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Signal integration in the （m）tORC1 growth pathway

Frontiers in Biology 2018年第4期13卷 237-262页

作者： Kailash Ramlaul christopher h. S. Aylett Section of Structural Biology Department of Medicine Imperial College London SW7 2AZ UK

BACKGROUND： the protein kinase target Of Rapamycin （tOR） is a nexus for the regulation of eukaryotic cell growth. tOR assembles into one of two distinct signalling complexes, tOR complex 1 （tORC1） and tORC2 （mtORC1/2 in mammals）, with a set of largely non-overlapping protein partners. （m）tORC 1 activation occurs in response to a series of stimuli relevant to cell growth, including nutrient availability, growth factor signals and stress, and regulates much of the cell＇s biosynthetic activity, from proteins to lipids, and recycling through autophagy, mtORC1 regulation is of great therapeutic significance, since in humans many of these signalling complexes, alongside subunits of mtORC1 itself, are implicated in a wide variety of pathophysiologies, including multiple types of cancer, neurological disorders, neurodegenerative diseases and metabolic disorders including diabetes. MEthODOLOGY： Recent years have seen numerous structures determined of （m）tOR, which have provided mechanistic insight into （m）tORC 1 activation in particular, however the integration of cellular signals occurs upstream of the kinase and remains incompletely understood. here we have collected and analysed in detail as many as possible of the molecular and structural studies which have shed light on （m）tORC 1 repression, activation and signal integration. CONCLUSIONS： A molecular understanding of this signal integration pathway is required to understand how （m）tORC1 activation is reconciled with the many diverse and contradictory stimuli affecting cell growth. We discuss the current level of molecular understanding of the upstream components of the （m）tORC1 signalling pathway, recent progress on this key biochemical frontier, and the future studies necessary to establish a mechanistic understanding of this master-switch for eukaryotic cell growth.

关键词： mtORC 1 nutrient sensing GAtOR complex tSC complex Rag GtPases Rheb

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Social Vulnerability to Natural hazards in Brazil

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International Journal of Disaster Risk Science 2016年第2期7卷 111-122页

作者： Beatriz Maria de Loyola hummell Susan L.Cutter christopher t.Emrich American Red Cross Southwest Washington ChapterHumanitarian Services hazards & Vulnerability Research Institute Department of Geography University of South Carolina

Although social vulnerability has recently gained attention in academic studies, Brazil lacks frameworks and indicators to assess it for the entire *** vulnerability highlights differences in the human capacity to prepare for, respond to, and recover from disasters. It varies over space and time, and among and between social groups, largely due to differences in socioeconomic and demographic characteristics. this article provides a social vulnerability index(SoVI~) replication study for Brazil and shows how SoVI~concepts and indicators were adapted to the country. SoVI~Brazil follows the place-based framework adopted in the Social Vulnerability Index initially developed for the United States. Using a principal component analysis(PCA), 45city-level indicators were reduced to 10 factors that explain about 67 % of the variance in the data. Clearly identified spatial patterns showed a concentration of the most socially vulnerable cities in the North and Northeast regions of Brazil, as well as the social vulnerability of metropolitan areas and state capitals in the South and Southeast *** least vulnerable cities are mainly concentrated in the inland regions of the Southeast. Although different factors contribute to the social vulnerability in each city, the overall results confirm the social and economic disparities among Brazilian’s regions and reflect a differential vulnerability to natural hazards at local to regional scales.

关键词： Brazil Natural hazards Social vulnerability Social vulnerability index(SoVI)

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C_4 Plants as Biofuel Feedstocks: Optimising Biomass Production and Feedstock Quality from a Lignocellulosic Perspective

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Journal of Integrative Plant Biology 2011年第2期53卷 120-135页

作者： Caitlin S.Byrt christopher P.L.Grof Robert t.Furbank School of Environmental and Life Sciences University of NewcastleUniversity Drive CSIRO Plant Industry and high Resolution Plant Phenomics Centre

the main feedstocks for bioethanol are sugarcane （Saccharum offic- inarum） and maize （Zea mays）, both of which are C4 grasses, highly efficient at converting solar energy into chemical energy, and both are food crops. As the systems for lignocellulosic bioethanol production become more efficient and cost effective, plant biomass from any source may be used as a feedstock for bioethanol production. thus, a move away from using food plants to make fuel is possible, and sources of biomass such as wood from forestry and plant waste from cropping may be used. however, the bioethanol industry will need a continuous and reliable supply of biomass that can be produced at a low cost and with minimal use of water, fertilizer and arable land. As many C4 plants have high light, water and nitrogen use efficiency, as compared with C3 species, they are ideal as feedstock crops. We consider the productivity and resource use of a number of candidate plant species, and discuss biomass ＇quality＇, that is, the composition of the plant cell wall.

关键词： C4 Plants as Biofuel Feedstocks Optimising Biomass Production and Feedstock Quality from a Lignocellulosic Perspective

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Long-term outcomes of focal laser photocoagulation for the treatment of polypoidal choroidal vasculopathy

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International Journal of Ophthalmology(English edition) 2021年第9期14卷 1402-1407页

作者： Sooyeon Choe hyun Goo Kang Kyu hyung Park christopher Seungkyu lee Se Joon Woo Department of Ophthalmology Seoul National University College of MedicineSeoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Institute of Vision ResearchGangnam Severance HospitalYonsei University College of MedicineSeoul 06273Republic of Korea Department of Ophthalmology Seoul National University Bundang HospitalSeongnam 13620Republic of Korea Department of Ophthalmology Institute of Vision ResearchSeverance HospitalYonsei University College of MedicineSeoul 03722Republic of Korea

AIM:to evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy(PCV).MEthODS:Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2 y after focal laser photocoagulation *** patients were diagnosed with PCV using indocyanine green angiography,and eyes with other comorbid ocular diseases were *** measurement outcomes of the study were the post-treatment regression and recurrence of polyps,complications,and changes in visual *** t-test was performed to compare visual outcome before and after the ***:the mean age of the 13 patients was 70.2±5.5 y,and the follow-up period was 72.3±31.0(range,25-118)*** eyes had juxtafoveal polyps and 10 eyes had extrafoveal *** the 13 eyes,9 eyes(69.2%)had regression of polyps 1.7±1.2(range,0.9-4)mo after focal laser *** eyes(55.6%)showed recurrence of polyps during the follow-up periods,and the recurrence period was 12.8±18.9(range,1.9-48)*** subretinal hemorrhage occurred in two eyes(15.4%)27 and 72 d after laser treatment,*** were no statistically significant differences in visual acuities at baseline;1,2,3 y post-treatment(all P>0.05);and last follow-up(0.63±0.5,0.73±0.70,0.67±0.57,0.75±0.7,and 0.95±0.8 log MAR,respectively).CONCLUSION:Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term ***,it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

关键词： long-term efficacy polypoidal choroidal vasculopathy focal laser photocoagulation

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high-Content Screening and Analysis of Stem Cell-Derived Neural Interfaces Using a Combinatorial Nanotechnology and Machine Learning Approach

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Research 2023年第1期2022卷 153-167页

作者： Letao Yang Brian M.Conley Jinho Yoon christopher Rathnam thanapat Pongkulapa Brandon Conklin Yannan hou Ki-Bum lee Department of Chemistry and Chemical Biology Rutgers UniversityThe State University of New JerseyPiscatawayNJ 08854USA

A systematic investigation of stem cell-derived neural interfaces can facilitate the discovery of the molecular mechanisms behind cell behavior in neurological disorders and accelerate the development of stem cell-based ***,high-throughput investigation of the cell-type-specific biophysical cues associated with stem cell-derived neural interfaces continues to be a significant obstacle to *** this end,we developed a combinatorial nanoarray-based method for high-throughput investigation of neural interface micro-/nanostructures(physical cues comprising geometrical,topographical,and mechanical aspects)and the effects of these complex physical cues on stem cell fate ***,by applying a machine learning(ML)-based analytical approach to a large number of stem cell-derived neural interfaces,we comprehensively mapped stem cell adhesion,differentiation,and proliferation,which allowed for the cell-type-specific design of biomaterials for neural interfacing,including both adult and human-induced pluripotent stem cells(hiPSCs)with varying genetic *** short,we successfully demonstrated how an innovative combinatorial nanoarray and ML-based platform technology can aid with the rational design of stem cell-derived neural interfaces,potentially facilitating precision,and personalized tissue engineering applications.

关键词： overcome neural rational

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transport of gold by h_2S-rich oil field waters, and the origin of Carlin-type deposits

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Chinese Science Bulletin 1999年第S2期44卷 161-162页

作者： christopher h. Gammons Diane Wolfgram Montana tech of the University of Montana Dept. of Geological Engineering Butte MT 59701 USA

DURING the course of hydrocarbon evolution and migration, large quantities of h 2S are often *** process is most familiar to petroleum geologists, and may lead to forming of natural gas deposits. themost important h2S-forming reactions are bacterial sulfate reduction （BSR）, and thermochemical sulfatereduction （tSR）. Whereas BSR is restricted to relatively low temperature （<100℃） and shallowdepths, tSR becomes important at elevated temperature （>150℃） and greater depth of burial. Becauseh2S is highly soluble in water, any groundwater in the vicinity of a tSR-active zone will also become enriched in h2S. the central hypothesis of this paper is that hot groundwaters associated with tSR in carbonate terrains acquire the ability to transport gold and other elements （e.g. Ag, hg, As, Sb, tl）

关键词： transpore gold oil field water origin Carlin-type deposit.

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Structural Flexibility Enables Alternative Maturation, ARGONAUtE Sorting and Activities of miR168, a Global Gene Silencing Regulator in Plants

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Molecular Plant 2018年第8期11卷 1008-1023页

作者： taichiro Iki Antoine Cléry Nicolas G. Bologna Alexis Sarazin christopher A. Brosnan Nathan Pumplin Frédéric h.t. Allain Olivier Voinnet Department of Biology Swiss Federal Institute of Technology (ETH) Universit&tstrasse 2 ZUrich 8092 Switzerland Institute of Molecular Biology and Biophysics Department of Biology Swiss Federal Institute of Technology (ETH) Zürich Switzerland Biomolecular NMR spectroscopy Platform ETH Zürich Switzerland Present address: Laboratory of Germline Biology Graduate School of Frontier Biosciences Osaka University 1-3 Yamadaoka Suita Osaka Japan

In eukaryotes, the RNase-Ⅲ Dicer often produces length/sequence microRNA （miRNA） variants, called ＂isomiRs＂, owing to intrinsic structural/sequence determinants of the miRNA precursors （pre-miRNAs）. In this study, we combined biophysics, genetics and biochemistry approaches to study Arabidopsis miR168, the key feedback regulator of central plant silencing effector protein ARGONAUtE1 （AGO1）. We identified a motif conserved among plant premiR168 orthologs, which enables flexible internal basepairing underlying at least three metastable structural configurations. these configurations promote alternative, accurate Dicer cleavage events generating length and structural isomiR168 variants with distinctive AGO sorting properties and modes of action. Among these isomiR168s, a duplex with a 22-nt guide strand exhibits strikingly preferential affinity for AGO10, the closest AGO1 paralog. the 22-nt miR168-AGO10 complex antagonizes AGO1 accumulation in part via ＂transitive RNAi＂, a silencing-amplification process, to maintain appropriate AGO1 cellular homeostasis. Furthermore, we found that the tombusviral P19 silencing-suppressor protein displays markedly weaker affinity for the 22-nt form among its isomiR168 cargoes, thereby promoting AGO10-directed suppression of AGOl-mediated antiviral silencing. taken together, these findings indicate that structural flexibility, a previously overlooked property of premiRNAs, considerably increases the versatility and regulatory potential of individual MIRNA genes, and that some pathogens might have evolved the capacity or mechanisms to usurp this property.

关键词： microRNA miR168 Dicer ARGONAUtE tombusvirus P19

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Wing, tail, and vocal contributions to the complex acoustic signals of courting Calliope hummingbirds

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Current Zoology 2011年第2期57卷 187-196页

作者： christopher James CLARK Peabody Museum of Natural history Yale University PO Box 208106 New Haven CT 06511 USA Museum of Vertebrate Zoology University of California- Berkeley Berkeley CA USA

Multi-component signals contain multiple signal parts expressed in the same physical modality. One way to identify individual components is if they are produced by different physical mechanisms. here, I studied the mechanisms generating acoustic signals in the courtship displays of the Calliope hummingbird Stellula calliope. Display dives consisted of three synchronized sound elements, a high-frequency tone （hfl）, a low frequency tone （lft）, and atonal sound pulses （asp）, which were then followed by a frequency-modulated fall. Manipulating any of the rectrices （tail-feathers） of wild males impaired production of the lft and asp but not the hfl or fall, which are apparently vocal. I tested the sound production capabilities of the rectrices in a wind tunnel. Single rectrices could generate the lft but not the asp, whereas multiple rectrices tested together produced sounds sitlfilar to the asp when they fluttered and collided with their neighbors percussively, representing a previously unknown mechanism of sound production. During the shuttle display, a trill is generated by the wings during pulses in which the wingbeat frequency is elevated to 95 hz, 40% higher than the typical hovering wingbeat frequency. the Calliope hummingbird courtship displays include sounds produced by three independent mechanisms, and thus include a minimum of three acoustic signal components. these acoustic mechanisms have different constraints and thus potentially contain different messages. Producing multiple acoustic signals via multiple mechanisms may be a way to escape the constraints present in any single mechanism .

关键词： Calliope hummingbird Courtship Multicomponent Signal Sonation Wind tunnel

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Cirrhotic ascites review: Pathophysiology, diagnosis and management

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World Journal of hepatology 2013年第5期5卷 251-263页

作者： christopher M Moore David h Van thiel Section of hepatology Department of MedicineRush University Medical CenterChicagoIL 60612United States

Ascites is a pathologic accumulation of peritoneal fluidcommonly observed in decompensated cirrhotic states. Its causes are multi-factorial, but principally involve significant volume and hormonal dysregulation in the setting of portal hypertension. the diagnosis of ascites is considered in cirrhotic patients given a constellation of clinical and laboratory findings, and ultimately confirmed, with insight into etiology, by imaging and paracentesis procedures. treatment for ascites is multimodal including dietary sodium restriction, pharmacologic therapies, diagnostic and therapeutic paracentesis, and in certain cases transjugular intra-hepatic portosystemic shunt. Ascites is associated with numerous complications including spontaneous bacterial peritonitis, hepato-hydrothorax and hepatorenal syndrome. Given the complex nature of ascites and associatedcomplications, it is not surprising that it heralds increased morbidity and mortality in cirrhotic patients and increased cost-utilization upon the health-care system. this review will detail the pathophysiology of cirrhotic ascites, common complications derived from it, and pertinent treatment modalities.

关键词： Ascites Cirrhosis hepato-hydrothorax hepatorenal syndrome Spontaneous bacterial peritonitis

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Selective androgen receptor modulators for the treatment of late onset male hypogonadism

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Asian Journal of Andrology 2014年第2期16卷 256-261,I0009页

作者： christopher C Coss Amanda Jones Michael L hancock Mitchell S Steiner James t Dalton Gtx Inc. Memphis Tennessee USA.

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. these therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. the brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

关键词： hypogonadism late onset hypogonadism selective androgen receptor modulators testosterone

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