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Bacteria encode diverse defence systems, including restriction-modification and CRISPR-Cas, that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate that many recently identified antiphage defence operons comprise a nuclease and NTPase protein, suggesting that additional nucleic acid-targeting systems remain to be understood. Here we develop large-scale compa

Long RSH enzymes, Rel and RelA, are master regulators of bacterial (p)ppGpp alarmones levels. Bifunctional Rel transitions between a compact hydrolysis-competent (HD ON) state, a relaxed catalytically inactive (HD OFF/SYNTH OFF) state, and an elongated synthesis-competent (SYNTH ON) state, whereas RelA samples only the latter two. The distribution of these states is controlled by starved ribosomes

Grain boundary interaction with second-phase particles having different degrees of coherency is investigated using the phase field crystal (PFC) method. Both the enveloping and pass-through mechanisms are studied with regards to grain boundary pressure, passage time and interface evolution. It is found that coherent particles exert a stronger retardation effect on grain boundaries compared to incoGrain boundary interaction with second-phase particles having different degrees of coherency is investigated using the phase field crystal (PFC) method. Both the enveloping and pass-through mechanisms are studied with regards to grain boundary pressure, passage time and interface evolution. It is found that coherent particles exert a stronger retardation effect on grain boundaries compared to inco

6G systems, such as Large Intelligent Surfaces, will require distributed, complex, and coordinated decisions throughout a very heterogeneous and cell free infrastructure. This will require a fundamentally redesigned software infrastructure accompanied by massively distributed and heterogeneous computing resources, vastly different from current wireless networks.To address these challenges, in this6G systems, such as Large Intelligent Surfaces, will require distributed, complex, and coordinated decisions throughout a very heterogeneous and cell free infrastructure. This will require a fundamentally redesigned software infrastructure accompanied by massively distributed and heterogeneous computing resources, vastly different from current wireless networks.To address these challenges, in this

Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed huma

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased ab

Background: Metabolite profiles provide snapshots of the overall effect of numerous exposures accumulated over life courses, which may lead to health outcomes in the future. Objective: We hypothesized that the risk of all-cause mortality is linked to alterations in metabolism earlier in life, which are reflected in plasma metabolite profiles. We aimed to identify plasma metabolites associated with

The discovery that the CRISPR/Cas9 system could be used for genome editing purposes represented a major breakthrough in the field. This advancement has notably facilitated the introduction or correction of disease-specific mutations in healthy or disease stem cell lines respectively; therefore, easing disease modeling studies in combination with differentiation protocols. For many years, variabili

ObjectivesDiet has received attention as a factor possibly contributing to the development of Rheumatoid arthritis (RA). Several dietary exposures have been examined in various populations using different diet assessment methods. The aim of this study was to systematically assess the literature on the relation between dietary patterns, different food and food groups, macronutrients, non-alcoholic

As people age the home environment becomes increasingly important. Retirement commonly leads to spending more time in one’s home, and relocating from your own home in older age could be associated with reduced health or wellbeing. The relationship between home and person is complex and perceived aspects of one’s housing such as social, emotional and cognitive ties are considered important factors

α-Synuclein (aSyn) is a 140 residue long protein present in presynaptic termini of nerve cells. The protein is associated with Parkinson's disease, in which case it has been found to self-Assemble into long amyloid fibrils forming intracellular inclusions that are also rich in lipids. Furthermore, its synaptic function is proposed to involve interaction with lipid membranes, and hence, it is of in

BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.METHODS: The authors created hybridomas from an unimmunized l

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper-or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimu

The recent advent of Optical Photothermal IR (O-PTIR), has enabled for the first time, submicron infrared microscopy in far-field reflection mode with the combination of Raman for simultaneous, correlative IR+Raman microscopy. These unique and exciting synergistic capabilities are now spawning interest in life science application. A broad range of life science applications, otherwise impossible wi

Pure hydrocarbons with shape and conjugation properties that can be switched by external stimuli is an intriguing prospect in the design of new responsive materials and single-molecule electronics. Here, we develop an oligomeric [8]annulene-based material that combines a remarkably efficient topological switching upon redox changes with structural simplicity, stability, and straightforward synthes

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 μm × 100 μm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoust

Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesti