IP PATTERNS OF MOVEMENTS IN VSO TYPOLOGY: THE CASE OF ARABIC

The aim of this article is to explore a particular instantiation of the order in Arabic and to demonstrate that VSO and SVO are frequent alternatives for the language. The article will offer a range of views that have been expressed on the subject in order to give a comparative orientation to this study and will include and cover a range of empirical data in an attempt to discover and to understand the interaction of the IP (Inflectional Phrase) components of the languages underlying system. There will be two kinds of arguments advanced in support of the claim we make with regard to such movement: empirical arguments based on the data provided and theoretical or conceptual arguments based on the internal consistency of the system and the literature that deals with similar issues elsewhere

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey†

Predicting breast cancer outcome based on SLN node status without ALND is currently an area of uncertainty in SLN+ patients. These uncertainties influence the decision-making of adjuvant nodal irradiation. The NORA Survey was designed to examine the patterns of RNI practice in Europe to provide a basis for designing future trials in areas of equipoise in clinical decision-making concerning RN

Production and purification of xylooligosaccharides from oil palm empty fruit bunch fibre by a non-isothermal process

Oil palm empty fruit bunches (OPEFB) fibre, a by-product generated from non-woody, tropical perennial oil palm crop was evaluated for xylooligosaccharides (XOS) production. Samples of OPEFB fibre were subjected to non-isothermal autohydrolysis treatment using a temperature range from 150 to 220 ºC. The highest XOS concentration, 17.6 g/L which relayed from solubilisation of 63 g/100 g xylan was achieved at 210 ºC and there was a minimum amount of xylose and furfural being produced. The chromatographic purification which was undertaken to purify the oligosaccharide-rich liquor resulted in a product with 74–78% purity, of which 83–85% was XOS with degree of polymerisation (DP) between 5 and 40

Subchondral Bone Trabecular Integrity Predicts and Changes Concurrently with Radiographic and MRI Determined Knee Osteoarthritis Progression

OBJECTIVE: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. METHODS: Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. RESULTS: Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. CONCLUSION: BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials. Copyright 2013 by the American College of Rheumatology

S100P enhances the motility and invasion of human trophoblast cell lines

S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation

Offspring of Mothers Fed a High Fat Diet Display Hepatic Cell Cycle Inhibition and Associated Changes in Gene Expression and DNA Methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction

Functional and Transcriptional Induction of Aquaporin-1 Gene by Hypoxia; Analysis of Promoter and Role of Hif-1α

Aquaporin-1 (AQP1) is a water channel that is highly expressed in tissues with rapid O2 transport. It has been reported that this protein contributes to gas permeation (CO2, NO and O2) through the plasma membrane. We show that hypoxia increases Aqp1 mRNA and protein levels in tissues, namely mouse brain and lung, and in cultured cells, the 9L glioma cell line. Stopped-flow light-scattering experiments confirmed an increase in the water permeability of 9L cells exposed to hypoxia, supporting the view that hypoxic Aqp1 up-regulation has a functional role. To investigate the molecular mechanisms underlying this regulatory process, transcriptional regulation was studied by transient transfections of mouse endothelial cells with a 1297 bp 5′ proximal Aqp1 promoter-luciferase construct. Incubation in hypoxia produced a dose- and time-dependent induction of luciferase activity that was also obtained after treatments with hypoxia mimetics (DMOG and CoCl2) and by overexpressing stabilized mutated forms of HIF-1α. Single mutations or full deletions of the three putative HIF binding domains present in the Aqp1 promoter partially reduced its responsiveness to hypoxia, and transfection with Hif-1α siRNA decreased the in vitro hypoxia induction of Aqp1 mRNA and protein levels. Our results indicate that HIF-1α participates in the hypoxic induction of AQP1. However, we also demonstrate that the activation of Aqp1 promoter by hypoxia is complex and multifactorial and suggest that besides HIF-1α other transcription factors might contribute to this regulatory process. These data provide a conceptual framework to support future research on the involvement of AQP1 in a range of pathophysiological conditions, including edema, tumor growth, and respiratory diseases

A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.

Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits

The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size

Background We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations. Methodology/Principal Findings We analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by −40.4 g, 95%CI −61.4, −19.5; birth length −0.14 cm, 95%CI −0.23, −0.05; head circumference −0.09 cm 95%CI −0.15, −0.02) and neighborhood disparity (birthweight −28.8 g, 95%CI −47.7, −10.0; birth length −0.12 cm, 95%CI −0.20, −0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles. Conclusions/Significance Social adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults