MUC-1 aptamer targeted superparamagnetic iron oxide nanoparticles for magnetic resonance imaging of pancreatic cancer in vivo and in vitro experiment

This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T₂, and the magnetic resonance transverse relaxation rate (ΔR²) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T₂ signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis.     

Tracing the trilobite tree from the root to the tips: A model marriage of fossils and phylogeny

Trilobites are a highly diverse group of extinct arthropods that persisted for nearly 300 million years. During that time, there was a profusion of morphological form, and they occupied a plethora of marine habitats. Their diversity, relative abundance, and complex morphology make them excellent candidates for phylogenetic analysis, and partly as a consequence they have been the subject of many cladistic studies. Although phylogenetic knowledge is certainly incomplete, our understanding of evolutionary patterns within the group has dramatically increased over the last 30 years. Moreover, trilobites have formed an important component of various studies of macroevolutionary processes. Here, we summarize the phylogenetic breadth of knowledge on the Trilobita, and present various hypotheses about phylogenetic patterns within the group, from the highest to the lowest taxonomic levels. Key topics we consider include the question of trilobite monophyly, the phylogenetic position of trilobites vis à vis extant arthropod groups, and inter- and intra-ordinal relationships.     

The race concept in six regions: variation without consensus

Race, once the central concept in physical anthropology worldwide, now varies in the degree of support it receives in different regions. We present the currently available information on the status of the concept in the United States, the Spanish language areas, Poland, Europe, Russia, and China. Rejection of race ranges from high to low with the highest rejection occurring among anthropologists in the United States (and Canada). Rejection of race is moderate in Europe, sizeable in Poland and Cuba, and lowest in Russia and China. A discussion on the scientific and contextual reasons influencing these variations is presented. The tension between scientific evidence and social influences varies from region to region. The methods used in the studies reported here included questionnaires and content analysis. Response rates to questionnaires were often around 50 percent (with exception of the Polish studies). We discuss reasons for the low rates. Although a uniform method of data gathering is desirable, it may not suit scientists working in different traditions of theory and research. We conclude that it is once again timely to discuss the race concept in international meetings where all scientific and political changes occurring throughout the world in recent past decades are taken into account.     

The tomato homolog of the gene encoding UV-damaged DNA binding protein 1 (DDB1) underlined as the gene that causes the<Emphasis Type="Italic"> high pigment-1</Emphasis> mutant phenotype

A tomato EST sequence, highly homologous to the human and Arabidopsis thaliana UV-damaged DNA binding protein 1 (DDB1), was mapped to the centromeric region of the tomato chromosome 2. This region was previously shown to harbor the HP-1 gene, encoding the high pigment-1 (hp-1) and the high pigment-1^w (hp-1^w) mutant phenotypes. Recent results also show that the A. thaliana DDB1 protein interacts both genetically and biochemically with the protein encoded by DEETIOLATED1, a gene carrying three tomato mutations that are in many respects isophenotypic to hp-1: high pigment-2 (hp-2), high pigment-2^j (hp-2^j) and dark green (dg). The entire coding region of the DDB1 gene was sequenced in an hp-1 mutant and its near-isogenic normal plant in the cv. Ailsa Craig background, and also in an hp-1^w mutant and its isogenic normal plant in the GT breeding line background. Sequence analysis revealed a single A⁹³¹-to-T⁹³¹ base transversion in the coding sequence of the DDB1 gene in the hp-1 mutant plants. This transversion results in the substitution of the conserved asparagine at position 311 to a tyrosine residue. In the hp-1^w mutant, on the other hand, a single G²³⁹²-to-A²³⁹² transition was observed, resulting in the substitution of the conserved glutamic acid at position 798 to a lysine residue. The single nucleotide polymorphism that differentiates hp-1 mutant and normal plants in the cv. Ailsa Craig background was used to design a pyrosequencing genotyping system. Analysis of a resource F₂ population segregating for the hp-1 mutation revealed a very strong linkage association between the DDB1 locus and the photomorphogenic response of the seedlings, measured as hypocotyl length (25<LOD score<26, R²=62.8%). These results strongly support the hypothesis that DDB1 is the gene encoding the hp-1 and hp-1^w mutant phenotypes.Communicated by R. Hagemann     

Effects of food processing on masticatory strain and craniofacial growth in a retrognathic face

Changes in the technology of food preparation over the last few thousand years (especially cooking, softening, and grinding) are hypothesized to have contributed to smaller facial size in humans because of less growth in response to strains generated by chewing softer, more processed food. While there is considerable comparative evidence to support this idea, most experimental tests of this hypothesis have been on non-human primates or other very prognathic mammals (rodents, swine) raised on hard versus very soft (nearly liquid) diets. Here, we examine facial growth and in vivo strains generated in response to raw/dried foods versus cooked foods in a retrognathic mammal, the rock hyrax (Procavia capensis). The results indicate that the hyrax cranium resembles the non-human primate cranium in having a steep gradient of strains from the occlusal to orbital regions, but differs from most non-anthropoids in being primarily twisted; the hyrax mandible is bent both vertically and laterally. In general, higher strains, as much as two-fold at some sites, are generated by masticating raw versus cooked food. Hyraxes raised on cooked food had significantly less growth (approximately 10%) in the ventral (inferior) and posterior portions of the face, where strains are highest, resembling many of the differences evident between humans raised on highly processed versus less processed diets. The results support the hypothesis that food processing techniques have led to decreased facial growth in the mandibular and maxillary arches in recent human populations.     

Does morality have a biological basis? An empirical test of the factors governing moral sentiments relating to incest.

Kin-recognition systems have been hypothesized to exist in humans, and adaptively to regulate altruism and incest avoidance among close genetic kin. This latter function allows the architecture of the kin recognition system to be mapped by quantitatively matching individual variation in opposition to incest to individual variation in developmental parameters, such as family structure and co-residence patterns. Methodological difficulties that appear when subjects are asked to disclose incestuous inclinations can be circumvented by measuring their opposition to incest in third parties, i.e. morality. This method allows a direct test of Westermarck's original hypothesis that childhood co-residence with an opposite-sex individual predicts the strength of moral sentiments regarding third-party sibling incest. Results support Westermarck's hypothesis and the model of kin recognition that it implies. Co-residence duration objectively predicts genetic relatedness, making it a reliable cue to kinship. Co-residence duration predicts the strength of opposition to incest, even after controlling for relatedness and even when co-residing individuals are genetically unrelated. This undercuts kin-recognition models requiring matching to self (through, for example, major histocompatibility complex or phenotypic markers). Subjects' beliefs about relatedness had no effect after controlling for co-residence, indicating that systems regulating kin-relevant behaviours are non-conscious, and calibrated by co-residence, not belief.     

Dopamine and alcohol relapse: D1 and D2 antagonists increase relapse rates in animal studies and in clinical trials

A considerable number of animal studies on the effects of dopaminergic agents on alcohol intake behavior have been performed. Acute alcohol administration in rats induces dopamine release in the caudate nucleus and in the nucleus accumbens, an effect related among others to reinforcement. It has been repeatedly suggested that D1 and D2 receptor activation mediates reward. As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blind multicenter clinical trial, comparing the D1, D2, D3 antagonist flupenthixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation possible. It could be shown in which patients flupenthixol administration was followed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo.