Universal quantum operations and ancilla-based read-out for tweezer clocks.

Enhancing the precision of measurements by harnessing entanglement is a long-sought goal in quantum metrology. Yet attaining the best sensitivity allowed by quantum theory in the presence of noise is an outstanding challenge, requiring optimal probe-state generation and read-out strategies. Neutral-atom optical clocks, which are the leading systems for measuring time, have shown recent progress in terms of entanglement generation but at present lack the control capabilities for realizing such schemes.

Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury.

Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

Microbiome and infectious disease: diagnostics to therapeutics.

Over 300 years of research on the microbial world has revealed their importance in human health and disease. This review explores the impact and potential of microbial-based detection methods and therapeutic interventions, integrating research of early microbiologists, current findings, and future perspectives.

Achieving the Fundamental Quantum Limit of Linear Waveform Estimation.

Sensing a classical signal using a linear quantum device is a pervasive application of quantum-enhanced measurement. The fundamental precision limits of linear waveform estimation, however, are not fully understood. In certain cases, there is an unexplained gap between the known waveform-estimation quantum Cramér-Rao bound and the optimal sensitivity from quadrature measurement of the outgoing mode from the device.

Loss and microglia phagocytosis of synaptic proteins in frontotemporal lobar degeneration with TDP-43 proteinopathy.

Cortical synaptic loss has emerged as an early abnormality in Alzheimer's disease (AD) with a strong relationship to cognitive performance. However, the status of synapses in frontotemporal lobar degeneration (FTLD) has received meager experimental attention. The purpose of this study was to investigate changes in cortical synaptic proteins in FTLD with tar DNA binding protein-43 (TDP-43) proteinopathy.

Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota.

Reversible genomic DNA inversions control the expression of numerous gut bacterial molecules, but how this impacts disease remains uncertain. By analyzing metagenomic samples from inflammatory bowel disease (IBD) cohorts, we identified multiple invertible regions where a particular orientation correlated with disease. These include the promoter of polysaccharide A (PSA) of Bacteroides fragilis, which induces regulatory T cells (Tregs) and ameliorates experimental colitis.

Quantum Precision Limits of Displacement Noise-Free Interferometers.

Current laser-interferometric gravitational wave detectors suffer from a fundamental limit to their precision due to the displacement noise of optical elements contributed by various sources. Several schemes for displacement noise-free interferometers (DFI) have been proposed to mitigate their effects. The idea behind these schemes is similar to decoherence-free subspaces in quantum sensing; i.

Gut microbial signatures are associated with Lynch syndrome (LS) and cancer history in Druze communities in Israel.

Lynch syndrome (LS) is a hereditary cancer syndrome caused by autosomal dominant mutations, with high probability of early onset for several cancers, mainly colorectal cancer (CRC). The gut microbiome was shown to be influenced by host genetics and to be altered during cancer development. Therefore, we aimed to determine alterations in gut microbiome compositions of LS patients with and without cancer.

Combinatorial fluorescent labeling of live anaerobic bacteria via the incorporation of azide-modified sugars into newly synthesized macromolecules.

The human gut microbiome modulates physiological functions and pathologies; however, a mechanistic understanding of microbe-host and microbe-microbe interactions remains elusive owing to a lack of suitable approaches to monitor obligate anaerobic bacterial populations. Common genetically encoded fluorescent protein reporters, derived from the green fluorescent protein, require an oxidation step for fluorescent light emission and therefore are not suitable for use in anaerobic microbes residing in the intestine. Fluorescence in situ hybridization is a useful alternative to visualize bacterial communities in their natural niche; however, it requires tissue fixation.

Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43.

Objective: Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).

Shades of gray in human white matter.

Anatomists have long expressed interest in neurons of the white matter, which is by definition supposed to be free of neurons. Hypotheses regarding their biochemical signature and physiological function are mainly derived from animal models. Here, we investigated 15 whole-brain human postmortem specimens, including cognitively normal cases and those with pathologic Alzheimer's disease (AD).

Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies.

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy.

A sound mind in a sound body: Stress-induced glucocorticoids exacerbate gut inflammation.

The notion that psychological stress can deteriorate our health is widely accepted. However, the mechanisms at play are poorly understood. In this issue of Cell, Schneider et al.

Extracellular vesicles of the Gram-positive gut symbiont Bifidobacterium longum induce immune-modulatory, anti-inflammatory effects.

The gut microbiota is now well known to affect the host's immune system. One way of bacterial communication with host cells is via the secretion of vesicles, small membrane structures containing various cargo. Research on vesicles secreted by Gram-positive gut bacteria, their mechanisms of interaction with the host and their immune-modulatory effects are still relatively scarce.

Frontotemporal Degeneration with Transactive Response DNA-Binding Protein Type C at the Anterior Temporal Lobe.

The anatomical distribution of most neurodegenerative diseases shows considerable interindividual variations. In contrast, frontotemporal lobar degeneration with transactive response DNA-binding protein type C (TDP-C) shows a consistent predilection for the anterior temporal lobe (ATL). The relatively selective atrophy of ATL in TDP-C patients has highlighted the importance of this region for complex cognitive and behavioral functions.

Creating the Pick's disease International Consortium: Association study of H2 haplotype with risk of Pick's disease.

Background: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the gene.

Differential vulnerability of the dentate gyrus to tauopathies in dementias.

The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer's type due to Alzheimer's disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles-3R Pick's disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group.

Quantum metrology with imperfect measurements.

The impact of measurement imperfections on quantum metrology protocols has not been approached in a systematic manner so far. In this work, we tackle this issue by generalising firstly the notion of quantum Fisher information to account for noisy detection, and propose tractable methods allowing for its approximate evaluation. We then show that in canonical scenarios involving N probes with local measurements undergoing readout noise, the optimal sensitivity depends crucially on the control operations allowed to counterbalance the measurement imperfections-with global control operations, the ideal sensitivity (e.

Integrity of Neuronal Size in the Entorhinal Cortex Is a Biological Substrate of Exceptional Cognitive Aging.

Average aging is associated with a gradual decline of memory capacity. SuperAgers are humans ≥80 years of age who show exceptional episodic memory at least as good as individuals 20-30 years their junior. This study investigated whether neuronal integrity in the entorhinal cortex (ERC), an area critical for memory and selectively vulnerable to neurofibrillary degeneration, differentiated SuperAgers from cognitively healthy younger individuals, cognitively average peers ("Normal Elderly"), and individuals with amnestic mild cognitive impairment.

Resistance of Basal Forebrain Cholinergic Neurons to TDP-43 Proteinopathy in Primary Progressive Aphasia.

Basal forebrain cholinergic neurons (BFCN) display accumulation of neurofibrillary tangles and degeneration in Alzheimer disease and are targets of therapeutic intervention. This study determined vulnerability of BFCN to accumulation of TDP-43 in primary progressive aphasia with TDP-43 proteinopathy (PPA-TDP). Brains from 16 PPA participants with pathologically confirmed TDP-43 proteinopathy, with available paraffin-embedded sections (Group 1), or systematically sampled frozen sections (Group 2), were studied.

Global Thiol Proteome Analysis Provides Novel Insights into the Macrophage Inflammatory Response and Its Regulation by the Thioredoxin System.

Oxidative modifications of cysteine (Cys) thiols regulate various physiological processes, including inflammatory responses. The thioredoxin (Trx) system plays a key role in thiol redox control. The aim of this study was to characterize the dynamic cysteine proteome of human macrophages upon activation by the prototypical proinflammatory agent, bacterial lipopolysaccharide (LPS), and/or perturbation of the Trx system.