Photoinducible Oncometabolite Detection

Dysregulated metabolism can fuel cancer by altering the production of bioenergetic building blocks and directly stimulating oncogenic gene-expression programs. However, relatively few optical methods for the direct study of metabolites in cells exist. To address this need and facilitate new approaches to cancer treatment and diagnosis, herein we report an optimized chemical approach to detect the oncometabolite fumarate. Our strategy employs diaryl tetrazoles as cell-permeable photoinducible precursors to nitrileimines. Uncaging these species in cells and cell extracts enables them to undergo 1,3-dipolar cycloadditions with endogenous dipolarophile metabolites such as fumarate to form pyrazoline cycloadducts that can be readily detected by their intrinsic fluorescence. The ability to photolytically uncage diaryl tetrazoles provides greatly improved sensitivity relative to previous methods, and enables the facile detection of dysregulated fumarate metabolism through biochemical activity assays, intracellular imaging, and flow cytometry. Our studies showcase an intersection of bioorthogonal chemistry and metabolite reactivity that can be applied for biological profiling, imaging, and diagnostics.     

Patterns of stability in adult attachment: An empirical test of two models of continuity and change.

One of the core assumptions of attachment theory is that attachment representations are stable over time. Unfortunately, the data on attachment stability have been ambiguous, and as a result, alternative theoretical perspectives have evolved to explain them. The objective of the present research was to evaluate alternative models of stability by studying adults in 2 intensive longitudinal investigations. Specifically, we assessed attachment representations in 1 sample (N = 203) daily over a 30-day period and in the other sample (N = 388) weekly over a year. Analyses show that the patterns of stability that exist in adult attachment are most consistent with a prototype model—a model assuming that there is a stable factor underlying temporary variations in attachment. Moreover, although the Big Five personality traits exhibited a pattern of stability that was similar to that of attachment, they did not account for the stability observed in attachment. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Impacts of stress on estimation performance in Hong Kong

Cost estimation not only requires precise technical and analytical input from estimators but also involves the use of subjective judgement. An investigation on the impact of stress on estimation performance was conducted involving 177 professional estimators in Hong Kong. Using correlation analysis, regression analysis and structural equation modelling, the relationships between stress and various aspects of estimation performance are examined and a causal structural model is developed. The results indicate that stress is a cause of negative estimation performance (resulting in weak interpersonal relationships, unfamiliarity with organization and ineffective process), while, simultaneously, it is beneficial to the professional estimation performance. Furthermore, there is an inverted U‐shaped relationship between stress and the organizational relationship.     

Dietary Influences on Bovine Milk cis-9,trans-11-Conjugated Linoleic Acid Content

The effects of grass dry matter (DM) allowance and dietary supplements of full fat rapeseeds on levels of cis-9,trans-11 octadecadienoic (CLA) acid in bovine milk were investigated. Grass allowance of 16 kg/(cow*day) resulted in reduced (p<0.05) milk fat CLA levels (3.91 mg CLA/g fat) compared to 20 kg/(cow*day) after 19 wk treatment. CLA levels increased in milk fat from cows on a high-rapeseed-supplemented diet (p<0.001) (1650 g/(cow*day) full fat rapeseed) compared to the control (pasture) and low rapeseed (p<0.01) (825 g/(cow*day) full fat rapeseed) supplemented diets. The variation in milk fat CLA levels among individual cows over both trials was 1.5–16 mg/g.     

Routine testing of producers' milk supplies for compositional quality using randomly selected samples

In a study over a number of months, involving over 500 milk producers in three locations, and representing bulk milk collection from cans as well as mobile and stationary refrigerated bulk milk tanks, the precision of various random sampling and testing frequencies in estimating the fat, protein and lactose content of milk was evaluated. In addition, the traditional procedure of estimating the composition of milk supplies from chemically preserved composites was compared to values obtained by analysis of fresh samples. While sampling and testing every milk collection gave the most precise estimate of milk composition for each producer, it was found that for producers using refrigerated bulk milk tanks with ex-farm collection, four random samples per month gave a precision of ±4% (or ±0.14% fat approx) for monthly fat content and ±l.2% (or ±0.04% fat approx) for annual fat content. Due to lower variability the precision for both protein and lactose estimation was much higher. The sample compositing procedure, while capable of a relatively high level of precision, did not always achieve this in practice and tended to underestimate the constituents in milk, especially protein and lactose.     

The Lysosomal Protein Saposin B Binds Chloroquine

Chloroquine (CQ) has been widely used in the treatment of malaria since the 1950s, though toxicity and resistance is increasingly limiting its use in the clinic. More recently, CQ is also becoming recognized as an important therapeutic compound for the treatment of autoimmune disorders and has shown activity as an anticancer agent. However, the full extent of CQ pharmacology in humans is still unclear. Herein, we demonstrate that the lysosomal protein saposin B (sapB), critical for select lipid degradation, binds CQ with implications for both CQ function and toxicity. Using isothermal titration calorimetry (ITC) and fluorescence quenching experiments, CQ was shown to bind to the dimeric form of sapB at both pH 5.5 and pH 7.4 with an average binding affinity of 2.3×10⁴ m ^?1. X‐ray crystallography confirmed this, and the first complete crystal structure of sapB with a bound small molecule (CQ) is reported. The results suggest that sapB might play a role in mitigating CQ‐based toxicity and that sapB might itself be overwhelmed by CQ causing impaired lipid degradation.     

Antioxidant and anticancer capacity of saponin‐enriched Carica papaya leaf extracts

The papaya (Carica papaya) leaf (PL) contains high levels of saponins and polyphenolic compounds, and historically, it has been used as a folk medicine for numerous ailments, including cancer. PL is traditionally prepared by hot water extraction; however, optimised extraction conditions have not been assessed. This study optimised conditions for the extraction of saponins from PL and assessed their antioxidant capacity and antipancreatic cancer activity. Optimisation was achieved using response surface methodology. Saponins and total phenolic compounds were assessed for their antioxidant, free radical scavenging, ion‐reducing capacity, and antipancreatic cancer activity. Optimal aqueous extraction conditions were 85 °C, 25 min. and a water‐to‐leaf ratio of 20:1 mL g^?1. Ethanol extracts demonstrated higher antioxidant, free radical scavenging and ion‐reducing capacity, as well as antipancreatic cancer activity. This study revealed that the PL contains numerous bioactive compounds, with significant anticancer activity warranting further studies on the isolation and characterisation of individual bioactive compounds from the PL.     

Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury.     

Using revealed mate preferences to evaluate market force and differential preference explanations for mate selection.

In this article the authors illustrate how revealed preferences (i.e., preferences inferred through an individual’s differential attraction to multiple targets) can be used to investigate the nature of mate preferences. The authors describe how revealed preferences can be estimated and how the reliability of these estimates can be established. Revealed preference estimates were used to explore the level of consensus in judgments of who is and is not attractive and whether revealed preferences are systematically related to self-reported mate preferences and personality traits. Revealed preference estimates were created for over 4,000 participants by examining their attraction to 98 photographs. Participants of both genders showed substantial consensus in judgments of whom they found attractive and unattractive, although men showed higher consensus than women. Revealed preference estimates also showed relationships with corresponding self-rated preferences and with other dispositional characteristics such as personality traits and age. Although the findings demonstrate the existence of meaningful individual differences in preferences, they also indicate an important role for consensual preferences in mate selection processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)