Publications by authors named "Shahid Mehmood"

55 Publications

A p-n Heterojunction Based Pd/[email protected] Organic Frameworks for High-Sensitivity Room-Temperature Formaldehyde Gas Sensor.

Front Chem 2021 20;9:742488. Epub 2021 Sep 20.

College of Electronics and Information Engineering, Shenzhen University, Shenzhen, China.

As formaldehyde is an extremely toxic volatile organic pollutant, a highly sensitive and selective gas sensor for low-concentration formaldehyde monitoring is of great importance. Herein, metal-organic framework (MOF) derived Pd/[email protected] porous nanostructures were synthesized through hydrothermal method followed by calcination processes Specifically, porous Pd/[email protected] nanomaterials with large surfaces were synthesized using MOFs as sacrificial templates. During the calcination procedure, an optimized temperature of 500°C was used to form a stable structure. More importantly, intensive [email protected] inside the material and composite interface provides lots of p-n heterojunction to efficiently manipulate room temperature sensing performance. As the height of the energy barrier at the junction of [email protected] exponentially influences the sensor resistance, the Pd/[email protected] nanomaterials exhibit high sensitivity (38.57% for 100 ppm) at room temperature for 1-ppm formaldehyde with satisfactory selectivity towards (ammonia, acetone, methanol, and IPA). Besides, due to the catalytic effect of Pd and PdO, the adsorption and desorption of the gas molecules are accelerated, and the response and recovery time is as small as 256 and 264 s, respectively. Therefore, this MOF-driven strategy can prepare metal oxide composites with high surface area, well-defined morphology, and satisfactory room-temperature formaldehyde gas sensing performance for indoor air quality control.
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http://dx.doi.org/10.3389/fchem.2021.742488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489732PMC
September 2021

Development of a fluorogenic ADAMTS-7 substrate.

J Enzyme Inhib Med Chem 2021 Dec;36(1):2160-2169

Department of Immunology and Inflammation, Imperial College London, London, UK.

The extracellular protease ADAMTS-7 has been identified as a potential therapeutic target in atherosclerosis and associated diseases such as coronary artery disease (CAD). However, ADAMTS-7 inhibitors have not been reported so far. Screening of inhibitors has been hindered by the lack of a suitable peptide substrate and, consequently, a convenient activity assay. Here we describe the first fluorescence resonance energy transfer (FRET) substrate for ADAMTS-7, ATS7FP7. ATS7FP7 was used to measure inhibition constants for the endogenous ADAMTS-7 inhibitor, TIMP-4, as well as two hydroxamate-based zinc chelating inhibitors. These inhibition constants match well with IC values obtained with our SDS-PAGE assay that uses the N-terminal fragment of latent TGF-β-binding protein 4 (LTBP4S-A) as a substrate. Our novel fluorogenic substrate ATS7FP7 is suitable for high throughput screening of ADAMTS-7 inhibitors, thus accelerating translational studies aiming at inhibition of ADAMTS-7 as a novel treatment for cardiovascular diseases such as atherosclerosis and CAD.
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http://dx.doi.org/10.1080/14756366.2021.1983808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494430PMC
December 2021

Bioaccumulation and transfer of zinc in soil plant and animal system: a health risk assessment for the grazing animals.

Environ Sci Pollut Res Int 2021 Aug 10. Epub 2021 Aug 10.

Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan.

Heavy metals pollution has thorough worldwide apprehensions due to the instantaneous growth of industries. Farming regions are irrigated mainly with wastewater which contains both municipal and industrial emancipations. Keeping in view the above scenario, a study was designed in which three sites irrigated with ground, canal, and municipal wastewater in the District Jhang were selected to determine the zinc accumulation and its transfer in the soil, plant, and animal food chain. Zinc concentration was ranged as 18.85-35.59mg/kg in the soil, 26.42-42.67 mg/kg in the forage, and 0.982-2.85mg/kg in the animal samples. Investigated zinc concentration in soil and forages was found to be within the recommended WHO/FAO limits, but blood samples exceed the standards of NRC (2007). The maximum level of pollution load index (0.427-0.805mg/kg) and enrichment factor (0.373-0.894 mg/kg) for zinc was noticed upon wastewater irrigation. Daily intake (0.039 to 0.082 mg/kg/day) and health risk index (0.130 to 0.275 mg/kg/day) of zinc metal was higher in the buffaloes that feed on wastewater-irrigated forages. Bio-concentration factor (0.840 to 2.01mg/kg) for soil-forage was >1 which represents that these plants accumulated the zinc concentration into their tissues and raised health issues in grazing animals on consumption of wastewater-contaminated forages. As animal-derived products are part of human food, then zinc toxicity prevailed in livestock tissues ultimately affects the human food chain. Overall, findings of this study concluded that animal herds should be monitored periodically to devise preventive measures regarding the toxic level of heavy metals availability to livestock.
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http://dx.doi.org/10.1007/s11356-021-15808-zDOI Listing
August 2021

Optimisation of user-selectable volumetric modulated arc therapy (VMAT) planning parameters: VMAT arcs for prostate and head-and-neck cancers.

J Pak Med Assoc 2021 Apr;71(4):1093-1099

Department of Mathematics, NAMAL INSTITUTE Mianwali, Pakistan.

Objective: To evaluate different VMAT planning techniques for a multi-leaf collimator (MLC)providing maximum aperture of 21 × 16 cm².

Methods: A VMAT planning study of nine prostate and nine head-and-neck cancer patients was carried out. The patients were previously treated with Intensity Modulated Radiotherapy (IMRT) technique during 2014-15, at radiation oncology SanBortolo Hospital, Vicenza, Italy. Three VMAT plans for each of prostate and head-and-neck cancer patient were optimized using Pinnacle treatment planning system for 6MV photon beam from ElektaSynergyS®Linac system. Single arc, dual arc and combined two independent-single-arcs were optimized for collimator angle 45°. VMAT treatment planning comparison was made among single-arc dual-arc and combined two independent-single-arcs. The student's t-test (two-sided) with p ≤ 0.05 was applied for significant difference between dose volume indices of plans.

Results: All VMAT techniques produced clinically acceptable plans for prostate, while for head-and-neck, DA and ISAs significantly improved target coverage compared to SA. Single arc is sufficient for prostate, while inefficient in case of head-and-neck dose-planning. In spite of having different VMAT optimization approach dual arc and two combined independent-single-arcs provided very similar target coverage, while dual arc improved sparing of organs-at-risk. Similar treatment delivery times were observed for DA and ISAs VMAT techniques.

Conclusions: Single arc is sufficient for prostate, while inefficient in case of head-and-neck dose-planning. Dual arc and two combined independent-single-arcs provided similar PTV coverage, while DA provided better sparing of organs at risk.
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http://dx.doi.org/10.47391/JPMA.710DOI Listing
April 2021

Interventions in mating strategies of broiler breeder during peak and post peak phase influence hatching traits.

Poult Sci 2021 Jul 11;100(7):101095. Epub 2021 Mar 11.

Department of Poultry Production, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

The study evaluated the effect of housing system, insemination frequency, and sperm concentration on hatching traits of commercial broiler breeder. Experiment was set up as 2 × 4 × 4 factorial arrangement under completely randomized design. A total of 960 broiler breeder females (Ross-308) were divided evenly (480) into two groups for Artificial Insemination in cages (AIC) and on deep litter floor (AIF) with 41 and 48 males were allocated for aforesaid flocks, respectively. Females birds of both flocks (AIC and AIF) were further divided into 4 treatment groups to apply 4 various insemination frequencies at 4, 6, 8, and 10th days. These treated groups were further divided into 4 subgroups to apply each of insemination frequencies with 4 different sperm concentrations per insemination dose 100, 125, 150, and 175 × 10 sperms during peak phase of production which were replaced with 200, 225, 250, and 275 × 10 sperms in post peak phase. According to the results, significantly higher egg production, fertility, hatchability and number of chicks were documented when AI was conducted in cages as compared to deep litter floor. Although, the best reproductive performance was observed on 4 and 6th day insemination frequencies on all subjected sperm concentrations during peak; however, these parameters were found better on only 4th day during post peak. Sperms concentrations of 150, 175 × 10 during peak and 250 and 275 × 10 during post peak brought forth the best reproductive performance on all insemination frequencies. Although, embryonic mortality was significantly higher, when AI was conducted in floored flocks particularly when repeated after 4th day; however, various sperm concentrations found inert. In conclusion, AI found advantageous in caged flock as compared to floored. The consortium of different insemination frequencies and sperms concentrations are required for sustainable reproductive traits with progression of breeder age.
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http://dx.doi.org/10.1016/j.psj.2021.101095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165571PMC
July 2021

Structural characterisation of the Chaetomium thermophilum Chl1 helicase.

PLoS One 2021 10;16(5):e0251261. Epub 2021 May 10.

Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, London, United Kingdom.

Chl1 is a member of the XPD family of 5'-3' DNA helicases, which perform a variety of roles in genome maintenance and transmission. They possess a variety of unique structural features, including the presence of a highly variable, partially-ordered insertion in the helicase domain 1. Chl1 has been shown to be required for chromosome segregation in yeast due to its role in the formation of persistent chromosome cohesion during S-phase. Here we present structural and biochemical data to show that Chl1 has the same overall domain organisation as other members of the XPD family, but with some conformational alterations. We also present data suggesting the insert domain in Chl1 regulates its DNA binding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251261PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109800PMC
November 2021

Updating Sacbrood Virus Quantification PCR Method Using a TaqMan-MGB Probe.

Vet Sci 2021 Apr 13;8(4). Epub 2021 Apr 13.

College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Sacbrood virus (SBV) is a common honey bee virus disease. SBV variants and strains identified in Asian honey bees, , have created confusion in identifications. Although the regional names indicated the expansions of the virus in new regions, pathogenesis, and genomes of these variants are not distinct enough to be a separate virus species. However, current SBV qPCR methods may not detect newly identified SBV variants (Ac SBV) according to the genome sequences. Since these Ac SBV can naturally infect and possibly other hymenopterans, ignorance of Ac SBV variants in detection methods is simply unwise. In this report, we updated the qPCR method based on Blanchard's design that used conserved regions of VP1 to design a TaqMan method with an MGB (minor groove binder) probe. We tested the method in bees and hornets, including , , and . The updated primers and the probe can match published SBV and Ac SBV genomes in databases, and this updated method has reasonable sensitivity and flexibility to be applied as a detection and quantification method before the discovery of variants with more mutated VP1 gene.
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http://dx.doi.org/10.3390/vetsci8040063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070565PMC
April 2021

Improving the performance of opportunistic routing using min-max range and optimum energy level for relay node selection in wireless sensor networks.

PeerJ Comput Sci 2020 7;6:e326. Epub 2020 Dec 7.

School of Computer Science and Electronic Engineering, University of Essex, Colchester, United Kingdom.

Opportunistic routing is an emerging routing technology that was proposed to overcome the drawback of unreliable transmission, especially in Wireless Sensor Networks (WSNs). Over the years, many forwarder methods were proposed to improve the performance in opportunistic routing. However, based on existing works, the findings have shown that there is still room for improvement in this domain, especially in the aspects of latency, network lifetime, and packet delivery ratio. In this work, a new relay node selection method was proposed. The proposed method used the minimum or maximum range and optimum energy level to select the best relay node to forward packets to improve the performance in opportunistic routing. OMNeT++ and MiXiM framework were used to simulate and evaluate the proposed method. The simulation settings were adopted based on the benchmark scheme. The evaluation results showed that our proposed method outperforms in the aspect of latency, network lifetime, and packet delivery ratio as compared to the benchmark scheme.
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http://dx.doi.org/10.7717/peerj-cs.326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924681PMC
December 2020

Impact of light stimulation during incubation on hatching traits and post-hatch performance of commercial broilers.

Trop Anim Health Prod 2021 Jan 9;53(1):107. Epub 2021 Jan 9.

Department of Poultry Production, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

Light in terms of photo- and scoto-periods is the key ambient factor affecting the physiology of birds through establishing normal biological clock and circadian rhythms. In natural incubation light significantly influences embryonic development, however, at commercial setups eggs are incubated under a dark environment. Presently not a single commercial poultry hatchery is using light during incubation; hence, comprehensive studies are needed to address the industry for considering light as a potential embryonic growth stimulant. In the present study, white Light-emitting diodes (LEDs; 5000 K) were installed in the incubator and 250 lx light intensity was provided for 0, 12, and 24 h per day during the whole incubation period. A total of 900 broiler hatching eggs (Hubbard classic; from 58 weeks old parents) were randomly allocated to 3 treatment groups, having 5 replicates of 60 eggs each, a tray was considered as replicate during incubation and these eggs were incubated under standard incubation protocols. After hatching, a total of 300 chicks were picked and divided into 3 described treatments (0, 12, and 24 h of photo-stimulation to eggs during incubation) having 5 replicates of 20 birds each. The results indicated that incubation of eggs under 12 and 24 h of lighting significantly improved (P ≤ 0.05) hatch window, hatchability % (0.0002), a hatch of fertile % (0.001), and carcass yield % (0.0454). Embryonic mortality, dead germs, and dead in shell embryos were lower in eggs incubated under 12 h light. Significantly better FCR (0.0006), stress susceptibilities such as H/L ratio (0.0227), and physical asymmetry (0.0065) were observed among the birds incubated under 12 h light (P ≤ 0.05). In conclusion, an appropriate light stimuli (12 h) may help to improve hatching traits and post-hatch performance of commercial broiler.
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http://dx.doi.org/10.1007/s11250-020-02492-3DOI Listing
January 2021

Identification of the prepared foods promising for dietary folate intake in Beijing, China.

Food Sci Nutr 2020 Dec 3;8(12):6557-6567. Epub 2020 Nov 3.

Biotechnology Research Institute Chinese Academy of Agricultural Sciences Beijing China.

The aim of the present study was to analyze folate content and composition in foods consumed daily by Chinese people. The concentration of seven folate derivatives in sixty-four selected foods was determined by a liquid-chromatography tandem-mass spectrometry method. The total folate levels ranged from 0.28 to 129 µg/100 g fresh weight, with an average of 21.18 μg/100 g. The highest folate content was found in boiled egg yolk and waxy corn (>120 µg/100 g), abundant folate levels in cooked vegetables such as hot pepper, spinach, soybean sprout, stem lettuce, coriander, and broccoli (44-72 µg/100 g), and lowest in Coca Cola (0.28 µg/100 g). 5-Methyl-tetrahydrofolate was the major folate derivative in various foods, accounting for 72% of the total folates on average, with the highest being 90% in egg yolk. These data will enable estimation of the daily folate intake and allow dietary recommendations to improve folate status in humans.
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http://dx.doi.org/10.1002/fsn3.1945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723199PMC
December 2020

Tyrosine kinase inhibitors and their unique therapeutic potentialities to combat cancer.

Int J Biol Macromol 2021 Jan 5;168:22-37. Epub 2020 Dec 5.

Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, 64849, Mexico. Electronic address:

Cancer is one of the leading causes of death with a mortality rate of 12%. Although significant progress has been achieved in cancer research, the effective treatment of cancer remains the greatest global challenge in medicine. Dysregulation of tyrosine kinases (TK) is one of the characteristics of several types of cancers. Thus, drugs that target and inhibit these enzymes, known as TK inhibitors (TKIs), are considered vital chemotherapeutics to combat various types of cancer. The oral bioavailability of available TKIs and their targeted therapy are their potential benefits. Based on these characteristics, most TKIs are included in first/second-line therapy for the treatment of different cancers. This review aims to shed light on orally-active TKIs (natural and synthetic molecules) and their promising implication in the therapy of numerous types of tumors along with their mechanisms of action. Further, recent progress in the development of synthetic and isolation of natural TKIs is reviewed. A significant growth in research regarding the development of new-generation TKIs is made with time (23 FDA-approved TKIs from 2018) due to their better therapeutic response. Oral bioavailability should be considered as an important parameter while developing of new-generation TKIs; however, drug delivery systems can also be used to address issue of poor bioavailability to a certain extent. Moreover, clinical trials should be designed in consideration of the development of resistance and tumor heterogeneity.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.009DOI Listing
January 2021

The electrochemical reaction controlled optical response of cholestrol oxidase (COx) conjugated CdSe/ZnS quantum dots.

Sci Rep 2020 11 24;10(1):20439. Epub 2020 Nov 24.

Centre for Micro & Nano Devices, Department of Physics, COMSATS University Islamabad, Park Road Campus, Islamabad, 45550, Pakistan.

This paper reports the enhanced performance of cholesterol oxidase (COx) conjugated CdSe/ZnS quantum dots (QDs) by using water-soluble mercaptoacitic acid (MAA) as linker. The functionalized MAA-CdSe/ZnS QDs conjugated in four different dilutions of cholesterol oxidase significantly affected QDs photoluminescence intensities, which affected the process of charge transfer from QDs to MAA. The conjugation of COx to MAA-QDs in increased dilutions resulted in the regain of PL intensities, which were attributed to the passivation of MAA HOMO/LUMO states. The electrochemical impedance spectroscopy and cyclic voltammetry of the conjugated QDs were performed to get study the charge transfer mechanism. The 1:1000 diluted COx conjugated MAA-CdSe/ZnS QDs was found to have the lowest charge transfer resistance of 228 Ω, the highest diffusion (~ 1.39 × 10 cm/s) and charge transfer rates (~ 4.5 × 10 s) between the electrode and the redox species. The current study demonstrated the sensitivity of electrochemical and optical based detection on the alkaline.
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http://dx.doi.org/10.1038/s41598-020-77499-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686357PMC
November 2020

Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide.

Nat Chem Biol 2021 02 16;17(2):187-195. Epub 2020 Nov 16.

Department of Chemistry, University of Oxford, Oxford, UK.

Lipopolysaccharide (LPS) transport to the outer membrane (OM) is a crucial step in the biogenesis of microbial surface defenses. Although many features of the translocation mechanism have been elucidated, molecular details of LPS insertion via the LPS transport (Lpt) OM protein LptDE remain elusive. Here, we integrate native MS with hydrogen-deuterium exchange MS and molecular dynamics simulations to investigate the influence of substrate and peptide binding on the conformational dynamics of LptDE. Our data reveal that LPS induces opening of the LptD β-taco domain, coupled with conformational changes on β-strands adjacent to the putative lateral exit gate. Conversely, an antimicrobial peptide, thanatin, stabilizes the β-taco, thereby preventing LPS transport. Our results illustrate that LPS insertion into the OM relies on concerted opening movements of both the β-barrel and β-taco domains of LptD, and suggest a means for developing antimicrobial therapeutics targeting this essential process in Gram-negative ESKAPE pathogens.
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http://dx.doi.org/10.1038/s41589-020-00694-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116625PMC
February 2021

Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.

Mol Cell 2020 10 9;80(1):72-86.e7. Epub 2020 Sep 9.

Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Electronic address:

Membrane protein biogenesis faces the challenge of chaperoning hydrophobic transmembrane helices for faithful membrane insertion. The guided entry of tail-anchored proteins (GET) pathway targets and inserts tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane with an insertase (yeast Get1/Get2 or mammalian WRB/CAML) that captures the TA from a cytoplasmic chaperone (Get3 or TRC40, respectively). Here, we present cryo-electron microscopy reconstructions, native mass spectrometry, and structure-based mutagenesis of human WRB/CAML/TRC40 and yeast Get1/Get2/Get3 complexes. Get3 binding to the membrane insertase supports heterotetramer formation, and phosphatidylinositol binding at the heterotetramer interface stabilizes the insertase for efficient TA insertion in vivo. We identify a Get2/CAML cytoplasmic helix that forms a "gating" interaction with Get3/TRC40 important for TA insertion. Structural homology with YidC and the ER membrane protein complex (EMC) implicates an evolutionarily conserved insertion mechanism for divergent substrates utilizing a hydrophilic groove. Thus, we provide a detailed structural and mechanistic framework to understand TA membrane insertion.
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http://dx.doi.org/10.1016/j.molcel.2020.08.012DOI Listing
October 2020

The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site.

mBio 2020 09 8;11(5). Epub 2020 Sep 8.

Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom

RH5 is a secreted parasite ligand that is essential for erythrocyte invasion through direct interaction with the host erythrocyte receptor basigin. RH5 forms a tripartite complex with two other secreted parasite proteins, CyRPA and RIPR, and is tethered to the surface of the parasite through membrane-anchored P113. Antibodies against RH5, CyRPA, and RIPR can inhibit parasite invasion, suggesting that vaccines containing these three components have the potential to prevent blood-stage malaria. To further explore the role of the P113-RH5 interaction, we selected monoclonal antibodies against P113 that were either inhibitory or noninhibitory for RH5 binding. Using a Fab fragment as a crystallization chaperone, we determined the crystal structure of the RH5 binding region of P113 and showed that it is composed of two domains with structural similarities to rhamnose-binding lectins. We identified the RH5 binding site on P113 by using a combination of hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis. We found that a monoclonal antibody to P113 that bound to this interface and inhibited the RH5-P113 interaction did not inhibit parasite blood-stage growth. These findings provide further structural information on the protein interactions of RH5 and will be helpful in guiding the development of blood-stage malaria vaccines that target RH5. Malaria is a deadly infectious disease primarily caused by the parasite It remains a major global health problem, and there is no highly effective vaccine. A parasite protein called RH5 is centrally involved in the invasion of host red blood cells, making it-and the other parasite proteins it interacts with-promising vaccine targets. We recently identified a protein called P113 that binds RH5, suggesting that it anchors RH5 to the parasite surface. In this paper, we use structural biology to locate and characterize the RH5 binding region on P113. These findings will be important to guide the development of new antimalarial vaccines to ultimately prevent this disease, which affects some of the poorest people on the planet.
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http://dx.doi.org/10.1128/mBio.01566-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482062PMC
September 2020

A small molecule inhibitor of HER3: a proof-of-concept study.

Biochem J 2020 09;477(17):3329-3347

Protein Phosphorylation Laboratory, The Francis Crick Institute, London, U.K.

Despite being catalytically defective, pseudokinases are typically essential players of cellular signalling, acting as allosteric regulators of their active counterparts. Deregulation of a growing number of pseudokinases has been linked to human diseases, making pseudokinases therapeutic targets of interest. Pseudokinases can be dynamic, adopting specific conformations critical for their allosteric function. Interfering with their allosteric role, with small molecules that would lock pseudokinases in a conformation preventing their productive partner interactions, is an attractive therapeutic strategy to explore. As a well-known allosteric activator of epidermal growth factor receptor family members, and playing a major part in cancer progression, the pseudokinase HER3 is a relevant context in which to address the potential of pseudokinases as drug targets for the development of allosteric inhibitors. In this proof-of-concept study, we developed a multiplex, medium-throughput thermal shift assay screening strategy to assess over 100 000 compounds and identify selective small molecule inhibitors that would trap HER3 in a conformation which is unfavourable for the formation of an active HER2-HER3 heterodimer. As a proof-of-concept compound, AC3573 bound with some specificity to HER3 and abrogated HER2-HER3 complex formation and downstream signalling in cells. Our study highlights the opportunity to identify new molecular mechanisms of action interfering with the biological function of pseudokinases.
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http://dx.doi.org/10.1042/BCJ20200496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489893PMC
September 2020

Influence of Long-Distance Transportation Under Various Crating Densities on Broiler Meat Quality During Hot and Humid Weather.

J Poult Sci 2020 Jul;57(3):246-252

Department of Meat Science and Technology, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

The objective of the study was to investigate the effect of transportation distance and crating density on broiler meat quality during hot and humid weather. Breast meat samples were collected from broilers (Ross-308) after transportation for 80, 160, and 240 km at crating densities of 10, 12, and 15 birds per crate. The broilers were transported in plastic crates of 0.91 × 0.55 × 0.31 m (length × width × height) in summer at an ambient temperature of 27.2-33.6°C and relative humidity of 52.7-62.9%. The birds were then slaughtered, and the meats' physicochemical characteristics, marination and cooking attributes were measured. Meat pH at 2 hours (h) postmortem (PM) was significantly higher in birds transported for 80 and 160 km compared to those transported for up to 240 km, while meat pH at 24 h PM was higher in birds transported for up to 160 km compared to the other treatments; however, no effect of different crating densities on meat pH and drip loss was observed. Meat losses such as drip loss, thaw loss, cooking loss in raw and marinated breast, and meat shear force were significantly higher in birds transported for up to 240 km compared to the other treatments. An increase in crating density above 12 birds per crate also increased thaw loss, whereas crating density of 12 birds per crate and higher increased cooking loss and meat shear force. Meat lightness also increased significantly with the increase in transportation distance above 160 km and crating density above 12 birds per crate. In conclusion, transportation of broilers for more than 80 km with crating density higher than 12 birds per crate during summer was associated with severe losses in yield and deterioration in physical appearance and functional characteristics of meat.
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http://dx.doi.org/10.2141/jpsa.0190087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387949PMC
July 2020

Effects of different mating strategies in broiler breeder during peak and postpeak phase on subsequent broiler performance.

Poult Sci 2020 Jul 17;99(7):3501-3510. Epub 2020 Apr 17.

Department of Theriogenology, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan.

Two experimental trials on commercial broiler (Ross-308) were conducted to evaluate the carryover effect of artificial insemination (AI) in parent flock (PF) kept in cages (C), and on floor (F) in comparison to natural mating (NM) in floored PF. A total of 900 broiler chicks were obtained from 38-week-old PF (peak production), representing C, F, and NM evenly during first trial, whereas in second trial, similar number of chicks were obtained from same PF during postpeak phase (55 wk of age). Subsequent effects of AI and NM in PF were evaluated by bacteriology, posthatch mortality, growth performance, immune response, and carcass traits on experimental birds (broiler). Chicks being produced through NM exhibited significantly (P ≤ 0.05) improved growth performance (feed conversion ratio, weight gain, European efficiency factor) along with the least (P ≤ 0.05) posthatch mortality and prevalence of Escherichia coli, Salmonella Pullorum, and Mycoplasma gallisepticum. Moreover, the experimental chicks obtained from floored PF subjected to AI particularly during postpeak phase expressed the highest (P ≤ 0.05) contamination of the said pathogens along with posthatch mortality. However, immune response against New Castle disease and infectious bronchitis vaccines and slaughtering parameters remained nonsignificant (P > 0.05) among the 3 treatments under both trials. It is concluded that the best growth performance along with the least depletion and microbial load of concerned pathogens were being pertained by the experimental birds representing NM.
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http://dx.doi.org/10.1016/j.psj.2020.03.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597820PMC
July 2020

Mitigation of environmentally-related hazardous pollutants from water matrices using nanostructured materials - A review.

Chemosphere 2020 Aug 12;253:126770. Epub 2020 Apr 12.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey, NL, CP 64849, Mexico. Electronic address:

An unprecedented rise in population growth and rapid worldwide industrial development are associated with the increasing discharge of a range of toxic and baleful compounds. These toxic pollutants including dyes, endocrine-disrupters, heavy metals, personal care products, and pharmaceuticals are destructing nature's balance and intensifying environmental toxicity at a disquieting rate. Therefore, finding better, novel and more environmentally sound approaches for wastewater remediation are of great importance. Nanoscale materials have opened up some new horizons in various fields of science and technology. Among a range of treatment technologies, nanostructured materials have recently received incredible interest as an emerging platform for wastewater remediation owing to their exceptional surface-area-to-volume ratio, unique electrical and chemical properties, quantum size effects, high scalability, and tunable surface functionalities. An array of nanomaterials including noble metal-based nanostructures, transition metal oxide nanomaterials, carbon-based nanomaterials, carbon nanotubes, and graphene/graphene oxide nanomaterials to their novel nanocomposites and nanoconjugates have been attempted as the promising catalysts to overcome environmental dilemmas. In this review, we summarized recent advances in nanostructured materials that are particularly engineered for the remediation of environmental contaminants. The toxicity of various classes of relevant tailored nanomaterials towards human health and the ecosystem along with perspectives is also presented. In our opinion, an overview of the up-to-date advancements on this emerging topic may provide new ideas and thoughts for engineering low-cost and highly-efficient nanostructured materials for the abatement of recalcitrant pollutants for a sustainable environment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126770DOI Listing
August 2020

Meat Quality and Cooking Characteristics in Broilers Influenced by Winter Transportation Distance and Crate Density.

J Poult Sci 2020 Apr;57(2):175-182

Department of Meat Science and Technology, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

A study was conducted to determine the effect of transportation distance and crating density on meat quality traits during winter. ROSS-308 broilers aged 35 days were divided into 10 treatment groups based on three transportation distances (80, 160, and 240 km) with three crating densities (10, 12, and 15 birds per crate) along with birds slaughtered on farm without crating as a control group. Each treatment was replicated 10 times and placed at various locations in the truck. The birds were transported in plastic crates of 0.91 m×0.55 m×0.30 m at ambient temperature and relative humidity of 3.6-9.5°C and 63.3-78.8%, respectively. The breast meat quality parameters including pH, color, drip loss, shear force, marinade uptake and retention, cooking losses, and yield were determined. The results showed significantly higher pH 15 min post-slaughter (PS), drip loss, lightness, marinade uptake, raw meat cooking yield, and shear force in birds slaughtered on farm without any transportation. The birds transported for 240 km had significantly higher pH at 2 hours (h) PS, marinade retention, and cooking yield. Whereas, pH at 24 h PS, meat redness, yellowness, chroma, and marinated meat cooking yield were significantly higher in all transported treatments compared to the control group. Among different crating densities, the birds transported with 10 birds per crate showed significantly higher meat redness, marinade retention, and cooking yield. The crating density of 15 birds per crate had significantly higher lightness, hue, cooking loss, and shear force. However, no effect of crating density was observed on meat pH, drip loss, and marinade uptake. It can be concluded that an increase in transportation distance and low crating density during winter can negatively affect physical quality of meat with significant improvement in marination and cooking characteristics.
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http://dx.doi.org/10.2141/jpsa.0190014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248002PMC
April 2020

Microneedles in Smart Drug Delivery.

Adv Wound Care (New Rochelle) 2021 04 28;10(4):204-219. Epub 2020 May 28.

Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico.

In biomedical setup, at large, and drug delivery, in particular, transdermal patches, hypodermal needles, and/or dermatological creams with the topical appliance are among the most widely practiced routes for transdermal drug delivery. Owing to the stratum corneum layer of the skin, traditional drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. The current advancement at the microlevel and nanolevel has revolutionized the drug delivery sector. Particularly, various types of microneedles (MNs) are becoming popular for drug delivery applications because of safety, patient compliance, and smart action. Herein, we reviewed state-of-the-art MNs as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of MNs is discussed. Different types of MNs, that is, solid, hollow, coated, dissolving, and hydrogel forming, are discussed with suitable examples. The latter half of the work is focused on the applied perspective and clinical translation of MNs. Furthermore, a detailed overview of clinical applications and future perspectives is also included in this review. Regardless of ongoing technological and clinical advancement, the focus should be diverted to enhance the efficacy and strength of MNs. Besides, the possible immune response or interference should also be avoided for successful clinical translation of MNs as an efficient drug delivery system.
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http://dx.doi.org/10.1089/wound.2019.1122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906867PMC
April 2021

Optimal VMAT Delivery for Elekta MLC Beam Modulator: A Study of Collimator Rotation for Head and Neck Planning.

J Med Imaging Radiat Sci 2020 06 28;51(2):289-298. Epub 2020 Mar 28.

Medical Physics Department, San Bortolo Hospital, Vicenza, Italy.

Background: Well-optimized treatment planning parameters are vital for optimum beam delivery in advanced radiotherapy techniques. The Elekta "Beam-Modulator" (BM) is a high-resolution multileaf collimation system where each individual leaf is 4 mm wide at the isocentre, without backup diaphragms and jaws. Its maximum aperture is 21 × 16 cm, which results in a limited clinical use for the target geometry of maximum 20 cm in length. The collimator rotation provides an opportunity to treat slightly extended treatment length with optimal target coverage. The study aims to observe the collimator rotation influence on volumetric modulated arc therapy (VMAT) plan quality for different head and neck target geometries using limited field collimator of BM.

Methods: Ten patients with head and neck cancer were planned by means of simultaneous integrated boost to deliver VMAT for five patients with three dose levels (70/60/56) and five patients with two dose levels (60/54). The single arc, dual arc, and combined two independent single arcs of 356° each were well optimized for four collimator angles (C) 15°,30°, 45°, and 90°. The plans were prepared for BM with SmartArc module of Pinnacle³ treatment planning system. Statistical significance (P ≤ .05) among collimator angles for planning target volume dose-volume indices was calculated with Student's t-test. Organ-at-risk doses were compared and monitor units were also evaluated as a parameter for dose-delivery efficiency and out-of-field dose index.

Results: The dual arc and combined two independent single arcs achieved planning objectives for C15°, C30°, and C45°. Single arc for all collimator angles and C90° for all VMAT schemes failed to achieve planning objectives. The spread of low dose bath 20, 35, and 40 Gy and deterioration of doses were higher towards periphery at C90° and statistically significant.

Conclusion: The small and medium collimator angles for dual-arc VMAT scheme(s) are suitable, whereas single arc and C90° are not suitable in VMAT implementation for Elekta Beam-Modulator collimation system.
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http://dx.doi.org/10.1016/j.jmir.2020.02.001DOI Listing
June 2020

Visualizing Sacbrood Virus of Honey Bees via Transformation and Coupling with Enhanced Green Fluorescent Protein.

Viruses 2020 02 18;12(2). Epub 2020 Feb 18.

College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Sacbrood virus (SBV) of honey bees is a picornavirus in the genus . Given its relatively small and simple genome structure, single positive-strand RNA with only one ORF, cloning the full genomic sequence is not difficult. However, adding nonsynonymous mutations to the bee iflavirus clone is difficult because of the lack of information about the viral protein processes. Furthermore, the addition of a reporter gene to the clones has never been accomplished. In preliminary trials, we found that the site between 3' untranslated region (UTR) and poly(A) can retain added sequences. We added enhanced green fluorescent protein (EGFP) expression at this site, creating a SBV clone with an expression tag that does not affect virus genes. An intergenic region internal ribosome entry site (IRES) from Black queen cell virus (BQCV) was inserted to initiate EGFP expression. The SBV-IRES-EGFP clone successfully infected and , and in larvae, it was isolated and passaged using oral inoculation. The inoculated larvae had higher mortality and the dead larvae showed sacbrood symptoms. The added IRES-EGFP remained in the clone through multiple passages and expressed the expected EGFP in all infected bees. We demonstrated the ability to add gene sequences in the site between 3'-UTR and poly(A) in SBV and the potential to do so in other bee iflaviruses; however, further investigations of the mechanisms are needed. A clone with a desired protein expression reporter will be a valuable tool in bee virus studies.
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http://dx.doi.org/10.3390/v12020224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077286PMC
February 2020

Production analysis of broiler farming in central Punjab, Pakistan.

Trop Anim Health Prod 2020 May 29;52(3):1125-1131. Epub 2019 Oct 29.

Department of Wildlife & Ecology, Faculty of Fisheries and Wildlife, University of Veterinary and Animal Sciences, Lahore, Pakistan.

This study examined the analysis of personal and production performance of broiler farming in 10 cities of central Punjab (Lahore, Sheikhupura, Kasur, Okara, Sargodha, Sahiwal, Gujranwala, Gujrat, Nankana, and Kamalia) of Pakistan. These districts are densely populated and renowned for broiler production. Primary data were collected through a survey of 100 poultry farmers. Personal and production information were collected from the respondents. Descriptive statistics was employed in the form of averages and percentages. The comparison among different districts was made through one-way ANOVA technique followed by Tukey's HSD test. Parameters were observed significantly in experience of farmer, age, number of sheds, capacity of farm, and flock/annuum during the survey of Gujranwala and Kasur, while the high percentage of graduate farmers was observed in Lahore and Sheikhupura regions. Significant results were observed during the production performance feed efficiency and mortality in Okara and Kasur as well as maximum administration of both live and killed vaccine in Lahore through drinking water in Nankana. In the districts of Sheikhupura and Kamalia, farmers due to lake of education left their dead birds on the surface ground. In conclusion, this study pointed out the exact trend of modern broiler farming and its price fluctuation in Punjab (Pakistan) as well as the reason behind the losses to the farmers.
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http://dx.doi.org/10.1007/s11250-019-02107-6DOI Listing
May 2020

State-of-the-Art Genetic Modalities to Engineer Cyanobacteria for Sustainable Biosynthesis of Biofuel and Fine-Chemicals to Meet Bio-Economy Challenges.

Life (Basel) 2019 Jun 27;9(3). Epub 2019 Jun 27.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey CP 64849, N.L., Mexico.

In recent years, metabolic engineering of microorganisms has attained much research interest to produce biofuels and industrially pertinent chemicals. Owing to the relatively fast growth rate, genetic malleability, and carbon neutral production process, cyanobacteria has been recognized as a specialized microorganism with a significant biotechnological perspective. Metabolically engineering cyanobacterial strains have shown great potential for the photosynthetic production of an array of valuable native or non-native chemicals and metabolites with profound agricultural and pharmaceutical significance using CO as a building block. In recent years, substantial improvements in developing and introducing novel and efficient genetic tools such as genome-scale modeling, high throughput omics analyses, synthetic/system biology tools, metabolic flux analysis and clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease (CRISPR/cas) systems have been made for engineering cyanobacterial strains. Use of these tools and technologies has led to a greater understanding of the host metabolism, as well as endogenous and heterologous carbon regulation mechanisms which consequently results in the expansion of maximum productive ability and biochemical diversity. This review summarizes recent advances in engineering cyanobacteria to produce biofuel and industrially relevant fine chemicals of high interest. Moreover, the development and applications of cutting-edge toolboxes such as the CRISPR-cas9 system, synthetic biology, high-throughput "omics", and metabolic flux analysis to engineer cyanobacteria for large-scale cultivation are also discussed.
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http://dx.doi.org/10.3390/life9030054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789541PMC
June 2019

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

Cell 2019 06 13;178(1):216-228.e21. Epub 2019 Jun 13.

Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.

The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.
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http://dx.doi.org/10.1016/j.cell.2019.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602525PMC
June 2019

Gold nanoworms: Optical properties and simultaneous SERS and fluorescence enhancement.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Sep 10;220:117111. Epub 2019 May 10.

Materials Laboratory, Department of Physics, COMSAST University Islamabad, 45500, Pakistan. Electronic address:

Fabrication of platforms for efficient Raman and fluorescence enhancement is very attractive for plasmon-based molecular sensing. For superior sensitivity, the plasmonic constituents of such platforms should be effective electromagnetic field enhancers. Furthermore, nanoparticles having plasmon peak in the spectral range of therapeutic window are superior for biomedical application. Herein, we show that worm-shaped Au nanoparticles can be used for simultaneous surface enhanced Raman scattering (SERS) and metal enhanced fluorescence (MEF). Gold nanoworms (Au-NWs) with an intense plasmon absorption in the therapeutic window were synthesized using a facile single-stepped recipe. Electron microscopy imaging revealed that Au-NWs have a non-uniform surface. Owing to their special morphology, three distinct plasmon bands were seen in the experimental spectrum. The presence of three plasmon peaks was also verified by finite element based simulations. The simulation results further show that Au-NWs can provide intense near field enhancement for multiple excitation wavelengths. As a proof of concept, we have used Au-NWs based platforms for simultaneous enhancement of fluorescence and Raman signal of rhodamine 6G (R6G) dye molecule.
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http://dx.doi.org/10.1016/j.saa.2019.05.016DOI Listing
September 2019

Losing the Arms Race: Greater Wax Moths Sense but Ignore Bee Alarm Pheromones.

Insects 2019 Mar 23;10(3). Epub 2019 Mar 23.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650000, China.

The greater wax moth, L., is one of main pests of honeybees. The larvae burrow into the wax, damaging the bee comb and degenerating bee products, but also causes severe effects like driving the whole colony to abscond. In the present study, we used electroantennograms, a Y maze, and an oviposition site choice bioassay to test whether the greater wax moth can eavesdrop on bee alarm pheromones (isopentyl acetate, benzyl acetate, octyl acetate, and 2-heptanone), to target the bee colony, or if the bee alarm pheromones would affect their preference of an oviposition site. The results revealed that the greater wax moth showed a strong electroantennogram response to these four compounds of bee alarm pheromones even in a low concentration (100 ng/μL), while they showed the highest response to octyl acetate compared to the other three main bee alarm components (isopentyl acetate, benzyl acetate, and 2-heptanone). However, the greater wax moth behavioral results showed no significant preference or avoidance to these four bee alarm pheromones. These results indicate that bees are currently losing the arms race since the greater wax moth can sense bee alarm pheromones, however, these alarm pheromones are ignored by the greater wax moth.
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http://dx.doi.org/10.3390/insects10030081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468870PMC
March 2019

Membrane Protein-Lipid Interactions Probed Using Mass Spectrometry.

Annu Rev Biochem 2019 06 22;88:85-111. Epub 2019 Mar 22.

Department of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom; email:

Membrane proteins that exist in lipid bilayers are not isolated molecular entities. The lipid molecules that surround them play crucial roles in maintaining their full structural and functional integrity. Research directed at investigating these critical lipid-protein interactions is developing rapidly. Advancements in both instrumentation and software, as well as in key biophysical and biochemical techniques, are accelerating the field. In this review, we provide a brief outline of structural techniques used to probe protein-lipid interactions and focus on the molecular aspects of these interactions obtained from native mass spectrometry (native MS). We highlight examples in which lipids have been shown to modulate membrane protein structure and show how native MS has emerged as a complementary technique to X-ray crystallography and cryo-electron microscopy. We conclude with a short perspective on future developments that aim to better understand protein-lipid interactions in the native environment.
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http://dx.doi.org/10.1146/annurev-biochem-013118-111508DOI Listing
June 2019

Prevalence of bee viruses in Apis cerana cerana populations from different locations in the Fujian Province of China.

Microbiologyopen 2019 09 18;8(9):e00830. Epub 2019 Mar 18.

College of Bee Science, Fujian Agriculture and Forestry University, Fuzhou, China.

Prevalence of honeybee viral diseases has recently been causing major problems in the beekeeping industry, causing economic losses worldwide. Honeybees are susceptible to a variety of diseases and various pathogens. Among these pathogens, prevalence viruses, along with other factors, are seriously threatening the health of bee species. In the present study, samples were collected from 80 Apis cerana cerana (A. c. cerana) colonies from three different locations, Cangshan, Fuan, and Yongtai, in the Fujian Province of China. All samples were screened using the reverse transcription polymerase chain reaction (RT-PCR) method for detection of seven honeybee viruses, namely, Chinese sacbrood virus (CSBV), deformed wing virus (DWV), Israeli acute paralysis virus (IAPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), acute bee paralysis virus (ABPV), and Kashmir bee virus (KBV). Our results showed that CSBV was the most prevalent as it was detected in (90%), of the samples, DWV was detected in (81.25%), and IAPV was detected in (26.25%). In contrast, insignificant prevalence results were obtained from all apiaries for BQCV, CBPV, APBV, and KBV, which were not detected in any sample. Here, we are providing the first report on the molecular detection of honeybee viruses, especially the prevalence of IAPV, from different regions in the Fujian Province of China with a high prevalence of bee viruses, on A. c. cerana, and there is great concern for the presence of honeybee viruses in the population of the native honeybee (A. c. cerana) in China.
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http://dx.doi.org/10.1002/mbo3.830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741300PMC
September 2019
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