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

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

Histological Observation of Islet Hemorrhage Induced by Diagnostic Ultrasound with Contrast Agent in Rat Pancreas

Contrast enhanced diagnostic ultrasound CEDUS has been shown to induce capillary hemorrhage in heart and kidney. This study characterized the capillary hemorrhage induced in rat pancreas. The pancreata of anesthetized hairless rats were accessed by laparotomy. A 1.5 MHz diagnostic ultrasound probe with 2.3 MPa peak rarefactional pressure amplitude and 1 s intermittent trigger was used to scan the pancreas, located at the focus (3.8 cm), through saline coupling. The probe was swept to expose the entire organ in 5 min during infusion of Definity® contrast agent at 10 µL/kg/min, and this was repeated in a reverse sweep. The entire pancreas was removed, spread flat for fixation and histological slides were prepared from the mid-plane. Slides were scored blind for islet hemorrhage over the entire area of the organ. Intra-islet microlesions were evident and hemorrhage surrounded many islets. The hemorrhage often impacted nearby acini, and expanded into inter-lobular septa. In CEDUS pancreata removed soon after scanning, 76.2±11.8% (n = 6) of islets had evidence of hemorrhage and/or islet microlesions compared to 1.1±2.5% (n = 5) for sham CEDUS (P<0.001). In pancreata removed after 4 hr, fibrin formation was detected by immunohistology in the hemorrhage and intra-islet microlesions. Diagnostic ultrasound with contrast agent induced substantial capillary hemorrhage in rat pancreas, concentrated particularly in the islets

Clinical Value of the Diagonal Earlobe Crease in Patients with Chest Pain for Diagnosing Coronary Heart Disease

Jie Gao,1,&ast; Jie Dou,1,&ast; Hui-Hui Yang,1 Ruo-Ling Guo,1 Chao Jiang,1 Gary Tse,2– 4 Tong Liu,2 Jian-Wei Liu,5 Dong-Lei Luo6 1Chengde Medical University, Chengde, 067000, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, 999077, People’s Republic of China; 4Epidemiology Research Unit, Cardiovascular Analytics Group, PowerHealth Limited, Hong Kong, 999077, People’s Republic of China; 5Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China; 6Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Lei Luo, Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China, Email [email protected] Jian-Wei Liu, Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China, Email [email protected]: To investigate the clinical application value of diagonal earlobe crease (DELC) in patients with chest pain for the diagnosis of coronary heart disease (CHD) and to construct a risk model by multivariate logistic regression.Patients and Methods: Our trial enrolled prospectively and consecutively 706 chest pain patients with suspected CHD between January 2021 to June 2023 from Chengde Central Hospital. According to coronary angiography results, they were categorized into the CHD (n=457) and non-CHD groups (n=249).Results: The trial demonstrated a significant positive relationship between DELC and CHD. Independent risk factors were sex, age, hypertension, diabetes mellitus, LP (a), Cys C, and DELC, whilst HDL-C was a protective factor, for CHD. Patients with-DELC were older than those in the without-DELC arm (P< 0.001) and had a higher proportion of males than females (61.6% vs 50.0%, P=0.026). After multifactorial correction, independent risk factors for CHD included DELC (OR=1.660, 95% CI:1.153 to 2.388, P=0.006), age (OR=1.024, 95% CI:1.002 to 1.045, P=0.030), gender (OR=1.702, 95% CI:1.141 to 2.539, P=0.009), hypertension (OR=1.744, 95% CI:1.226 to 2.482, P=0.002), diabetes mellitus (OR=2.113, 95% CI:1.404 to 3.179, P< 0.001), LP(a) (OR=1.010, 95% CI:1.003 to 1.017, P=0.005), Cys C (OR=3.549, 95% CI:1.605 to 7.846, P=0.002). The Hosmer and Lemeshow (H-L) test (P=0.818) suggests a high goodness of fit, and the area under the ROC curve was calculated to be 0.721 (95% CI:0.682 to 0.760, P< 0.001), which demonstrates that the model has a superior diagnostic value for CHD.Conclusion: DELC is an independent risk factor for CHD after adjusting for sex, age, hypertension, diabetes mellitus, smoking index, LP (a), Cys C, and HDL-C. Our model can be used clinically for assessing the risk of CHD.Keywords: coronary heart disease, diagonal earlobe crease, coronary angiography, mode

Reflection and transmission of Gaussian beam by a chiral slab

Based on the generalized Lorenz–Mie theory framework, the reflection and transmission of an incident Gaussian beam by a chiral slab were investigated, by expanding the incident Gaussian beam, reflected beam, internal beam as well as transmitted beam in terms of cylindrical vector wave functions. The unknown expansion coefficients were determined by virtue of the boundary conditions. For a localized beam model, numerical results of the normalized field intensity distributions are presented, and the propagation characteristics are discussed concisely in this paper

Sequence Variants of the Phytophthora sojae RXLR Effector Avr3a/5 Are Differentially Recognized by Rps3a and Rps5 in Soybean

The perception of Phytophthora sojae avirulence (Avr) gene products by corresponding soybean resistance (Rps) gene products causes effector triggered immunity. Past studies have shown that the Avr3a and Avr5 genes of P. sojae are genetically linked, and the Avr3a gene encoding a secreted RXLR effector protein was recently identified. We now provide evidence that Avr3a and Avr5 are allelic. Genetic mapping data from F2 progeny indicates that Avr3a and Avr5 co-segregate, and haplotype analysis of P. sojae strain collections reveal sequence and transcriptional polymorphisms that are consistent with a single genetic locus encoding Avr3a/5. Transformation of P. sojae and transient expression in soybean were performed to test how Avr3a/5 alleles interact with soybean Rps3a and Rps5. Over-expression of Avr3a/5 in a P. sojae strain that is normally virulent on Rps3a and Rps5 results in avirulence to Rps3a and Rps5; whereas silencing of Avr3a/5 causes gain of virulence in a P. sojae strain that is normally avirulent on Rps3a and Rps5 soybean lines. Transient expression and co-bombardment with a reporter gene confirms that Avr3a/5 triggers cell death in Rps5 soybean leaves in an appropriate allele-specific manner. Sequence analysis of the Avr3a/5 gene identifies crucial residues in the effector domain that distinguish recognition by Rps3a and Rps5

Facilitated Monocyte-Macrophage Uptake and Tissue Distribution of Superparmagnetic Iron-Oxide Nanoparticles

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery. METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T(2) measures using magnetic resonance imaging (MRI) were used to monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab')(2) fragments and for Alexa Fluor(R) 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab')(2), and/or Alexa Fluor(R) 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO was found stable at 4 degrees C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated SPIO, intravenous injection of IgG-SPIO afforded enhanced and sustained lymphoid tissue distribution over 24 hours as demonstrated by MRI. CONCLUSIONS: Facilitated uptake of coated SPIO in monocytes and MDM was achieved. Uptake was linked to particle size and was time and concentration dependent. The ability of SPIO to be rapidly taken up and distributed into lymphoid tissues also demonstrates feasibility of macrophage-targeted nanoformulations for diagnostic and drug therapy

Strategies in a metallophyte species to cope with manganese excess

The effect of exposure to high Mn concentration was studied in a metallophyte species, Erica andevalensis, using hydroponic cultures with a range of Mn concentrations (0.06, 100, 300, 500, and 700 mg L-1). At harvest, biomass production, element uptake, and biochemical indicators of metal stress (leaf pigments, organic acids, amino acids, phenols, and activities of catalase, peroxidase, superoxide dismutase) were determined in leaves and roots. Increasing Mn concentrations led to a decrease in biomass accumulation, and tip leaves chlorosis was the only toxicity symptom detected. In a similar way, photosynthetic pigments (chlorophylls a and b, and carotenoids) were affected by high Mn levels. Among organic acids, malate and oxalate contents in roots showed a significant increase at the highest Mn concentration, while in leaves, Mn led to an increasing trend in citrate and malate contents. An increase of Mn also induced an increase in superoxide dismutase activity in roots and catalase activity in leaves. As well, significant changes in free amino acids were induced by Mn concentrations higher than 300 mg L-1, especially in roots. No significant changes in phenolic compounds were observed in the leaves, but root phenolics were significantly increased by increasing Mn concentrations in treatments. When Fe supply was increased 10 and 20 times (7–14 mg Fe L-1 as Fe-EDDHA) in the nutrient solutions at the highest Mn concentration (700 mg Mn L-1), it led to significant increases in photosynthetic pigments and biomass accumulation. Manganese was mostly accumulated in the roots, and the species was essentially a Mn excluder. However, considering the high leaf Mn concentration recorded without toxicity symptoms, E. andevalensis might be rated as a Mn-tolerant speciesinfo:eu-repo/semantics/publishedVersio

Epigenetic Regulation of Histone H3 Serine 10 Phosphorylation Status by HCF-1 Proteins in C. elegans and Mammalian Cells

BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation