Faculty reviewsPub Date : 2022-07-22eCollection Date: 2022-01-01DOI: 10.12703/r/11-19
Jorge Ortiz-Garcia, Camilo R Gomez, Michael J Schneck, José Biller
{"title":"Recent advances in the management of transient ischemic attacks.","authors":"Jorge Ortiz-Garcia, Camilo R Gomez, Michael J Schneck, José Biller","doi":"10.12703/r/11-19","DOIUrl":"10.12703/r/11-19","url":null,"abstract":"<p><p>Transient ischemic attack (TIA) constitutes an important clinical condition, indicating the presence of considerable risk for a subsequent ischemic stroke. Its prompt diagnosis and management have the potential for reducing the risk of neurologic disability, highlighting the critical need to prioritize the care of patients with TIA. The risk of ischemic stroke following a TIA is directly related to its etiopathogenesis, and recognizable causes are commonly categorized within one of three domains: cerebrovascular pathology, cardiac dysfunction, and hematologic disorders. Therefore, the clinical approach to patients suspected of having suffered a TIA demands a comprehensive evaluation, including testing of possible etiologic conditions in all three of these domains, best carried out in an expedited fashion since the stroke risk is greatest in the hours and days that follow the index event. The present is a review of the existing literature addressing the diagnosis, evaluation, prioritization, and management strategies available to clinicians who provide care to patients with TIA.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40708529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-07-21eCollection Date: 2022-01-01DOI: 10.12703/r-01-0000013
Peter Friedl, Konstantinos Konstantopoulos, Erik Sahai, Orion Weiner
{"title":"Adhesion-independent topography-based leukocyte migration.","authors":"Peter Friedl, Konstantinos Konstantopoulos, Erik Sahai, Orion Weiner","doi":"10.12703/r-01-0000013","DOIUrl":"10.12703/r-01-0000013","url":null,"abstract":"<p><p>Cells need to couple intracellular actin flows with the substrate to generate forward movement. This has traditionally been studied in the context of specific transmembrane receptors, particularly integrin adhesion receptors, which link extracellular adhesive molecules to the actin cytoskeleton. However, leukocytes and other cells can also migrate using integrin-independent strategies both <i>in vivo</i> and <i>in vitro</i>, though the cellular and environmental requirements for this mode are not fully understood. In seminal recent work, Reversat <i>et al</i>.<sup>1</sup> develop a range of innovative 2D and 3D engineered microdevices and probe the biophysical mechanisms underlying T lymphocytes and dendritic cells in conditions of limited substrate adhesion. They identify a physical principle of mechano-coupling between retrograde actin flow and irregular extracellular confinement, which allows the cell to generate mechanical resistance and move in the absence of receptor-mediated adhesion. Through the combined use of experiments and theoretical modeling, this work resolves a long-standing question in cell biology and establishes mechanical interaction with an irregular-shaped 3D environment which may be relevant to cell migration in a range of tissue contexts.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":"11 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354731/pdf/facrev-11-18.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-06-27eCollection Date: 2022-01-01DOI: 10.12703/r-01-0000012
Larry I Benowitz, John E Dowling, Roman J Giger, Thomas V Johnson, Donald J Zack
{"title":"Restoring partial vision to a blind patient.","authors":"Larry I Benowitz, John E Dowling, Roman J Giger, Thomas V Johnson, Donald J Zack","doi":"10.12703/r-01-0000012","DOIUrl":"10.12703/r-01-0000012","url":null,"abstract":"<p><p>This paper reports an important breakthrough in partially restoring sight to a man who had lost his vision due to retinitis pigmentosa (RP), a heritable retinal degenerative disease that affects approximately 1 in 4000 people. Long considered an insurmountable challenge, a stellar team of vision scientists, engineers, basic biologists, and others, working together for many years, has enabled a man who had been legally blind for decades to begin distinguishing objects and navigating his environment<sup>1</sup>.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":"11 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239363/pdf/facrev-11-17.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-06-10eCollection Date: 2022-01-01DOI: 10.12703/r-01-0000010
David C Fajgenbaum, Adrian C Hayday, Angela J Rogers, Greg J Towers, Andreas Wack, Ivan Zanoni
{"title":"Anti-type I interferon antibodies as a cause of severe COVID-19.","authors":"David C Fajgenbaum, Adrian C Hayday, Angela J Rogers, Greg J Towers, Andreas Wack, Ivan Zanoni","doi":"10.12703/r-01-0000010","DOIUrl":"10.12703/r-01-0000010","url":null,"abstract":"<p><p>COVID-19 ranges from asymptomatic through to respiratory failure and death. Although specific pre-existing conditions such as age and male sex have been associated with poor outcomes, we remain largely ignorant of the mechanisms predisposing to severe disease. In this study, the authors discovered that approximately 10% of 987 patients with life-threatening COVID-19 harbored neutralizing antibodies to Type I interferons (IFNs)<sup>1</sup>. They demonstrated that these antibodies could neutralize high concentrations of the corresponding IFN and could rescue SARS-CoV-2 infection from inhibition by IFN <i>in vitro</i>. Importantly, anti-IFN antibodies were associated with low levels of serum IFN. These observations suggest that disease severity in these individuals results from a failure to control SARS-CoV-2 replication because of antibody-mediated IFN inhibition. The study suggests specific treatments and diagnostics for this class of severe COVID-19.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":"11 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239362/pdf/facrev-11-15.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9150950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in connexin gap junction biology","authors":"P. Lampe, D. Laird","doi":"10.12703/r/11-14","DOIUrl":"https://doi.org/10.12703/r/11-14","url":null,"abstract":"Connexins are assembled into dodecamer intercellular channels, a collection of which is termed a gap junction, and their canonical function allowing direct exchange of ions and metabolites has been unequivocally established. When initially assembled into undocked cell surface connexin hemichannels, healthy cells may also engage in cell signaling via a regulated small-molecule release. Recent advances in the field have led to an expanded view of the functional roles of intercellular channels and hemichannels in both physiology and pathology. As more of the 21-member human connexin family is intensely interrogated, mounting evidence points to the biological uniqueness of each member, and no longer can we confidently refer to all connexins engaging in the same cellular processes. Innovations in high-resolution cryo-electron microscopy have revealed important insights into the structure of functionally important domains of both hemichannels and channels. These and other studies have established a foundation of knowledge that should allow inhibitory smart drug design for situations where enhanced intercellular or hemichannel activity is at the root of a connexin-linked disease. Assessment of the connexin interactome, which varies widely for each connexin subtype, continues to provide regulatory insights into the assembly and function of connexins that exhibit a short half-life. As the most intensely studied, Cx43 is found in about 50% of all human cell types and is extensively regulated by multiple inhibitory and enhancing phosphorylation events that have direct implications on tissue function and outcomes of disease, including cancer. Here, we briefly discuss these advances and give our thoughts on where the field is headed.","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46824929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-05-11eCollection Date: 2022-01-01DOI: 10.12703/r-01-000009
Paola Arlotta, Fei Chen, Simona Lodato, Troy W Margrie, Tomasz J Nowakowski, Thoru Pederson, Beatriz Rico
{"title":"Dissecting cellular diversity of cortical GABAergic cells across multiple modalities: A turning point in neuronal taxonomy.","authors":"Paola Arlotta, Fei Chen, Simona Lodato, Troy W Margrie, Tomasz J Nowakowski, Thoru Pederson, Beatriz Rico","doi":"10.12703/r-01-000009","DOIUrl":"https://doi.org/10.12703/r-01-000009","url":null,"abstract":"<p><p>Decoding the complexity of the brain requires an understanding of the architecture, function, and development of its neuronal circuits. Neuronal classifications that group neurons based on specific features/behaviors have become essential to further analyze the different subtypes in a systematic and reproducible way. A comprehensive taxonomic framework, accounting for multiple defining and quantitative features, will provide the reference to infer generalized rules for cells ascribed to the same neuronal type, and eventually predict cellular behaviors, even in the absence of experimental measures. Technologies that enable cell-type classification in the nervous system are rapidly evolving in scalability and resolution. While these approaches depict astonishing diversity in neuronal morphology, electrophysiology, and gene expression, a robust metric of the coherence between different profiling modalities leading to a unified classification is still largely missing. Focusing on GABAergic neurons of the cerebral cortex, Gouwens <i>et al</i>.<sup>1</sup> pioneered the first integrated cell-type classification based on the simultaneous analysis of the transcriptional networks, the recording of intrinsic electrophysiological properties, and the reconstruction of 3D morphologies of the same cell. Their comprehensive and high-quality data provide a new framework to shed light on what may be considered a \"neuronal cell type.\"</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190211/pdf/facrev-11-13.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40000048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-05-10eCollection Date: 2022-01-01DOI: 10.12703/r-01-000008
Jacob O Brunkard, Caren Chang, Bruce J Mayer, Christian Meyer, Jen Sheen
{"title":"ConducTORs of a Signaling Symphony: Metabolic and Hormone Responses Converge on TOR and EIN2 in plants.","authors":"Jacob O Brunkard, Caren Chang, Bruce J Mayer, Christian Meyer, Jen Sheen","doi":"10.12703/r-01-000008","DOIUrl":"https://doi.org/10.12703/r-01-000008","url":null,"abstract":"<p><p>Development is coordinated by dozens of signals that act in overlapping pathways to orchestrate multicellular growth. Understanding how signaling pathways intersect and diverge at a molecular level is critical to predicting how organisms will react to dynamic environmental conditions. In plants, two antagonistic signaling hubs are strictly required to sense and respond to many nutrients and hormones: TARGET OF RAPAMYCIN (TOR) and ETHYLENE INSENSITIVE 2 (EIN2). In this Landmark report, Fu <i>et al.</i> discover that TOR and EIN2 directly interact to choreograph growth and define an unexpected molecular mechanism at the intersection of hormonal and metabolic signaling networks<sup>1</sup>.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190210/pdf/facrev-11-12.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40000047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-05-10DOI: 10.12703/r-01-0000011
B. Alberts, M. Robertson
{"title":"Scientists and journals must work together to protect the integrity of the scientific literature","authors":"B. Alberts, M. Robertson","doi":"10.12703/r-01-0000011","DOIUrl":"https://doi.org/10.12703/r-01-0000011","url":null,"abstract":"The scientific literature has for some years reflected serious concerns over the irreproducibility of many published scientific results; yet the problem persists. We review here how the prevailing culture contributes to this problem and suggest what needs to change to address it. We build on the evaluation of Buonarati et al. (1) in (2) to illustrate some of the general concerns over current publishing practices – focusing on questionable incentives for authors, editors and publishers of research journals. We then suggest some ways that the integrity of the scientific literature might be strengthened.","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44223772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome","authors":"L. Tiranini, R. Nappi","doi":"10.12703/r/11-11","DOIUrl":"https://doi.org/10.12703/r/11-11","url":null,"abstract":"Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate to severe physical, affective, or behavioral symptoms that impair daily activities and quality of life. PMS and PMDD have recently raised great interest in the research community for their considerable global prevalence. The etiology of PMS/PMDD is complex. Ovarian reproductive steroids (estradiol and progesterone) are considered pathogenetic effectors, but the key feature seems to be an altered sensitivity of the GABAergic central inhibitory system to allopregnanolone, a neurosteroid derived from progesterone produced after ovulation. Also, a reduced availability of serotonin seems to be involved. New insights point to a role for genetic and epigenetic modifications of hormonal and neurotransmitter pathways, and inflammation is the potential link between peripheral and neurological integrated responses to stressors. Thus, new therapeutic approaches to PMS/PMDD include inhibition of progesterone receptors in the brain (i.e., with ulipristal acetate), reduced conversion of progesterone to its metabolite allopregnanolone with dutasteride, and possible modulation of the action of allopregnanolone on the brain GABAergic system with sepranolone. Further research is needed to better understand the interaction between peripheral inflammatory molecules (cytokines, interleukins, C-reactive protein, and reactive oxygen species) and the brain neurotransmitter systems in women with PMS/PMDD. If confirmed, neuroinflammation could lead both to develop targeted anti-inflammatory therapies and to define prevention strategies for the associated chronic inflammatory risk in PMS/PMDD. Finally, the observed association between premenstrual disorders and psychological diseases may guide prompt and adequate interventions to achieve a better quality of life.","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48012097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faculty reviewsPub Date : 2022-04-20eCollection Date: 2022-01-01DOI: 10.12703/r/11-9
Martyn C Stott, Lucy Oldfield, Jessica Hale, Eithne Costello, Christopher M Halloran
{"title":"Recent advances in understanding pancreatic cancer.","authors":"Martyn C Stott, Lucy Oldfield, Jessica Hale, Eithne Costello, Christopher M Halloran","doi":"10.12703/r/11-9","DOIUrl":"10.12703/r/11-9","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients.</p>","PeriodicalId":73016,"journal":{"name":"Faculty reviews","volume":" ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46712233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}