The 37-residue islet amyloid polypeptide (IAPP) is thought to play an important role in the pathogenesis of type II diabetes. Despite a growing body of evidence implicating membrane interaction in ...IAPP toxicity, the membrane-bound form has not yet been well characterized. Here we used circular dichroism (CD) and fluorescence spectroscopy to investigate the molecular details of the interaction of IAPP with lipid membranes of varying composition. In the presence of membranes containing negatively charged phosphatidylserine (PS), we observed significant acceleration in the formation of IAPP aggregates. This acceleration is strongly modulated by the PS concentration and ionic strength, and is also observed at physiologically relevant PS concentrations. CD spectra of IAPP obtained immediately after the addition of membranes containing PS revealed features characteristic of an α-helical conformation approximately ∼15−19 residues in length. After a longer incubation with membranes, IAPP gave rise to CD spectra characteristic of a β-sheet conformation. Taken together, our CD and fluorescence data indicate that conditions that promote weakly stable α-helical conformations may promote IAPP aggregation. The potential roles of IAPP−membrane interaction and the novel membrane-bound α-helical conformation in IAPP aggregation are discussed.
Self-controlled practice schedules have been shown to enhance motor learning in several contexts, but their effectiveness in structural learning tasks, where the goal is to eventually learn an ...underlying structure or rule, is not well known. Here we examined the use of self-controlled practice in a novel control interface requiring structural learning. In addition, we examined the effect of 'nudging'-i.e., whether altering task difficulty could influence self-selected strategies, and hence facilitate learning. Participants wore four inertial measurement units (IMUs) on their upper body and the goal was to use motions of the upper body to move a screen cursor to different targets presented on the screen. The structure in this task that had to be learned was based on the fact that the signals from the IMUs were linearly mapped to the x- and y- position of the cursor. Participants (N = 62) were split into 3 groups (random, self-selected, nudge) based on whether they had control over the sequence in which they could practice the targets. To test whether participants learned the underlying structure, participants were tested both on the trained targets, as well as novel targets that were not practiced during training. Results showed that during training, the self-selected group showed shorter movement times relative to the random group, and both self-selected and nudge groups adopted a strategy of tending to repeat targets. However, in the test phase, we found no significant differences in task performance between groups, indicating that structural learning was not reliably affected by the type of practice. In addition, nudging participants by adjusting task difficulty did not show any significant benefits to overall learning. These results suggest that although self-controlled practice influenced practice structure and facilitated learning, it did not provide any additional benefits relative to practicing on a random schedule in this task.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Key message
Elite wheat pollinators are critical for successful hybrid breeding. We identified
Rht
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B1
and
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D1
loci affecting multiple pollinator traits and therefore represent major targets ...for improving hybrid seed production.
Hybrid breeding has a great potential to significantly boost wheat yields. Ideal male pollinators would be taller in stature, contain many spikelets well-spaced along the spike and exhibit high extrusion of large anthers. Most importantly, flowering time would match with that of the female parent. Available genetic resources for developing an elite wheat pollinator are limited, and the genetic basis for many of these traits is largely unknown. Here, we report on the genetic analysis of pollinator traits using biparental mapping populations. We identified two anther extrusion QTLs of medium effect, one on chromosome 1BL and the other on 4BS coinciding with the semi-dwarfing
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B1
locus. The effect of
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B1
alleles on anther extrusion is genotype dependent, while tall plant
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B1a
allele is consistently associated with large anthers. Multiple QTLs were identified at the
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D1
locus for anther length, spikelet number and spike length, with the photoperiod-sensitive
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D1b
allele associated with favourable pollinator traits in the populations studied. We also demonstrated that homeoloci,
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D1
and
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B1
, influence anther length among other traits. These results suggest that combinations of
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B1
and
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D1
alleles control multiple pollinator traits and should be major targets of hybrid wheat breeding programs.
Increasing evidence suggests that the misfolding and deposition of IAPP plays an important role in the pathogenesis of type II, or non-insulin-dependent diabetes mellitus (T2DM). Membranes have been ...implicated in IAPP-dependent toxicity in several ways: Lipid membranes have been shown to promote the misfolding and aggregation of IAPP. Thus, potentially toxic forms of IAPP can be generated when IAPP interacts with cellular membranes. In addition, membranes have been implicated as the target of IAPP toxicity. IAPP has been shown to disrupt membrane integrity and to permeabilize membranes. Since disruption of cellular membranes is highly toxic, such a mechanism has been suggested to explain the observed IAPP toxicity. Here, we review IAPP–membrane interaction in the context of (1) catalyzing IAPP misfolding and (2) being a potential origin of IAPP toxicity.
The role of proprioceptive feedback on motor lateralization remains unclear. We asked whether motor lateralization is dependent on proprioceptive feedback by examining a rare case of proprioceptive ...deafferentation (GL). Motor lateralization is thought to arise from asymmetries in neural organization, particularly at the cortical level. For example, we have previously provided evidence that the left hemisphere mediates optimal motor control that allows execution of smooth and efficient arm trajectories, while the right hemisphere mediates impedance control that can achieve stable and accurate final arm postures. The role of proprioception in both of these processes has previously been demonstrated empirically, bringing into question whether loss of proprioception will disrupt lateralization of motor performance. In this study, we assessed whether the loss of online sensory information produces deficits in integrating specific control contributions from each hemisphere by using a reaching task to examine upper limb kinematics in GL and five age-matched controls. Behavioral findings revealed differential deficits in the control of the left and right hands in GL and performance deficits in each of GL's hands compared with controls. Computational simulations can explain the behavioral results as a disruption in the integration of postural and trajectory control mechanisms when no somatosensory information is available. This rare case of proprioceptive deafferentation provides insights into developing a more accurate understanding of handedness that emphasizes the role of proprioception in both predictive and feedback control mechanisms.
The role of proprioceptive feedback on the lateralization of motor control mechanisms is unclear. We examined upper limb kinematics in a rare case of peripheral deafferentation to determine the role of sensory information in integrating motor control mechanisms from each hemisphere. Our empirical findings and computational simulations showed that the loss of somatosensory information results in an impaired integration of control mechanisms, thus providing support for a complementary dominance hypothesis of handedness.
The crude glycerol produced as a byproduct of transesterification synthesis has very few applications because it comprises of significant amounts of methanol, catalyst, and soap. On the other hand, ...transesterifications of highly acidic oil in the presence of an alkaline catalyst are problematic due to the presence of high amounts of free fatty acids. In this study, the free fatty acid level of high acid oil, which was initially determined to be 19.25%, was decreased to permit the direct production of biodiesel via glycerolysis with pure glycerol, making direct transesterification feasible. Through a process of purification, crude glycerol was refined to 92.5% purity. It was revealed that the physiochemical parameters of density, moisture content, ash content, matter organic non-glycerol content, pH, and Na/K concentrations of generated purified glycerol are equal to those of commercially available glycerol. In contrast, glycerolysis treatment successfully decreased the free fatty acid level to less than 2% under optimal conditions, which were determined to be 200 °C, a glycerol-to-oil molar ratio of 4:1, and a KOH catalyst concentration of 1.6 wt.% at 350 rpm. The inclusion of hexane as a co-solvent accelerated the glycerolysis process, and the weight ratio of oil-to-hexane was 8:1. Moreover, it was viable to use waste methanol for biodiesel synthesis and purified crude glycerol as a raw material in a variety of industries, including biodiesel production. In addition, compared to acid esterification, the FFA concentration of oil with a high acid value fell significantly.
Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated ...mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As Murraya koenigii leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardioprotective potential of Murraya leaf extract against doxorubicin-induced cardiotoxicity in rats. Rats were randomly divided into five groups with 10 animals in each group. Doxorubicin was administered intraperitonially at 18 mg/kg while lyophilized plant extract was administered orally at 2 g/kg. Dexrazoxane, at 180 mg/kg, was used as the positive control. Cardiac damage of doxorubicin control was evident with a significant increase (p<0.05) in cardiac troponin I, NT-pro BNP, AST, and LDH compared to the normal control. Plant-treated group showed cardioprotective effect by significantly reducing (p < 0.05) all of the above parameters compared to doxorubicin control (p<0.05). Increased oxidative stress in doxorubicin control was evident with a significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity and a significant increase in lipid peroxidation compared to the control. Interestingly, treatment with Murraya leaf extract showed a significant increase in all of the above antioxidant parameters and a significant reduction in lipid peroxidation by showing an antioxidant effect. A significant increase in myeloperoxidase activity confirmed the increased inflammatory activity in doxorubicin control group whereas plant-treated group showed a significant reduction (p<0.05) which expressed the anti-inflammatory effect of Murraya leaf extract. Doxorubicin-treated group showed histological evidence of extensive damage to the myocardium while plant-treated group showed a preserved myocardium with lesser degree of damage. Pretreatment with Murraya leaf extract may replenish cardiomyocytes with antioxidants and promote the defense against doxorubicin-induced cardiotoxicity.
The increased demand for cladding in high-rise buildings has prompted engineers to explore alternative products utilizing recycled materials. However, ensuring fire compliance in these alternative ...claddings, which are predominantly composed of low-volume polymer-based composites, poses a critical challenge. Traditional experimental methods for fire evaluation are costly, time consuming, and environmentally impactful. Considering this, a numerical approach was proposed for evaluating the fire performance of glass-polymer composite materials, which contain a high proportion of recycled glass and a lower percentage of rigid polyurethane. A cone calorimeter test was simulated using Computational Fluid Dynamics (CFD) software to investigate the flammability of the novel glass–polymer composite material. This validated numerical model was employed to assess the combustibility of the glass–polyurethane composite materials and identify influential parameters using the Design of Experiments (DoE) method. Statistical analysis revealed that three material properties, namely, the heat of combustion, the absorption coefficient, and the heat of reaction, significantly influenced the peak heat release rate (pHRR) of the glass–polyurethane composite materials compared to other properties. Based on these findings, an empirical equation was proposed that demonstrates a reasonable correlation with the pHRR of low-polymer recycled glass composite materials. The outcomes of this study hold considerable importance for understanding and predicting the combustibility behaviour of low-polymer–glass composites. By providing a validated numerical model and identifying critical material properties, this research contributes to the development of sustainable fire safety solutions for buildings, enabling the use of recycled materials and reducing reliance on conventional claddings.
Impairment of arm movements poststroke often results in the use of compensatory trunk movements to complete motor tasks. These compensatory movements have been mostly observed in tightly controlled ...conditions, with very few studies examining them in more naturalistic settings. In this study, the authors quantified the presence of compensatory movements during a set of continuous reaching and manipulation tasks performed with both the paretic and nonparetic arm (in 9 chronic stroke survivors) or the dominant arm (in 20 neurologically unimpaired control participants). Kinematic data were collected using motion capture to assess trunk and elbow movement. The authors found that trunk displacement and rotation were significantly higher when using the paretic versus nonparetic arm (P = .03). In contrast, elbow angular displacement was significantly lower in the paretic versus nonparetic arm (P = .01). The reaching tasks required significantly higher trunk compensation and elbow movement than the manipulation tasks. These results reflect increased reliance on compensatory trunk movements poststroke, even in everyday functional tasks, which may be a target for home rehabilitation programs. This study provides a novel contribution to the rehabilitation literature by examining the presence of compensatory movements in naturalistic reaching and manipulation tasks.
In Sri Lanka, rabies prevention initiatives are hindered by fragmented and delayed information-sharing that limits clinicians' ability to follow patients and impedes public health surveillance.
In a ...project led by the health ministry, we adapted existing technologies to create an electronic platform for rabies surveillance. Information is entered by trained clinical staff, and both aggregate and individual patient data are visualized in real time. An automated short message system (SMS) alerts patients for vaccination follow-up appointments and informs public health inspectors about incidents of animal bites.
The platform was rolled out in June 2016 in four districts of Sri Lanka, linking six rabies clinics, three laboratories and the public health inspectorate.
Over a 9-month period, 12 121 animal bites were reported to clinics and entered in the registry. Via secure portals, clinicians and public health teams accessed live information on treatment and outcomes of patients started on post-exposure prophylaxis (9507) or receiving deferred treatment (2614). Laboratories rapidly communicated the results of rabies virus tests on dead mammals (328/907 positive). In two pilot districts SMS reminders were sent to 1376 (71.2%) of 1933 patients whose contact details were available. Daily SMS reports alerted 17 public health inspectors to bite incidents in their area for investigation.
Existing technologies in low-resource countries can be harnessed to improve public health surveillance. Investment is needed in platform development and training and support for front-line staff. Greater public engagement is needed to improve completeness of surveillance and treatment.
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