The Pattern and Loci of Training-Induced Brain Changes in Healthy Older Adults Are Predicted by the Nature of the Intervention

There is enormous interest in designing training methods for reducing cognitive decline in healthy older adults. Because it is impaired with aging, multitasking has often been targeted and has been shown to be malleable with appropriate training. Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects, as well as provide models for selecting appropriate training methods. The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes - a result that might relate to differences in training formats. The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice. Forty-eight older adults were randomly allocated to one of three training programs. In the SINGLE REPEATED training, participants practiced an alphanumeric equation and a visual detection task, each under focused attention. In the DIVIDED FIXED training, participants practiced combining verification and detection by divided attention, with equal attention allocated to both tasks. In the DIVIDED VARIABLE training, participants completed the task by divided attention, but were taught to vary the attentional priority allocated to each task. Brain activation was measured with fMRI pre- and post-training while completing each task individually and the two tasks combined. The three training programs resulted in markedly different brain changes. Practice on individual tasks in the SINGLE REPEATED training resulted in reduced brain activation whereas DIVIDED VARIABLE training resulted in a larger recruitment of the right superior and middle frontal gyrus, a region that has been involved in multitasking. The type of training is a critical factor in determining the pattern of brain activation.     

Structural evidence for cooperative microtubule stabilization by Taxol and the endogenous dynamics regulator MAP4

Microtubules (MTs) composed of αβ-tubulin heterodimers are highly dynamic polymers, whose stability can be regulated by numerous endogenous and exogenous factors. Both the antimitotic drug Taxol and microtubule-associated proteins (MAPs) stabilize this dynamicity by binding to and altering the conformation of MTs. In the current study, amide hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) was used to examine the structural and dynamic properties of the MT complex with the microtubule binding domain of MAP4 (MTB-MAP4) in the presence and absence of Taxol. The changes in the HDX levels indicate that MTB-MAP4 may bind to both the outside and the luminal surfaces of the MTs and that Taxol reduces both of these interactions. The MTB-MAP4 binding induces conformational rearrangements of α- and β-tubulin that promote an overall stabilization of MTs. Paradoxically, despite Taxol's negative effects on MAP4 interactions with the MTs, its binding to the MTB-MAP4-MT complex further reduces the overall deuterium incorporation, suggesting that a more stable complex is formed in the presence of the drug.     

Depot-specific regulation of autotaxin with obesity in human adipose tissue

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of a bioactive mediator: lysophosphatidic. ATX is abundantly produced by adipocytes and exerts a negative action on adipose tissue expansion. In both mice and humans, ATX expression increases with obesity in association with insulin resistance. In the present study, fat depot-specific regulation of ATX was explored in human. ATX mRNA expression was quantified in visceral and subcutaneous adipose tissue in obese (BMI?>?40?kg/m²; n?=?27) and non-obese patients (BMI?<?25?kg/m²; n?=?10). Whatever the weight status of the patients is, ATX expression was always higher (1.3- to 6-fold) in subcutaneous than in visceral fat. Nevertheless, visceral fat ATX was significantly higher (42?%) in obese than in non-obese patients, whereas subcutaneous fat ATX remained unchanged. In obese patients, visceral fat ATX expression was positively correlated with diastolic arterial blood pressure (r?=?0.67; P?=?0.001). This correlation was not observed with subcutaneous fat ATX. Visceral fat ATX was mainly correlated with leptin (r?=?0.60; P?=?0.001), inducible nitric oxide synthase (r?=?0.58; P?=?0,007), and apelin receptor (r?=?0.50; P?=?0.007). These correlations were not observed with subcutaneous fat ATX. These results reveal that obesity-associated upregulation of human adipose tissue ATX is specific to the visceral fat depot.     

Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells

Hyperproliferation of vascular smooth muscle cells is a hallmark of atherosclerosis and related vascular complications. Microtubules are important for many aspects of mammalian cell responses including growth, migration and signaling. alpha-Tubulin, a component of the microtubule cytoskeleton, is unique amongst cellular proteins in that it undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyr-tubulin). Whereas the reversible detyrosination/tyrosination cycle of alpha-tubulin has been implicated in regulating various aspects of cell biology, the precise function of this posttranslational modification has remained poorly characterized. Herein, we provide evidence suggesting that alpha-tubulin detyrosination is a required event in the proliferation of vascular smooth muscle cells. Proliferation of rat aortic smooth muscle cells in response to serum was temporally associated with the detyrosination of alpha-tubulin, but not acetylation of alpha-tubulin; Glu-tubulin reached maximal levels between 12 and 18h following cell cycle initiation. Inclusion of 3-nitro-l-tyrosine (NO(2)Tyr) in the culture medium resulted in the selective nitrotyrosination of alpha-tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation. Nitrotyrosination of alpha-tubulin did not induce necrotic or apoptotic death of rat aortic smooth muscle cells, but instead led to cell cycle arrest at the G(1)/S boundary coincident with decreased DNA synthesis. Collectively, these results suggest that the C-terminus of alpha-tubulin and its detyrosination are functionally important as a molecular switch that regulates cell cycle progression in vascular smooth muscle cells.     

Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents

The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3′,4,4′,5′-tetramethoxychalcone (1) and 3′,4,4′,5′-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy.     

Resequencing Microarray Technology for Genotyping Human Papillomavirus in Cervical Smears

There are more than 40 human papillomaviruses (HPVs) belonging to the alpha genus that cause sexually transmitted infections; these infections are among the most frequent and can lead to condylomas and anogenital intra-epithelial neoplasia. At least 18 of these viruses are causative agents of anogenital carcinomas. We evaluated the performance of a resequencing microarray for the detection and genotyping of alpha HPV of clinical significance using cloned HPV DNA. To reduce the number of HPV genotypes tiled on microarray, we used reconstructed ancestral sequences (RASs) as they are more closely related to the various genotypes than the current genotypes are among themselves. The performance of this approach was tested by genotyping with a set of 40 cervical smears already genotyped using the commercial PapilloCheck kit. The results of the two tests were concordant for 70% (28/40) of the samples and compatible for 30% (12/40). Our findings indicate that RASs were able to detect and identify one or several HPV in clinical samples. Associating RASs with homonym sequences improved the genotyping of HPV present in cases of multiple infection. In conclusion, we demonstrate the diagnostic potential of resequencing technology for genotyping of HPV, and illustrate its value both for epidemiological studies and for monitoring the distribution of HPV in the post-vaccination era.     

Presence of gastric Helicobacter species in children suffering from gastric disorders in Southern Turkey

Background

Infections with gastric Helicobacter spp. are associated with gastritis, peptic ulceration, and malignancies. Helicobacter pylori is the most prevalent Helicobacter species colonizing the human stomach. Other gastric non‐H. pylori helicobacters (NHPHs) have been described in 0.2%‐6% of human patients with gastric disorders. Nevertheless, due to difficulties in the diagnosis of NHPH infections and lack of routine screening, this is most likely an underestimation of their true prevalence. To the best of our knowledge, no studies have been performed in the presence of Helicobacter spp. in children suffering from gastric disorders in Southern Turkey.

Materials and methods

In total, 110 children with gastric complaints were examined at the Cukurova University Balcali hospital, Turkey. Gastroscopy was performed to evaluate the presence of gastric mucosal lesions. Biopsies of the pyloric gland zone were taken for histopathological analysis, rapid urease testing, and presence of Helicobacter spp. DNA by PCR.

Results

Based on the PCR results, the prevalence of Helicobacter spp. was 32.7% (36/110). H. pylori was found in 30.9% (34/110), H. suis in 1.8% (2/110), and H. heilmannii/H. ailurogastricus in 0.9% (1/110) of the human patients. A mixed infection with H. pylori and H. suis was present in one patient. The presence of mucosal abnormalities, such as nodular inflammation, ulceration, and hyperemia, as well as gastritis, was significantly higher in Helicobacter spp. positive patients.

Conclusion

Helicobacter pylori, H. suis, and H. heilmannii/H. ailurogastricus were present in children with gastric complaints. Infection with these pathogens may be involved in the development of gastritis and ulceration.     

Herbaceous Angiosperms Are Not More Vulnerable to Drought-Induced Embolism Than Angiosperm Trees

The water transport pipeline in herbs is assumed to be more vulnerable to drought than in trees due to the formation of frequent embolisms (gas bubbles), which could be removed by the occurrence of root pressure, especially in grasses. Here, we studied hydraulic failure in herbaceous angiosperms by measuring the pressure inducing 50% loss of hydraulic conductance (P₅₀) in stems of 26 species, mainly European grasses (Poaceae). Our measurements show a large range in P₅₀ from −0.5 to −7.5 MPa, which overlaps with 94% of the woody angiosperm species in a worldwide, published data set and which strongly correlates with an aridity index. Moreover, the P₅₀ values obtained were substantially more negative than the midday water potentials for five grass species monitored throughout the entire growing season, suggesting that embolism formation and repair are not routine and mainly occur under water deficits. These results show that both herbs and trees share the ability to withstand very negative water potentials without considerable embolism formation in their xylem conduits during drought stress. In addition, structure-function trade-offs in grass stems reveal that more resistant species are more lignified, which was confirmed for herbaceous and closely related woody species of the daisy group (Asteraceae). Our findings could imply that herbs with more lignified stems will become more abundant in future grasslands under more frequent and severe droughts, potentially resulting in lower forage digestibility.Terrestrial biomes provide numerous ecosystem services to humans, such as biodiversity refuges, forage supply, carbon sequestration, and associated atmospheric feedback (Bonan, 2008). Drought frequency and severity are predicted to increase across various ecosystems (Dai, 2013), and its impact on the fate of terrestrial biomes has aroused great concern for stakeholders over the past decade. For instance, worldwide forest declines have been associated with drought events (Allen et al., 2010), and the sustainability of grasslands, one of the most important agro-ecosystems representing 26% of the world land area, is threatened due to increasing aridity in the light of climate change (Tubiello et al., 2007; Brookshire and Weaver, 2015). Since the maintenance of grasslands is of prime importance for livestock, and several of the most valuable crops are grasses, herbaceous species deserve more attention from a hydraulic point of view to understand how they will cope with shifts in precipitation and temperature patterns.During water deficit, hydraulic failure in trees has been put forward as one of the primary causes of forest decline (Anderegg et al., 2015, 2016). Drought exacerbates the negative pressure inside the water conducting cells, making the liquid xylem sap more metastable, and thus more vulnerable, to air entry (i.e. gas embolism; Lens et al., 2013a). Extensive levels of embolisms may lead to desiccation, leaf mortality, branch sacrifice, and ultimately plant death (Barigah et al., 2013; Urli et al., 2013). Plant resistance to embolism is therefore assumed to represent a key parameter in determining the drought tolerance of trees and is estimated using so-called vulnerability curves (VCs), from which the P₅₀, i.e. the sap pressure inducing 50% loss of hydraulic conductivity, can be estimated (Cochard et al., 2013). P₅₀ values are therefore good proxies for drought stress tolerance in woody plants and have been published for hundreds of angiosperm and gymnosperm tree species (Delzon et al., 2010; Choat et al., 2012), illustrating a wide range from −0.5 to −19 MPa (Larter et al., 2015).Studies focusing on P₅₀ values of herbs are limited to stems of ∼14 angiosperm species (see Supplemental Table S1 and references cited therein). Half of the herbaceous angiosperms studied so far (Supplemental Table S1) have a stem P₅₀ between 0 and −2 MPa, indicating that many herbs are highly vulnerable to embolism. Moreover, positive root pressure has been reported in various herbs, including many grasses (Poaceae) with hydathodes in their leaves (Evert, 2006), and root pressure is hypothesized to refill embolized conduits overnight when transpiration is low (Miller, 1985; Neufeld et al., 1992; Cochard et al., 1994; Macduff and Bakken, 2003; Saha et al., 2009; Cao et al., 2012). This could suggest that embolism formation and repair follow a daily cycle in herbs. In other words, the midday water potential that herbs experience in the field may often be more negative than P₅₀, which would result in an extremely vulnerable hydraulic pipeline characterized by a negative hydraulic safety margin (expressed as the minimum midday water potential minus P₅₀). In contrast to herbs, most trees operate at a slightly positive hydraulic safety margin (Choat et al., 2012), and woody plants are often too tall to allow refilling by positive root and/or stem pressure in the upper stems (Ewers et al., 1997; Fisher et al., 1997). Therefore, it could be postulated that herbaceous species possess a hydraulic system that is more vulnerable to embolism than that of woody species. In this study, we want to underpin possible differences in embolism resistance between stems of herbaceous and woody angiosperms.The scarcity of P₅₀ measures in herbaceous angiosperms, including grasses and herbaceous eudicots, is mainly due to their fragile stems and low hydraulic conductivity, making VCs technically more challenging. Using minor adaptations to existing centrifuge techniques (Supplemental Text S1), we obtained a P₅₀ stem data set of 26 herbaceous angiosperm species (mainly grasses) from various collection sites in France and Switzerland. In addition, we compared our data set with published data from woody (gymnosperm and angiosperm) species, confronted some of our herbaceous eudicot measurements with original P₅₀ data from derived, woody relatives, and performed anatomical observations in grasses to investigate a possible link between stem anatomical characters and differences in P₅₀ among the species studied. Three main research questions are central in our article: (1) Are stems of herbaceous angiosperms more vulnerable to embolism than those of woody angiosperms? (2) Do grasses operate with highly vulnerable, negative hydraulic safety margins? (3) Do grasses show structure-function trade-offs in their stems with respect to embolism resistance?     

Nematode endoparasites do not codiversify with their stick insect hosts

Host–parasite coevolution stems from reciprocal selection on host resistance and parasite infectivity, and can generate some of the strongest selective pressures known in nature. It is widely seen as a major driver of diversification, the most extreme case being parallel speciation in hosts and their associated parasites. Here, we report on endoparasitic nematodes, most likely members of the mermithid family, infecting different Timema stick insect species throughout California. The nematodes develop in the hemolymph of their insect host and kill it upon emergence, completely impeding host reproduction. Given the direct exposure of the endoparasites to the host's immune system in the hemolymph, and the consequences of infection on host fitness, we predicted that divergence among hosts may drive parallel divergence in the endoparasites. Our phylogenetic analyses suggested the presence of two differentiated endoparasite lineages. However, independently of whether the two lineages were considered separately or jointly, we found a complete lack of codivergence between the endoparasitic nematodes and their hosts in spite of extensive genetic variation among hosts and among parasites. Instead, there was strong isolation by distance among the endoparasitic nematodes, indicating that geography plays a more important role than host‐related adaptations in driving parasite diversification in this system. The accumulating evidence for lack of codiversification between parasites and their hosts at macroevolutionary scales contrasts with the overwhelming evidence for coevolution within populations, and calls for studies linking micro‐ versus macroevolutionary dynamics in host–parasite interactions.