Eph receptors and their ligands: Promising molecular biomarkers and therapeutic targets in prostate cancer

Although at present, there is a high incidence of prostate cancer, particularly in the Western world, mortality from this disease is declining and occurs primarily only from clinically significant late stage tumors with a poor prognosis. A major current focus of this field is the identification of new biomarkers which can detect earlier, and more effectively, clinically significant tumors from those deemed “low risk”, as well as predict the prognostic course of a particular cancer. This strategy can in turn offer novel avenues for targeted therapies. The large family of Receptor Tyrosine Kinases, the Ephs, and their binding partners, the ephrins, has been implicated in many cancers of epithelial origin through stimulation of oncogenic transformation, tumor angiogenesis, and promotion of increased cell survival, invasion and migration. They also show promise as both biomarkers of diagnostic and prognostic value and as targeted therapies in cancer. This review will briefly discuss the complex roles and biological mechanisms of action of these receptors and ligands and, with regard to prostate cancer, highlight their potential as biomarkers for both diagnosis and prognosis, their application as imaging agents, and current approaches to assessing them as therapeutic targets. This review demonstrates the need for future studies into those particular family members that will prove helpful in understanding the biology and potential as targets for treatment of prostate cancer.     

Polyamines affect the cellular growth and structure of pro‐embryogenic masses in Araucaria angustifolia embryogenic cultures through the modulation of proton pump activities and endogenous levels of polyamines

Polyamines (PAs) are abundant polycationic compounds involved in many physiological processes in plants, including somatic embryogenesis. This study investigates the role of PAs on cellular growth and structure of pro‐embryogenic masses (PEMs), endogenous PA and proton pump activities in embryogenic suspension cultures of Araucaria angustifolia. The embryogenic suspension cultures were incubated with putrescine (Put), spermidine (Spd), spermine (Spm) and the inhibitor methylglyoxal‐bis(guanylhydrazone) (MGBG), respectively (1 mM). After 24 h and 21 days, the cellular growth and structure of PEMs, endogenous PA contents and proton pump activities were analyzed. The addition of Spm reduced the cellular growth and promoted the development of PEMs in embryogenic cultures, which could be associated with a reduction in the activities of proton pumps, such as H⁺‐ATPase P‐ and V‐types and H⁺‐PPases, and alterations in the endogenous PA contents. Spm significantly affected the physiology of the A. angustifolia somatic embryogenesis suspension, as it potentially affects cellular growth and structure of PEMs through the modulation of proton pump activities. This work demonstrates the involvement of exogenous PAs in the modulation of cellular growth and structure of PEMs, endogenous PA levels and proton pump activities during somatic embryogenesis. To our knowledge, this study is the first to report a relationship between PAs and proton pump activities in these processes. The results obtained in this study offer new perspectives for studies addressing the role of PAs and proton pump on somatic embryogenesis in this species.     

Microfragmentation concept explains non-positive environmental heterogeneity–diversity relationships

Although recent studies have revealed that the relationship between diversity and environmental heterogeneity is not always positive, as classical niche theory predicts, scientists have had difficulty interpreting these results from an ecological perspective. We propose a new concept—microfragmentation—to explain how small-scale heterogeneity can have neutral or even negative effect on species diversity. We define microfragmentation as a community level process of splitting habitat into a more heterogeneous environment that can have non-positive effects on the diversity through habitat loss and subsequent isolation. We provide support for the microfragmentation concept with results from spatially explicit heterogeneity–diversity model simulations, in which varying sets of species (with different ratios of specialist and generalist species) were modeled at different levels of configurational heterogeneity (meaning that only the habitat structure was changed, not its composition). Our results indicate that environmental heterogeneity can affect community diversity in the same way as fragmentation at the landscape level. Although generalist species might not be seriously affected by microfragmentation, the persistence of specialist species can be seriously disturbed by small-scale patchiness. The microfragmentation concept provides new insight into community level diversity dynamics and can influence conservation and management strategies.     

Base-Calling Algorithm with Vocabulary (BCV) Method for Analyzing Population Sequencing Chromatograms

Sanger sequencing is a common method of reading DNA sequences. It is less expensive than high-throughput methods, and it is appropriate for numerous applications including molecular diagnostics. However, sequencing mixtures of similar DNA of pathogens with this method is challenging. This is important because most clinical samples contain such mixtures, rather than pure single strains. The traditional solution is to sequence selected clones of PCR products, a complicated, time-consuming, and expensive procedure. Here, we propose the base-calling with vocabulary (BCV) method that computationally deciphers Sanger chromatograms obtained from mixed DNA samples. The inputs to the BCV algorithm are a chromatogram and a dictionary of sequences that are similar to those we expect to obtain. We apply the base-calling function on a test dataset of chromatograms without ambiguous positions, as well as one with 3–14% sequence degeneracy. Furthermore, we use BCV to assemble a consensus sequence for an HIV genome fragment in a sample containing a mixture of viral DNA variants and to determine the positions of the indels. Finally, we detect drug-resistant Mycobacterium tuberculosis strains carrying frameshift mutations mixed with wild-type bacteria in the pncA gene, and roughly characterize bacterial communities in clinical samples by direct 16S rRNA sequencing.     

Science Educational Outreach Programs That Benefit Students and Scientists

Both scientists and the public would benefit from improved communication of basic scientific research and from integrating scientists into education outreach, but opportunities to support these efforts are limited. We have developed two low-cost programs—"Present Your PhD Thesis to a 12-Year-Old" and "Shadow a Scientist”—that combine training in science communication with outreach to area middle schools. We assessed the outcomes of these programs and found a 2-fold benefit: scientists improve their communication skills by explaining basic science research to a general audience, and students'' enthusiasm for science and their scientific knowledge are increased. Here we present details about both programs, along with our assessment of them, and discuss the feasibility of exporting these programs to other universities.     

Borderline Personality and the Detection of Angry Faces

Background

Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients’ ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients’ ability to detect angry faces.

Methods

To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n₁ = 342, n₂ = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured.

Results

Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects.

Conclusions

In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.