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General Psychiatry 2020年第1期33卷 23-29页

作者： Donald J Robinaugh Mackenzie L Brown Olivia M Losiewicz Payton J Jones Luana Marques amanda w baker Department of Psychiatry Massachusetts General HospitalBostonMassachusettsUSA Department of Psychiatry Harvard Medical SchoolBostonMassachusettsUSA Department of Psychology Harvard UniversityCambridgeMassachusettsUSA

Background Treatments for anxiety disorders are among the most effective in ***,there is considerable room for *** In this paper,we discuss the value of ecological momentary assessment as a research method and clinical *** we begin by describing ecological momentary assessment and its advantages,including the ability to collect ecologically valid information about mental disorders,in real time,in individual *** then illustrate the value of this approach for anxiety disorder treatment using two patients with panic disorder who completed ecological momentary assessments for 2 weeks before and after a cognitive-behavioural therapy *** focus especially on two key pieces of information provided by ecological momentary assessment data:information about symptom dynamics and information about the relationships among symptoms as they unfold overtime within individual *** Although considerable work is needed to further develop this methodology in the context of anxiety disorder treatment,we believe that these pieces of information may ultimately inform our understanding of how anxiety disorder treatments have their effect and how those treatments can be tailored to individual patients.

关键词： disorders moment treatment

The pig as a preclinical traumatic brain injury model:current models,functional outcome measures,and translational detection strategies

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Neural Regeneration Research 2019年第3期14卷 413-424页

作者： Holly A.Kinder Emily w.baker Franklin D.west Regenerative Bioscience Center University of Georgia Department of Animal and Dairy Science University of Georgia

Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.

关键词： traumatic brain injury large animal model pig model diffuse axonal injury functional outcome assessment measures controlled cortical impact model fluid percussion injury model magnetic resonance imaging,biomarkers

Labial tip sensilla of Blissus leucopterus leucopterus （Hemiptera： Blissidae）： Ultrastructure and behavior

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Insect Science 2008年第3期15卷 271-275页

作者： Gerald T. baker Xiong Chen Peter w.K. Ma Department of Entomology and Plant Pathology Box 9775 Mississippi State University Mississippi State MS 39762 USA

The cuticular sensory receptors that are found on the apex of the labium of hemipterans play an important role in their feeding behavior. In this study we describe the ultrastructure, number, and distribution of sensilla on the labium apex of the chinch bug, Blissus leucopterus leucopterus. Each apical field of sensilla on the labium contains 11 uniporous peg sensilla and one sensillum chaeticum. The uniporous peg sensilla are innervated by 4-5 bipolar neurons that send dendrites in the lumen of each peg. Three neurons are associated with each sensillum chaeticum, two neurons have dendrites in the lumen of the sensillum, and the third dendrite ends in a tubular body at the base of the sensillum. Behavioral tests that involve chemical blockage of the sensory receptors show the importance of the labial sensilla in feeding behavior. Both morphological and behavioral evidence indicate that the labial sensilla have a chemosensitive function.

关键词： behavioral tests chinch bug electron microscopy labial sensilla Nmethylmaleimide

Cross-Polarized GPR Imaging of Fracture Flow Channeling

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Journal of Earth Science 2015年第6期26卷 776-784页

作者： Georgios P.Tsoflias Christopher Perll Matthew baker Matthew w.Becker Department of Geology the University of Kansas Chesapeake Energy Marathon Oil Corporation California State University Long Beach

Ground penetrating radar（GPR） can be used to image fractures and monitor fluid flow in the subsurface. Conventional GPR imaging uses single-polarization, co-polarized acquisition. we examine the use of cross-polarized GPR signals for imaging flow channeling in a discrete horizontal fracture. Numerical modeling（FDTD） demonstrates that when the fracture channel is oriented at an oblique angle to the survey line, depolarization of the GPR signal results in scattered energy along the cross-polarized components. when the channel is oriented parallel or orthogonal to the survey line, all scattered energy is captured by the co-polarized components and no signal is present in the cross-polarized orientation. Multipolarization, time-lapse 3D GPR field data were acquired at the Altona Flat Rock test site in New York State. The GPR surveys were conducted during background fresh fracture water conditions and during a natural gradient saline tracer test which was used to highlight flow channels along a sub-horizontal fracture. Amplitude analysis of the cross-polarized data reveals flow channeling that is in agreement with the co-polarized GPR images and with independent hydraulic tests. This investigation demonstrates that cross-polarized components of GPR signals can be used to enhance imaging of flow channels in fractured media.

关键词： GPR single-polarization cross-polarized data rapid flow saline tracer fractured rock.

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

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Protein & Cell 2014年第8期5卷 569-579页

作者： Jie Na Duncan baker Jing Zhang Peter w. Andrews Ivana Barbaric School of Medicine Tsinghua University Beijing 100084 China Sheffield Diagnostic Genetic Services Sheffield Children's Hospital Sheffield S10 2TH UK Centre for Stem Cell Biology Department of Biomedical Science The University of Sheffield Sheffield S10 2TN UK

Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. we point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.

关键词： human pluripotent stem cells (hPSCs),culture adaptation aneuploidy cancer genetic changes

Computationally designed protein activation

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National Science Review 2019年第4期6卷 609-610页

作者： David baker Department of Biochemistry Institute for Protein Design University of Washington Howard Hughes Medical Institute

Time-resolved tools for activating proteins of interest in living systems can allow monitoring of the dynamics of biological processes such as signal transduction. Various approaches have been developed to engineer both constitutive and inducible protein activation (e.g. genetic fusion of light switchable proteins).Active-site decaging is another strategy,but the limited number of genetically encoded unnatural amino acids and associ-

关键词： pro Rosetta Computationally designed protein activation

The role of phosphorus in the metabolism of arsenate by a freshwater green alga, Chlorella vulgaris

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Journal of Environmental Sciences 2016年第11期28卷 169-178页

作者： Josh baker Dirk wallschlager Trent University Environmental and Life Sciences Graduate Program 1600 West Bank Dr Peterborough ON K9L 0G2 Canada School of the Environment Department of Chemistry and Water Quality Centre Trent University 1600 West Bank Dr Peterborough ONK9L 0G2 Canada

A freshwater microalga, Chlorella vulgaris, was grown in the presence of varying phosphate concentrations（〈 10–500 μg/L P） and environmentally realistic concentrations of arsenate（As（Ⅴ））（5–50 μg/L As）. Arsenic speciation in the culture medium and total cellular arsenic were measured using AEC-ICP-MS and ICP-DRC-MS, respectively, to determine arsenic biotransformation and uptake in the various phosphorus scenarios. At high phosphate concentration in the culture medium, 〉 100 μg/L P, the uptake and biotransformation of As（Ⅴ） was minimal and dimethylarsonate（DMAs（Ⅴ）） was the dominant metabolite excreted by C. vulgaris, albeit at relatively low concentrations. At common environmental P concentrations, 0–50 μg/L P, the uptake and biotransformation of As（Ⅴ） increased. At these higher As-uptake levels, arsenite（As（Ⅲ）） was the predominant metabolite excreted from the cell. The concentrations of As（Ⅲ） in these low P conditions were much higher than the concentrations of methylated arsenicals observed at the various P concentrations studied. The switchover threshold between the（small） methylation and（large） reduction of As（Ⅴ） occurred around a cellular As concentration of 1 fg/cell. The observed nearly quantitative conversion of As（Ⅴ） to As（Ⅲ） under low phosphate conditions indicates the importance of As（Ⅴ） bio-reduction at common freshwater P concentrations. These findings on the influence of phosphorus on arsenic uptake, accumulation and excretion are discussed in relation to previously published research. The impact that the two scenarios of As（Ⅴ） metabolism, As（Ⅲ） excretion at high As（Ⅴ）-uptake and methylarsenical excretion at low As（Ⅴ）-uptake, have on freshwater arsenic speciation is discussed.

关键词： Arsenic Speciation Phosphorus Freshwater algae Toxicity Biotransformation

The ＇omics revolution and our understanding of sperm cell biology

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Asian Journal of Andrology 2011年第1期13卷 6-10页

作者： Mark A baker School of Environmental and Life Sciences University of Newcastle Research Fellow Priority Research Centre in Reproductive Science University of Newcastle Callaghan NSW 2308 Australia

The foundations of proteomics are to study gene products and their regulatory roles within cells. Paradoxically, the only evidence that sperm cells make new proteins is through mitochondrial protein synthesis. Yet despite this, spermatozoa are the perfect candidates for mass spectrometry and hence, proteomic analysis. These enterprising cells use a plethora of post-translational modifications in order to gain functionality following their production within the testis. By using a combination of two-dimensional polyacrylamide gel electrophoresis （2D-PAGE）, and more recently liquid chromatography-mass spectrometry （LC-MS）/MS, recent advances in sperm cell biology, through the use of proteomics, is making unparalleled progress. The protein inventory lists being generated have shed light on transmembrane proteins, kinases and chaperones never previously recognized. In addition, the ability to isolate either phosphopeptides or glycopeptides and quantify the differences between cells of two different populations make proteomic analysis of spermatozoa a real chance to finally answer some age old questions.

关键词： capacitation DIGE epididymis LC-MS proteomics quantitation sperm maturation spermatozoa

Nucleotide sequence conservation of novel and established cis-regulatory sites within the tyrosine hydroxylase gene promoter

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Frontiers in Biology 2015年第1期10卷 74-90页

作者： Meng wANG Kasturi BANERJEE Harriet baker John w. CAVE Burke Medical Research Institute White Plains NY 10605 USA weill Cornell Medical College Brain and Mind Research Institute NY 10065 USA

Tyrosine hydroxylase （TH） is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter （〈 1 kb upstream from the transcription start site） is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these dements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority. In this study, we align TH proximal promoter nucleotide sequences from several vertebrate species to identify evolutionarUy conserved motifs. This analysis identified three elements （a TATA box, cyclic AMP response element （CRE） and a 5＇-GGTGG-3＇ site） that constitute the core of an ancient vertebrate TH promoter. Focusing on only eutherian mammals, two regions of high conservation within the proximal promoter were identified： a -250 bp region adjacent to the transcription start site and a -85 bp region located approximately 350 bp further upstream. within both regions, conservation of previously reported cis-regulatory motifs and human single nucleotide variants was evaluated. Transcription reporter assays in a TH-expressing cell line demonstrated the functionality of highly conserved motifs in the proximal promoter regions and electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding （CREB） protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cisregulatory motifs that underlie a core set of regulatory mechanisms in mammals.

关键词： catecholamine dopamine transcription evolution

Evaluation and assessment of semen for IVF/ICSI

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Asian Journal of Andrology 2002年第4期4卷 281-285页

作者： D.Y. Liu H.w.G. baker University of Melbourne Department of Obstetrics and Gynaecology and Melbourne IVF and Reproductive Services Royal Women's Hospital Carlton Victoria 3053 AustraliaUniversity of Melbourne Department of Obstetrics and Gynaecology and Melbourne IVF and Reproductive Services Royal Women's Hospital Carlton Victoria 3053 Australia

Evaluation and assessment of semen is very important for both diagnosis of male infertility and selection of patients for treatment with IVF or ICSI. In standard IVF, sperm function is essential for normal fertilization: sperm must be able to bind to zona pellucida (ZP), undergo the acrosome reaction and penetrate the ZP and fuse with the oolemma before fertilization takes place. In contrast, most sperm functions are not required for fertilization in ICSI since sperm bypass the ZP and oolemma by injection of a single sperm directly into cytoplasm of oocyte. Therefore, the clinical decision on treatment of patients with either IVF or ICSI is mostly dependent on results of sperm tests. However, conventional semen analyses do not provide accurate information about sperm fertilizing ability since many patients with subtle sperm defects can not be detected. More advanced sperm function tests are required to detect sperm defects that may lead to failure of fertilization in standard IVF. In the last 15 years we performed extensive studies on relationship between sperm functions and fertilization rates by logistic regression analysis in large numbers of IVF patients including 370 patients with zero fertilization rate by IVF. we confirmed sperm morphology assessed strictly was strongly related to fertilisation rate with standard IVF. Thus sperm morphology assessment is very useful for selection of patients for ICSI. we also developed a number of new tests including sperm-ZP binding, sperm-ZP penetration and the ZP-induced AR and evaluated the clinical value of these tests. Sperm-ZP binding and sperm-ZP penetration tests are the most powerful indicators for sperm fertilizing ability in vitro. The ZP-induced AR is highly correlated with sperm-ZP penetration. we discovered a condition we call disordered ZP-induced AR which causes serve infertility in up to 25% men with otherwise idiopathic infertility In conclusion, the combination of semen analysis with advanced sperm function

关键词： male infertility sperm function tests sperm-oocyte interactions IVF/ICSI