Schistosoma japonicum infection in pregnant mice.

Ten 1-week and ten 2-weeks pregnant female NMRI mice were experimentally exposed to 70 Schistosoma japonicum cercariae. Ten littermice from each group were examined for worms by perfusion 4, 6 and 8 weeks post infection. Although the mothers (n = 15) were found infected with 15.5 +/- 13.4 worms at perfusion 6 and 7 weeks post infection, no worms were found in any of the examined littermice, as well as no detection of faecal or tissue eggs. Litter sizes did not differ from control groups and all littermice were healthy. The present study therefore suggests that congenital infection with S. japonicum does not occur in percutaneously infected mice and that infection of the mother during pregnancy does not seem to affect the offspring.     

Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy

Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL‐1β is recognized by specialized secretory autophagy cargo receptor TRIM16 and that this receptor interacts with the R‐SNARE Sec22b to recruit cargo to the LC3‐II⁺ sequestration membranes. Cargo secretion is unaffected by downregulation of syntaxin 17, a SNARE promoting autophagosome–lysosome fusion and cargo degradation. Instead, Sec22b in combination with plasma membrane syntaxin 3 and syntaxin 4 as well as SNAP‐23 and SNAP‐29 completes cargo secretion. Thus, secretory autophagy utilizes a specialized cytosolic cargo receptor and a dedicated SNARE system. Other unconventionally secreted cargo, such as ferritin, is secreted via the same pathway.     

NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture

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A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)

Background

There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.

Methods and Findings

Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.

Conclusions

For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).     

Complete mitochondrial genome sequences of the Arctic Ocean codfishes <Emphasis Type="Italic">Arctogadus glacialis</Emphasis> and <Emphasis Type="Italic">Boreogadus saida</Emphasis> reveal oriL and tRNA gene duplications

We have determined the complete mitochondrial genome sequences of the codfishes Arctogadus glacialis and Boreogadus saida (Order Gadiformes, Family Gadidae). The 16,644 bp and 16,745 bp mtDNAs, respectively, contain the same set of 37 structural genes found in all vertebrates analyzed so far. The gene organization is conserved compared to other Gadidae species, but with one notable exception. B. saida contains heteroplasmic rearrangement-mediated duplications that include the origin of light-strand replication and nearby tRNA genes. Examination of the mitochondrial control region of A. glacialis, B. saida, and four additional representative Gadidae genera identified a highly variable domain containing tandem repeat motifs in A. glacialis. Mitogenomic phylogeny based on the complete mitochondrial genome sequence, the concatenated protein-coding genes, and the derived protein sequences strongly supports a sister taxa affiliation of A. glacialis and B. saida.     

Host-cell apoptosis in Taenia solium-induced brain granulomas in naturally infected pigs

To assess whether apoptosis occurs in pig brain granulomas due to Taenia solium cysticerci, brain tissues from 30 pigs naturally infected with T. solium cysticercosis were evaluated by terminal deoxynucleotidyl transferase-end labelling (TUNEL) staining. In addition, tissues were stained with CD3 marker to identify T lymphocytes. Examination of TUNEL-stained tissues showed apoptotic cells in early lesions that contained viable cysticerci. Apoptotic cells were primarily found interspersed with normal cell types, and were mostly located in the inflammatory infiltrate. Late or advanced granulomas with disintegrated scolices did not show TUNEL-positive cells. CD3+ cells were found in both early and advanced lesions and apoptosis mainly co-localized with CD3+ T lymphocytes. This suggests that these cells are constantly undergoing apoptosis and thus die as soon as they arrive at the site of infection. Apoptosis indeed may be one way by which T. solium cysticerci down-regulate the host's cellular immune response in early cysticercosis. Therefore, further research is needed to establish if other cells besides T-lymphocytes are also a target for destruction by cysticerci in early cysticercosis as well as studies to assess if cysteine protease is expressed by viable cysticerci in situ.