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Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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Science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran Olivia Cano-Garrido Naroa Serna Hector Lopez-Laguna laura sanchez-garcia Mireia Pesarrodona Alejandro sanchez-Chardi Ramon Mangues Antonio Villaverde Esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 *** these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

Removal of saxitoxin and anatoxin-a by PAC in the presence and absence of microcystin-LR and/or cyanobacterial cells

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Journal of Environmental Sciences 2023年第6期128卷 161-170页

作者： Justin Rorar laura Davila garcia Teresa Cutright Department of Civil Engineering The University of AkronOH 44325-3905USA

Cyanobacteria can produce cyanotoxins such as microcystin-LR(MC),saxitoxin(STX),and anatoxin-a(ANTX-a)which are harmful to humans and other *** removal efficiencies of STX and ANTX-a by powdered activated carbon(PAC)was investigated,aswell as when MC-LR and cyanobacteriawere *** conductedwith distilled water and then source water,using the PAC dosages,rapid mix/flocculation mixing intensities and contact times of two drinking water treatment plants in northeast *** pH 8 and 9,STX removal was 47%-81%in distilled water and 46%-79%in source water,whereas it was 0-28%for pH 6 in distilled water and 31%-52%in source *** 1.6μg/L or 20μg/L MC-LR was present with STX,STX removal was increased with PAC simultaneously removing 45%-65%of the 1.6μg/L MC-LR and 25%-95%of the 20μg/L MC-LR depending on the ***-a removal at pH 6 was 29%-37%for distilled water and 80%for source water,whereas it was 10%-26%for pH 8 in distilled water and 28%for pH 9 in source *** presence of cyanobacteria cells decreased ANTX-a removal by at least 18%.When 20μg/L MC-LR was present with ANTX-a in source water,59%-73%ANTX-a and 48%-77%of MCLR was removed at pH 9 depending on the PAC *** general,a higher PAC dose led to higher cyanotoxin *** study also documented that multiple cyanotoxins can be effectively removed by PAC for water at pH’s between 6 and 9.

关键词： pH Cyanotoxins Cyanobacteria PAC Microcystin Saxitoxin Anatoxin-a

Reconstruction of lateral root formation through single-cell RNA sequencing reveals order of tissue in itiation

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Molecular Plant 2021年第8期14卷 1362-1378页

作者： laura Serrano-Ron Pablo Perez-garcia Alvaro sanchez-Corrionero Inmaculada Gude Javier Cabrera Pui-Leng Ip Kenneth D.Birnbaum Miguel A.Moreno-Risueno Centro de Biotecnologia y Genomica de Plantas Universidad Politecnica de Madrid(UPM)-lnstituto Naci on al de Investigacion y Tec no logia Agraria y Alimentaria(INIA)Pozuelo de Alarcon28223 MadridSpain Departamento de Biotecnologia-Biologia Vegetal Escuela Tecnica Superior de Ingenieria AgronomicaAlimentaria y de BiosistemasUniversidad Politecnica de Madrid(UPM)28040 MadridSpain Center for Genomics and Systems Biology Department of BiologyNew York UniversityNew YorkNYUSA

Postembryonic organogenesis is critical for plant ***,lateral roots(LRs)form the bulk of mature root systems,yet the ontogeny of the LR primordium(LRP)is not *** this study,we performed the single-cell RNA sequencing through the first four stages of LR formation in *** analysis led to a model in which a single group of precursor cells,with a cell identity different from their pericycle origins,rapidly reprograms and splits into a mixed ground tissue/stem cell niche fate and a vascular precursor *** ground tissue and stem cell niche fates soon separate and a subset of more specialized vascular cells form sucrose transporting phloem cells that appear to connect to the primary *** did not detect cells resembling epidermis or root cap,suggesting that outer tissues may form later,preceding LR *** this stage,some remaining initial precursor cells form the primordium flanks,while the rest create a reservoir of pluripotent cells that are able to replace the LR if *** ablation of the central and lateral LRP regions showed that remaining cells restart the sequence of tissue initiation to form a ***,our study reveals an ontological hierarchy for LR formation with an early and sequential split of main root tissues and stem cells.

关键词： organogenesis patterning stem cells single-cell RNA-seq cell fate regeneration

Social correlates of sedentary behavior in young people:The UP&DOWN study

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Journal of Sport and Health Science 2020年第2期9卷 189-196页

作者： Veronica Cabanas-sanchez laura garcia-Cervantes laura Esteban-Gonzalo Maria Jose Girela-Rejon Jose Castro-Pinero Oscar L.Veiga Department of Physical Education Sport and Human MovementAutonomous University of MadridMadrid 28049Spain Research Centre in Physical Activity Health and Leisure(CIAFEL)Faculty of SportUniversity of PortoPorto 4200-450Portugal Nursing Department Faculty of Biomedical and Health SciencesUniversidad Europea de MadridVillaviciosa de OdonMadrid 28670Spain Department of Didactic of Corporal Expression Faculty of Education SciencesUniversity of GranadaGranada 18010Spain Department of Physical Education School of EducationUniversity of CadizPuerto RealCadiz 11519Spain

Purpose:The aim of the present study was to analyze the associations of youths' sedentary behavior(SB) with parents' and siblings' SB and physical activity(PA),as well as the associations of youths' coparticipation with parents,siblings,and friends in PA and SB with youths' ***:The sample consisted of 1543 youths(12.02±2.51 years;788 boys) enrolled in the baseline cohort of the UP&DOWN *** was assessed by accelerometry and *** reported the time spent by their parents and siblings watching television,playing videogames,surfing the Internet,sitting/resting,and doing ***,participants reported coparticipation with parents,siblings,and friends in these *** mixed models,including school and city as random effects,were ***:Parents' television time was positively associated with youths' screen-based *** with friends in playing videogames(in boys) and in surfing the Internet(in girls) showed a positive association with screen-based SB and a negative association with educational-based ***,coparticipation with siblings and friends in PA was inversely associated with accelerometer-based SB in boys and ***:Our results emphasize the important role of social modeling in the development of sedentary lifestyles in *** aimed at reducing health risk behaviors in youths could be more effective if they are oriented from a social perspective that involves their families and networks of their closest friends.

关键词： Friends Parents Sedentary behavior Siblings Social environment

Correlations between corneal and optic nerve head variables in healthy subjects and patients with primary open angle glaucoma

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International Journal of Ophthalmology(English edition) 2015年第6期8卷 1156-1161页

作者： Federico Saenz-Frances Luis Janez Lara Borrego-Sanz Clara Berrozpe-Villabona Jose Maria Martinez-de-la-Casa laura Morales-Fernandez Julian garcia-sanchez Enrique Santos-Bueso Julian garcia-Feijoo Department of Ophthalmology Clinico San Carlos HospitalComplutense University of Madrid Technology of Knowledge Institute Complutense University of Madrid

AIMTo correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG).METHODSMeasurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the *** following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P<0.0001), Zone I-DAr (-0.503; P<0.0001) and Zone II-DAr (-0.443; P<0.0001); and in the POAG group: CCT-cup-to-disc area ratio (CDRa) (-0.402; P<0.0001), Zone I-CDRa (-0.418; P<0.0001), Zone II-CDRa (-0.405; P=0.006), Zone I-cup shape measure (CSM) (-0.415; P=0.002), Zone II-CSM (-0.405; P=0.001), Zone IV-height variation contour (HVC) (0.378; P=0.002); Zone V-HVC (0.388, P<0.0001).CONCLUSIONSIn the healthy subjects, significant negative correlation was detected between central and paracentral corneal thickness and optic disc area. In contrast, the POAG patients showed significant negative correlation between central and paracentral corneal thickness and the cup-disc ratio and CSM, and positive correlation between peripheral corneal thickness and HVC.

关键词： glaucoma optic nerve head corneal thickness

Dependence of dynamic contour and Goldmann applanation tonometries on peripheral corneal thickness

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International Journal of Ophthalmology(English edition) 2017年第10期10卷 1521-1527页

作者： Federico Saenz-Frances Claudia Sanz-Pozo Lara Borrego-Sanz Luis Ja?ez laura MoralesFernandez Jose Maria Martinez-de-la-Casa Julian garcia-sanchez Julian garcia-Feijoo Enrique Santos-Bueso Ophthalmology Department Clinico Universitario San Carlos HospitalComplutense University Institute of Knowledge Technology Complutense University

AIM：To determine the effects of peripheral corneal thickness（PCT）on dynamic contour tonometry（DCT）and Goldmann applanation tonometry（GAT）.METHODS：A cross-sectional *** created a software which calculates the corneal contour（CC）as a function of the radius from the corneal apex to each pixel of the *** software generates a central circumference with a radius of 1 mm and the remainder of the cornea is segmented in 5 rings concentric with corneal apex being its diameter not constant around the corneal circumference as a consequence of the irregular CC but keeping constant the diameter of each ring in each direction of the *** was determined as the mean thickness of the most eccentric *** weighted scatterplot smoothing（LOWESS）regression was used to determine the pattern of the relationship between PCT and both DCT and GAT ***,two multivariable linear regression models were *** each of them,the dependant variable was intraocular pressure（IOP）as determined using GAT and DCT *** both of the models the predictive variable was PCT though LOWESS regression pattern was used to model the relationship between the dependant variables and the predictor *** and sex were also introduced control variables along with their first-degree interactions with *** outcome measures include amount of IOP variation explained through regression models（R2）and regression coefficients（B）.RESULTS：Subjects included 109 eyes of 109 healthy *** regression suggested that a 2nd-degree polynomial would be suitable to model the relationshipbetween both DCT and GAT with *** PCT was introduced in both models as a linear and quadratic *** age nor sex nor interactions were statistically significant in both *** GAT model,R2was 17.14%（F=9.02;P=0.0002）,PCT linear term B was-1.163（95%CI：-1.163,-0.617）.PCT quadratic term B was 0.00081（95%CI：0.00043,0.00118）.For DCT model R2was 14.28%（F=9.29;P=0.0002

关键词： Goldmann applanation tonometry dynamic contour tonometry peripheral corneal thickness corneal thickness

Attosecond twisted beams from high-order harmonicgeneration driven by optical vortices

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High Power Laser Science and Engineering 2017年第1期5卷 12-19页

作者： Carlos Hernandez-garcia laura Rego Julio San Roman Antonio Picon Luis Plaja Grupo de Investigacion en Aplicaciones del Laser y Fotonica Departamento de Fisica AplicadaUniversity of SalamancaE-37008SalamancaSpain Argonne National Laboratory Argonne1L 60439USA

Optical vortices are structures of the electromagnetic field with a spiral phase ramp about a point-phase singularity,carrying orbital angular momentum(OAM). Recently, OAM has been imprinted to short-wavelength radiation through high-order harmonic generation(HHG), leading to the emission of attosecond twisted beams in the extreme-ultraviolet(XUV) regime. We explore the details of the mapping of the driving vortex to its harmonic spectrum. In particular, we show that the geometry of the harmonic vortices is convoluted, arising from the superposition of the contribution from the short and long quantum paths responsible of HHG. Finally, we show how to take advantage of transverse phase-matching to select twisted attosecond beams with different spatiotemporal properties.

关键词： attosecond science extreme-ultraviolet vortices high harmonic generation orbital angular momentum twisted beams vortexbeams

A scoping review on the field validation and implementation of rapid diagnostic tests for vector-borne and other infectious diseases of poverty in urban areas

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Infectious Diseases of Poverty 2018年第1期7卷 879-896页

作者： Lyda Osorio Jonny Alejandro garcia Luis Gabriel Parra Victor garcia laura Torres Stephanie Degroote Valery Ridde Epidemiology and Population Health Research Group School of Public HealthUniversidad del ValleCalle 4B No.36-00 Edif 118 Escuela de Salud PúblicaUniversidad del Valle Campus San FernandoCaliColombia School of Medicine Universidad del ValleCaliColombia University of Montreal Public Health Research Institute(IRSPUM) MontrealCanada French Institute for Research on Sustainable Development(IRD) Paris Descartes UniversityPopulation and Development Center(CEPED)UniversiteParis Sorbonne CiteNational Institute of Health and Medical Research(INSERM)HealthVulnerabilities and Gender Relations South(SAGESUD)ParisFrance

Background:Health personnel face challenges in diagnosing vector-borne and other diseases of poverty in urban *** is a need to know what rapid diagnostic technologies are available,have been properly assessed,and are being implemented to improve control of these diseases in the urban *** paper characterizes evidence on the field validation and implementation in urban areas of rapid diagnostics for vector-borne diseases and other diseases of *** body:A scoping review was ***-reviewed and grey literature were searched using terms describing the targeted infectious diseases,diagnostics evaluations,rapid tests,and urban *** review was limited to studies published between 2000 and 2016 in English,Spanish,French,and *** and exclusion criteria were refined post hoc to identify relevant literature regardless of study design and geography.A total of 179 documents of the 7806 initially screened were included in the ***(n=100)and tuberculosis(n=47)accounted for the majority of studies that reported diagnostics performance,impact,and implementation *** studies,assessing mainly performance,were identified for visceral leishmaniasis(n=9),filariasis and leptospirosis(each n=5),enteric fever and schistosomiasis(each n=3),dengue and leprosy(each n=2),and Chagas disease,human African trypanosomiasis,and cholera(each n=1).Reported sensitivity of rapid tests was variable depending on several ***,specificities were high(>80%),except for schistosomiasis and *** and implementation outcomes,mainly acceptability and cost,followed by adoption,feasibility,and sustainability of rapid tests are being evaluated in the *** to implementing rapid tests range from cultural to technical and administrative ***:Rapid diagnostic tests for vector-borne and other diseases of poverty are being used in the urban context with demonstrated impact on case ***

关键词： Communicable diseases Diagnostic services Point-of-care testing Field evaluation Sensitivity and specificity Implementation Evaluation studies Urban health

Comparison of ART outcomes in men with altered mRNA protamine 1/protamine 2 ratio undergoing intracytoplasmic sperm injection with ejaculated and testicular spermatozoa

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Asian Journal of Andrology 2020年第6期22卷 623-628页

作者： Jonas Sarasa Maria Enciso laura garcia Andrea Leza Klaus Steger Jon Aizpurua iGLS Alicante 03540SpainMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany IVF-Spain Alicante 03540SpainMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany Department of Urology Pediatric Urology and AndrologyMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany

Assisted reproductive technologies invoIving the use of spermatozoa and eggs for in vitro fertilization(IVF)have come as the solution for many infertile couples to become ***,in some cases,the use of ejaculated spermatozoa delivers poor IVF *** studies have suggested the use of testicular spermatozoa in severe male in fertility cases,but no guideli nes regarding their utilization are currently *** the present study,we found the mRNA protamine 1/protamine 2(P1/P2)ratio to be a valuable biomarker of poor sperm function that could be used as a diagnostic key for the identification of cases that would benefit from the use of testicular spermatozoa.A total of 23 couples undergoing egg donation cycles with at least one previous cycle failure were *** couples underwent two consecutive intracytoplasmic sperm injection(ICSI)cycles with either ejaculated or testicular spermatozoa(TESA).The sperm mRNA P1/P2 ratio,fertilization rate,blastocyst rate,and pregnancy and live birth rate were *** showed improved ICSI and clinical outcomes in cycles with testicular spermatozoa in men with altered mRNA P1/P2 *** cycles presented significantly higher rates of fertilization(mean±standard deviation:76.1%±15.1%vs 65.5%±18.8%),blastocyst formation(55.0%±20.3%vs 30.8%±23.8%),and good morphological quality blastocyst(28.9%±22.9%vs 13.5%±17.9%)and also improvements on pregnancy(60.9%vs 0%)and healthy birth rates(56.5%vs 0%)than EJACULATE *** results described here suggest that in patients with previous IVF/ICSI failures and aberrant mRNA protamine ratios,the use of testicular spermatozoa may be a good alternative to improve clinical outcomes.

关键词： DNA damage male infertility mRNA protamine ratio sperm chromatin testicular spermatozoa