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1.
Semin Cell Dev Biol ; 103: 31-40, 2020 07.
Article in English | MEDLINE | ID: mdl-31757584

ABSTRACT

Pancreatic ß-cells are responsible for maintaining glucose homeostasis. Therefore, their dysregulation leads to diabetes. Pancreas or islet transplants can be used to treat diabetes but these human tissues remain in short supply. Significant progress has now been made in differentiating human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into pancreatic ß-like cells for potential cell replacement therapy. Additionally, these hPSC-derived ß-like cells represent a new invaluable model for studying diabetes disease mechanisms. Here, we review the use of hPSC-derived ß-like cells as a platform to model various types of defects in human ß-cells in diabetes, comparing them against existing animal models, ex vivo human islets and human ß-cell line. We also discuss how hPSC-derived ß-like cells are being used as a platform for screening novel therapeutic compounds. Last but not least, we evaluate the strengths and limitations of this human cell-based platform as an avenue to study and reveal new insights into human ß-cell biology.


Subject(s)
Cell Biology/standards , Diabetes Mellitus/metabolism , Induced Pluripotent Stem Cells/metabolism , Cell Differentiation , Humans
2.
Semin Cell Dev Biol ; 105: 12-26, 2020 09.
Article in English | MEDLINE | ID: mdl-32146031

ABSTRACT

γ-Secretase cleavage is essential for many biological processes and its dysregulation is linked to disease, including cancer and Alzheimer's disease. Therefore, understanding the regulation of its activity is of major importance to improve drug design and develop novel therapeutics. γ-Secretase belongs to the family of intramembrane cleaving proteases (i-CLiPs), which cleaves its substrates in a process termed regulated intramembrane proteolysis (RIP). During RIP, type-I transmembrane proteins are first cleaved within their ectodomain by a sheddase and then within their transmembrane domain by γ-secretase. γ-Secretase is composed of four integral membrane proteins that are all essential for its function: presenilin (PSEN), anterior pharynx defective 1 (APH1), nicastrin (NCT) and presenilin enhancer 2 (PEN-2). Given the presence of two PSEN homologues (PSEN1 & 2) and several APH1 isoforms, a heterogeneity exists in cellular γ-secretase complexes. It is becoming clear that each of these complexes has overlapping as well as distinct biological characteristics. This review summarizes our current knowledge on complex formation, trafficking, subcellular localization, interactors and the structure of γ-secretase, with a focus, when possible or known, on the contribution of PSEN1 and PSEN2 herein.


Subject(s)
Alzheimer Disease/genetics , Amyloid Precursor Protein Secretases/metabolism , Cell Biology/standards , Presenilins/metabolism , Humans
3.
PLoS Biol ; 15(4): e2001438, 2017 04.
Article in English | MEDLINE | ID: mdl-28414712

ABSTRACT

Cell lines are used in life science research worldwide as biological surrogates. All cell lines are subject to major limitations when used as research tools, including (i) cross-contamination with other cells cultured in the same laboratory environment and (ii) evolution in vitro that renders a given cell line inappropriate as a surrogate for a specific biological hypothesis. There is ample evidence that cross-contamination or phenotypic drift of cells in culture can generate irreproducible or misleading data. A small number of scientific journals-the International Journal of Cancer being at the forefront-and funding agencies have recently moved forward to ask for obligatory cell line authentication data. The history of implementing such rules by the International Journal of Cancer exemplifies the difficulties encountered when installing mandatory quality measures in life sciences.


Subject(s)
Cell Biology/standards , Cell Line , Serial Publications/standards , Animals , Consensus , Genotype , Humans , Workflow
4.
Semin Cell Dev Biol ; 117: 1-5, 2021 09.
Article in English | MEDLINE | ID: mdl-34172396
5.
Cytotherapy ; 20(6): 785-795, 2018 06.
Article in English | MEDLINE | ID: mdl-29699860

ABSTRACT

The emergence of cell-based therapeutics has increased the need for high-quality, robust and validated measurements for cell characterization. Cell count, being one of the most fundamental measures for cell-based therapeutics, now requires increased levels of measurement confidence. The National Institute of Standards and Technology (NIST) and the US Food and Drug Administration (FDA) jointly hosted a workshop focused on cell counting in April 2017 entitled "NIST-FDA Cell Counting Workshop: Sharing Practices in Cell Counting Measurements." The focus of the workshop was on approaches for selecting, designing and validating cell counting methods and overcoming gaps in obtaining sufficient measurement assurance for cell counting. Key workshop discussion points, representing approximately 50 subject matter experts from industry, academia and government agencies, are summarized here. A key conclusion is the need to design the most appropriate cell counting method, including control/measurement assurance strategies, for a specific counting purposes. There remains a need for documentary standards for streamlining the process to develop, qualify and validate cell counting measurements as well as community-driven efforts to develop new or improved biological and non-biological reference materials.


Subject(s)
Cell Biology/standards , Inventions/standards , United States Food and Drug Administration/standards , Cell Biology/education , Cell Count/methods , Cell Count/standards , Consensus Development Conferences as Topic , Humans , Professional Practice/standards , Professional Practice/statistics & numerical data , Quality Control , Reference Standards , United States
7.
J Cell Sci ; 127(Pt 10): 2123-5, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24955457
8.
Toxicol Pathol ; 39(2): 435-48, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21300792

ABSTRACT

This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant-induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used successfully, and which one is selected will depend on the expertise, preference of the facility, and the nature of the change in the bone marrow. Other specialized techniques such as clonogenic assays or electron microscopy are used rarely to further characterize hematotoxicity. The indications and techniques to successfully employ histological, cytological, or flow cytometric evaluation as well as clonogenic assays and electron microscopy are reviewed.


Subject(s)
Bone Marrow/pathology , Guidelines as Topic , Hematopoiesis , Animals , Benchmarking , Cell Biology/standards , Evaluation Studies as Topic , Flow Cytometry/standards , Hematopoietic System , Histology/standards , Humans , Staining and Labeling , Toxicology/standards
11.
Cell Death Differ ; 28(9): 2634-2650, 2021 09.
Article in English | MEDLINE | ID: mdl-33762741

ABSTRACT

The brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.


Subject(s)
Cell Biology/standards , Cerebellum/immunology , RNA, Long Noncoding/genetics , Synapses/genetics , Animals , Humans , Mice
12.
Protoplasma ; 258(2): 449-454, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33462719

ABSTRACT

Plants are not only sensitive to exogenous anaesthetics, but they also produce multitudes of endogenous substances, especially when stressed, that often have anaesthetic and anelgesic properties when applied to both humans and animals. Moreover, plants rely on neurotransmitters and their receptors for cell-cell communication and integration in a similar fashion to the use of neural systems in animals and humans. Plants also use their plant-specific sensory systems and neurotransmitter-based communication, including long-distance action potentials, to manage stress via cognition-like plant-specific behaviour and adaptation.


Subject(s)
Anesthetics/therapeutic use , Cell Biology/standards , Cognition/physiology , Plants/chemistry , Anesthetics/pharmacology , Humans
13.
J Am Soc Cytopathol ; 10(6): 535-542, 2021.
Article in English | MEDLINE | ID: mdl-34362716

ABSTRACT

INTRODUCTION: Cytopathology has well-defined and objective quality metrics for monitoring the performance of cytopathologists (CPs) and cytotechnologists (CTs). We transformed these metrics into dashboards for real-time visualization and on-demand feedback. METHODS: Dashboards were constructed with data from the previous 10 calendar years using the software Tableau. The dashboards for CPs were designed to display 2 gynecologic metrics and 1 nongynecologic metric: the ASCUS:SIL ratio, the percentage of high-risk human papillomavirus (HPV)-positive ASCUS interpretations (HPV+ ASCUS rate), and the proportion of AUS/FLUS thyroid interpretations. CT dashboards were designed to include these plus 2 others: the percentage of Papanicolaou tests referred for CP review and the percentage of Papanicolaou tests interpreted as unsatisfactory. Established professional benchmarks or standard deviations were used to set color-coded "goal," "borderline," and "attention" zones. RESULTS: Personal dashboards were successfully developed and implemented for CPs and CTs in the laboratory, with results that are automatically updated every week, requiring minimal curation. Each CP and CT has a unique link that allows them access to their results at any time. Color-coded displays show the individual their quality metrics over the past 10 years, with a snapshot of data from the past 3 months. The laboratory director has a unique link that allows the director access to results for each individual and the laboratory in aggregate. CONCLUSIONS: Personalized dashboards enable individuals to access their performance metrics on demand and examine recent performance as well as patterns over time. This facilitates self-motivation to improve performance and adhere to professional benchmarks.


Subject(s)
Cell Biology/standards , Cervix Uteri/pathology , Papanicolaou Test , Quality Improvement , Thyroid Gland/pathology , Vaginal Smears , Biopsy, Fine-Needle , Female , Humans
14.
Acta Cytol ; 65(3): 199-204, 2021.
Article in English | MEDLINE | ID: mdl-33857951

ABSTRACT

BACKGROUND: Faced with changes in cytodiagnostics, cervical cancer screening programs, the introduction and application of new methods, the cytotechnological educational program requires the necessary changes and additions. Insufficient, uneven as well as inaccessible education of cytotechnologists in European countries was the basis for making these recommendations. SUMMARY: The results of previous research and publications related to the currently available education of cytotechnologists in Europe, the needs and suggestions were given by the European Advisory Committee of Cytotechnology (EACC) and European Federation of Cytology Societies (EFCS) for optimal education of future generations of cytotechnologists were used in the preparation of these recommendations. The EACC and EFCS propose a 1-year education and training program divided into 3 modules: gynecological, nongynecological exfoliative, and fine-needle aspiration cytology. Training programs should be organized by an accredited university, preferably a combination of internal education in a cytology laboratory and theoretical education at the university. Cytopathologists and cytotechnologists with at least 5 years of work experience in cytodiagnostics should participate in education. Upon completion of the training program, the EACC and EFCS propose an official name: EFCS certified cytotechnologist. Key Messages: The EACC and EFCS believe that it is extremely important that these recommendations are recognized and implemented by institutions that provide education for cytotechnologists so that they can meet the growing requirements of the profession with their acquired knowledge and competencies.


Subject(s)
Cell Biology/education , Cytodiagnosis , Cytological Techniques , Education, Professional , Cell Biology/standards , Clinical Competence , Consensus , Curriculum , Cytodiagnosis/standards , Cytological Techniques/standards , Education, Professional/standards , Educational Status , Europe , Humans
15.
J Am Soc Cytopathol ; 10(5): 485-494, 2021.
Article in English | MEDLINE | ID: mdl-34167909

ABSTRACT

BACKGROUND: Primary stakeholders in the Accreditation Council for Graduate Medical Education (ACGME) Milestones Project are: ACGME, Residency Programs, Residents, Fellowship Programs, Fellows, and Certification Boards. The intent of the Milestones is to describe the educational and professional developmental trajectory of a trainee from the first stages of their postgraduate education through the completion of their clinical training. The Milestones 2.0 project includes changes made based on experience with Milestones 1.0. METHODS: The ACGME solicited volunteers to participate in the development of subspecialty Milestones 2.0. The workgroup was charged with reviewing/making any additions to the four "Harmonized Milestones", developing subspecialty specific milestones for the Patient Care and Medical Knowledge competencies, and creating a supplemental guide. The Milestones were finalized following review of input from an open comment period. RESULTS: The Cytopathology Milestones 2.0 will go into effect July 2021. They include additional subcompetencies in the 4 harmonized competency areas and cytopathology-specific edits to the patient care and medical knowledge subcompetencies. Although the number of subcompetencies has increased from 18 to 21, within each subcompetency, the number of milestone trajectories has decreased. Additionally, within each subcompetency, the wording has been streamlined. A supplemental guide was created and Milestones 1.0 were compared to 2.0; however, curriculum mapping has been left to programs to develop. CONCLUSIONS: The ultimate goal of the Cytopathology Milestones 2.0 is to provide better real-time documentation of the progress of cytopathology fellows. The expected outcome is to produce highly competent cytopathologists, improving the care they provide, regardless of the program at which they trained.


Subject(s)
Cell Biology/education , Cytological Techniques , Education, Medical, Graduate , Pathologists/education , Pathology/education , Biopsy , Cell Biology/standards , Certification , Clinical Competence , Curriculum , Cytological Techniques/standards , Education, Medical, Graduate/standards , Humans , Pathologists/standards , Pathology/standards , Specialization
16.
J Am Soc Cytopathol ; 10(5): 517-524, 2021.
Article in English | MEDLINE | ID: mdl-34119449

ABSTRACT

INTRODUCTION: Papanicolaou test quality metrics include the ASC rate, ASC:SIL ratio, and ASC HPV+ rate. What a laboratory should do when metrics show a worrisome trend is not well defined. In 2015, our laboratory noted a worrisome trend in our quality metrics and decided to implement a systemic education program in 2016; we monitored the effectiveness of our program. METHODS: An educational intervention was designed for March/April 2016. Cytotechnologist education consisted of: group meeting on March 10 to discuss metrics, lecture, and written materials on ASC-US criteria, a quiz on challenging ASC-US cases, encouragement to seek consultation, and each cytotechnologist received quarterly individual metrics. The cytopathologist education consisted of: group meeting on April 16 to discuss metrics, encouragement to bring borderline cases to consensus conference, and each faculty received quarterly individual metrics. The ASC rate, ASC:SIL ratio, and ASC HPV+ rate was collected for the institution and each individual faculty in 2016 for January to March (pre-interventions, Q1), April to June (post-interventions, Q2), and July to September (post-interventions, Q3). ASC-H was included in the calculation of ASC %, ASC:SIL, and ASC HPV+ rates. RESULTS: There was a substantial decline in the lab ASC rate and ASC:SIL ratio, and the ASC HPV+ rate increased. Individual faculty changes in ASC:SIL ratio and ASC HPV+ rate also improved. CONCLUSIONS: In our institution, an educational program has been very effective in improving Papanicolaou test metrics. It is helpful to perform re-education at all levels within the department.


Subject(s)
Atypical Squamous Cells of the Cervix/pathology , Cell Biology/education , Education, Medical, Graduate , Papanicolaou Test , Papillomavirus Infections/pathology , Pathologists/education , Pathology/education , Vaginal Smears , Atypical Squamous Cells of the Cervix/virology , Benchmarking , Cell Biology/standards , Certification , Clinical Competence , Curriculum , Education, Medical, Graduate/standards , Female , Humans , Papanicolaou Test/standards , Papillomavirus Infections/virology , Pathologists/standards , Pathology/standards , Predictive Value of Tests , Program Evaluation , Quality Improvement , Quality Indicators, Health Care , Specialization , Vaginal Smears/standards
17.
J Cell Biol ; 219(6)2020 06 01.
Article in English | MEDLINE | ID: mdl-32346721

ABSTRACT

P values and error bars help readers infer whether a reported difference would likely recur, with the sample size n used for statistical tests representing biological replicates, independent measurements of the population from separate experiments. We provide examples and practical tutorials for creating figures that communicate both the cell-level variability and the experimental reproducibility.


Subject(s)
Biostatistics/methods , Cell Biology/standards , Reproducibility of Results , Models, Statistical , Sample Size
18.
Cell Death Dis ; 11(9): 800, 2020 09 24.
Article in English | MEDLINE | ID: mdl-32973162

ABSTRACT

Macrophages are plastic cells that can switch among different states according to bioenergetic or biosynthetic requirements. Our previous work demonstrated that the transcription factor Forkhead Box Protein 1 (FoxO1) plays a pivotal role in regulating the function of macrophages, but the underlying mechanisms are still unclear. Here we identify FoxO1 as a regulator of macrophage function through metabolic reprogramming. Transcriptomic and proteomic analyses showed that the deficiency of FoxO1 results in an alternatively activated (M2) phenotype of macrophages, with lower expression of inflammatory response- and migration-associated genes. Using the high content screening and analysis technology, we found that deletion of FoxO1 in macrophages slows their migration rate and impairs their function to limit tumor cell growth in vitro. Next, we demonstrated that glycolysis is inhibited in FoxO1-deficient macrophages, which leads to the observed functional changes and the reduced tumor suppression capability. This prospective study shows that FoxO1 serves as a bridge between metabolism and macrophage function.


Subject(s)
Cell Biology/standards , Cellular Reprogramming/immunology , Forkhead Box Protein O1/metabolism , Macrophages/metabolism , Proteomics/methods , Humans
19.
J Clin Pathol ; 73(10): 681-685, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32601067

ABSTRACT

This review article summarises systems for categorisation of diagnostic errors in pathology and cytology with regard to diagnostic accuracy and the published information on human factors (HFs) in pathology to date. A 12-point event-based checklist for errors of diagnostic accuracy in histopathology and cytopathology is proposed derived from Dupont's 'Dirty Dozen' HF checklist, as used in the aerospace industry for aircraft maintenance. This HF checklist comprises 12 HFs; (1) Failure of communication. (2) Complacency. (3) Lack of knowledge. (4) Distractions. (5) Lack of teamwork. (6) Fatigue. (7) Lack of resources. (8) Pressure. (9) Lack of assertiveness. (10) Stress. (11) Norms. (12) Lack of awareness. The accompanying article explains practical examples of how each of these 12 HFs may cause errors in diagnostic accuracy in pathology. This checklist could be used as a template for analysis of accuracy and risk of diagnostic error in pathology either retrospectively 'after the event' or prospectively at the time of diagnosis. There is a need for further evaluation and validation of this proposed 12-point HF checklist and similar systems for categorisation of diagnostic errors and diagnostic accuracy in pathology based on HF principles.


Subject(s)
Cell Biology/standards , Checklist/instrumentation , Cytodiagnosis/standards , Diagnostic Errors , Pathology, Clinical/standards , Humans
20.
J Am Soc Cytopathol ; 9(6): 579-585, 2020.
Article in English | MEDLINE | ID: mdl-32622857

ABSTRACT

INTRODUCTION: As the coronavirus pandemic swept across national and state borders, institutions of higher learning, including cytology, began closing campuses and moving instruction online. We have described a method of remotely teaching cytology in our institution, including using the telecytology concept used with rapid onsite evaluation and remote conferencing and educational tools to conduct eCytology learning. This is a cost-effective method to transition a traditional in-classroom program into online teaching for cytology. It can also be implemented quickly. MATERIALS AND METHODS: In March 2020, our cytology program developed a method for teaching cytology remotely. The distance-learning teaching method included the use of remote conferencing (Zoom platform) and learning management platforms (Canvas) to present lectures and administer tests. Remote multihead sessions were conducted by adapting the telecytology rapid onsite evaluation concept, which attaches a mobile device to the microscope to transmit live video to remote learners. RESULTS: When asked about their experience with online learning, the students had responded positively. All the students indicated a willingness to attend classes remotely in the future, even when the traditional in-classroom learning option is available. CONCLUSIONS: We have presented a method for educating students remotely using existing technology that is affordable and can be implemented quickly by nearly all cytology education programs.


Subject(s)
Cell Biology/education , Cell Biology/standards , Education, Distance/methods , Education, Distance/standards , Education, Distance/trends , Humans , Learning
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