Metastatic bladder cancer cells distinctively sense and respond to physical cues of collagen fibril-mimetic nanotopography

Tumor metastasis is characterized by enhanced invasiveness and migration of tumor cells through the extracellular matrix (ECM), resulting in extravasation into the blood and lymph and colonization at secondary sites. The ECM provides a physical scaffold consisting of components such as collagen fibrils, which have distinct dimensions at the nanoscale. In addition to the interaction of peptide moieties with tumor cell integrin clusters, the ECM provides a physical guide for tumor cell migration. Using nanolithography we set out to mimic the physical dimensions of collagen fibrils using lined nanotopographical silicon surfaces and to explore whether metastatic tumor cells are uniquely able to respond to these physical dimensions. Etched silicon surfaces containing nanoscale lined patterns with varying trench and ridge sizes (65–500 nm) were evaluated for their ability to distinguish between a non-metastatic (253J) and a highly metastatic (253J-BV) derivative bladder cancer cell line. Enhanced alignment was distinctively observed for the metastatic cell lines on feature sizes that mimic the dimensions of collagen fibrils (65–100 nm lines, 1:1–1:1.5 pitch). Further, these sub-100 nm lines acted as guides for migration of metastatic cancer cells. Interestingly, even at this subcellular scale, metastatic cell migration was abrogated when cells were forced to move perpendicular to these lines. Compared to flat surfaces, 65 nm lines enhanced the formation of actin stress fibers and filopodia of metastatic cells. This was accompanied by increased formation of focal contacts, visualized by immunofluorescent staining of phospho-focal adhesion kinase along the protruding lamellipodia. Simple lined nanotopography appears to be an informative platform for studying the physical cues of the ECM in a pseudo-3D format and likely mimics physical aspects of collagen fibrils. Metastatic cancer cells appear distinctively well adapted to sense these features using filopodia protrusions to enhance their alignment and migration.     

Examining the Causes and Consequences of Short-Term Behavioral Change during the Middle Stone Age at Sibudu,South Africa

Sibudu in KwaZulu-Natal (South Africa) with its rich and high-resolution archaeological sequence provides an ideal case study to examine the causes and consequences of short-term variation in the behavior of modern humans during the Middle Stone Age (MSA). We present the results from a technological analysis of 11 stratified lithic assemblages which overlie the Howiesons Poort deposits and all date to ~58 ka. Based on technological and typological attributes, we conducted inter-assemblage comparisons to characterize the nature and tempo of cultural change in successive occupations. This work identified considerable short-term variation with clear temporal trends throughout the sequence, demonstrating that knappers at Sibudu varied their technology over short time spans. The lithic assemblages can be grouped into three cohesive units which differ from each other in the procurement of raw materials, the frequency in the methods of core reduction, the kind of blanks produced, and in the nature of tools the inhabitants of Sibudu made and used. These groups of assemblages represent different strategies of lithic technology, which build upon each other in a gradual, cumulative manner. We also identify a clear pattern of development toward what we have previously defined as the Sibudan cultural taxonomic unit. Contextualizing these results on larger geographical scales shows that the later phase of the MSA during MIS 3 in KwaZulu-Natal and southern Africa is one of dynamic cultural change rather than of stasis or stagnation as has at times been claimed. In combination with environmental, subsistence and contextual information, our high-resolution data on lithic technology suggest that short-term behavioral variability at Sibudu can be best explained by changes in technological organization and socio-economic dynamics instead of environmental forcing.     

Deletion of 2q37 and duplication of 10q24: two cases in the same family and review of the literature.

We describe two patients (first cousins, once removed) with an unusual head shape, high arched palate, flat nasal bridge, abnormal ears, hand and feet abnormalities and other anomalies. The patients were ascertained independently and it was initially unknown that they were related to each other. Cytogenetic and fluorescent in situ hybridization (FISH) analysis identified a der(2)t(2;10)(q37.3;q24.1) unbalanced translocation resulting in loss of 2q37.3-qter and duplication 10q24.1-qter. The clinical features of these two patients are compared with previously described cases of 2q deletion and 10q duplication. These patients also emphasize the difficulty in some families of understanding and sharing genetic information and in the difficulties in obtaining an accurate pedigree in a genetics clinic.     

Vegetation development and human occupation in the Damascus region of southwestern Syria from the Late Pleistocene to Holocene

Rockshelter Baaz in the Damascus region of Syria provided a variety of botanical remains from the Late Pleistocene and Early Holocene period. These remains provide new information about the vegetation evolution in this region. The earliest occupational levels correspond with a moisture peak during the Late Pleistocene, between ca. 34–32 kyr b.p., when pine expanded. The next occupations took place during extreme arid conditions, ca. 23–21 kyr b.p., and probably during the Last Glacial Maximum when a steppe vegetation was established. The occupation level of the Younger Dryas, represented by Natufian remains, suggests that the area had been covered by almond-pistachio steppe, similar to later periods of the Early Holocene, and was probably located just outside the range of dense wild cereal stands. There is no drastic impact of the Younger Dryas visible on the vegetation in the botanical remains. The lack of fruits and seeds at Baaz indicates that the site was more likely to have been a temporary hunting post rather than a plant processing site for much of its history. It is ideally suited to this purpose because of its location over the Jaba′deen Pass and the associated springs. However, archaeological remains from the Natufian period, suggest that the site was more permanently occupied during this time. A. Dodonov deceased.     

The Challenges of Hazard Identification and Classification of Insoluble Metals and Metal Substances for the Aquatic Environment

The OECD is currently harmonizing procedures for aquatic hazard identification of substances. Such a system already exists in Europe where it is recognized that special consideration must be given to sparingly soluble metals and metal compounds (SSMMCs) because standard hazard testing procedures designed for organic chemicals do not accommodate the characteristics of SSMMCs. Current aquatic hazard identification procedures are based on persistence, bioaccumulation, and toxicity (PBT) measurements. Persistence measurements typically used for organic substances (biodegradation) do not apply to metals. Alternative measurements such as complexation and precipitation are more appropriate. Metal bioaccumulation is important in terms of nutritional sufficiency and potential food chain transfer and toxicity. Unlike organic substances, metal bioaccumulation potential cannot be estimated using log octanol-water partition coefficients. Further, bioaccumulation and bioconcentration factors are often inversely related to exposure concentration for most metals and organisms, and hence are not reliable predictors of chronic toxicity or food chain accumulation. Metal toxicity is due predominately to the free metal ion in solution. In order to assess the toxicity of SSMMCs, the rate and extent of transformation to a soluble form must be measured.     

Lysogenic phages of Closrtidium perfringens: mapping of the chromosomal attachment sites

The sites of insertion for two lysogenic bacteriophages have been mapped on the chromosome of Clostridium perfringens strain CPN50 using two techniques based on pulsed field gel electrophoresis. Phage phi 29 was mapped to the 1 Mb region of the 3.6 Mb genome, near nanH which encodes a potential virulence factor, while phi 59 was found to have inserted at 2.9 Mb.