Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Identification of a new member of the phage shock protein response in Escherichia coli, the phage shock protein g (PspG)

The phage shock protein operon (pspABCDE) of Escherichia coli is strongly up-regulated in response to overexpression of the filamentous phage secretin protein IV (pIV) and by many other stress conditions including defects in protein export. PspA has an established role in maintenance of the proton-motive force of the cell under stress conditions. Here we present evidence for a new member of the phage shock response in E. coli. Using transcriptional profiling, we show that the synthesis of pIV in E. coli leads to a highly restricted response limited to the up-regulation of the psp operon genes and yjbO. The psp operon and yjbO are also up-regulated in response to pIV in Salmonella enterica serovar Typhimurium. yjbO is a highly conserved gene found exclusively in bacteria that contain a psp operon but is physically unlinked to the psp operon. yjbO encodes a putative inner membrane protein that is co-controlled with the psp operon genes and is predicted to be an effector of the psp response in E. coli. We present evidence that yjbO expression is driven by sigma(54)-RNA polymerase, activated by PspF and integration host factor, and negatively regulated by PspA. PspF specifically regulates only members of the PspF regulon: pspABCDE and yjbO. We found that increased expression of YjbO results in decreased motility of bacteria. Because yjbO is co-conserved and co-regulated with the psp operon and is a member of the phage shock protein F regulon, we propose that yjbO be renamed pspG

An in vivo platform to select and evolve aggregation-resistant proteins

Protein biopharmaceuticals are highly successful, but their utility is compromised by their propensity to aggregate during manufacture and storage. As aggregation can be triggered by non-native states, whose population is not necessarily related to thermodynamic stability, prediction of poorly-behaving biologics is difficult, and searching for sequences with desired properties is labour-intensive and time-consuming. Here we show that an assay in the periplasm of E. coli linking aggregation directly to antibiotic resistance acts as a sensor for the innate (un-accelerated) aggregation of antibody fragments. Using this assay as a directed evolution screen, we demonstrate the generation of aggregation resistant scFv sequences when reformatted as IgGs. This powerful tool can thus screen and evolve ‘manufacturable’ biopharmaceuticals early in industrial development. By comparing the mutational profiles of three different immunoglobulin scaffolds, we show the applicability of this method to investigate protein aggregation mechanisms important to both industrial manufacture and amyloid disease

Maximizing the effectiveness of qualitative systematic reviews: A case study on terrestrial arthropod conservation translocations

Systematic literature reviews are frequently used in biodiversity conservation to identify knowledge gaps and strategies for improvement. Despite their important role, systematic reviews are not standardized and often use different methods, standards for success, and data sources. We compared two systematic reviews on terrestrial arthropod conservation translocations, unknowingly conducted by two research groups at the same time. Both studies found geographic and taxonomic biases, with most projects focusing on certain countries (e.g., United States, United Kingdom) and taxa (e.g., butterflies, grasshoppers), and found similar success rates (range: 52–58%). However, the studies had different conclusions about which factors significantly influenced trans-location success, driven by the data sources used (published literature vs. data from corresponding authors). Release numbers reported by corresponding authors were approximately double those in the published literature, causing the two studies’ data sets to differ dramatically. The results show that improved communication among researchers and practitioners is needed to ensure access to current data and prevent duplication of efforts. We recommend that: i) planned, ongoing, and unpublished work be integrated as best possible in reviews; ii) expert perspectives be included alongside quantitative measures; iii) online tools be used more to promote communi-cation; iv) an online catalogue of translocation projects be established to facilitate awareness and contact among researchers; and v) standardization of translocation reporting be increased. We provide practical pathways and actions to help achieve these recommendations. These improved review practices can benefit both systematic reviewers and conservation practitioners by increasing the quality and accuracy of systematic reviews

Microglial Cx3cr1 knockout reduces prion disease incubation time in mice.

Microglia are resident mononuclear phagocytes of the brain that become activated in response to insults including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and prion disease. In the central nervous system the chemokine Cx3cl1 (Fractalkine) is expressed by neurons and its exclusive receptor Cx3cr1 is expressed solely on microglia. Cx3cl1/Cx3cr1 signalling is thought to maintain microglia in their resting state and disrupting this equilibrium may allow microglia to become activated. In prion disease, microglial proliferation has been suggested to contribute to overall disease progression, however, in different mouse models of neurodegeneration, loss of Cx3cr1 has been shown to either worsen or improve the phenotype depending on the paradigm

Implementing neuroimaging and eye tracking methods to assess neurocognitive development of young infants in low- and middle-income countries

Infants and children in low- and middle-income countries (LMICs) are frequently exposed to a range of environmental risk factors which may negatively affect their neurocognitive development. The mechanisms by which factors such as undernutrition and poverty impact development and cognitive outcomes in early childhood are poorly understood. This lack of knowledge is due in part to a paucity of objective assessment tools which can be implemented across different cultural settings and in very young infants. Over the last decade, technological advances, particularly in neuroimaging, have opened new avenues for research into the developing human brain, allowing us to investigate novel biological associations. This paper presents functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG) and eye tracking (ET) as objective, cross-cultural methods for studying infant neurocognitive development in LMICs, and specifically their implementation in rural Gambia, West Africa. These measures are currently included, as part of a broader battery of assessments, in the Brain Imaging for Global Health (BRIGHT) project, which is developing brain function for age curves in Gambian and UK infants from birth to 24 months of age. The BRIGHT project combines fNIRS, EEG and ET with behavioural, growth, health and sociodemographic measures. The implementation of these measures in rural Gambia are discussed, including methodological and technical challenges that needed to be addressed to ensure successful data acquisition. The aim is to provide guidance to other groups seeking to implement similar methods in their research in other LMICs to better understand associations between environmental risk and early neurocognitive development

A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouse

Prion disease incubation time in mice is determined by many factors including genetic background. The prion gene itself plays a major role in incubation time; however, other genes are also known to be important. Whilst quantitative trait loci (QTL) studies have identified multiple loci across the genome, these regions are often large, and with the exception of Hectd2 on Mmu19, no quantitative trait genes or nucleotides for prion disease incubation time have been demonstrated. In this study, we use the Northport heterogeneous stock of mice to reduce the size of a previously identified QTL on Mmu15 from approximately 25 to 1.2 cM. We further characterised the genes in this region and identify Cpne8, a member of the copine family, as the most promising candidate gene. We also show that Cpne8 mRNA is upregulated at the terminal stage of disease, supporting a role in prion disease. Applying these techniques to other loci will facilitate the identification of key pathways in prion disease pathogenesis

Ultrafast optical control of entanglement between two quantum dot spins

The interaction between two quantum bits enables entanglement, the two-particle correlations that are at the heart of quantum information science. In semiconductor quantum dots much work has focused on demonstrating single spin qubit control using optical techniques. However, optical control of entanglement of two spin qubits remains a major challenge for scaling from a single qubit to a full-fledged quantum information platform. Here, we combine advances in vertically-stacked quantum dots with ultrafast laser techniques to achieve optical control of the entangled state of two electron spins. Each electron is in a separate InAs quantum dot, and the spins interact through tunneling, where the tunneling rate determines how rapidly entangling operations can be performed. The two-qubit gate speeds achieved here are over an order of magnitude faster than in other systems. These results demonstrate the viability and advantages of optically controlled quantum dot spins for multi-qubit systems.Comment: 24 pages, 5 figure

Outlier Edge Detection Using Random Graph Generation Models and Applications

Outliers are samples that are generated by different mechanisms from other normal data samples. Graphs, in particular social network graphs, may contain nodes and edges that are made by scammers, malicious programs or mistakenly by normal users. Detecting outlier nodes and edges is important for data mining and graph analytics. However, previous research in the field has merely focused on detecting outlier nodes. In this article, we study the properties of edges and propose outlier edge detection algorithms using two random graph generation models. We found that the edge-ego-network, which can be defined as the induced graph that contains two end nodes of an edge, their neighboring nodes and the edges that link these nodes, contains critical information to detect outlier edges. We evaluated the proposed algorithms by injecting outlier edges into some real-world graph data. Experiment results show that the proposed algorithms can effectively detect outlier edges. In particular, the algorithm based on the Preferential Attachment Random Graph Generation model consistently gives good performance regardless of the test graph data. Further more, the proposed algorithms are not limited in the area of outlier edge detection. We demonstrate three different applications that benefit from the proposed algorithms: 1) a preprocessing tool that improves the performance of graph clustering algorithms; 2) an outlier node detection algorithm; and 3) a novel noisy data clustering algorithm. These applications show the great potential of the proposed outlier edge detection techniques.Comment: 14 pages, 5 figures, journal pape