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How do small birds evolve in response to climate change?Data from the long-term record at La Brea tar pits

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Integrative Zoology 2020年第4期15卷 249-261页

作者： katherine L.long Donald r.PrOTHErO Valerie J.P.SYVErSON Department of Geological Sciences Cal Poly PomonaPomonaCaliforniaUSA Natural History Museum of Los Angeles County Los AngelesCaliforniaUSA Department of Geosciences University of Wisconsin MadisonMadisonWisconsinUSA

Biology textbooks describe the small changes in the beaks of the Galápagos finches as exemplars of how birds evolve in response to environmental ***,recent studies of the abundant fossil birds at rancho La Brea find no evidence of evolutionary responses to the dramatic climate changes of the glacial–interglacial cycle over the past 35000 years:none of the large birds exhibit any change in body size or limb proportions,even during the last glacial maximum approximately 18000–20000 years ago,when the southern California chaparral was replaced by snowy coniferous ***,these are all large birds with large ranges and broad habitat preferences,capable of living in many different *** the smaller birds at La Brea,which have smaller home ranges and narrower habitats,might respond to climate more like Galápagos *** only 3 common small birds at La Brea are the western meadowlark,the yellow-billed magpie and the *** this study,we demonstrate that these birds also show complete stasis over the last glacial–interglacial cycle,with no statistically significant changes between dated *** research suggests that the small-scale changes over short timescales seen in the Galápagos finches are merely fluctuations around a stable morphology,and rarely lead to long-term accumulation of changes or ***,the prevalence of stasis supports the view that long-term directional changes in morphology are quite *** directional changes in morphology occur frequently over short(long term such changes only rarely remain stable for.long enough to appear in the fossil record.

关键词： birds evolution macroevolution microevolution Pleistocene

Circulating tumor cells(CTCs)in breast cancer:a diagnostic tool for prognosis and molecular analysis

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Chinese Journal of Cancer research 2012年第4期24卷 388-398页

作者： Xiaoshen Dong r.katherine Alpaugh Massimo Cristofanilli Department of Surgical Oncology First Affiliated HospitalChina Medical University Fox Chase Cancer Center 333 Cottman AvePhiladelphia

Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression- free survival （PFS） and overall survival （OS） in MBC patients. Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.

关键词： Circulating tumor cells (CTCs) metastatic breast cancer (MBC) epithelial-mesenchymal transition(EMT) cancer stem cells

Air-stable n-type transistors based on assembled aligned carbon nanotube arrays and their application in complementary metal-oxide-semiconductor electronics

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Nano research 2022年第2期15卷 864-871页

作者： Zhen Li katherine r.Jinkins Dingzhou Cui Mingrui Chen Zhiyuan Zhao Michael S.Arnold Chongwu Zhou Ming Hsieh Department of Electrical Engineering Mork Family Department of Chemical Engineering and Materials Scienceand Department of Physics and AstronomyUniversity of Southern CaliforniaLos AngelesCalifornia 90089USA Department of Materials Science and Engineering University of Wisconsin-MadisonMadisonWisconsin 53706USA

Carbon nanotubes(CNTs)are ideal candidates for beyond-silicon nano-electronics because of their high mobility and low-cost ***,assembled massively aligned CNTs have emerged as an important platform for semiconductor ***,realizing sophisticated complementary nano-electronics has been challenging due to the p-type nature of carbon nanotubes in *** of n-type behavior field effect transistors(FETs)based on assembled aligned CNT arrays is needed for advanced CNT *** in this paper,we report a scalable process to make n-type behavior FETs based on assembled aligned CNT ***-stable and high-performance n-type behavior CNT FETs are achieved with high yield by combining the atomic layer deposition dielectric and metal contact *** also systematically studied the contribution of metal contacts and atomic layer deposition passivation in determining the transistor *** on these experimental results,we report the successful demonstration of complementary metal-oxide-semiconductor inverters with good performance,which paves the way for realizing the promising future of carbon nanotube nano-electronics.

关键词： carbon nanotube field effect transistor air-stable complementary metal-oxide-semiconductor

Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders

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Translational Neurodegeneration 2014年第1期3卷 180-203,179页

作者： Kristi M Anderson katherine E Olson katherine A Estes Ken Flanagan Howard E Gendelman r Lee Mosley Department of Pharmacology and Experimental Neuroscience Center for Neurodegenerative DisordersThe University of Nebraska Medical CenterOmahaNE 68198USA Prothena Biosciences Inc.650 Gateway BoulevardSouth San FranciscoCA 94080USA

Inappropriate T cell responses in the central nervous system(CNS)affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include,but are not limited to,multiple sclerosis,amyotrophic lateral sclerosis,Alzheimer’s disease and Parkinson’s *** the one hand immune responses can exacerbate neurotoxic responses;while on the other hand,they can lead to neuroprotective *** temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent ***,immune responses that affect neurodegeneration may occur within or outside the *** of antigen-specific CD4+T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal *** destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T ***,immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the *** responses with predominate T cell subtypes may differentially manifest migratory,regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific *** final result is altered glial and neuronal behaviors that influence the disease ***,discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.

关键词： Neurodegeneration Neuroprotection Migration MPTP MCAM regulatory T cell Effector T cell,Neuroinflammation

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral Science 2013年第3期5卷 130-140页

作者： Carol L Fischer katherine S Walters David r Drake Deborah V Dawson Derek r Blanchette Kim A Brogden Philip W Wertz Dows Institute for Dental research College of Dentistry The University of Iowa Central Microscopy research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric Dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

Integrating brain imaging endophenotypes with GWAS for Alzheimer’s disease

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Quantitative Biology 2021年第2期9卷 185-200页

作者： katherine AKnutson Wei Pan Division of Biostatistics University of MinnesotaMinneapolisMN 55455USA

Background:Genome wide association studies(GWAS)have identified many genetic variants associated with increased risk of Alzheimer^disease(AD).These susceptibility loci may effect AD indirectly through a combination of physiological brain *** of these neuropathologic features are detectable via magnetic resonance imaging(MrI).Methods:In this study,we examine the effects of such brain imaging derived phenotypes(IDPs)with genetic etiology on AD,using and comparing the following methods:two-sample Mendelian randomization(2SMr),generalized summary statistics based Mendelian randomization(GSMr),transcriptome wide association studies(TWAS)and the adaptive sum of powered score(aSPU)*** methods do not require individual-level genotypic and phenotypic data but instead can rely only on an external reference panel and GWAS summary ***:Using publicly available GWAS datasets from the International Genomics of Alzheimer's Project(IGAP)and UK Biobank's(UKBB)brain imaging initiatives,we identify 35 IDPs possibly associated with AD,many of which have well established or biologically plausible links to the characteristic cognitive impairments of this neurodegenerative ***:Our results highlight the increased power for detecting genetic associations achieved by multiple correlated SNP-based methods,i.e.,aSPU,GSMr and TWAS,over Mr methods based on independent SNPs(as instrumental variables).

关键词： aSPU test Mendelian randomization MrI SPU tests Sum test TWAS

Terpenoid Biosynthesis and Specialized Vascular Cells of Conifer Defense

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Journal of Integrative Plant Biology 2010年第1期52卷 86-97页

作者： katherine G. Zulak Jrg Bohlmann Michael Smith Laboratories University of British Columbia

Defense-related terpenoid biosynthesis in conifers is a dynamic process closely associated with specialized anatomical structures that allows conifers to cope with attack from many potential pests and pathogens. The constitutive and inducible terpenoid defense of conifers involves several hundred different monoterpenes, sesquiterpenes and diterpenes. Changing arrays of these many compounds are formed from the general isoprenoid pathway by activities of large gene families for two classes of enzymes, the terpene synthases and the cytochrome P450-dependent monooxygenases of the CYP720B group. Extensive studies have been conducted on the genomics, proteomics and molecular biochemical characterization of these enzymes. Many of the conifer terpene synthases are multi-product enzymes, and the P450 enzymes of the CYP720B group are promiscuous in catalyzing multiple oxidations, along homologous series of diterpenoids, from a broad spectrum of substrates. The terpene synthases and CYP720B genes respond to authentic or simulated insect attack with increased transcript levels, protein abundance and enzyme activity. The constitutive and induced oleoresin terpenoids for conifer defense accumulate in preformed cortical resin ducts and in xylem trauma-associated resin ducts. Formation of these resin ducts de novo in the cambium zone and developing xylem, following insect attack or treatment of trees with methyl jasmonate, is a unique feature of the induced defense of long-lived conifer trees.

关键词： Terpenoid Biosynthesis and Specialized Vascular Cells of Conifer Defense GPPS

Clinical approaches to non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第7期20卷 1712-1723页

作者： katherine JP Schwenger Johane P Allard Institute of Medical Science University of Toronto1 King’s CircleToronto M5S 1A8Canada Department of Medicine Toronto General HospitalUniversity Health NetworkToronto M5G 2C4Canada

Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease *** is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and *** can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to *** progression varies between individuals and is linked to a number of risk *** involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal *** loss through improved diet and increased physical activity has been the cornerstone therapy of *** therapies such as pioglitazone and vitamin E have been shown to be *** 3 polyunsaturated fatty acids and statins may offer additional *** surgery should be considered in morbidly obese *** research is needed to assess the impact of these treatments on a long-term *** objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.

关键词： Non-alcoholic fatty liver disease Steatohepatitis Cirrhosis Steatosis Pathogenesis Diagnosis Management Treatment

long-term modifications of blood pressure in normotensive and spontane-ously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase

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Cell research 2005年第9期 42-49页

作者： katherine CIANFLONE Montreal Mike rosenbloom Laboratory for Cardiovascular research Canada McGill University Health Center Quebec H3A 1A1

Arachidonic acid cytochrome P-450 (CYP) hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adeno- associated viral vector (rAAV) to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHr), respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hypertension. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV·4A1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV·anti4A1-treated SHr rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mrNA and protein levels. In anti-4A1-treated SHr, CYP4A mrNA in various tissues was probed, especially in kidneys, but 4A1 protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxy- lases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hyperten- sion by blocking expression of CYP 4A in kidneys.

关键词： Arachidonic acid cytochrome P450 4A1 hypertension recombinant adeno-associated virus 20- Hydroxyeicosatetraenoic acids spontaneously hypertensive rats.