Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific ...functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal functional dissociations with a particular focus on the CA3 subregion. We first discuss the cellular functions of IEGs and the brain system interactions that govern their dynamic expression in hippocampal neurons to provide a more solid framework for interpreting the findings from IEG studies. We show the pitfalls and shortcomings of conventional IEG imaging studies and describe advanced methods using IEGs for imaging of neuronal activity or functional intervention. We review the current IEG evidence of hippocampal function, subregional-specific contribution to different stages of memory formation, systems consolidation, functional dissociation between memory and anxiety/behavioral inhibition along the septotemporal axis, and different neural network properties of hippocampal subregions. In total, IEG studies provide support for (1) the role of the hippocampus in spatial and contextual learning and memory, (2) its role in continuous encoding of ongoing experience, (3) septotemporal dissociations between memory and anxiety, and (4) a dynamic relationship between pattern separation and pattern completion in the CA3 subregion. In closing, we provide a framework for how cutting-edge IEG imaging and intervention techniques will likely contribute to better understanding of the specific functions of CA3 and other hippocampal subregions.
Many scenarios of physics beyond the standard model predict the existence of new gauge singlets, which might be substantially lighter than the weak scale. The experimental constraints on additional ...scalars with masses in the MeV to GeV range could be significantly weakened if they interact predominantly with leptons rather than quarks. At an e+e− collider, such a leptophilic scalar (ϕL) would be produced predominantly through radiation from a τ lepton. We report herein a search for e+e−→τ+τ−ϕL, ϕL→ℓ+ℓ− (ℓ=e, μ) using data collected by the BABAR experiment at SLAC. No significant signal is observed, and we set limits on the ϕL coupling to leptons in the range 0.04<mϕL<7.0 GeV. These bounds significantly improve upon the current constraints, excluding almost entirely the parameter space favored by the observed discrepancy in the muon anomalous magnetic moment below 4 GeV at 90% confidence level.
The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its ...physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins.
•FUS phase transitions between monomer, liquid droplet, and hydrogel states•FUS mutants induce further phase transition into irreversible fibrillar hydrogels•Irreversible hydrogels sequester RNP cargo and impair RNP granule function•Formation of non-amyloid fibrillar hydrogels provides a compelling causative mechanism for neurodegeneration
Murakami et al. show that FUS transitions between monomer, liquid droplet, and hydrogel states during uptake and release of RNP granule cargo. FUS mutations accelerate transition into fibrillar hydrogels that trap RNP cargo, impair RNP granule function, and cause neurodegeneration.
We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data collected with the BABAR detector at the PEP-II B-Factory. We look for events with a single high-energy photon and a ...large missing momentum and energy, consistent with production of a spin-1 particle A^{'} through the process e^{+}e^{-}→γA^{'}; A^{'}→invisible. Such particles, referred to as "dark photons," are motivated by theories applying a U(1) gauge symmetry to dark matter. We find no evidence for such processes and set 90% confidence level upper limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV. In particular, our limits exclude the values of the A^{'} coupling suggested by the dark-photon interpretation of the muon (g-2)_{μ} anomaly, as well as a broad range of parameters for the dark-sector models.
Based on the full BABAR data sample, we report improved measurements of the ratios R(D(*))=B(B̄→D(*)τ⁻ν¯τ)/B(B̄→D(*)ll¯ν¯l), where l is either e or μ. These ratios are sensitive to new physics ...contributions in the form of a charged Higgs boson. We measure R(D)=0.440±0.058±0.042 and R(D*)=0.332±0.024±0.018, which exceed the standard model expectations by 2.0σ and 2.7σ, respectively. Taken together, our results disagree with these expectations at the 3.4σ level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model.
Background
Postprandial dysmetabolism, an important cardiovascular disease risk factor, can be improved by exercise. Further systematic review and meta-analysis is needed to compare the effects of ...accumulated exercise with a single session of energy-matched continuous exercise on postprandial glucose (PPG), insulin, and triglycerides in adults with or without diabetes.
Methods
Eight electronic databases were searched on August 28, 2020, and updated on April 27, 2021. Eligible studies were randomized, quasi-randomized, or non-randomized controlled or crossover trials that evaluated the acute or longitudinal effects of accumulated exercise compared with a single session of energy-matched continuous exercise on PPG, postprandial insulin, and triglycerides in diabetic and non-diabetic adults. Same-day and second-morning effects were assessed separately for acute intervention studies. Subgroup analyses were conducted based on the number of exercise bouts (2–3 bouts or frequent brief bouts (e.g., 1–6 min) throughout the day at 20–60-min intervals (known as physical activity PA breaks, ≥ 5 bouts)), exercise intensity, and populations. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. Pooled effects were reported as standardized mean differences (SMD) and 95% CI using a random effects model.
Results
Twenty-seven studies (635 participants) were included. A significant difference was found for same-day PPG control, which favored accumulated exercise over one bout of energy-matched continuous exercise (SMD − 0.36 95%CI: (− 0.56, − 0.17),
P
= 0.0002,
I
2
= 1%), specifically in accumulated exercise with PA breaks (SMD − 0.36 95%CI: (− 0.64, − 0.08),
P
= 0.01,
I
2
= 30%), low-moderate intensity exercise (SMD − 0.38 (95%CI: (− 0.59, − 0.17),
P
= 0.0005,
I
2
= 0%), and in non-diabetic populations (SMD − 0.36 95%CI: (− 0.62, − 0.10),
P
= 0.007,
I
2
= 16%). No differences were found for same-day postprandial insulin and triglycerides, and second-morning effects (postprandial or fasting glucose, insulin, and triglycerides) between different exercise patterns.
Conclusion
Compared with one session of continuous exercise, accumulated exercise—specifically in subgroups of PA breaks, low-moderate intensity exercises—produced greater acute effects on same-day PPG control for non-diabetic adults. There were no differences between continuous and accumulated patterns of exercise in terms of same-day postprandial insulin and triglycerides, and second-morning effects on all previously mentioned markers. The findings provide additional PA options for PPG control for individuals with limited time or exercise capacity to engage in PA in one session.
Registration: PROSPERO (identification code: CRD42021251325).
Dark sectors charged under a new Abelian interaction have recently received much attention in the context of dark matter models. These models introduce a light new mediator, the so-called dark photon ...(A^{'}), connecting the dark sector to the standard model. We present a search for a dark photon in the reaction e^{+}e^{-}→γA^{'}, A^{'}→e^{+}e^{-}, μ^{+}μ^{-} using 514 fb^{-1} of data collected with the BABAR detector. We observe no statistically significant deviations from the standard model predictions, and we set 90% confidence level upper limits on the mixing strength between the photon and dark photon at the level of 10^{-4}-10^{-3} for dark photon masses in the range 0.02-10.2 GeV. We further constrain the range of the parameter space favored by interpretations of the discrepancy between the calculated and measured anomalous magnetic moment of the muon.
Many models of physics beyond the standard model predict the existence of new Abelian forces with new gauge bosons mediating interactions between "dark sectors" and the standard model. We report a ...search for a dark boson Z' coupling only to the second and third generations of leptons in the reaction e super(+) e super(?)arrowrightmu super(+)mu super(?)Z',Z'arrowrightmu super(+) mu? using 514fb super(?1) of data collected by the BABAR experiment. No significant signal is observed for Z' masses in the range 0.212-10 GeV. Limits on the coupling parameter g' as low as 7x10 super(?4) are derived, leading to improvements in the bounds compared to those previously derived from neutrino experiments.
We search for the rare flavor-changing neutral current process B^{+}→K^{+}τ^{+}τ^{-} using data from the BABAR experiment. The data sample, collected at the center-of-mass energy of the ϒ(4S) ...resonance, corresponds to a total integrated luminosity of 424 fb^{-1} and to 471×10^{6} BBover ¯ pairs. We reconstruct one B meson, produced in the ϒ(4S)→B^{+}B^{-} decay, in one of many hadronic decay modes and search for activity compatible with a B^{+}→K^{+}τ^{+}τ^{-} decay in the rest of the event. Each τ lepton is required to decay leptonically into an electron or muon and neutrinos. Comparing the expected number of background events with the data sample after applying the selection criteria, we do not find evidence for a signal. The resulting upper limit, at the 90% confidence level, is B(B^{+}→K^{+}τ^{+}τ^{-})<2.25×10^{-3}.
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