Water relations determine short time leaf growth patterns in the mangrove Avicennia marina (Forssk.) Vierh.

High‐resolution leaf growth is rarely studied despite its importance as a metric for plant performance and resource use efficiency. This is in part due to methodological challenges. Here, we present a method for in situ leaf growth measurements in a natural environment. We measured instantaneous leaf growth on a mature Avicennia marina subsp. australasica tree over several weeks. We measured leaf expansion by taking time‐lapse images and analysing them using marker tracking software. A custom‐made instrument was designed to enable long‐term field studies. We detected a distinct diel growth pattern with leaf area shrinkage in the morning and leaf expansion in the afternoon and at night. On average, the observed daily shrinkage was 37% of the net growth. Most of the net growth occurred at night. Diel leaf area shrinkage and recovery continued after growth cessation. The amount of daily growth was negatively correlated with shrinkage, and instantaneous leaf growth and shrinkage were correlated with changes in leaf turgor. We conclude that, at least in this tree species, instantaneous leaf growth patterns are very strongly linked to, and most likely driven by, leaf water relations, suggesting decoupling of short‐term growth patterns from carbon assimilation.     

The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling

Cellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1 KO cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.     

Functional insight into LOAD-associated microglial response genes

Alzheimer''s disease (AD) is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), neuronal and synaptic loss and inflammation of the central nervous system (CNS). The majority of AD research has been dedicated to the understanding of two major AD hallmarks (i.e. Aβ and NFTs); however, recent genome-wide association studies (GWAS) data indicate neuroinflammation as having a critical role in late-onset AD (LOAD) development, thus unveiling a novel avenue for AD therapeutics. Recent evidence has provided much support to the innate immune system''s involvement with AD progression; however, much remains to be uncovered regarding the role of glial cells, specifically microglia, in AD. Moreover, numerous variants in immune and/or microglia-related genes have been identified in whole-genome sequencing and GWAS analyses, including such genes as TREM2, CD33, APOE, API1, MS4A, ABCA7, BIN1, CLU, CR1, INPP5D, PICALM and PLCG2. In this review, we aim to provide an insight into the function of the major LOAD-associated microglia response genes.     

Hormone‐mediated foraging strategies in an uncertain environment: Insights into the at‐sea behavior of a marine predator

1. Hormones are extensively known to be physiological mediators of energy mobilization and allow animals to adjust behavioral performance in response to their environment, especially within a foraging context.
2. Few studies, however, have narrowed focus toward the consistency of hormonal patterns and their impact on individual foraging behavior. Describing these relationships can further our understanding of how individuals cope with heterogeneous environments and exploit different ecological niches.
3. To address this, we measured between‐ and within‐individual variation of basal cortisol (CORT), thyroid hormone T3, and testosterone (TEST) levels in wild adult female Galápagos sea lions (Zalophus wollebaeki) and analyzed how these hormones may be associated with foraging strategies. In this marine predator, females exhibit one of three spatially and temporally distinct foraging patterns (i.e., “benthic,” “pelagic,” and “night” divers) within diverse habitat types.
4. Night divers differentiated from other strategies by having lower T3 levels. Considering metabolic costs, night divers may represent an energetically conservative strategy with shorter dive durations, depths, and descent rates to exploit prey which migrate up the water column based on vertical diel patterns.
5. Intriguingly, CORT and TEST levels were highest in benthic divers, a strategy characterized by congregating around limited, shallow seafloors to specialize on confined yet reliable prey. This pattern may reflect hormone‐mediated behavioral responses to specific risks in these habitats, such as high competition with conspecifics, prey predictability, or greater risks of predation.
6. Overall, our study highlights the collective effects of hormonal and ecological variation on marine foraging. In doing so, we provide insights into how mechanistic constraints and environmental pressures may facilitate individual specialization in adaptive behavior in wild populations.

     

Effects of high pressure and temperature on the wild-type and F29W mutant forms of the N-domain of avian troponin C

The N-domain of troponin C (residues 1-90) regulates muscle contraction through conformational changes induced by Ca2+ binding. A mutant form of the isolated domain of avian troponin C (F29W) has been used in previous studies to observe conformational changes that occur upon Ca2+ binding, and pressure and temperature changes. Here we set out to determine whether the point mutation itself has any effects on the protein structure and its stability to pressure and temperature in the absence of Ca2+. Molecular dynamics simulations of the wild-type and mutant protein structures suggested that both structures are identical except in the main chain and the loop I region near the mutation site. Also, the simulations proposed that an additional cavity had been created in the core of the mutant protein. To determine whether such a cavity would affect the behavior of the protein when subjected to high pressures and temperatures, we performed 1H-NMR experiments at 300, 400, and 500 MHz on the wild-type and F29W mutant forms of the chicken N-domain troponin C in the absence of Ca2+. We found that the mutant protein at 5 kbar pressures had a destabilized beta-sheet between the Ca2+-binding loops, an altered environment near Phe-26, and reduced local motions of Phe-26 and Phe-75 in the core of the protein, probably due to a higher compressibility of the mutant. Under the same pressure conditions, the wild-type domain exhibited little change. Furthermore, the hydrophobic core of the mutant protein denatured at temperatures above 47 degrees C, while the wild-type was resistant to denaturation up to 56 degrees C. This suggests that the partially exposed surface mutation (F29W) significantly destabilizes the N-domain of troponin C by altering the packing and dynamics of the hydrophobic core.     

Dendritic h channelopathy in epileptogenesis

Recent work has suggested a link between h channels and epilepsy. In this issue of Neuron, Shah et al. demonstrate that a robust, postseizure decrease in h channels during a critical phase of epileptogenesis mechanistically underlies dendritic hyperexcitability in entorhinal-hippocampal pyramidal cells.     

Molecular tools for a molecular medicine: analyzing genes, transcripts and proteins using padlock and proximity probes

Procedures and reagents are needed to specifically detect all the macromolecules that are being identified in the course of genome projects. We discuss how this challenge may be met using a set of ligation-based reagents termed padlock probes and proximity ligation probes. These probes include elements with affinity for specific nucleic acid and protein molecules, respectively, along with unique identifier DNA sequence elements that encode the identity of the recognized target molecules. The information content of DNA strands that form in the detection reactions are recorded after amplification, allowing the recognized target molecules to be identified. The procedures permit highly specific solution-phase or localized analyses of large sets of target molecules as required in future molecular analyses.     

Studies on gangliosides with affinity for Helicobacter pylori: binding to natural and chemically modified structures

Helicobacter pylori, like many other microbes, has the ability to bind to carbohydrate epitopes. Several sugar sequences have been reported as active for the bacterium, including some neutral, sulfated, and sialylated structures. We investigated structural requirements for the sialic acid-dependent binding using a number of natural and chemically modified gangliosides. We have chosen for derivatization studies two kinds of binding-active glycolipids, the simple ganglioside S-3PG (Neu5Ac alpha 3Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer, sialylparagloboside) and branched polyglycosylceramides (PGCs) of human origin. The modifications included oxidation of the sialic acid glycerol chain, reduction of the carboxyl group, amidation of the carboxyl group, and lactonization. Binding experiments confirmed a preference of H. pylori for 3-linked sialic acid and penultimate 4-linked galactose. As expected, neolacto gangliosides (with Gal beta 4GlcNAc in the core structure) were active in our assays, whereas gangliosides with lacto (Gal beta 3GlcNAc) and ganglio (Gal beta 3GalNAc) carbohydrate chains were not. Negative binding results were also obtained for disialylparagloboside (with terminal NeuAc alpha 8NeuAc) and NeuAc alpha 6-containing glycolipids. Chemical studies revealed dependence of the binding on Neu5Ac and its glycerol and carboxyl side chains. Most of the derivatizations performed on these groups abolished the binding; however, some of the amide forms turned out to be active, and one of them (octadecylamide) was found to be an excellent binder. The combined data from molecular dynamics simulations indicate that the binding-active configuration of the terminal disaccharide of S-3PG is with the sialic acid in the anticlinal conformation, whereas in branched PGCs the same structural element most likely assumes the synclinal presentation.     

Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a population from the northern United Kingdom

BACKGROUND: A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white, U.S. citizens carrying at least one 2x 28-bp repeat allele have recently been shown to be at a four-fold increased risk of spina bifida (SB). We investigated the association between this polymorphism and risk of NTD in families affected by NTDs and controls from the northern United Kingdom (UK). METHODS: PCR was performed on genomic DNA extracted from blood or mouth swabs of family members affected by NTDs (mothers, fathers, and cases), and unaffected controls (mothers and infants) to determine the number of 28-bp repeat units within the promoter region of TYMS. Case-control and TDT analyses of the influence of TYMS genotype on risk of NTD, or NTD pregnancy, were conducted. RESULTS: Odds ratio (OR) analysis indicated that individuals carrying the 2x 28-bp repeat allele either in homozygous or heterozygous form, are not at increased risk of NTDs, or of having an NTD affected pregnancy. Control population allele frequencies are seen to be markedly different between the U.S. controls and those in this study. CONCLUSIONS: TYMS polymorphism appears to be not universally associated with NTD risk across Caucasian samples. The elevated risk of spina bifida in U.S. samples appears to be driven by an unusually low risk allele (2x 28 bp) frequency in control samples. Family based (TDT) testing of U.S. samples is therefore advocated.