Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology

Molecular Biology Reports - The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result...     

From clinical specimens to human cancer preclinical models—a journey the NCI-cell line database—25 years later

The intramural the National Cancer Institute (NCI) and more recently the University of Texas Southwestern Medical Center with many different collaborators comprised a complex, multi-disciplinary team that collaborated to generated large, comprehensively annotated, cell-line related research resources which includes associated clinical, and molecular characterization data. This material has been shared in an anonymized fashion to accelerate progress in overcoming lung cancer, the leading cause of cancer death across the world. However, this cell line collection also includes a range of other cancers derived from patient-donated specimens that have been remarkably valuable for other types of cancer and disease research. A comprehensive analysis conducted by the NCI Center for Research Strategy of the 278 cell lines reported in the original Journal of Cellular Biochemistry Supplement, documents that these cell lines and related products have since been used in more than 14 000 grants, and 33 207 published scientific reports. This has resulted in over 1.2 million citations using at least one cell line. Many publications involve the use of more than one cell line, to understand the value of the resource collectively rather than individually; this method has resulted in 2.9 million citations. In addition, these cell lines have been linked to 422 clinical trials and cited by 4700 patents through publications. For lung cancer alone, the cell lines have been used in the research cited in the development of over 70 National Comprehensive Cancer Network clinical guidelines. Finally, it must be underscored again, that patient altruism enabled the availability of this invaluable research resource.     

Snipe taxonomy based on vocal and non-vocal sound displays: the South American Snipe is two species

We analysed breeding sounds of the two subspecies of South American Snipe Gallinago paraguaiae paraguaiae and Gallinago paraguaiae magellanica to determine whether they might be different species: loud vocalizations given on the ground, and the tail-generated Winnow given in aerial display. Sounds of the two taxa differ qualitatively and quantitatively. Both taxa utter two types of ground call. In G. p. paraguaiae, the calls are bouts of identical sound elements repeated rhythmically and slowly (about five elements per second (Hz)) or rapidly (about 11 Hz). One call of G. p. magellanica is qualitatively similar to those of G. p. paraguaiae but sound elements are repeated more slowly (about 3 Hz). However, its other call type differs strikingly: it is a bout of rhythmically repeated sound couplets, each containing two kinds of sound element. The Winnow of G. p. paraguaiae is a series of sound elements that gradually increase in duration and energy; by contrast, that of G. p. magellanica has two or more kinds of sound element that roughly alternate and are repeated as sets, imparting a stuttering quality. Sounds of the related Puna Snipe (Gallinago andina) resemble but differ quantitatively from those of G. p. paraguaiae. Differences in breeding sounds of G. p. paraguaiae and G. p. magellanica are strong and hold throughout their geographical range. Therefore we suggest that the two taxa be considered different species: G. paraguaiae east of the Andes in much of South America except Patagonia, and G. magellanica in central and southern Chile, Argentina east of the Andes across Patagonia, and Falklands/Malvinas.     

Predicting the accuracy of multiple sequence alignment algorithms by using computational intelligent techniques

Multiple sequence alignments (MSAs) have become one of the most studied approaches in bioinformatics to perform other outstanding tasks such as structure prediction, biological function analysis or next-generation sequencing. However, current MSA algorithms do not always provide consistent solutions, since alignments become increasingly difficult when dealing with low similarity sequences. As widely known, these algorithms directly depend on specific features of the sequences, causing relevant influence on the alignment accuracy. Many MSA tools have been recently designed but it is not possible to know in advance which one is the most suitable for a particular set of sequences. In this work, we analyze some of the most used algorithms presented in the bibliography and their dependences on several features. A novel intelligent algorithm based on least square support vector machine is then developed to predict how accurate each alignment could be, depending on its analyzed features. This algorithm is performed with a dataset of 2180 MSAs. The proposed system first estimates the accuracy of possible alignments. The most promising methodologies are then selected in order to align each set of sequences. Since only one selected algorithm is run, the computational time is not excessively increased.     

The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population

Prolactin (PRL) is a hormone–cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism − 1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL − 1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL − 1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case–control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR–RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p = 0.022) and allelic (p = 0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT + TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45–0.92; p = 0.011). The T allele carriers (GT + TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p = 0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1 > 0.72 > 0.19; CS: 1 > 0.54 > 0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL − 1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.     

Unexpected microanatomical variation among Eocene Antarctic stem penguins (Aves: Sphenisciformes)

The microanatomical and histological structure of Eocene Antarctic stem penguin tarsometatarsi is examined in order to characterise the bone microstructure. Eight adult tarsometatarsi belonging to eight fossil species (Palaeeudyptes gunnari, Palaeeudyptes klekowskii, Anthropornis grandis, Anthropornis nordenskjoeldi, Archaeospheniscus wimani, Marambiornis exilis, Delphinornis arctowskii and Delphinornis larseni) collected from the Antarctic A. nordenskjoeldi Biozone (La Meseta Formation, ～34.2 Ma) were examined. The thin sections revealed a distinctive microanatomical variation among taxa. Whereas Anthropornis spp., A. wimani and P. gunnari possess massive, clearly osteosclerotic bones (medullary cavities absent or strongly reduced), the bones of Delphinornis spp., P. klekowski and M. exilis exhibit well-developed medullary cavities. The cortical bone in all the specimens consists of primary, well-vascularised fibro-lamellar bone and variable amounts of secondary bone. Medullary cavities are coated by a thick layer of lamellar bone tissue and coarse compacted cancellous bone. Although several causes can explain the striking microanatomical variation (e.g. ontogeny), we interpret that such variation is related to differential adaptations to the aquatic life, for which taxa with more massive bones were possibly adapted to deeper and more prolonged diving excursions.     

A new hadrosaurid dentary from the latest Maastrichtian of the Pyrenees (north Spain) and the high diversity of the duck-billed dinosaurs of the Ibero-Armorican Realm at the very end of the Cretaceous

In the latest Maastrichtian, the European hadrosauroid fauna was more diverse than those of North America and Asia. The European record of hadrosaurid dentaries is an example of this diversity, and most of the sites with mandibular remains are located in the Ibero-Armorican Realm. Within the Iberian Peninsula, most of the remains are located in the Tremp Basin (South Central Pyrenees). Two of the three valid hadrosaurid taxa defined in this basin are from the Blasi sites (Arén, Huesca province): Arenysaurus ardevoli (Blasi-3) and Blasisaurus canudoi (Blasi-1). A new locality in Blasi (Blasi 3.4) has provided a new dentary from an indeterminate euhadrosaurid. This dentary presents some characters intermediate between Arenysaurus and Blasisaurus, some characters similar to Pararhabdodon isonensis (from the nearby province of Lleida), and some characters of its own. Nevertheless, due to its fragmentary character, without dentition or its edentulous anterior part, it cannot be determined above the level of Euhadrosauria. It thus represents a fourth Iberian euhadrosaurian taxon in the Ibero-Armorican Realm, different from Arenysaurus, Blasisaurus and Pararhabdodon, increasing the diversity of hadrosauroids in this realm at the very end of the Cretaceous.     

Morphological and molecular species delimitation within the Holarctic Ilybius angustior complex with a focus on Beringia (Coleoptera: Dytiscidae)

A fourth species of the Holarctic Ilybius angustior complex, Ilybius minakawai n. sp., is described from the Island of Sakhalin in the Russian far east. Male genitalia are diagnostic within this species complex, although from body size and shape the new species cannot be separated from I. churchillensis Wallis from north Alaska and the Canadian low arctic. The small and narrow body characteristic of these two species represents an extreme of the cold climate form of the widespread I. angustior (Gyllenhal). Low variation within the studied large ribosomal and cytochrome c oxidase subunit I mitochondrial genes suggest that speciation events within the I. angustior-complex are fairly recent. In combination with known geographical ranges, the low genetic variation within this species complex suggest speciation within Pleistocene refugia including Beringia.     

Rodent Diversity and Land Use in Montebello,Chiapas, Mexico

We analyzed the abundance and diversity of Heteromyid and Murid rodents in the Lagos de Montebello National Park and adjacent areas, Chiapas, Mexico. We sampled three habitat types with different degrees of disturbance: pine-oak-liquidambar forest, ecotone and crop farming lands. Habitat types were defined considering characteristics such as heterogeneity, structural complexity and arboreal cover. We obtained ancillary habitat data considered important for small mammal requirements. Data on rodent communities were obtained by capture-mark-recapture between February and October 1996. We made 410 captures in 3820 trap-nights effort. Ten species were recorded, including one endemic with restricted distribution in Chiapas. Mouse diversity in the forest was significantly higher than within the farm lands. A Kendall correlation analysis showed positive relationship between rodent community species richness and habitat heterogeneity. Diversity of rodents was associated with the habitat complexity and structural elements, and negatively correlated with farming intensity. We found a high beta diversity and low similarity of the rodent communities in the three different habitats. Community composition strongly changed from the forest through the ecotone into the farm lands, with five species gained and seven species lost. The highest species richness was found in the ecotone; however, it showed a strong dominance of a single species that can convert into a plague of crops, and relatively low abundance of the other species. The pine-oak-liquidambar forest had the highest diversity indices, sheltering a particular rodent community within the study area, it therefore probably has the most important role in the conservation of the local biodiversity.