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Venture capital investment and hedge fund investment are two asset classes of alternative investment fund portfolios. The purpose of this study was to determine whether the digital currency named bitcoin truly adds to diversification in an alternative investment fund portfolio. Vector auto regression was used to determine any unidirectional or bidirectional relationship between variables. The DCC-GARCH test was conducted to determine any conditional correlations that impact volatility transmission over a shorter and longer duration of time between variables. The results showed that there was no unidirectional or bidirectional relationship between bitcoin and FTSE venture capital index, as well as between bitcoin and the Barclays Hedge Fund Index. The DCC model showed no volatility transmission between bitcoin and the Barclays Hedge Fund Index, whereas volatility persists between bitcoin and the FTSE Venture Capital Index, connecting risk between the financial time series with only low correlations. These findings suggest that bitcoin could be used by investors, policy makers, and hedgers for diversification in alternative investment fund portfolios.

PurposeCoronavirus disease 2019 (COVID-19) has disrupted global supply chains, revealing dreadful gaps and exposing vulnerabilities. Retailers are challenged to tackle risks and organise themselves to fit into the “new normal” scenario. This global outbreak has established a volatile environment for supply chains; it has raised the question of survival in the market, forcing companies to rethink resilient strategies to be adopted for the post-pandemic situation to mitigate the long-term effects of this virus. This study explores the priorities for retail supply chains (RSCs) to align their business operations and strategies for the post-pandemic world.Design/methodology/approachThis study has utilised integrated full consistency model (FUCOM) – best–worst method (BWM) for assessment of RSCs to enhance their business performance irrespective of pandemic disruptions. The FUCOM has been employed to identify the priorities of determinants enhancing business performance, whereas RSC strategies are evaluated using the BWM method.FindingsThe current study identifies “Collaboration Efficiency” as the main criterion for accelerating the performance of RSCs in a dynamic social environment. Also, the study concludes that “Order Fulfilment” and “Digital RSCs” are the most appropriate resilient business strategies to mitigate the long-term effects.Research limitations/implicationsSupply-demand balancing is a challenging task at the moment, but highly significant for the future. The pandemic disruptions have placed intense pressure on retailers to deliver products as per consumers' changing behaviours towards the purchase of essentials and other products. Hence, “Order Fulfilment” and “Digital RSCs” should be adopted for meeting customer requirements and to ensure sustainability in the post-pandemic business world.Originality/valueThis work sets out a comprehensive framework which will be helpful for accelerating RSCs performance against pandemic disruption by adopting resilient strategies to mitigate the long-term effects.

Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50 mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein’s expression. 18βGA (20 and 50 mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGA dramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50 mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats. Graphical Abstract

In this paper, we studied the influence of interest rates on a US-based real estate private equity index as well US Wilshire public equity REIT Index. The interest rates that are chosen as independent variables include Monthly LIBOR, Yearly LIBOR and the Federal Cost of Funds Index. The dependent variables include US-based real estate private equity index that includes quarterly returns of 1,035 real estate funds, including liquidated funds formed between 1986 and 2018. The other dependent variable is the US Wilshire REIT Index. The variance of returns of interest rates considerably influences the variance of returns of the US PERE Index, whereas variance of returns of interest rates doesn’t influence the variance of returns of the US Wilshire REIT Index. Also, the real estate index is positively correlated to interest rates and so rising interest rates influence the returns of US PERE Index in a positive manner. The study shows that private equity real estate investors should expect higher return as the cost of funds increase.

Physiologically, α-synuclein chaperones soluble NSF attachment protein receptor (SNARE) complex assembly and may also perform other functions; pathologically, in contrast, α-synuclein misfolds into neurotoxic aggregates that mediate neurodegeneration and propagate between neurons. In neurons, α-synuclein exists in an equilibrium between cytosolic and membrane-bound states. Cytosolic α-synuclein appears to be natively unfolded, whereas membrane-bound α-synuclein adopts an α-helical conformation. Although the majority of studies showed that cytosolic α-synuclein is monomeric, it is unknown whether membrane-bound α-synuclein is also monomeric, and whether chaperoning of SNARE complex assembly by α-synuclein involves its cytosolic or membrane-bound state. Here, we show using chemical cross-linking and fluorescence resonance energy transfer (FRET) that α-synuclein multimerizes into large homomeric complexes upon membrane binding. The FRET experiments indicated that the multimers of membrane-bound α-synuclein exhibit defined intermolecular contacts, suggesting an ordered array. Moreover, we demonstrate that α-synuclein promotes SNARE complex assembly at the presynaptic plasma membrane in its multimeric membrane-bound state, but not in its monomeric cytosolic state. Our data delineate a folding pathway for α-synuclein that ranges from a monomeric, natively unfolded form in cytosol to a physiologically functional, multimeric form upon membrane binding, and show that only the latter but not the former acts as a SNARE complex chaperone at the presynaptic terminal, and may protect against neurodegeneration. Significance Physiologically, α-synuclein promotes soluble NSF attachment protein receptor (SNARE) complex assembly during synaptic exocytosis. Pathologically, however, α-synuclein forms neurotoxic aggregates that promote neurodegeneration and represent hallmarks of Parkinson's disease and other synucleinopathies. α-Synuclein exists in a monomeric unfolded state in solution and in an α-helical folded state upon binding to membranes. Yet the relation between these conformational states and their physiological and pathological roles remain unknown. Here, we demonstrate that α-synuclein multimerizes during membrane binding and that the membrane-bound, multimeric form of α-synuclein mediates SNARE complex assembly in presynaptic terminals. Our data delineate a folding pathway for α-synuclein that ranges from a monomeric unfolded form in cytosol to a physiologically functional multimeric form that is membrane bound and chaperones SNARE complex assembly, and that may protect against neurodegeneration.

Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.

Considerable evidence supports the release of pathogenic aggregates of the neuronal protein α-Synuclein (αSyn) into the extracellular space. While this release is proposed to instigate the neuron-to-neuron transmission and spread of αSyn pathology in synucleinopathies including Parkinson’s disease, the molecular-cellular mechanism(s) remain unclear. To study this, we generated a new mouse model to specifically immunoisolate neuronal lysosomes, and established a long-term culture model where αSyn aggregates are produced within neurons without the addition of exogenous fibrils. We show that neuronally generated pathogenic species of αSyn accumulate within neuronal lysosomes in mouse brains and primary neurons. We then find that neurons release these pathogenic αSyn species via SNARE-dependent lysosomal exocytosis. The released aggregates are non-membrane enveloped and seeding-competent. Additionally, we find that this release is dependent on neuronal activity and cytosolic Ca 2+ . These results propose lysosomal exocytosis as a central mechanism for the release of aggregated and degradation-resistant proteins from neurons. Release of α-synuclein aggregates by neurons instigates spread of pathology in synucleinopathies, but the mechanism remains unclear. Here the authors show that neuronally generated α-synuclein aggregates accumulate within neuronal lysosomes and are released via SNARE-dependent lysosomal exocytosis.

Asthma is a polygenic chronic inflammatory respiratory disease devastating the quality of life and state economies. Therefore, utilization of natural products as a therapeutic approach has attained wider consideration for development of novel drugs for asthma management. Bromelain, a mixture of natural bioactive cysteine proteases abundantly found in pineapple stem, has allured attention for its pharmacological activities. However, poor stability in gastric milieu, high dose and immunogenicity associated with prolonged use hinders its oral use. Therefore, need exists to explore alternative route of bromelain administration to achieve its plausible benefits. The present study investigated the preclinical prospects of nasal administration of bromelain on systemic bioavailability, tissue distribution and it’s in vivo anti-histaminic, bronchodilator and anti-asthmatic activity in animal models. Pharmacokinetic studies revealed 1.43-fold higher relative bioavailability with faster absorption of bromelain on nasal administration at one-fourth oral dose. The enhanced cellular uptake and localization of bromelain in tissues of lung was observed significantly. Furthermore, faster onset and enhanced antihistaminic, bronchodilator and anti-asthmatic activity on bromelain’s nasal administration signified faster absorption and higher in vivo stability of bromelain. Nasal administration significantly achieved decrease in level of oxidative and immunological markers along with restoration of antioxidant enzymes at considerably one-fourth dose administered orally. These findings distinctly manifested that nasal administration could be a substantial and effective route for bromelain delivery with enduring competency in asthma management.

Significant attention has been given to low‐carbon smart manufacturing (SM) as a strategy for promoting sustainability and carbon‐free emissions in the manufacturing industry. The implementation of intelligent algorithms and procedures enables the attainment and enhancement of low‐carbon clever manufacturing processes. These algorithms facilitate real‐time monitoring and predictive maintenance, ensuring efficient and sustainable operations and data‐driven decision‐making, increasing resource utilisation, waste reduction, and energy efficiency. The research examines the utilisation of algorithms in the context of low‐carbon smart manufacturing, encompassing machine learning, optimisation algorithms, and predictive analytics. A comprehensive literature evaluation spanning from 2011 to 2023 is conducted to assess the significance of low‐carbon approaches in the context of smart manufacturing. An integrated approach is used using content analysis, network data analysis, bibliometric analysis, and cluster analysis. Based on the published literature the leading contributors to low‐carbon manufacturing research are India, China, United States, United Kingdom, Singapore, and Italy. The results have shown five main themes—Low‐carbon smart manufacturing and applications of Algorithms; Industry 4.0 technologies for low‐carbon manufacturing; low carbon and green manufacturing; Low‐carbon Manufacturing, and Product design and control; Lean Systems and Smart Manufacturing. The purpose of this study is to provide policymakers and researchers with a guide for the academic development of low‐carbon manufacturing by evaluating research efforts in light of identified research deficits. Highlights (1) A systematic literature review (SLR) on the utilisation of algorithms, such as machine learning, optimisation algorithms, and predictive analytics, within the realm of low‐carbon smart manufacturing. (2) The authors reviewed 264 studies intending to categorise and classify the research findings in the field. (3) The contributions highlighted enhance low‐carbon smart manufacturing. (4) The implications reveal that adopting intelligent algorithms and methodologies can significantly enhance the implementation of low‐carbon smart manufacturing practices. (5) A comprehensive framework was formulated to outline the key thematic areas for future research in this field.