The pancreas is densely innervated, and neural signals play a significant role in glucose regulation by modulating pancreatic hormone release. However, relatively little is known about the anatomical relationships between islets and nerves across the whole pancreas. In this webinar, Dr. Sarah Stanley and Dr. Alexandra Alvarsson will discuss their research using tissue clearing and whole organ imaging of the pancreas to identify the 3D structure of pancreatic nerves and islets.
In particular, they will provide an overview of their methodology, which provides detailed information and quantification of pancreatic innervation in healthy pancreas, in canonical models of diabetes and in samples from nondiabetic and diabetic donors. They will also present their findings, demonstrating greatly enriched innervation in the islets with regional variations. They will also discuss beta cell innervation in mouse models of diabetes and in pancreata from human donors with type 2 diabetes.
Key Topics Include:
- Tissue clearing and 3D imaging to allow the mapping of nerves in peripheral organs
- Innervation of peripheral organs such as the pancreas
- How pancreatic nerves are remodeled in diabetes
Cable fault location has often been seen as a dark art, as the causes of faults are different and varied. Successfully locating faults locations depends on an experienced operator. The challenge to Megger’s engineering team was to remove the mysteries from fault locating, and to make the whole process more logical. This methodical approach was used to define a feature set that would satisfy fault location needs in the varied conditions where the tester would be used around the world.
Megger cable fault location solutions include : low voltage TDR underground cable fault locators, surge generator fault locators, cable fault pinpointing, high voltage DC test sets and high voltage (11kV-33kV-66kV-132kV) underground cable fault locators.
Various techniques and principles of MV system neutral groundings summed up together-May be interesting and useful for practicing Electrtical engineers
Cable fault location has often been seen as a dark art, as the causes of faults are different and varied. Successfully locating faults locations depends on an experienced operator. The challenge to Megger’s engineering team was to remove the mysteries from fault locating, and to make the whole process more logical. This methodical approach was used to define a feature set that would satisfy fault location needs in the varied conditions where the tester would be used around the world.
Megger cable fault location solutions include : low voltage TDR underground cable fault locators, surge generator fault locators, cable fault pinpointing, high voltage DC test sets and high voltage (11kV-33kV-66kV-132kV) underground cable fault locators.
Various techniques and principles of MV system neutral groundings summed up together-May be interesting and useful for practicing Electrtical engineers
To identify and simulate conventional type of disturbance on the overhead transmission line by using PSCAD / EMTDC software package
To develop mathematical model for various type of disturbance on overhead transmission line.
To develop a smart algorithm for fault detection using Artificial Neural Network (ANN) and Particle Swarm Optimization (PSO).
ARVD is one of important coardiomyopathy in our clinical practice,early diagnosis, risk stratification and early diagnosis of CHF, management of VT will make big difference in patient life
Basics of Power systems
Network topology
Transmission and Distribution
Load and Resource Balance
Economic Dispatch
Steady State System Analysis
Power flow analysis
Dynamic System Analysis
Transient stability
GRID INTERCONNECTION OF RENEWABLE ENERGY SOURCES AT DISTRIBUTION LEVEL WITH P...Pradeep Avanigadda
Renewable energy resources (RES) are being increasingly connected in distribution systems utilizing power electronic converters. This project presents a novel control strategy for achieving maximum benefits from these grid-interfacing inverters when installed in 3-phase 4-wire distribution systems. The inverter is controlled to perform as a multi-function device by incorporating active power filter functionality. The inverter can thus be utilized as: 1) power converter to inject power generated from RES to the grid, and 2) shunt APF to compensate current unbalance, load current harmonics, load reactive power demand and load neutral current. All of these functions may be accomplished either individually or simultaneously. With such a control, the combination of grid-interfacing inverter and the 3-phase 4-wire linear/non-linear unbalanced load at point of common coupling appears as balanced linear load to the grid. This new control concept is demonstrated with extensive MATLAB/ Simulink simulation studies and validated through digital signal processor-based laboratory experimental results.
Fault location and correction are important in case of any power systems. This process has to be prompt and accurate so that system reliability can be improved , outage time can be reduced and restoration of system from fault can be accelerated.
Fault location calculation using Magnetoresistance sensor is described here.
HVDC Bridge and Station Configurations
1. General HVDC – HVAC Comparisons
2. Components of a Converter Bridge
3. HVDC scheme configurations
Operation of the HVDC converter
1. General assumptions
2. Rectifier operation with uncontrolled valves and X = 0
3. Rectifier operation with controlled valves and X = 0
4. Rectifier operation with controlled valves and X 0
5. Inverter operation with controlled valves and X 0
6. Commutation and Commutation Failure
7. Reactive Power Requirements
8. Short-circuit capacity requirements for an HVDC terminal.
9. Harmonics and filtering on the AC and DC sides
Case-1:
A 23 years old medical student presented with occasional palpitation, shortness of breath and chest discomfort. He had the following ECG.
A 53 years old gentleman presented with palpitations for last 5 hours. He is smoker, diabetic, dyslipidemic and hypertensive. He had exertional chest discomfort for last 5 years and did coronary angiogram 3 years back and CAG revealed TVD and advised for revascularization. But he refused and was irregular in medication and reluctant for life style modification. He came to emergency department with this ECG.
To identify and simulate conventional type of disturbance on the overhead transmission line by using PSCAD / EMTDC software package
To develop mathematical model for various type of disturbance on overhead transmission line.
To develop a smart algorithm for fault detection using Artificial Neural Network (ANN) and Particle Swarm Optimization (PSO).
ARVD is one of important coardiomyopathy in our clinical practice,early diagnosis, risk stratification and early diagnosis of CHF, management of VT will make big difference in patient life
Basics of Power systems
Network topology
Transmission and Distribution
Load and Resource Balance
Economic Dispatch
Steady State System Analysis
Power flow analysis
Dynamic System Analysis
Transient stability
GRID INTERCONNECTION OF RENEWABLE ENERGY SOURCES AT DISTRIBUTION LEVEL WITH P...Pradeep Avanigadda
Renewable energy resources (RES) are being increasingly connected in distribution systems utilizing power electronic converters. This project presents a novel control strategy for achieving maximum benefits from these grid-interfacing inverters when installed in 3-phase 4-wire distribution systems. The inverter is controlled to perform as a multi-function device by incorporating active power filter functionality. The inverter can thus be utilized as: 1) power converter to inject power generated from RES to the grid, and 2) shunt APF to compensate current unbalance, load current harmonics, load reactive power demand and load neutral current. All of these functions may be accomplished either individually or simultaneously. With such a control, the combination of grid-interfacing inverter and the 3-phase 4-wire linear/non-linear unbalanced load at point of common coupling appears as balanced linear load to the grid. This new control concept is demonstrated with extensive MATLAB/ Simulink simulation studies and validated through digital signal processor-based laboratory experimental results.
Fault location and correction are important in case of any power systems. This process has to be prompt and accurate so that system reliability can be improved , outage time can be reduced and restoration of system from fault can be accelerated.
Fault location calculation using Magnetoresistance sensor is described here.
HVDC Bridge and Station Configurations
1. General HVDC – HVAC Comparisons
2. Components of a Converter Bridge
3. HVDC scheme configurations
Operation of the HVDC converter
1. General assumptions
2. Rectifier operation with uncontrolled valves and X = 0
3. Rectifier operation with controlled valves and X = 0
4. Rectifier operation with controlled valves and X 0
5. Inverter operation with controlled valves and X 0
6. Commutation and Commutation Failure
7. Reactive Power Requirements
8. Short-circuit capacity requirements for an HVDC terminal.
9. Harmonics and filtering on the AC and DC sides
Case-1:
A 23 years old medical student presented with occasional palpitation, shortness of breath and chest discomfort. He had the following ECG.
A 53 years old gentleman presented with palpitations for last 5 hours. He is smoker, diabetic, dyslipidemic and hypertensive. He had exertional chest discomfort for last 5 years and did coronary angiogram 3 years back and CAG revealed TVD and advised for revascularization. But he refused and was irregular in medication and reluctant for life style modification. He came to emergency department with this ECG.
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
Malnutrition in the Peritoneal Dialysis population is highly prevalent. This presentation will address the common problem and explore the many benefits of Intraperitoneal Nutrition (IPN) using research-based evidence
Discuss causes of malnutrition in Peritoneal Dialysis patients
Identify patients based on reimbursement criteria
Identify methods to overcome barriers to achieving optimum outcomes from IPN therapy
Toward Precision Medicine in Neurological Disease by David GoldsteinKnome_Inc
View the webinar at http://www.knome.com/webinar-toward-precision-medicine-neurological-disease. In this presentation, Dr. Goldstein reports progress in identifying pathogenic mutations large-scale scale studies in epilepsy, in particular focusing on identifying de novo mutations as a cause of the epileptic encephalopathies. Next he discusses how sequencing is being used to diagnose rare serious unresolved genetic conditions. Finally, Dr. Goldstein describes a number of examples in which a secure genetic diagnosis has led directly to a change in clinical management.
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...InsideScientific
Join Prof. Victoria Hutter and Dr. Louis Scott as they showcase the application of high-content imaging and advanced cell lines for drug safety assessment.
Safety concerns play a significant role in the unsuccessful progression of candidate compounds in the later stages of drug development. Establishing the connection between in vitro endpoints and human health outcomes is essential.
In this webinar, Prof. Victoria Hutter and Dr. Louis Scott present a novel tool for in vitro safety assessment in drug development. The morph_ONE™ assay provides a human-centric approach to potentially fill specific regulatory gaps concerning safety issues. This tool is capable of profiling both human and rat alveolar macrophages, offering valuable insights for hazard identification and toxicity assessments. By bridging the divide between cellular effects and overall risk, it has the potential to enhance our understanding of safety-related aspects in drug development.
Key Topics Include:
- Explore distinct in vitro screening techniques for evaluating the safety of emerging inhaled products, facilitating early and informed decisions in compound selection and development.
- How high-content image analysis (HCIA) cell painting assays can be used as a forward-looking high-throughput screening tool, distinguishing unique response patterns in alveolar macrophages.
- Understand the use of the ImmuPHAGE™ and ImmuLUNG™ models in conducting customized evaluations focused on inhalation safety.
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...InsideScientific
In this webinar, Aditya Pratapa and Lorcan Sherry present a new workflow for analyzing multiplex immunoflurescence images.
Spatial Signatures are a new class of highly predictive biomarkers that measure the interactions and cellular densities of tumor and immune cells that compose the tumor microenvironment. Based on multiplex immunofluorescence, spatial signatures provide a deeper understanding of complex interactions between tumors and the immune system, enabling improved patient stratification for immunotherapies. A significant hurdle to date has been in developing a data analysis workflow that is straightforward and user-friendly to transform the data rich images into meaningful quantitative spatial signatures.
In this webinar, Aditya and Lorcan review the key features of the new PhenoImager HT 2.0 data analysis workflow. This workflow introduces a simplified framework from scanning to analyzing spectrally unmixed multiplex immunofluorescence images generated on the PhenoImager HT platform. The ready-to-analyze data can be directly imported into image analysis software such as Visiopharm. This presentation covers key aspects of data analysis elements such as image QC, segmentation, phenotyping, and verification – all essential for creating outputs that support the development of a spatial signature.
Key Topics Include:
- Understand Akoya’s new HT 2.0 data analysis workflow
- The challenges in multiplex immunofluorescence analysis and the use of AI and cell
lineage segmentation considerations
- Explore OracleBio’s image analysis workflow incorporating Visiopharm
- Evaluation of analysis data to facilitate spatial profiling and interpretation
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...InsideScientific
In this webinar, Dr. Sabine Kuss will discuss the importance of transmembrane molecule exchange and how to detect and quantify membrane transport of molecules in cells.
Complex biological processes, such as the transport of molecules across cell membranes, are difficult to understand using purely biological methodologies. Investigating cellular transport processes is challenging, because of the highly complex chemical composition of cells and the diffusion of molecules in and around cells at low concentrations. The development and advancement of electroanalytical methods over the last two decades has enabled the monitoring of living cells and their interaction with the environment, including external stimuli, such as pharma-molecules.
This presentation emphasizes electrochemical and electrophysiological methods of detection and quantification but also makes a comparison to other bioanalytical approaches. Join us to discover a substantial diversity in methods used to monitor the transport of cell metabolites, crucial for cell survival, and pharmaceutical compounds, involved in cell characteristics such as drug resistance.
Key Topics Include:
- Understanding transmembrane molecule transport through bioanalytical methods
- Electrochemical approaches to monitor molecule transport across cell membranes
- What bioanalytical and especially electrochemical approaches can reveal
- Challenges associated with instrument limitations
Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in ...InsideScientific
In this webinar, Dr. Victor Arrieta highlights the link between p-ERK activation and improved survival in rGBM patients using anti-PD-1 immunotherapy.
Recurrent glioblastoma (rGBM) has displayed a varied response to anti-PD-1 immunotherapy, necessitating the identification of predictive biomarkers. Through extensive analyses and 3 clinical studies, we have identified that activation of the MAPK/ERK signaling pathway, particularly ERK1/2 phosphorylation (p-ERK), is associated with longer overall survival (OS) in rGBM patients receiving PD-1 blockade. Initially, enrichment of BRAF/PTPN11 mutations was reported in 30% of responsive rGBM patients, prompting the investigation of p-ERK as a potential marker beyond these mutations.
Our research has unraveled an association between p-ERK abundance and better clinical outcomes following PD-1 blockade, with p-ERK mainly localized in tumor cells. Notably, high p-ERK GBMs contained unique microglia and macrophage phenotypes with elevated MHC class II expression, suggesting a novel interplay between MAPK activation and the tumor immune microenvironment.
While these insights establish a pivotal role for p-ERK in predicting PD-1 blockade response in rGBM, the implementation in clinical settings calls for further validation and accuracy. Nonetheless, these findings pave the way for more personalized and effective immunotherapy strategies, emphasizing the significance of the tumor microenvironment and its interaction with therapeutic interventions in GBM.
Key Topics Include:
- The activation of the MAPK signaling pathway, specifically ERK1/2 phosphorylation (p-ERK), is identified as a predictive biomarker for longer overall survival in recurrent glioblastoma (eGBM) patients undergoing PD-1 blockade
- High p-ERK tumors in rGBM present a distinct myeloid cell phenotype with elevated MHC class II expression, signifying a connection between MAPK pathway activation and the immune microenvironment
- The implementation of p-ERK as a predictive biomarker in clinical settings requires further validation and exploration of variables impacting its evaluation
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...InsideScientific
Dr. Reilly Enos and Dr. Eran Levin discuss estrogen's metabolic impact and how isotopic labeling and 13C-labeled nutrients can be used for animal physiology and nutrition research.
Reilly Enos, PhD – Harnessing the power of estrogen to regulate metabolic processes
Dr. Reilly Enos’ research focuses on the role that sex steroids and their receptors play in regulating metabolic processes, particularly in the setting of obesity. In this webinar, Dr. Enos will discuss his research on tissue-specific fluctuations of sex steroids throughout the estrous cycle in mice, provide insights into the importance of the quantity of estrogen necessary to impact physiological processes, as well as an understanding of the central versus peripheral effects of estrogen action.
Eran Levin, PhD – Unlocking Insights: Utilizing 13C Labeled Nutrients for Cutting-Edge Physiology and Nutrition Research
Dr. Eran Levin will discuss the potential of using 13C-labeled nutrients in physiology and nutrition research in animal models. Specifically, he will share practical tips for designing and conducting experiments using isotopic labeling techniques and demonstrate how they can provide unprecedented insights into metabolic pathways, nutrient utilization, and behaviors in both vertebrate and invertebrate models including insects, reptiles, and mammals.
Key Topics Include:
- The role that estrogen plays in regulating metabolic and behavioral processes in males and females
- The tissue-specific fluctuations of sex steroids throughout the estrous cycle
- Insight into the importance of tissue-specificity in developing hormonal therapies
- The importance of estrogen quantity in regulating physiological processes
- Understand the diverse range of 13C labeled nutrients available
- Specific applications of labeled amino acids in studies of protein metabolism, cellular signaling, and typical nutrient utilization
- How to integrate 13C labeling techniques with respirometry for a comprehensive assessment of metabolic processes, energy expenditure, and substrate utilization in animal models
- How to calculate metabolic rates in free-flying animals using 13C bicarbonate
Longitudinal Plasma Samples: Paving the Way for Precision OncologyInsideScientific
Experts present a cell-free plasma biobank and describe the role of longitudinal plasma samples for cancer research, disease monitoring, and biomarker development.
Through liquid biopsies, it is now possible to repeatedly and non-invasively interrogate the molecular landscape of solid tumors via a blood draw over the whole treatment course. Until now, liquid biopsies can be used for screening, disease monitoring and prognosis. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have been the most explored targets in this technology for commercial applications up to the present time.
In collaboration with a continuously expanding oncology network, Indivumed Services has established a unique high-quality cell-free plasma biobank that is exclusively focused on collecting longitudinal whole blood samples from cancer patients. This allows molecular insight by providing quick access to longitudinal plasma from cancer patients that have undergone treatment. ctDNA can then be isolated from longitudinal cell-free plasma to allow for monitoring of disease progression by providing diagnostic and prognostic information, potentially in real time.
Key Topics Include:
- Gain insights into Indivumed Services’ longitudinal plasma collection process
- Understand the advantages and benefits of utilizing longitudinal plasma samples for cancer research
- Explore applications of longitudinal plasma samples for biomarker research and development of companion diagnostics
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...InsideScientific
In this webinar, experts present a standardized stem cell line and its differentiation into neural cells for disease modeling and assay development.
Reproducible research with human induced pluripotent stem cells (iPSCs) depends on thoroughly characterized and quality-controlled cell lines. In this webinar, Dr. Andrew Gaffney and Dr. Erin Knock from STEMCELL Technologies describe the generation of a standardized induced pluripotent stem cell (iPSC) line. Developed with the upcoming ISSCR Standards Initiative characterization guidelines in mind, this highly characterized line is karyotypically stable, demonstrates trilineage differentiation potential, and expresses undifferentiated cell markers. Further, STEMCELL has developed a highly pure, ready-to-use neural progenitor cell product expressing PAX6 and SOX1 over multiple passages.
Dr. Knock shows how these multipotent cells are suitable for customized downstream differentiation to various CNS cell types, such as forebrain neurons, midbrain neurons, and astrocytes. These progenitor cells are the ideal controls for standardizing downstream differentiation protocols, modeling diseases, and assay development.
Key Topics Include:
- Discover how STEMCELL’s induced pluripotent stem cell lines are derived and characterized
- Learn how to differentiate induced pluripotent stem cell lines into all three germ layers
- Explore the features of STEMCELL’s neural progenitor cell product
- Differentiate neural progenitor cells into a variety of neural cell types, including neurons and glia
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...InsideScientific
Ian Foster and Steven Loo-Yong-Kee discuss Artisan Bio's STAR-CRISPR system for optimized gene editing in cell therapy, with a focus on the genetifc modification of T cells for cancer immunotherapy.
Cell therapy is an emerging field with great promise for the treatment of various diseases. One of the most exciting areas of cell therapy is the use of T cells that have been genetically modified to recognize and kill cancer cells. While the use of T cells for cancer immunotherapy has tremendous promise, there is still room for improvement. The efficiency, expansion, and functionality of T cells can be enhanced by genetic modification using the STAR-CRISPR system.
Artisan Bio is a biotechnology company focused on developing a CRISPR-mediated editing platform to improve the efficacy and safety of cell therapy products. In this webinar, we will provide a comprehensive overview of Artisan Bio’s STAR-CRISPR system, which is designed to improve the specificity and efficiency of gene editing for cell therapies. We will explain the system’s key components and how we are using a risk-based approach to optimize and validate the editing platform. The webinar will focus on Artisan Bio’s approach to building T cell OS/APPS through iterative improvements to achieve best-in-class editing capabilities and improved cell health metrics.
Key Topics Include:
- Learn about Artisan Bio’s proprietary high-performance STAR-CRISPR system for improving the specificity and efficiency of gene editing for cell therapies
- Explore Artisan Bio’s risk-based, systems approach to technology development, including how to implement Design of Experiments (DoE) and Quality by Design (QbD) principles to optimize and validate any process
- Case study of the application of QbD to Artisan Bio’s STAR-CRISPR platform to edit T cells for cancer immunotherapy with preliminary data showing improved efficacy, expansion, and functionality
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...InsideScientific
Dr. Bert Bond and Max Weston will present an overview on their study investigating the effects high-intensity interval exercise has on cerebrovascular health.
Physical activity reduces the risk of developing cardiovascular diseases (CVD) and dementia. This benefit cannot be explained by changes in traditional CVD risk factors alone, and direct improvements in vascular health are thought to play a key role. However, our understanding of how exercise can be optimized for improvements in blood-vessel health is limited.
High-intensity interval exercise (HIIE) is known to improve peripheral vascular function, and there is a growing interest in the effects of HIIE on cerebrovascular health. However, it is not clear whether the acute improvements in peripheral vascular function following HIIE are also seen in the major blood-vessels of the brain.
In the Bond lab’s study, 30 minutes of HIIE completed at both 75% and 90% V̇O2max improved peripheral vascular function 1 and 3h following exercise in healthy young adults, compared with work-matched continuous moderate-intensity exercise and a sedentary control condition. By contrast, cerebrovascular function was unchanged following all conditions. This is the first study to identify that acute improvements in peripheral vascular function following high-intensity interval exercise are not mirrored by improvements in cerebrovascular function in healthy young adults.
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...InsideScientific
Dr. Sam Sternberg discusses a novel CRISPR-Cas9 system using programmable, RNA-guided transposase, and highlights its implications for kilobase-scale genome engineering in cell and gene therapies.
The utility of programmable, RNA-guided CRISPR-Cas systems in genome engineering continues to evolve. Nature has afforded scientists novel and diverse gene editing functionality, from nuclease-dependent CRISPR-Cas9 to second-generation base and prime editors that do not produce double-strand breaks.
In this webinar, Dr. Sam Sternberg describes a new CRISPR-Cas9 paradigm relying on nuclease-deficient bacterial transposons that catalyze RNA-guided integration of mobile genetic elements into the genome. The discovery of a fully programmable, RNA-guided transposase lays the foundation for kilobase-scale genome engineering with broad applications for developing cell and gene therapies.
Key Topics Include:
- The basics of first- and second-generation CRISPR-Cas technologies from a scientist at the forefront of their development
- Mechanisms, accommodation, and cell type diversity of CRISPR-Cas programmable transposition
- How transposase factor coordination enables highly specific, genome-wide DNA integration to target sites
- Implications of programmable transposases that obviate the need for DNA double-strand breaks and homologous recombination
Simple Tips to Significantly Improve Rodent Surgical OutcomesInsideScientific
Dr. Marcel Perret-Gentil presents six simple-to-implement techniques to significantly improve surgical outcomes.
You may feel proficient, even confident in performing rodent surgery; however, you may be surprised how simple improvements can have a huge impact to your animal’s recovery and data. The presentation is designed for individuals who have minimal or no rodent surgical skills but is also a great opportunity for those with considerable experience wanting to improve outcomes as well as teach such key principles.
Key Topics Include:
- Improve surgical outcomes that will lessen post-op morbidity and mortality
- Improve data yield after rodent surgery
- Implementation of key principles into a rodent surgical program
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...InsideScientific
A world-wide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pandemic and generated over 600 million reported cases around the globe. A substantial portion of patients who suffered Corona Virus Disease 2019 (COVID-19) have not recovered completely but continue to experience lingering symptoms for months to years. This novel clinical syndrome has been termed Long COVID or Post-acute Sequalae of COVID-19 (PASC).
Observational studies have indicated that in about one third of cases PASC can be associated with cardiovascular (CV) autonomic dysfunction including postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension, reflex syncope and microvascular dysfunction. The presence of CV autonomic dysfunction in PASC is important to detect since although frequently overlooked, it may be effectively treated in contrast to many other Long COVID-related symptoms.
This webinar highlights CV dysautonomia as a specific sequalae of acute COVID-19 and guides the audience in the diagnostic work-up of PASC patients with suspected cardiovascular complications.
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemInsideScientific
Cell lines are the core of biological research. Scientists need cell lines for drug development, basic biology research, safety testing, and biologic therapeutic production. Since the 1980s, genetic manipulation has allowed researchers to tailor cell lines to the experiment or production purpose. Over time, the requirements for these cell lies have risen. In many cases, the cells require multiple genetic edits and must produce data that passes FDA. Moreover, the current funding environment often requires rapid delivery of these cells so scientists can produce data to support further budget and/or investment. This is particularly acute for knock-in cell lines. Current technologies may take months to complete a cell line, allow a limited number of edits, and often have off-target effects that are not suitable for FDA filings. ExpressCells uses its patented FAST-HDR plasmid--along with CRISPR, to address these problems. The FAST-HDR process can precisely knock-in multiple genes (while supporting other types of genetic modifications), ensure precise placement of these edits, and deliver them months faster than competing technologies.
This webinar will discuss the basis of the FAST-HDR technology and illustrate several uses. The first part is a presentation by Oscar Perez-Leal, MD, the inventor of the technology. Oscar will discuss the problems he faced as a researcher and how FAST-HDR was designed to address them. He will outline the details of the technology, the history of its development, and several examples where he used FAST-HDR. The second part is a conversation with Jon Weidanz, PhD. Jon will outline the challenges he faced at AbeXXa and how he selected a FAST-HDR custom cell line for his project. He'll outline the learnings from using this cell line, some of which were unexpected, but valuable to future development.
By attending this program, attendees will:
- Understand the current challenges in creating custom gene-edited cell lines
- Know the technology underlying the FAST-HDR gene-editing system, including its use with CRISPR
- Be able to describe the advantages of the FAST-HDR system
- Learn about several case studies using gene-edited cell lines
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...InsideScientific
Watch Dr. Sarah Greising discuss the current pathophysiologic understanding of the skeletal muscle remaining following traumatic musculoskeletal injuries.
Volumetric muscle loss (VML) injuries result in the abrupt loss of skeletal muscle fibers, causing chronic functional disability in part due to limited muscle regeneration and vast co-morbidities. With a focus on clinically relevant outcome measurements for skeletal muscle function in both small and large animal models of VML injury, this webinar presents various near-term interventions for the restoration of tissue function following complex injuries. Interventions evaluated focus on regenerative rehabilitation approaches using regenerative pharmaceuticals to correct underlying muscle pathophysiology.
Designing Causal Inference Studies Using Real-World DataInsideScientific
In this webinar, experts provide an overview of causal inference, along with step-by-step guidance to designing these studies using real-world healthcare data.
Causal inference is used to answer cause and effect research questions and yield estimates of effect. Causal study design considerations and statistical methods address the effects of confounding variables and other potential biases and allow researchers to answer questions such as, “Does treatment A produce better patient outcomes compared to Treatment B?”
Causal study interpretations have traditionally been restricted to randomized controlled trials; however, causal inference applied to observational healthcare data is growing in importance, driven by the need for generalizable and rapidly delivered real-world evidence to inform regulatory, payer, and patient/provider decision making. The application of causal inference methods leads to stronger and more powerful evidence. When these techniques are applied to observational data, the results generated are both from and for the real world.
Presenters walk through several real-world case studies including the PCORI-funded BESTMED study and a collaborative study with a prominent pharmacy payer.
Social Media Data: Opportunities and Insights for Clinical ResearchInsideScientific
Many new data are emerging in recent years - real time data is collected through digital health technologies, including apps and wearables, monitoring data, social media data, public datasets, and patient organization data, in addition to primary and secondary datasets.
Real life data are highly informative and can be used to address a range of challenges throughout the product life cycle. Data from social media can generate valuable insights as patients often gather in digital communities to get answers and share their experiences. Conversations on social networks merit special consideration as they can have real world influence over treatment management decisions.
Social media data can reveal the motivations that impact patient healthcare decisions and behaviors through each stage of the care pathway. These data provide both the patient and caregiver perspectives at the same time. For this reason, conversations on social networks offer an opportunity to deepen our understanding on:
- The fears and hopes associated with patient treatments
- Daily needs and difficulties patients are facing in managing their disease
- The impact of disease on patient health related quality of life
- Identification in real life of the stages of the care pathway and patient perceptions
- Reactions to health policies
Watch this webinar for insights on how to collect, use, analyze, and interpret social media data in different contexts. Our experts share knowledge from over fifteen years of successfully developing and adapting algorithms to treat this kind of data.
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...InsideScientific
To learn more visit: https://insidescientific.com/webinar/we-are-more-than-what-we-eat-dietary-interventions-depend-on-sex-and-genetic-background/
Despite evidence that sex and genetic background are key factors in the response to diet, most studies of how diet regulates metabolic health and even longevity in mice examine only a single strain and sex.
Using multiple strains and both male and female mice, Dr Lamming's team has found that improvements in metabolic health and in longevity in response to reduced levels of protein or specific amino acids strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, they observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, they identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, gaining new insight into role of the energy balance hormone FG21 in the response to protein restriction.
Antibody Discovery by Single B Cell Screening on Beacon®InsideScientific
Amy Sheng, PhD provides an overview of antibody screening platforms and presents applications and case studies using the Beacon® platform for antibody discovery.
Single B cell screening is a powerful and efficient strategy for generating antigen-specific monoclonal antibodies. Distinguished with fluorescence-activated B cell sorting, the Beacon® platform is based on plasma cell screening, making it easier to obtain antibody genes.
The Beacon® single-cell optofluidic system combines a unique optoelectro positioning (OEP) technology with novel microfluidic technology. It can be used to accurately select single cells on a chip, perform multiple single-cell assays, and export target cells based on specific results. The Beacon® optofluidic platform preserves the diversity of B cells, generating high-quality positive hits at an early stage of discovery and avoiding the loss of “good clones”.
Key Topics Include:
- B cell differentiation and development
- Pros and cons of mainstream antibody screening platforms
- Mechanisms, applications, and case studies using the Beacon® platform for antibody screening
- Sino Biological’s capacity using the Beacon® platform
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...InsideScientific
Phil Griffiths, PhD, presents a summary of chronic cardiovascular telemetry studies and considerations for experimental design.
Ensuring you collect the best and most physiologically accurate data from your chronic telemetry experiments requires careful planning and experimental design. This webinar will give an insight into the practical aspects of designing chronic animal experiments to set you on the best path for success. The benefits of chronic studies, how to select the most appropriate sample size for your study, some basic tips and tricks for data acquisition and handling, and how to ensure high animal welfare are discussed.
Key Topics Include:
- What are the benefits of chronic over acute studies?
- How to decide the best sample sizes and the length of experiments?
- Basic tips for data acquisition and handling
- How to maintain high animal welfare standards
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...InsideScientific
In this webinar, Dr. Dennis Turner delves into dementia syndrome, the metabolic changes that occur, and the importance of proper physiological monitoring of animal models.
Brain metabolism transforms with normal aging, and transient, dynamic metabolic insufficiency may underlie critical progression from aging into dementia syndrome and Alzheimer’s disease (AD). Age-related brain metabolism balances vascular-related substrate supply and transport mechanisms into extracellular space to neurons with cellular metabolic needs and utilization. Dynamic metabolic insufficiency can occur when there is intermittent supply-demand mismatch.
Adequacy of neurovascular coupling to provide sufficient cerebral blood flow (CBF) to meet neuronal demand in vivo in a mouse AD model, compared to aged controls were studied. Dr. Turner’s lab analyzed the response to maximal neuronal metabolic demands, spreading depression and anoxia, using imaging, CBF measurements, and oxygen and glucose levels. These in vivo studies require human-similar anesthesia conditions, through monitoring temperature, blood pressure/pulse oximetry, and respiration, to maintain homeostasis. The lab confirmed abnormal neurovascular coupling in a mouse model of AD in response to these metabolic challenges, showing disruption much earlier in dementia than in equivalently aged individuals. Chronic metabolic treatments could influence dementia syndrome progression.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
2. Remodeling
of pancreatic
innervation
in diabetes
Dr. Sarah Stanley and Dr. Alexandra
Alvarsson discuss the use of whole-organ
imaging of the pancreas to reveal close
interactions between nerves and islets
and dynamic regulation of islet
innervation in diabetes.
3. Dr. Sarah Stanley
Dr. Alexandra Alvarsson
Diabetes, Obesity and
Metabolism Institute
Remodeling of
pancreatic innervation
in diabetes
4. • Consultant to Redpin Therapeutics
• Patent and patent applications
US patent WO 2016/049031 “Compositions and Methods to
Modulate Cell Activity”
US patent application PCT/US15/51457 “Compositions and Methods
to Modulate Cell Activity”
Disclosure
6. • Glucose is virtually the sole fuel for the brain
• Brain consumes 60-70% of whole body glucose use in the resting state
Glucose-6-phospate
Hexokinase
1
Glucos
e
GLU
T1
GLU
T3
Glucose
Hexokinase
1
Endothelial
cells
Pericytes
Astrocytes
Neuron
The CNS relies on glucose as a fuel
8. Lateral Arcuate
13% GE
1% GI
Nucleus of
solitary tract
10% GE
8% GI
Medial Arcuate
4% GE
14% GI
Paraventricular
nucleus
19% GE
8% GI
Ventromedial
hypothalamus
13-14% GE
8-16% GI
Dorsomedal
hypothalamus
15% GE
14% GI
Lateral
hypothalamus
20% GE
27-38% GI
Glucose-sensing neurons form a
distributed network
9. CNS regions sensing glucose connect to
autonomic outflow
0
2
4
6 0
2
4
6
0
2
4
6
8 - 2 - 4
4 2 0 -2 - 4 - 6 - 8
Bregma
Bregma
0
2
4
6 0
2
4
6
0
2
4
6
8 - 2 - 4
4 2 0 -2 - 4 - 6 - 8
Bregma
Bregma
PVT
PVH
ARC
DMH
VMH
Amygdala
LH
DMV
NTS
AP
D
C
B
E
A B C D
E
IML
RVLM
PARASYMPATHETIC
EFFERENTS
SYMPATHETIC EFFERENTS
Rostral
ventrolate
ral
medulla
Intermedi
o
lateral
nucleus
Dorsal
motor
nucleus of
vagus
10. • Increase glucagon
release
• Suppress insulin
release
• Altered insulin
sensitivity
• Reduced β cell
proliferation and
mass
Autonomic nerves innervate organs critical to
glucose regulation
• Increase insulin
release
• Increase β cell
proliferation and
mass
Parasympathetic Nervous System Sympathetic Nervous System
11. 11
Human studies
• Regional CNS activation with
hypoglycemia
• Cephalic phase insulin
release
• Altered glucose metabolism
with deep brain stimulation
and TCM
• Abnormal glucose tolerance
after vagotomy
• Abnormal response to
exercise and hypoglycemia
post pancreatic transplant
Neural regulation of glucose in humans
Rare pathologies
• Hypothalamic pathology
o high insulin levels
o insulin resistance
o impaired glucose
tolerance.
• Glucose abnormalities in
patients with demyelination
• Autonomic neuropathy
impairs hypoglycemic
responses
12. Spinal Sensory
Sympathetic efferent
Parasympathetic sensory
Nodose ganglion
Dorsal root
ganglia
Coeliac
ganglia
Intrapancreatic
ganglia
Multiple Inputs into pancreatic innervation
Parasympathetic efferent
Enteroendocrine
Dorsal motor nucleus
of vagus
13. Parasympathetic Inputs into the pancreas
Parasympathetic efferent
Dorsal motor nucleus
of vagus
• Cell bodies in dorsal motor
nucleus of vagus
• Anterograde tracing shows
inputs to intrapancreatic ganglia
(rat)
Berthoud and Powley 1991
• Vagal activation induces c-fos in
10-30% of intrapancreatic
ganglia (rats)
Wang et al 1999
14. Sympathetic Inputs into the pancreas
• Preganglionic neurons in
intermediolateral column project
to coeliac ganglia in splanchnic
nerves
Quinson et al 2001
• Sympathetic post-ganglionic
fibers project to intrapancreatic
ganglia, islets, vasculature and
lymph nodes.
Sympathetic efferent
Coeliac
ganglia
15. Sensory innervation of the pancreas
• Extensive sensory innervation
Fasanella et al 2008
• Vagal sensory innervation
involves exocrine and endocrine
pancreas
• Primarily chemosensors
Makhmutova et al, 2020
• Spinal sensory innervation from
T5 – T13
• Express substance P, TRPV1
and CGRP
Fasanella et al 2008
• Both mechano- and
chemosensors
Schloithe et al, 2008
Spinal Sensory
Parasympathetic sensory
Nodose ganglion
Dorsal root
ganglia
16. Intrapancreatic ganglia
• Mesh of intrapancreatic neurons
and intrapancreatic ganglia
• Often adjacent to islets to form
neuro-insular complexes
Tang et al, 2018
• Primarily cholinergic cell bodies
and fibers with neuropeptide
expression
De Giorgio et al, 1992
17. Imaging pancreatic innervation in 2 dimensions
• Extensive investigation of
pancreatic islet structure and
innervation using
immunohistochemistry
Chien et al, 2016
Parween et al, 2016
Fowler et al 2018
• Defined extensive
parasympathetic and
sympathetic innervation in
rodent islets.
• Sparse, primarily sympathetic
innervation in human islets
Rodriguez-Diaz et al, 2012
Spinal Sensory
Sympathetic efferent
Parasympathetic sensory
Nodose ganglion
Dorsal root
ganglia
Coeliac
ganglia
Intrapancreatic
ganglia
Parasympathetic efferent
Enteroendocrine
Dorsal motor nucleus of
vagus
18. Imaging pancreatic innervation in 2 dimensions
PRO
• Allow high resolution imaging
particularly of fine innervation
• Identify target structures
CON
• Highly heterogenous organ
• Laborious serial sectioning
• Tracing over long distances
difficult
• May miss regional differences
Insulin/TH
Insulin/synapsin
Dapi/synapsin
Immunohistochemistry in 2D
3D imaging
19. Imaging pancreatic innervation in 3 dimensions
• Recent resurgence in optical
clearing methods examining
pancreatic structure.
Richardson et al, 2015
• Advances in volumetric imaging
e.g. lightsheet microscopy,
optical projection tomography,
swept confocal aligned planar
excitation (SCAPE) microscopy.
• Progress 3D volumetric image
processing software advances
e.g. Image J, Matlab,
Neurolucida, Imaris etc.
2
0
Fructose
Ethyl cinnamate
Insulin/TH/vasculature
20. Imaging pancreatic innervation in 3 dimensions
Examination of sympathetic innervation in diabetic mice
• Fluorescent lectins and immunolabeling to examine vasculature and innervation
• Focusclear tissue clearing and confocal imaging
• Increased intra-islet sympathetic fibers associated with vasculature in STZ but not
NOD mice Chiu et al, 2012
Insulin/Vasculature/TH
21. Imaging pancreatic innervation in 3 dimensions
Examination of innervation and intrapancreatic ganglia in db/db mice
• Immunolabeling to examine innervation and islets
• RapiClear tissue clearing and tiled confocal imaging
• Identified intrapancreatic ganglia, increased connections with increasing size
• Increased pancreatic sympathetic innervation in db/db mice Tang et al, 2018a
22. Imaging pancreatic innervation in 3 dimensions
Examination of innervation in human pancreatic tissue
• Sympathetic innervation of islet vasculature and islet core
• Parasympathetic innervation of islet core Tang et al, 2018b
• Sensory innervation (SubP+) of intrapancreatic ganglia, not islets Chien et al,
2019
• Sympathetic innervation of islets, not exocrine pancreas, reduced in autoAb+
individuals compared to T1D. Campbell-Thompson et al, 2021
23. AIMS
To use optical clearing by iDISCO+ combined with
advanced 3D rendering to determine the distribution
of islets and innervation throughout the whole
pancreas in healthy animals, in mouse models of
diabetes, and in human donors without and with
diabetes.
23
24. • Duodenal vs. splenic region
C57BL/6N mice
• Nondiabetic vs. diabetic state
Non-Obese Diabetic (NOD) mice (NOD/ShiLtJ females, 12 - 16 weeks)
- Spontaneously develop type 1 diabetes with insulitis
- Two consecutive blood glucose measurements of >300 mg/dl Diabetic
- Littermates with blood glucose <200 mg/dl Nondiabetic controls
- Average nonfasting blood glucose:
115 ± 4 mg/dl (Nondiabetic) and 495 ± 62 mg/dl (Diabetic)
Multiple low-dose Streptozotocin (STZ)-treated mice (C57BL6/6N males,10 weeks)
- Progressive model of type 1 diabetes (beta cell toxin, insulitis)
- Treated with STZ (40 mg/kg) in citrate-saline buffer (pH 4.5) for five consecutive days
- Sacrificed at 5 or 15 days following the final STZ injection.
- Non–STZ-treated littermates were used as controls
- Average nonfasting blood glucose:
123 ± 9 mg/dl (Controls), 259 ± 18 mg/dl (Day 5), and 430 ± 17 mg/dl (Day 15)
Human donors without and with type 2 diabetes
AIMS
31. 31
T: Total
D: Duodenal
S: Splenic
REGIONAL VARIATION IN ISLET
CHARACTERISTICS IN CONTROL MICE
Islet
volume
Islet
density
Insulin
conten
t
Regional variation in islet volume
and insulin content
C57Bl/6
mice
NOD
mice
STZ
mice
32. 32
C57Bl/6
mice
NOD
mice
STZ
mice
Dramatic loss of islet volume and
density in diabetic NOD mice
(greater effect in S).
Islet
volume
Islet
density
Insulin
conten
t
REGIONAL VARIATION IN ISLET
CHARACTERISTICS IN NOD MICE
33. 33
C57Bl/6
mice
NOD
mice
STZ
mice
Low-dose STZ treatment reduces islet
volume and insulin content, but not the
islet density
Islet
volume
Islet
density
Insulin
conten
t
REGIONAL VARIATION IN ISLET
CHARACTERISTICS IN STZ MICE
34. Beta cell volume and islet
numbers highly variable.
The average islet volume lower in
diabetic donors.
Islet number per mm3 greater than
mice, but beta cell volume (%) was
similar.
Islet
volume
Islet
density
REGIONAL VARIATION IN ISLET
CHARACTERISTICS IN HUMANS
35. Control mice NOD mice STZ mice Human donors
ISLET VOLUME DISTRIBUTION
A shift towards smaller islets in human type 2 diabetes
36.
37. GLUCAGON IN NOD MICE
Increased glucagon to insulin
ratio in diabetic NOD mice
38. GLUCAGON IN STZ MICE
Low-dose STZ
treatment reduced
glucagon volume and
increased glucagon to
insulin ratio
39.
40. Regional variation in
endocrine innervation
in control mice
40
Islet innervation shows
regional variation in C57BL/6
mice.
Islet innervation
µm3/islet % of islet volume
41. 41
Islet innervation
µm3/islet % of islet volume
Exocrine
innervation
Regional variation in
endocrine innervation in
control mice
42. 42
Islet innervation (%) increased
in diabetic NOD mice,
particularly in the splenic
pancreas.
Islet innervation
µm3/islet % of insulin volume
Regional variation in
endocrine innervation in
NOD mice
46. 46
NF200+ endocrine innervation
highly variable
The endocrine nerve volume (%)
was greater in samples from
diabetic individuals
Regional variation in
endocrine innervation in
humans
Islet innervation
µm3/islet % of islet volume
47. Regional variation in
endocrine innervation in
humans
No enrichment in NF200+
endocrine innervation compared to
exocrine tissue.
Islet innervation
µm3/islet % of islet volume
48. Control mice
ENDOCRINE NERVE DISTANCE
Insulin
Ins+ islets located <1.6
um from innervation:
Total: 6%
Duodenal: 6.5%
Splenic: 6%
49. NOD mice
ENDOCRINE NERVE DISTANCE
Insulin Glucagon
Alpha cell clusters
located <1.6 um from
innervation:
Nondiabetic: 15%
Diabetic: 34%
Ins+ islets located <1.6
um from innervation:
Nondiabetic: 15%
Diabetic: 10%
50. STZ mice
ENDOCRINE NERVE DISTANCE
Insulin Glucagon
Alpha cell clusters
located <1.6 um from
innervation:
Control: 26%
Day 5: 17%
Day 15: 22%
Ins+ islets located <1.6
um from innervation:
Control: 6%
Day 5: 6%
Day 15: 8%
51. Human donors
ENDOCRINE NERVE DISTANCE
Insulin
Ins+ islets located <1.6
um from innervation:
Control: 11%
Type 2 Diabetes: 29%
Altered nerve /
endocrine cell
associations in
diabetes?
52.
53. GANGLIA AND ENDOCRINE NERVE CONTACTS
3D analysis of intrapancreatic NF200+ ganglia in IMARIS
Alvarsson et al., Bio-Protocol, 2021
• Number of ganglia per mm3
• Average ganglion volume
• Average distance between ganglia and insulin+ islets
54. GANGLIA AND ENDOCRINE NERVE CONTACTS
Alvarsson et al., Bio-Protocol, 2021
Distance analysis of α and β cell nerve contacts in IMARIS
• The Imaris Distance Transform Matlab XTension was used to
determine distance between NF200+ nerves and individual α or β
cells
• A distance of 0 was used to indicate a nerve contact
57. Intrapancreatic ganglia in
NOD mice
Preserved number and volume, but
significantly prolonged distance
between NF200+ intrapancreatic
ganglia and islets due to islet loss.
58. Endocrine nerve
contacts in NOD mice
No difference in alpha and beta
cell nerve contacts between
nondiabetic and diabetic NOD
mice
More alpha cell vs. beta cell
contacts
59. Intrapancreatic ganglia in
STZ mice
Preserved number and islet
distance, but reduced volume of
NF200+ ganglia with STZ-induced
diabetes.
60. Endocrine nerve
contacts in STZ mice
No difference in alpha and beta
cell nerve contacts between
nondiabetic and diabetic STZ
mice
More alpha cell vs. beta cell
contacts
62. Endocrine nerve
contacts in human
donors
No difference in beta cell nerve
contacts between nondiabetic
and diabetic human donors
63.
64. TH in control mice
No significant regional
variation in TH+
exocrine and endocrine
innervation
65. VAChT in control mice
No significant regional
variation in VAChT+
exocrine and endocrine
innervation
66. 66
CONCLUSIONS
1. Innervation is highly enriched (10-fold) in the mouse endocrine
pancreas, with significant differences between duodenal and
splenic regions.
2. There is a close association between nerves and islets in both
mouse and human pancreata, which is maintained in diabetes.
3. Islet innervation was enriched (2-fold) in the pancreas of diabetic
NOD mice, and also during the progression of T1D induced by
STZ treatment (2-fold).
4. Islet innervation was also enriched in pancreata of human donors
with type 2 diabetes.
67. 67
• Cause of neuronal remodeling in diabetes
• Consequences of neuronal remodeling in diabetes
• Contribution of sympathetic, parasympathetic and sensory
innervation in diabetes
FUTURE DIRECTIONS
68. Acknowledgements
Stanley Lab
Dr. Sarah A. Stanley
Dr. Maria Jiménez-González
Rosemary Li
Kavya Devarakonda
Rollie Hampton
Garcia-Ocaña Lab
Dr. Adolfo Garcia-Ocaña
Dr. Carolina Rosselot
Dr. Andrew F Stewart
DIABETES, OBESITY
& METABOLISM
INSTITUTE
Dr. Zhuhao Wu
DEPARTMENT OF
NEUROSCIENCE
THE MICROSCOPY
CORE AND ADVANCED
BIOIMAGING CENTER,
ISMMS
Dr. Deanna Benson
Dr. Nikolaos Tzavaras
69. 1. To learn more about Dr. Sarah Stanley
and Dr. Alexandra Alvarsson’s research,
go to: https://labs.icahn.mssm.edu/stanleylab/
2. To learn more about light sheet microscopy for
high-resolution 3D imaging, go to:
www.miltenyibiotec.com/products/macs-imaging-
and-microscopy/light-sheet-microscopy.html
3. To learn more about
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