM and/or extrathyroidal disease extension were included. The reference standard was defined as histopathology/cytology or imaging follow-up. Independent title and abstract review (2515 studies) followed by full-text review (145 studies) was completed by multiple investigators. DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were followed. Methodologic and diagnostic accuracy data were abstracted independently by multiple investigators. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool independently and in duplicate. Bivariate random-effects model meta-analysis and multivariable meta-regression modeling was used. MAIN OUTCOMES AND MEASURES: Diagnostic test accuracy of US and CT of the neck for lateral and central compartment CLNM, as well as for extrathyroidal disease extension, determined prior to study commencement. RESULTS: A total of 47 studies encompassing 31 942 observations for thyroid cancer (12 771 with CLNM; 1747 with extrathyroidal thyroid extension) were included; 21 and 26 studies were at low and high risk for bias, respectively. Based on comparative design studies, US and CT demonstrated no significant difference in sensitivity (73% [95% CI, 64%-80%] and 77% [95% CI, 67%-85%], respectively; P = .11) or specificity (89% [95% CI, 80%-94%] and 88% [95% CI, 79%-94%], respectively; P = .79) for lateral compartment CLNM. For central compartment metastasis, sensitivity was higher in CT (39% [95% CI, 27%-52%]) vs US (28% [95% CI, 21%-36%]; P = .004), while specificity was higher in US (95% [95% CI, 92%-98%]) vs CT (87% [95% CI, 77%-93%]; P

Due to the wide presence of carbohydrates in nature and their crucial roles in numerous important biological processes, oligosaccharides have attracted a lot of attention in synthetic organic chemistry community. Many innovative synthetic methods have been developed for oligosaccharide synthesis, among which the pre-activation based glycosylation is particularly noteworthy. Traditionally, glycosylation reactions are carried out when the glycosyl donor and the acceptor are both present when the promoter is added. In comparison, the pre-activation based glycosylation is unique, where the glycosyl donor is activated by the promoter in the absence of the acceptor. Upon complete donor activation, the acceptor is added to the reaction mixture enabling glycosylation. The key step in any oligosaccharide synthesis is the stereoselective formation of the glycosidic bond. As donor activation and acceptor glycosylation are temporally separated, pre-activation based glycosylation can bestow unique stereochemical control. This review systematically discusses factors impacting the stereochemical outcome of a pre-activation based glycosylation reaction including substituents on the glycosyl donor, reaction solvent, and additives. Applications of pre-activation based stereoselective glycosylation in assembly of complex oligosaccharides are also discussed.

N-Linked glycopeptides have highly diverse structures in nature. Herein, we describe the first synthesis of rare multi-antennary N-glycan bearing glycan chains on 6-OH of both α1,6- and α1,3-linked mannose arms. To expedite divergent generation of N-glycan structures, four orthogonal protective groups were installed at the branching points on the core tetrasaccharide, which could be removed individually without affecting one another. In addition, the synthetic route is flexible, allowing a bisecting glucosamine moiety to be introduced at a late stage of the synthesis, further expanding the diversity of sequences that could be achieved. The bisecting glucosamine unit significantly reduced the glycosylation yields of adjacent mannoses, which was attributed to steric hindrance imposed by the glucosamine based on molecular modelling analysis. The N-glycans were then transformed to oxazoline donors and ligated with a glycopeptide acceptor from haptoglobin promoted by the wild type Arthrobacter endo-β-N-acetylglucosaminidase (Endo-A). Endo-A exhibited interesting substrate preferences depending on donor sizes, which was rationalized through molecular dynamics studies. This is the first time that a glycopeptide bearing a bisecting N-acetyl glucosamine (GlcNAc), the rare N-glycan branch, and two LewisX trisaccharide antennae was synthesized, enabling access to this class of complex glycopeptide structures.

The objectives of this study were to achieve phenotypic characterization of three domestic Egyptian goose populations collected from three different geographical zones (Kafr El-Sheikh, Fayoum and Luxor) and to perform genetic characterization of these three populations based on mtDNA D-loop and 12 microsatellite markers. The body measurements of 402 domestic mature geese belonging to these three governorates showed that the lengths of the head, culmen and tarsus and the live body weight varied significantly among the three studied Egyptian goose populations. After alignment of a 710-base-pair segment of the goose mtDNA control region, there was a single haplotype in the three Egyptian goose populations, indicating the same maternal origins. The genotyping of the 12 microsatellite markers showed low diversity indices, including average observed (NA) and effective (NE) number of alleles and observed (HO) and expected heterozygosity (HE) (3.333, 1.760, 0.277 and 0.352, respectively), and a high inbreeding coefficient (FIS = 0.203) across the three Egyptian goose populations. The high inbreeding and low genetic and morphological differentiation of Egyptian geese could be corrected by establishing a large base population through capturing small populations with the highest genetic variation. The findings of the current study can therefore serve as an initial guide to design further investigations for developing conservation programs of Egyptian geese genetic resources.