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211.
212.
Abstract. Vicariance on a microplate dispersed by the formation of the Western Mediterranean is the probable origin of Melanopsis etrusca Villa in Brot, the only melanopsid (Gastopoda: Melanopsidae) living in the Italian Peninsula. It is distantly related to extant melanopsids in Iberia and Morocco, and is restricted to thermal springs in the Maremma of southern Tuscany. This area was an island throughout the Miocene, inferred to have become detached geographically from the Corso—Sardinian block. Alternative explanations conflict with geological, paleontological, ecological and systematic evidence. In the geologically young Italian Peninsula fossil freshwater melanopsids are known only from Lower Pleistocene sites located around the area occupied by living populations. Their similarity to extant specimens supports the hypothesis that they represent the same lineage, having expanded its range during a brief, favourable period. Introduction of M. etrusca by humans, birds or wind is most improbable given its distinctness, similarity to local fossils, and inability for passive dispersal. Long-distance dispersal along brackish lagoons during the late Messinian conflicts with the inferred inability of melanopsids living there to colonize freshwater habitats. Indeed, there are ecological, phylogenetic and geological reasons against invoking the Messinian salinity crisis in order to explain the distribution of most taxa. Other freshwater taxa show distribution patterns similar to that of living and fossil melanopsids. However, congruent area cladograms or generalized tracks may not constitute reliable evaluators of biogeographical hypotheses. The detection of vicariance, as that of any other cause, requires robust reconstructions of the past. By pointing at areas of endemism that deserve urgent action, biogeography can provide a contribution to conservation. 相似文献
213.
Nicholas P. Barton Benjamin R. Bellenie Andrew T. Doran Amanda J. Emmons Jag P. Heer Cristian M. Salvagno 《Bioorganic & medicinal chemistry letters》2009,19(2):528-532
The optimisation of a tertiary sulfonamide high-throughput screening hit is described. A combination of high-throughput chemistry, pharmacophore analysis and in silico PK profiling resulted in the discovery of potent sulfonamide oxytocin receptor antagonists with oral exposure and good selectivity over vasopressin receptors. 相似文献
214.
Joel W. Aspden Carol L. Armstrong Cristian I. Gutierrez-Ibanez Richard Hawkes Andrew N. Iwaniuk Tobias Kohl David J. Graham Douglas R. Wylie 《PloS one》2015,10(2)
Aldolase C, also known as Zebrin II (ZII), is a glycolytic enzyme that is expressed in cerebellar Purkinje cells of the vertebrate cerebellum. In both mammals and birds, ZII is expressed heterogeneously, such that there are sagittal stripes of Purkinje cells with high ZII expression (ZII+), alternating with stripes of Purkinje cells with little or no expression (ZII-). The patterns of ZII+ and ZII- stripes in the cerebellum of birds and mammals are strikingly similar, suggesting that it may have first evolved in the stem reptiles. In this study, we examined the expression of ZII in the cerebellum of the western diamondback rattlesnake (Crotalus atrox). In contrast to birds and mammals, the cerebellum of the rattlesnake is much smaller and simpler, consisting of a small, unfoliated dome of cells. A pattern of alternating ZII+ and ZII- sagittal stripes cells was not observed: rather all Purkinje cells were ZII+. This suggests that ZII stripes have either been lost in snakes or that they evolved convergently in birds and mammals. 相似文献
215.
Rebecca J. Laver Cristian H. Morales Matthew P. Heinicke Tony Gamble Kristin Longoria Aaron M. Bauer Juan D. Daza 《Journal of morphology》2020,281(2):213-228
Armored skin resulting from the presence of bony dermal structures, osteoderms, is an exceptional phenotype in gekkotans (geckos and flap-footed lizards) only known to occur in three genera: Geckolepis, Gekko, and Tarentola. The Tokay gecko (Gekko gecko LINNAEUS 1758) is among the best-studied geckos due to its large size and wide range of occurrence, and although cranial dermal bone development has previously been investigated, details of osteoderm development along a size gradient remain less well-known. Likewise, a comparative survey of additional species within the broader Gekko clade to determine the uniqueness of this trait has not yet been completed. Here, we studied a large sample of gekkotans (38 spp.), including 18 specimens of G. gecko, using X-rays and high-resolution computed tomography for visualizing and quantifying the dermal armor in situ. Results from this survey confirm the presence of osteoderms in a second species within this genus, Gekko reevesii GRAY 1831, which exhibits discordance in timing and pattern of osteoderm development when compared with its sister taxon, G. gecko. We discuss the developmental sequence of osteoderms in these two species and explore in detail the formation and functionality of these enigmatic dermal ossifications. Finally, we conducted a comparative analysis of endolymphatic sacs in a wide array of gekkotans to explore previous ideas regarding the role of osteoderms as calcium reservoirs. We found that G. gecko and other gecko species with osteoderms have highly enlarged endolymphatic sacs relative to their body size, when compared to species without osteoderms, which implies that these membranous structures might fulfill a major role of calcium storage even in species with osteoderms. 相似文献
216.
Valentina Diehl Martin Wegner Paolo Grumati Koraljka Husnjak Simone Schaubeck Andrea Gubas Varun
Jayeshkumar Shah Ibrahim
H Polat Felix Langschied Cristian Prieto-Garcia Konstantin Müller Alkmini Kalousi Ingo Ebersberger Christian
H Brandts Ivan Dikic Manuel Kaulich 《Nucleic acids research》2021,49(10):5684
Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale. 相似文献
217.
Guntram Schernthaner Chaim Lotan Elina Baltadzhieva-Trendafilova Jonas Ceponis Martin Clodi Kristine Ducena Eva Goncalvesova Cristian Guja Marek Honka Andrej Janež Nebojša Lalić Roger Lehmann Noémi Nyolczas Priit Pauklin Andrzej Rynkiewicz Igor Sergienko Lea Smirčić Duvnjak 《Cardiovascular diabetology》2018,17(1):145
Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be ‘silent’ or ‘asymptomatic’, but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit. 相似文献
218.
Claudio Farías-Valenzuela Cristian Pérez-Luco Rodrigo Ramírez-Campillo Cristian Álvarez Mauricio Castro-Sepúlveda 《Revista espa?ola de geriatría y gerontología》2018,53(3):141-144
Background
Handgrip strength (HS) and peak oxygen consumption (Vo2peak) are powerful predictors of cardiovascular risk, although it is unknown which of the two variables is the better predictor.Aim
The objective of the following study was to relate HS and Vo2peak to cardiovascular risk markers in older Chilean women.Methods
Physically active adult women (n = 51; age, 69 ± 4.7 years) participated in this study. The HS and Vo2peak were evaluated and related to the anthropometric variables of body mass, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist ratio (WR), and waist height ratio (WHR), as well as with the cardiovascular variables systolic (SBP) and diastolic (DBP) and cardiac recovery in one minute (RHR1). A multilinear regression model was used for the analysis of the associated variables (P < .05).Results
The cardiovascular risk markers associated (P < .05) with the handgrip strength of the dominant limb (HSDL) were body mass, BMI, WR, and WHR. The handgrip strength of the non-dominant limb (HSNDL) was associated with body mass. Vo2peak was associated with body mass, BMI, HC and RHR1. The multilinear regression model showed a value of r = 0.43 in HSDL, r = 0.39 in HSNDL and r = 0.69 in peak Vo2.Conclusion
Although HS and Vo2peak were related to cardiovascular risk markers, Vo2peak offers greater associative power with these cardiovascular risk factors. 相似文献219.
Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis 下载免费PDF全文
Pietro Fratta Jose M Brito‐Armas Bernadett Kalmar Agnieszka Ule Yichao Yu Nicol Birsa Cristian Bodo Toby Collins Alexander E Conicella Alan Mejia Maza Alessandro Marrero‐Gagliardi Michelle Stewart Joffrey Mianne Silvia Corrochano Warren Emmett Gemma Codner Michael Groves Ryutaro Fukumura Yoichi Gondo Mark Lythgoe Erwin Pauws Emma Peskett Philip Stanier Lydia Teboul Martina Hallegger Andrea Calvo Adriano Chiò Adrian M Isaacs Nicolas L Fawzi Eric Wang David E Housman Francisco Baralle Linda Greensmith Emanuele Buratti Vincent Plagnol Abraham Acevedo‐Arozena 《The EMBO journal》2018,37(11)
TDP‐43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP‐43 function at physiological levels both in vitro and in vivo. Interestingly, we find that mutations within the C‐terminal domain of TDP‐43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP‐43 loss‐ and gain‐of‐function effects. TDP‐43 gain‐of‐function effects in these mice reveal a novel category of splicing events controlled by TDP‐43, referred to as “skiptic” exons, in which skipping of constitutive exons causes changes in gene expression. In vivo, this gain‐of‐function mutation in endogenous Tardbp causes an adult‐onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain‐of‐function and skiptic exons in ALS patient‐derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP‐43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages. 相似文献
220.
Christian Espinosa-Bustos Annika Frank Sandra Arancibia-Opazo Cristian O. Salas Angelica Fierro Holger Stark 《Bioorganic & medicinal chemistry letters》2018,28(17):2890-2893
This work describes the microwave assisted synthesis of twelve novel histamine H3 receptor ligands. They display pyrrolo[2,3-d]pyrimidine derivatives with rigidized aliphatic amines as warheads. The compounds were screened for H3R and H4R binding affinities in radioligand displacement assays and the most potent compounds were evaluated for H3R binding properties in vitro and in docking studies. The combination of a rigidized H3R warhead and the pyrrolo[2,3-d]pyrimidine scaffold resulted in selective activity at the H3 receptor with a pKi value of 6.90 for the most potent compound. A bipiperidine warhead displayed higher affinity than a piperazine or morpholine motif, while a naphthyl moiety in the arbitrary region increased affinity compared to a phenyl derivative. The compounds can be starting points for novel, simply synthesized histamine H3 receptor ligands. 相似文献