Bacillus licheniformis BlaR1 L3 loop is a Zinc metalloprotease activated by self-proteolysis

in PLoS ONE (2012), 7

Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.

in PLoS ONE (2012), 7(8), 42704

Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern ... [more ▼]

Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression. [less ▲]

The Neural Substrates of Memory Suppression: A fMRI Exploration of Directed Forgetting

in PLoS ONE (2012), 7(1), 29905

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The ... [more ▼]

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes. [less ▲]

Circadian preference modulates the neural substrate of conflict processing across the day

in PLoS ONE (2012), 7(1), 29658

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that ... [more ▼]

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions. [less ▲]

Barcoding by Next-Generation Sequencing for Rodent Species Identification from Fresh, Degraded and Environmental Samples

in PLoS ONE (2012), 7(11), 48374

Rodentia are one of the most diverse orders among mammals, with more than 2,000 species currently described. Species assignation based on morphological data alone can present enormous challenges. In this ... [more ▼]

Rodentia are one of the most diverse orders among mammals, with more than 2,000 species currently described. Species assignation based on morphological data alone can present enormous challenges. In this study, we compared the applicability of 100 bp mini-barcodes from cytochrome b and cytochrome c oxidase 1 genes to enable rodent species identification. Based on GenBank sequence datasets of 115 rodent species, a 136 bp fragment of cytochrome b combined with universal rodent primers was selected as the most discriminatory mini-barcode. The efficacy of this new molecular tool was assessed on 946 samples including rodent tissues, feces, museum samples and feces/pellets from predators known to ingest rodents. Utilizing next generation sequencing technologies able to sequence multiple DNAs, 1,140 amplicons were tagged, multiplexed and sequenced together in one single 454 GS-FLX run. Our method was initially validated on a reference sample set including 265 clearly identified rodent tissues, corresponding to 103 different species. Following validation, 85.6% of 555 rodent samples from Europe, Asia and Africa whose species identity was unknown were able to be identified using the BLASTN program and GenBank reference sequences. In addition, our method proved effective even on degraded rodent DNA samples: 91.8% and 75.9% of samples from feces and museum specimens respectively were correctly identified. Finally, we succeeded in determining the diet of 66.7% of the investigated carnivores from their feces and 81.8% of owls from their pellets. Non-rodent species were also identified suggesting that our method is sensitive enough to investigate complete predator diets. This study demonstrates how this molecular identification method combined with high throughput sequencing can open new realms of possibilities in achieving fast, accurate and inexpensive species identification. [less ▲]

Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.

in PLoS ONE (2012), 7(1), 29072

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]

A deletion in the bovine FANCI gene compromises fertility by causing fetal death and brachyspina.

in PLoS ONE (2012), 7(8), 43085

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping ... [more ▼]

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that despite the very low incidence of BS (<1/100,000), carrier frequency is as high as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is likely due to the fact that a large proportion of homozygous mutant calves die during pregnancy. We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility, and propose a genotype-driven screening strategy to detect the corresponding deleterious mutations. [less ▲]

Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats

in PLoS ONE (2011), 6

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food ... [more ▼]

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine , the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes. [less ▲]

Will Elephants Soon Disappear from West African Savannahs?

in PLoS ONE (2011), 6(6),

Precipitous declines in Africa’s native fauna and flora are recognized, but few comprehensive records of these changes have been compiled. Here, we present population trends for African elephants in the 6 ... [more ▼]

Precipitous declines in Africa’s native fauna and flora are recognized, but few comprehensive records of these changes have been compiled. Here, we present population trends for African elephants in the 6,213,000 km2 Sudano-Sahelian range of West and Central Africa assessed through the analysis of aerial and ground surveys conducted over the past 4 decades. These surveys are focused on the best protected areas in the region, and therefore represent the best case scenario for the northern savanna elephants. A minimum of 7,745 elephants currently inhabit the entire region, representing a minimum decline of 50% from estimates four decades ago for these protected areas. Most of the historic range is now devoid of elephants and, therefore, was not surveyed. Of the 23 surveyed elephant populations, half are estimated to number less than 200 individuals. Historically, most populations numbering less than 200 individuals in the region were extirpated within a few decades. Declines differed by region, with Central African populations experiencing much higher declines (276%) than those in West Africa (233%). As a result, elephants in West Africa now account for 86% of the total surveyed. Range wide, two refuge zones retain elephants, one in West and the other in Central Africa. These zones are separated by a large distance (,900 km) of high density human land use, suggesting connectivity between the regions is permanently cut. Within each zone, however, sporadic contacts between populations remain. Retaining such connectivity should be a high priority for conservation of elephants in this region. Specific corridors designed to reduce the isolation of the surveyed populations are proposed. The strong commitment of governments, effective law enforcement to control the illegal ivory trade and the involvement of local communities and private partners are all critical to securing the future of elephants inhabiting Africa’s northern savannas. [less ▲]

A potential role for bat tail membranes in flight control

in PLoS ONE (2011), 6(3), 18214

Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus, indicated that the position of the tail membrane (uropatagium) can significantly influence flight control. Adjusting ... [more ▼]

Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus, indicated that the position of the tail membrane (uropatagium) can significantly influence flight control. Adjusting tail position by increasing the angle of the legs relative to the body, has a two-fold effect; increasing leg-induced wing camber (i.e. locally increased camber and angle of attack of the inner wing surface) and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and nose-down pitching moment produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had a much smaller effect on the level of lift and drag produced. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control. [less ▲]