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Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate

World Journal of Gastrointestinal Surgery 2021年第5期13卷 406-418页

作者： Mahmoud Aldyab Tony El Jabbour megan Parilla Hwajeong Lee Department of Pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States Department of Pathology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis,and paraduodenal pancreatitis can present as mass lesions and may mimicpancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thoroughhistologic examination with attention to certain morphologic features can assist indeciphering neoplastic from reactive, however small biopsies often remain achallenge. Variable histologic patterns in conventional PDAC may also confoundthe diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such asadenosquamous and squamous cell carcinoma, colloid carcinoma, medullarycarcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitateexcluding metastasis from other sites prior to rendering the diagnosis ofpancreatic carcinoma. The use of immunohistochemical staining and molecularmarkers can aid in separating benign from malignant and PDAC from *** expresses a few non-specific epithelial and mucin immunomarkers such asCK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemicalmarker that is specific for PDAC in the right clinical context is *** of SMAD4 within atypical glands and ducts supports the diagnosis of PDACin a limited sample. Unfortunately, this finding is seen only in 50% of PDACcases. The identification of certain mutations can help support a diagnosis ofPDAC when benign conditions are in the differential. At the molecular level,KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequentneoplastic progression is driven by additional mutations of tumor suppressorgenes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also providean insight to the prognosis. For instance, the loss of SMAD4 is associated with apoor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associatedwith improved survival.

关键词： Pancreas Pancreatitis Autoimmune SMAD4 Molecular

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AML1-ETO driven acute leukemia:insights into pathogenesis and potential therapeutic approaches

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Frontiers of Medicine 2012年第3期6卷 248-262页

作者： megan A.Hatlen Lan Wang Stephen D.Nimer Molecular Pharmacology and Chemistry Program Sloan-Kettering InstituteMemorial Sloan-Kettering Cancer CenterNew YorkNY 10065USA Weill Cornell Medical College New YorkNY 10065USA

The AML1-ETO fusion transcription factor is generated by the t(8;21)translocation,which is present in approximately 4%-12% of adult and 12%-30% of pediatric acute myeloid leukemia(AML)*** human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary *** this review,we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in *** also discuss potential therapeutic strategies for t(8;21)positive AML that involve targeting the fusion protein itself,the proteins that bind to it,or the genes that it *** published studies suggest that a targeted therapy for t(8;21)positive AML is feasible and may be coming sometime soon.

关键词： AML1-ETO mouse model leukemia t(8,21) pathway hits mutation hematopoiesis Kasumi-1 CD34^(+)

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Coaches’ Evaluations of Match Performance in Academy Soccer Players in Relation to the Adolescent Growth Spurt

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Journal of Science in Sport and Exercise 2020年第4期2卷 359-366页

作者： megan Hill Sam Scott Darragh McGee Sean Cumming Department for Health University of BathBath BA27AYUK Sports Science and Medicine Department Southampton Football ClubSouthamptonUK

Individual differences in biological maturation present challenges for coaches involved with youth soccer *** in the same chronological age group vary in terms of stage of maturity(pre,circum-and post-pubescent)and rate of growth,but how this affects coaches’evaluations of player performance is *** aim of this study was to compare youth soccer coaches’evaluations of players match performances before,during and post growth spurt in a professional English soccer academy across four *** hundred and seventy-eight male soccer players in the under-9 to under-16 age-groups had their performances evaluated by their coach on a 4-point Likert *** each game,players were categorised by their maturity status estimated using percentage of predicted adult height at the time of observation.A one-way ANCOVA control-ling for the level of opposition and game outcome revealed that coaches’evaluations declined from the pre-to during growth spurt stages,however,this was only significant in the under 12 ***,coaches’evaluations increased again in the post-growth spurt stage,although only significant in the under 15 *** evaluations of player performance appear to vary in accordance with stage of maturity and rate of *** in youth soccer should understand the extent to which maturity status may adversely impact performance and consider this when making talent selection decisions.

关键词： Soccer Maturity Growth Adolescence Evaluation

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Developmental rate： A unifying mechanism for sympatric divergence in postglacial fishes？

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Current Zoology 2012年第1期58卷 21-34页

作者： Mcphee, megan V. Noakes, David L. G. Allendorf, Fred W. Fisheries Division University of Alaska Fairbanks Juneau Alaska 99801 USA Department of Fisheries and Wildlife and Oregon Hatchery Research Center Oregon State University Corvallis Oregon 97331-3803 USA Division of Biological Sciences University of Montana Missoula MT 59812 USA

Morphologically divergent ecotypes arise in fish populations on postglacial time scales, and resource polymorphisms are often invoked to explain their origin. However, genetic recombination can constrain the ability of divergent selection to pro- duce reproductive isolation in sympatry. Recombination breaks up favorable combinations of traits （＂adaptive suites＂） if indivi- dual traits are affected by different loci. Recombination also breaks up any association between traits under divergent selection and traits contributing to reproductive isolation. Thus, ecological speciation in the absence of preexisting barriers to gene flow is more likely when pleiotropy minimizes the number of loci involved. Here, we revisit research conducted by Carl Hubbs in the early 1900s on the effects of developmental rate on morphological traits in fishes. Hubbs＇ work provides a mechanism to explain how sympatric divergence by trophic polymorphism can occur despite the challenges of recombination. We consider the implica- tions of Hubbs＇ observations for ecological speciation with gene flow in fishes, as well as rapid evolution in captive fish popula- tions [Current Zoology 58 （1）： 21-34, 2012].

关键词： Pleiotropy Resource polymorphism Selection-recombination antagonism

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Phase Specific Comparisons of High and Low Vertical Jump Performance in Collegiate Female Athletes

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Journal of Science in Sport and Exercise 2023年第4期5卷 322-327页

作者： Paul T Donahue megan Rush Ayden K McInnis Thomas Littlefield School of Kinesiology and Nutrition University of Southern MississippiHattiesburgMSUSA

Introduction Countermovement vertical jump testing has become a staple in athlete assessment *** the popularity of jump testing has grown,a need and interest has also grown in identifying the factors that underpin high-level *** jump height alone as a variable in evaluating vertical jump performance has been questioned in athletic populations,other variables such as the reactive strength index modified(RSIm)allow for not only evaluating the outcome,but the strategy used in obtaining that *** Thus,the purpose of this investigation was to examine the differences in high and low vertical jump performances,as determined by the RSIm in female collegiate *** Thirty NCAA Division I female volleyball and basketball athletes performed countermovement vertical jump trials on a force *** sample was then broken into two groups as determined by median RSIm *** sample t-test were then used to compare *** High RSIm group displayed greater jump heights(P<0.05).Additionally,the high performing group displayed lower eccentric duration times(P<0.05).No differences between groups were seen in kinetic *** The high performing group displayed faster eccentric times which translated to lower values in time to take-off though not statistical *** higher RSIm values appear to be a result of both greater jump heights and reduced time to take ***,focus being placed on the speed of the movement during training would be of benefit in improving RSIm values.

关键词： Reactive Strength Index modified Countermovement Jump Athlete Monitoring

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L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction

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Bone Research 2020年第1期8卷 53-62页

作者： Meenakshi AChellaiah megan CMoorer Sunipa Majumdar Hanan Aljohani Sharon CMorley Vanessa Yingling Joseph PStains Department of Oncology and Diagnostic Sciences School of DentistryUniversity of MarylandBaltimoreMDUSA Department of Orthopedics University of Maryland School of MedicineBaltimoreMDUSA Department of Pediatrics Division of Infectious Diseasesand Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA Department of Kinesiology California State UniversityEast BayHaywardCAUSA

Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones(NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin(Ser-5 and-7 to Ala-5 and-7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8-and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.

关键词： sealing impaired fused

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What makes a cry a cry？ A review of infant distress vocalizations

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Current Zoology 2012年第5期58卷 698-726页

作者： Susan LINGLE megan T. WYMAN Radim KOTRBA Lisa J. TEICHROEB Cora A. ROMANOW Department of Biology University of Winnipeg Manitoba R3B 2E9 Canada Department of Population Health and Reproduction School of veterinary Medicine University of California-Davis One Shields Avenue Davis CA 95616 U.S.A. 3 Department of Animal Science and Food Processing in Tropics and Subtropics Czech University of Life Sciences Prague Czech Republic Department of Ethology Institute of Animal Science Prague Czech Republic

In contrast to the cries of human infants, sounds made by non-human infants in different stressful behavioral contexts （hunger or physical discomfort, isolation, capture by humans or predators） are usually treated as distinct types of vocalizations. However, if distress vocalizations produced by different species and in different contexts share a common motivational state and associated neurochemical pathways, we can expect them to share a common acoustic structure and adaptive function, showing only limited variation that corresponds to the infant＇s level of arousal. Based on this premise, we review the acoustic structure and adaptive function of two types of distress calls, those given when infants were isolated from their mothers （isolation caUs） or captured by humans （capture calls）. We conducted a within-context comparison examining the two call types across a diverse se- lection of mammalian species and other vertebrate groups, followed by a comparison of how acoustic structure and function dif- fers between these contexts. In addition, we assessed acoustic traits that are critical to the response of caregivers. Across verte- brate species, distress vocalizations produced in these two behavioral contexts tend to be tonal with a simple chevron, flat or de- scending pattern of frequency modulation. Reports that both isolation and capture calls of vertebrate infants serve to attract care- givers are universal, and the fundamental frequency of infant vocalizations is often critical to this response. The results of our re- view are consistent with the hypothesis that differences in the acoustic structure of isolation and capture distress vocalizations re- flect differences in arousal, and not discrete functions. The similarity in acoustic structure and caregiver response observed across vertebrates adds support to the hypothesis that the production and processing of distress vocalizations are part of a highly-conserved system of social vocal behaviour in vertebrate

关键词： Crying Mother-infant communication Isolation calls Distress calls Motivational-structural rules Parental care Phylogeny

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Soil fungal and prokaryotic community structure exhibits differential short-term responses to timber harvest in the Pacific Northwest

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Pedosphere 2020年第1期30卷 109-125页

作者： Rachel E.DANIELSON megan L.MCGINNIS Scott M.HOLUB David D.MYROLD Department of Crop and Soil Science Oregon State UniversityCorvallis OR 97331-7306(USA) United State Forest Service Helena-Lewis and Clark National Forest2880 Skyway DriveHelena MT 59602(USA) Weyerhaeuser Company PO Box 275Springfield OR 97477(USA) Department of Land Airand Water ResourcesUniversity of CaliforniaDavis CA 95616USA

Conventional clear-cut timber harvest is a widespread industrial practice across the Pacific Northwest;however,information regarding how these practices impact soil microbial community structure at the regional scale is *** evidence of consistent and substantial impact of harvest on soil microbial functional profiles across the region(despite a range of environmental conditions),the objective of this study was to determine the extent to which harvest also influences the structure of prokaryotic and fungal soil microbial communities,and how generalized these trends are throughout the geographic *** soil samples were collected one year before and after harvest across nine second-growth Douglas-fir forests in the Pacific *** community DNA was extracted from the soils,and high-throughput targeted gene sequencing of the 16 S r RNA gene for prokaryotes and the internal transcribed spacer(ITS)gene for fungi was *** diversity was consistently and significantly higher after harvest;it was moderately so for fungal communities(+14.6%),but only marginally so for prokaryotic communities(+2.0%).Similarly,on average,a greater proportion of the variation in the community structure of fungi(20.1%)at each site was associated with forest harvest compared to that of prokaryotes(13.2%).Overall,the greatest influence of timber harvest on soil microbial communities appeared to be a relative depletion of ectomycorrhizal fungi,with a concomitant enrichment of saprotrophic *** the short-term responses of soil microbial communities across the region,particularly those of tree root-associated symbionts,may aid our understanding of the role soil microbial communities play in ecological succession.

关键词： clear-cut Douglas-fir forest ectomycorrhizal fungi forest soil microbial community microbial diversity root-associated symbiont saprotrophic fungi

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Advances in targeted nanotherapeutics： From bioconjugation to biomimicry

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Nano Research 2018年第10期11卷 4999-5016页

作者： Danielle M. Valcourt Jenna Harris Rachel S. Riley megan Dang Jianxin Wang Emily S. Day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown Stanton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

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First complete genome sequence in Arborophila and comparative genomics reveals the evolutionary adaptation of Hainan Partridge(Arborophila ardens)

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Avian Research 2019年第1期10卷 63-70页

作者： Chuang Zhou Shuai Zheng Xue Jiang Wei Liang megan Price Zhenxin Fan Yang Meng Bisong Yue Key Laboratory of Bioresources and Ecoenvironment(Ministry of Education) College of Life SciencesSichuan University Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife College of Life SciencesSichuan University Ministry of Education Key Laboratory for Ecology of Tropical Islands College of Life SciencesHainan Normal University

Background:The Hainan Partridge(Arborophila ardens,Phasianidae,Galliformes) is an endemic species of Hainan Island,China,and it is classified as globally vulnerable *** are at least 16 species in genus Arborophila and no genome sequence is ***:The whole genome of Hainan Partridge was de novo sequenced(with shotgun approach on the Illumina 2000 platform) and ***:The genome size of Arborophila ardens is about 1.05 Gb with a high N50 scaffold length of 8.28 Mb and it is the first high quality genome announced in Arborophila *** 9.19% of the genome was identified as repeat sequences and about 5.88 million heterozygous SNPs were detected.A total of 17,376 protein-coding genes were predicted and their functions were *** genome comparison between Hainan Partridge and Red Junglefowl(Gallus gallus) demonstrated a conserved genome *** phylogenetic analysis indicated that the Hainan Partridge possessed a basal phylogenetic position in Phasianidae and it was most likely derived from a common ancestor approximately 36.8 million years ago(Mya).We found that the Hainan Partridge population had experienced bottleneck and its effective population decreased from about 1,040,000 individuals 1.5 Mya to about 200,000 individuals 0.2 Mya,and then recovered to about 460,000 *** number of 1:1 orthologous genes that were predicted to have undergone positive selection in the Hainan Partridge was 504 and some environmental adaptation related categories,such as response to ultraviolet radiation were represented in GO distribution ***:We announced the first high quality genome in Arborophila genus and it will be a valuable genomic resource for the further studies such as evolution,adaption,conservation,not only on Hainan Partridge but also on Arborophila or Phasianidae species.

关键词： Hainan Partridge Arborophila ardens Comparative genomics Positive selection

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