Cell-specific expression of key mitochondrial enzymes limits OXPHOS in astrocytes of the adult human neocortex and hippocampal formation

\ua9 The Author(s) 2024.The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis. (Figure presented.

A systematic practice review: Providing palliative care for people with Parkinson’s disease and their caregivers

Background: People with Parkinson’s disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered. Aim: The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson’s disease and their caregivers. Design: A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the ‘do’, ‘do not do’ and ‘do not know’ recommendations for palliative care. Data sources: Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care. Results: A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early. Conclusions: Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson’s disease and their caregivers

<i>Staphylococcus aureus</i> and the ecology of the nasal microbiome

The human microbiome can play a key role in host susceptibility to pathogens, including in the nasal cavity, a site favored by Staphylococcus aureus. However, what determines our resident nasal microbiota—the host or the environment—and can interactions among nasal bacteria determine S. aureus colonization? Our study of 46 monozygotic and 43 dizygotic twin pairs revealed that nasal microbiota is an environmentally derived trait, but the host’s sex and genetics significantly influence nasal bacterial density. Although specific taxa, including lactic acid bacteria, can determine S. aureus colonization, their negative interactions depend on thresholds of absolute abundance. These findings demonstrate that nasal microbiota is not fixed by host genetics and opens the possibility that nasal microbiota may be manipulated to prevent or eliminate S. aureus colonization

Staphylococcus aureus and the ecology of the nasal microbiome

The human microbiome can play a key role in host susceptibility to pathogens, including in the nasal cavity, a site favored by Staphylococcus aureus. However, what determines our resident nasal microbiota—the host or the environment—and can interactions among nasal bacteria determine S. aureus colonization? Our study of 46 monozygotic and 43 dizygotic twin pairs revealed that nasal microbiota is an environmentally derived trait, but the host’s sex and genetics significantly influence nasal bacterial density. Although specific taxa, including lactic acid bacteria, can determine S. aureus colonization, their negative interactions depend on thresholds of absolute abundance. These findings demonstrate that nasal microbiota is not fixed by host genetics and opens the possibility that nasal microbiota may be manipulated to prevent or eliminate S. aureus colonization

The exponential law: Monopole detectors, Bogoliubov transformations, and the thermal nature of the Euclidean vacuum in RP^3 de Sitter spacetime

We consider scalar field theory on the RP^3 de Sitter spacetime (RP3dS), which is locally isometric to de Sitter space (dS) but has spatial topology RP^3. We compare the Euclidean vacua on RP3dS and dS in terms of three quantities that are relevant for an inertial observer: (i) the stress-energy tensor; (ii) the response of an inertial monopole particle detector; (iii) the expansion of the Euclidean vacuum in terms of many-particle states associated with static coordinates centered at an inertial world line. In all these quantities, the differences between RP3dS and dS turn out to fall off exponentially at early and late proper times along the inertial trajectory. In particular, (ii) and (iii) yield at early and late proper times in RP3dS the usual thermal result in the de Sitter Hawking temperature. This conforms to what one might call an exponential law: in expanding locally de Sitter spacetimes, differences due to global topology should fall off exponentially in the proper time.Comment: 22 pages, REVTex v3.1 with amsfonts and epsf, includes 2 eps figures. (v2: Minor typos corrected, references updated.

Creation of a Compact Topologically Nontrivial Inflationary Universe

If inflation can occur only at the energy density V much smaller than the Planck density, which is the case for many inflationary models based on string theory, then the probability of quantum creation of a closed or an infinitely large open inflationary universe is exponentially suppressed for all known choices of the wave function of the universe. Meanwhile under certain conditions there is no exponential suppression for creation of topologically nontrivial compact flat or open inflationary universes. This suggests, contrary to the standard textbook lore, that compact flat or open universes with nontrivial topology should be considered a rule rather than an exception.Comment: 9 pages 2 figures, new materials and references adde

Risk assessment of the biocontrol product Nemaslug 2.0 with the active organisms Phasmarhabditis californica (strain P19D) and Moraxella osloensis

publishedVersio

Racetrack Inflation

We develop a model of eternal topological inflation using a racetrack potential within the context of type IIB string theory with KKLT volume stabilization. The inflaton field is the imaginary part of the K\"ahler structure modulus, which is an axion-like field in the 4D effective field theory. This model does not require moving branes, and in this sense it is simpler than other models of string theory inflation. Contrary to single-exponential models, the structure of the potential in this example allows for the existence of saddle points between two degenerate local minima for which the slow-roll conditions can be satisfied in a particular range of parameter space. We conjecture that this type of inflation should be present in more general realizations of the modular landscape. We also consider `irrational' models having a dense set of minima, and discuss their possible relevance for the cosmological constant problem.Comment: 23 pages 7 figures. The final version with minor modifications, to appear in JHE

A broad range quorum sensing inhibitor working through sRNA inhibition

Abstract For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline