Analysis of gas chromatography/mass spectrometry data for catalytic lignin depolymerization using positive matrix factorization

Various catalytic technologies are being developed to efficiently convert lignin into renewable chemicals. However, due to its complexity, catalytic lignin depolymerization often generates a wide and complex distribution of product compounds. Gas chromatography/mass spectrometry (GC-MS) is a common analytical technique to profile the compounds that comprise lignin depolymerization products. GC-MS is applied not only to determine the product composition, but also to develop an understanding of the catalytic reaction pathways and of the relationships among catalyst structure, reaction conditions, and the resulting compounds generated. Although a very useful tool, the analysis of lignin depolymerization products with GC-MS is limited by the quality and scope of the available mass spectral libraries and the ability to correlate changes in GC-MS chromatograms to changes in lignin structure, catalyst structure, and other reaction conditions. In this study, the GC-MS data of the depolymerization products generated from organosolv hybrid poplar lignin using a copper-doped porous metal oxide catalyst and a methanol/dimethyl carbonate co-solvent was analyzed by applying a factor analysis technique, positive matrix factorization (PMF). Several different solutions for the PMF model were explored. A 13-factor solution sufficiently explains the chemical changes occurring to lignin depolymerization products as a function of lignin, reaction time, catalyst, and solvent. Overall, seven factors were found to represent aromatic compounds, while one factor was defined by aliphatic compounds

Pasteurella multocida Heddleston serovar 3 and 4 strains share a common lipopolysaccharide biosynthesis locus but display both inter- and intrastrain lipopolysaccharide heterogeneity

Pasteurella multocida is a Gram-negative multispecies pathogen and the causative agent of fowl cholera, a serious disease of poultry which can present in both acute and chronic forms. The major outer membrane component lipopolysaccharide (LPS) is both an important virulence factor and a major immunogen. Our previous studies determined the LPS structures expressed by different P. multocida strains and revealed that a number of strains belonging to different serovars contain the same LPS biosynthesis locus but express different LPS structures due to mutations within glycosyltransferase genes. In this study, we report the full LPS structure of the serovar 4 type strain, P1662, and reveal that it shares the same LPS outer core biosynthesis locus, L3, with the serovar 3 strains P1059 and Pm70. Using directed mutagenesis, the role of each glycosyltransferase gene in LPS outer core assembly was determined. LPS structural analysis of 23 Australian field isolates that contain the L3 locus revealed that at least six different LPS outer core structures can be produced as a result of mutations within the LPS glycosyltransferase genes. Moreover, some field isolates produce multiple but related LPS glycoforms simultaneously, and three LPS outer core structures are remarkably similar to the globo series of vertebrate glycosphingolipids. Our in-depth analysis showing the genetics and full range of P. multocida lipopolysaccharide structures will facilitate the improvement of typing systems and the prediction of the protective efficacy of vaccines

Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines—Executive summary

[This is the executive summary of Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines: full guideline, doi: 10.1093/rheumatology/kez640

Awareness and practice of emergency contraception at a private university in Nigeria.

BACKGROUND: The pursuit of formal education now causes many people in developing countries to marry later in life, thereby leading to increased premarital sex and unintended pregnancies. Efforts have been made to characterize awareness and use of emergency contraception (EC) among undergraduate students in public universities in Nigeria; however, it is not known if students in private tertiary institutions adopt different practices or if having an affluent family background plays a role. This pilot study therefore aimed to assess the awareness and use of EC among students at a private Nigerian university toward assisting education planners in developing strategies in improving students' reproductive well-being. RESULTS: Out of 94 female students, 42 (44.7%) had sexual experience, but only 32 (34.0%) were currently sexually active. Six students (6.4%) had had unwanted pregnancies, of which all but one were terminated. Fifty-seven respondents (60.6%) were aware of EC, though only 10 (10.6%) ever practiced it. The greatest source of EC information was from health workers and peers; the lowest source was family or relatives. Most respondents desired orientation and availability of EC on campus. EC awareness among the students was predicted by upper social class background (adjusted odds ratio [OR], 2.73; 95% confidence interval [CI], 1.06-7.45) and upbringing in the Federal Capital Territory (adjusted OR, 4.45; 95% CI, 1.56-14.22). CONCLUSIONS: Though awareness of EC was higher among the private university students in this study than at most public universities, there was no difference in EC usage. A high pregnancy termination rate was observed; dilatation and curettage were mainly adopted. In Nigeria, youth-friendly reproductive health information and access should not be limited to government-owned tertiary institutions but also extended to private ones

Regulation of Mouse Small Heat Shock Protein αb-Crystallin Gene by Aryl Hydrocarbon Receptor

The stress-inducible small heat shock protein (shsp)/αB-crystallin gene is expressed highly in the lens and moderately in other tissues. Here we provide evidence that it is a target gene of the aryl hydrocarbon receptor (AhR) transcription factor. A sequence (−329/−323, CATGCGA) similar to the consensus xenobiotic responsive element (XRE), called here XRE-like, is present in the αBE2 region of αB-crystallin enhancer and can bind AhR in vitro and in vivo. αB-crystallin protein levels were reduced in retina, lens, cornea, heart, skeletal muscle and cultured muscle fibroblasts of AhR−/− mice; αB-crystallin mRNA levels were reduced in the eye, heart and skeletal muscle of AhR−/− mice. Increased AhR stimulated αB-crystallin expression in transfection experiments conducted in conjunction with the aryl hydrocarbon receptor nuclear translocator (ARNT) and decreased AhR reduced αB-crystallin expression. AhR effect on aB-crystallin promoter activity was cell-dependent in transfection experiments. AhR up-regulated αB-crystallin promoter activity in transfected HeLa, NIH3T3 and COS-7 cells in the absence of exogenously added ligand (TCDD), but had no effect on the αB-crystallin promoter in C2C12, CV-1 or Hepa-1 cells with or without TCDD. TCDD enhanced AhR-stimulated αB-crystallin promoter activity in transfected αTN4 cells. AhR could bind to an XRE-like site in the αB-crystallin enhancer in vitro and in vivo. Finally, site-specific mutagenesis experiments showed that the XRE-like motif was necessary for both basal and maximal AhR-induction of αB-crystallin promoter activity. Our data strongly suggest that AhR is a regulator of αB-crystallin gene expression and provide new avenues of research for the mechanism of tissue-specific αB-crystallin gene regulation under normal and physiologically stressed conditions

The Menin Tumor Suppressor Protein Is Phosphorylated in Response to DNA Damage

Multiple endocrine neoplasia type 1 (MEN1) is a heritable cancer syndrome characterized by tumors of the pituitary, pancreas and parathyroid. Menin, the product of the MEN1 gene, is a tumor suppressor protein that functions in part through the regulation of transcription mediated by interactions with chromatin modifying enzymes.Here we show menin association with the 5' regions of DNA damage response genes increases after DNA damage and is correlated with RNA polymerase II association but not with changes in histone methylation. Furthermore, we were able to detect significant levels of menin at the 3' regions of CDKN1A and GADD45A under conditions of enhanced transcription following DNA damage. We also demonstrate that menin is specifically phosphorylated at Ser394 in response to several forms of DNA damage, Ser487 is dynamically phosphorylated and Ser543 is constitutively phosphorylated. Phosphorylation at these sites however does not influence the ability to interact with histone methyltransferase activity. In contrast, the interaction between menin and RNA polymerase II is influenced by phosphorylation, whereby a phospho-deficient mutant had a higher affinity for the elongating form of RNA polymerase compared to wild type. Additionally, a subset of MEN1-associated missense point mutants, fail to undergo DNA damage dependent phosphorylation.Together, our findings suggest that the menin tumor suppressor protein undergoes DNA damage induced phosphorylation and participates in the DNA damage transcriptional response

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

<p>Abstract</p> <p>Background</p> <p>Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia.</p> <p>Methods</p> <p>Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2.</p> <p>Results</p> <p>Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia.</p> <p>Conclusion</p> <p>Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.</p

Quality of life and cost-effectiveness of interferon-alpha in malignant melanoma: results from randomised trial

A definitive conclusion regarding the value of low-dose extended duration adjuvant interferon-alpha therapy in the treatment of malignant melanoma is only possible once data on health-related quality of life (HRQoL) and costs have been considered. This trial randomised 674 patients to interferon alpha-2a (3 megaunits three times per week for 2 years or until recurrence) or placebo. Health-related quality of life (QoL) was to be assessed up to 60 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Data for the economic analysis, including cost information and the EQ-5D were also collected. Patients in the observation (OBS) group had significantly better mean follow-up quality of on five dimensions of the EORTC QLQ-C30 functional scales: role functioning (P=0.033), emotional functioning (P=0.003), cognitive functioning (P=0.001), social functioning (P=0.003) and global health status (P=0.001). Patients in the OBS group had significantly better mean follow-up symptom scores on seven dimensions of the EORTC QLQ-C30 V1 symptom scales. Economic data showed that costs were £3066 higher in the interferon group and produces an incremental cost per quality-adjusted life year of £41 432 at 5 years. The results show that interferon has significant effects on QoL and symptomatology and is unlikely to be cost-effective in this patient group in the UK