This study evaluated the effects of an extract from Aphanizomenon flos-aquae (AFA) containing a novel ligand for human L-selectin on stem cell physiology. Methods showed AFA contains a ligand composed of two proteins that binds to L-selectin. In vitro, AFA reduced L-selectin antibody binding and inhibited fucoidan-induced CXCR4 expression on stem cells, indicating it is an L-selectin blocker. In vivo, consumption of an AFA extract enriched in the ligand resulted in a transient 25% increase in circulating stem cells within 60 minutes, returning to baseline by 3-4 hours later.
Recombinant Transferrin and Albumin Improves Mononuclear and Hematopoietic St...The Cell Culture Dish
Improving the expansion of mononuclear and stem cells is a major challenge in
regenerative medicine. The majority of current serum-free stem cell expansion media
contain animal-derived components in order to enhance performance. The advantages
of using animal-free recombinant transferrin and albumin as media components were
determined for the expansion of mononuclear and CD34+ stem cells isolated from
umbilical cord blood.
SmartScreen Technology for Building a Better AssayKristin Rider
A lipid derived nanoparticle the recreates the cellular membrane in solution based assays. See increased enzymatic activity, identify more relevant biological substrates, find novel hits from the compound library.
Recombinant Transferrin and Albumin Improves Mononuclear and Hematopoietic St...The Cell Culture Dish
Improving the expansion of mononuclear and stem cells is a major challenge in
regenerative medicine. The majority of current serum-free stem cell expansion media
contain animal-derived components in order to enhance performance. The advantages
of using animal-free recombinant transferrin and albumin as media components were
determined for the expansion of mononuclear and CD34+ stem cells isolated from
umbilical cord blood.
SmartScreen Technology for Building a Better AssayKristin Rider
A lipid derived nanoparticle the recreates the cellular membrane in solution based assays. See increased enzymatic activity, identify more relevant biological substrates, find novel hits from the compound library.
Proteomics of small proteins from plant tissuesExpedeon
Small genes and the proteins that they encode can play important biological roles including signaling, development, and mediation of plant-microbe interactions in organisms ranging from bacteria to plants to mammals (Frith et al.; Basrai et al.; Galindo et al.; Hemm et al. 2008, 2010; Kastenmeyer et al.). However, genes that encode proteins containing <100 residues are difficult to identify reliably solely by DNA sequence analysis (Dinger et al.)
ABSTRACT- Aberrant glycosylation has been recognized as hallmark of cancer. Exploiting differences in glycosylation between malignant and healthy tissues offers excellent opportunities to identify sensitive and specific cancer biomarkers. Plant lectins have demonstrated the ability to specifically agglutinate malignant transformed cells. Lectins are sugar binding proteins or glycoprotein of non-immune origin which agglutinate cells or precipitate glycol-conjugates. Some lectins shown to the anti- proliferative effect on cancer cells. A wide scope of this application of lectins is that it can be used for diagnosis as well as therapeutics of cancer. The objective of the present study was to purify a lectin from tubers of Arisaema intermedium and evaluate in vitro anti-proliferative potential towards HCT-15, a human colon cancer cell line. The present study was conceived as an offshoot to the ongoing work on lectins in our laboratory. The already reported Arisaema intermedium (AIL) lectin was purified on asialofetuin linked amino-activated silica bead matrix. The purity of the affinity purified lectin was ascertained by SDS-PAGE, pH-8.3. The lectin activity was assessed by hemagglutination and protein concentration was determined by Lowry’s method. The cytotoxicity of AIL towards HCT-15 was evaluated by MTT assay. The mechanism of anti-proliferative effect was assessed by evaluation of cell morphology, trypan blue exclusion assay, DNA fragmentation and nucleic acid content determination.
Key-words- Araceae, Arisaema, Asialofetuin, Antiproliferative effect, Apoptosis, Cytotoxicity Lectins, Mechanistic
Proteomics of small proteins from plant tissuesExpedeon
Small genes and the proteins that they encode can play important biological roles including signaling, development, and mediation of plant-microbe interactions in organisms ranging from bacteria to plants to mammals (Frith et al.; Basrai et al.; Galindo et al.; Hemm et al. 2008, 2010; Kastenmeyer et al.). However, genes that encode proteins containing <100 residues are difficult to identify reliably solely by DNA sequence analysis (Dinger et al.)
ABSTRACT- Aberrant glycosylation has been recognized as hallmark of cancer. Exploiting differences in glycosylation between malignant and healthy tissues offers excellent opportunities to identify sensitive and specific cancer biomarkers. Plant lectins have demonstrated the ability to specifically agglutinate malignant transformed cells. Lectins are sugar binding proteins or glycoprotein of non-immune origin which agglutinate cells or precipitate glycol-conjugates. Some lectins shown to the anti- proliferative effect on cancer cells. A wide scope of this application of lectins is that it can be used for diagnosis as well as therapeutics of cancer. The objective of the present study was to purify a lectin from tubers of Arisaema intermedium and evaluate in vitro anti-proliferative potential towards HCT-15, a human colon cancer cell line. The present study was conceived as an offshoot to the ongoing work on lectins in our laboratory. The already reported Arisaema intermedium (AIL) lectin was purified on asialofetuin linked amino-activated silica bead matrix. The purity of the affinity purified lectin was ascertained by SDS-PAGE, pH-8.3. The lectin activity was assessed by hemagglutination and protein concentration was determined by Lowry’s method. The cytotoxicity of AIL towards HCT-15 was evaluated by MTT assay. The mechanism of anti-proliferative effect was assessed by evaluation of cell morphology, trypan blue exclusion assay, DNA fragmentation and nucleic acid content determination.
Key-words- Araceae, Arisaema, Asialofetuin, Antiproliferative effect, Apoptosis, Cytotoxicity Lectins, Mechanistic
Fixing a leaky bucket; Observations on the Global LEI SystemPaul Houle
We apply bitemporal analysis to more than 500 daily data files supplied by the Global Legal Entity Identifier Foundation to show that churn dominates the dynamics of growth, such that the number of paid up records in full standing has been flat over the last year. Our analysis reveals occasional daily glitches in the past that affected thousands of records. These appear to be in better control now, but a high lapse rate is the primary challenge to the Global LEI System right now
AWS re:Invent 2016: Case Study: Data-Heavy Healthcare: UPMCe’s Transformative...Amazon Web Services
Today's health care systems generate massive amounts of protected health information (PHI) — patient electronic health records, imaging, prescriptions, genomic profiles, insurance records, even data from wearable devices. In this session, UPMCe dives deep into two efforts: Their "Data Liberation Project"—a next-gen petabyte-scale software solution that provides responsible management of PHI within their own environments as well as externally, and “Neutrino” a real time medical document aggregator which utilizes natural language processing techniques to unlock hidden value from unstructured narratives. UPMC Enterprises (UPMCe), a division of University of Pittsburgh Medical Center, builds technology and invests in health care companies, from new startups to large established partners, with an eye toward revolutionizing healthcare. They embody the startup mentality with a focus on innovation and creating new data-heavy applications—all in support of new spin-off companies, furthering economic development, and disrupting healthcare. Join us to learn how they do security management and governance using Amazon S3, Amazon EC2, AWS Config, AWS CloudTrail, and other Amazon services help UPMCe think big about healthcare data in the public sector.
AWS re:Invent 2016: Amazon s2n: Cryptography and Open Source at AWS (NET405)Amazon Web Services
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AWS re:Invent 2016: Tableau Rules of Engagement in the Cloud (STG306)Amazon Web Services
You have billions of events in your fact table, all of it waiting to be visualized. Enter Tableau… but wait: how can you ensure scalability and speed with your data in Amazon S3, Spark, Amazon Redshift, or Presto? In this talk, you’ll hear how Albert Wong and Srikanth Devidi at Netflix use Tableau on top of their big data stack. Albert and Srikanth also show how you can get the most out of a massive dataset using Tableau, and help guide you through the problems you may encounter along the way. Session sponsored by Tableau.
AWS Competency Partner
Novozymes Veltis® – Engineerd albumins for optimized drug dosingNiklas Andersson
Novozymes Veltis® is a clinically-proven half-life extension technology based on engineered albumins that allows drug developers to optimize dose size and frequency to achieve improved patient compliance.
Comparative Cytotoxic Activities of the Flavonoid-Rich Ethyl Acetate Fruit Ex...inventionjournals
The fruit of Pouteriacampechianahas been previously reported to contain flavonoids and polyphenolic substances with high in vitro anti-oxidative effects. Its anti-tumorigenic activities have not been previously demonstrated. This study seeks to demonstrate the cytotoxic effects of the flavonoid-rich ethyl acetate fraction of the fruit extract of P. campechiana(EAFFPC) against K562 leukemic cell lines and healthy human whole blood cells. The standardized MTT-dye cell viability assay was carried out to measure the cytotoxicity of EAFFPC against the aforementioned cell lines cultured in RPMI. The assay showed that at a 60 µg well concentration, EAFFPC exhibited a 55.4% cell viability which is significantly lower than the cell viability obtained with 10 µg of vincristine. In contrast, EAFFPC demonstrated concentration-dependent cytoprotective properties in healthy human whole blood cells (HHWBC). This study confirms specific nonconcentration-dependent cytotoxic effects on K562 leukemic cell lines while exhibiting a concentrationdependent cytoprotective effects in HHWBC
Strategie nutraceutiche per ridurre l'infiammazione.CreAgri Europe
I polifenoli estratti dalle olive sono in grado di ridurre l'infiammazione mediata da TNF alfa. Esiste inoltre un effetto sinergico nella riduzione dello stato infiammatorio tra idrossitirosolo e glucosammina.
- inglese - testo scientifico -
SAGE Student Research Conference Poster- The Effect of Purified Acetaminophen...Melissa McCoy, MS, MBA
What is acetaminophen? Acetaminophen (APAP) is the active pharmaceutical ingredient of Tylenol® and other pharmaceutical generics, used as an analgesic. Previous experiments and data has suggested this molecule can potentially induce negative off-target effects in healthy, biological cells and tissues of the human body [1,2,3]. The specific effects discovered, of this small molecule included decreasing cell proliferative function, alter morphology, and omit intercellular protein interactions of normal cells [1,2,3]. If studies can biologically isolate the APAP’s function of causing these biological negative feedbacks, then experimental research on cancer cells should be eminent. It was originally hypothesized that the additive effects of Tylenol®, Advil®, and Aleve®, causes off-target effects on mouse lymphocytic leukemia cells (L1210) and over time, kill off the entire population. It was narrowed down to APAP, having the most extreme and quickest change in this cell’s proliferation and adhesion functions in a given time interval. Immortalized Human T Lymphocytes (Jurkat) were decided on because it needs to be seen if there is a biosimilar effect on a human cancer cell line. Therefore, it was hypothesized that APAP will suppress the Jurkat cell’s proliferative function, alter membrane shape, change the intercellular behavior, and induce apoptosis, due to the highly suggestive evidence that APAP signals to off-target proteins in biological cells. Knowing this information can potentially have researchers and biotech companies alike, further work with APAP and adjust it accordingly, as a potential oncotoxic molecule for cancer therapy.
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
The publishing industry has been selling digital audiobooks and ebooks for over a decade and has found its groove. What’s changed? What has stayed the same? Where do we go from here? Join a group of leading sales peers from across the industry for a conversation about the lessons learned since the popularization of digital books, best practices, digital book supply chain management, and more.
Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
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👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
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Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
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Connector Corner: Automate dynamic content and events by pushing a buttonDianaGray10
Here is something new! In our next Connector Corner webinar, we will demonstrate how you can use a single workflow to:
Create a campaign using Mailchimp with merge tags/fields
Send an interactive Slack channel message (using buttons)
Have the message received by managers and peers along with a test email for review
But there’s more:
In a second workflow supporting the same use case, you’ll see:
Your campaign sent to target colleagues for approval
If the “Approve” button is clicked, a Jira/Zendesk ticket is created for the marketing design team
But—if the “Reject” button is pushed, colleagues will be alerted via Slack message
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And...
Speakers:
Akshay Agnihotri, Product Manager
Charlie Greenberg, Host
Let's dive deeper into the world of ODC! Ricardo Alves (OutSystems) will join us to tell all about the new Data Fabric. After that, Sezen de Bruijn (OutSystems) will get into the details on how to best design a sturdy architecture within ODC.
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
"Impact of front-end architecture on development cost", Viktor TurskyiFwdays
I have heard many times that architecture is not important for the front-end. Also, many times I have seen how developers implement features on the front-end just following the standard rules for a framework and think that this is enough to successfully launch the project, and then the project fails. How to prevent this and what approach to choose? I have launched dozens of complex projects and during the talk we will analyze which approaches have worked for me and which have not.
"Impact of front-end architecture on development cost", Viktor Turskyi
Medical study summary
1. A novel cyanobacterial ligand for human L-selectin extracted from
Aphanizomenon flos aquae – potential role for stem cell biology in vitro and in vivo?
Introduction
The objective of this study was to evaluate the in vitro and in vivo effects of StemEnhance®, an
extract from Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human L-selectin,
on stem cell physiology. L-selectin is a
cell adhesion molecules involved in
cellular migration, cellular adhesion, and
the retention versus release of bone
marrow stem cells into the blood
circulation. Stimulation of L-selectin
leads to the externalization of pre-formed
CXCR4 chemokine receptors, which are
specific for the chemokine Stromal
Derived Factor-1 (SDF-1) (Figure 1). Figure 1
Binding to SDF-1 to CXCR4 leads to the
externalization of adhesion molecules that
anchor the stem cell in the bone marrow. SDF-1 acts as a potent attractant for stem cells and
therefore assists in retaining stem cells within the bone marrow environment.
It was demonstrated that any interference with the CXCR4/SDF-1 axis is one of several
contributing mechanisms involved in the release of stem cells from the bone marrow. Therefore,
any compound that interferes with CXCR4 or SDF-1 has the potential of acting as a stem cell
mobilizer.
2. There are many ways to support stem cell mobilization. For example, Granulocyte Colony-
Stimulating Factor (G-CSF), the natural compound in the body stimulating stem cell
mobilization works at least in part by raising the level of specific proteolytic enzymes that
degrade SDF-1, thereby disrupting the CXCR4/SDF-1 axis. Other compounds such as AMD-
3100 promote stem cell mobilization by blocking CXCR4, once again disrupting the
CXCR4/SDF-1 axis. Finally, L-selectin blockers reduce the density of CXCR4 on the surface of
the stem cells’ membrane, thereby down-regulating the CXCR4/SDF-1 axis. Due to the
physiological processes involved in each of these mechanisms of action, the mobilizations
triggered by each of these mechanisms show different magnitude, time of onset, and duration.
Mobilization triggered by G-CSF and AMD-3100 begins within a few days, last for a few days
and can lead to an increase in the number of circulating stem cells by up to 100-fold.
Conversely, mobilization triggered by L-selectin blockers is more transient and of a much lesser
magnitude. The mobilization observed after consumption of StemEnhance was rapid, transient
and mild, therefore we hypothesized that AFA contained an L-selectin blocker.
Methods & Results
AFA contains a ligand for human L-selectin
In order to determine whether AFA contained an L-
selectin ligand (binding molecule), paramagnetic
Dynabeads coated with human L-selectin were
incubated with a water extract of AFA (AFA-W)
(Figure 2). After incubation, Dynabeads were
washed and any bound material from the AFA
extract was detached from the L-selectin molecules
and run on gel-electrophoresis. Figure 2
3. This process revealed that AFA contains an L-
selectin ligand that appears to be a dimmer
made of two proteins having apparent
molecular weights of 57 and 54 kDa
respectively (Figure 3).
Using the same protocol on Spirulina, it was
determined that Spirulina does not contain an
Figure 3 L-selectin ligand.
AFA-W specifically reduces TQ1 immunostaining of L-selectin on human PMN cells
L-selectin possesses one specific binding site whose activation leads to the externalization of
CXCR4. In order to determine whether the L-selectin ligand present in AFA was binding to the
active binding site of L-selectin, we tested the effect of AFA-W on the binding properties of TQ1
anti-human L-selectin monoclonal antibody. TQ1 is an antibody that specifically binds to the
physiological active binding site of L-selectin. Incubation of lymphocytes with AFA-W reduced
the binding of TQ1 by approximately 50-fold, indicating that the AFA L-selectin ligand does
bind to the active binding site of L-selectin.
AFA-W inhibits the fucoidan-induced CXCR4 expression on CD34+ cells from bone
marrow
It was important to determine whether the L-selectin ligand found in AFA was a stimulant or an
inhibitor of L-selectin. We know that stimulation of L-selectin leads to an increase in the
externalization of CXCR4, which can be quantified by measuring the density of CXCR4
receptors on the surface of stem cells. Incubation of bone marrow stem cells with AFA-W did
not have any effect on CXCR4 density, indicating that the AFA L-selectin ligand was not a
stimulant of L-selectin (Figure 4; green line).
4. 35 Figure 4
CXCR-4 Expression (MFI) 30
25
20
15
Untreated
10 Fucoidan
Fucoidan w ith AFA
AFA Alone
5
0
0 15 30 45 60
Time (min)
To investigate whether the ligand was a blocker of L-selectin we tested the effect of AFA-W on
fucoidan-induced increase in CXCR4 density (Figure 4). Fucoidan is a sulfated polysaccharide
known to stimulate L-selectin. Fucoidan triggered an 8-fold increase in CXCR4 density (blue
line) which was inhibited (≈50%) by incubation with AFA-W (red line). Therefore, AFA
contains a blocker of L-selectin.
Consumption of StemEnhance® resulted in a transient increase of circulating CD34+ cells.
As previously described in the scientific literature, L-selectin blockers have the potential of being
effective stem cell mobilizers by modulating the CXCR4/SDF-1 axis. Therefore, we tested the
mobilizing ability of the AFA L-selectin ligand in humans. Using a double-blind cross-over
paradigm, the level of circulating CD34+ stem cells was compared in 15 individuals before and
after ingestion of 1 gram of StemEnhance® or placebo. StemEnhance® (STEMTech
HealthSciences, Inc., CA) is a proprietary blend of the cytoplasmic and cell wall-rich fractions of
the whole plant biomass, enriched approximately 5-fold in content of the L-selectin ligand
compared to the raw AFA biomass.
5. Consumption of StemEnhance® resulted Figure 5
130%
in a 25 ± 1% increase in the number of
p<0.0001
circulating stem cells at 60 minutes (p< 125%
120%
0.0001) (Figure 5). The number of
circulating CD34+ stem cells returned
% of Start
to baseline level around 3-4 hours after 110%
consumption. This was in contrast to
placebo, which resulted in only minor 100%
+
fluctuations of the levels of CD34 cells
in the blood circulation over 2 hours.
90%
0 30 60 90 120
Time (min)
Figure 6
In order to test the repeatability of the effect of
consumption of StemEnhance® on the levels of CD34+
cells in the peripheral blood, 16 separate experiments
were performed on one volunteer. The average increase
in the number of circulating stem cells was 53 ± 16%,
with a median of 36% and a highest and lowest increase
of 233% and -4%, respectively (Figure 6).
6. Discussion
Dietary strategies for supporting stem cell biology represent an emerging field of nutritional and
medical research. The cyanobacterium AFA has been studied for its anti-oxidant properties and
immuno-modulatory effects both in human and in vitro. AFA contains a number of compounds
that have been subject to much research, including the potent antioxidant phycocyanin, a
complex polysaccharide with potent immuno-modulatory properties, and the neuromodulator
phenylethylamine responsible for the experience of mental energy reported by consumers.
It is reported here that AFA also contains a novel compound that specifically binds to the ligand-
binding area of human L-selectin. It is composed of two subunits with apparent molecular
weight around 54-57 kDa. This ligand for human L-selectin, obtained from AFA water extract,
was able to modulate the functional response on human lymphocytes in vitro. The expression of
the chemokine receptor CXCR4, which is induced by the known L-selectin ligand fucoidan, was
down-regulated when fucoidan and AFA water extract were added simultaneously, indicating
that the L-selectin ligand from AFA was competing with fucoidan for binding to L-selectin.
A double-blinded placebo-controlled cross-over study showed that consumption of
StemEnhance® resulted in a small but significant increase in the number of circulating CD34+
stem cells, peaking at 1 hour after consumption. The effect was statistically significant
(p<0.0001). There is however a significant fluctuation from one day to another in the effect of
StemEnhance® or in the ability to quantify the effect accurately. Therefore, in order to test the
nature of this fluctuation, we tested one individual on 16 different experimental days. The
increase in the number of circulating stem cells after consumption of StemEnhance® averaged 52
± 16% and varied greatly from 96% to 333% of baseline value. Interestingly, the average
response in the one individual tested repeatedly and the average response to StemEnhance® in
the double-blind randomized study involving 12 people were similar, indicating the relative
consistency of the response and that the double-blind trial may in fact have understated the effect
of StemEnhance®.
Recent studies have put in evidence the potential role of stem cell mobilizers in the maintenance
of optimal health. Recently, a number of studies concluded that the level of circulating CD34+
stem cells was a good indicator of health.