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Activating transcription factor 6 (ATF6) is an endoplasmic reticulum (ER) stress-regulated transcription factor that induces expression of major molecular chaperones in the ER. We recently reported that ATF6β, a subtype of ATF6, promoted survival of hippocampal neurons exposed to ER stress and excitotoxicity, at least in part by inducing expression of calreticulin, an ER molecular chaperone with high Ca2+-binding capacity. In the present study, we demonstrate that ATF6β deficiency in mice also decreases calreticulin expression and increases expression of glucose-regulated protein 78, another ER molecular chaperone, in emotional brain regions such as the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala. Comprehensive behavioral analyses revealed that Atf6b−/− mice exhibit anxiety-like behavior in the light/dark transition test and hyperactivity in the forced swim test. Consistent with these results, PFC and hypothalamic corticotropin-releasing hormone (CRH) expression was increased in Atf6b−/− mice, as was circulating corticosterone. Moreover, CRH receptor 1 antagonism alleviated anxiety-like behavior in Atf6b−/− mice. These findings suggest that ATF6β deficiency produces anxiety-like behavior and hyperactivity via a CRH receptor 1-dependent mechanism. ATF6β could play a role in psychiatric conditions in the emotional centers of the brain. [ABSTRACT FROM AUTHOR]

While ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of its paralogue ATF6β remains elusive, especially in the central nervous system (CNS). Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin (CRT), a molecular chaperone in the ER with a high Ca2+-binding capacity. CRT expression was reduced to ~ 50% in the CNS of Atf6b−/− mice under both normal and ER stress conditions. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death. The higher levels of death in Atf6b−/− neurons were recovered by ATF6β and CRT overexpressions, or by treatment with Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and with an ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in the hippocampi of Atf6b−/− and Calr+/− mice, and restored by administration of 2-APB and salubrinal. These results suggest that the ATF6β-CRT axis promotes neuronal survival under ER stress and excitotoxity by improving intracellular Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • CQDs/AuNPs were synthesized and thoroughly characterized by XRD, XPS, IR, UV–Vis and TEM. • Linear increase of fluorescence intensity recovery with amikacin concentration. • Wide linear range from 10-10 to 10-8 M, high accuracy, very low LOD of 0.02 ppb. • High selectivity for amikacin detection towards different commonly antibiotics. • Successfully applied for amikacin detection in drugs and surface water samples. Amikacin is an aminoglycoside antibiotic widely used to treat various bacterial infections in humans. However, elevated concentrations of amikacin can damage the cochlear nerve. Thus, accurate and rapid amikacin detection is crucial. In this study, we developed an "on-off" fluorescence nanosensor for highly sensitive amikacin determination based on a composite of carbon quantum dots (CQDs) and gold nanoparticles (AuNPs). The method quenches CQD fluorescence (turn-off) when they bind to AuNPs but restores it (turn-on) when amikacin binds and releases the CQDs. Adding Cu2+ enhances sensitivity by cross-linking amikacin-coated AuNPs. Under optimal conditions (pH 4, 1 mM Na 2 SO 4 , 1 mM CuSO 4), the method achieved a low detection limit of 3.5 × 10-11 M (0.02 ppb), a wide linear range (10-10 to 10-8 M), high precision (RSD < 5 %), and a rapid 2-minute response time. Exceptional selectivity was observed over other antibiotics. The CQDs/AuNPs-based sensor successfully detected amikacin in pharmaceutical and surface water samples. This approach offers a fast on-site analytical method for amikacin detection, with potential applications in clinical and environmental settings. [ABSTRACT FROM AUTHOR]

We study the collapse of a many-body system which is used to model two-component Bose–Einstein condensates with attractive intra-species interactions and either attractive or repulsive inter-species interactions. Such a system consists a mixture of two different species for N identical bosons in R 2 , interacting with potentials rescaled in the mean-field manner - N 2 β - 1 w (σ) (N β x) with ∫ R 2 w (σ) (x) d x = 1 . Assuming that 0 < β < 1 / 2 , we first show that the leading order of the quantum energy is captured correctly by the Gross–Pitaevskii energy. Secondly, we investigate the blow-up behavior of the quantum energy as well as the ground states when N → ∞ , and either the total interaction strength of intra-species and inter-species or the strengths of intra-species interactions of each component approach sufficiently slowly a critical value, which is the critical strength for the focusing Gross–Pitaevskii functional. We prove that the many-body ground states fully condensate on the (unique) Gagliardo–Nirenberg solution. [ABSTRACT FROM AUTHOR]

We consider a 3D quantum system of N identical bosons in a trapping potential | x | p , with p ≥ 0 , interacting via a Newton potential with an attractive interaction strength a N . For a fixed large N and the coupling constant a N smaller than a critical value a ∗ (Chandrasekhar limit mass), in an appropriate sense, the many-body system admits a ground state. We investigate the blow-up behavior of the ground state energy as well as the ground states when a N approaches a ∗ sufficiently slowly in the limit N → ∞. The blow-up profile is given by the Gagliardo–Nirenberg solutions. [ABSTRACT FROM AUTHOR]

We study the Chandrasekhar variational model for neutron stars, with or without an external potential. We prove the existence of minimizers when the attractive interaction strength τ is strictly smaller than the Chandrasekhar limit τc and investigate the blow-up phenomenon in the limit τ ↑ τc. We show that the blow-up profile of the minimizer(s) is given by the Lane–Emden solution. [ABSTRACT FROM AUTHOR]

We study minimizers of the pseudo-relativistic Hartree functional $${\mathcal {E}}_{a}(u):=\Vert (-\varDelta +m^{2})^{1/4}u\Vert _{L^{2}}^{2}+\int _{{\mathbb {R}}^{3}}V(x)|u(x)|^{2}\mathrm{d}x-\frac{a}{2}\int _{{\mathbb {R}}^{3}}(\left| \cdot \right| ^{-1}\star |u|^{2})(x)|u(x)|^{2}\mathrm{d}x$$ under the mass constraint $$\int _{{\mathbb {R}}^3}|u(x)|^2\mathrm{d}x=1$$ . Here $$m>0$$ is the mass of particles and $$V\ge 0$$ is an external potential. We prove that minimizers exist if and only if a satisfies $$0\le a0$$ . [ABSTRACT FROM AUTHOR]

We consider the gravitational collapse for neutron stars in the Hartree–Fock–Bogoliubov theory. We prove that when the number particle becomes large and the gravitational constant is small such that the attractive interaction strength approaches the Chandrasekhar limit mass slowly, the minimizers develop a universal blow-up profile. It is given by the Lane–Emden solution. [ABSTRACT FROM AUTHOR]

A graphitic carbon nitride functionalized gold nanoparticles (g-C 3 N 4 /AuNPs) based fluorometric assay was developed for simple and rapid on-site amikacin determination. g-C 3 N 4 fluorescence is reduced (turn-off) when they bind to AuNPs but recovers (turn-on) when amikacin binds to AuNPs and releases the g-C 3 N 4. The assay is based on the effective property of AuNPs as absorbers in inner filter effect (IFE) systems. Under optimized conditions of 25 mM Na 2 SO 4 , pH 6.0, 3.0 mg mL−1 g-C 3 N 4, and incubation time of 12 min, the proposed method achieved a low detection limit of 5 × 10−9 M (2.9 ppb), wide linear range from 10−8 to 10−6 M, high precision (RSD <5 %) and high selectivity over other ions including Ca2+, Mg2+, Fe2+, NO 3 −, and PO 4 3− as well as several antibiotics, namely naproxen, levofloxacin, vancomycin, ceftriaxone, amoxicillin. The fluorometric sensor based on g-C 3 N 4 /AuNPs has produced good agreement quantifying amikacin in pharmaceutical samples, as cross-checked with LC-MS/MS method. The developed fluorometric sensor is promising for rapid on-site detection of other organic and inorganic substances with high sensitivity, selectivity, and minimal reagent consumption. • g-C 3 N 4 /AuNPs were synthesized and confirmed by XRD, IR, UV–Vis, TEM and SEM/EDS. • The recovery in fluorescence intensity of g-C 3 N 4 /AuNPs witnessed a linear increase with amikacin concentration. • A large linear range from 10−8 to 10−6 M, high accuracy, selectivity and low LOD of 5 × 10−9 M (2.9 ppb) of amikacin. • The proposed method was successfully applied for amikacin determination in pharmaceutical samples. [ABSTRACT FROM AUTHOR]

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP‐ribosyl cyclase to produce cyclic ADP–ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial‐expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults. Synopsis: Postnatal expression of the ADP‐ribosyl cyclase CD38 in astrocytes regulates neuronal circuit formation and social behavior in adults.Postnatal expression, but not adult expression, of CD38 in astrocytes regulates social memory.Astrocytic CD38 promotes excitatory synapse formation in the medial prefrontal cortex and hippocampal CA1 and CA2.Astrocytic CD38 promotes secretion of the synaptogenic protein SPARCL1 via cyclic ADP–ribose and calcium signaling. [ABSTRACT FROM AUTHOR]

Neuroinflammation is initiated by activation of the brain's innate immune system in response to an inflammatory challenge. Insufficient control of neuroinflammation leads to enhanced or prolonged pathology in various neurological conditions including multiple sclerosis and Alzheimer's disease. Nicotinamide adenine dinucleotide (NAD+) plays critical roles in cellular energy metabolism and calcium homeostasis. Our previous study demonstrated that deletion of CD38, which consumes NAD+, suppressed cuprizone‐induced demyelination, neuroinflammation, and glial activation. However, it is still unknown whether CD38 directly affects neuroinflammation through regulating brain NAD+ level. In this study, we investigated the effect of CD38 deletion and inhibition and supplementation of NAD+ on lipopolysaccharide (LPS)‐induced neuroinflammation in mice. Intracerebroventricular injection of LPS significantly increased CD38 expression especially in the hippocampus. Deletion of CD38 decreased LPS‐induced inflammatory responses and glial activation. Pre‐administration of apigenin, a flavonoid with CD38 inhibitory activity, or nicotinamide riboside (NR), an NAD+ precursor, increased NAD+ level, and significantly suppressed induction of cytokines and chemokines, glial activation and subsequent neurodegeneration after LPS administration. In cell culture, LPS‐induced inflammatory responses were suppressed by treatment of primary astrocytes or microglia with apigenin, NAD+, NR or 78c, the latter a specific CD38 inhibitor. Finally, all these compounds suppressed NF‐κB signaling pathway in microglia. These results suggest that CD38‐mediated neuroinflammation is linked to NAD+ consumption and that boosting NAD+ by CD38 inhibition and NR supplementation directly suppress neuroinflammation in the brain. [ABSTRACT FROM AUTHOR]

Biodiversity assessment has been the focus of intense debate and conceptual and methodological advances in recent years. The cultural, academic and aesthetic impulses to recognise and catalogue the diversity in our surroundings, in this case of living objects, is furthermore propelled by the urgency of understanding that we may be responsible for a dramatic reduction of biodiversity, comparable in magnitude to geological mass extinctions. One of the most important advances in this attempt to characterise biodiversity has been incorporating DNA-based characters and molecular taxonomy tools to achieve faster and more efficient species delimitation and identification, even in hyperdiverse tropical biomes. In this assay we advocate for a broad understanding of Biodiversity as the inventory of species in a given environment, but also the diversity of their interactions, with both aspects being attainable using molecular markers and phylogenetic approaches. We exemplify the suitability and utility of this framework for large-scale biodiversity assessment with the results of our ongoing projects trying to characterise the communities of leaf beetles and their host plants in several tropical setups. Moreover, we propose that approaches similar to ours, establishing the inventories of two ecologically inter-related and species-rich groups of organisms, such as insect herbivores and their angiosperm host-plants, can serve as the foundational stone to anchor a comprehensive assessment of diversity, also in tropical environments, by subsequent addition of trophic levels. [ABSTRACT FROM AUTHOR]

• NDRG2 expression increased during postnatal brain development. • NDRG2 deficiency altered gene expression in the brain, including Bmp4 and Per2. • NDRG2 knockout mice showed abnormal social behavior. N-myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family, has multiple functions in cell proliferation, differentiation, and stress responses, and is predominantly expressed by astrocytes in the central nervous system. Previous studies including ours demonstrated that NDRG2 is involved in various central nervous system pathologies. However, the significance of NDRG2 in neurodevelopment is not fully understood. Here, we investigated the expression profile of NDRG2 during postnatal brain development, the role of NDRG2 in social behavior, and transcriptome changes in the brain of NDRG2-deficient mice. NDRG2 expression in the brain increased over time from postnatal day 1 to adulthood. Deletion of NDRG2 resulted in abnormal social behavior, as indicated by reduced exploratory activity toward a novel mouse in a three-chamber social interaction test. Microarray analysis identified genes differentially expressed in the NDRG2-deficient brain, and upregulated gene expression of Bmp4 and Per2 was confirmed by quantitative PCR analysis. Expression of both these genes and the encoded proteins increased over time during postnatal brain development, similar to NDRG2. Gene expression of Bmp4 and Per2 was upregulated in cultured astrocytes isolated from NDRG2-deficient mice. These results suggest that NDRG2 contributes to brain development required for proper social behavior by modulating gene expression in astrocytes. [ABSTRACT FROM AUTHOR]