Miracle-dz/UniFAR-FTUs huggingface dataset:
Causally investigating cortical dynamics and signal processing by targeting natural system attractors with precisely timed stimulation

Electrical stimulation is a promising tool for interacting with neuronal dynamics to identify neural mechanisms that underlie cognitive function. Since effects of a single short stimulation pulse typically vary greatly and depend on the current network state, many experimental paradigms have rather resorted to continuous or periodic stimulation in order to establish and maintain a desired effect. However, such an approach explicitly leads to forced and ‘unnatural’ brain activity. Further, continuous stimulation can make it hard to parse the recorded activity and separate neural signal from stimulation artifacts. In this study we propose an alternate strategy: by monitoring a system in realtime, we use the existing preferred states or attractors of the network and to apply short and precise pulses in order to switch between its preferred states. When pushed into one of its attractors, one can use the natural tendency of the system to remain in such a state to prolong the effect of a stimulation pulse, opening a larger window of opportunity to observe the consequences on cognitive processing. To elaborate on this idea, we consider flexible information routing in the visual cortex as a prototypical example. When processing a stimulus, neural populations in the visual cortex have been found to engage in synchronized gamma activity. In this context, selective signal routing is achieved by changing the relative phase between oscillatory activity in sending and receiving populations (communication through coherence, CTC). In order to explore how perturbations interact with CTC, we investigate a biophysically realistic network exhibiting similar synchronization and signal routing phenomena. We develop a closed-loop stimulation paradigm based on the phase-response characteristics of the network and demonstrate its ability to establish desired synchronization states. By measuring information content throughout the model, we evaluate the effect of signal contamination caused by the stimulation in relation to the magnitude of the injected pulses and intrinsic noise in the system. Finally, we demonstrate that, up to a critical noise level, precisely timed perturbations can be used to artificially induce the effect of attention by selectively routing visual signals to higher cortical areas.
Wave-like activity patterns in the neuropil of striatal cholinergic interneurons in freely moving mice represent their collective spiking dynamics

Cholinergic interneurons (ChIs) are believed to form synchronous cell assemblies that modulate striatal microcircuitry and possibly orchestrate local dopamine release. We expressed genetically encoded calcium indicators (GECIs) selectively in ChIs and visualized dorsal striatum in freely moving mice using microendoscopes. Bouts of synchronous activation of the cholinergic neuropil revealed wave-like patterns of activity that preceded the signal from individual somata. To investigate the nature of the neuropil signal and why it precedes the somatic signal, we target-patched GECI-expressing ChIs in acute striatal slices while imaging them with single- and multiphoton microscopy. We found that only back-propagating action potentials but not synchronous optogenetic activation of thalamic inputs elicits observable calcium transients in ChI dendrites. Our data suggest that the spatiotemporal neuropil patterns are a newly described physiological measure of the collective recurrent ChI network activity.
Nell2 regulates the contralateral-versus-ipsilateral visual projection as a layer-specific positional cue

SUMMARY STATEMENT Nell2 is an ipsilateral layer-specific axon guidance cue in the visual thalamus and contributes to establishment of the eye-specific retinogeniculate projection by specifically inhibiting contralateral retinal axons. ABSTRACT In mammals with binocular vision, retinal ganglion cell (RGC) axons from each eye project to eye-specific layers in the contralateral and ipsilateral dorsal lateral geniculate nucleus (dLGN). Although layer-specific axon guidance cues that discriminate contralateral and ipsilateral RGC axons have long been postulated as a key mechanism for development of the eye-specificretinogeniculate projection, the molecular nature of such cues has remained elusive. Here we show that the extracellular glycoprotein Nell2 (also known as Nel) is expressed in the dorsomedial region of the dLGN, which corresponds to the layer receiving ipsilateral RGC axons. In Nell2 mutant mice, contralateral RGC axons invaded the ipsilateral layer of the dLGN, and ipsilateral axons terminated in partially fragmented patches, forming a mosaic pattern of contralateral and ipsilateral axon termination zones. In vitro, Nell2 exerted inhibitory effects on contralateral, but not ipsilateral, RGC axons. These results provide evidence that Nell2 acts as a layer-specific positional label in the dLGN that discriminates contralateral and ipsilateral RGC axons, and that it plays essential roles in establishment of the eye-specific projection patterns in the retinogeniculate system.
Cost utility analysis of end stage renal disease treatment in Ministry of Health dialysis centres, Malaysia: Hemodialysis versus continuous ambulatory peritoneal dialysis

OBJECTIVES In Malaysia, there is exponential growth of patients on dialysis. Dialysis treatment consumes a considerable portion of healthcare expenditure. Comparative assessment of their cost effectiveness can assist in providing a rational basis for preference of dialysis modalities. METHODS A cost utility study of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was conducted from a Ministry of Health (MOH) perspective. A Markov model was also developed to investigate the cost effectiveness of increasing uptake of CAPD to 55% and 60 % versus current practice of 40% CAPD in a five-year temporal horizon. A scenario with 30% CAPD was also measured. The costs and utilities were sourced from published data which were collected as part of this study. The transitional probabilities and survival estimates were obtained from the Malaysia Dialysis and Transplant Registry (MDTR). The outcome measures were cost per life year (LY), cost per quality adjusted LY (QALY) and incremental cost effectiveness ratio (ICER) for the Markov model. Sensitivity analyses were performed. RESULTS LYs saved for HD was 4.15 years and 3.70 years for CAPD. QALYs saved for HD was 3.544 years and 3.348 for CAPD. Cost per LY saved was RM39,791 for HD and RM37,576 for CAPD. The cost per QALY gained was RM46,595 for HD and RM41,527 for CAPD. The Markov model showed commencement of CAPD in 50% of ESRD patients as initial dialysis modality was very cost-effective versus current practice of 40% within MOH. Reduction in CAPD use was associated with higher costs and a small devaluation in QALYs. CONCLUSIONS These findings suggest provision of both modalities is fiscally feasible; increasing CAPD as initial dialysis modality would be more cost-effective.
Action Research: A Pathway to Action, Knowledge and Learning

Action Research is the first title in the Qualitative Research Methods series. Action Research: - briefly describes the origin of that research method; - explores the layers and strands of work that are involved in the method; - offers a practical guide to uncovering the issues which arise from the method; - reviews the status of that method relative to other research methodologies; - explores the notion of subjectivity; - describes other ways to strengthen the extent to which the findings of action research can be generalised. The Qualitative Research Methods series is intended primarily to assist postgraduate research students in understanding the different qualitative research methods and to enable students to choose the most appropriate method for their particular research. Each monograph will also provide guidance on conducting research throughout candidature.
Extrastriate Connectivity of the Mouse Dorsal Lateral Geniculate Thalamus

The mammalian visual system is one of the most well-studied brain systems. Visual information from the retina is relayed to the dorsal lateral geniculate nucleus of the thalamus (LGd). The LGd then projects topographically to primary visual cortex (VISp) to mediate visual perception. In this view, the VISp is a critical network hub where visual information must traverse LGd-VISp circuits to reach higher-order ‘extrastriate’ visual cortices. However, decades of conflicting reports in a variety of mammals support or refute the existence of extrastriate LGd connections that can bypass the VISp. Here, we provide evidence of bidirectional extrastriate connectivity with the mouse LGd. Using small, discrete coinjections of anterograde and retrograde tracers within the thalamus and cortex, our cross-validated approach identified bidirectional thalamocortical connectivity between LGd and extrastriate visual cortices. Our findings support the existence of extrastriate LGd circuits and provide novel understanding of LGd organization in rodent visual system.
Dynamic Functional Network Connectivity In Schizophrenia With MEG And fMRI, Do Different Time Scales Tell A Different Story?

The importance of how brain networks function together to create brain states has become increasingly recognized. Therefore, an investigation of eyes-open resting state dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) via both fMRI and a novel MEG pipeline was completed. The fMRI analysis used a spatial independent component analysis (ICA) to determine the networks on which the dFNC was based. The MEG analysis utilized a source-space activity estimate (MNE/dSPM) whose result was the input to a spatial ICA, on which the networks of the MEG dFNC was based. We found that dFNC measures reveal significant differences between HC and SP, which depended upon the imaging modality. Consistent with previous findings, a dFNC analysis predicated on fMRI data revealed HC and SP remain in different overall brain states (defined by a k-means clustering of network correlations) for significantly different periods of time, with SP spending less time in a highly-connected state. The MEG dFNC, in contrast, revealed group differences in more global statistics: SP changed between meta-states (k-means cluster states that are allowed to overlap in time) significantly more often and to states which were more different, relative to HC. MEG dFNC also revealed a highly connected state where a significant difference was observed in inter-individual variability, with greater variability among SP. Overall, our results show that fMRI and MEG reveal between-group functional connectivity differences in distinct ways, highlighting the utility of using each of the modalities individually, or potentially a combination of modalities, to better inform our understanding of disorders such as schizophrenia.
Study on Prevalence of Bovine Trypanosomosis and Tsetse Density in Kindo Koysha Woreda of Wolaita Zone, Ethiopia

Trypanosomosis is a parasitic disease caused by unicellular protozoan parasites of the genus trypanosoma and family trpanosomatidae. They multiply in blood stream, lymphatic vessels and tissue, including cardiac muscle and the central nervous system (Soulsby, 1992). Trypanosomosis is transmitted by tsetse flies (Glossina spp) are believed to be the most important infectious disease holding back development of livestock production in Africa (Itard, 1981).
OpenMC: A State-of-the-Art Monte Carlo Code for Research and Development

This paper gives an overview of OpenMC, an open source Monte Carlo particle transport code recently developed at the Massachusetts Institute of Technology. OpenMC uses continuous-energy cross sections and a constructive solid geometry representation, enabling high-fidelity modeling of nuclear reactors and other systems. Modern, portable input/output file formats are used in OpenMC: XML for input, and HDF5 for output. High performance parallel algorithms in OpenMC have demonstrated near-linear scaling to over 100,000 processors on modern supercomputers. Other topics discussed in this paper include plotting, CMFD acceleration, variance reduction, eigenvalue calculations, and software development processes.
Utilising the boundary layer to help restore the connectivity of fish habitats and populations

Significance Habitat fragmentation is a significant contributor to the worldwide decline of freshwater ecosystem health, the most pervasive cause of which is culverts. Culverts act as a barrier to fish movement, impacting feeding, predator avoidance, spawning, and community structures. Here we show that a common remediation strategy that involves baffles, is detrimental to the successful passage of small bodied and juvenile fish at high velocities. To remedy this widespread problem, we present a novel remediation design that benefits a range of small-bodied species and juvenile fish at the same high velocities, regardless of morphology or ecological niche. The application of this remediation design may be expanded to any smooth surfaced anthropogenic structure, to improve fish passage and restore ecosystem functionality. Abstract Culverts are a major cause of habitat fragmentation in freshwater ecosystems, are a barrier to fish movement, and are regarded as a significant contributor in the decline of freshwater fish populations globally. To try to address this, various culvert remediation designs have been implemented, including the installation of vertical baffles and the provision of naturalistic (rock) substrates. While remediation strategies generally aim to reduce the velocity of water flowing through the structure, there is often resistance to their use because the resultant reduction in culvert discharge can negatively impact upstream flooding while also resulting in debris clogging and increased culvert maintenance costs. In addition, baffles markedly increase water turbulence that may be detrimental to passage by some fish species or size classes. Here we present some novel remediation designs that exploit the reduced water velocity in boundary layers along the culvert wall to enhance fish passage without significantly compromising discharge capacity. These longitudinal designs produce an expanded reduced velocity zone along the culvert margins that generate minimal turbulence. We show that these novel designs are significantly advantageous to the swimming endurance and traversability for six small-bodied Australian fish species. We also provide data on how and why some culvert baffle designs may impede small-bodied fish passage. This data scales with increasing water velocity, encompassing inter-specific differences in swimming capacity. These results have broad implications for fish community structure and the requirement of juvenile cohort of large-bodied commercially important species where baffles have been implemented to facilitate fish passage.
The Construction of Multiple Identities in the Acknowledgement Section of a Masters Dissertation

Following the work of Hyland (2003, 2004), several studies have investigated the structural, linguistic, and socio-cultural features of dissertation acknowledgements (DAs). This research explores the interface between identity construction and the linguistic features of a Master’s DA, written by a student of Literary Studies, using a two-pronged analytical framework. Three key findings emerged from the analysis. First, the paper observed a two-move generic structure adopted in the text under study. The paper also demonstrates that the writer of the acknowledgement systematically varies linguistic choices at the lexical, grammatical, and discoursal levels, in order to construct varying and different identities. The third point concerns the hybridization of the DA in terms of the incorporation of formal and informal linguistic elements. Based on these findings, it can be said that the paper has implications for the identity theory, academic (thesis) writing, and further research on DA.
Characterizing the pathogenic, genomic, and chemical traits of Aspergillus fischeri, a close relative of the major human fungal pathogen Aspergillus fumigatus

Aspergillus fischeri is closely related to Aspergillus fumigatus, the major cause of invasive mold infections. Even though A. fischeri is commonly found in diverse environments, including hospitals, it rarely causes invasive disease; why that is so is unclear. Comparison of A. fischeri and A. fumigatus for diverse pathogenic, genomic, and secondary metabolic traits revealed multiple differences for pathogenesis-related phenotypes, including that A. fischeri is less virulent than A. fumigatus in multiple animal models of disease, grows slower in low oxygen environments, and is more sensitive to oxidative stress. In contrast, the two species exhibit high genomic similarity; ~90% of the A. fumigatus proteome is conserved in A. fischeri, including 48/49 genes known to be involved in A. fumigatus virulence. However, only 10/33 A. fumigatus biosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved in A. fischeri and only 13/48 A. fischeri BGCs are conserved in A. fumigatus. Detailed chemical characterization of A. fischeri cultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Interestingly, an A. fischeri deletion mutant of laeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the non-pathogenic A. fischeri possesses many of the genes important for A. fumigatus pathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism. Importance Aspergillus fumigatus is the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide. A. fischeri is a close relative of A. fumigatus, but is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of host-relevant biological and chemical characteristics. We found that disease progression in multiple A. fischeri mouse models was slower and caused less mortality than A. fumigatus. The two species also exhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of reactive oxygen species-inducing agents. Interestingly, we also found that the vast majority of A. fumigatus genes known to be involved in virulence are conserved in A. fischeri, whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we identified are the first step toward understanding the evolutionary origin of a major fungal pathogen.
SarcTrack

Rationale: Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues. Objective: We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate. Methods and Results: We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C (MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment. Conclusions: SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants.
Effect of cadmium accumulation on the performance of plants and of herbivores that cope differently with organic defences

Some plants can accumulate in their shoots metals that are toxic to most other organisms. This ability may serve as a defence against herbivores. Although both metal accumulation and the production of organic defences may be costly to the plant, the two mechanisms may interact on their effect on herbivores. However, this interplay between metal-based and ‘classical’ organic defences remains overlooked. To fill this gap, we studied the interactions between tomato (Solanum lycopersicum), a plant that accumulates cadmium, and two spider-mites, Tetranychus urticae and T. evansi that respectively induce and suppress organic plant defences, measurable via the activity of trypsin inhibitors. We exposed plants to different concentrations of cadmium and measured their effect on mites and plants. The oviposition of both spider-mite species was higher on plants exposed to low concentrations of Cd than on control plants but decreased at concentrations above 0.5 mM. Therefore, herbivores with contrasting responses to organic defences responded similarly to metal accumulation by the plants. On the plant, despite clear evidence for Cd accumulation, we did not detect any effect of Cd on traits that reflect the general response of the plant, such as biomass, water content and carbon/nitrogen ratio. Still, we found an effect of Cd supply upon the quantity of soluble sugars and leaf reflectance changes that may reflect structural modifications in the cells. In turn, these changes in plant traits interfered with the performance of spider mites feeding on those plants. Additionally, we show that the induction and suppression of plant defences by spider mites was not affected by Cd supply to the plants. Furthermore, the effect of metal supply on spider-mite performance was not affected by previous infestation. Together, our results suggest no interaction between metal-based and organic plant defences, on our system. This may be useful for plants living in heterogeneous environments, as they may use one or the other defence mechanism, depending on their relative performance in each environment. This may be relevant to studies on the interactions between herbivores and plants, from physiology to ecology.