Weekly Top Scientific Research Review (11/3/2017-17/3/2017)

This week’s topic are about Early tumour growth, Class IIa HDAC inhibition, Antibody therapy, Neanderthal behaviour and Autophagy. Are you attracted by these interesting discoveries? Don’t wait, let’s browse together!

1. Early tumour growth halted.

Cells that eventually give rise to tumours attract immune cells that help to shield them from the body’s defences. This may be one of the earliest events in tumour formation. Bin Zhao at Zhejiang University in Hangzhou, China, and his colleagues studied liver cancer in mice and found that tumour-initiating cells (TICs) turn on production of Yes-associated protein (YAP). This molecule promotes cell proliferation and attracts immune cells called macrophages, which boost tumour growth. The TICs began doing this at an early stage of tumour growth, when they existed as single cells.

Blocking macrophage recruitment prevented TICs from developing into tumours and caused the immune system to eliminate them rapidly. The team also discovered YAP activation and macrophage recruitment in a small sample of precancerous lesions from human livers, suggesting that similar mechanisms might be involved in some human cancers. Targeting YAP or macrophages could be a therapeutic strategy for liver cancer, the authors suggest.

Read more, please click http://www.nature.com/nature/journal/v543/n7644/full/543152b.html

2. Class IIa HDAC inhibition reduces breast tumours and metastases through antitumour macrophages.

Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition)or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success.

Jennifer L. Guerriero at Dana-Farber Cancer Institute in Massachusetts, USA, and her colleagues hypothesized that pharmacologic modulation of macrophage phenotype could produce an anti-tumour effect. The team previously reported that a first-in-class selective class IIa histone deacetylase (HDAC) inhibitor, TMP195, influenced human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro. Here, they utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonary metastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumours. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction. These data introduce class IIa HDAC inhibition as a means to harness the anti-tumour potential of macrophages to enhance cancer therapy.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21409.html

3. Early antibody therapy can induce long-lasting immunity to SHIV.

Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease.

Here, Yoshiaki Nishimura at National Institutes of Health in Maryland, USA, and his colleagues  show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control. Animals challenged with SHIV_AD8-EO by mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074). Viraemia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4⁺) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 10⁶ circulating CD4⁺ T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8β monoclonal antibody to the controller animals led to a specific decline in levels of CD8⁺ T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Their results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8⁺ T-cell immunity able to durably suppress virus replication.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21435.html

4. Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus.

Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease.

Laura S. Weyrich at School of Biological Sciences and The Environment Institute, University of Adelaide in Adelaide, South Australia, and his colleagues described the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)—the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution, the authors suggest.

Read more, please click http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21674.html

5. Autophagy maintains the metabolism and function of young and old stem cells.

With age, haematopoietic stem cells lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress.

Theodore T. Ho at Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California in California, USA, and his colleagues show that loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs haematopoietic stem-cell self-renewal activity and regenerative potential. Strikingly, most haematopoietic stem cells in aged mice share these altered metabolic and functional features. However, approximately one-third of aged haematopoietic stem cells exhibit high autophagy levels and maintain a low metabolic state with robust long-term regeneration potential similar to healthy young haematopoietic stem cells. Their results demonstrate that autophagy actively suppresses haematopoietic stem-cell metabolism by clearing active, healthy mitochondria to maintain quiescence and stemness, and becomes increasingly necessary with age to preserve the regenerative capacity of old haematopoietic stem cells.

Read more, please click http://www.nature.com/nature/journal/v543/n7644/full/nature21388.html

CD45 Monoclonal Antibody Review

CD45 is a type I transmembrane protein that interacts directly with antigen receptor complex proteins or activates Src family kinases involved in the regulation of T- and B-cell antigen receptor signaling. CD45 appears to be both a positive and a negative regulator that conducts signals depending on specific stimuli and cell type. Human leukocytes including lymphocytes, eosinophils, monocytes, basophils, and neutrophils express CD45, while erythrocytes and platelets are negative for CD45 expression.

Abbkine CD45 Monoclonal Antibody is produced by immunizing mouse with recombinant protein specific to human CD45 protein. Its applications are WB, IHC-p and IF, with a recommended starting dilution of 1:2000 for WB, 1:200 for IHC-p and IF. The investigator is however advised to determine the optimal working dilutions through experiments. The antibody recognizes endogenous levels of total CD45 protein.

Immunohistochemical analysis of paraffin-embedded Human-lung-cancer tissue using Abbkine CD45 Monoclonal Antibody, it gave a positive signal.  I tried the protocol Abbkine suggested. The antibody was diluted at 1:200, incubated with tissue sections at 4°C overnight. Sodium citrate pH 6.0 was used for antibody retrieval (>98°C, 20min). Goat anti-mouse secondary antibody was diluted at 1:200 (room temperature, 30min). Negative control was used by secondary antibody only. Obviously, I got the exact result I hope. It saves a lot of precious time which let my test proceeding under my control.

Abbkine Scientific Announces There Newly Improved Antibody Purification Protein A/G Kit

Wuhan, China. 430074. 14^th March 2017. The Abbkine Scientific Company has unveiled its highest quality of Protein A/G Agarose as its premium-quality affinity resin for antibody purification. The Purkine™ Protein A/G Agarose consist of recombinant fusions protein A/G that are covalently immobilized onto high-quality beads of cross-linked 4% Agarose for using in lgG purification applications. Tests confirm that the protein A/G resins exceed or equal popular recombinant Protein A/G from leading suppliers and it does not decrease in performance for at least five repeated use.

These particular antibody purifiers from Abbkine provides the most versatile combination features for high purity purification and high yield of the whole lgG from serum samples. The Agarose beads used have chemical and physical properties that are suitable for many affinity purification systems. In addition to the properties and affinity purification, its high flow properties make protein A/G an excellent option for scaling up.

Abbkine Purkine™ Antibody Purification Protein A/G Kit features and benefits include:

• High capacity: contains more than 7mg of human resin lgG per mL.


• High performance: the combination between the lgG domains of both protein G and protein A together with the recombinant Protein A/G beads contains four Fc-binding domains making it a more convenient tool for purifying immunoglobins and for investigating.


• Cost effective: offers the same performance for at least five repeated uses.


• Flexible: you can find it in three different formats of bulk resin, spin column, and complete kits.


• Robust: because of its highly cross-linked beads, it has a linear tolerate flow rate of up to 300cm/hour.


• Easy to use: available in pre-formulated buffers.

The Protein A/G Purification system is an effective purification affinity of lgG from ascites fluid, serum, cell supernatant and other antibody samples. To minimize nonspecific binding of proteins from recombinant protein A/G, it is chemically modified using the propriety method. It binds well to all lgG subclasses including the human LgG subclasses but does not bind with the lgM, serum albumin or the lgA. The portfolio allows the optimization of solubility, maximum protein yield and stability processe.

Using the latest cutting-edge techniques rather than traditional methods, Abbkine has managed to manufacture a series of unique purifications for development and accessories optimization. Their tools are available for samples with improved productivity of nucleic acids, biomolecules markers, antibodies and fusion proteins that are cost effective and makes the workflow easier.

About Abbkine Scientific

Abbkine Scientific Co., Ltd. was founded by a number of scientists and marketing experts in the field of life science in California, USA in 2012. With growing demands from Asia Pacific, it move its headquarters to China. Combining cutting edge technology from United States with China's manufacturing engineering and cost advantages, we aim to provide innovative, high quality assay kits, recombinant proteins, antibodies and other research tools to accelerate life science fundamental research, drug discovery, etc.

Weekly Top Scientific Research Review (3/6/2017-3/10/2017)

1. Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice.

Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.

2. Single-Cell Multiomics: Multiple Measurements from Single Cells.

Single-cell sequencing provides information that is not confounded by genotypic or phenotypic heterogeneity of bulk samples. Sequencing of one molecular type (RNA, methylated DNA or open chromatin) in a single cell, furthermore, provides insights into the cell’s phenotype and links to its genotype. Nevertheless, only by taking measurements of these phenotypes and genotypes from the same single cells can such inferences be made unambiguously. In this review, we survey the first experimental approaches that assay, in parallel, multiple molecular types from the same single cell, before considering the challenges and opportunities afforded by these and future technologies.

3. Pyruvate and Metabolic Flexibility: Illuminating a Path Toward Selective Cancer Therapies.

Dysregulated metabolism is an emerging hallmark of cancer, and there is abundant interest in developing therapies to selectively target these aberrant metabolic phenotypes. Sitting at the decision-point between mitochondrial carbohydrate oxidation and aerobic glycolysis (i.e., the ‘Warburg effect’), the synthesis and consumption of pyruvate is tightly controlled and is often differentially regulated in cancer cells. This review examines recent efforts toward understanding and targeting mitochondrial pyruvate metabolism, and addresses some of the successes, pitfalls, and significant challenges of metabolic therapy to date.

4. Tumor–Host Cell Interactions in Ovarian Cancer: Pathways to Therapy Failure.

Although most ovarian cancer patients are highly responsive to chemotherapy, they frequently present with recurrent metastatic lesions that result in poor overall survival, a situation that has not changed in the last 20 years. This review discusses new insights into the regulation of ovarian cancer chemoresistance with a focus on the emerging role of immune and other host cells. Here, we summarize the complex molecular pathways that regulate the interaction between tumor and host cells, discuss the limitations of current in vitro and in vivo models for translational studies, and present perspectives for the development of innovative therapies

5. Developing Cures: Targeting Ontogenesis in Cancer.

Cancer has long been known to histologically resemble developing embryonic tissue. Since this early observation, a mounting body of evidence suggests that cancer mimics or co-opts developmental processes to facilitate tumor initiation and progression. Programs important in both normal ontogenesis and cancer progression broadly fall into three domains: the lineage commitment of pluripotent stem cells, the appropriation of primordial mechanisms of cell motility and invasion, and the influence of multiple aspects of the microenvironment on the parenchyma. In this review we discuss how derangements in these developmental pathways drive cancer progression with a particular focus on how they have emerged as targets of novel treatment strategies.

6. Contributions of Mammalian Chimeras to Pluripotent Stem Cell Research.

Chimeras are widely acknowledged as the gold standard for assessing stem cell pluripotency, based on their capacity to test donor cell lineage potential in the context of an organized, normally developing tissue. Experimental chimeras provide key insights into mammalian developmental mechanisms and offer a resource for interrogating the fate potential of various pluripotent stem cell states. We highlight the applications and current limitations presented by intra- and inter-species chimeras and consider their future contribution to the stem cell field. Despite the technical and ethical demands of experimental chimeras, including human-interspecies chimeras, they are a provocative resource for achieving regenerative medicine goals.

HSP70 Monoclonal Antibody Review

The HSP70 monoclonal antibody is a unique antibody from popular scientific research company, Abbkine Scientific Company Limited. The research outfit headquartered in China has launched different research products including antibodies and the HSP70 Monoclonal Antibody is another amazing scientific discovery, made to help research scientist carry out their task easier and more effectively.

The product otherwise known as HSPA1 Antibody is unique due to its features and inherent benefits, especially when compared to other products of similar nature. The HSPA1L encodes a 70kDa heat shock protein, a distinct attribute of the product. This is in addition to encoding other heat shock proteins and heat shock protein family A (Hsp70) member 1, helping to stabilize existing proteins against aggregation and also mediating the folding of proteins that are newly translated in the cytosol and in organelles.

HSPA1L is found in the main histocompatibility complex class III region, located in a cluster with two different but closely related genes that also encode isoforms of the 70kDa heat shock protein.

Features of the HSP70 Monoclonal Antibody

The product comes with different features that do not only distinguish from the competition, but make it one of the most sought-after monoclonal antibody in the science research world. Some of these features are listed below.

. The HSP70 is formulated in a liquid solution, ensuring ease of use by science researchers and other such users.

. The product has a 1 mg/ml concentration, making it one of the best in the market.

. The storage buffer is PBS, pH 7.4, containing 0.02% sodium oxide as Preservative and 50% Glycerol, helping to maintain its efficiency.

. The HSP70’s immunogen is synthetic peptide.

. The product has a relatively long life span if stored under recommended conditions. The storage instruction of the HSP70 states that the product can be stable for as much as a year at a temperature of -20°C from the shipment date.

. The HSP70 is easy to recover from storage, with a recommended method of centrifuging the original vial after thawing and prior to removing the cap. Aliquot to avoid repeated freezing and thawing.

. The mouse is the host and the HSP70 reacts with rat, mouse and human.

. Its applications are IF and WB, with a recommended starting dilution of between 1:1000 and 2000 for WB, and 1:100 and 200 or IF. The investigator is however advised to determine the optimal working dilutions through experiments.

. It is monoclonal with Mouse IgG1 isotype.

Pros and Cons of the HSP70

There has been no reported case of cons, defects or unsatisfactory remarks about the antibody. This however does not take away the fact that such situations might arise as time passes, but with the continuous effort of the team at Abbkine, defects are expected to be corrected almost immediately they are spotted.

One of the pros of the HSP70 is its purification, as it was affinity-purified from mouse ascites using specific immunogen to guarantee its safety.

Its relatively long lifespan is another merit of the HSP70 as it can last for as long as one year after the shipment date if stored under proper conditions stated above.

The effective detection of endogenous HSP70 proteins is another advantage of the HSP70.

Conclusion

Abbkine have warned against using the product for clinical or human diagnosis as it was specifically made for research use. The HSP70 monoclonal antibody is one that would greatly benefit the science world and researchers in particular, thanks to its amazing features and benefits.

New Anti-β-Tubulin Mouse Monoclonal Antibody (3G6) has been released by Abbkine

Wuhan, China. 430074. 11^th March 2017. The Tubulin belongs to a group of several members of a small family of proteins known as the globular proteins. The globular proteins are the major consistent of microtubules. Alpha-tubulin and beta-tubulin are the two most common members of the tubulin family and together they form microtubules from their dimers. After the dimer is incorporated into microtubule, the GTP bounds to the beta-tubulin that eventually hydrolyzes into GDP along with the microtubule protofilament. Dimers bound to GDP fall apart while those bound to GTP tend to assemble into microtubules. Each of the molecule weight approximately 55kDa.

Antibodies from Beta-tubulin is usually used as a loading control for western blot. It is used to normalize the levels of proteins by checking that the protein loading is the same across the gel. However, the level of B-tubulin is not stable in certain cells, such as adipose tissue. Abbkine offers the best quality anti-β-tubulin mouse monoclonal antibody for WB and IHC-p.

Western blotting accurately measures the change of a specific protein under different circumstances and conditions. There are multiple steps involved during the process, including sample loading, sample preparation, protein transfer, signal detections, electrophoresis, and antibody incubation. In order to accurately interpret the results of western blot experiment, it’s advisable to use quality anti-β-tubulin throughout the loading control process. The same amount of protein sample should be used in each loading lane.

Anti-β-tubulin monoclonal antibody from Abbkine has an optimal working dilution that should be determined by investigators during experiments. We suggest that you start diluting as follows, WB 1:5000 or IHC-p 1:200. Using specific immunogenic and the affinity chromatography method, the antibody was affinity-purified from mouse ascites. They are from the monoclonal clonality and Mouse lgG1 isotope. The Anti-β tubulin monoclonal antibody can be reactive in dog, monkey, chicken, rabbit, rat, insects, and humans and also yeast.

When shipped at -20℃, the anti-β tubulin mouse monoclonal antibody is stable for a year from the shipment date. Aliquot to avoid freezing or melting and in the case of product recovery, centrifuge the original vial prior to removing the cap after melting. This product is best for research use only, the Abbkine Scientific Company is not responsible for any patent infringements or violations.

About Abbkine Scientific

Abbkine Scientific Co., Ltd. was founded by a number of scientists and marketing experts in the field of life science in California, USA in 2012. With growing demands from Asia Pacific, it moves its headquarters to China. Combining cutting edge technology from United States with China's manufacturing engineering and cost advantages, we aim to provide innovative, high quality assay kits, recombinant proteins, antibodies and other research tools to accelerate life science fundamental research, drug discovery, etc.

HER2 Monoclonal Antibody Review

The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity. Amplification of the ErbB2 gene and overexpression of its product are detected in almost 40% of human breast cancers. ErbB2 is a key therapeutic target in the treatment of breast cancer and other carcinomas and targeting the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway is one potential therapeutic strategy.

Abbkine HER2 Monoclonal Antibody are produced by immunizing mouse with a synthetic peptide. The isotype of the antibody is mouse IgG1. HER2 Monoclonal Antibody detects endogenous levels of total HER2 protein. The antibody does not cross-react with related kinases. Test confirmed the antibody can applied in WB, IF and IHC-p with Human, Mouse and Rat samples. Abbkine suggested the dilutions are: WB: 1:2000-4000, IHC: 1:200 and IF 1:200.

I purchased Abbkine HER2 Monoclonal Antibody for  immunofluorescence analysis of Rat-spleen tissue. I dilute the antibody according to the recommendation which is 1:200 for 4°C, overnight. Cy3 labled secondary antibody was diluted at 1:300 at room temperature for 50min. I show my picture in the left . I am very satisfied with this product-high quality research product with affordable price.