The patatin-related phospholipase A (pPLA) hydrolyzes membrane glycerolipids to produce monoacyl compounds and free fatty acids. Phospholipids are cleaved by pPLAIIα at the sn-1 and sn-2 positions, and galactolipids, including those containing oxophytodienoic acids, can also serve as substrates. Ablation of pPLAIIα decreased lysophosphatidylcholine and lysophosphatidylethanolamine levels, but increased free linolenic acid. pPLAIIα-deficient plants displayed a higher level of jasmonic acid and methyl jasmonate, as well as the oxylipin-biosynthetic intermediates 13-hydroperoxylinolenic acid and 12-oxophytodienoic acid than wild-type (WT) plants. The expression of genes involved in oxylipin production was also higher in the pPLAIIα-deficient mutant than in WT plants. The mutant plants lost water more quickly than WT plants. The stomata of WT and mutant plants responded similarly to abscisic acid. In response to desiccation, the mutant and WT leaves produced abscisic acid at the same rate, but, after 4 h of desiccation, the jasmonic acid level was much higher in mutant than WT leaves. These results indicate that pPLAIIα negatively regulates oxylipin production and suggest a role in the removal of oxidatively modified fatty acids from membranes.

Background

Bioimpedance analysis (BIA) has been reported as helpful in identifying hypervolemia. Observation data showed that hypervolemic maintenance hemodialysis (MHD) patients identified using BIA methods have higher mortality risk. However, it is not known if BIA-guided fluid management can improve MHD patients’ survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management compared with standard care.

Methods

This is a multicenter, prospective, randomized, controlled trial. More than 1300 participants from 16 clinical sites will be included in the study. The enrolment period will last 6 months, and minimum length of follow-up will be 36 months. MHD patients aged between 18 years and 80 years who have been on MHD for at least 3 months and meet eligibility criteria will be invited to participate in the study. Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arms of the study. In the BIA arm, additional BCM measurements will be performed every 2 months. The primary intent-to-treat analysis will compare outcomes for a composite endpoint of death, acute myocardial infarction, stroke or incident peripheral arterial occlusive disease between groups. Secondary endpoints will include left ventricular wall thickness, blood pressure, medications, and incidence and length of hospitalization.

Discussions

Previous results regarding the benefit of strict fluid control are conflicting due to small sample sizes and unstable dry weight estimating methods. To our knowledge this is the first large-scale, multicentre, prospective, randomized controlled trial to assess whether BIS-guided volume management improves outcomes of MHD patients. The endpoints of the BOCOMO study are of utmost importance to health care providers. In order to obtain that aim, the study was designed with very careful important considerations related to the endpoints, sample size, inclusion criteria, exclusion criteria and so on. For example, annual mortality of Beijing MHD patients was around 10%. To reach statistical significance, the sample size will be very large. By using composite endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to patients with urine volume less than 800 ml/day the day before dialysis session will limit confounding due to residual renal function effects on the measured parameters. Patients who had received BIS measurement within 3 months prior to enrolment are excluded as data from such measurements might lead to protocol violation. Although not all patients enrolled will be incident patients, we will record the vintage of dialysis in the multivariable analysis.

Trial registration

Current Controlled Trials NCT01509937

Introduction

With the increase in joint revision surgery after arthroplasty, defects of hydroxyapatite (HA)-coated prostheses have been observed increasingly often. These defects adversely affect the prosthetic stability in vivo. This study has analyzed the potential effect of the adhesive strength of HA coating on the stability of HA-coated prostheses in vivo after its implantation.

Material and methods

Sixty experimental rabbits were divided into HA- and Ti-coated groups. HA-coated prostheses were implanted into the bilateral epicondyle of rabbits femurs. Ti-coated prostheses were implanted as control. At different time points(4, 9, and 15 weeks) after implantation, bone tissue samples were fetched out respectively for histomorphometric analysis. Push-out testing was used to detect the ultimate shear strength at the bone-prosthesis interface. Scanning electron microscope (SEM) observation and energy-dispersive X-ray spectroscopy (EDX) analysis were used to observe the changes in surface composition of the prostheses after the ultimate shear strength testing. The coating adhesive strength of two kinds of coatings were also examined by scratch testing.

Results

Hydroxyapatite coating has an obvious advantage in facilitating osteogenesis and its plays a critical role in the stability of prostheses. However, the ultimate shear strength of HA-coated prostheses is much lower than that of Ti-coated implants (p < 0.01). Further study has demonstrated that the stability of HA-coated prostheses in vivo is affected by the relatively low adhesive strength between coating and substrate.

Conclusions

Obvious advantage in facilitating osteogenesis around HA-coated prostheses is not the only factor that determines the stability of prostheses in vivo.

With the superiority of digital imaging, conventional preoperative acetate templating is gradually being replaced by digital templating in total hip arthroplasty (THA). The purpose of this study was to assess the utility of digital templating for patients with Crowe type II and III dysplastic hips. In this study, 41 THA patients with Crowe type II or III dysplastic hips and 48 THA patients with other primary diseases were retrospectively reviewed. All patients were fitted with cementless prostheses in 2008. For the THA patients with dysplastic hips, we attempted to restore their hip centres to the position of the true acetabulum. Digital templating was the method chosen to achieve hip centre restoration. The prosthesis prediction accuracy (within ± one size using digital templating) was 20 (48.8%) for the cup size and 30 (73.2%) for the stem size. Meanwhile, for patients with other primary diseases, the accuracy for the cup size within ± one size was 34 (70.8%) and for the stem size accuracy was within ± one size in 38 (79.2%). Between the two patient groups, there was a significant difference in the predicted cup size. In patients with dysplastic hips, the low accuracy of the predicted cup size may have resulted from difficulty in predicting the vertical location of the hip centre. Despite this limitation, preoperative planning using digital templating is a convenient technique for THA patients with Crowe type II and III dysplastic hips.

In the title coordination polymer, [Cd(C8H5N2O2S)2(C10H8N2)]n, the CdII ion is coordinated by a bidentate 2,2-bipyridyl ligand, two O,O′-chelating 2-amino-1,3-benzothia­zole-6-carboxyl­ate (ABTC) ligands and one N-bonded ABTC ligand. The resulting CdN3O4 coordination polyhedron approximates to a very distorted penta­gonal bipramid with one O and one N atom in axial positions. One of the ABTC ligands is bridging to an adjacent metal atom, generating an infinite chain propagating in [100]. A three-dimensional network is constructed from N—H⋯O and N—H⋯N hydrogen bonds and aromatic π–π stacking inter­actions [centroid–centroid separations = 3.641 (2) and 3.682 (3) Å].

Two virtually superimposable mol­ecules comprise the asymmetric unit of the title compound, C27H27N3. The range of dihedral angles between the central 1,3,5-triazine ring and the attached benzene rings is 20.88 (14)–31.36 (14)°, and the shape of each mol­ecule is of a flattened bowl. The crystal packing features weak C—H⋯π bonds and π–π inter­actions between triazine and benzene rings [centroid–centroid separations = 3.7696 (17) and 3.7800 (18) Å] that result in the formation of supra­molecular layers in the ac plane. The crystal studied was a non-merohedral twin with a minor twin component of 20.7 (3)%.

Mycoplasma, the smallest self-replicating organism with a minimal metabolism and little genomic redundancy, is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. This study employs comparative evolutionary analysis of twenty Mycoplasma genomes to gain an improved understanding of essential genes. By analyzing the core genome of mycoplasmas, we finally revealed the conserved essential genes set for mycoplasma survival. Further analysis showed that the core genome set has many characteristics in common with experimentally identified essential genes. Several key genes, which are related to DNA replication and repair and can be disrupted in transposon mutagenesis studies, may be critical for bacteria survival especially over long period natural selection. Phylogenomic reconstructions based on 3,355 homologous groups allowed robust estimation of phylogenetic relatedness among mycoplasma strains. To obtain deeper insight into the relative roles of molecular evolution in pathogen adaptation to their hosts, we also analyzed the positive selection pressures on particular sites and lineages. There appears to be an approximate correlation between the divergence of species and the level of positive selection detected in corresponding lineages.

In the zwitterionic title compound, C17H11NO5, the dihedral angle between the two aromatic rings is 76.90 (7)°. The dihedral angles between the carboxyl groups and the benzene ring are 64.02 (9) and 21.67 (9)°, the larger angle being associated with an intra­molecular N—H⋯Ocarbox­yl hydrogen bond, resulting from proton transfer from the carb­oxy­lic acid group to the quinoline N atom and giving an S(9) ring motif. In the crystal, mol­ecules are connected by O—H⋯O hydrogen bonds into chains extending along the b-axis direction. An overall two-dimensional network structure is formed through π–π inter­actions between the quinoline rings [minimum ring-centroid separation = 3.6068 (6) Å].

Microsomes are derived mostly from endoplasmic reticulum and are an ideal target to investigate compound metabolism, membrane-bound enzyme functions, lipid-protein interactions, and drug-drug interactions. To better understand the molecular mechanisms of the liver and its diseases, mouse liver microsomes were isolated and enriched with differential centrifugation and sucrose gradient centrifugation, and microsome membrane proteins were further extracted from isolated microsomal fractions by the carbonate method. The enriched microsome proteins were arrayed with two-dimensional gel electrophoresis (2DE) and carbonate-extracted microsome membrane proteins with one-dimensional gel electrophoresis (1DE). A total of 183 2DE-arrayed proteins and 99 1DE-separated proteins were identified with tandem mass spectrometry. A total of 259 nonredundant microsomal proteins were obtained and represent the proteomic profile of mouse liver microsomes, including 62 definite microsome membrane proteins. The comprehensive bioinformatics analyses revealed the functional categories of those microsome proteins and provided clues into biological functions of the liver. The systematic analyses of the proteomic profile of mouse liver microsomes not only reveal essential, valuable information about the biological function of the liver, but they also provide important reference data to analyze liver disease-related microsome proteins for biomarker discovery and mechanism clarification of liver disease.

In the title complex, [Ir(C17H13N2)2(C5H7O2)], the IrIII atom is hexa­coordinated in a distorted octa­hedral geometry by two C,N-bidentate 2-(5-methyl-3-phenyl­pyrazin-2-yl)phenyl (mdpp) ligands and one O,O-bidentate acetyl­acetonate ligand. The dihedral angles between the phenyl rings and the pyrazine ring are 9.56 (14) and 58.99 (14)° for one mdpp ligand and 9.34 (14) and 79.94 (15)° for the other.

Background

Sinorhizobium meliloti is a soil bacterium, known for its capability to establish symbiotic nitrogen fixation (SNF) with leguminous plants such as alfalfa. S. meliloti 1021 is the most extensively studied strain to understand the mechanism of SNF and further to study the legume-microbe interaction. In order to provide insight into the metabolic characteristics underlying the SNF mechanism of S. meliloti 1021, there is an increasing demand to reconstruct a metabolic network for the stage of SNF in S. meliloti 1021.

Results

Through an iterative reconstruction process, a metabolic network during the stage of SNF in S. meliloti 1021 was presented, named as iHZ565, which accounts for 565 genes, 503 internal reactions, and 522 metabolites. Subjected to a novelly defined objective function, the in silico predicted flux distribution was highly consistent with the in vivo evidences reported previously, which proves the robustness of the model. Based on the model, refinement of genome annotation of S. meliloti 1021 was performed and 15 genes were re-annotated properly. There were 19.8% (112) of the 565 metabolic genes included in iHZ565 predicted to be essential for efficient SNF in bacteroids under the in silico microaerobic and nutrient sharing condition.

Conclusions

As the first metabolic network during the stage of SNF in S. meliloti 1021, the manually curated model iHZ565 provides an overview of the major metabolic properties of the SNF bioprocess in S. meliloti 1021. The predicted SNF-required essential genes will facilitate understanding of the key functions in SNF and help identify key genes and design experiments for further validation. The model iHZ565 can be used as a knowledge-based framework for better understanding the symbiotic relationship between rhizobia and legumes, ultimately, uncovering the mechanism of nitrogen fixation in bacteroids and providing new strategies to efficiently improve biological nitrogen fixation.

Background

The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells.

Results

We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins.

Conclusion

The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.

Background

Primary open-angle glaucoma (POAG) is the most common form of glaucoma which is an irreversible blind leading disease and lacks effective remedies. In recent years, POAG has been linked to the gene MYOC encoding myocilin that has been identified to harbor causal mutations. A variety of studies show that the mutant myocilin acts by gain of function. The mutant MYOC protein induces endoplasmic reticulum (ER) stress and the resultant unfolded protein response (UPR) induces apoptosis in the trabecular meshwork cells, which then leads to an increase in resistance to aqueous humor outflow, elevated intraocular pressure (IOP), and, ultimately, glaucoma. Culturing human trabecular meshwork (HTM) cells at a condition facilitating protein folding promotes secretion of mutant myocilin, normalizes cell morphology and reverses cell lethality.

Presentation of the Hypothesis

We speculate that a complete elimination of mutant myocilin expression in trabecular meshwork cells is safe and that gives the possibility of avoiding the POAG phenotype.

Testing the Hypothesis

We propose RNA interference (RNAi) as a gene silencing therapy to eliminate the mutant myocilin proteins in the trabecular meshwork cells, either in a mutation-dependent or mutation-independent way due to the different engineering of the small interfering (si) RNA.

Implications of the Hypothesis

The RNAi strategy can reverse the pathological process of trabecular meshwork cells and thus treat the POAG caused by myocilin gene mutation. This strategy can also be applicable to many protein-misfolding diseases caused by gain-of-function mutant proteins.

Purpose

This study was designed to analyze two candidate genes, myocilin (MYOC) and cytochrome P450 1B1 (CYP1B1), in a Chinese pedigree of juvenile glaucoma with goniodysgenesis.

Methods

In a three-generation family of juvenile glaucoma with goniodysgenesis (13 members), six of them were patients with glaucoma and the rest were asymptomatic. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database.

Results

Elevated intraocular pressure (IOP) and visual function impairment was found in all patients, and goniodysgenesis was noticed in five of them (nine eyes) with relatively transparent corneas. One MYOC heterozygous mutation, c.1109 C>T (P370L), in exon 3 was identified in all six patients but not in the asymptomatic family members. Two CYP1B1 single nucleotide polymorphisms (SNPs), g.3947 C>G (R48G) in exon 2 and 372−12 C>T in intron 1, were identified in all six patients and but not in the asymptomatic family members except the proband’s grandmother. Three SNPs were identified, 730 + 35 A>G in intron 2 of MYOC and g.8131 G>C (V432L) and g.8184 T>C (D449D) in exon 3 of CYP1B1.

Conclusions

The presence of a P370L mutation of MYOC in all six glaucoma patients suggests a casual association between this mutation and juvenile glaucoma with goniodysgenesis. The possible role of SNPs of CYP1B1 in the pathogenesis of the disease remains to be elucidated.

In the title complex, [Cu(C2H3O2)(C10H8N2)2](CH3CH2OSO3)0.5(CH3OSO3)0.5, the CuII ion is bis-chelated by two 2,2′-bipyridine lignds and coordinated by an O atom of an acetate ligand in a CuN4O disorted square-pyramidal environment. In the structure, equal amounts of methyl sulfate and ethyl sulfate anions are disordered on the same crystallographic sites. The crystal structure is stabilized by weak inter­molecular C—H⋯O inter­actions.