Evaluation of inter-batch differences in stem-cell derived neurons

AbstractDifferentiated cells retain the genetic information of the donor but the extent to which phenotypic differences between donors or batches of differentiated cells are explained by variation introduced during the differentiation process is not fully understood. In this study, we evaluated four separate batches of commercially available neurons originating from the same iPSCs to investigate whether the differentiation process used in manufacturing iPSCs to neurons affected genome-wide gene expression and modified cytosines, or neuronal sensitivity to drugs. No significant changes in gene expression, as measured by RNA-Seq, or cytosine modification levels, as measured by the Illumina 450K arrays, were observed between batches relative to changes over time. As expected, neurotoxic chemotherapeutics affected neuronal outgrowth, but no inter-batch differences were observed in sensitivity to paclitaxel, vincristine and cisplatin. As a testament to the utility of the model for studies of neuropathy, we observed that genes involved in neuropathy had relatively higher expression levels in these samples across different time points. Our results suggest that the process used to differentiate iPSCs into neurons is consistent, resulting in minimal intra-individual variability across batches. Therefore, this model is reasonable for studies of human neuropathy, druggable targets to prevent neuropathy, and other neurological diseases

Application of Stem Cell Derived Neuronal Cells to Evaluate Neurotoxic Chemotherapy

The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy. We demonstrate differential sensitivity of neurons to mechanistically distinct classes of chemotherapeutics. We also show a dose-dependent reduction of electrical activity as measured by mean firing rate of the neurons following treatment with paclitaxel. We compared neurite outgrowth and cell viability of iPSC-derived cortical (iCell® Neurons) and peripheral (Peri.4U) neurons to cisplatin, paclitaxel and vincristine. Goshajinkigan, a Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but not oxaliplatin as measured by morphological phenotypes. Thus, we have demonstrated the utility of human iPSC-derived neurons as a useful model to distinguish drug class differences and for studies of a potential neuroprotectant for the prevention of chemotherapy-induced peripheral neuropathy

Creativity and Resiliency in the Archives: Challenges in Uncovering the History of an Allied Health Sciences Division

The Clinical Rehabilitation and Mental Health Counseling (CRMH) division within the Department of Allied Health Sciences (DAHS) requested help from a librarian in researching the history of the division. The CRMH division believes it has an upcoming anniversary to celebrate and wishes to have a timeline of the divison’s development, along with notable historical documents that highlight milestones and key figures in its history. Archive finding aids and other strategies support the discovery of university documents relevant to the history of the division. The project has been underway for more than a year and is still ongoing. It presents several challenges requiring elements of resiliency, flexibility and creativity

Dysfunctional Tissue Correlates of Unrelated Naming Errors in Acute Left Hemisphere Stroke

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalised with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within the parietal lobe—was an important error predictor, especially for the unimpaired group. In both groups, higher unrelated error proportions were associated with primarily ventral stream damage, the language route critical for processing meaning. Nonetheless, brain metrics implicated in unrelated errors were distinct from semantic error correlates

Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery

Purpose The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients. Methods and materials Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation. Results: PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects. Conclusions: Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching

Experiential Learning: Voices of Librarians-to-Be

Academic libraries, and particularly specialized ones, often can provide a broad range of career-building opportunities to those thinking about or in the process of becoming librarians. Participants in a variety of experiences at one of UNC’s specialized libraries have ranged from teens to graduate students to recent graduates transitioning to new careers in libraries. Hear several current and recent librarians-to-be discuss their efforts to acquire hands-on practical skills, learn more about the field of librarianship, receive mentoring and career planning assistance, and participate in library meetings, events and other professional activities inside and outside of the library. Challenges include matching potential candidates with appropriate experiential opportunities tailored to their needs, while meeting Human Resources requirements and ensuring students enrolled for credit satisfy the expectations of their specific institutions and programs. To further aid in making career resources more accessible to fledgling professionals, the library also created an online guide

Changing patterns in the prevalence of posttraumatic stress disorder, major depressive episode and generalized anxiety disorder over 24 months following a road traffic crash: results from the UQ SuPPORT study

Objective: To examine the prevalence and changing patterns of PTSD, major depressive episode (MDE), and generalized anxiety disorder (GAD) in adult claimants who sustained a non-catastrophic injury in a road traffic crash (RTC) in Queensland, Australia. Method: Participants (N = 284) were assessed at approximately 6, 12, and 24 months post-RTC using the composite international diagnostic interview (CIDI) modules for PTSD, and CIDI-short form for MDE, and GAD. Results: The prevalence of at least one of these disorders was 48.2%, 52.5%, and 49.3%, at 6, 12, and 24 months, respectively. Comorbidity was common (20.8% at 6 months, 27.1% at 12 months, and 21.1% at 24 months) and only 33.1% of participants never met PTSD, GAD, or MDE criteria. A substantial proportion of participants (42.3%) had an unstable diagnostic pattern over time. Participants with multiple diagnoses at 6 months were more likely to continue to meet diagnostic criteria for any disorder at 12 and 24 months than participants with a single diagnosis. Participants with PTSD (with or without MDE/GAD) were more likely to meet criteria for any disorder at 24 months than participants with another diagnosis. Preinjury psychiatric history increased the likelihood of any disorder at 24 months post-injury, but did not significantly increase the likelihood of PTSD. Conclusions: People injured in a RTC are at risk of having complex psychological presentations over time. Interventions to prevent mental disorders, especially PTSD, in the early post-injury period are needed to prevent chronic psychological injury, including consideration of comorbidity and dynamic course

Sect and House in Syria: History, Architecture, and Bayt Amongst the Druze in Jaramana

This paper explores the connections between the architecture and materiality of houses and the social idiom of bayt (house, family). The ethnographic exploration is located in the Druze village of Jaramana, on the outskirts of the Syrian capital Damascus. It traces the histories, genealogies, and politics of two families, bayt Abud-Haddad and bayt Ouward, through their houses. By exploring the two families and the architecture of their houses, this paper provides a detailed ethnographic account of historical change in modern Syria, internal diversity, and stratification within the intimate social fabric of the Druze neighbourhood at a time of war, and contributes a relational approach to the anthropological understanding of houses

The Grizzly, September 11, 2003

Unique Organizations Attract New Members at Activities Fair • To Party or Not to Party: How is the Question • Reflections on the Post-September 11th World • An Anniversary Like No Other • A Major Decision • A Day in the Life: Lounge Living • Student Spotlight: Locks for Love • Activities Coming to You • Family Day at UC • John Mayer & Counting Crows • Opinions: Please Read: E-mail Abuse is Annoying; A Continuing Story: Out of the Middle East; The [De] Stabilized Situation in Iraq • 9/11: Reliving the Tragedy • SIGI Plus to the Rescue • UC on File Sharing: Joining the Bandwagon • Party Etiquette 101 • Price Comparison: Popular CDs • The Wit and Wisdom of J. D. Salinger • Bears Knock Out Susquehanna, 24-17 • Volleyball Team Makes it Three in a Row • TCNJ Field Hockey Blanks Ursinus • Men\u27s Soccer Comes out Even • Ursinus Women Dominate Soccer Classic • The Kobe Bryant Sagahttps://digitalcommons.ursinus.edu/grizzlynews/1540/thumbnail.jp