Algebraic Geometry of Quantum Graphical Models

Algebro-geometric methods have proven to be very successful in the study of graphical models in statistics. In this paper we introduce the foundations to carry out a similar study of their quantum counterparts. These quantum graphical models are families of quantum states satisfying certain locality or correlation conditions encoded by a graph. We lay out several ways to associate an algebraic variety to a quantum graphical model. The classical graphical models can be recovered from most of these varieties by restricting to quantum states represented by diagonal matrices. We study fundamental properties of these varieties and provide algorithms to compute their defining equations. Moreover, we study quantum information projections to quantum exponential families defined by graphs and prove a quantum analogue of Birch's Theorem.Comment: 20 pages, comments welcome

Effect of a multinutrient intervention after ischemic stroke in female C57Bl/6 mice.

Stroke can affect females very differently from males, and therefore preclinical research on underlying mechanisms and the effects of interventions should not be restricted to male subjects, and treatment strategies for stroke should be tailored to benefit both sexes. Previously, we demonstrated that a multinutrient intervention (Fortasyn) improved impairments after ischemic stroke induction in male C57Bl/6 mice, but the therapeutic potential of this dietary treatment remained to be investigated in females. We now induced a transient middle cerebral artery occlusion (tMCAo) in C57Bl/6 female mice and immediately after surgery switched to either Fortasyn or an isocaloric Control diet. The stroke females performed several behavioral and motor tasks before and after tMCAo and were scanned in an 11.7 Tesla MRI scanner to assess brain perfusion, integrity and functional connectivity. To assess brain plasticity, inflammation and vascular integrity, immunohistochemistry was performed after sacrifice of the mice. We found that the multinutrient intervention had diverse effects on the stroke-induced impairments in females. Similar to previous observations in male stroke mice, brain integrity, sensorimotor integration and neurogenesis benefitted from Fortasyn, but impairments in activity and motor skills were not improved in female stroke mice. Overall, Fortasyn effects in the stroked females seem more modest in comparison to previously investigated stroked male mice. We suggest that with further optimization of treatment protocols more information on the efficacy of specific interventions in stroked females can be gathered. This in turn will help with the development of (gender-specific) treatment regimens for cerebrovascular diseases such as stroke

The pale spear-nosed bat : a neuromolecular and transgenic model for vocal learning

Funding: UK Research and Innovation (Grant Number(s): MR/T021985/1; Grant recipient(s): Sonja Vernes). Max-Planck-Gesellschaft (Grant Number(s): Max Planck Research Group ; Grant recipient(s): Sonja Vernes). Human Frontier Science Program (Grant Number(s): RGP0058/2016, RGP0058/2016; Grant recipient(s): Uwe Firzlaff, Sonja Vernes).Vocal learning, the ability to produce modified vocalizations via learning from acoustic signals, is a key trait in the evolution of speech. While extensively studied in songbirds, mammalian models for vocal learning are rare. Bats present a promising study system given their gregarious natures, small size, and the ability of some species to be maintained in captive colonies. We utilize the pale spear-nosed bat (Phyllostomus discolor) and report advances in establishing this species as a tractable model for understanding vocal learning. We have taken an interdisciplinary approach, aiming to provide an integrated understanding across genomics (Part I), neurobiology (Part II), and transgenics (Part III). In Part I, we generated new, high-quality genome annotations of coding genes and noncoding microRNAs to facilitate functional and evolutionary studies. In Part II, we traced connections between auditory-related brain regions and reported neuroimaging to explore the structure of the brain and gene expression patterns to highlight brain regions. In Part III, we created the first successful transgenic bats by manipulating the expression of FoxP2, a speech-related gene. These interdisciplinary approaches are facilitating a mechanistic and evolutionary understanding of mammalian vocal learning and can also contribute to other areas of investigation that utilize P. discolor or bats as study species.Publisher PDFPeer reviewe

Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr^−/−.Leiden mice

The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr−/−.Leiden mice. Ldlr−/−.Leiden mice received 16 weeks either a high-fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD-fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD-control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD-induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1-positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD-induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD-induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.</p

Impaired mitochondrial complex I function as a candidate driver in the biological stress response and a concomitant stress-induced brain metabolic reprogramming in male mice

Mitochondria play a critical role in bioenergetics, enabling stress adaptation, and therefore, are central in biological stress responses and stress-related complex psychopathologies. To investigate the effect of mitochondrial dysfunction on the stress response and the impact on various biological domains linked to the pathobiology of depression, a novel mouse model was created. These mice harbor a gene trap in the first intron of the Ndufs4 gene (Ndufs4GT/GT mice), encoding the NDUFS4 protein, a structural component of complex I (CI), the first enzyme of the mitochondrial electron transport chain. We performed a comprehensive behavioral screening with a broad range of behavioral, physiological, and endocrine markers, high-resolution ex vivo brain imaging, brain immunohistochemistry, and multi-platform targeted mass spectrometry-based metabolomics. Ndufs4GT/GT mice presented with a 25% reduction of CI activity in the hippocampus, resulting in a relatively mild phenotype of reduced body weight, increased physical activity, decreased neurogenesis and neuroinflammation compared to WT littermates. Brain metabolite profiling revealed characteristic biosignatures discriminating Ndufs4GT/GT from WT mice. Specifically, we observed a reversed TCA cycle flux and rewiring of amino acid metabolism in the prefrontal cortex. Next, exposing mice to chronic variable stress (a model for depression-like behavior), we found that Ndufs4GT/GT mice showed altered stress response and coping strategies with a robust stress-associated reprogramming of amino acid metabolism. Our data suggest that impaired mitochondrial CI function is a candidate driver for altered stress reactivity and stress-induced brain metabolic reprogramming. These changes result in unique phenomic and metabolomic signatures distinguishing groups based on their mitochondrial genotype

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

Contains fulltext : 157496.pdf (publisher's version ) (Open Access)APOE epsilon4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging