A Review of DUSP26: Structure, Regulation and Relevance in Human Disease

Dual specificity phosphatases (DUSPs) play a crucial role in the regulation of intracellular signalling pathways, which in turn influence a broad range of physiological processes. DUSP malfunction is increasingly observed in a broad range of human diseases due to deregulation of key pathways, most notably the MAP kinase (MAPK) cascades. Dual specificity phosphatase 26 (DUSP26) is an atypical DUSP with a range of physiological substrates including the MAPKs. The residues that govern DUSP26 substrate specificity are yet to be determined; however, recent evidence suggests that interactions with a binding partner may be required for DUSP26 catalytic activity. DUSP26 is heavily implicated in cancer where, akin to other DUSPs, it displays both tumour-suppressive and -promoting properties, depending on the context. Here we review DUSP26 by evaluating its transcriptional patterns, protein crystallographic structure and substrate binding, as well as its physiological role(s) and binding partners, its role in human disease and the development of DUSP26 inhibitors

Modelling the impact of prescribed global warming on runoff from headwater catchments of the Irrawaddy River and their implications for the water level regime of Loktak Lake, northeast India

Climate change is likely to have major implications for wetland ecosystems, which will include altered water level regimes due to modifications in local and catchment hydrology. However, substantial uncertainty exists in the precise impacts of climate change on wetlands due in part to uncertainty in GCM projections. This paper explores the impacts of climate change upon river discharge within three sub-catchments of Loktak Lake, an internationally important wetland in northeast India. This is achieved by running pattern-scaled GCM output through distributed hydrological models (developed using MIKE SHE) of each sub-catchment. The impacts of climate change upon water levels within Loktak Lake are subsequently investigated using a water balance model. Two groups of climate change scenarios are investigated. Group 1 uses results from seven different GCMs for an increase in global mean temperature of 2 A degrees C, the purported threshold of ''dangerous'' climate change, whilst Group 2 is based on results from the HadCM3 GCM for increases in global mean temperature between 1 A degrees C and 6 A degrees C. Results from the Group 1 scenarios show varying responses between the three sub-catchments. The majority of scenario-sub-catchment combinations (13 out of 21) indicate increases in discharge which vary from < 1% to 42% although, in some cases, discharge decreases by as much as 20%. Six of the GCMs suggest overall increases in river flow to Loktak Lake (2-27%) whilst the other results in a modest (6%) decline. In contrast, the Group 2 scenarios lead to an almost linear increase in total river flow to Loktak Lake with increasing temperature (up to 27% for 6 A degrees C), although two sub-catchments experience reductions in mean discharge for the smallest temperature increases. In all but one Group 1 scenario, and all the Group 2 scenarios, Loktak Lake water levels are higher, regularly reaching the top of a downstream hydropower barrage that impounds the lake and necessitating the release of water for barrage structural stability. Although elevated water levels may permit enhanced abstraction for irrigation and domestic uses, future increases in hydropower generation are limited by existing infrastructure. The higher water levels are likely to exacerbate existing ecological deterioration within the lake as well as enhancing problems of flooding of lakeside communities

Quantifying hypoxia with diffuse reflectance spectroscopy for advanced prognostication and real-time response monitoring in rectal cancer: an in vivo feasibility study

Tumour hypoxia is a critical factor in treatment failure and resistance, and its accurate measurement with diffuse reflectance spectroscopy (DRS) could be used for prognostic and response monitoring purposes. In this in vivo characterisation study, we sequentially measured oxygenation trends over the entire course of tumour growth in mice using a multi-depth, fibre-optic DRS probe. Results demonstrated a clear downtrend in oxygenation over time. This progression was not always linear, with significant heterogeneity over time and between mice. Our findings will be further validated against gold standards prior to investigating whether hypoxia can be used to predict radiotherapy responses

Fostering collective intelligence education

New educational models are necessary to update learning environments to the digitally shared communication and information. Collective intelligence is an emerging field that already has a significant impact in many areas and will have great implications in education, not only from the side of new methodologies but also as a challenge for education. This paper proposes an approach to a collective intelligence model of teaching using Internet to combine two strategies: idea management and real time assessment in the class. A digital tool named Fabricius has been created supporting these two elements to foster the collaboration and engagement of students in the learning process. As a result of the research we propose a list of KPI trying to measure individual and collective performance. We are conscious that this is just a first approach to define which aspects of a class following a course can be qualified and quantified.Postprint (published version

Memory network plasticity after temporal lobe resection: a longitudinal functional imaging study

Anterior temporal lobe resection can control seizures in up to 80% of patients with temporal lobe epilepsy. Memory decrements are the main neurocognitive complication. Preoperative functional reorganization has been described in memory networks, but less is known of postoperative reorganization. We investigated reorganization of memory-encoding networks preoperatively and 3 and 12 months after surgery. We studied 36 patients with unilateral medial temporal lobe epilepsy (19 right) before and 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were studied at three equivalent time points. All subjects had neuropsychological testing at each of the three time points. A functional magnetic resonance imaging memory-encoding paradigm of words and faces was performed with subsequent out-of-scanner recognition assessments. Changes in activations across the time points in each patient group were compared to changes in the control group in a single flexible factorial analysis. Postoperative change in memory across the time points was correlated with postoperative activations to investigate the efficiency of reorganized networks. Left temporal lobe epilepsy patients showed increased right anterior hippocampal and frontal activation at both 3 and 12 months after surgery relative to preoperatively, for word and face encoding, with a concomitant reduction in left frontal activation 12 months postoperatively. Right anterior hippocampal activation 12 months postoperatively correlated significantly with improved verbal learning in patients with left temporal lobe epilepsy from preoperatively to 12 months postoperatively. Preoperatively, there was significant left posterior hippocampal activation that was sustained 3 months postoperatively at word encoding, and increased at face encoding. For both word and face encoding this was significantly reduced from 3 to 12 months postoperatively. Patients with right temporal lobe epilepsy showed increased left anterior hippocampal activation on word encoding from 3 to 12 months postoperatively compared to preoperatively. On face encoding, left anterior hippocampal activations were present preoperatively and 12 months postoperatively. Left anterior hippocampal and orbitofrontal cortex activations correlated with improvements in both design and verbal learning 12 months postoperatively. On face encoding, there were significantly increased left posterior hippocampal activations that reduced significantly from 3 to 12 months postoperatively. Postoperative changes occur in the memory-encoding network in both left and right temporal lobe epilepsy patients across both verbal and visual domains. Three months after surgery, compensatory posterior hippocampal reorganization that occurs is transient and inefficient. Engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery

Dynamics of <em>Prochlorococcus </em>Diversity and Photoacclimation During Short-Term Shifts in Water Column Stratification at Station ALOHA

\ua9 Copyright \ua9 2018 Thompson, van den Engh, Ahlgren, Kouba, Ward, Wilson and Karl.The cyanobacterium Prochlorococcus is the dominant phototroph in surface waters of the vast oligotrophic oceans, the foundation of marine food webs, and an important component of global biogeochemical cycles. The prominence of Prochlorococcus across the environmental gradients of the open ocean is attributed to its extensive genetic diversity and flexible chlorophyll physiology, enabling light capture over a wide range of intensities. What remains unknown is the balance between temporal dynamics of genetic diversity and chlorophyll physiology in the ability of Prochlorococcus to respond to a variety of short (approximately 1 day) and longer (months to year) changes in the environment. Previous field research established depth-dependent Prochlorococcus single cell chlorophyll distributions in the North Pacific Subtropical Gyre. Here, we examined whether the shifts in chlorophyll distributions correspond to changes in Prochlorococcus genetic diversity (i.e., ecotype-level community structure) or photoacclimation of stable communities over short time intervals. We report that community structure was relatively stable despite abrupt shifts in Prochlorococcus chlorophyll physiology, due to unexpected physiological plasticity of high-light adapted Prochlorococcus ecotypes. Through comparison with seasonal-scale changes, our data suggest that variability on daily scales triggers shifts in Prochlorococcus photoacclimation, while seasonal-scale dynamics trigger shifts in community structure. Together, these data highlight the importance of incorporating the process of photoacclimation and chlorophyll dynamics into interpretations of phytoplankton population dynamics from chlorophyll data as well as the importance of daily-scale variability to Prochlorococcus ecology

Memory reorganization following anterior temporal lobe resection: a longitudinal functional MRI study

Anterior temporal lobe resection controls seizures in 50-60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy

Cognitive outcomes of temporal lobe epilepsy surgery in older patients

Purpose: To examine the cognitive risks of temporal lobe surgery in patients aged 50 years and older. / Methods: We analysed data from 55 patients who underwent temporal lobe surgery (26 left-sided:29 right sided) from 1988 to 2012 at our centre. Pre-surgical and one year post-operative memory and naming capacity were compared to data obtained from two younger cohorts; 185 aged 18–30 and 220 aged 31–49. / Results: Pre-operative memory impairments were most marked for the oldest cohort and were associated with a longer duration of epilepsy. Naming capacity improved with age and better performance was associated with a later age at epilepsy onset. Post-operative declines were largest in older patients, achieving statistical significance for verbal memory, naming and subjective ratings. Left temporal lobe resections carried the greatest risk of memory and naming decline. Cognitive outcomes were unrelated to seizure outcome, VIQ or mood. / Conclusion: Our findings indicate the cognitive risks of TLE surgery are greater for older patients. Cognitive outcomes need to be considered when assessing the efficacy of epilepsy surgery in older cohorts and pre-operative performance levels need to be taken into account

On Semiclassical Limits of String States

We explore the relation between classical and quantum states in both open and closed (super)strings discussing the relevance of coherent states as a semiclassical approximation. For the closed string sector a gauge-fixing of the residual world-sheet rigid translation symmetry of the light-cone gauge is needed for the construction to be possible. The circular target-space loop example is worked out explicitly.Comment: 12 page

Nuclei in Strongly Magnetised Neutron Star Crusts

We discuss the ground state properties of matter in outer and inner crusts of neutron stars under the influence of strong magnetic fields. In particular, we demonstrate the effects of Landau quantization of electrons on compositions of neutron star crusts. First we revisit the sequence of nuclei and the equation of state of the outer crust adopting the Baym, Pethick and Sutherland (BPS) model in the presence of strong magnetic fields and most recent versions of the theoretical and experimental nuclear mass tables. Next we deal with nuclei in the inner crust. Nuclei which are arranged in a lattice, are immersed in a nucleonic gas as well as a uniform background of electrons in the inner crust. The Wigner-Seitz approximation is adopted in this calculation and each lattice volume is replaced by a spherical cell. The coexistence of two phases of nuclear matter - liquid and gas, is considered in this case. We obtain the equilibrium nucleus corresponding to each baryon density by minimizing the free energy of the cell. We perform this calculation using Skyrme nucleon-nucleon interaction with different parameter sets. We find nuclei with larger mass and charge numbers in the inner crust in the presence of strong magnetic fields than those of the zero field case for all nucleon-nucleon interactions considered here. However, SLy4 interaction has dramatic effects on the proton fraction as well as masses and charges of nuclei. This may be attributed to the behaviour of symmetry energy with density in the sub-saturation density regime. Further we discuss the implications of our results to shear mode oscillations of magnetars.Comment: presented in "Exciting Physics Symposium" held in Makutsi, South Africa in November, 2011 and to be published in a book by Springer Verla