Impaired mitophagosome-lysosome fusion mediates olanzapine-induced aging.

The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects.

Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.

Background: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect.

Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: A phase IV randomized controlled crossover study.

Background: Guidelines recommend intramuscular injection of 500 μg adrenaline (epinephrine) for anaphylaxis in teenagers and adults; however, most autoinjectors deliver a maximum 300 μg dose. We evaluated plasma adrenaline levels and cardiovascular parameters (including cardiac output) following self-injection with 300 μg or 500 μg adrenaline in teenagers at risk of anaphylaxis.

Methods: Subjects were recruited to a randomized, single-blind two period crossover trial.

Parkin Mediates Cannabidiol Prevention of Amyloid-Beta-Induced Senescence in Human Astrocytes.

As aging is the leading risk factor for Alzheimer's disease (AD), ablation of senescent cells is a promising therapeutic approach to prevent AD. It is known that astrocytes lose their ability to maintain a healthy brain environment when aging. Studies have recently shown that cannabidiol (CBD) provides a promising therapeutic avenue for AD; however, if or how CBD prevents astrocyte aging is not known.

Room-temperature structural studies of SARS-CoV-2 protein NendoU with an X-ray free-electron laser.

NendoU from SARS-CoV-2 is responsible for the virus's ability to evade the innate immune system by cleaving the polyuridine leader sequence of antisense viral RNA. Here we report the room-temperature structure of NendoU, solved by serial femtosecond crystallography at an X-ray free-electron laser to 2.6 Å resolution.

Butyrate Attenuates Hepatic Steatosis Induced by a High-Fat and Fiber-Deficient Diet via the Hepatic GPR41/43-CaMKII/HDAC1-CREB Pathway.

Scope: Hepatic steatosis is a major health issue that can be attenuated by a healthy diet. This study investigates the effects and molecular mechanisms of butyrate, a dietary fiber metabolite of gut microbiota, on lipid metabolism in hepatocytes.

Methods And Results: This study examines the effects of butyrate (0-8 mM) on lipid metabolism in primary hepatocytes.

Structural and biophysical properties of FopA, a major outer membrane protein of Francisella tularensis.

Francisella tularensis is an extremely infectious pathogen and a category A bioterrorism agent. It causes the highly contagious zoonosis, Tularemia. Currently, FDA approved vaccines against tularemia are unavailable.

Structural insights into the function of the catalytically active human Taspase1.

Taspase1 is an Ntn-hydrolase overexpressed in primary human cancers, coordinating cancer cell proliferation, invasion, and metastasis. Loss of Taspase1 activity disrupts proliferation of human cancer cells in vitro and in mouse models of glioblastoma. Taspase1 is synthesized as an inactive proenzyme, becoming active upon intramolecular cleavage.

Construction of gateway-compatible baculovirus expression vectors for high-throughput protein expression and in vivo microcrystal screening.

Baculovirus mediated-insect cell expression systems have been widely used for producing heterogeneous proteins. However, to date, there is still the lack of an easy-to-manipulate system that enables the high-throughput protein characterization in insect cells by taking advantage of large existing Gateway clone libraries. To resolve this limitation, we have constructed a suite of Gateway-compatible pIEx-derived baculovirus expression vectors that allow the rapid and cost-effective construction of expression clones for mass parallel protein expression in insect cells.

Enhanced X-ray diffraction of in vivo-grown μNS crystals by viscous jets at XFELs.

μNS is a 70 kDa major nonstructural protein of avian reoviruses, which cause significant economic losses in the poultry industry. They replicate inside viral factories in host cells, and the μNS protein has been suggested to be the minimal viral factor required for factory formation. Thus, determining the structure of μNS is of great importance for understanding its role in viral infection.

Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography.

Background: Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases.

Results: Here, we demonstrate a general method for capturing enzyme catalysis "in action" by mix-and-inject serial crystallography (MISC).

Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation.

Crystal structure determination of biological macromolecules using the novel technique of serial femtosecond crystallography (SFX) is severely limited by the scarcity of X-ray free-electron laser (XFEL) sources. However, recent and future upgrades render microfocus beamlines at synchrotron-radiation sources suitable for room-temperature serial crystallography data collection also. Owing to the longer exposure times that are needed at synchrotrons, serial data collection is termed serial millisecond crystallography (SMX).

Structural enzymology using X-ray free electron lasers.

Mix-and-inject serial crystallography (MISC) is a technique designed to image enzyme catalyzed reactions in which small protein crystals are mixed with a substrate just prior to being probed by an X-ray pulse. This approach offers several advantages over flow cell studies. It provides (i) room temperature structures at near atomic resolution, (ii) time resolution ranging from microseconds to seconds, and (iii) convenient reaction initiation.

In silico characterization of a RNA binding protein of cattle filarial parasite Setaria digitata.

Human lymphatic filariasis (HLF) is a neglected tropical disease which threatens nearly 1.4 billion people in 73 countries worldwide. Wuchereria bancrofti is the major causative agent of HLF and it closely resembles cattle filarial parasite Setaria digitata.

Bayer-activities of daily living scale in mild and moderate dementia of the Alzheimer type.

The main purpose of this study is to examine the reliability of the Bayer-Activities of Daily Living (B-ADL) scale when used as a cognitive screening instrument for mild and moderate dementia of the Alzheimer type. This is a retrospective study of 66 patients with dementia. The B-ADL scale was completed by the caregiver or the family member at the first encounter.

Prolonged abulia following putaminal hemorrhage.

Abulia, akinetic mutism, and other conditions causing reduced activity and slowness are a continuum of severity of behavior. Unilateral lesions usually cause transient symptoms. This article describes a patient with prolonged abulia lasting 12 weeks after aspontaneous left putaminal hemorrhage.

The development of panic attacks and social phobia after stroke.

A patient developed panic attacks and social phobia after a stroke. The magnetic resonance imaging scan showed a focal abnormality in the right temporal lobe together with abnormalities extending into the occipital lobe. A pathogenic relationship between the panic attacks and the focal lesion in the temporal lobe is invoked.

Clinical effects of anterior cerebral artery infarction.

Anterior cerebral artery infarction is uncommon. We studied the topographical distribution of the lesions and the resulting clinical effects for a better understanding of their relationship and the functional outcome. There were 17 patients; the mean age of the cohort was 71 years.

Left anterior choroidal artery infarction and uncontrollable crying.

Uncontrollable crying following a left anterior choroidal artery infarction and responding to fluoxetine is described. It is possible that this region has a role in the regulation of emotion.

The accusers in dementia.

The purpose of this retrospective study of 116 dementia patients with and without accusatory behavior was to determine its frequency and evaluate its relationship to individual characteristics, behavioral and psychological symptoms, and certain dementia-related domains, namely, cognitive impairment, stage of disease, language difficulties, and functional disability. Little more than one third (38%) of the patients studied had accusatory behavior. The average age of the patients with accusatory behavior was 74 years, and the male to female ratio was 2.

Validation of the Cumulative Illness Rating Scale (CIRS) in hospitalized nonagenarians.

This is a retrospective analysis of patients aged 90-99 years, admitted over a 6-month period to a district hospital. One hundred three patients were included in the study with an average age of 92 years and a male to female ratio of 1:3. Fifty-five percent of the patients hospitalized came from nursing care facilities.

Secondary mania of vascular origin in elderly patients: a report of two clinical cases.

The concept of secondary mania continues to be debated together with unresolved or partially resolved issues such as lateralization, localization, age of onset, disinhibition syndromes, and others. We have described two patients with secondary mania following a stroke. One had a large left hemisphere cerebral infarction and the symptoms arose about 2.

The vestibular dysfunction and anxiety disorder interface: a descriptive study with special reference to the elderly.

Vestibular abnormalities co-existing with anxiety disorders are not uncommon and there has been a renewal of interest in recent times. Although well known over centuries, there is often a delay in the recognition of this relationship by the primary care physician and the specialist alike. Dizziness embracing vertigo, unsteadiness and imbalance are common in the elderly, so is generalized anxiety disorder, which is a common psychiatric problem in later life.