Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P < .001, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis

cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans

SummaryDramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg) gene. The divergent allele reduces expression in gill and skin tissue and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans

A Fully-Flexible Solution-Processed Autonomous Glucose Indicator

We present the first demonstration of a fully-flexible, self-powered glucose indicator system that synergizes two flexible electronic technologies: a flexible self-powering unit in the form of a biofuel cell, with a flexible electronic device - a circuit-board decal fabricated with biocompatible microbial nanocellulose. Our proof-of-concept device, comprising an enzymatic glucose fuel cell, glucose sensor and a LED indicator, does not require additional electronic equipment for detection or verification; and the entire structure collapses into a microns-thin, self-adhering, single-centimeter-square decal, weighing less than 40 mg. The flexible glucose indicator system continuously operates a light emitting diode (LED) through a capacitive charge/discharge cycle, which is directly correlated to the glucose concentration. Our indicator was shown to operate at high sensitivity within a linear glucose concentration range of 1 mM-45 mM glucose continuously, achieving a 1.8 VDC output from a flexible indicator system that deliver sufficient power to drive an LED circuit. Importantly, the results presented provide a basis upon which further development of indicator systems with biocompatible diffusing polymers to act as buffering diffusion barriers, thereby allowing them to be potentially useful for low-cost, direct-line-of-sight applications in medicine, husbandry, agriculture, and the food and beverage industries

Detection of local-scale population declines through optimized tidal marsh bird monitoring design

Evaluating the efficacy of monitoring designs is crucial for the successful monitoring and conservation of populations. For tidal marsh bird species of conservation concern, detecting population declines at local spatial scales within actionable time frames is a top priority. We examined and compared the effectiveness of alternative monitoring strategies for detecting local-scale population declines using count data from 1176 spatially-independent salt marsh sampling points throughout the northeastern United States (Maine to Virginia). We used abundance estimates that accounted for imperfect detection as initial conditions to simulate annual population declines of 5%, 10%, 30%, and 50% over a 5-year sampling period. Under an optimal monitoring design with biennial sampling, we were able to successfully detect annual population declines of ≥30% for each species and for all species combined. However, this required a minimum of 15–20 points per site being sampled. Power to detect declines, although low for detecting smaller annual declines (i.e., \u3c10%), improved substantially when points were visited twice per season, yet a third visit provided a reduced benefit. When testing factors that could potentially influence power to detect declines, we found that the power within sites was positively related to species abundance. Power was similar between biennial sampling (3 of 5 years) and annual sampling (5 of 5 years), suggesting a more cost-effective approach would be to sample every other year. We found that within most sites, detecting annual declines of 10% or less over a relatively short 5-year duration would be difficult. Hence, we recommend that salt marsh bird monitoring programs in the northeastern United States conduct two visits to each site per sampling year, include 15 or more sampling points per site (without confounding spatial independence), and conduct monitoring efforts every other year. This approach will maximize the efficacy of site-level monitoring of tidal marsh birds, which can aid in assessments of coastal wetland conservation and related habitat management efforts

Facial recognition from DNA using face-to-DNA classifiers

Facial recognition from DNA refers to the identification or verification of unidentified biological material against facial images with known identity. One approach to establish the identity of unidentified biological material is to predict the face from DNA, and subsequently to match against facial images. However, DNA phenotyping of the human face remains challenging. Here, another proof of concept to biometric authentication is established by using multiple face-to-DNA classifiers, each classifying given faces by a DNA-encoded aspect (sex, genomic background, individual genetic l

In the blood: the myth and reality of genetic markers of identity

The differences between copies of the human genome are very small, but tend to cluster in different populations. So, despite the fact that low inter-population differentiation does not support a biological definition of races statistical methods are nonetheless claimed to be able to predict successfully the population of origin of a DNA sample. Such methods are employed in commercial genetic ancestry tests, and particular genetic signatures, often in the male-specific Y-chromosome or maternally-inherited mitochondrial DNA, have become widely identified with particular ancestral or existing groups, such as Vikings, Jews, or Zulus. Here, we provide a primer on genetics, and describe how genetic markers have become associated with particular groups. We describe the conflict between population genetics and individual-based genetics and the pitfalls of over-simplistic genetic interpretations, arguing that although the tests themselves are reliable, the interpretations are unreliable and strongly influenced by cultural and other social forces.</p

Photoionization efficiency spectroscopy and density functional theory investigations of RhHo2On, (n=0-2) clusters

The experimental and theoretical adiabatic ionization energies (IEs) of the rhodium-holmium bimetallic clusters RhHo(2)O(n) (n=0-2) have been determined using photoionization efficiency spectroscopy and density functional theory (DFT) calculations. Both sets of data show the IE of RhHo(2)O to be significantly lower than the values for RhHo(2) and RhHo(2)O(2), which are found to be similar. This indicates that there are significant changes in electronic properties upon sequential addition of oxygen atoms to RhHo(2). The DFT investigations show that the lowest energy neutral structures are a C(2v) triangle for RhHo(2), a C(2v) planar structure for RhHo(2)O where the O atom is doubly bridged to the Ho-Ho bond, and a C(2v) nonplanar structure for RhHo(2)O(2), where the O(2) is dissociative and each O atom is doubly bridged to the Ho-Ho bond in the cluster above and below the RhHo(2) trimer plane. Good correlation between the experimental and computational IE data imply that the lowest energy neutral structures calculated are the most likely isomers ionized in the molecular beam. In particular, the theoretical adiabatic IE for the dissociative RhHo(2)O(2) structure is found to compare better with the experimentally determined value than the corresponding lowest energy O(2) associative structure.Alexander S. Gentleman, Matthew A. Addicoat, Viktoras Dryza, Jason R. Gascooke, Mark A. Buntine, and Gregory F. Meth

Determinants of Glycan Receptor Specificity of H2N2 Influenza A Virus Hemagglutinin

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.National Institute of General Medical Sciences (U.S.) (GM57073)National Institute of General Medical Sciences (U.S.) (U54 GM62116)Singapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technolog