Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist

Topics overview: Targeting FimH with M4284 can reduce intestinal colonization of genetically diverse UPEC isolates; Insights into the generalizable, underlying features of epitope-specific repertoires and adaptive immune recognition; The function of H3K9me2 and H3K9me3; The association of Parkinson’s disease with alleles of the major histocompatibility complex; Analytical tools to identify which host species are likely to harbour the next human virus.

1. Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually. Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTIs. In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections. UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs. UPEC isolates encode up to 16 distinct chaperone-usher pathway pili, and each pilus type may enable colonization of a habitat in the host or environment. For example, the type 1 pilus adhesin FimH binds mannose on the bladder surface, and mediates colonization of the bladder. However, little is known about the mechanisms underlying UPEC persistence in the gut. Here, using a mouse model, Caitlin N. Spaulding at Washington University in Missouri, USA and his colleagues show that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, they show that targeting FimH with M4284, a high-affinity inhibitory mannoside, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without notably disrupting the structural configuration of the gut microbiota. By selectively depleting intestinal UPEC reservoirs, mannosides could markedly reduce the rate of UTIs and recurrent UTIs.

Read more, please click http://www.nature.com/nature/journal/v546/n7659/full/nature22972.html

2. Quantifiable predictive features define epitope-specific T cell receptor repertoires.

T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10¹⁵to as high as 10⁶¹ possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity. Here Pradyot Dash at St Jude Children’s Research Hospital in Tennessee, USA and his colleagues report the in-depth characterization of ten epitope-specific TCR repertoires of CD8⁺ T cells from mice and humans, representing over 4,600 in-frame single-cell-derived TCRαβ sequence pairs from 110 subjects. They developed analytical tools to characterize these epitope-specific repertoires: a distance measure on the space of TCRs that permits clustering and visualization, a robust repertoire diversity metric that accommodates the low number of paired public receptors observed when compared to single-chain analyses, and a distance-based classifier that can assign previously unobserved TCRs to characterized repertoires with robust sensitivity and specificity. Their analyses demonstrate that each epitope-specific repertoire contains a clustered group of receptors that share core sequence similarities, together with a dispersed set of diverse ‘outlier’ sequences. By identifying shared motifs in core sequences, they were able to highlight key conserved residues driving essential elements of TCR recognition. These analyses provide insights into the generalizable, underlying features of epitope-specific repertoires and adaptive immune recognition.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22383.html

3. Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription.

Heterochromatic DNA domains play important roles in regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway. Typically, sRNAs, originating from long noncoding RNAs, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and tri-methylation (H3K9me2 and H3K9me3, respectively) and heterochromatin formation. H3K9me is in turn required for recruitment of RNAi to chromatin to promote sRNA amplification. Yet, how heterochromatin formation, which silences transcription, can proceed by a co-transcriptional mechanism that also promotes sRNA generation remains paradoxical. Here, using Clr4, the fission yeast S. pombe homolog of mammalian SUV39H H3K9 methyltransferases, Gloria Jih at Harvard Medical School in Massachusetts, USA and her colleagues designed active site mutations that block H3K9me3, but allow H3K9me2 catalysis. They show that H3K9me2 defines a functionally distinct heterochromatin state that is sufficient for RNAi-dependent co-transcriptional gene silencing (CTGS) at pericentromeric DNA repeats. Unlike H3K9me3 domains, which are transcriptionally silent, H3K9me2 domains are transcriptionally active, contain modifications associated with euchromatic transcription, and couple RNAi-mediated transcript degradation to the establishment of H3K9me domains. The two H3K9me states recruit reader proteins with different efficiencies, explaining their different downstream silencing functions. Furthermore, transition from H3K9me2 to H3K9me3 is required for RNAi-independent epigenetic inheritance of H3K9me domains. Their findings demonstrate that H3K9me2 and H3K9me3 define functionally distinct chromatin states and uncover a mechanism for formation of transcriptionally permissive heterochromatin that is compatible with its broadly conserved role in sRNA-mediated genome defense.

Read more, please click http://www.nature.com/nature/journal/vaap/ncurrent/full/nature23267.html

4. T cells from patients with Parkinson’s disease recognize α-synuclein peptides.

Genetic studies have shown the association of Parkinson’s disease with alleles of the major histocompatibility complex. Here David Sulzer at Columbia University in New York, USA and his colleagues show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson’s disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson’s disease. These responses may explain the association of Parkinson’s disease with specific major histocompatibility complex alleles.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22815.html

5. Host and viral traits predict zoonotic spillover from mammals.

The majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, HIV, Ebola and SARS). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. However, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species boundaries. Here Kevin J. Olival at EcoHealth Alliance in New York, USA and his colleagues conduct a comprehensive analysis of mammalian host–virus relationships and show that both the total number of viruses that infect a given species and the proportion likely to be zoonotic are predictable. After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy and human population within a species range—which may reflect human–wildlife contact. They demonstrate that bats harbour a significantly higher proportion of zoonotic viruses than all other mammalian orders. They also identify the taxa and geographic regions with the largest estimated number of ‘missing viruses’ and ‘missing zoonoses’ and therefore of highest value for future surveillance. They then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22975.html

 

Anti-COX IV Mouse Monoclonal Antibody (14Y2) joins the Abbkine Scientific family

Wuhan, China. 430074, 29^th June 2017. Abbkine Scientific Co. Ltd has announced the release of its new Anti-COX IV Mouse Monoclonal Antibody (14Y2). COX IV, also called Cytochrome c Oxidase or Complex IV (EC 1.9.3.1), which is a large trans-membrane protein complex found in bacteria and the mitochondrion. It is located in the mitochondrial (or bacterial) membrane and is the last enzyme in the respiratory electron transport chain.

Otherwise known as the Cytochrome c oxidase polypeptide IV antibody, the COX IV antibody has a human, mouse and rat reactivity with a recombinant protein immunogen. The product is available in a liquid solution and affinity-purified from mouse ascites by affinity-chromatography using specific immunogen.

The monoclonal antibody is hosted in the mouse, with Mouse IgG1 Isotype. The uniqueness of the antibody stems from its flexibility and durability, as it can be stored for about twelve months from the date of shipment. While it is advised that investigators determine the optimal working dilutions experimentally, the suggested starting dilutions are WB 1:1000-3000, reiterating its flexibility.

COX IV antibody is usually as a Mitochondrial Loading Control.

About Abbkine Scientific

Abbkine Scientific Company Limited is a life science research company headquartered in California. Founded in 2012, the establishment has been able to spread its tentacles across the globe with increasing presence and acceptance from Asia Pacific thanks to its continuous efforts to make the world a better place.

Abbkine combines cutting edge technology with manufacturing engineering and cost advantage to provide innovative, high-quality assay kits and other research and scientific products enhance life science fundamental research and drug discovery amongst others.

PDGFRα Mouse Monoclonal Antibody (7A3) Review

PDGFRα, platelet-derived growth factor receptor alpha, also termed PDGFRA, encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. This receptor binds to certain isoforms of platelet-derived growth factors (PDGFs) and thereby becomes active in stimulating cell signaling pathways that elicit responses such as cellular growth and differentiation. The receptor is critical for the development of certain tissues and organs during embryogenesis and for the maintenance of these tissues and organs, particularly hematologic tissues, throughout life. Mutations in PDGFRA have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers.

Abbkine PDGFRα Mouse Monoclonal Antibody (7A3) takes synthetic peptide of PDGFRα at AA range of 1010-1090 as immunogen. The antibody was affinity-purified from mouse ascites by affinity-chromatography. The antibody could be used to detect endogenous levels of PDGFRA in the samples of human, rat and mouse. It has been validated in IF and IHC-p experiments. Suggested starting dilutions are: IHC-p: 1:100-200, and the researchers should explore optimal concentrations for your own tests.

Our lab bought this antibody one week ago. I stained mouse brain sections at a dilution 1:200 and there are strong signals in corpus callosum. In one word, this antibody is an excellent antibody. Also, my other colleague conducted the immunohistochemical analysis of rat spleen tissue. PDGFRα Mouse Monoclonal Antibody (7A3) was diluted at 1:200. It works well for IHC staining.

ABCB5 Monoclonal Antibody Review

ATP-binding cassette sub-family B member 5 also known as P-glycoprotein ABCB5 is a plasma membrane-spanning protein that in humans is encoded by the ABCB5 gene. ABCB5 is an ABC transporter and P-glycoprotein family member principally expressed in physiological skin and human malignant melanoma. ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma. It is commonly over-expressed on circulating melanoma tumour cells.

Abbkine ABCB5 Monoclonal Antibody was affinity-purified from mouse ascites by affinity-chromatography using specific immunogen. The antibody was validated for WB, IF, IHC-p and tested to react with Human. Abbkine suggested the starting dilutions are as follows: WB: 1:2000, IF: 1:200, IHC-p: 1:200. Optimal working dilutions should be determined by users.

After several times failure of using other brands of ABCB5 Antibody, I found Abbkine through internet. What I have to say: the antibody is amazing. It saves my experiment and my time. I applied the antibody in WB, IF, IHC. All the results are in line with my expectations. Compared with other brands, the price of this antibody is even lower. There is no doubt that I’ll purchase products from Abbkine again.

Abbkine Scientific launches the PurKine™ Protein L Resin

The PurKine™ Protein L Resin is the latest addition to the resin family from the stables of scientific research giant, Abbkine Scientific Company Limited. The company recently announced the official launch of the product designed to purify monoclonal antibodies from culture supernatant or ascites known to have the kappa light chain in gravity column procedures.

Otherwise known as Protein L Resin, the product has been largely described as being perfect for affinity purification of mammalian IgG containing particular kappa light chains from ascites fluid, serum, cell culture supernatant and a host of other antibody samples.

The Antibody Purification Protein L is designed to minimize nonspecific binding proteins, thanks to the proprietary modification method employed in its production. Protein L Agarose is also known to be very useful in purifying VLk-containing monoclonal antibodies from culture supernatant, as it does not bind bovine immunoglobulin present in the media serum supplement.

Available in a liquid solution, the Protein L resin consists of 90μm beads of cross-linked 4% agarose, to which Recombinant protein L has been coupled. The cost-effectiveness of the product has been validated after test results show no decrease in performance after at least five repeated uses.

The product is available in multiple formats including bulk resin, spin columns and complete kits, allowing for flexibility on the part of the users.

About Abbkine Scientific Co. Ltd

Abbkine Scientific Co. Ltd is headquartered in California. The life science research company was founded in 2012 and has subsequently reached the rest of the world, with a wide range of high quality science products and services.

Abbkine Scientific combines cutting edge technology with manufacturing engineering and cost advantage, providing high-quality and innovative assay kits and other research and scientific products designed to enhance life science fundamental research and drug discovery amongst others.

Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation

Topics overview: What's Metafluidics; How to solve the Cpf1 function limitation in BV3L6 and Lachnospiraceae bacterium ND2006; The breakthrough of single-cell genome sequencing to large cell populations; Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut; TACCA was applied to produce a high-quality (N50 of 9.76 Mb) de novo chromosome assembly of the wheat line CH Campala Lr22a in only 4 months.

1.  Open-source, community-driven microfluidics with Metafluidics.

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. David S Kong at Massachusetts Institute of Technology Lincoln Laboratory in Massachusetts, USA and his colleagues present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. They use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.

Read more, please click http://www.nature.com/nbt/journal/v35/n6/full/nbt.3873.html

2. Engineered Cpf1 variants with altered PAM specificities.

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, Linyi Gao at Broad Institute of MIT and Harvard in Massachusetts, USA and his colleagues performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. They engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which they further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ~11 bp.

Read more, please click http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3900.html

3. Single-cell genome sequencing at ultra-high-throughput with microfluidic droplet barcoding.

The application of single-cell genome sequencing to large cell populations has been hindered by technical challenges in isolating single cells during genome preparation. Here Freeman Lan at University of California in California, USA and his colleagues present single-cell genomic sequencing (SiC-seq), which uses droplet microfluidics to isolate, fragment, and barcode the genomes of single cells, followed by Illumina sequencing of pooled DNA. They demonstrate ultra-high-throughput sequencing of >50,000 cells per run in a synthetic community of Gram-negative and Gram-positive bacteria and fungi. The sequenced genomes can be sorted in silico based on characteristic sequences. They use this approach to analyze the distributions of antibiotic-resistance genes, virulence factors, and phage sequences in microbial communities from an environmental sample. The ability to routinely sequence large populations of single cells will enable the de-convolution of genetic heterogeneity in diverse cell populations.

Read more, please click http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3880.html

4. Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation.

Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of technologies to accomplish this has been hindered by the susceptibility of synthetic genetic circuits to mutation and unpredictable function during extended gut colonization. Here, David T Riglar at Harvard Medical School in Massachusetts, USA and his colleagues report stable, engineered bacterial strains that maintain their function for 6 months in the mouse gut. They engineered a commensal murine Escherichia coli strain to detect tetrathionate, which is produced during inflammation. Using their engineered diagnostic strain, which retains memory of exposure in the gut for analysis by fecal testing, they detected tetrathionate in both infection-induced and genetic mouse models of inflammation over 6 months. The synthetic genetic circuits in the engineered strain were genetically stable and functioned as intended over time. The durable performance of these strains confirms the potential of engineered bacteria as living diagnostics.

Read more, please click http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3879.html

5. Rapid cloning of genes in hexaploid wheat using cultivar-specific long-range chromosome assembly.

Cereal crops such as wheat and maize have large repeat-rich genomes that make cloning of individual genes challenging. Moreover, gene order and gene sequences often differ substantially between cultivars of the same crop species. A major bottleneck for gene cloning in cereals is the generation of high-quality sequence information from a cultivar of interest. In order to accelerate gene cloning from any cropping line, Anupriya Kaur Thind at University of Zurich in Zurich, Switzerl and and his colleagues report 'targeted chromosome-based cloning via long-range assembly' (TACCA). TACCA combines lossless genome-complexity reduction via chromosome flow sorting with Chicago long-range linkage to assemble complex genomes. They applied TACCA to produce a high-quality (N50 of 9.76 Mb) de novo chromosome assembly of the wheat line CH Campala Lr22a in only 4 months. Using this assembly they cloned the broad-spectrum Lr22a leaf-rust resistance gene, using molecular marker information and ethyl methanesulfonate (EMS) mutants, and found that Lr22a encodes an intracellular immune receptor homologous to the Arabidopsis thaliana RPM1 protein.

Read more, please click http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3877.html

Anti-Plant Actin Mouse Monoclonal Antibody (3T3) becomes the latest addition to the Abbkine family

Abbkine Scientific Co. Ltd is known for making quality life science products and tools and it recently announced the official launch of its new antibody – the Anti-Plant Actin Mouse Monoclonal Antibody (3T3).

The antibody otherwise known as AT3G12110 antibody is a Plant Actin Antibody, which is an essential component of cell cytoskeleton. The substance also plays a critical role in the streaming of cytoplasmic, determination of cell shape, cell division and extension growth.

The product is available in a liquid solution and hosted by mouse hence, Plant Actin Mouse mAb. The antibody is also a Recombinant Protein immunogen, with plant reactivity. The antibody like many of its other counterparts is affinity-purified from mouse ascites using specific immunogen by affinity-chromatography.

The Anti-Plant Actin Mouse Monoclonal Antibody (3T3) is made solely for research purpose and not intended for clinical or human use. It can also be stored for as long as one year at -20°C from date of shipment.

Optimal working dilutions for the Anti-Plant Actin Mouse Monoclonal Antibody (3T3) should be determined by the investigator after experiments. However, the suggested starting dilutions are WB 1:2000-5000.

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About Abbkine Scientific

Abbkine Scientific Company Limited is a life science research company headquartered in California. Founded in 2012, the establishment has been able to spread its tentacles across the globe with increasing presence and acceptance from Asia Pacific thanks to its continuous efforts to make the world a better place.

Abbkine combines cutting edge technology with manufacturing engineering and cost advantage to provide innovative, high-quality assay kits and other research and scientific products enhance life science fundamental research and drug discovery amongst others.

TTR Mouse Monoclonal Antibody(1D7) Review

Transthyretin (TTR) is a transport protein in the serum and cerebrospinal fluid that carries the thyroid hormone thyroxine (T4) and retinol-binding protein bound to retinol. The liver secretes transthyretin into the blood, and the choroid plexus secretes TTR into the cerebrospinal fluid. More than 80 different mutations in TTR have been reported; most mutations are related to amyloid deposition, affecting predominantly peripheral nerve and/or the heart, and a small portion of the gene mutations is non-amyloidogenic. The diseases caused by mutations include amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis, carpal tunnel syndrome, etc.

Abbkine TTR Mouse Monoclonal Antibody(1D7) was affinity-purified from mouse ascites by affinity-chromatography using TTR recombinant protein antigen. This antibody could be applied to IF, IHC-p, WB, which has been validated. This antibody can react with Human samples. Optimal working dilutions should be determined experimentally by researchers. Abbkine suggest that the starting dilutions are: WB: 1:500-2000, IHC-p: 1:50-2000.

There are a lot of antibody brands in the market, it maybe a little difficult for a beginner to choose an appropriate antibody for his experiment. Hope my experience could help you. I used many antibodies from different firms. Through the comparison, and I think Abbkine is a good selection, which has high quality with lower price, as well as perfect protein specificity and strong technical support. Abbkine provide the primary antibodies that involve many fields. I bought some antibodies to do IHC experiments, including TTR Mouse Monoclonal Antibody(1D7), and they both make good performances. You could save the costs along with satisfactory results.

FH Monoclonal Antibody Review

The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). Fumarase participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate. Mutations in FH can cause fumarase deficiency and lead to progressive encephalopathy.

Abbkine FH Monoclonal Antibody was affinity-purified from mouse ascites by affinity-chromatography using specific immunogen. The antibody has been validated for WB, IF, IHC-P and tested in Human, Mouse and Rat. Abbkine suggested the starting dilutions are as follows: WB: 1:3000, IF, IHC-P: 1:200. The optimal working dilutions should be determined experimentally by users.

Immunofluorescence image of Abbkine FH Monoclonal Antibody (ABM40073) stained human liver cancer tissue sections. The sections were incubated with ABM40073 at 5µg/ml over night at 4°C. The secondary antibody was (red) IFKine red  anti-mouse IgG. DAPI was used to stain the cell nuclei (blue). Target protein signal was strong.

Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy

Topics overview: Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy, learned carry-over effects generalize over time and across routes of drug administration—independent of conscious expectations, Infection with a mutant parasite with impaired hemoglobin digestion that produces little hemozoin, a major Plasmodium by-product, did not cause bone loss, proteasome variations influence T cell repertoire selection and may contribute to the difference in individual susceptibility to autoimmunity,  pre-DC compartment contains distinct lineage-committed subpopulations.

1. Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer.

Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, Emma Nolan at Walter and Eliza Hall Institute of Medical Research in Victoria, Australia and her colleagues explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model. BRCA1-mutated triple-negative breast cancers (TNBCs) exhibited an increased somatic mutational load and greater numbers of tumor-infiltrating lymphocytes, with increased expression of immunomodulatory genes including PDCD1 (PD-1) and CTLA4, when compared to TNBCs from BRCA1–wild-type patients. Cisplatin treatment combined with dual anti–programmed death-1 and anti–cytotoxic T lymphocyte–associated antigen 4 therapy substantially augmented antitumor immunity in Brca1-deficient mice, resulting in an avid systemic and intratumoral immune response. This response involved enhanced dendritic cell activation, reduced suppressive FOXP3+ regulatory T cells, and concomitant increase in the activation of tumor-infiltrating cytotoxic CD8+ and CD4+ T cells, characterized by the induction of polyfunctional cytokine-producing T cells. Dual (but not single) checkpoint blockade together with cisplatin profoundly attenuated the growth of Brca1-deficient tumors in vivo and improved survival. These findings provide a rationale for clinical studies of combined immune checkpoint blockade in BRCA1-associated TNBC.

Read more, please click http://stm.sciencemag.org/content/9/393/eaal4922

2. The effects of treatment failure generalize across different routes of drug administration.

 Failure of medical treatments can hamper responses to subsequent treatments. It has been suggested that changing the route of drug administration could reduce such negative carry-over effects, but direct evidence for this approach is lacking. Matthias Zunhammer at University Hospital Essen in Essen, Germany and his colleagues therefore investigated in 211 healthy volunteers whether changes in drug administration route reduce such carry-over effects. A positive or negative treatment history with topical analgesic treatments was induced experimentally in a mock clinical trial setting. Subsequently, a different inert drug was introduced via the same (topical) or another (oral) route of administration and its analgesic efficacy was tested. Changing the route of drug administration induced expectations of positive treatment effects in the subjects but did not actually counteract the negative carry-over effects on treatment efficacy. These findings indicate that learned carry-over effects generalize over time and across routes of drug administration—independent of conscious expectations. Other strategies are needed to prevent negative carry-over effects of treatment failure from influencing the results of subsequent treatment attempts.

Read more, please click http://stm.sciencemag.org/content/9/393/eaal2999

3. Plasmodium products persist in the bone marrow and promote chronic bone loss.

Although malaria is a life-threatening disease with severe complications, most people develop partial immunity and suffer from mild symptoms. However, incomplete recovery from infection causes chronic illness, and little is known of the potential outcomes of this chronicity. Michelle S. J. Lee at Immunology Frontier Research Center (IFReC), Osaka University in Osaka, Japan and his colleagues found that malaria causes bone loss and growth retardation as a result of chronic bone inflammation induced by Plasmodium products. Acute malaria infection severely suppresses bone homeostasis, but sustained accumulation of Plasmodium products in the bone marrow niche induces MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression and overstimulation of osteoclastogenesis, favoring bone resorption. Infection with a mutant parasite with impaired hemoglobin digestion that produces little hemozoin, a major Plasmodium by-product, did not cause bone loss. Supplementation of alfacalcidol, a vitamin D3 analog, could prevent the bone loss. These results highlight the risk of bone loss in malaria-infected patients and the potential benefits of coupling bone therapy with antimalarial treatment.

Read more, please click http://immunology.sciencemag.org/content/2/12/eaam8093

4. Human thymoproteasome variations influence CD8 T cell selection.

The proteasome is a multi-subunit protease complex essential for housekeeping protein degradation and the production of the major histocompatibility complex (MHC) class I-bound antigen peptides that are essential for recognition by CD8 T cells. MHC variations dramatically contribute to T cell selection and autoimmunity, but genetic variations of peptide processing machinery including proteasome genes have been poorly explored in this context. In the computational analysis of human proteasome gene variation, Takeshi Nitta at University of Tokyo in Tokyo, Japan and his colleagues documented that PSMB11 was highly enriched for nucleotide changes that interfere with protein function. This gene encodes β5t, a thymus-specific catalytic subunit that regulates positive selection of CD8 T cells by producing a distinct set of MHC class I-bound peptides. The introduction of PSMB11 variations into the mouse genome by genome-editing revealed that these variations impaired the development of CD8 T cells in vivo. One of the PSMB11 polymorphisms altered the CD8 T cell repertoire in mice and was associated with a higher risk of an autoimmune disease in humans. Their findings suggest that, in addition to the MHC haplotype, proteasome variations influence T cell repertoire selection and may contribute to the difference in individual susceptibility to autoimmunity.

Read more, please click http://immunology.sciencemag.org/content/2/12/eaan5165

5. Mapping the human DC lineage through the integration of high-dimensional techniques.

Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, Peter See at Singapore Immunology Network (SIgN) in Singapore and his colleagues combine two high-dimensional technologies—single-cell messenger RNA sequencing (scmRNAseq) and cytometry by time-of-flight (CyTOF)—to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed subpopulations, including one early uncommitted CD123 high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.

Read more, please click http://science.sciencemag.org/content/356/6342/eaag3009

 

Abbkine Scientific adds PurKine™ His-Tag Ni-Super Resin to the its product list

Wuhan, China. 430074, 15^th June 2017. Abbkine Scientific has added the PurKine™ His-Tag Ni-Super Resin to its long list of high-quality scientific research product. Also known as the His tag resin, the product is made using the latest synthetic process of resin production, combined with cutting-edge techniques for the resin development and accessories optimization.

The product is created to simplify and enhance the process of purification, based on innovative high-capacity IMAC matrix, ensuring single-step purification of His-tag proteins from total lysates. The Ni-Super resin as it is also known is effective for purifying his-tag proteins from samples that can cause Ni stripping from the medium, such as secreted proteins in liquids containing chelators.

The resin comes with two distinct benefits compared to Ni-NTA and Ni-IDA, which are high tolerance and easy cleaning. Unlike other resins, the product is more tolerable to various chemicals including reducing, chelating agents, with easy cleaning using NaOH.

The resin comes in a liquid solution and is available in multiple formats including bulk resin, spin columns and complete kits, allowing for flexibility. In addition to its easy cleaning feature, the product is also versatile and cost-effective, showing no decrease in performance after about five repeated uses of the same batch of resin.

The Ni-Super resin is for research use only and is not intended for use in human or clinical diagnosis.

About Abbkine Scientific Co. Ltd

Abbkine Scientific Co. Ltd is headquartered in California. The life science research company was founded in 2012 and has subsequently reached the rest of the world, with a wide range of high quality science products and services.

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Abbkine Scientific combines cutting edge technology with manufacturing engineering and cost advantage, providing high-quality and innovative assay kits and other research and scientific products designed to enhance life science fundamental research and drug discovery amongst others.

CD10 Monoclonal Antibody review

CD10 is a cell surface enzyme with neutral metalloendopeptidase activity. CD10 is also known as CALLA (common acute lymphocytic leukemia antigen). It serves as a marker for the common form of ALL (acute lymphocytic leukemia) as well as for Burkitt lymphoma and follicular germinal center lymphoma. CD10/CALLA is normally present on the surface of early lymphoid cells as well as on a number of other types of normal cells, such as especially cells in the kidney.

Abbkine CD10 Monoclonal Antibody was affinity-purified from mouse ascites by affinity-chromatography using specific peptide to detect endogenous CD10 proteins. The antibody has been validated for IHC-P, IF and tested in Human, Mouse and Rat. Supplied in liquid solution, the concentration of the antibody is 1mg/ml. The antibody is for research use only.

To validate the staining in rat kidney tissue sections, we chose Abbkine CD10 Monoclonal Antibody as the primary antibody. A goat polyclonal to mouse IgG1 was used as the secondary antibody. A positive result was found and no non-specific background. Negative control was used by secondary antibody only. I was happy with the result. I found it to be worth the cost and plan to use them again.

Structure of the human multidrug transporter ABCG2

Topics overview: Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival, How oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells, Scientist uncover a new inducer of mammalian heart regeneration, highlighting fundamental roles of the ECM in cardiac repair, Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and Structure of the human multidrug transporter ABCG2.

1. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer

The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here Sushrut Kamerkar at University of Texas MD Anderson Cancer Center in Texas, USA and his colleagues show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras^G12D, a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Their results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22341.html

2. Nutrient acquisition strategies of mammalian cells

Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, Wilhelm Palm at Memorial Sloan Kettering Cancer Center in New York, USA and his colleagues review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. They also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

Read more, please click http://www.nature.com/nature/journal/v546/n7657/full/nature22379.html

3. The extracellular matrix protein Agrin promotes heart regeneration in mice

The adult mammalian heart is non-regenerative due to the post-mitotic nature of cardiomyocytes. The neonatal mouse heart can regenerate, but only for the first week of life. Here Elad Bassat at Weizmann Institute of Science in Rehovot, Israel and his colleagues show that changes in the composition of the extracellular matrix (ECM) during this week can affect cardiomyocyte growth and differentiation in mice. They identify Agrin, a component of neonatal ECM, as required for the full regenerative capacity of neonatal mouse hearts. In vitro, recombinant Agrin promotes the division of mouse and human iPSC-derived cardiomyocytes via a mechanism that involves the disassembly of the dystrophin glycoprotein complex and Yap and ERK-mediated signaling. In vivo, a single administration of Agrin promotes cardiac regeneration in adult mice after myocardial infarction, although the degree of cardiomyocyte proliferation observed in this model suggests additional therapeutic mechanisms. Collectively, they uncover a new inducer of mammalian heart regeneration, highlighting fundamental roles of the ECM in cardiac repair.

Read more, please click http://www.nature.com/nature/journal/vaap/ncurrent/full/nature22978.html

4. A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here Ujjini H. Manjunatha at Novartis Institute for Tropical Diseases in Chromos, Singapore and his colleagues establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, they identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Their results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22337.html

5. Structure of the human multidrug transporter ABCG2

ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here Nicholas M. I. Taylor at University of Basel in Basel, Switzerland and his colleagues present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. They visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. They observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, their results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature22345.html

PurKine™ Protein SulfyBind Resin is the latest addition to the Abbkine resin family

Wuhan, China. 430074, 8^th June 2017. Announcing the launch of its PurKine™ Protein SulfyBind Resin, Abbkine Scientific Company Limited stated the features and benefits of the PurKine™ Protein SulfyBind Resin, especially when compared with its peers in the market.

Formulated in a liquid solution with 50% slurry in 20% ethanol, PurKine™ Protein SulfyBind Resin is a simple and efficient system of affinity chromatography. Allowing covalent immobilization of sulfhydryl-containing peptides, protein, and other ligands to the medium agarose support for use in affinity purification procedures, the portfolio ensures optimization of the process. This subsequently leads to maximum protein yield, stability, and solubility.

Consisting of 90μm beads of highly cross-linked 4% agarose coupled with Iodoacetic acid, the performance of the resin has been reported to equal or even surpass popular SulfoLink resins from other suppliers.

Other features and benefits of the kit include Reduced Cysteine Residues and effective Antibody Purification. Its high capacity, cost-effectiveness, flexibility, and high performance are features that further distinguish it from its peers.

The PurKine™ Protein SulfyBind Resin is available in two basic formats - prepacked spin column and kit and has been tested to retain its effectiveness even after five repeated uses. This establishes the cost-effectiveness of the product.

About Abbkine Scientific Co. Ltd.

Abbkine Scientific Co. Ltd is a scientific research institute headquartered in China. Founded by a team of scientists and marketing experts, the serves the field of sciences by perfectly combining cutting edge technology from the United States with China's manufacturing engineering and cost advantages, to provide state-of-the-art recombinant proteins, antibodies, and other scientific research tools.

HP-1γ Mouse Monoclonal Antibody (2F5) review

The family of Heterochromatin Protein 1 (HP1) ("Chromobox Homolog", CBX) consists of highly conserved proteins, which have important functions in the cell nucleus. All three HP1 family members (α, β, and γ) are primarily associated with centromeric heterochromatin; however, HP1β and γ also localize to euchromatic sites in the genome. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a Hinge region. HP1 is also found at euchromatic sites, where its binding correlates with gene repression. The protein encoded by CBX3（chromobox 3) binds DNA and is a component of heterochromatin. This protein also can bind lamin B receptor, an integral membrane protein found in the inner nuclear membrane. The dual binding functions of the encoded protein may explain the association of heterochromatin with the inner nuclear membrane. This protein binds histone H3 tails methylated at Lys-9 sites. This protein is also recruited to sites of ultraviolet-induced DNA damage and double-strand breaks. Two transcript variants encoding the same protein but differing in the 5' UTR, have been found for CBX3.

Abbkine HP-1γ Mouse Monoclonal Antibody was affinity-purified from mouse ascites by affinity-chromatography using specific immunogen. This antibody has been verified in IF, IHC-p, WB experiments and shows good effects. You can detect endogenous HP-1γ protein in the samples of Human, Mouse and Rat. About the dilutions, you need to design pre-experiment to determine the optimal concentration, which suits for your specimen.

As researchers, we all know that choosing an appropriate antibody is very important step for the success of an experiment. And I believe Abbkine antibody is a good choice for you. Two months ago, I purchased a HP-1γ Mouse Monoclonal Antibody from Abbkine to finish my graduation thesis. It's very convenient to order items and I received the product very soon. Compared with other famous companies, the price is quite cost-effective with the same quality. During the process of my experiments, I met some problems. The technical staff offered me very professional guidance and help me analysis the reasons with great patience. Finally, I obtained satisfied results and graduated smoothly. Through the story of my experience, I strongly recommend AbbKine products for you.

Getting more research benefts from innovative Cell Counting Kit-8 with less cost!

Abbkine Cell counting kit-8 is a colorimetric assay kit for cell number counting, cell prolifration and cytotoxicity assays. By adding CCK-8 directly to the cell media, CCK-8 kit shows fast, high-throughput screening without a solubilization process, obtaining highly reproducible and accurate results.

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SuperLumia HRP ECL & ECL Plus Substrate Kits

Abbkine SuperLumia ECL HRP Substrate Kits are value-priced, classical peroxidase substrates for enhanced chemiluminescence (ECL) that directly replaces costlier products without the need to re-optimize conditions.

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Review of CD5 Monoclonal Antibody

Abbkine Scientific is one of the most trusted names in the field of life science research, providing innovative research tools and products since it was founded some years back. The Chinese based scientific research company recently announced the official launch of its new product – the CD5 Monoclonal antibody.

The CD5 antibody as it is also referred to as is another product from the stables of the research giant. The product like many other tools from Abbkine Scientific is designed to help simplify and enhance research processes, leading to more effective results.

The T-cell surface glycoprotein CD5 antibody has come under scrutiny from different quarters, especially researchers and investigators alike. Below is a review of the product, detailing the features, benefits, pros and cons of the newly-launched antibody.

Overview of CD Monoclonal Antibody

CD5 also designated as Lyt-1 is a popular substance famous for being a trans-membrane glycoprotein, which is expressed on 70% of normal peripheral blood lymphocytes. It has also been identified on practically all T lymphocytes in thymus and peripheral blood.

In addition, the activation of T cells via the T cell receptor also known as TCR leads to tyrosine phosphorylation of CD5 and the absence of CD5 renders T cells hyper-responsive to TCR-mediated activation.

CD5 has been discovered to associate with TCR/CD3-z chain, and the Src family kinase Lck p56. Vitro studies have revealed a significant increase in the kinase activity of Lck bound to CD5, by as much as ten to fifteen folds.

CD72, which is the B cell antigen, serves as a receptor for CD5. The effect of CDG binding with its cognate receptor is not readily known at the moment. However, report has it that it plays a role in the selection of thymic.

Features of the CD Monoclonal Antibody

The CD5 Monoclonal antibody comes with a number of features or properties. While it shares some of the features with its counterparts, it possesses some unique attributes that distinguishes it from other such products.

Some of the features are mentioned below

• Formulation – liquid solution


• Concentration - 1 mg/ml


• Immunogen – synthetic peptide


• Host – Mouse


• Reactivity – Human, Mouse, Rat


• Applications – IF, IHC-p


• Isotype - Mouse IgG1


• Clonality – Monoclonal


• Storage buffer - PBS, pH 7.4, containing 0.02% sodium azide as Preservative and 50% Glycerol

One of the unique features of the CD5 monoclonal antibody is the method of purification employed while producing it, as it is affinity-purified from mouse ascites by affinity-chromatography using specific immunogen.

Another relatively unique feature of the antibody is the ability of investigators to determine the best working dilutions that suits the purpose of the experiment. While the manufacturer suggests starting dilutions of IHC-p: 1:200, IF: 1:200, investigators are advised to determine the optimal working dilutions experimentally.

The Pros of CD5 Monoclonal Antibody

Also known as LEU1 antibody, the product has been identified to have a number of pros especially when compared with other antibodies in its category. One of the pros of the product is its durability as users can store it for as long as one year at -20°C from date of shipment.

Another advantage of the product is its ability to detect endogenous CD5 proteins.

Its availability in a liquid solution and flexible dilutions also allows for flexibility for investigators and researchers alike.

The Cons of CD5 Monoclonal Antibody

Currently, there are no known negative effects or cons of the CD5 Monoclonal Antibody. However, the manufacturers have warned against using it for human or clinical diagnosis, as it is strictly for research purposes only.

Conclusion

The CD5 Monoclonal Antibody is another great product from Abbkine Scientific Company Limited and tends to satisfy the desire of most scientific investigators and researchers.

Abbkine Scientific launches the PurKine™ Protein AminoBind Resin 4FF for researchers and investigators

Wuhan, China. 430074, 2^nd June 2017. The PurKine™ Protein AminoBind Resin 4FF is a new product from the stables of the famous international scientific research company, Abbkine Scientific. The product is designed to aid researchers and investigators alike, by ensuring optimum performance.

PurKine™ Protein AminoBind Resin 4FF is crosslinked having 4% beaded agarose resin, which contains N-hydroxysuccinimide (NHS) functional groups. Otherwise called the NHS-Activated Agarose Resin, the product can be used for the preparation of affinity purification procedures, which can isolate specific substances from complex mixtures, helping to achieve very high purity in a single step.

The resin is a pre-activated agarose matrix that increases the choice of coupling chemistries available. It is suitable for amino-containing smaller proteins and peptides coupling. It is also great for scaling-up due to its high flow properties.

The resin is unlike any other NHS-Activated Sepharose, with distinguishing features and benefits. Some of them include flexibility, high capacity, and cost-effectiveness. Formulated in liquid solution with 50% slurry in 100% isopropanol, the product can be easily used by researchers and investigators.

Abbkine Scientific has clearly stated the prohibition of the use of the product for clinical or human diagnosis as it is exclusively manufactured for research purpose.

About Abbkine Scientific Co. Ltd.

Abbkine Scientific Co. Ltd is a scientific research institute headquartered in China. Founded by a team of scientists and marketing experts, the serves the field of sciences by perfectly combining cutting edge technology from the United States with China's manufacturing engineering and cost advantages, to provide state-of-the-art recombinant proteins, antibodies, and other scientific research tools.

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The company has subsequently established itself as a scientific research heavyweight with the provision of generic and customized solutions to clients across the globe.