Advances in Engineering and Application of Optogenetic Indicators for Neuroscience

Our ability to investigate the brain is limited by available technologies that can record biological processes in vivo with suitable spatiotemporal resolution. Advances in optogenetics now enable optical recording and perturbation of central physiological processes within the intact brains of model organisms. By monitoring key signaling molecules noninvasively, we can better appreciate how information is processed and integrated within intact circuits. In this review, we describe recent efforts engineering genetically-encoded fluorescence indicators to monitor neuronal activity. We summarize recent advances of sensors for calcium, potassium, voltage, and select neurotransmitters, focusing on their molecular design, properties, and current limitations. We also highlight impressive applications of these sensors in neuroscience research. We adopt the view that advances in sensor engineering will yield enduring insights on systems neuroscience. Neuroscientists are eager to adopt suitable tools for imaging neural activity in vivo, making this a golden age for engineering optogenetic indicators. Keywords: optogenetic tools; neuroscience; calcium sensor; voltage sensor; neurotransmitter

A shifting enemy: analysing the BBC’s representations of “al-Qaeda” in the aftermath of the September 11th 2001 attacks

This article seeks to explore how the BBC made sense of the al-Qaeda phenomenon in its flagship “News at Ten” bulletin during the aftermath of the September 11th 2001 attacks. Using Critical Multimodal Discourse Analysis, it shows how the BBC’s representations function as a dynamic and continually shifting site upon which a range of fears, identities, discourses and forms of knowledge and power struggle and contend, and through which a number of different “al-Qaedas” manifest themselves. In particular, three shifting modes of visual and verbal representation are identified within the BBC’s coverage which each correspond to a separate understanding of al-Qaeda: the “Islamic” mode, the “Personalised” mode and the “Elusive” mode. These representations both draw upon and challenge the dominant discourses surrounding Islam, non-state terrorism and the identities of terrorist suspects, providing audiences with a variety of often conflicting ways of seeing and speaking about this entity. As such, the article provides insight into the complex nature of the BBC’s representations of al-Qaeda during its coverage of the September 11th 2001 attacks, and shows how such complexity serves, albeit inadvertently, to legitimise the far-reaching counterterrorism policies that were enacted in the aftermath of these attacks

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Prospectus, October 10, 1984

SO YOU AND THE BULLY ON THE BLOCK ARE GOING TO DESTROY THE WORLD?\u27; PC Digest; Use your vote to make needed changes; First semester headaches; Auntie Miranda-Yes? or No?; Dear Reader; PC Happenings; Lifelong Learners to meet; Parkalnd schedules special registration; Workshop focuses on time management; Animal Health Technicians conference set; Health issues series continues; Emotional problems reason for help, not condemnation; Consumer Health Care Hotline; Notes of interest Prospectus read far and wide; Pictures worth more than a thousand words and dollars; Parkland instructor to teach GM class; Staff profile-Jim Scott-Entertainment writer; Advice from the duodenum-by Auntie Miranda; Wallace and Gray assets to both Parkland and \u27Taken in Marriage\u27; Music Poll; Explore the workings of the brain; Who\u27s top in pop?; Chick\u27s newest more than child\u27s play; Don\u27t miss a night of hilarity; Creative Corner...Especially for you!!; \u27The Foreigner\u27; The alarm clock-Monday morning blues; Natural selection; Bittersweet Memory; Pathways; Beautiful Stranger; Too Late; Love in the winter woods; \u27Doom Story\u27 the nightmare begins; Eternity; Green Eyes; Our day; Rejoice the Poet; Life Choices; Our place; Classifieds; Trust and acceptance provide supportive atmosphere; Change brings creation of destiny; Did You Know...; Kirby leads Cobra harriers to 7th; Lady Cobras win three, improve record to 18-5; A Tale of Three Freshmen; IM Volleyball; IM Football; Kirby says \u27Running is good for heart\u27; Schriefer takes pride in Parkland X-Country; Stewart places 3rd to lead Lady Cobras; Mullen twins guests on Cobra Raphttps://spark.parkland.edu/prospectus_1984/1009/thumbnail.jp

Hi-MC: a novel method for high-throughput mitochondrial haplogroup classification

Effective approaches for assessing mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for mitochondrial haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for mitochondrial haplogroup classification that is cost effective and applicable to large sample sizes making mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American mitochondrial haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Context, cognition and communication in language

Questions pertaining to the unique structure and organisation of language have a long history in the field of linguistics. In recent years, researchers have explored cultural evolutionary explanations, showing how language structure emerges from weak biases amplified over repeated patterns of learning and use. One outstanding issue in these frameworks is accounting for the role of context. In particular, many linguistic phenomena are said to to be context-dependent; interpretation does not take place in a void, and requires enrichment from the current state of the conversation, the physical situation, and common knowledge about the world. Modelling the relationship between language structure and context is therefore crucial for developing a cultural evolutionary approach to language. One approach is to use statistical analyses to investigate large-scale, cross-cultural datasets. However, due to the inherent limitations of statistical analyses, especially with regards to the inadequacy of these methods to test hypotheses about causal relationships, I argue that experiments are better suited to address questions pertaining to language structure and context. From here, I present a series of artificial language experiments, with the central aim being to test how manipulations to context influence the structure and organisation of language. Experiment 1 builds upon previous work in iterated learning and communication games through demonstrating that the emergence of optimal communication systems is contingent on the contexts in which languages are learned and used. The results show that language systems gradually evolve to only encode information that is informative for conveying the intended meaning of the speaker - resulting in markedly different systems of communication. Whereas Experiment 1 focused on how context influences the emergence of structure, Experiments 2 and 3 investigate under what circumstances do manipulations to context result in the loss of structure. While the results are inconclusive across these two experiments, there is tentative evidence that manipulations to context can disrupt structure, but only when interacting with other factors. Lastly, Experiment 4 investigates whether the degree of signal autonomy (the capacity for a signal to be interpreted without recourse to contextual information) is shaped by manipulations to contextual predictability: the extent to which a speaker can estimate and exploit contextual information a hearer uses in interpreting an utterance. When the context is predictable, speakers organise languages to be less autonomous (more context-dependent) through combining linguistic signals with contextual information to reduce effort in production and minimise uncertainty in comprehension. By decreasing contextual predictability, speakers increasingly rely on strategies that promote more autonomous signals, as these signals depend less on contextual information to discriminate between possible meanings. Overall, these experiments provide proof-of-concept for investigating the relationship between language structure and context, showing that the organisational principles underpinning language are the result of competing pressures from context, cognition, and communication

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society