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Sources of transcription variation in Plasmodium falciparum

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Journal of Genetics and Genomics 2022年第10期49卷 965-974页

作者： lindsey B.Turnbull Katrina A.Button-Simons Nestor Agbayani michael T.Ferdig Department of Pediatrics Indiana University School of MedicineIndianapolisIN 46202USA Department of Biological Sciences Eck Institute for Global HealthUniversity of Notre DameNotre DameIN 46556USA Rush School of medicine ChicagoIL 60612USA

Variation in transcript abundance can contribute to both short-term environmental response and long-term evolutionary *** studies are designed to assess differences in mean transcription levels and do not consider other potentially important and confounding sources of transcriptional *** quantification of variation sources will improve our ability to detect and identify the mechanisms that contribute to genome-wide transcription changes that underpin adaptive *** quantify innate levels of expression variation,we measured m RNA levels for more than 5000 genes in the malaria parasite,Plasmodium falciparum,among clones derived from two parasite strains across biologically and experimentally replicated *** a mixed effects model,we partitioned the total variation among four sources—between strain,within strain,environmental batch effects,and stochastic *** found 646 genes with significant variation attributable to at least one of these *** genes were categorized by their predominant variation source and further examined using gene ontology enrichment analysis to associate function with each source of *** with environmental batch effect and within strain transcript variation may contribute to phenotypic plasticity,while genes with between strain variation may contribute to adaptive responses and processes that lead to parasite strain-specific survival under varied conditions.

关键词： Expression variation malaria Transcription Cloning microarray

Response to osimertinib in a colorectal cancer patient with an EGFR T790m mutation: A case report

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World Journal of Gastrointestinal Oncology 2023年第10期15卷 1829-1834页

作者： Blake Buzard lindsey Douglass Beth Gustafson Jennifer Buckley marc Roth Lara Kujtan Dhruv Bansal Cancer Institute St.Luke's HospitalKansasMO 64111United States Department of medical Oncology University of Missouri-Kansas CityKansasMO 64108United States Department of Hematology/Oncology St.Luke's Cancer InstituteKansasMO 64111United States

BACKGROUND Although common in lung cancer,somatic epidermal growth factor receptor(EGFR)mutations are rarely found in colorectal cancer,occurring in approximately 3%of *** with anti-EGFR antibodies is commonplace,but EGFR tyrosine kinase inhibitors are not standard treatments in colorectal *** we report a case of sustained response to osimertinib in a colorectal cancer patient with an EGFR T790m mutation on cell-free DNA *** SUmmARY A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair,scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic *** generation sequencing revealed a RAS/RAF wild-type,microsatellite stable,PD-L1 negative *** in TP3 and APC were also identified,as well as EGFR ***-free DNA analysis revealed an EGFR T790m *** was unable to tolerate first-line treatment with panitumumab,5-fluorouracil and leucovorin,progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab,and was unable to tolerate third-line treatment with *** was started on fourth-line treatment with off-label osimertinib,with clinical response–decrease in size of hepatic metastases and a pericardial *** remained on treatment with osimertinib for seven *** This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.

关键词： Colorectal cancer Osimertinib Epidermal growth factor receptor T790m Precision oncology Tyrosine kinase inhibitor Case report

Epstein-Barr virus infection mechanisms

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Chinese Journal of Cancer 2014年第11期33卷 545-548页

作者： Liudmila S.Chesnokova lindsey m.Hutt-Fletcher Department of microbiology and Immunology Center for Molecular Tumor Virology and Feist-Weiller Cancer CenterLouisiana State University Health Sciences CenterShreveportLA 71130USA

Epstein-Barr virus(EBV) infection occurs by distinct mechanisms across different cell types. EBV infection of B cells in vitro minimally requires 5 viral glycoproteins and 2 cellular proteins. By contrast, infection of epithelial cells requires a minimum of 3 viral glycoproteins, which are capable of interacting with one or more of 3 different cellular proteins. The full complement of proteins involved in entry into all cell types capable of being infected in vivo is unknown. This review discusses the events that occur when the virus is delivered into the cytoplasm of a cell, the players known to be involved in these events, and the ways in which these players are thought to function.

关键词：病毒感染机制蛋白质相互作用病毒糖蛋白细胞类型细胞蛋白上皮细胞 EBV

Trait allometries generate super-honesty in Anolis dewlaps and may underlie sexual dimorphism

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Integrative Zoology 2017年第2期12卷 97-111页

作者： maria PETELO lindsey SWIERK Department of Biology University of Hawaiʻi at MānoaHonoluluUSA Las Cruces Biological Station Organization for Tropical StudiesSan VitoCoto BrusCosta Rica School of Forestry and Environmental Studies Yale UniversityNew HavenConnecticutUSA

Whether or not sexually selected traits consistently exhibit positive allometry(*** disproportionately large in larger individuals)is an ongoing *** models and exceptions to this rule suggest that the underlying drivers of sexual trait allometry are ***,we compare allometries of sexual and non-sexual traits of a species(Anolis aquaticus)within a well-studied lizard genus to test the competing hypotheses that sexual traits are,or are not,defined by positive *** further consider the relationships of trait functions,which are relatively well understood in the genus Anolis,and allometry to identify potential drivers of allometric *** particular,we explore how trait allometries interact to influence total organism function and generate sexual *** quantified size(of targeted traits)and color of a sexual signal(the dewlap)in Anolis aquaticus in the *** dewlap conveyed information relevant to intra-sexual combat and exhibited positive ***,our results suggest that using single-trait allometries as indicators of past selection provides only an incomplete understanding of trait *** the function of positive allometry in some individual sexual signals(*** conveying“super-honest”information)may be straightforward,we illustrate how scaling relationships interact synergistically to influence the function of phenotypes and propose avenues for future research.

关键词： Anolis[Norops]aquaticus color morphology reproductive strategy scaling

Clonidine use during dexmedetomidine weaning:A systematic review

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World Journal of Critical Care medicine 2023年第1期12卷 18-28页

作者： Sanu Rajendraprasad molly Wheeler Erin Wieruszewski Joseph Gottwald lindsey A.Wallace Danielle Gerberi Patrick m Wieruszewski Nathan J Smischney Department of Pulmonary&Critical Care Mayo ClinicRochesterMN 55905United States Department of Pharmacy Mayo ClinicRochesterMN 55905United States Department of Anesthesiology&Perioperative medicine Mayo ClinicRochesterMN 55905United States Critical Care medicine Independent multidisciplinary Program Mayo ClinicRochesterMN 55905United States mayo medical Libraries Mayo ClinicRochesterMN 55905United States

BACKGROUND Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit(ICU),with prolonged use increasing risk of withdrawal symptoms upon sudden *** clonidine is an enterally available alpha-2A adrenergic agonist,it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal *** appropriate dosing and conversion strategies for using enteral clonidine in this context are not *** objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal *** To systematically review the practice,dosing schema,and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill *** This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults(≥18 years).Randomized controlled trials,prospective cohorts,and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were *** primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine *** secondary outcomes included prevalence of adverse events associated with enteral clonidine use,re-initiation of dexmedetomidine,duration of mechanical ventilation,and ICU length of *** A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 *** three studies were observational,two being prospective and one *** all included studies,the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the *** time ranged from 13 to 167 h on *** clonidine was started in the prospective studies in a similar protocolized method,with 0.3 mg every 6 *** starti

关键词： Clonidine Dexmedetomidine Intensive care unit Withdrawal Weaning

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

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Bone Research 2023年第4期11卷 737-750页

作者： lindsey H.Remark Kevin Leclerc malissa Ramsukh Ziyan Lin Sooyeon Lee Backialakshmi Dharmalingam Lauren Gillinov Vasudev V.Nayak Paulo El Parente margaux Sambon Pablo J.Atria mohamed A.E.Ali Lukasz Witek Alesha B.Castillo Christopher Y.Park Ralf H.Adams Aristotelis Tsirigos Sophie m.morgani Philipp Leucht Department of Orthopaedic Surgery NYU Robert I.Grossman School of MedicineNew YorkNYUSA Applied Bioinformatics Laboratories NYU Grossman School of MedicineNew YorkNYUSA Institute of Comparative molecular Endocrinology Ulm UniversityUlmGermany max Planck Institute for molecular Biomedicine Department of Tissue Morphogenesisand University of MünsterFaculty of MedicineD-48149 MünsterGermany Department of Biochemistry and molecular Biology University of Miami Miller School of MedicineMiamiFLUSA Department of Pathology NYU Robert I.Grossman School of MedicineNew YorkNYUSA Biomaterials Division New York University College of DentistryNew YorkNYUSA Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of MedicineNew York UniversityNew YorkNYUSA Department of Biomedical Engineering Tandon School of EngineeringNew York UniversityBrooklynNYUSA Department of Cell Biology NYU Robert I.Grossman School of MedicineNew YorkNYUSA

Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.

关键词： Notch skeletal elevated

Effects of Victim Innocence and BJW （Belief in a Just World） Upon Derogation of an Ingroup/Outgroup Victim

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Psychology Research 2012年第2期2卷 135-141页

作者： Rickard A. Sebby lindsey m. Johnston Southeast missouri State University Cape Girardeau USA

According to the BJW (belief in a just world) theory, a person is more likely to derogate a victim when that victim threatens their BJW. An innocent victim and a victim who is more similar (an ingroup member) are more threatening to a person"s BJW than a non-innocent outgroup victim with such a threat resulting in greater victim derogation. In the present study, group membership and victim innocence were manipulated. Group membership was based on status (college students vs. non-college students). College students (n = 162) were randomly assigned to either a BJW threating or BJW confirming condition. A 2 × 2 × 2 ANOVA (analysis of variance) found an interaction between the BJW manipulation and group membership; participants whose BJW was threatened derogated the non-student (outgroup) more than the control. Contrary to expected results, the college student (ingroup) victim was not as highly derogated as the outgroup member. We suggest that more subtle social categories (not just differences associated with traditional racial or ethnic prejudice) may influence the ways individuals defend or reestablish their BJW.

关键词：受害者世界公正大学生随机分配相互作用方差分析威胁

Cellular crosstalk during cholestatic liver injury

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Liver Research 2017年第1期1卷 26-33页

作者： Joanne Thomson Laura Hargrove lindsey Kennedy Jennifer Demieville Heather Francis Research Central Texas Veterans Healthcare SystemTXUSA Digestive Disease Research Center Baylor Scott&White HealthTXUSA medicine Texas A&M Health Science CenterTempleTXUSA

The functions of the liver are very *** detoxifying blood to storing glucose in the form of glycogen and producing bile to facilitate fat digestion,the liver is a very active and important *** liver is comprised of many varied cell types whose functions are equally *** line the biliary tree and aid in transporting and adjusting the composition of bile as it travels to the *** stellate cells and portal fibroblasts are located in different areas within the liver architecture,but both contribute to the development of fibrosis upon activation after liver *** cells,including those that constitute the peribiliary vascular plexus,are involved in functions other than blood delivery to and from the liver,such as supporting the growth of the biliary tree during *** cells are normally found in healthy livers but in very low ***,after injury,mast cell numbers greatly increase as they infiltrate and release factors that exacerbate the fibrotic *** not an all-inclusive list,these cells have individual roles within the liver,but they are also able to communicate with each other by cellular *** this review,we examine some of these pathways that can lead to an increase in the homeostatic dysfunction seen in liver injury.

关键词： mast cells Paracrine Cholangiocytes Hepatic stellate cells Crosstalk

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

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Liver Research 2017年第1期1卷 34-41页

作者： lindsey Kennedy Heather Francis Fanyin meng Shannon Glaser Gianfranco Alpini Research Central Texas Veterans Health Care SystemTempleTXUSA Department of medicine Texas A&M Health Science CenterCollege of MedicineTempleTXUSA Baylor Scott&White Digestive Disease Research Center Baylor Scott&White HealthTempleTXUSA

Cholangiopathies are a group of rare,devastating diseases that arise from damaged cholangiocytes,the cells that line the intra-and extra-hepatic bile ducts of the biliary *** result in significant morbidity and mortality and are a major cause of liver transplantation.A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy progression is necessary,considering the dismal prognosis associated with these *** are a class of small,non-coding RNAs that regulate post-transcriptional mRNA expression of specific *** role of microRNAs has expanded to include the initiation and development of many diseases,including *** microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these *** this review,the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic potential of microRNAs in cholangiopathies.

关键词： microRNAs Cholangiopathies Diagnosis Therapy