Maternal protein malnutrition induces autism-like symptoms in rat offspring

Objective: We tested the correlation between maternal protein malnutrition and autistic-like symptoms using behavioral tests in rodents that measure main behavioral characteristics observed in humans with autism spectrum disorder (ASD).

Methods: Pregnant female rats were fed a normal diet or a hypoproteic diet during gestation and lactation periods. The litters were weighed every 3 days during lactation, and the offspring were tested in behavioral tasks during infancy (postnatal day (PND) 5: quantification of ultrasonic vocalizations; PND 13: homing behavior test) and adolescence (PND 30–32: open field, hole-board, play social behavior, and object recognition tests) in order to capture the prevalence of some of the core and associated symptoms of ASD.

Results: Litters of the hypoproteic diet group had a lesser weight gain during lactation. In addition, pups of dams fed with a hypoproteic diet vocalized less compared to those fed with a normal diet, and they showed impaired social discrimination abilities in the homing behavior test. In adolescence, both male and female offspring of the hypoproteic diet group showed no impairment in locomotor activity; however, they exhibited stereotypic behavior in the hole-board test and a decrease in social play behaviors. Male offspring showed increased interest in exploring a familiar object rather than a novel object.

Conclusion: Our results show that maternal protein malnutrition in rats causes offspring behaviors that resemble core and associated ASD symptoms.     

Calnexin Regulates Apoptosis Induced by Inositol Starvation in Fission Yeast

Inositol is a precursor of numerous phospholipids and signalling molecules essential for the cell. Schizosaccharomyces pombe is naturally auxotroph for inositol as its genome does not have a homologue of the INO1 gene encoding inositol-1-phosphate synthase, the enzyme responsible for inositol biosynthesis. In this work, we demonstrate that inositol starvation in S. pombe causes cell death with apoptotic features. This apoptotic death is dependent on the metacaspase Pca1p and is affected by the UPR transducer Ire1p. Previously, we demonstrated that calnexin is involved in apoptosis induced by ER stress. Here, we show that cells expressing a lumenal version of calnexin exhibit a 2-fold increase in the levels of apoptosis provoked by inositol starvation. This increase is reversed by co-expression of a calnexin mutant spanning the transmembrane domain and C-terminal cytosolic tail. Coherently, calnexin is physiologically cleaved at the end of its lumenal domain, under normal growth conditions when cells approach stationary phase. This cleavage suggests that the two naturally produced calnexin fragments are needed to continue growth into stationary phase and to prevent cell death. Collectively, our observations indicate that calnexin takes part in at least two apoptotic pathways in S. pombe, and suggest that the cleavage of calnexin has regulatory roles in apoptotic processes involving calnexin.     

What are the roles of microRNAs at the mammalian synapse?

The modification of neuronal connections in response to stimuli is believed to be the basis of long-term memory formation. It is currently accepted that local protein synthesis critically contributes to site-restricted modulation of individual synapses. Here, we summarize recent evidence implicating miRNAs in this process, leading to altered dendrite morphogenesis and synaptic plasticity. Second, we discuss findings in non-neuronal systems about how RNA-binding proteins can modulate miRNA–mRNA interactions, and how these mechanisms might apply to neurons. Finally, we review recent findings that P-bodies may be important sites for miRNA action at the synapse.     

Rapid Screening of Cognitive Change in Patients with Questionable Dementia Using the Memory Impairment Screen and the Isaacs Set Test

OBJECTIVES: To assess the efficacy of combining the Memory Impairment Screen (MIS) and the Isaacs Set Test (IST) in predicting short-term development of dementia in a group of people with questionable dementia (QD) at baseline.
DESIGN: Performances of the weighted sum of MIS and IST and the ≪or≫ rule were compared with each other and with the Mini-Mental State Examination.
SETTING: Database of the Regional Network for Diagnostic Aid and Management of Patients with Cognitive Impairment in the Franche-Comté geographical area in France.
PARTICIPANTS: A cohort of 106 patients aged 65 and older with QD were followed up for a mean of 14.9 months (range 6–24 months).
MEASUREMENTS: Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the combination of these two tests.
RESULTS: The weighted sum had a sensitivity of 0.74 and a specificity of 0.84. The ≪or≫ rule (MIS<6 or IST<25) had a sensitivity of 0.74 and a specificity of 0.81. When range values were applied, low scores on the MIS and the IST (MIS<6 and IST<25) led to a high probability of dementia, whereas high scores (MIS>7 and IST>29) suggested a high probability of remaining dementia-free in the study follow-up.
CONCLUSION: This quickly performed tool (5 minutes) is simple to use and score. When including cutscores (MIS<6 or IST<25) or range values, this test could be considered a useful screening procedure for all types of dementias.     

Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus carrying SCCmecIV in a university hospital in Porto Alegre,Brazil

We evaluated clinical outcomes and molecular epidemiology of methicillin-resistant Staphylococcus aureus carrying SCCmecIV recovered from patients who attended at a teaching hospital from Porto Alegre, Brazil. All Panton–Valentine leukocidin (PVL)-producer isolates belonged to clonal complex (CC) 30 (11 isolates, related to Oceania Southwest Pacific clone [OSPC]), and the PVL-negative isolates were typed as CC5 (2 isolates, related to the pediatric clone). Five patients had health care-associated infections (HCAIs) with hospital-onset, 5 HCAIs with community-onset, and 3 community-acquired infections without risks. A high overall mortality (30.8%) was found. This study show that OSPC isolates are not only causing community-associated infections but are also involved in HCAI in our country.     

Local injection of BDNF producing mesenchymal stem cells increases neuronal survival and synaptic stability following ventral root avulsion

The present study proposed to graft mesenchymal stem cells (MSCs), which continuously produce BDNF, into the spinal cord ventral horn, after ventral root avulsion. Neurotrophin expression was naturally achieved by culturing MSCs in an undifferentiated state for at least 10 weeks. Lewis rats were subjected to unilateral avulsion of lumbar ventral roots, receiving 3 × 10⁵ cells injected through the lateral funiculus. Two weeks after surgery, the animals were sacrificed and neuronal survival, astroglial reaction and synaptic inputs within the motor nucleus analyzed. The results indicated that the MSCs treatment significantly rescued avulsed motoneurons. Such neuronal survival was related to in vivo mRNA up regulation as well as expression of BDNF and GDNF. Such increase was correlated to the preservation of synaptophysin- positive nerve terminals. Thus it was proposed that when maintained undifferentiated for a period of 10 weeks, MSCs may be used as a continuous source of BDNF, positively influencing neuronal survival and synaptic plasticity.     

Angiosarcoma of the gallbladder: case report and review of the literature.

A 62-year-old white woman with an unremarkable past medical history presented with acute cholecystitis. A cholecystectomy was performed, revealing an acute hemorrhagic and chronic cholecystitis associated with cholelithiasis. Two months after the operation, the patient developed a massive hemoperitoneum and died by hypo-volemic shock. At autopsy, an angiosarcoma measuring 5 cm in diameter was found in the liver, at the site of the gallbladder fossa. There were multiple hepatic, splenic, ovarian and peritoneal metastases and a massive hemoperitoneum consisting of 8 L of blood and blood clots. Review of the tissue sections from the patient's gallbladder confirmed the presence of an acute hemorrhagic and chronic cholecystitis and also revealed residual foci of an angiosarcoma. A review of eight previously reported cases of gallbladder angiosarcoma is also presented.     

Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans

 Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with psychotogenic and dissociative effects in healthy humans. These cognitive and perceptual effects in humans are reportedly reduced by benzodiazepine premedication. This study assessed the interactive effects of a ketamine (IV bolus of 0.26 mg/kg followed by an infusion of 0.65 mg/kg per hour) and lorazepam 2 mg., PO, in humans. Twenty-three healthy subjects completed 4 test days involving the oral administration of lorazepam or matched placebo 2 h prior to the IV infusion of ketamine or placebo. Ketamine: 1) produced behaviors similar to the positive and negative symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale (BPRS); 2) evoked perceptual alterations as measured by the Clinician-Administered Dissociative States Scale (CADSS); 3) impaired performance on the Wisconsin Card Sorting Test (WCST) and other tests sensitive to frontal cortical impairment; and 4) had amnestic effects. Lorazepam produced attention impairments, concrete proverb interpretations, and recall impairments. Lorazepam reduced ketamine-associated emotional distress and there was a non-significant trend for it to decrease perceptual alterations produced by ketamine. However, it failed to reduce many cognitive and behavioral effects of ketamine, including psychosis. Further, lorazepam exacerbated the sedative, attention-impairing, and amnestic effects of ketamine. There was no evidence of pharmacokinetic interaction between these medications. These data suggest that subhypnotic lorazepam and ketamine show a spectrum of interactive effects, ranging from antagonism to potentiation. Received: 1 April 1996/Final version: 20 May 1997