Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of tumour associated antigen RCAS1 is implicated in high stages of colorectal cancer

Background: RCAS1 (receptor binding cancer antigen expressed on SiSo cells) is a tumour associated antigen. It is involved in immune evasion by tumour cells, by binding to receptors on cells involved in the immune response, such as T cells and natural killer cells, and inducing apoptosis. High expression of RCAS1 has been demonstrated immunohistochemically in tumours of the cervix, breast, lung, and stomach; however, the expression of RCAS1 has never been investigated in colorectal cancer. Aims: To investigate the expression of RCAS1 in colorectal cancer and identify at which stages of colorectal carcinogenesis it is expressed. Methods: Sixty surgically resected colorectal cancer specimens obtained from Rajavithi Hospital, Bangkok, Thailand were studied. RCAS1 expression was detected immunohistochemically using monoclonal anti–RCAS1 antibody. RCAS1 mRNA expression was also investigated by reverse transcription polymerase chain reaction in the freshly isolated tissues, and serum RCAS1 was measured by enzyme linked immunosorbent assay. Results: Staining for the RCAS1 protein was intense in high stages of colorectal cancer, but weak in normal tissues. The RCAS1 mRNA results correlated with the immunohistochemistry results. Positive serum RCAS1 concentrations were found in 10 of 18 patients with stage II disease and 12 of 32 with stage III and IV, but not in patients with stage I disease. All lymph node and liver metastases showed high expression of RCAS1 protein. Conclusions: RCAS1 appears to be upregulated in high stages of colorectal cancer, both in the serum and the tissue. RCAS1 expression might be a useful additional criterion for staging this cancer.
Clinical aspects of ALS in Gulf War Veterans

The increased incidence of ALS in military veterans of the first Persian Gulf War raised speculation that they may have a ‘Persian Gulf’ variant of ALS with atypical clinical features. Medical records of military veterans with ALS, previously identified in our epidemiological study, were evaluated for clinical features (age and site of onset, race, unexplained atypical findings) and ventilator-free survival. Comparisons between deployed versus non-deployed cohorts were made with deployment status based on designation by the Department of Defense Manpower Data Center (DMDC) or by self-report. Other than the young age of onset in both cohorts (40.8 years overall mean; 40.1 years for DMDC deployed, 41.2 years for DMDC non-deployed), review of the medical records failed to document any atypical features. After adjusting for bulbar onset, median survival from symptom onset in those ≥40 years of age was 35.5 months (2.96 years) compared to 64.7 months (5.39 years) in the group <40 years of age (hazard ratio (HR)=0.47, 95% CI 0.30–0.73, p=0.0006). After adjusting for age, median survival was 45.4 months (3.78 years) and 54.8 months (4.57 years) in bulbar- versus non-bulbar onset groups, respectively (HR=1.41, 95% CI 0.83–2.39, p=0.20). After adjusting for age and site of onset, deployed veterans had significantly shorter survival than non-deployed (40.2 vs. 57.0 months, HR=0.62, 95% CI 0.40–0.96, p=0.03) using DMDC data. In conclusion, although veterans developing ALS after deployment to the Persian Gulf in 1990–1991 exhibited otherwise typical clinical features, they experienced shorter ventilator-free survival than non-deployed veterans.
Analysis of the Exochelin Locus inMycobacterium smegmatis: Biosynthesis Genes Have Homology with Genes of the Peptide Synthetase Family

ABSTRACT Mycobacteria secrete the siderophore exochelin when grown under iron-limiting conditions. In order to understand iron uptake mechanisms in mycobacteria, we have taken a genetic approach to identify those genes involved in exochelin biosynthesis and transport in Mycobacterium smegmatis. Of the 6,000 chemically mutagenized clones of M. smegmatismc2155 screened on agar plates containing chrome azural S, 19 mutants that had lost the ability to produce or secrete exochelin were identified. Thirteen of these mutants were complemented by a single M. smegmatis cosmid. Sequence analysis of this cosmid revealed nine open reading frames, three of which are homologous to genes encoding transporter proteins, which are likely involved in exochelin transport. Complementation and Tn10 mutagenesis analysis identified two new genes,fxbB and fxbC, which are required for exochelin biosynthesis. The fxbB andfxbC genes encode large proteins of 257 and 497 kDa, respectively, which are highly homologous to peptide synthetases, indicating that exochelin biosynthesis occurs by a nonribosomal mechanism.
From Residential Energy Demand to Fuel Poverty: Income-induced Non-linearities in the Reactions of Households to Energy Price Fluctuations

The residential energy demand is growing steadily and the trend is expected to continue in the near future. At the same time, under the impulse of economic crises and environmental and energy policies, many households have experienced reductions in real income and higher energy prices. In the residential sector, the number of fuel-poor households is thus expected to rise. A better understanding of the determinants of residential energy demand, in particular of the role of income and the sensitivity of households to changes in energy prices, is crucial in the context of recurrent debates on energy efficiency and fuel poverty. We propose a panel threshold regression (PTR) model to empirically test the sensitivity of French households to energy price fluctuations—as measured by the elasticity of residential heating energy prices—and to analyze the overlap between their income and fuel poverty profiles. The PTR model allows to test for the non-linear effect of income on the reactions of households to fluctuations in energy prices. Thus, it can identify specific regimes differing by their level of estimated price elasticities. Each regime represents an elasticity-homogeneous group of households. The number of these regimes is determined based on an endogenously PTR-fixed income threshold. Thereafter, we analyze the composition of the regimes (i.e. groups) to locate the dominant proportion of fuel-poor households and analyse their monetary poverty characteristics. Results show that, depending on the income level, we can identify two groups of households that react differently to residential energy price fluctuations and that fuel-poor households belong mostly to the group of households with the highest elasticity. By extension, results also show that income poverty does not necessarily mean fuel poverty. In terms of public policy, we suggest focusing on income heterogeneity by considering different groups of households separately when defining energy efficiency measures. We also suggest paying particular attention to targeting fuel-poor households by examining the overlap between fuel and income poverty.
Canopy-microclimate effects on the antagonism between Trichoderma stromaticum and Moniliophthora perniciosa in shaded cacao

The collective impact of several environmental factors on the biocontrol activity of Trichoderma stromaticum ( Ts ) against Moniliophthora perniciosa ( Mp ), the cause of cacao witches’ broom disease, was assessed under ﬁeld conditions of shaded cacao ( Theobroma cacao ) in south-eastern Bahia, Brazil. Biocontrol experiments were performed adjacent to an automated weather station, with sensors and Ts -treated brooms placed at different canopy heights. Sporulation occurred at the same dates for all Ts isolates, but in different quantities. Broom moisture >30%, air temperature of approximately 23 ± 3 (cid:2) C, relative humidity >90%, solar radiation intensities <0 Æ 12 KW m ) 2 and wind speed near zero were the key environmental parameters that preceded Ts sporulation events. A multiple logistic regression indicated that these weather variables combined were capable of distinguishing sporulation from non-sporulation events, with a signiﬁcant effect of wind speed. Analyses of environmental factors at ground level indicated similar pre-sporulation conditions, with a soil moisture content above a threshold of 0 Æ 34 m 3 m ) 3 preceding all sporulation events. The sporulation of ﬁve selected Ts isolates was compared at four different canopy heights. Isolates responded differently to weather variation in terms of sporulation and antagonism to Mp at different canopy levels, indicating that different microclimates are established along the vertical proﬁle of a shaded cacao plantation. The potential of these ﬁndings for development of predictive mathematical models and disease-management approaches is discussed. incidence and severity in non- sporulating brooms indicate brooms presence of Mp after ﬁeld 100% colonized
African Swine Fever Virus Protein p54 Interacts with the Microtubular Motor Complex through Direct Binding to Light-Chain Dynein

ABSTRACT Dynein is a minus-end-directed microtubule-associated motor protein involved in cargo transport in the cytoplasm. African swine fever virus (ASFV), a large DNA virus, hijacks the microtubule motor complex cellular transport machinery during virus infection of the cell through direct binding of virus protein p54 to the light chain of cytoplasmic dynein (LC8). Interaction of p54 and LC8 occurs both in vitro and in cells, and the two proteins colocalize at the microtubular organizing center during viral infection. p50/dynamitin, a dominant-negative inhibitor of dynein-dynactin function, impeded ASFV infection, suggesting an essential role for dynein during virus infection. A 13-amino-acid domain of p54 was sufficient for binding to LC8, an SQT motif within this domain being critical for this binding. Direct binding of a viral structural protein to LC8, a small molecule of the dynein motor complex, could constitute a molecular mechanism for microtubule-mediated virus transport.
Electrical properties of phrenic motoneurons in the cat: correlation with inspiratory drive.

1. Resting membrane potential (Vmp), input resistance (Rn), rheobase (Irh), and after hyperpolarization duration (AHPdur) and amplitude (AHPamp) were measured in 38 phrenic motoneurons of anesthetized, paralyzed, and artificially ventilated cats during hypocapnic apnea. The mean +/- SD and range of values for these variables were as follows: Vmp, -68 +/- 5mV (range: -60 to -82); Rn, 1.3 +/- 0.6 M omega (0.6-2.4); Irh, 9.7 +/- 5 nA (2-20); AHPdur, 68 +/- 19 ms (37-134); AHPamp, 3.3 +/- 1.8 mV (1.0-8.5). In 31 motoneurons, the membrane potential level at which firing occurred (Vthr) during intracellular current injection was measured. The mean value of Vthr was -58 +/- 3 mV (range: -52 to -64). 2. A histogram of Rn revealed a bimodal distribution. Also a plot of Irh against Rn showed a grouping of the motoneurons into two subpopulations: 1) low-Rn and high-Irh cells, called type L neurons, and 2) high-Rn, low-Irh cells, called type H neurons. The overall negative linear correlation between Irh and Rn (r = -0.85; P less than 0.0001) resulted from this grouping rather than from a strictly linear relation between these two variables. 3. Electrical properties were compared for type L (n = 20) and type H (n = 18) phrenic motoneurons. The following mean values were found for each group, respectively: Rn, 0.8 and 1.8 M omega; Irh, 13.7 and 5.3 nA; AHPdur, 58 and 79 ms; AHPamp, 2.4 and 4.4 mV. All differences were significant (t test, P less than 0.001). Mean Vthr was the same for the two groups. 4. Comparison of these data with those available for lumbosacral motoneurons revealed that almost all investigated electrical properties of type L and type H phrenic motoneurons are similar to the analogous properties of type F (fast twitch) and type S (slow twitch) lumbosacral motoneurons, respectively. The apparent exception is the lower mean value of Irh for type L phrenic motoneurons compared with type F lumbosacral motoneurons. 5. For 13 cells, membrane potential was continuously monitored while spontaneous respiratory activity was restored by increasing CO2. It was found that at approximately the same end-tidal CO2 (about 7%) and a similar end-expiratory mean membrane potential level (approximately -70 mV), mean amplitude of peak inspiratory synaptic depolarization was higher in type H motoneurons (8.8 mV, n = 5) than in type L (2.9 mV, n = 8; P less than 0.001). (ABSTRACT TRUNCATED AT 400 WORDS)
Feeding Immaturity in Preterm Neonates: Risk Factors for Oropharyngeal Aspiration and Timing of Maturation

Objective: Oropharyngeal aspiration (OPA) is a common cause of morbidity in premature neonates. We sought to identify significant risk factors and determine the timing of feeding maturation in preterm infants with OPA. Methods: We performed a retrospective medical record review of 148 former preterm neonates referred for modified barium swallow study (MBSS) during a 3-year period. We looked at the MBSS results and potential clinical and demographic risk factors and performed bivariate and multivariable logistic regression analyses to evaluate predictors of failure. We evaluated the timing of resolution of OPA based on MBSS results. Results: Of the 148 infants comprising our study cohort, 47 (32%) passed their initial MBSS and 101 (68%) were found to aspirate thin liquids. Infants who aspirate had younger corrected gestational age (CGA) and postnatal age at the time of testing. Increasing CGA led to lower odds of failing. Infants passed a MBSS at a median CGA of 53 weeks and those who failed an initial MBSS eventually passed after a median of ∼3.4 months from the first study. Infants with bronchopulmonary dysplasia had lower odds of failing their MBSS (odds ratio 0.16), but those taking inhaled corticosteroids and diuretics had higher odds of failing, and infants who were multiples also had higher odds of failing. Conclusions: We determined the median CGA for passing MBSS and identified risk factors for OPA in this population. This information can help guide providers when counseling families on timing of feeding maturity and anticipation of appropriate timing for follow-up MBSS testing.
Vítor Constâncio: Monetary policy and the European recovery

I start by thanking Círculo de Economia for inviting me to participate in this prestigious event. The theme of this year’s conference is on ways to “consolidate the recovery”. The ECB’s monetary policy measures aim at precisely that: supporting the recovery in order to reach our price stability objective. Our policies have however, a broader impact, also being part of the European response to the challenges that the euro area has been confronted with for some time.
Work disability among adults with asthma.

OBJECTIVE To estimate the incidence of work disability among adults with asthma and to evaluate a clinically based illness severity score as a predictor of such disability. DESIGN Baseline and follow-up telephone interviews and medical record review. SETTING University-based outpatient pulmonary specialty practice. PATIENTS Fifty-six patients interviewed at baseline; 42 reinterviewed 2 years later. MEASUREMENTS Work disability ascertained by interview report and defined as change in job duties, reduction in pay, or change in job or employment status attributed to asthma. Severity of asthma score derived from medical records and based on respiratory symptom frequency, asthma history, and prescribed medications. Pulmonary function by routine testing. Logistic regression analysis of the 5-year incidence of work disability on severity score and forced expiratory volume in 1 s (FEV1). RESULTS The 5-year work disability cumulative incidence was 19 percent for change in duties, 17 percent for reduction in pay, 20 percent for change in job or work status, and 36 percent for any of these measures. The median asthma score was 10 (range, 2 to 26). The mean FEV1 as a percent predicted (FEV1 percent) was 88 +/- 25 percent. Score and FEV1 percent were statistically correlated (r = -0.6, p < 0.0001). Severity of asthma score statistically predicted each measure of work disability (p < 0.01). Addition of FEV1 percent added little additional explanatory power to the logistic regression model (maximum chi 2 = 1.3, p > 0.2). CONCLUSIONS Work disability is common among adults with asthma. A severity of asthma score based on clinical variables is statistically correlated with lung function but appears to be a stronger predictor of disability than airflow measured at one point in time.
The Behavioral and Neurochemical Effects of a Novel d-Amino Acid Oxidase Inhibitor Compound 8 [4H-Thieno [3,2-b]pyrrole-5-carboxylic Acid] and d-Serine

Multiple studies indicate that N-methyl-d-aspartate (NMDA) receptor hypofunction underlies some of the deficits associated with schizophrenia. One approach for improving NMDA receptor function is to enhance occupancy of the glycine modulatory site on the NMDA receptor by increasing the availability of the endogenous coagonists d-serine. Here, we characterized a novel d-amino acid oxidase (DAAO) inhibitor, compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and compared it with d-serine. Compound 8 is a moderately potent inhibitor of human (IC50, 145 nM) and rat (IC50, 114 nM) DAAO in vitro. In rats, compound 8 (200 mg/kg) decreased kidney DAAO activity by ∼96% and brain DAAO activity by ∼80%. This marked decrease in DAAO activity resulted in a significant (p < 0.001) elevation in both plasma (220% of control) and cerebrospinal fluid (CSF; 175% of control) d-serine concentration. However, compound 8 failed to significantly influence amphetamine-induced psychomotor activity, nucleus accumbens dopamine release, or an MK-801 (dizocilpine maleate)-induced deficit in novel object recognition in rats. In contrast, high doses of d-serine attenuated both amphetamine-induced psychomotor activity and dopamine release and also improved performance in novel object recognition. Behaviorally efficacious doses of d-serine (1280 mg/kg) increased CSF levels of d-serine 40-fold above that achieved by the maximal dose of compound 8. These findings demonstrate that pharmacological inhibition of DAAO significantly increases d-serine concentration in the periphery and central nervous system. However, acute inhibition of DAAO appears not to be sufficient to increase d-serine to concentrations required to produce antipsychotic and cognitive enhancing effects similar to those observed after administration of high doses of exogenous d-serine.
Increase of Calcitonin Gene-Related Peptide Immunoreactivity in the Axonal Fibers of the Gracile Nuclei of Adult and Aged Rats after Complete and Partial Sciatic Nerve Injuries

Neuropeptide changes in primary sensory neurons are thought to be involved in the pathological mechanisms of neuropathic pain caused by peripheral nerve injuries. In this study, using immunocytochemistry, we observed that calcitonin gene-related peptide (CGRP) immunoreactive (IR) fibers were increased, qualitatively and quantitatively, in the injured side gracile nuclei of adult (2 months old) and aged (16 months old) rats 2 weeks following complete transection (CSNT) or chronic constriction injury (CCI) of sciatic nerves. This increase was more pronounced after CCI than after CSNT. In aged rats, the CGRP-IR fibers which appeared were dystrophic. In contrast to the increases which we saw in the gracile nucleus, after both types of injury there was a decrease in CGRP-IR in all laminae of the dorsal horn. The percentage of CGRP-IR DRG neurons was decreased after CSNT, but unchanged after CCI. We interpret our results in terms of local sprouting in the gracile nucleus and suggest that the increased response following CCI is due to the involvement of fibers from DRG neurons spared by the partial nerve injury. Increased CGRP release from spared afferents in the gracile nucleus might be important in neuropathic pain.
Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P < .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P < .001), and neurotoxicity was more frequent with VDS-P (P < .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.
Rapid Transposon Liquid Enrichment Sequencing (TnLE-seq) for Gene Fitness Evaluation in Underdeveloped Bacterial Systems

ABSTRACT Whole-genome fitness analysis in microbes that uses saturating transposon mutagenesis combined with massively parallel sequencing (Tn-seq) is providing a measure of the contribution of each gene to a given growth condition. With this technique, gene fitness profiles and essential genes are discovered by simultaneous analyses of whether the absence of each gene product alters the growth kinetics of the bacterium. Here we modify the standard Tn-seq procedure to simplify and shorten the process by including delivery of the transposon through conjugation and liquid culture enrichment of the mutant pool, creating transposon liquid enrichment sequencing (TnLE-seq). To illustrate the success of these modifications and the robustness of the procedure, analyses of gene fitness of two cultures of the strictly anaerobic bacterium Desulfovibrio vulgaris Hildenborough were performed, with growth on lactate as the electron donor and sulfate as the electron acceptor. These data demonstrate reproducibility and provide a base condition for analysis of fitness changes in deletion mutants and in various growth conditions. The procedural modifications will facilitate the application of this powerful genetic analysis to microbes lacking a facile genetic system. Pilot studies produced 2.5 × 105 and 3.4 × 105 unique insertion mutants in the anaerobe Desulfovibrio vulgaris Hildenborough grown under typical laboratory conditions in rich medium. These analyses provided two similar high-resolution maps of gene fitness across the genome, and the method was also applied to growth in minimal medium. These results were also compared to the coverage obtained with a ca. 13,000-member cataloged transposon library constructed by sequencing transposon insertion sites in individual mutants.