Importance of the initial response to GPi deep brain stimulation in dystonia: A nine year quality of life study.

Background: Long-term efficacy of deep brain stimulation (DBS) on health-related quality-of-life (HRQoL) for isolated dystonia is not well established. This study aims to determine the long-term impact of DBS on HRQoL outcomes and identify clinical predictors.

Methods: We retrospectively investigated 16 inherited or idiopathic isolated dystonia patients treated with bilateral globus pallidus internus DBS who were followed beyond 9 years at our center.

Clinical correlates of repetitive speech disorders in Parkinson's disease.

Objectives: This study aimed to explore clinical correlates of repetitive speech disorders in patients with Parkinson's disease (PD).

Methods: This study investigated speech function (Assessment of Motor Speech for Dysarthria and Stuttering Severity Instrument-3), motor function (Unified Parkinson's Disease Rating Scale III [UPDRS-III] and UPDRS-IV), cognitive function (Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], Stroop color-word test, verbal fluency, digit span tests, and line orientation), and activities of daily living of 113 PD patients. Comparison between groups (independent t-tests, Mann-Whitney U tests, or χ test) and linear regression analyses were performed to determine clinical correlates of repetitive speech disorders.

Adeno-Associated Virus as an Effective Malaria Booster Vaccine Following Adenovirus Priming.

An ideal malaria vaccine platform should potently induce protective immune responses and block parasite transmission from mosquito to human, and it should maintain these effects for an extended period. Here, we have focused on vaccine development based on adeno-associated virus serotype 1 (AAV1), a viral vector widely studied in the field of clinical gene therapy that is able to induce long-term transgene expression without causing toxicity . Our results show the potential utility of AAV1 vectors as an extremely potent booster vaccine to induce durable immunity when combined with an adenovirus-priming vaccine in a rodent malaria model.

Sexually Dimorphic Regulation of Behavioral States by Dopamine in .

Sex differences in behavior allow animals to effectively mate and reproduce. However, the mechanism by which biological sex regulates behavioral states, which underlie the regulation of sex-shared behaviors, such as locomotion, is largely unknown. In this study, we studied sex differences in the behavioral states of and found that males spend less time in a low locomotor activity state than hermaphrodites and that dopamine generates this sex difference.

Green Fluorescent Protein-Based Glucose Indicators Report Glucose Dynamics in Living Cells.

Glucose is the most important energy source for living animals. Here, we developed a series of single fluorescent protein (FP)-based glucose indicators, named as "Green Glifons", to understand the hierarchal and mutual relationships between molecules involved in energy metabolism. Three indicators showed a different EC for glucose (50, 600, and 4000 μM), producing a ∼7-fold change in fluorescence intensity in response to glucose.

Biomonitoring of organophosphate flame retardants and plasticizers in children: Associations with house dust and housing characteristics in Japan.

Indoor environments contain a wide range of new chemicals such as phosphate flame retardants and plasticizers (PFRs). Despite recent epidemiological evidence suggesting that children might be affected by widespread exposure to PFRs, questions remain about the various exposure pathways to these chemicals. Therefore, the aim of this study was to investigate exposure to PFRs by measuring the concentrations a set of urinary metabolites for schoolchildren from Japan (n = 128) and associating them with house dust concentrations and housing characteristics.

Identification of domains within Pfs230 that elicit transmission blocking antibody responses.

A transmission-blocking vaccine (TBV) against Plasmodium falciparum is likely to be a valuable tool in a malaria eradication program. Pfs230 is one of the major TBV candidates, and multiple Pfs230-based vaccines induced antibodies, which prevented oocyst formation in mosquitoes as determined by a standard membrane-feeding assay (SMFA). Pfs230 is a >300 kDa protein consisting of 14 cysteine motif (CM) domains, and the size and cysteine-rich nature of the molecule have hampered its production as an intact protein.

Targets of complement-fixing antibodies in protective immunity against malaria in children.

Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation.

3-O-Laurylglyceryl ascorbate improves the development of sensitive skin through the reduction of oxidative stress.

Skin sensitivity is a serious problem for many people, and it can be induced by various factors such as UV irradiation, physical and mental stresses, air pollution, dry air and so on. Skin dryness triggered by UV and dry air is one of the most important causes inducing the development of sensitive skin, and it has been reported that oxidative stress contributes to skin dryness. In this study, we investigated whether treatment with 3-O-laurylglyceryl ascorbate (VC-3LG), which is an amphipathic ascorbic acid derivative, can suppress the development of sensitive skin.

Synthesis of Fused and Linked Benzofurans from 2-Alkynylphenol Derivatives through Rhodium(I)-catalyzed Domino-type Addition Reactions.

A rhodium(I)-catalyzed domino-type sequential 5-/5- cyclization reaction of [(2-acylphenyl) ethynyl]phenols produces indene/benzofuran-fused alcohols. A moderate asymmetric induction is observed when chiral diphosphine ligands are used for rhodium. Indene/indole-fused compounds are synthesized by a similar reaction of [(2-acetylphenyl)ethynyl]anilines.

Low Levels of PaO after Long-term Noninvasive Ventilation are a Poor Prognostic Factor in Patients with Restrictive Thoracic Disease.

Objective The effects of partial pressure of arterial oxygen (PaO) after introducing long-term noninvasive ventilation (NIV) on the prognosis of patients with restrictive thoracic disease and chronic respiratory failure are not exactly known. Methods Data from 141 patients with restrictive thoracic disease under long-term nocturnal NIV were retrospectively examined. We divided the patients into 2 groups according to the daytime PaO value while breathing spontaneously with prescribed oxygen at 12 months after introducing NIV: PaO≥80 Torr group (n=76) and PaO<80 Torr group (n=65).

Identification of a PH domain-containing protein which is localized to crystalloid bodies of Plasmodium ookinetes.

Background: For the success of the malaria control and eradication programme it is essential to reduce parasite transmission by mosquito vectors. In the midguts of mosquitoes fed with parasite-infected blood, sexual-stage parasites fertilize to develop into motile ookinetes that traverse midgut epithelial cells and reside adjacent the basal lamina. Therefore, the ookinete is a promising target of transmission-blocking vaccines to break the parasite lifecycle in mosquito vectors.

The Plasmodium yoelii microgamete surface antigen (PyMiGS) induces anti-malarial transmission blocking immunity that reduces microgamete motility/release from activated male gametocytes.

Malaria transmission-blocking vaccines aim to inhibit the development of malaria parasites in mosquitoes by inducing antibodies targeting surface proteins of sexual stage parasites. We have recently identified PyMiGS, a protein specifically expressed in the osmiophilic body of male gametocytes of Plasmodium yoelii (Py). PyMiGS is translocated to the surface of microgametes, and potent transmission-blocking activity was observed in mosquitoes fed on mice passively immunized with antibodies against PyMiGS.

Anti-MSP11 IgG inhibits Plasmodium falciparum merozoite invasion into erythrocytes in vitro.

Merozoite surface proteins (MSPs) are considered as promising blood-stage malaria vaccine candidates. MSP3 has long been evaluated for its vaccine candidacy, however, the candidacy of other members of MSP3 family is insufficiently characterized. Here, we investigated Plasmodium falciparum MSP11 (PF3D7_1036000), a member of the MSP3 family, for its potential as a blood-stage vaccine candidate.

Quantitative evaluation of incomplete preweaning lethality in mice by using the CRISPR/Cas9 system.

Various molecular biology techniques implementing genome editing have made it possible to generate mouse mutants for nearly all known genes; as a result, the International Mouse Phenotyping Consortium (IMPC) database listing the phenotypes of genetically modified mice has been established. Among mouse phenotypes, lethality is crucial to evaluate the importance of genes in mouse survival. Although many genes are reported to show "preweaning lethality, incomplete penetrance" in the IMPC database, the survival rates of homozygous knockout mice are highly variable.

Antibodies against a Plasmodium falciparum RON12 inhibit merozoite invasion into erythrocytes.

Proteins coating Plasmodium merozoite surface and secreted from its apical organelles are considered as promising vaccine candidates for blood-stage malaria. The rhoptry neck protein 12 of Plasmodium falciparum (PfRON12) was recently reported as a protein specifically expressed in schizonts and localized to the rhoptry neck of merozoites. Here, we assessed its potential as a vaccine candidate.

Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands.

Malaria parasite transmission to humans is initiated by the inoculation of Plasmodium sporozoites into the skin by mosquitoes. Sporozoites develop within mosquito midgut oocysts, first invade the salivary glands of mosquitoes, and finally infect hepatocytes in mammals. The apical structure of sporozoites is conserved with the infective forms of other apicomplexan parasites that have secretory organelles, such as rhoptries and micronemes.

Plasmodium RON12 localizes to the rhoptry body in sporozoites.

Invasion of host cells by apicomplexan parasites is mediated by proteins released from microneme, rhoptry, and dense granule secretory organelles located at the apical end of parasite invasive forms. Microneme secreted proteins establish interactions with host cell receptors and induce exocytosis of the rhoptry organelle. Rhoptry proteins are involved in target cell invasion as well as the formation of the parasitophorous vacuole in which parasites reside during development within the host cell.

Comprehensive analysis of antibody responses to Plasmodium falciparum erythrocyte membrane protein 1 domains.

Acquired antibodies directed towards antigens expressed on the surface of merozoites and infected erythrocytes play an important role in protective immunity to Plasmodium falciparum malaria. P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major parasite component of the infected erythrocyte surface, has been implicated in malaria pathology, parasite sequestration and host immune evasion.

Association of filaggrin gene mutations and childhood eczema and wheeze with phthalates and phosphorus flame retardants in house dust: The Hokkaido study on Environment and Children's Health.

Background And Aim: Exposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG.

De novo UNC13B mutation identified in a bipolar disorder patient increases a rare exon-skipping variant.

Aim: We previously performed the first trio-based exome study for bipolar disorder and identified 71 de novo mutations. Among these mutations, the only mutation located at the splice donor site was in UNC13B. We focused on and analyzed the functions of the mutation.

Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children.

Background: Phosphate flame retardants (PFRs) are ubiquitously detected in indoor environments. Despite increasing health concerns pertaining to PFR exposure, few epidemiological studies have examined PFR exposure and its effect on children's allergies.

Objectives: To investigate the association between PFRs in house dust, their metabolites in urine, and symptoms of wheeze and allergies among school-aged children.

Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy.

Objective: We examined the anatomical involvement related to cognitive impairment in patients with multiple system atrophy (MSA).

Methods: We examined 30 patients with probable MSA and 15 healthy controls. All MSA patients were assessed by the Unified MSA-Rating scale and Addenbrooke's Cognitive Examination-Revised (ACE-R).