LabCaS: Labeling calpain substrate cleavage sites from amino acid sequence using conditional random fields

The calpain family of Ca²⁺‐dependent cysteine proteases plays a vital role in many important biological processes which is closely related with a variety of pathological states. Activated calpains selectively cleave relevant substrates at specific cleavage sites, yielding multiple fragments that can have different functions from the intact substrate protein. Until now, our knowledge about the calpain functions and their substrate cleavage mechanisms are limited because the experimental determination and validation on calpain binding are usually laborious and expensive. In this work, we aim to develop a new computational approach (LabCaS) for accurate prediction of the calpain substrate cleavage sites from amino acid sequences. To overcome the imbalance of negative and positive samples in the machine‐learning training which have been suffered by most of the former approaches when splitting sequences into short peptides, we designed a conditional random field algorithm that can label the potential cleavage sites directly from the entire sequences. By integrating the multiple amino acid features and those derived from sequences, LabCaS achieves an accurate recognition of the cleave sites for most calpain proteins. In a jackknife test on a set of 129 benchmark proteins, LabCaS generates an AUC score 0.862. The LabCaS program is freely available at: http://www.csbio.sjtu.edu.cn/bioinf/LabCaS . Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Variations in the timing of reinforcement as a training technique for foals (Equus caballus)

Abstract

Horses are used worldwide for a range of activities. Their usefulness and welfare in these pursuits are strongly influenced by their trainability, which may in turn be influenced by learning ability. Handling and riding horses can expose both handler and horse to a considerable risk of injury. This risk can be reduced by employing correct handling procedures that can facilitate learning in horses. As with all training, efficacy is influenced by consistency and timing. To determine the optimum timing of reinforcement, 16 unweaned naïve foals, that had previously undergone minimal human–animal interaction (i.e., not had a headcollar previously applied), of warmblood (WB; n = 6), thoroughbred (TB; n = 5) or warmblood x thoroughbred (WB x TB; n = 6) breeding were randomly assigned to three treatment groups for testing on ten training days at approximately 14-day intervals. Pressure applied to a headcollar via a lead rope was used as the stimulus for each foal to walk forward, and this was repeated until the foal had walked a distance of 8 m. The effects of three different latencies of negative reinforcement were evaluated by releasing the pressure either immediately: as the first foreleg step commenced (Treatment 1); when the second step of the forelegs was completed (Treatment 2) or when the fourth step of the forelegs was completed (Treatment 3). Each foal's rate of learning was measured by the proportion of correct responses relative to the total number of responses performed. Behavioral responses exhibited (rears, strikes, head shakes, falls, sideways movement and hops) and the steps taken over the distance were also recorded.

Initially, the foals undergoing Treatment 1 appeared to learn more quickly than those foals undergoing Treatments 2 and 3, suggesting that Treatment 1 was associated with the greatest compliance and the quickest learning. However, the foals undergoing Treatment 3 ultimately achieved significantly (p < 0.001) more correct responses, suggesting that the longer delay of reinforcement (i.e., the longer duration of aversive stimulus) may enhance learning via the negative reinforcement inherent in lead training in foals. While some conflict behaviors were shown in all treatment groups, most were exhibited on training day 2. This was reflected in the analysis of composite behaviors performed, with training days 1 and 2 being different (p < 0.001) from training day 3, and training days 1–3 being different (p < 0.001) from training days 4–10. These changes indicate that learning occurred in all treatment groups.

The foals used in this study were sired by five different stallions. While the foals sired by stallion 2 (WB) performed significantly (p < 0.001) more correct responses, those foals sired by WB stallions were significantly (p < 0.001) less likely to perform correct responses when compared with those foals of TB or WB x TB breeding. Colts were significantly (p < 0.001) more likely to perform correct responses than were fillies.     

Morningness-eveningness preferences,learning approach and academic achievement of undergraduate medical students

ABSTRACT

Several studies have focused on determining the effect of chronotype and learning approach on academic achievement separately indicating that morning types have an academic advantage over the evening types and so have the deep learners over the surface learners. But, surprisingly none have assessed the possible relationship between chronotype and learning approach. So, the current study aimed to evaluate this association and their individual influence on academic performance as indicated by the Cumulative Grade Point Average (CGPA) as well as the effect of their interaction on academic performance. The study included 345 undergraduate medical students who responded to reduced Morningness-Eveningness Questionnaire and Biggs Revised Two-Factor Study Process Questionnaire. Morning types indulged in deep learning while evening types in surface learning. Morning and evening types did not differ on academic performance but deep learners had better academic outcomes than their counterparts. The interaction between chronotype and learning approach was significant on determining academic achievement. Our findings gave the impression that chronotype could have an impact on academic performance not directly but indirectly through learning approaches.     

Unaltered Instrumental Learning and Attenuated Body-Weight Gain in Rats During Non-rotating Simulated Shiftwork

Exposure to shiftwork has been associated with multiple health disorders and cognitive impairments in humans. We tested if we could replicate metabolic and cognitive consequences of shiftwork, as reported in humans, in a rat model comparable to 5 wks of non-rotating night shifts. The following hypotheses were addressed: (i) shiftwork enhances body-weight gain, which would indicate metabolic effects; and (ii) shiftwork negatively affects learning of a simple goal-directed behavior, i.e., the association of lever pressing with food reward (instrumental learning), which would indicate cognitive effects. We used a novel method of forced locomotion to model work during the animals' normal resting period. We first show that Wistar rats, indeed, are active throughout a shiftwork protocol. In contrast with previous findings, the shiftwork protocol attenuated the normal weight gain to 76?±?8?g in 5 wks as compared to 123?±?15?g in the control group. The discrepancy with previous work may be explained by the concurrent observation that with our shiftwork protocol rats did not adjust their between-work circadian activity pattern. They maintained a normal level of activity during the “off-work” periods. In the control experiment, rats were kept active during the dark period, normally dominated by activity. This demonstrated that forced activity, per se, did not affect body-weight gain (mean±SEM: 85?±?11?g over 5 wks as compared to 84?±?11?g in the control group). Rats were trained on an instrumental learning paradigm during the fifth week of the protocol. All groups showed equivalent increases in lever pressing from the first (3.8?±?.7) to the sixth (21.3?±?2.4) session, and needed a similar amount of sessions (5.1?±?.3) to reach a learning criterion (≥27 out of 30 lever presses). These results suggest that while on prolonged non-rotating shiftwork, not fully reversing the circadian rhythm might actually be beneficial to prevent body-weight gain and cognitive impairments. (Author correspondence: C.Leenaars@nin.knaw.nl)     

Education for sustainability in higher education: a multiple-case study of three courses

Education for sustainability (EfS) in higher education is an emerging specialisation within the general field of EfS. EfS encompasses cognitive, affective and behavioural aspects, and aims at enhancing a variety of learning outcomes in these domains and reaching students from all programmes. One of the main challenges for higher education educators is to design courses in a way that will effectively promote the various learning outcomes of EfS. A central question is how sustainability should be integrated into the curriculum; which topics should be taught and which pedagogies ought to be applied to improve students’ knowledge, skills and motivation to promote sustainable living. The present study aimed to contribute to the knowledge about students’ learning outcomes yielded by different designs of EfS courses. This multiple-case study of three courses used a mixed-methods design. For each course, we identified its characteristics and analysed students’ self-reported learning outcomes. We found that: (1) a course with a higher degree of participatory learning, employing a system approach, promoted the highest and most varied learning outcomes; (2) the lecture-based course yielded the fewest learning outcomes; and (3) field trips promoted learning outcomes only when accompanied by more advanced pedagogies.     

Protease‐activated receptor‐1 modulates hippocampal memory formation and synaptic plasticity

Protease‐activated receptor‐1 (PAR1) is an unusual G‐protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1?/? mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1?/? mice have deficits in hippocampus‐dependent memory. We also show that while PAR1?/? mice have normal baseline synaptic transmission at Schaffer collateral‐CA1 synapses, they exhibit severe deficits in N‐methyl‐d ‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR‐mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR‐dependent processes subserving memory formation and synaptic plasticity.     

Learning and signal copying facilitate communication among bird species

Signals relevant to different sets of receivers in different contexts create a conflict for signal design. A classic example is vocal alarm signals, often used both during intraspecific and interspecific interactions. How can signals alert individuals from a variety of other species in some contexts, while also maintaining efficient communication among conspecifics? We studied heterospecific responses to avian alarm signals that drive the formation of anti-predator groups but are also used during intraspecific interactions. In three species-rich communities in the western Himalayas, alarm signals vary drastically across species. We show that, independently of differences in their calls, birds respond strongly to the alarm signals of other species with which they co-occur and much more weakly to those of species with which they do not co-occur. These results suggest that previous exposure and learning maintain heterospecific responses in the face of widespread signal divergence. At an area where only two species regularly interact, one species'' calls incorporate the call of the other. We demonstrate experimentally that signal copying allows strong responses even without previous exposure and suggest that such hybrid calls may be especially favoured when pairwise interactions between species are strong.     

Reception and learning of electric fields in bees

Honeybees, like other insects, accumulate electric charge in flight, and when their body parts are moved or rubbed together. We report that bees emit constant and modulated electric fields when flying, landing, walking and during the waggle dance. The electric fields emitted by dancing bees consist of low- and high-frequency components. Both components induce passive antennal movements in stationary bees according to Coulomb''s law. Bees learn both the constant and the modulated electric field components in the context of appetitive proboscis extension response conditioning. Using this paradigm, we identify mechanoreceptors in both joints of the antennae as sensors. Other mechanoreceptors on the bee body are potentially involved but are less sensitive. Using laser vibrometry, we show that the electrically charged flagellum is moved by constant and modulated electric fields and more strongly so if sound and electric fields interact. Recordings from axons of the Johnston organ document its sensitivity to electric field stimuli. Our analyses identify electric fields emanating from the surface charge of bees as stimuli for mechanoreceptors, and as biologically relevant stimuli, which may play a role in social communication.     

When to approach novel prey cues? Social learning strategies in frog-eating bats

Animals can use different sources of information when making decisions. Foraging animals often have access to both self-acquired and socially acquired information about prey. The fringe-lipped bat, Trachops cirrhosus, hunts frogs by approaching the calls that frogs produce to attract mates. We examined how the reliability of self-acquired prey cues affects social learning of novel prey cues. We trained bats to associate an artificial acoustic cue (mobile phone ringtone) with food rewards. Bats were assigned to treatments in which the trained cue was either an unreliable indicator of reward (rewarded 50% of the presentations) or a reliable indicator (rewarded 100% of the presentations), and they were exposed to a conspecific tutor foraging on a reliable (rewarded 100%) novel cue or to the novel cue with no tutor. Bats whose trained cue was unreliable and who had a tutor were significantly more likely to preferentially approach the novel cue when compared with bats whose trained cue was reliable, and to bats that had no tutor. Reliability of self-acquired prey cues therefore affects social learning of novel prey cues by frog-eating bats. Examining when animals use social information to learn about novel prey is key to understanding the social transmission of foraging innovations.