Improving the tokenisation of identifier names

Identifier names are the main vehicle for semantic information during program comprehension. For tool-supported program comprehension tasks, including concept location and requirements traceability, identifier names need to be tokenised into their semantic constituents. In this paper we present an approach to the automated tokenisation of identifier names that improves on existing techniques in two ways. First, it improves the tokenisation accuracy for single-case identifier names and for identifier names containing digits, which existing techniques largely ignore. Second, performance gains over existing techniques are achieved using smaller oracles, making the approach easier to deploy. Accuracy was evaluated by comparing our algorithm to manual tokenizations of 28,000 identifier names drawn from 60 well-known open source Java projects totalling 16.5 MSLOC. Moreover, the projects were used to perform a study of identifier tokenisation features (single case, camel case, use of digits, etc.) per object-oriented construct (class names, method names, local variable names, etc.), thus providing an insight into naming conventions in industrial-scale object-oriented code. Our tokenisation tool and datasets are publicly available

CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity

BACKGROUND: CP-31398 is a small molecule that has been reported to stabilize the DNA-binding core domain of the human tumor suppressor protein p53 in vitro. The compound was also reported to function as a potential anti-cancer drug by rescuing the DNA-binding activity and, consequently, the transcription activation function of mutant p53 protein in mammalian tissue culture cells and in mice. RESULTS: We performed a series of gene expression experiments to test the activity of CP-31398 in yeast and in human cell cultures. With these cell-based assays, we were unable to detect any specific stimulation of mutant p53 activity by this compound. Concentrations of CP-31398 that were reported to be active in the published work were highly toxic to the human H1299 lung carcinoma and Saos-2 cell lines in our experiments. CONCLUSION: In our experiments, the small molecule CP-31398 was unable to reactivate mutant p53 protein. The results of our in vivo experiments are in agreement with the recently published biochemical analysis of CP-31398 showing that this molecule does not bind p53 as previously claimed, but intercalates into DNA

Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions

A phosphatase cascade by which rewarding stimuli control nucleosomal response

ArticleInternational audienceDopamine orchestrates motor behaviour and reward-driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases the phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascad

Expression of Calmodulin and Myosin Light Chain Kinase during Larval Settlement of the Barnacle Balanus amphitrite

Barnacles are one of the most common organisms in intertidal areas. Their life cycle includes seven free-swimming larval stages and sessile juvenile and adult stages. The transition from the swimming to the sessile stages, referred to as larval settlement, is crucial for their survivor success and subsequent population distribution. In this study, we focused on the involvement of calmodulin (CaM) and its binding proteins in the larval settlement of the barnacle, Balanus ( = Amphibalanus) amphitrite. The full length of CaM gene was cloned from stage II nauplii of B. amphitrite (referred to as Ba-CaM), encoding 149 amino acid residues that share a high similarity with published CaMs in other organisms. Quantitative real-time PCR showed that Ba-CaM was highly expressed in cyprids, the stage at which swimming larvae are competent to attach and undergo metamorphosis. In situ hybridization revealed that the expressed Ba-CaM gene was localized in compound eyes, posterior ganglion and cement glands, all of which may have essential functions during larval settlement. Larval settlement assays showed that both the CaM inhibitor compound 48/80 and the CaM-dependent myosin light chain kinase (MLCK) inhibitor ML-7 effectively blocked barnacle larval settlement, whereas Ca2+/CaM-dependent kinase II (CaMKII) inhibitors did not show any clear effects. The subsequent real-time PCR assay showed a higher expression level of Ba-MLCK gene in larval stages than in adults, suggesting an important role of Ba-MLCK gene in larval development and competency. Overall, the results suggest that CaM and CaM-dependent MLCK function during larval settlement of B. amphitrite

Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

There is a long-standing paradox that N-methyl-D-aspartate receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington’s disease and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling

Slow versus fast proteins in the stimulation of beta-cell response and the activation of the entero-insular axis in type 2 diabetes

Background We tested whether ingestion of whey protein can induce greater post-prandial amino acid (AA) levels in the plasma and a higher beta-cell response than casein ingestion in type 2 diabetes mellitus patients. Methods The study was designed as a double-blind, randomized, and controlled cross-over clinical trial. Twelve post-absorptive type 2 diabetic subjects who were withdrawn from their usual hypoglycemic therapy were studied. A medium calorie (approximate to 6 kca/kg BW), high protein (approximate to 50% of total kcal) mixed meal, containing whey protein, casein, or a free amino acid (FREE AA) mixture matching the casein AA composition, was randomly administered on three different occasions. Results Following ingestion of whey protein, plasma concentrations of total, branched chain, and essential AA were 25-50% greater than after ingestion of casein (p < 0.0001), and were similar to those observed after the FREE AA meal. With whey protein, C-peptide, insulin, and pro-insulin concentrations were greater by 12-40% (p < 0.02 or less) than with casein, and similar to those with FREE AA. Glucagon-like polypeptide 1 (GLP-1) response tended to be lower with casein than with whey protein. Glucose-dependent insulinotropic polypeptide (GIP) response was greater with either whey protein or casein than with FREE AA. Post-prandial glucose concentrations were similar after whey protein and casein ingestion, but lower after the FREE AA meal. Conclusions In type 2 diabetes, the ingestion of a fast-absorbable protein results in a greater post-prandial aminoacidemia and a higher beta-cell secretion than the ingestion of a 'slow' protein. Whether these changes can be maintained chronically in combination with hypoglycemic therapy, possibly also resulting in better glycemic control, remains to be establishe

Importin α transports CaMKIV to the nucleus without utilizing importin β

Ca(2+)/calmodulin-dependent protein kinase type IV (CaMKIV) plays an essential role in the transcriptional activation of cAMP response element-binding protein-mediated signaling pathways. Although CaMKIV is localized predominantly in the nucleus, the molecular mechanism of the nuclear import of CaMKIV has not been elucidated. We report here that importin α is able to carry CaMKIV into the nucleus without the need for importin β or any other soluble proteins in digitonin-permeabilized cells. An importin β binding-deficient mutant (ΔIBB) of importin α also carried CaMKIV into the nucleus, which strongly suggests that CaMKIV is transported in an importin β-independent manner. While CaMKIV directly interacted with the C-terminal region of importin α, the CaMKIV/importin α complex did not form a ternary complex with importin β, which explains the nonrequirement of importin β for the nuclear transport of CaMKIV. The cytoplasmic microinjection of importin α-ΔIBB enhanced the rate of nuclear translocation of CaMKIV in vivo. This is the first report to demonstrate definitely that mammalian importin α solely carries a cargo protein into the nucleus without utilizing the classical importin β-dependent transport system