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Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： SANDRA STICKLER BARBARA RATH gERHARD hamilton Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for ***,the most common KRAS mutations in PDAC are g12D(44%),g12V(34%)and g12R(20%)that are not amenable to treatment by KRAS g12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** g12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS g12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(gEF)Son of Sevenless 1 that drives *** agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

Development of PROTACS degrading KRAS and SOS1

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Oncology Research 2024年第8期32卷 1257-1264页

作者： gERHARD hamilton MARIE-THERESE EggERSTORFER SANDRA STICKLER Institute of Pharmacology Medical University of ViennaVienna1090Austria

The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung ***,KRAS g12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of ***,the range of other KRAS mutations is not amenable to treatment and the g12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 *** approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of ***,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal *** of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not *** CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental *** to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin *** highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

关键词： Proteolysis-targeting chimeras(PROTACs) Kirsten rat sarcoma virus(KRAS) Son of sevenless 1(SOS1) Von Hippel-Lindau Cereblon

Optical measurements of dissolved organic matter as proxies for COD_(Mn)and BOD_(5)in plateau lakes

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Environmental Science and Ecotechnology 2024年第3期19卷 132-138页

作者： Xuan Yang Yongqiang Zhou Xiaoying Yang Yunlin Zhang Robert g.M.spencer Justin D.Brookes Erik Jeppesen Hucai Zhang Qichao Zhou Institute for Ecological Research and Pollution Control of Plateau Lakes School of Ecology and Environmental SciencesYunnan UniversityKunming650500China Institute of International River and Eco-security Yunnan UniversityKunming650500China Zhejiang College of Security Technology Wenzhou325016China Taihu Laboratory for Lake Ecosystem Research State Key Laboratory of Lake Science and EnvironmentNanjing Institute of Geography and LimnologyChinese Academy of SciencesNanjing210008China Department of Earth Ocean and Atmospheric ScienceFlorida State UniversityTallahassee32306United States Water Research Centre School of Biological ScienceThe University of AdelaideAdelaide5005Australia Department of Ecoscience Aarhus UniversityAarhus8000Denmark Sino-Danish Centre for Education and Research Chinese Academy of SciencesBeijing100101China Limnology Laboratory Department of Biological Sciences and Centre for Ecosystem Research and ImplementationMiddle East Technical UniversityAnkara06800Turkey Institute of Marine Sciences Middle East Technical UniversityErdemliMersin33731Turkey Yunnan Key Laboratory of Pollution Process and Management of Plateau Lake-Watershed Yunnan Research Academy of Eco-environmental SciencesKunming650034China

The presence of organic matter in lakes profoundly impacts drinking water supplies,yet treatment processes involving coagulants and disinfectants can yield carcinogenic disinfection *** assessments of organic matter,such as chemical oxygen demand(COD_(Mn))and biochemical oxygen demand(BOD_(5)),are often ***,optical measurements of dissolved organic matter(DOM)offer a rapid and reliable means of obtaining organic matter composition *** we employed DOM optical measurements in conjunction with parallel factor analysis to scrutinize COD_(Mn)and BOD_(5)*** was performed using an independent dataset encompassing six lakes on the Yungui Plateau from 2014 to 2016(n=256).Leveraging multiple linear regressions(MLRs)applied to DOM absorbance at 254 nm(a254)and fluorescence components C1-C5,we successfully traced COD_(Mn)and BOD_(5)variations across the entire plateau(68 lakes,n=271,R^(2)>0.8,Pgher R^(2))of COD_(Mn)and BOD_(5)during the rainy season compared to the dry season and demonstrated increased accuracy(R^(2)>0.9)in mesotrophic lakes compared to oligotrophic and eutrophic *** study underscores the utility of MLR-based DOM indices for inferring COD_(Mn)and BOD_(5)variability in plateau lakes and highlights the potential of integrating in situ and remote sensing platforms for water pollution early warning.

关键词： Dissolved organic matter Chemical oxygen demand Biochemical oxygen demand Water quality Yungui plateau lakes

Colorful facial markings are associated with foraging rates and affiliative relationships in a wild group-living cichlid fish

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Current Zoology 2024年第1期70卷 70-78页

作者： Brett M.Culbert James B.Barnett Isaac Y.Ligocki Matthew g.Salena Marian Y.L.Wong Ian M.hamilton Sigal Balshine Department of Integrative Biology University of GuelphGuelphOntarioCanada Department of Psychology Neuroscience&BehaviourMcMaster UniversityHamiltonOntarioCanada Department of Evolution Ecologyand Organismal BiologyThe Ohio State UniversityColumbusOHUSA Department of Biology Millersville UniversityMillersvillePAUSA School of Earth Atmospheric and Life SciencesUniversity of WollongongWollongongNew South WalesAustralia Department of Mathematics The Ohio State UniversityColumbusOHUSA

Many animals use color to signal their quality and/or behavioral *** signals have been well studied in the contexts of competi-tion and mate choice;however,the role of these signals in nonsexual,affiliative relationships is not as well ***,we used wild social groups of the cichlid fish Neolamprologus pulcher to investigate whether the size of a brightly colored facial patch was related to 1)individual quality,2)social dominance,and/or 3)affiliative *** with larger patches spent more time foraging and tended to perform more aggressive acts against conspecific territory *** did not find any evidence that the size of these yellow patches was related to social rank or body size,but dominant males tended to have larger patches than dominant ***,patch size had a rank-specific relationship with the number of affiliative interactions that individuals engaged *** males with large patches received fewer affiliative acts from their groupmates compared to dominant males with small ***,subordinates with large patches tended to receive more affiliative acts from their groupmates while performing fewer affiliative acts *** together,our results suggest that patch size reflects interindividual variation in foraging effort in this cichlid fish and offer some of the first evidence that colorful signals may shape affiliative relationships withinwildsocialgroups.

关键词： affiliation foraging Lake Tanganyika Neolamprologus pulcher visual signals

Importance of periphytic biofilms for carbon cycling in paddy fields:A review

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Pedosphere 2024年第1期34卷 36-43页

作者： Lei ZHOU Yonghong WU Junzhuo LIU Pengfei SUN Ying XU Jan DOLFINg Robert gMspencer Erik JEPPESEN State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China Zigui Three gorges Reservoir Ecosystem Observation and Research Station of Ministry of Water Resources of the People's Republic of ChinaYichang 443605China College of Nanjing University of Chinese Academy of SciencesNanjing 211135China Faculty of Energy and Environment Northumbria UniversityNewcastle upon Tyne NE18QHUK Department of Earth Ocean and Atmospheric ScienceFlorida State UniversityTallahassee FL 32306USA Department of Ecoscience&Centre for Water Technology(WATEC) Aarhus UniversityAarhus DK-8000Denmark Sino-Danish Centre for Education and Research Beijing 100049China Limnology Laboratory Department of Biological Sciences and Centre for Ecosystem Research and Implementation(EKOSAM)Middle East Technical UniversityAnkara 06800Turkiye Institute of Marine Sciences Middle East Technical UniversityMersin 33731Turkiye

Paddy fields play an important role in global carbon(C) cycling and are an important source of methane(CH_(4)) emissions. Insights into the processes influencing the dynamics of soil organic C(SOC) in paddy fields are essential for maintaining global soil C stocks and mitigating climate change. Periphytic biofilms composed of microalgae, bacteria, and other microorganisms are ubiquitous in paddy fields, where they directly mediate the transfer of elements at the soil-water interface. However, their contributions to C turnover and exchange have been largely neglected. Periphytic biofilms affect and participate in soil C dynamics by altering both abiotic(e.g., pH and redox potential) and biotic conditions(e.g., microbial community composition and metabolism). This review summarizes the contributions of periphytic biofilms to soil C cycling processes, including carbon dioxide fixation, SOC mineralization, and CH_(4) emissions. Future research should be focused on: i) the mechanisms underlying periphytic biofilm-induced C fixation and turnover and ii) quantifying the contributions of periphytic biofilms to soil C uptake, stabilization, and sequestration in paddy fields.

关键词： carbon fixation carbon mineralization carbon sequestration methane emission microbial aggregates soil organic carbon

Permian–Triassic Charophytes: Distribution, Biostratigraphy and Biotic Events

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Journal of Earth Science 2018年第4期29卷 778-793页

作者： spencer g Lucas New Mexico Museum of Natural History 1801 Mountain Road N. W. Albuquerque New Mexico 87104 USA

Permian charophytes are known from the Ukraine, Russia, Kazakhstan, germany, Saudi Arabia, China, the USA, Brazil, Paraguay and India. Most of these records are of Middle- Late Permian Age and are the basis of local biostratigraphic zonation in southern Russia and China. Development of a robust Permian charophyte biostratigraphy will require a more extensive record. Triassic charopbytes are known from germany, Sweden, Poland, Slovenia, Bulgaria, the Ukraine, Russia, Morocco, Congo, the USA, Argentina, Kazakhstan and China. This encompasses records from all Triassic stages and has been the basis of detailed biostratigraphic zonation in southern Russia-Kazakhstan-eastern Europe. Permian and Triassic charophyte biostratigraphy at the level of genus does not provide detailed correlations beyond local or regional schemes. Nevertheless, it does identify some important evolutionary datums that constrain the timing of important biotic events in the Permian-Triassic evolutionary history of the Charophyta, including：（1） Early Permian extinction of the Palaeocharaceae; （2） Late Permian extinction of the ＂Trochiliscales＂（Moellerinales）; （3） Carboniferous origin of the paraphyletic Porocharaceae, soon followed during the Permian by the origin of the multicellular basal plate; and （4） an important generic turnover of charophytes across the Triassic-Jurassic boundary, though there are insufficient data to identify this as a mass extinction.

关键词： Permian Triassic charophytes biostratigraphy biotic events.

Corrigendum to“Optical measurements of dissolved organic matter as proxies for COD_(Mn)and BOD_(5)in plateau lakes”[***.19(2024)100326]

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Environmental Science and Ecotechnology 2024年第4期20卷 140-140页

The authors regret that the following statements in the original article were wrong and have been *** authors would like to apologise for any inconvenience caused.

关键词： plateau dissolved wrong

Determination of the Optimal Level of Equity Financing for global Banks

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Determination of the Optimal Level of Equity Financing for G...

Paleosols of the upper Paleozoic Sangre de Cristo Formation,north-central New Mexico:Record of early Permian palaeoclimate in tropical Pangaea

International Conference on Systems Science and Engineering(ICSSE’88)

作者： Leslie P.Anderson Janet g.hamilton Sufenne Hung Department of Finance Portland State University Portland OR 97207 Department of Finance Portland State University Portland OR 97207 Poly-Analytics Inc. Knoxville Tennessee

＜正＞ This paper discusses the determination of the optimal capital structure for banking institutions. An evaluation of the capital adequacy standards proposed by the Basle Committee is also presented. A major conclusion is that bankers are best left to determine the capital structure for these banks since regulatory imposed standards may result in sub-optimal banking activities.

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Journal of Palaeogeography 2017年第2期6卷 144-161页

作者： Lawrence H. Tanner spencer g. Lucas Department of Biological Sciences Le Moyne CollegeSyracuseNY 13214USA New Mexico Museum of Natural History 1801 Mountain Road N.W.AlbuquerqueNM 87014USA

The lower Permian(Wolfcampian) Sangre de Cristo Formation of northern New Mexico consists of silty mudstones and laterally discontinuous sandstones deposited on an aggrading alluvial ***,mudstones display a variety of pedogenic *** mudstone fabrics vary from platy to prismatic;some beds display prominent pedogenic ***-colored root traces are common throughout the section,as are calcareous nodules,which vary from small bodies with diffuse boundaries to vertically stacked,discrete,cm-scale nodules(rhizocretions),and less commonly form coalescing *** occur only in the lower portion of the ca.90-m measured *** of the mudstone beds contain calcretes that are immature(calcic Protosols to calcic Argillisols),but the lower to middle portion of the section also contains mature calcrete horizons(argillic Calcisols and Calcisols).Intercalated micritic limestone beds with sharp contacts containing root traces,are of laterally variable thickness and grade to nodular *** are interpreted as floodplain pond carbonates that have undergone pedogenic alteration(palustrine limestones),indicating long periods of exposure under strongly seasonal climatic *** isotopic composition of the pedogenic carbonate displays a substantial range of values,but most of the range of variation in isotopic composition is accounted for by isotopically heavier carbonate(both carbon and oxygen) precipitated in shallow ponds subject to intense pedogenic reworking(palustrine carbonate).During the early Permian,northern New Mexico was situated in a near equatorial position(ca.4° N).The overall character of the paleosols suggests a persistent warm,semi-humid,seasonal climate throughout most of the interval of deposition during the Wolfcampian,but with episodically increased aridity during formation of the more mature *** long-term trend of climate change is evident in the stratigraphic section examined for this study.

关键词： Sangre de Cristo Formation Wolfcampian Vertisol Argillisol Calcisol Protosol