Effects of subcutaneous LPS injection on gestational length and intrauterine and neonatal mortality in mice

BACKGROUND Infection during pregnancy can predispose offspring to develop various psychiatric disorders such as depression in later life. In order to investigate the potential mechanisms underlying these associations, animal models of maternal infection have been employed. As such, lipopolysaccharide (LPS) has been commonly used to mimic a bacterial infection in pregnant mice. OBJECTIVE The original aim of our study was to investigate the effects of different doses of subcutaneous LPS administration on affective behavior in adult mouse offspring. In the present paper, however, we report that subcutaneous LPS administration has a profound impact on gestational length, litter size, and perinatal mortality in the offspring, even at a relatively low dose. METHODS Pregnant mice were randomly divided into 3 groups, receiving either a high (2 mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of subcutaneous injection. Subsequently, the effects on gestational length, litter size, and perinatal mortality in the offspring were assessed. RESULTS After subcutaneous injection with a high dose of LPS, we observed a significant decrease in gestational length and an increase in neonatal mortality. When the low dose was administered, a tendency towards a reduced litter size was observed, most likely reflecting increased intrauterine mortality in response to prenatal maternal LPS exposure. CONCLUSIONS We showed that subcutaneous administration of 2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided because of high offspring mortality rates, whereas subcutaneous injection of 0.5 mg/kg LPS seems to result in reabsorption of the fetuses

Manipulating and monitoring nanoparticles in micellar thin film superstructures

Understanding the dynamics of discrete self-assembled structures under influence of external triggers is of interest to harvest the potential of nano- and mesoscale materials. In particular, controlling the hierarchical organization of (macro)molecular and nanoparticle building blocks in monolayer superstructures is of paramount importance for tuning properties and characteristics. Here we show how the electron beam in cryo-transmission electron microscopy can be exploited to induce and follow local migration of building blocks and global migration of micellar aggregates inside micrometer-sized superstructures. We employ stroboscopic exposure to heat up and convert the vitrified superstructure into a liquid-like thin film under cryogenic conditions, resulting in controlled evaporation of water that finally leads to rupture of the micelle-containing superstructure. Micelle-embedded nanoparticles prove a powerful tool to study the complex hierarchically built-up superstructures, and to visualize both global movement of individual dendrimicelles and local migration of nanoparticles inside the micellar core during the exposure series.</p

Amyloid β oligomers disrupt blood-CSF barrier integrity by activating matrix metalloproteinases

The blood-CSF barrier (BCSFB) consists of a monolayer of choroid plexus epithelial (CPE) cells that maintain CNS homeostasis by producing CSF and restricting the passage of undesirable molecules and pathogens into the brain. Alzheimer's disease is the most common progressive neurodegenerative disorder and is characterized by the presence of amyloid beta (A beta) plaques and neurofibrillary tangles in the brain. Recent research shows that Alzheimer's disease is associated with morphological changes in CPE cells and compromised production of CSF. Here, we studied the direct effects of A beta on the functionality of the BCSFB. Intracerebroventricular injection of A beta 1-42 oligomers into the cerebral ventricles of mice, a validated Alzheimer's disease model, caused induction of a cascade of detrimental events, including increased inflammatory gene expression in CPE cells and increased levels of proinflammatory cytokines and chemokines in the CSF. It also rapidly affected CPE cell morphology and tight junction protein levels. These changes were associated with loss of BCSFB integrity, as shown by an increase in BCSFB leakage. A beta 1-42 oligomers also increased matrix metalloproteinase (MMP) gene expression in the CPE and its activity in CSF. Interestingly, BCSFB disruption induced by A beta 1-42 oligomers did not occur in the presence of a broad-spectrum MMP inhibitor or in MMP3-deficient mice. These data provide evidence that MMPs are essential for the BCSFB leakage induced by A beta 1-42 oligomers. Our results reveal that Alzheimer's disease-associated soluble A beta 1-42 oligomers induce BCSFB dysfunction and suggest MMPs as a possible therapeutic target

Nanoparticles reveal Extreme Size-Sorting and Morphologies in Complex Coacervate Superstructures

We here provide detailed insight in self-assembled complex coacervate systems exploiting gold nanoparticles for cryoTEM contrast. Nanoparticle-containing dendrimicelles are formed from fifth-generation dendrimer-encapsulated nanoparticles (DENs) and dendrimer-stabilized nanoparticles (DSNs). The complex coacervate structures self-organize in biconcave thin water layers into size-sorted monolayer superstructures. The embedded nanoparticles are a straightforward tool to visualize dendrimicelles and determine the aggregation number and polydispersity. The superstructure shows extreme size-sorting patterns which, contrary to related systems with higher generation dendrimers, consists not only of dendrimicelles but also much bigger complex coacervate nanoassemblies, such as vesicles.</p

Seasonal changes in a sandy beach fish assemblage at Canto Grande, Santa Catarina, South Brazil

Copyright © 2004 Coastal Education and Research Foundation (CERF).Neste trabalho realizaramse amostragens, com uma rede de praia, de modo a estudar a comunidade de peixes de substrato arenoso na enseada de Canto Grande, Santa Catarina, Brasil. As amostragens realizaramse em intervalos de 3 horas durante períodos de 24 h, numa base bimensal, entre Abril de 1996 e Fevereiro de 1997. Verificouse existir uma variação sazonal no número de espécies, densidade de peixes e biomassa, tendo os valores mais elevados ocorrido em Fevereiro (38 espécies, 257.6 peixes 1000 mˉ², 2286.4 g 1000 mˉ²). Recolheuse um total de 67 espécies, pertencentes a 56 géneros e a 33 famílias, sendo a comunidade dominada por sete espécies pertencentes a três famílias: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola e Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus e Lycengraulis grossidens (Engraulidae). Tanto a diversidade de espécies (H′) como a equitabilidade (J′) foram médias a elevadas ao longo do ano devido à baixa dominância. A maior mudança na estrutura da comunidade ocorreu entre os meses de Inverno (Julho e Agosto) e as outras estações. Nenhuma das espécies dominantes pode ser classificada como residente. Os principais predadores foram Pomatomus saltator (Inverno) e Trichiurus lepturus (Verão). A maior parte das espécies observadas foram ou peixes juvenis ou espécies pelágicas de pequeno tamanho e fortemente gregárias.ABSTRACT: A shallow-water fish assemblage, over a soft, sandy bottom, at Canto Grande, Santa Catarina, Brazil, was sampled with a beach seine. Sampling was undertaken at 3 h intervals over 24 h on a bimonthly basis between April 1996 and February 1997. There was a seasonal variation in the number of species, density of fishes and biomass with the highest values in February (38 species, 257.6 fish 1000 mˉ², 2286.4 g 1000 mˉ²). A total of 67 species, belonging to 56 genera and 33 families were collected and the assemblage was dominated by seven species belonging to three families: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola and Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus and Lycengraulis grossidens (Engraulidae). Species diversity (H′) and equitability (J′) were medium to high throughout the year due to the low dominance. The largest change in the assemblage structure occurred between winter months (July and August) and the other seasons. None of the dominant species can be classified as a resident. Main predators were Pomatomus saltator (winter) and Trichiurus lepturus (summer). Most of the species observed were either juvenile fish or small pelagic and strongly gregarious species

Next-generation sequencing-based genome diagnostics across clinical genetics centers: Implementation choices and their effects

Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

Risk factors for infection after liver transplantation

AbstractInfection is a common cause of morbidity and mortality after liver transplantation. Risk factors relate to transplantation factors, donor and recipient factors. Transplant factors include ischaemia-reperfusion damage, amount of intra-operative blood transfusion, level and type of immunosuppression, rejection, and complications, prolonged intensive care stay with dialysis or ventilation, type of biliary drainage, repeat operations, re-transplantation, antibiotics, antiviral regimen, and environment. Donor risk factors include infection, prolonged intensive care stay, quality of the donor liver (e.g. steatosis), and viral status. For the recipient the most important are MELD score >30, malnutrition, renal failure, acute liver failure, presence of infection or colonisation, and immune status for viruses like cytomegalovirus. In recent years it has become clear that genetic polymorphisms in innate immunity, especially the lectin pathway of complement activation and in Toll-like receptors importantly contribute to the infection risk after liver transplantation. Therefore, the risk for infections after liver transplantation is a multifactorial problem and all factors need attention to reduce this risk