Miracle-dz/UniFAR-FTUs huggingface dataset:
Additive Effects of SbcCD and PolX Deficiencies in the In Vivo Repair of DNA Double-Strand Breaks in Deinococcus radiodurans

ABSTRACT Orthologs of proteins SbcD (Mre11) and SbcC (Rad50) exist in all kingdoms of life and are involved in a wide variety of DNA repair and maintenance functions, including homologous recombination and nonhomologous end joining. Here, we have inactivated the sbcC and/or sbcD genes of Deinococcus radiodurans, a highly radioresistant bacterium able to mend hundreds of radiation-induced DNA double-strand breaks (DSB). Mutants devoid of the SbcC and/or SbcD proteins displayed reduced survival and presented a delay in kinetics of DSB repair and cell division following γ-irradiation. It has been recently reported that D. radiodurans DNA polymerase X (PolX) possesses a structure-modulated 3′-to-5′ exonuclease activity reminiscent of specific nuclease activities displayed by the SbcCD complex from Escherichia coli. We constructed a double mutant devoid of SbcCD and PolX proteins. The double-mutant ΔsbcCD ΔpolX Dr (where Dr indicates D. radiodurans) bacteria are much more sensitive to γ-irradiation than the single mutants, suggesting that the deinococcal SbcCD and PolX proteins may play important complementary roles in processing damaged DNA ends. We propose that they are part of a backup repair system acting to rescue cells containing DNA lesions that are excessively numerous or difficult to repair.
Field superparasitism by Phymastichus coffea, a parasitoid of adult coffee berry borer, Hypothenemus hampei

Superparasitism by Phymastichus coffea LaSalle (Hymenoptera: Eulophidae), a parasitoid of adults of the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), was recorded under field conditions in a coffee plantation in Colombia. Parasitoid adults were released 1, 5, and 9 days after artificial infestations of 90‐, 150‐, and 210‐day‐old coffee berries with H. hampei females. The position of the beetle inside the berry and the number of P. coffea larvae per female host were assessed 10 days after each parasitoid release. Under laboratory conditions, P. coffea usually lays two eggs per host, one female and one male. In our studies, we often recorded more than six P. coffea larvae in an individual host and mean numbers of larvae per host ranged from two to 4.45. Superparasitism by P. coffea under field conditions was influenced by the age of the coffee berries, which is the most important factor determining the speed of penetration by H. hampei, and therefore the time the beetles are exposed to a P. coffea attack. The number of parasitoid larvae in each H. hampei female gradually decreased with the age of the berry, and also linearly decreased with the time of parasitoid release. Age‐dependent effects of coffee berries that alter the ratio of available hosts to searching parasitoids by providing refuges to the herbivore, largely determine the extent of superparasitism of H. hampei by P. coffea under fields conditions in Colombia.
Evaluation of biomarkers of exposure and potential harm in smokers, former smokers and never-smokers

Abstract Background: The objective of this study was to obtain baseline data on biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH) in smokers, former smokers and never-smokers. Methods: This was a cross-sectional study of 80 healthy male and female volunteers over 21 years old, self-selected for smoking status. Subjects were pre-screened by medical staff at an independent clinical research unit, within 1 week prior to a single overnight residential visit and sample collection. Results: All BoE were able to differentiate between the two smoking groups and smokers from all non-smokers. There was a strong correlation between cigarettes smoked per day and total urinary nicotine equivalents (TNE; r=0.85). TNE correlated better with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels than cigarettes smoked per day (r=0.75 and r=0.56, respectively). Of the BoPH included in this study, seven (11-dehydro-thromboxane B2, 2, 3-dinorthromboxane B2, 8-epi prostaglandin F2α, 8-hydroxy-2 deoxyguanosine, cis-thymidine glycol, low-density lipoprotein cholesterol and IgG) were significantly different between the group who smoked more cigarettes per day and never-smokers. These differences became more apparent and extended to the group who smoked 10 or less cigarettes per day, when total urinary recovery values were corrected for creatinine clearance. Conclusions: While BoE clearly differentiate between groups based on self-declared smoking status, most BoPH examined could not do so in a consistent manner. The dynamics of BoPH levels are not well understood. Future studies of BoPH should eliminate potential confounding factors and increase the number of subjects to allow the investigation of genetic polymorphism in metabolic pathways. Clin Chem Lab Med 2009;47:311–20.
Effect of valproic acid on hepatic function

Altered hepatic function tests occurred in four of 25 patients treated with valproic acid. An average dose reduction in three patients of 10 mg per kilogram per day resulted in reversion of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) to normal. The drug was discontinued in one patient. Careful monitoring of hepatic function is required of patients being treated with valproic acid, but our experience suggests that dose reduction alone may be effective in preventing untoward hepatic side effects.
Oral specific hyposensitization in the management of patients allergic to food.

Results are presented of a protocol of hyposensitizing treatment per os in 19 cases of food allergy (allergy to milk in 8, to egg in 8, to fish in 2, and to orange in one). Treatment, performed in the out-patients service, was successful in 14 out of the 15 patients who followed it correctly (i.e. 93.3% of cases). Treatment lasted between 3 and 12 months.
Measuring Learning Outcomes in Higher Education

With the pressing need for accountability in higher education, standardized outcomes assessments have been widely used to evaluate learning and inform policy. However, the critical question on how scores are influenced by students’ motivation has been insufficiently addressed. Using random assignment, we administered a multiple-choice test and an essay across three motivational conditions. Students’ self-report motivation was also collected. Motivation significantly predicted test scores. A substantial performance gap emerged between students in different motivational conditions (effect size as large as .68). Depending on the test format and condition, conclusions about college learning gain (i.e., value added) varied dramatically from substantial gain (d = 0.72) to negative gain (d = −0.23). The findings have significant implications for higher education stakeholders at many levels.
N‐acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat

Partial portal vein ligation (PPVL) leads to the development of a hyperdynamic circulation. It is associated with elevated levels of tumor necrosis factor (TNF‐α) and nitric oxide (NO) production, both of which can result in oxidant injury. In this study, we have investigated whether PPVL is associated with the development of oxidative stress, by measuring urinary F2‐isoprostanes. In addition, we have examined whether N‐acetylcysteine (NAC) can ameliorate oxidant injury and prevent the development of the hyperdynamic circulation. Urinary excretion of F2‐isoprostanes increased sixfold following PPVL together with a significant increase in plasma nitrite and nitrate. Treatment with NAC inhibited the formation of F2‐isoprostanes as well as the increase in plasma nitrite and nitrate. Hemodynamic studies in anesthetized rats showed that following PPVL, cardiac output and portal pressure increased, and systemic vascular resistance decreased, consistent with the development of a hyperdynamic circulation. These changes were prevented by chronic administration of NAC. We conclude that NAC prevents the development of the hyperdynamic circulation and that the formation of reactive oxygen species may be important in the pathogenesis of these hemodynamic changes.
Teaching children with autism to ask questions about hidden objects.

We taught 2 4-year-old children with autism to ask questions of an adult who held a closed box with a toy inside. The treatment package (modeling, prompting, and reinforcement) was evaluated with a multiple baseline design across the three question forms during training, generalization, and follow-up evaluations. The first question form ("What's that? ") produced the name of the hidden item. The second form ("Can I see it? ") produced sight of it, and the third form ("Can I have it? ") produced the item itself. Both children learned to ask questions about hidden objects.
A Serotonin Circuit Acts as an Environmental Sensor to Mediate Midline Axon Crossing through EphrinB2

Modulation of connectivity formation in the developing brain in response to external stimuli is poorly understood. Here, we show that the raphe nucleus and its serotonergic projections regulate pathfinding of commissural axons in zebrafish. We found that the raphe neurons extend projections toward midline-crossing axons and that when serotonergic signaling is blocked by pharmacological inhibition or by raphe neuron ablation, commissural pathfinding is disrupted. We demonstrate that the serotonin receptor htr2a is expressed on these commissural axons and that genetic knock-down of htr2a disrupts crossing. We further show that knock-down of htr2a or ablation of the raphe neurons increases ephrinB2a protein levels in commissural axons. An ephrinB2a mutant can rescue midline crossing when serotonergic signaling is blocked. Furthermore, we found that regulation of serotonin expression in the raphe neurons is modulated in response to the developmental environment. Hypoxia causes the raphe to decrease serotonin levels, leading to a reduction in midline crossing. Increasing serotonin in the setting of hypoxia restored midline crossing. Our findings demonstrate an instructive role for serotonin in axon guidance acting through ephrinB2a and reveal a novel mechanism for developmental interpretation of the environmental milieu in the generation of mature neural circuitry. SIGNIFICANCE STATEMENT We show here that serotonin has a novel role in regulating connectivity in response to the developmental environment. We demonstrate that serotonergic projections from raphe neurons regulate pathfinding of crossing axons. The neurons modulate their serotonin levels, and thus alter crossing, in response to the developmental environment including hypoxia. The findings suggest that modification of the serotonergic system by early exposures may contribute to permanent CNS connectivity alterations. This has important ramifications because of the association between premature birth and accompanying hypoxia, and increased risk of autism and evidence associating in utero exposure to some antidepressants and neurodevelopmental disorders. Finally, this work demonstrates that the vertebrate CNS can modulate its connectivity in response to the external environment.
Effects of the Soluble Fibre Pectin on Intestinal Cell Proliferation, Fecal Short Chain Fatty Acid Production and Microbial Population

Aim: Although pectin, a dietary fibre, has been suggested to possess some trophic effects on the intestine, the mechanisms involved remain unclear. This study aimed to evaluate the effects of pectin on rat intestinal cell proliferation and the intraluminal environment. Methods: Control and pectin-fed rats were given a fibre-free elemental diet (ED) and an ED containing 2.5% pectin, respectively. On the 15th day, the length, weight and number of Ki-67-positive cells from each intestinal segment, and the short chain fatty acids (SCFAs) and microbial population in the caecum were measured. Plasma glucagon-like peptide-2 (GLP-2) concentration and GLP-2 receptor (GLP-2R) mRNA levels in the epithelium were also determined. Results: Pectin supplementation resulted in significant increases in the length, weight, and number of Ki-67-positive cells in the ileum, caecum and colon. Although pectin supplementation did not affect the caecal microbial flora that produced SCFAs, the caecal SCFA content was significantly increased. Pectin supplementation also induced an increase in the plasma GLP-2 concentration, but did not affect the GLP-2R mRNA levels in the small intestine. Conclusions: The increases in the caecal SCFAs and plasma GLP-2 levels induced by pectin supplementation may cause mucosal proliferation in the lower intestinal tract.
Gender and the Physical and Psychosocial Work Environments are Related to Indoor Air Symptoms

Objectives: To assess gender differences in self-reported symptoms, psychosocial, subjective, and objective physical environments. Methods: Staff (N = 173) in four university buildings were investigated by questionnaires, blood samples, and objective assessment of indoor environment (temperature, air velocity, relative humidity, CO2, and dust [PM10]). Analyses were performed by linear and logistic regressions. Results: Women reported health symptoms more often than did men and complained more about physical but not psychosocial factors. Men's symptoms and complaints were more specifically associated to air velocity and humidity. For both genders, symptoms were related to both strain (P = 0.02) and perceived physical environments (P = 0.01). Lower relative humidity in the range of 15% to 35% was associated with perception of too low temperature and dry air. Conclusion: Gender, psychosocial, and physical environment factors were related to symptoms and perceived indoor climate.
Video-assisted thoracoscopic surgery lobectomy at 20 years: a consensus statement.

OBJECTIVE Video-assisted thoracoscopic surgery (VATS) lobectomy has been gradually accepted as an alternative surgical approach to open thoracotomy for selected patients with non-small-cell lung cancer (NSCLC) over the past 20 years. The aim of this project was to standardize the perioperative management of VATS lobectomy patients through expert consensus and to provide insightful guidance to clinical practice. METHODS A panel of 55 experts on VATS lobectomy was identified by the Scientific Secretariat and the International Scientific Committee of the '20th Anniversary of VATS Lobectomy Conference-The Consensus Meeting'. The Delphi methodology consisting of two rounds of voting was implemented to facilitate the development of consensus. Results from the second-round voting formed the basis of the current Consensus Statement. Consensus was defined a priori as more than 50% agreement among the panel of experts. Clinical practice was deemed 'recommended' if 50-74% of the experts reached agreement and 'highly recommended' if 75% or more of the experts reached agreement. RESULTS Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of standardized questionnaires. No statistically significant differences in the responses between the two rounds of questioning were identified. Consensus was reached on 21 controversial points, outlining the current accepted definition of VATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSION The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience.
SUPEROXIDE ANION OVERPRODUCTION IN SEPSIS: EFFECTS OF VITAMIN E AND SIMVASTATIN

Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2°−) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2°− production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2°− production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2°− production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2°− production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2°−. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation.
Functional Mutations in 5′UTR of the BMPR2 Gene Identified in Chinese Families with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasculopathy with significant morbidity and mortality. Bone morphogenetic protein receptor type 2 (BMPR2) has been well recognized as the principal gene responsible for heritable and sporadic PAH. Four unrelated Chinese patients with PAH and their family members, both symptomatic and asymptomatic, were genetically evaluated by sequencing all exons and the flanking regions of BMPR2. Functionality of the aberrant mutations at the 5′ untranslated region (UTR) of BMPR2 in the families with PAH was determined by site mutation, transient transfection, and promoter-reporter assays. Four individual mutations in the BMPR2 gene were identified in the 4 families, respectively: 10-GGC repeats, 13-GGC repeats, 4-AGC repeats in 5–UTR, and a novel missense mutation in exon 7 (c.961C>T; p.Arg321X). Moreover, we demonstrated that (1) these 5′UTR mutations decreased the transcription of BMPR2 and (2) the GGC repeats and AGC repeats in BMPR2 5′UTR bore functional binding sites of EGR-1 and MYF5, respectively. This is the first report demonstrating the presence of functional BMPR2 5′UTR mutations in familial patients with PAH and further indicating that EGR-1 and MYF5 are potential targets for correcting these genetic abnormalities for PAH therapy.
Intravitreal Aflibercept after Bilateral Bevacizumab-Induced Iritis

Purpose To present a case of neovascular age-related macular degeneration treated with aflibercept intravitreal injections after bilateral bevacizumab injections, administered on separate dates, resulted in bilateral iritis. Case Report A 73-year-old woman with a previous history of two episodes of nongranulomatous iritis in her right eye that was believed to be associated with her systemic diagnosis of rheumatoid arthritis was treated with intravitreal bevacizumab injections for bilaterally occurring neovascular age-related macular degeneration. Initial bevacizumab injections in each eye administered sequentially over a week’s time resulted in immediate-onset nongranulomatous iritis in each eye. Subsequent intravitreal injections of aflibercept were administered, and therapeutic benefit was achieved without occurrence of iritis. Conclusions In cases where intravitreal bevacizumab results in anterior uveitis, aflibercept may be a safe alternative therapeutic choice for the treatment of neovascular age-related macular degeneration.
Happiness and Time Preference: The Effect of Positive Affect in a Random-Assignment Experiment

We conduct a random-assignment experiment to investigate whether positive affect impacts time preference, where time preference denotes a preference for present over future utility. Our result indicates that, compared to neutral affect, mild positive affect significantly reduces time preference over money. This result is robust to various specification checks, and alternative interpretations of the result are considered. Our result has implications for the effect of happiness on time preference and the role of emotions in economic decision making, in general. Finally, we reconfirm the ubiquity of time preference and start to explore its determinants. (JEL D12, D83, I31)
Trafficking of dietary fat in lean rats.

Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA). An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, 14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic rate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 +/- 0.45 nmols) and CO2 (0.25 +/- 0.01 nmols) than was found in adipose tissue (0.71 +/- 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the 14C content of muscle, liver and GI tract, associated with a net rise in the 14C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10-24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term "trafficking" than by the more commonly used term "partitioning. " Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.