Differences in cue-dependent spatial navigation may be revealed by in-depth swimming analysis

Several factors can influence allocentric navigation in the Morris water maze (MWM), including the number of available distal visual cues. Using in-depth analytical measures investigating platform-based and swimming behaviour, we examine and compare animals exposed to either one or three distal visual cues during MWM acquisition. We demonstrate that, although animals exposed to one cue can acquire the task as well as those in a multiple cue condition, several subtle differences between the groups’ swimming behaviours are noted. Both groups actively use cues to guide them to the platform, but changing the number of cues alters the animals’ patterns of behaviour, wherein exposure to a single cue leads to a simpler strategy in which the cue appears to act as a beacon for navigation.     

Connectivity,regime shifts and the resilience of coral reefs

Connectivity of larvae among metapopulations in open marine systems can be a double-edged sword, allowing for the colonization and replenishment of both desirable and undesirable elements of interacting species-rich assemblages. This article studies the effect of recruitment by coral and macroalgae on the resilience of grazed reef ecosystems. In particular, we focus on how larval connectivity affects regime shifts between alternative assemblages that are dominated either by corals or by macroalgae. Using a model with bistability dynamics, we show that recruitment of coral larvae erodes the resilience of a macroalgae-dominated ecosystem when grazing is high, but has negligible effect when grazing is low. Conversely, recruitment by macroalgae erodes the resilience of a coral-dominated ecosystem when grazing is low, leading to a regime shift to macroalgae. Thus, spillover of coral recruits from highly protected areas will not restore coral cover or prevent flips to macroalgae in the surrounding seascape if grazing levels in these areas are depleted, but may be pivotal for re-building coral populations if grazing is high. Fishing restrictions and the re-introduction of herbivores should therefore be a prime conservation objective for preventing undesirable regime shifts. Connectivity by some components of coral reef assemblages (e.g., macroalgae, pathogens, crown-of-thorns starfish) may be detrimental to sustaining reefs, especially where overfishing and other drivers have eroded their resilience, making them more vulnerable to a regime shift.     

The dynamic ups and downs of genome size evolution in Brassicaceae

Crucifers (Brassicaceae, Cruciferae) are a large family comprisingsome 338 genera and c. 3,700 species. The family includes importantcrops as well as several model species in various fields ofplant research. This paper reports new genome size (GS) datafor more than 100 cruciferous species in addition to previouslypublished C-values (the DNA amount in the unreplicated gameticnuclei) to give a data set comprising 185 Brassicaceae taxa,including all but 1 of the 25 tribes currently recognized. Evolutionof GS was analyzed within a phylogenetic framework based ongene trees built from five data sets (matK, chs, adh, trnLF,and ITS). Despite the 16.2-fold variation across the family,most Brassicaceae species are characterized by very small genomeswith a mean 1C-value of 0.63 pg. The ancestral genome size (ancGS)for Brassicaceae was reconstructed as ^anc1C = 0.50 pg. Approximately50% of crucifer taxa analyzed showed a decrease in GS comparedwith the ancGS. The remaining species showed an increase inGS although this was generally moderate, with significant increasesin C-value found only in the tribes Anchonieae and Physarieae.Using statistical approaches to analyze GS, evolutionary gainsor losses in GS were seen to have accumulated disproportionatelyfaster within longer branches. However, we also found that GShas not changed substantially through time and most likely evolvespassively (i.e., a tempo that cannot be distinguished betweenneutral evolution and weak forms of selection). The data revealan apparent paradox between the narrow range of small GSs overlong evolutionary time periods despite evidence of dynamic genomicprocesses that have the potential to lead to genome obesity(e.g., transposable element amplification and polyploidy). Toresolve this, it is suggested that mechanisms to suppress amplificationand to eliminate amplified DNA must be active in Brassicaceaealthough their control and mode of operation are still poorlyunderstood.     

New vanadium-based magnetic resonance imaging probes: clinical potential for early detection of cancer

We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with a new class of cancer-specific contrast agents, containing vanadyl (VO²⁺)-chelated organic ligands, specifically bis(acetylacetonato)oxovanadium(IV) [VO(acac)₂]. Vanadyl compounds have been found to accumulate within cells, where they interact with intracellular glycolytic enzymes. Aggressive cancers are metabolically active and highly glycolytic; an MRI contrast agent that enters cells with high glycolytic activity could provide high-resolution functional images of tumor boundaries and internal structure, which cannot be achieved by conventional contrast agents. The present work demonstrates properties of VO(acac)₂ that may give it excellent specificity for cancer detection. A high dose of VO(acac)₂ did not cause any acute or short-term adverse reactions in murine subjects. Calorimetry and spectrofluorometric methods demonstrate that VO(acac)₂ is a blood pool agent that binds to serum albumin with a dissociation constant K _d ~ 2.5 ± 0.7 × 10⁻⁷ M and a binding stoichiometry n = 1.03 ± 0.04. Owing to its prolonged blood half-life and selective leakage from hyperpermeable tumor vasculature, a low dose of VO(acac)₂ (0.15 mmol/kg) selectively enhanced in vivo magnetic resonance images of tumors, providing high-resolution images of their interior structure. The kinetics of uptake and washout are consistent with the hypothesis that VO(acac)₂ preferentially accumulates in cancer cells. Although VO(acac)₂ has a lower relaxivity than gadolinium-based MRI contrast agents, its specificity for highly glycolytic cells may lead to an innovative approach to cancer detection since it has the potential to produce MRI contrast agents that are nontoxic and highly sensitive to cancer metabolism.     

Synthesis of novel Gn-RH analogues using Ugi-4MCR

An efficient method for the synthesis of some Gn-RH analogues based on Ugi reaction has been developed. Four-component reaction of N- and C-terminus peptides, aromatic aldehydes and isocyanides affords novel Gn-RH analogues derived from triptorelin and gonadorelin. All of the products were purified using preparative HPLC and the structures were assigned according to MALDI-mass spectrometry data.     

Maf1 regulates intracellular lipid homeostasis in response to DNA damage response activation

Surveillance of DNA damage and maintenance of lipid metabolism are critical factors for general cellular homeostasis. We discovered that in response to DNA damage–inducing UV light exposure, intact Caenorhabditis elegans accumulate intracellular lipids in a dose-dependent manner. The increase in intracellular lipids in response to exposure to UV light utilizes mafr-1, a negative regulator of RNA polymerase III and the apical kinases atm-1 and atl-1 of the DNA damage response (DDR) pathway. In the absence of exposure to UV light, the genetic ablation of mafr-1 results in the activation of the DDR, including increased intracellular lipid accumulation, phosphorylation of ATM/ATR target proteins, and expression of the Bcl-2 homology region genes, egl-1 and ced-13. Taken together, our results reveal mafr-1 as a component the DDR pathway response to regulating lipid homeostasis following exposure to UV genotoxic stress.     

Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty

Frailty is an important geriatric syndrome that predicts disability and mortality. Substantial evidence suggests inflammation marked by elevated IL-6 levels as a key pathophysiologic factor that contributes to frailty. CXCL-10, a potent pro-inflammatory chemokine, has increased levels with age and is implicated in several inflammatory conditions. To better understand molecular mechanisms of inflammation activation in frailty, we evaluated monocytic expression of CXCL-10 and other inflammatory pathway genes by pathway-specific gene array analysis and quantitative RT-PCR. Frailty status was determined by the validated criteria. Sixteen pairs of community-dwelling frail and age-, race-, and sex-matched non-frail participants (mean age 83 years, range 72–94) completed the study. Here we report that frail participants had higher CXCL-10 expression levels than matched non-frail controls (1.05 ± 0.88 versus 0.53 ± 0.39, p = 0.04). CXCL-10 expression correlated with IL-6 levels only in frail participants (Spearman correlation coefficient r = 0.52, p = 0.03). Furthermore, frailty-associated CXCL-10 upregulation was highly correlated with IL-6 elevation, both measured by frail-over-non-frail ratios (r = 0.93, p < 0.0001). These findings suggest upregulated monocytic expression of CXCL-10 as an important molecular mechanism that contributes to inflammation activation in frail older adults. Therapeutic implications include potential development of CXCL-10-based interventional strategies for the prevention and treatment of frailty in older adults.     

A novel fluorescent α-conotoxin for the study of α7 nicotinic acetylcholine receptors

Homomeric α7 nicotinic acetylcholine receptors are a well-established, pharmacologically distinct subtype. The more recently identified α9 subunit can also form functional homopentamers as well as α9α10 heteropentamers. Current fluorescent probes for α7 nicotinic ACh receptors are derived from α-bungarotoxin (α-BgTx). However, α-BgTx also binds to α9* and α1* receptors which are coexpressed with α7 in multiple tissues. We used an analog of α-conotoxin ArIB to develop a highly selective fluorescent probe for α7 receptors. This fluorescent α-conotoxin, Cy3-ArIB[V11L;V16A], blocked ACh-evoked α7 currents in Xenopus laevis oocytes with an IC₅₀ value of 2.0 nM. Observed rates of blockade were minute-scale with recovery from blockade even slower. Unlike FITC-conjugated α-BgTx, Cy3-ArIB[V11L;V16A] did not block α9α10 or α1β1δε receptors. In competition binding assays, Cy3-ArIB[V11L;V16A] potently displaced [¹²⁵I]-α-BgTx binding to mouse hippocampal membranes with a K _i value of 21 nM. Application of Cy3-ArIB[V11L;V16A] resulted in specific punctate labeling of KXα7R1 cells but not KXα3β2R4, KXα3β4R2, or KXα4β2R2 cells. This labeling could be abolished by pre-treatment with α-cobratoxin. Thus, Cy3-ArIB[V11L;V16A] is a novel and selective fluorescent probe for α7 receptors.