Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Left Ventricle Quantification Using Direct Regression with Segmentation Regularization and Ensembles of Pretrained 2D and 3D CNNs

Cardiac left ventricle (LV) quantification provides a tool for diagnosing cardiac diseases. Automatic calculation of all relevant LV indices from cardiac MR images is an intricate task due to large variations among patients and deformation during the cardiac cycle. Typical methods are based on segmentation of the myocardium or direct regression from MR images. To consider cardiac motion and deformation, recurrent neural networks and spatio-temporal convolutional neural networks (CNNs) have been proposed. We study an approach combining state-of-the-art models and emphasizing transfer learning to account for the small dataset provided for the LVQuan19 challenge. We compare 2D spatial and 3D spatio-temporal CNNs for LV indices regression and cardiac phase classification. To incorporate segmentation information, we propose an architecture-independent segmentation-based regularization. To improve the robustness further, we employ a search scheme that identifies the optimal ensemble from a set of architecture variants. Evaluating on the LVQuan19 Challenge training dataset with 5-fold cross-validation, we achieve mean absolute errors of 111 +- 76mm^2, 1.84 +- 0.9mm and 1.22 +- 0.6mm for area, dimension and regional wall thickness regression, respectively. The error rate for cardiac phase classification is 6.7%.Comment: Accepted at the MICCAI Workshop STACOM 201

Exploration of an innovative draw solution for a forward osmosis-membrane distillation desalination process

© 2017, Springer-Verlag Berlin Heidelberg. Forward osmosis (FO) has emerged as a viable technology to alleviate the global water crisis. The greatest challenge facing the application of FO technology is the lack of an ideal draw solution with high water flux and low reverse salt flux. Hence, the objective of this study was to enhance FO by lowering reverse salt flux and maintaining high water flux; the method involved adding small concentrations of Al2(SO4)3 to a MgCl2 draw solution. Results showed that 0.5 M MgCl2 mixed with 0.05 M of Al2(SO4)3 at pH 6.5 achieved a lower reverse salt flux (0.53 gMH) than that of pure MgCl2 (1.55 gMH) using an FO cellulose triacetate nonwoven (CTA-NW) membrane. This was due possibly to the flocculation of aluminum hydroxide in the mixed draw solution that constricted membrane pores, resulting in reduced salt diffusion. Moreover, average water fluxes of 4.09 and 1.74 L/m2-h (LMH) were achieved over 180 min, respectively, when brackish water (5 g/L) and sea water (35 g/L) were used as feed solutions. Furthermore, three types of membrane distillation (MD) membranes were selected for draw solution recovery; of these, a polytetrafluoroethylene membrane with a pore size of 0.45 μm proved to be the most effective in achieving a high salt rejection (99.90%) and high water flux (5.41 LMH) in a diluted draw solution

Forward osmosis–membrane distillation hybrid system for desalination using mixed trivalent draw solution

© 2020 Elsevier B.V. Finding suitable draw solutions is still a major problem when developing FO technologies. This study represents the first time a mixed trivalent draw solution containing of EDTA–2Na and Na3PO4 was systemically studied for FO performance. The objective here was to achieve simultaneously low reverse salt flux and high water flux. The FO results showed that the mixed trivalent draw solution-based 0.3 M EDTA–2Na and 0.55 M Na3PO4 underwent higher water flux (Jw = 9.17 L/m2⋅h) than that of pure 0.85 M EDTA-2Na (Jw = 7.02 L/m2⋅h) due to its lower viscosity. Additionally, the specific reverse salt flux caused by mixing 0.3 M EDTA–2Na with 0.55 M Na3PO4 draw solution was only 0.053 g/L using DI water as the feed solution. Donnan equilibrium force and formed complexation of [EDTANa]3-, [HPO4Na]- with the FO membrane are believed to constitute the main mechanism for minimizing salt leakage from the mixed draw solution. Moreover, the FO desalination process utilizing the mixed trivalent draw solution achieved water fluxes of 6.12 L/m2⋅h with brackish water (TDS = 5000 mg/L) and 3.10 L/m2⋅h with seawater (TDS = 35,000 mg/L) as the feed solution. Lastly, diluted mixed trivalent draw solution following the FO process was effectively separated using the MD process with salt rejection >99.99% at a mild feed temperature of 55 °C

Differences in the Population Structure of Invasive Streptococcus suis Strains Isolated from Pigs and from Humans in the Netherlands

Streptococcus suis serotype 2 is the main cause of zoonotic S. suis infection despite the fact that other serotypes are frequently isolated from diseased pigs. Studies comparing concurrent invasive human and pig isolates from a single geographical location are lacking. We compared the population structures of invasive S. suis strains isolated between 1986 and 2008 from human patients (N = 24) and from pigs with invasive disease (N = 124) in the Netherlands by serotyping and multi locus sequence typing (MLST). Fifty-six percent of pig isolates were of serotype 9 belonging to 15 clonal complexes (CCs) or singleton sequence types (ST). In contrast, all human isolates were of serotype 2 and belonged to two non-overlapping clonal complexes CC1 (58%) and CC20 (42%). The proportion of serotype 2 isolates among S. suis strains isolated from humans was significantly higher than among strains isolated from pigs (24/24 vs. 29/124; P<0.0001). This difference remained significant when only strains within CC1 and CC20 were considered (24/24 vs. 27/37,P = 0.004). The Simpson diversity index of the S. suis population isolated from humans (0.598) was smaller than of the population isolated from pigs (0.765, P = 0.05) indicating that the S. suis population isolated from infected pigs was more diverse than the S. suis population isolated from human patients. S. suis serotype 2 strains of CC20 were all negative in a PCR for detection of genes encoding extracellular protein factor (EF) variants. These data indicate that the polysaccharide capsule is an important correlate of human S. suis infection, irrespective of the ST and EF encoding gene type of S. suis strains

Absence of carious lesions at margins of glass-ionomer cement and amalgam restorations: An update of systematic review evidence

<p>Abstract</p> <p>Background</p> <p>This article aims to update the existing systematic review evidence elicited by Mickenautsch et al. up to 18 January 2008 (published in the European Journal of Paediatric Dentistry in 2009) and addressing the review question of whether, in the same dentition and same cavity class, glass-ionomer cement (GIC) restored cavities show less recurrent carious lesions on cavity margins than cavities restored with amalgam.</p> <p>Methods</p> <p>The systematic literature search was extended beyond the original search date and a further hand-search and reference check was done. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets extracted from the accepted trials.</p> <p>Results</p> <p>The database search (up to 10 August 2010) identified 1 new trial, in addition to the 9 included in the original systematic review, and 11 further trials were included after a hand-search and reference check. Of these 21 trials, 11 were excluded and 10 were accepted for data extraction and quality assessment. Thirteen dichotomous datasets of primary outcomes and 4 datasets with secondary outcomes were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall results of the computed datasets suggest that GIC has a higher caries-preventive effect than amalgam for restorations in permanent teeth. No difference was found for restorations in the primary dentition.</p> <p>Conclusion</p> <p>This outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection/performance bias is high. Thus, verification of the currently available results requires further high-quality randomised control trials.</p

RNAi-Mediated c-Rel Silencing Leads to Apoptosis of B Cell Tumor Cells and Suppresses Antigenic Immune Response In Vivo

c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases

Complete In Vitro Life Cycle of Trypanosoma congolense: Development of Genetic Tools

Trypanosoma congolense is a parasite responsible for severe disease of African livestock. Its life cycle is complex and divided into two phases, one in the tsetse fly vector and one in the bloodstream of the mammalian host. Molecular tools for gene function analyses in parasitic organisms are essential. Previous studies described the possibility of completing the entire T. congolense life cycle in vitro. However, the model showed major flaws including the absence of stable long-term culture of the infectious bloodstream forms, a laborious time-consuming period to perform the cycle and a lack of genetic tools. We therefore aimed to develop a standardized model convenient for genetic engineering. We succeeded in producing long-term cultures of all the developmental stages on long-term, to define all the differentiation steps and to finally complete the whole cycle in vitro. This improved model offers the opportunity to conduct phenotype analyses of genetically modified strains throughout the in vitro cycle and also during experimental infections

Inhibition of Post-Synaptic Kv7/KCNQ/M Channels Facilitates Long-Term Potentiation in the Hippocampus

Activation of muscarinic acetylcholine receptors (mAChR) facilitates the induction of synaptic plasticity and enhances cognitive function. In the hippocampus, M1 mAChR on CA1 pyramidal cells inhibit both small conductance Ca2+-activated KCa2 potassium channels and voltage-activated Kv7 potassium channels. Inhibition of KCa2 channels facilitates long-term potentiation (LTP) by enhancing Ca2+calcium influx through postsynaptic NMDA receptors (NMDAR). Inhibition of Kv7 channels is also reported to facilitate LTP but the mechanism of action is unclear. Here, we show that inhibition of Kv7 channels with XE-991 facilitated LTP induced by theta burst pairing at Schaffer collateral commissural synapses in rat hippocampal slices. Similarly, negating Kv7 channel conductance using dynamic clamp methodologies also facilitated LTP. Negation of Kv7 channels by XE-991 or dynamic clamp did not enhance synaptic NMDAR activation in response to theta burst synaptic stimulation. Instead, Kv7 channel inhibition increased the amplitude and duration of the after-depolarisation following a burst of action potentials. Furthermore, the effects of XE-991 were reversed by re-introducing a Kv7-like conductance with dynamic clamp. These data reveal that Kv7 channel inhibition promotes NMDAR opening during LTP induction by enhancing depolarisation during and after bursts of postsynaptic action potentials. Thus, during the induction of LTP M1 mAChRs enhance NMDAR opening by two distinct mechanisms namely inhibition of KCa2 and Kv7 channels