The use of non-invasive brain stimulation is widespread in studies of human cognitive neuroscience. This has led to some genuine advances in understanding perception and cognition, and has raised ...some hopes of applying the knowledge in clinical contexts. There are now several forms of stimulation, the ability to combine these with other methods, and ethical questions that are special to brain stimulation. In this Primer, we aim to give the users of these methods a starting point and perspective from which to view the key questions and usefulness of the different forms of non-invasive brain stimulation. We have done so by taking a critical view of recent highlights in the literature, selected case studies to illustrate the elements necessary and sufficient for good experiments, and pointed to questions and findings that can only be addressed using interference methods.
Parkin et al. describe the advances and challenges of non-invasive brain stimulation in humans. The consolidation of transcranial magnetic stimulation and the use of transcranial electrical stimulation are discussed critically in the light of recent investigations.
Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs ...when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells.
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•Lactate supports lysosomal acidification and autophagy in cancer•Lactate oxidation by LDHB yields protons that fuel lysosomal V-ATPase•Targeting LDHB selectively blocks autophagy in oxidative and glycolytic cancer cells•Targeting LDHB is a promising anticancer approach
Brisson et al. show that lactate dehydrogenase B (LDHB) is critical for lysosomal activity and autophagy in cancer cells. Silencing LDHB selectively inhibits the proliferation of both oxidative and glycolytic cancer cells over normal cells, suggesting inhibition of LDHB as a promising anticancer approach.
In order to formalize and extend on previous ad-hoc analysis and synthesis methods a theoretical treatment using vector representations of directional modulation (DM) systems is introduced and used ...to achieve DM transmitter characteristics. An orthogonal vector approach is proposed which allows the artificial orthogonal noise concept derived from information theory to be brought to bear on DM analysis and synthesis. The orthogonal vector method is validated and discussed via bit error rate (BER) simulations.
Adult stem cell (SC) maintenance and differentiation are known to depend on signals received from the niche. Here, however, we demonstrate a mechanism for SC specification and regulation that is ...niche independent. Using immunofluorescence, live imaging, genetics, cell-cycle analyses, in utero lentiviral transduction, and lineage-tracing, we show that in developing hair buds, SCs are born from asymmetric divisions that differentially display WNT and SHH signaling. Displaced WNTlo suprabasal daughters become SCs that respond to paracrine SHH and symmetrically expand. By contrast, basal daughters remain WNThi. They express but do not respond to SHH and hence maintain slow-cycling, asymmetric divisions. Over time, they become short-lived progenitors, generating differentiating daughters rather than SCs. Thus, in contrast to an established niche that harbors a fixed SC pool whose expelled progeny differentiate, asymmetric divisions first specify and displace early SCs into an environment conducive to expansion and later restrict their numbers by switching asymmetric fates.
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•Asymmetric divisions within hair buds differentially partition WNT and SHH signaling•This partitioning couples asymmetric cell division to asymmetric cell fate•WNTlo daughters that respond to, but do not produce, SHH expand symmetrically•WNThi SHH-producing cells ultimately cease producing stem cell daughters
A mechanism for specifying stem cell numbers and identity that is independent of a physical niche operates during skin development: reciprocal signaling between an asymmetrically dividing and transient population of cells and their fast-cycling, symmetrically dividing sisters fuels the regulatory system.
Monocarboxylate transporters in cancer Payen, Valéry L.; Mina, Erica; Van Hée, Vincent F. ...
Molecular metabolism (Germany),
03/2020, Letnik:
33
Journal Article
Recenzirano
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Tumors are highly plastic metabolic entities composed of cancer and host cells that can adopt different metabolic phenotypes. For energy production, cancer cells may use 4 main fuels that are ...shuttled in 5 different metabolic pathways. Glucose fuels glycolysis that can be coupled to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in oxidative cancer cells or to lactic fermentation in proliferating and in hypoxic cancer cells. Lipids fuel lipolysis, glutamine fuels glutaminolysis, and lactate fuels the oxidative pathway of lactate, all of which are coupled to the TCA cycle and OXPHOS for energy production. This review focuses on the latter metabolic pathway.
Lactate, which is prominently produced by glycolytic cells in tumors, was only recently recognized as a major fuel for oxidative cancer cells and as a signaling agent. Its exchanges across membranes are gated by monocarboxylate transporters MCT1-4. This review summarizes the current knowledge about MCT structure, regulation and functions in cancer, with a specific focus on lactate metabolism, lactate-induced angiogenesis and MCT-dependent cancer metastasis. It also describes lactate signaling via cell surface lactate receptor GPR81.
Lactate and MCTs, especially MCT1 and MCT4, are important contributors to tumor aggressiveness. Analyses of MCT-deficient (MCT+/- and MCT−/-) animals and (MCT-mutated) humans indicate that they are druggable, with MCT1 inhibitors being in advanced development phase and MCT4 inhibitors still in the discovery phase. Imaging lactate fluxes non-invasively using a lactate tracer for positron emission tomography would further help to identify responders to the treatments.
•In cancer, hypoxia and cell proliferation are associated to lactic acid production.•Lactate exchanges are at the core of tumor metabolism.•Transmembrane lactate trafficking depends on monocarboxylate transporters (MCTs).•MCTs are implicated in tumor development and aggressiveness.•Targeting MCTs is a therapeutic option for cancer treatment.
Monocarboxylate transporters in the brain and in cancer Pérez-Escuredo, Jhudit; Van Hée, Vincent F.; Sboarina, Martina ...
Biochimica et biophysica acta,
October 2016, 2016-10-00, Letnik:
1863, Številka:
10
Journal Article
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Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1–4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with ...protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1–4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
Heart failure is the leading cause of death worldwide, and current therapies only delay progression of the disease. Laboratory experiments and recent clinical trials suggest that cell-based therapies ...can improve cardiac function, and the implications of this for cardiac regeneration are causing great excitement. Bone-marrow-derived progenitor cells and other progenitor cells can differentiate into vascular cell types, restoring blood flow. More recently, resident cardiac stem cells have been shown to differentiate into multiple cell types present in the heart, including cardiac muscle cells, indicating that the heart is not terminally differentiated. These new findings have stimulated optimism that the progression of heart failure can be prevented or even reversed with cell-based therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The three-dimensional (3D) printing of flexible and stretchable materials with smart functions such as shape memory (SM) and self-healing (SH) is highly desirable for the development of future 4D ...printing technology for myriad applications, such as soft actuators, deployable smart medical devices, and flexible electronics. Here, we report a novel ink that can be used for the 3D printing of highly stretchable, SM, and SH elastomer via UV-light-assisted direct-ink-write printing. An ink containing urethane diacrylate and a linear semicrystalline polymer is developed for the 3D printing of a semi-interpenetrating polymer network elastomer that can be stretched by up to 600%. The 3D-printed complex structures show interesting functional properties, such as high strain SM and SM -assisted SH capability. We demonstrate that such a 3D-printed SM elastomer has the potential application for biomedical devices, such as vascular repair devices. This research paves a new way for the further development of novel 4D printing, soft robotics, and biomedical devices.
Pomegranate extracts have been used for centuries in traditional medicine to confer health benefits in a number of inflammatory diseases, microbial infections and cancer. Peel fruit are rich in ...polyphenols that exhibit antioxidant and anti-inflammatory capacities in vitro. Recent studies strongly suggest that the gut microbiota is an environmental factor to be taken into account when assessing the risk factors related to obesity. The aim of the present study was to test the prebiotic potency of a pomegranate peel extract (PPE) rich in polyphenols in a nutritional model of obesity associated with hypercholesterolaemia and inflammatory disorders. Balb/c mice were fed either a control diet or a high-fat (HF) diet with or without PPE (6 mg/d per mouse) over a period of 4 weeks. Interestingly, PPE supplementation increased caecal content weight and caecal pool of bifidobacteria. It did not significantly modify body weight gain, glycaemia, glucose tolerance and inflammatory markers measured in the serum. However, it reduced the serum level of cholesterol (total and LDL) induced by HF feeding. Furthermore, it counteracted the HF-induced expression of inflammatory markers both in the colon and the visceral adipose tissue. Together, these findings support that pomegranate constitutes a promising food in the control of atherogenic and inflammatory disorders associated with diet-induced obesity. Knowing the poor bioavailability of pomegranate polyphenols, its bifidogenic effect observed after PPE consumption suggests the involvement of the gut microbiota in the management of host metabolism by polyphenolic compounds present in pomegranate.
Bacillus cereus food intoxication and toxicoinfection Jovanovic, Jelena; Ornelis, Vincent F. M.; Madder, Annemieke ...
Comprehensive reviews in food science and food safety,
July 2021, Letnik:
20, Številka:
4
Journal Article
Recenzirano
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Bacillus cereus is one of the leading etiological agents of toxin‐induced foodborne diseases. Its omnipresence in different environments, spore formation, and its ability to adapt to varying ...conditions and produce harmful toxins make this pathogen a health hazard that should not be underestimated. Food poisoning by B. cereus can manifest itself as an emetic or diarrheal syndrome. The former is caused by the release of the potent peptide toxin cereulide, whereas the latter is the result of proteinaceous enterotoxins (e.g., hemolysin BL, nonhemolytic enterotoxin, and cytotoxin K). The final harmful effect is not only toxin and strain dependent, but is also affected by the stress responses, accessory virulence factors, and phenotypic properties under extrinsic, intrinsic, and explicit food conditions and host‐related environment. Infamous portrait of B. cereus as a foodborne pathogen, as well as a causative agent of nongastrointestinal infections and even nosocomial complications, has inspired vast volumes of multidisciplinary research in food and clinical domains. As a result, extensive original data became available asking for a new, both broad and deep, multifaceted look into the current state‐of‐the art regarding the role of B. cereus in food safety. In this review, we first provide an overview of the latest knowledge on B. cereus toxins and accessory virulence factors. Second, we describe the novel taxonomy and some of the most pertinent phenotypic characteristics of B. cereus related to food safety. We link these aspects to toxin production, overall pathogenesis, and interactions with its human host. Then we reflect on the prevalence of different toxinotypes in foods opening the scene for epidemiological aspects of B. cereus foodborne diseases and methods available to prevent food poisoning including overview of the different available methods to detect B. cereus and its toxins.
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