Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Decision-level and feature-level integration of remote sensing and geospatial big data for urban land use mapping

Information about urban land use is important for urban planning and sustainable development. The emergence of geospatial big data (GBD), increased the availability of remotely sensed (RS) data and the development of new methods for data integration to provide new opportunities for mapping types of urban land use. However, the modes of RS and GBD integration are diverse due to the differences in data, study areas, classifiers, etc. In this context, this study aims to summarize the main methods of data integration and evaluate them via a case study of urban land use mapping in Hangzhou, China. We first categorized the RS and GBD integration methods into decision-level integration (DI) and feature-level integration (FI) and analyzed their main differences by reviewing the existing literature. The two methods were then applied for mapping urban land use types in Hangzhou city, based on urban parcels derived from the OpenStreetMap (OSM) road network, 10 m Sentinel-2A images, and points of interest (POI). The corresponding classification results were validated quantitatively and qualitatively using the same testing dataset. Finally, we illustrated the advantages and disadvantages of both approaches via bibliographic evidence and quantitative analysis. The results showed that: (1) The visual comparison indicates a generally better performance of DI-based classification than FI-based classification; (2) DI-based urban land use mapping is easy to implement, while FI-based land use mapping enables the mixture of features; (3) DI-based and FI-based methods can be used together to improve urban land use mapping, as they have different performances when classifying different types of land use. This study provides an improved understanding of urban land use mapping in terms of the RS and GBD integration strategy

The Lsm2-8 complex determines nuclear localization of the spliceosomal U6 snRNA

Lsm proteins are ubiquitous, multifunctional proteins that are involved in the processing and/or turnover of many, if not all, RNAs in eukaryotes. They generally interact only transiently with their substrate RNAs, in keeping with their likely roles as RNA chaperones. The spliceosomal U6 snRNA is an exception, being stably associated with the Lsm2-8 complex. The U6 snRNA is generally considered to be intrinsically nuclear but the mechanism of its nuclear retention has not been demonstrated, although La protein has been implicated. We show here that the complete Lsm2-8 complex is required for nuclear accumulation of U6 snRNA in yeast. Therefore, just as Sm proteins effect nuclear localization of the other spliceosomal snRNPs, the Lsm proteins mediate U6 snRNP localization except that nuclear retention is the likely mechanism for the U6 snRNP. La protein, which binds only transiently to the nascent U6 transcript, has a smaller, apparently indirect, effect on U6 localization that is compatible with its proposed role as a chaperone in facilitating U6 snRNP assembly

Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study.

Background Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Methods and Results Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24‐hour urine albumin excretion. During an average of 6.3 years of follow‐up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine‐based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C‐based‐eGFR was 2.43 (2.10, 2.80), and 1 SD higher log‐albuminuria was 1.65 (1.53, 1.78), all P\u3c0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C‐based eGFR and higher log‐albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P=0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P=0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P\u3c0.001), interleukin‐6 (1.15, 95% CI 1.05, 1.25, P=0.002), and tumor necrosis factor‐α (1.10, 95% CI 1.00, 1.21, P=0.05) were all significantly and directly associated with incidence of heart failure. Conclusions Our study indicates that cystatin C‐based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine‐based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease

Ankle Brachial Index and Subsequent Cardiovascular Disease Risk in Patients With Chronic Kidney Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/1/jah31554.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/2/jah31554_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/3/jah31554-sup-0001-TableS1.pd

Fall prevention intervention technologies: A conceptual framework and survey of the state of the art

In recent years, an ever increasing range of technology-based applications have been developed with the goal of assisting in the delivery of more effective and efficient fall prevention interventions. Whilst there have been a number of studies that have surveyed technologies for a particular sub-domain of fall prevention, there is no existing research which surveys the full spectrum of falls prevention interventions and characterises the range of technologies that have augmented this landscape. This study presents a conceptual framework and survey of the state of the art of technology-based fall prevention systems which is derived from a systematic template analysis of studies presented in contemporary research literature. The framework proposes four broad categories of fall prevention intervention system: Pre-fall prevention; Post-fall prevention; Fall injury prevention; Cross-fall prevention. Other categories include, Application type, Technology deployment platform, Information sources, Deployment environment, User interface type, and Collaborative function. After presenting the conceptual framework, a detailed survey of the state of the art is presented as a function of the proposed framework. A number of research challenges emerge as a result of surveying the research literature, which include a need for: new systems that focus on overcoming extrinsic falls risk factors; systems that support the environmental risk assessment process; systems that enable patients and practitioners to develop more collaborative relationships and engage in shared decision making during falls risk assessment and prevention activities. In response to these challenges, recommendations and future research directions are proposed to overcome each respective challenge.The Royal Society, grant Ref: RG13082

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

On gene dosage balance in protein complexes: a comment on Semple JI, Vavouri T, Lehner B. A simple principle concerning the robustness of protein complex activity to changes in gene expression.

A comment on Semple JI, Vavouri T, Lehner B. A simple principle concerning the robustness of protein complex activity to changes in gene expression. BMC Syst Biol. 2008;2: