Challenges and advanced concepts for the assessment of learning and memory function in mice

The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments. Here, we will discuss available protocols for testing learning and memory using the example of the most prevalent animal species in research, the laboratory mouse. A wide range of protocols has been developed in mice to test, e.g., object recognition, spatial learning, procedural memory, sequential problem solving, operant- and fear conditioning, and social recognition. Those assays are carried out with individual subjects in apparatuses such as arenas and mazes, which allow for a high degree of standardization across laboratories and straightforward data interpretation but are not without caveats and limitations. In animal research, there is growing concern about the translatability of study results and animal welfare, leading to novel approaches beyond established protocols. Here, we present some of the more recent developments and more advanced concepts in learning and memory testing, such as multi-step sequential lockboxes, assays involving groups of animals, as well as home cage-based assays supported by automated tracking solutions; and weight their potential and limitations against those of established paradigms. Shifting the focus of learning tests from the classical experimental chamber to settings which are more natural for rodents comes with a new set of challenges for behavioral researchers, but also offers the opportunity to understand memory formation and retrieval in a more conclusive way than has been attainable with conventional test protocols. We predict and embrace an increase in studies relying on methods involving a higher degree of automatization, more naturalistic- and home cage-based experimental setting as well as more integrated learning tasks in the future. We are confident these trends are suited to alleviate the burden on animal subjects and improve study designs in memory research

An Investigation of High Frequency Motions in the Tropical Tropopause Layer near Convection

Indirect evidence indicates a role for vertical mixing in the Tropical Tropopause Layer (TTL). In the past 20 years, high altitude NASA aircraft such as the ER-2, WB-57, and GLobal Hawk have been making 20hz measurements of vertical velocity and other meteorological parameters in the Upper Tropospere-Lower Stratosphere region, many in the tropics, most recently in connection with the Airborne Tropical TRopopause EXperiment (ATTREX). In the stable environment of the UTLS, high frequency activity occurs in bursts, presumably in connection with nearby convection or strong vertical shear associated with larger scale gravity waves. This paper examines tropical high frequency aircraft data to obtain some basic information about the distribution and character of high frequency activity in vertical velocity in the TTL. In particular, we focus on relating the high frequency activity to nearby tropical convection

Challenges and advanced concepts for the assessment of learning and memory function in mice

The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments. Here, we will discuss available protocols for testing learning and memory using the example of the most prevalent animal species in research, the laboratory mouse. A wide range of protocols has been developed in mice to test, e.g., object recognition, spatial learning, procedural memory, sequential problem solving, operant- and fear conditioning, and social recognition. Those assays are carried out with individual subjects in apparatuses such as arenas and mazes, which allow for a high degree of standardization across laboratories and straightforward data interpretation but are not without caveats and limitations. In animal research, there is growing concern about the translatability of study results and animal welfare, leading to novel approaches beyond established protocols. Here, we present some of the more recent developments and more advanced concepts in learning and memory testing, such as multi-step sequential lockboxes, assays involving groups of animals, as well as home cage-based assays supported by automated tracking solutions; and weight their potential and limitations against those of established paradigms. Shifting the focus of learning tests from the classical experimental chamber to settings which are more natural for rodents comes with a new set of challenges for behavioral researchers, but also offers the opportunity to understand memory formation and retrieval in a more conclusive way than has been attainable with conventional test protocols. We predict and embrace an increase in studies relying on methods involving a higher degree of automatization, more naturalistic- and home cage-based experimental setting as well as more integrated learning tasks in the future. We are confident these trends are suited to alleviate the burden on animal subjects and improve study designs in memory research

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

The UK research assessment exercise and the narrowing of UK economics

The aim of this paper is to delineate an empirically grounded, structure-causal going concern recursive model of UK economics that, in the context of the RAE and local department decision-making, explains the progressive elimination of heterodox economics, the progressive homogenization of mainstream economics from 1992 to the present, and the continued rise to dominance of a select group of departments, and indicates whether these ‘regularities’ will continue under the Research Excellence Framework selectivity exercise in 2014

Molecular velocity auto-correlation of simple liquids observed by NMR MGSE method

The velocity auto-correlation spectra of simple liquids obtained by the NMR method of modulated gradient spin echo show features in the low frequency range up to a few kHz, which can be explained reasonably well by a $t^{-3/2}$ long time tail decay only for non-polar liquid toluene, while the spectra of polar liquids, such as ethanol, water and glycerol, are more congruent with the model of diffusion of particles temporarily trapped in potential wells created by their neighbors. As the method provides the spectrum averaged over ensemble of particle trajectories, the initial non-exponential decay of spin echoes is attributed to a spatial heterogeneity of molecular motion in a bulk of liquid, reflected in distribution of the echo decays for short trajectories. While at longer time intervals, and thus with longer trajectories, heterogeneity is averaged out, giving rise to a spectrum which is explained as a combination of molecular self-diffusion and eddy diffusion within the vortexes of hydrodynamic fluctuations.Comment: 8 pages, 6 figur

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.</p

JIB-04 has broad-spectrum antiviral activity and inhibits SARS-CoV-2 replication and coronavirus pathogenesis

Pathogenic coronaviruses are a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified small-molecule inhibitors that potently block the replication of severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with a 50% effective concentration of 695 nM, with a specificity index of greater than 1,000. JIB-04 showe