•Many hormones produced by the hypothalamo-pituitary axis are multifunctional.•Some growth and reproductive hormones have actions on energy balance and appetite.•Some peptides have a role in ...integrating feeding, metabolism, growth and reproduction.
Most endocrine systems in the body are influenced by the hypothalamic-pituitary axis. Within this axis, the hypothalamus delivers precise signals to the pituitary gland, which in turn releases hormones that directly affect target tissues including the liver, thyroid gland, adrenal glands and gonads. This action modulates the release of additional hormones from the sites of action, regulating key physiological processes, including growth, metabolism, stress and reproduction. Pituitary hormones are released by five distinct hormone-producing cell types: somatotropes (which produce growth hormone), thyrotropes (thyrotropin), corticotropes (adrenocorticotropin), lactotropes (prolactin) and gonadotropes (follicle stimulating hormone and luteinizing hormone), each modulated by specific hypothalamic signals. This careful and distinct organization of the hypothalamo-pituitary axis has been classically associated with the existence of many lineal axes (e.g., the hypothalamic-pituitary-gonadal axis) in charge of the control of the different physiological processes. While this traditional concept is valid, it is becoming apparent that hormones produced by the hypothalamo-pituitary axis have diverse effects. For instance, gonadotropin-releasing hormone II has been associated with a suppressive effect on food intake in fish. Likewise, growth hormone has been shown to influence appetite, swimming activity and aggressive behavior in fish. This review will focus on the hypothalamic and pituitary hormones classically involved in regulating growth and reproduction, and will attempt to provide a general overview of the current knowledge on their actions on energy balance and appetite in fish. It will also give a brief perspective of the role of some of these peptides in integrating feeding, metabolism, growth and reproduction.
Despite our increasing knowledge of molecular mechanisms guiding various aspects of human reproduction, those underlying human primordial germ cell (PGC) development remain largely unknown. Here, we ...conducted custom CRISPR screening in an in vitro system of human PGC-like cells (hPGCLCs) to identify genes required for acquisition and maintenance of PGC fate. Amongst our candidates, we identified TCL1A, an AKT coactivator. Functional assessment in our in vitro hPGCLCs system revealed that TCL1A played a critical role in later stages of hPGCLC development. Moreover, we found that TCL1A loss reduced AKT-mTOR signaling, downregulated expression of genes related to translational control, and subsequently led to a reduction in global protein synthesis and proliferation. Together, our study highlights the utility of CRISPR screening for human in vitro-derived germ cells and identifies novel translational regulators critical for hPGCLC development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Establishing a definitive diagnosis of pneumonia using conventional tests is difficult and expensive. Lateral flow immunoassays (LFIAs) are an advantageous point of care (POC) test option, but they ...have some limitations in terms of detection and quantification. In this work we have developed a lateral flow immunoassay for the ultrasensitive detection of penumolysin employing plasmonic Surface-Enhanced Resonance Raman Scattering (SERRS) tag as labelled probe. The combination of Au@Ag core-shell nanoparticles as plasmonic platform and Rhodamine B Isothiocyanate as Raman reporter has allowed us to fabricate a SERRS tag with high efficiency and reliability. The limit of detection of the SERRS-based LFIA was 1 pg mL
. This could be a strong foundation for a pneumonia diagnosis test based on pneumolysin detection.
In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic ...effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1
/
. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).
We make use of the Quantum Theory of Atoms in Molecules (QTAM) to partition the total energy of a many-electron system into intra- and interatomic terms, by explicitly computing both the one- and ...two-electron contributions. While the general scheme is formally equivalent to that by Bader et al., we focus on the separation and computation of the atomic self-energies and all the interaction terms. The partition is ultimately performed within the density matrices, in analogy with McWeeny's Theory of Electronic Separability, and then carried onto the energy. It is intimately linked with the atomistic picture of the chemical bond, not only allowing the separation of different two-body contributions (point-charge-like, multipolar, total Coulomb, exchange, correlation, ...) to the interaction between a pair of atoms but also including an effective many-body contribution to the binding (self-energy, formally one-body) due to the deformation of the atoms within the many-electron system as compared to the free atoms. Many qualitative ideas about the chemical bond can be quantified using this scheme.
Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators of AML cell fate, we ...performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene-expression programs. We show that KAT6A is the initiator of a newly described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small-molecule inhibitors could be of high therapeutic interest for mono-therapy or combinatorial differentiation-based treatment of AML.
AML is a poor-prognosis disease characterized by differentiation blockade. Through a cell-fate CRISPR screen, we identified KAT6A as a novel regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in a "writer-reader" epigenetic transcriptional control module. These results uncover a new epigenetic dependency and therapeutic opportunity in AML. This article is highlighted in the In This Issue feature, p. 587.
Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and ...can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation. This study aims to establish the potential role of TLR4 in both ethanol-induced glial activation and brain damage. Here we report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells since the knockdown of TLR4, by using both small interfering RNA or cells from TLR4-deficient mice, abolished the activation of microtubule-associated protein kinase and nuclear factor-kappaB pathways and the production of inflammatory mediators by astrocytes. Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates the immunoreactive levels of CD11b (microglial marker) and glial fibrillary acidic protein (astrocyte marker), and also increases caspase-3 activity and inducible nitric oxide synthase, COX-2, and cytokine levels interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6 in the cerebral cortex of female wild-type mice, TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.
This article shows how public offices in the early modern period became investment assets in Castile (Spain). Moreover, it demonstrates that offices fulfilled all the conditions for being viewed as ...safe assets. In particular, through the combination of qualitative sources with a novel hand‐collected database, it shows that offices did not suffer from adverse selection, were traded in liquid secondary markets, and increased their value during periods of economic distress. This research is a pioneer in revealing the existence in early modern times of a haven asset, other than coins and public debt, and showing at the same time the private financial uses of offices.
The effect of water deficit, salinity and both applied simultaneously on several physiological and morphological parameters in the ornamental plant Callistemon laevis was studied to identify the ...tolerance mechanisms developed by this species to these sources of stress and to evaluate their adaptability to such conditions. C. laevis plants were grown in pots outdoors and subjected to four irrigation treatments lasting ten months: control (0.8dSm−1, 100% water holding capacity), water deficit (0.8dSm−1, 50% of the amount of water supplied in control), saline (4.0dSm−1, same amount of water supplied as control) and saline water deficit (4.0dSm−1, 50% of the water supplied in the control). Water and saline stress, when applied individually, led to a reduction of 12% and 39% of total biomass, respectively, while overall plant quality (leaf color and flowering) was unaffected. However, saline water deficit affected leaf color and flowering and induced an excessive decrease of growth (68%) due to leaf tissue dehydration and a high leaf Cl and Na concentration. Biomass partitioning depended not only on the amount of water applied, but also on the electrical conductivity of the water. Water stress induced active osmotic adjustment and decreased leaf tissue elasticity. Although both Na and Cl concentrations in the plant tissues increased with salinity, Cl entry through the roots was more restricted. In plants submitted to salinity individually, Na tended to remain in the roots and stems, and little reached the leaves. However, plants simultaneously submitted to water and saline stress were not able to retain this ion in the woody parts. The decrease in stomatal conductance and photosynthesis was more marked in the plants submitted to both stresses, the effect of which decreased photosynthesis, and this together with membrane damage delayed plant recovery. The results show that the combination of deficit irrigation and salinity in C. laevis is not recommended since it magnifies the adverse effects of either when applied individually.
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