Miracle-dz/UniFAR-FTUs huggingface dataset:
Narrowing of the region of allelic loss in 21q11‐21 in squamous non‐small cell lung carcinoma and cloning of a novel ubiquitin‐specific protease gene from the deleted segment

We examined 42 fresh non‐small cell lung carcinomas for allelic loss using 4 microsatellite markers located in a 4.5 Mb region in 21q11‐21, a gene‐poor interval recently found by others to be homozygously deleted and exhibiting frequent allelic loss in lung cancer. We found allelic loss across the entire segment in 13/34 informative squamous carcinomas, with 2 cases showing loss in only part of the region. Analysis by fluorescence in situ hybridization of P1‐derived artificial chromosomes from the region directly on paraffin sections of the tumor is in concordance with the loss of heterozygosity (LOH) results, and tentatively excludes a 2 Mb segment bearing 2 of the only 3 known genes in the area. Exon trapping in the remaining segment of loss led to identification and cloning of a novel gene spanning 150 kb within the deletion. The full‐length gene encodes a protein of 1,055 amino acids with homology to ubiquitin‐specific proteases across the eukaryotic evolutionary spectrum. The expressed protein acts as a de‐ubiquitinating enzyme as proved by the ability to cleave ubiquitin from a model fusion protein. We found no mutations in the sequence of the functional domains of this gene in any of the LOH‐exhibiting tumor DNA samples. It is, however, interesting that genes of the same superfamily have been reported on 3p21, a locus showing the most frequent allelic instability and deletions in lung cancer. Genes Chromosomes Cancer 27:153–161, 2000. © 2000 Wiley‐Liss, Inc.
Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

Background: Factors mediating orofacial neuropathic pain are not well defined. Results: Trigeminal nerve injury-induced calcium channel α2δ1 protein up-regulation in trigeminal ganglia and spinal complex correlated with enhanced spinal presynaptic neurotransmission, excitatory synaptogenesis, and orofacial pain states. Conclusion: This neuroplasticity may mediate orofacial neuropathic pain states by enhancing dorsal horn excitatory synaptic neurotransmission. Significance: This reveals a mechanism underlying orofacial neuropathic pain states. To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2.
Catenary cultures of embryonic gastrointestinal tract support organ morphogenesis, motility, neural crest cell migration, and cell differentiation

The embryonic gastrointestinal tract develops from a simple tube into a coiled, flexed, and regionalized structure. The changes in gut morphology coincide with the differentiation of multiple cell types in concentric layers, and include colonization by migratory neuron precursors, and the development of gastrointestinal motility. We describe a reliable method for growing embryonic mouse intestine in vitro by the attachment of segments of intestinal tract by their cut ends, with the intervening region suspended in the culture medium. These are termed “catenary cultures. ” E11‐E11.5 mouse midgut, hindgut, or mid‐ plus hindgut segments were grown in catenary culture for up to 10 days and their growth, morphology, cell differentiation, ability to support neural precursor migration, and contractile activity were assessed. The increase in size of the cultured explants was not large, but morphogenesis proceeded, best exemplified by elongation of the caecum. Cell differentiation also proceeded. In the mucosa, goblet cells differentiated. Muscle layers, characterized by desmin expression, and kit‐positive interstitial cells of Cajal differentiated in the correct positions. Where segments initially included neural precursors in a small sub‐region, these migrated and proliferated to form uniform neuronal networks throughout the entire explant, and the cells expressed the neuron markers nitric oxide synthase and neuron specific enolase. Gut motility was attained 5–6 days into the culture period, and both contractile‐ and mixing‐type movements were observed. Thus, cell types representative of all three germ layer contributions developed, and in addition, the gut, being mainly free, was able to elongate and bend (unlike on solid support cultures), while retaining its rostrocaudal identity. Dev Dyn 1999;214:239–247. © 1999 Wiley‐Liss, Inc.
HIF 1 α-Induced by Lysophosphatidic Acid Is Stabilized via Interaction with MIF and CSN 5

Macrophage migration inhibitory factor (MIF) is a cytokine that has broad effects on immune system and inflammatory response. A growing body of evidence implicates the role of MIF in tumor growth and metastasis. Lysophosphatidic acid (LPA), a bioactive lipid mediator, regulates colon cancer cell proliferation, invasion, and survival through LPA2 receptor. Loss of LPA2 results in decreased expression of MIF in a rodent model of colon cancer, but the mechanism of MIF regulation by LPA is yet to be determined. In this study, we show that LPA transcriptionally regulates MIF expression in colon cancer cells. MIF knockdown decreased LPA-mediated proliferation of HCT116 human adenocarcinoma cells without altering the basal proliferation rates. Conversely, extracellular recombinant MIF stimulated cell proliferation, suggesting that the effect of MIF may in part be mediated through activation of surface receptor. We have shown recently that LPA increases hypoxia-inducible factor 1α (HIF1α) expression. We found that MIF regulation by LPA was ablated by knockdown of HIF1α, indicating that MIF is a transcriptional target of HIF1α. Conversely, knockdown of MIF ablated an increase in HIF1α expression in LPA-treated cells, suggesting a reciprocal relationship between HIF1α and MIF. LPA stimulated co-immunoprecipitation of HIF1α and MIF, indicating that their association is necessary for stabilization of HIF1α. It has been shown previously that CSN9 signalosome subunit 5 (CSN5) interacts with HIF1α to stabilize HIF1α under aerobic conditions. We found that LPA did not alter expression of CSN5, but stimulated its interaction with HIF1α and MIF. Depletion of CSN5 mitigated the association between HIF1α and MIF, indicating that CSN5 acts as a physical link. We suggest that HIF1α, MIF, and CSN5 form a ternary complex whose formation is necessary to prevent degradation of HIF1α under aerobic conditions.
Underconnectivity between voice-selective cortex and reward circuitry in children with autism

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.
Development of an Algorithm to Identify Preoperative Medical Consultations Using Administrative Data

Background:Preoperative consultation by internal medicine specialists may help improve the care of patients undergoing major surgery. Population-based administrative data are an efficient approach for studying these consultations at a population-level. However, administrative data in many jurisdictions lack specific codes to identify preoperative medical consultations, as opposed to consultations for nonoperative indications. Objective:To develop an accurate claims-based algorithm for identifying preoperative medical consultations before major elective noncardiac surgery. Research Design:We conducted a multicenter cross-sectional study in Ontario, Canada. Preoperative medical consultations identified by medical record abstraction were compared with those identified by linked administrative data (physician service claims, hospital discharge abstracts). Subjects:We randomly selected 606 individuals, aged older than 40 years, who underwent elective intermediate-to-high-risk noncardiac surgery at 8 randomly selected hospitals between April 1, 2002 and March 31, 2004. Results:Medical record abstraction identified preoperative medical consultations in 317 patients (52%). The optimal claims-based algorithm for identifying these consultations was a physician service claim for a consultation by a cardiologist, general internist, endocrinologist, geriatrician, or nephrologist within 4 months before the index surgical procedure. This algorithm had a sensitivity of 90% (95% confidence interval [CI]: 86–93), specificity of 92% (95% CI: 88–95), positive predictive value of 93% (95% CI: 89–95), and negative predictive value of 90% (95% CI: 86–93). Conclusions:A simple claims-based algorithm can accurately identify preoperative medical consultations before major elective noncardiac surgery. This algorithm may help enhance population-based evaluations of preoperative care, provided that the requisite linked administrative healthcare data are present.
Advances in directed molecular evolution of reporter genes

Many reporter genes, such as gfp, gusA, and lacZ, are widely used for research into plants, animals, and microorganisms. Reporter genes, which offer high levels of sensitivity and convenience of detection, have been utilized in transgenic technology, promoter analysis, drug screening, and other areas. Directed molecular evolution is a powerful molecular tool for the creation of designer proteins for industrial and research applications, including studies of protein structure and function. Directed molecular evolution is based mainly on in vitro recombination methods, such as error-prone PCR and DNA shuffling. The strategies of directed evolution of enzyme biocatalysts have been the subject of several recent reviews. Here, we briefly summarize successes in the field of directed molecular evolution of reporter genes and discuss some of the applications.
Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair

Objective Conflicting data have been reported in the association between maternal smoking and adverse effects during pregnancy and in neonates. Some studies, conducted on a limited number of patients have evaluated maternal consumption and fetal exposure by measuring nicotine and cotinine in the hair. Our aims were to evaluate the relationship among maternal cigarette consumption, fetal smoking exposure and outcome of pregnancy in a population of pregnant women who smoked.
Educating immigrant children in the United States: A mixed methods analysis of achievement of Hispanic students in Pennsylvania

The education of immigrant students in the U.S., especially those of Hispanic origin, poses an important challenge to education policy because: i) there is a considerable achievement gap between Hispanic students and White students; ii) Hispanic students are over-represented within the English language learner population; and iii) Hispanic students remain more likely than other immigrant students to come from disadvantaged families. This dissertation identifies the necessary determinants of achievement for Hispanic students while systematically illustrating a number of public policy challenges that constraint educators in Pennsylvania, a state experiencing a recent and a rapid surge of Hispanic immigrants. It specifically asks: What are the effects of student background characteristics and school attributes on individual performance of Hispanic students? What are the main challenges that schools encounter when serving this population? And, what policy recommendations could contribute to enhance the achievement of Hispanic students? To answer these questions satisfactorily, it draws on literatures and methods from three scholarships: Education, Applied Linguistics, and Sociology of Immigration. It utilizes case studies and applies Hierarchical Linear Modeling to a state representative sample of students who took the Pennsylvania System of School Achievement test during 2009, 2010, and 2011. Findings suggest that student background characteristics significantly predict achievement among Hispanic students and their effect is larger than those of school attributes. The major challenges that schools face in relation to teaching Hispanic students include the English language barrier, a poor academic background knowledge, and low parental involvement. Three strategies showed to be highly effective to address these challenges: constant monitoring of student’s achievement; use of achievement data to inform instructional decisions and tailor interventions to individual students’ needs; and the existence of ESL certified teachers and bilingual school staff. Based on these findings, policy recommendations are offered at the school and district level.
Comparison of the Lysis Centrifugation Method with the Conventional Blood Culture Method in Cases of Sepsis in a Tertiary Care Hospital

Introduction: Physicians and microbiologists have long recognized that the presence of living microorganisms in the blood of a patient carries with it considerable morbidity and mortality. Hence, blood cultures have become critically important and frequently performed test in clinical microbiology laboratories for diagnosis of sepsis. Objectives: To compare the conventional blood culture method with the lysis centrifugation method in cases of sepsis. Materials and Methods: Two hundred nonduplicate blood cultures from cases of sepsis were analyzed using two blood culture methods concurrently for recovery of bacteria from patients diagnosed clinically with sepsis – the conventional blood culture method using trypticase soy broth and the lysis centrifugation method using saponin by centrifuging at 3000 g for 30 minutes. Results: Overall bacteria recovered from 200 blood cultures were 17.5%. The conventional blood culture method had a higher yield of organisms, especially Gram positive cocci. The lysis centrifugation method was comparable with the former method with respect to Gram negative bacilli. The sensitivity of lysis centrifugation method in comparison to conventional blood culture method was 49.75% in this study, specificity was 98.21% and diagnostic accuracy was 89.5%. In almost every instance, the time required for detection of the growth was earlier by lysis centrifugation method, which was statistically significant. Contamination by lysis centrifugation was minimal, while that by conventional method was high. Time to growth by the lysis centrifugation method was highly significant (P value 0.000) as compared to time to growth by the conventional blood culture method. Conclusion: For the diagnosis of sepsis, combination of the lysis centrifugation method and the conventional blood culture method with trypticase soy broth or biphasic media is advocable, in order to achieve faster recovery and a better yield of microorganisms.
Supercooling Points of Murgantia histrionica (Hemiptera: Pentatomidae) and Field Mortality in the Mid-Atlantic United States Following Lethal Low Temperatures

Abstract The harlequin bug, Murgantia histrionica (Hahn), is a serious pest of brassicaceous vegetables in southern North America. While this insect is limited in its northern range of North America, presumably by severe cold winter temperatures, specific information on its cold hardiness remains unknown. We determined the supercooling points (SCPs) for Maryland and Virginia adult populations and found no significant difference among these populations. SCPs were similar for adults (x̄ = –10.35 °C; σX = 2.54) and early and late instar (x̄ = –11.00 °C; σX = 4.92) and between adult males and females. However, SCPs for first instars (x̄ = –21.56 °C; σX =1.47) and eggs (x̄ = –23.24°C; σX =1.00) were significantly lower. We also evaluated field survival of overwintering harlequin bug adults during extreme cold episodes of January 2014 and January 2015, which produced widespread air temperatures lower than –15 °C and subfreezing soil temperatures in the Mid-Atlantic Region. After the 48-h episode in 2014, bug mortality in exposed field sites averaged 88%, compared to <5% mortality of bugs sheltered in an unheated greenhouse (recorded minimum temperature 4.4 °C). After the 2015 episode, ∼80% of adults that were established in the field the previous November and then sheltered in an unheated garage during the episode, died, in contrast to 96% mortality in exposed field sites. Our results provide new information on M. histrionica overwintering biology, and thermal limitations to its distribution, which leads to improved predictive capabilities to forecast pest severity.
The Effects of High Performance Work Systems on International Governmental Organizations: A Study of the United Nations Relief and Works Agency for Palestine Refugees in the Near East Headquarters

In the last three decades, a growing body of research has suggested that using a mix or system of human resources management (HRM) practices can lead to superior organizational performance. These practices (such as selective recruitment and hiring procedures, performance-based compensation systems, employee participation, and training and development) have been referred to as high performance work systems (HPWS) and originated from the study of strategic human resource management (SHRM), where researchers have examined the impact of these systems on organizational performance outcomes. The relationship between HRM and organizational performance has received increasing interest from scholars and practitioners in the field of public administration. Scholars strive to identify the effects of HRM practices on organizational performance based on the notion that these practices will lead to enhanced attitudinal outcomes, such as organizational commitment, job satisfaction, and motivation, which will have positive impacts on organizational performance. This study contributes to further our understanding of the impact of management on performance in public organizations through empirical evidence drawn from theories of HRM. The growing interest among scholars in understanding the effects of management on performance presumes that the adoption of best practices will lead to improvements in organizational performance. The purpose of this mixed-methods study is to examine the effects of HPWS practices on individual worker attitudes in international governmental organizations (IGOs) by reporting the results of a staff survey and follow-up interviews conducted on a crosssection of the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) employees. The UNRWA is an international relief and human
Plasmacytoid Dendritic Cell Precursors Induce Allogeneic T‐Cell Hyporesponsiveness and Prolong Heart Graft Survival

Dendritic cell (DC) precursors were propagated from C57BL/10 (B10; H2b) mouse bone marrow in fms‐like tyrosine kinase 3 ligand. Cosignaling molecule (B7‐1/B7‐2 and B7‐H1) expression and stimulatory capacity of precursor (pre)‐plasmacytoid (p)DC (CD11c+B220+CD11b−CD19−) and classic myeloid DC (MDC) for allogeneic (C3H; H2k) T cells were compared. Unstimulated pre‐pDC exhibited very low levels of surface MHC class II and classic costimulatory molecules (B7‐1/B7‐2), whereas a minor population expressed B7‐H1 at levels higher than on MDC. The pre‐pDC were ineffective T‐cell stimulators and induced nonspecific hyporesponsiveness to rechallenge with donor alloantigens in vitro and in vivo. Following stimulation with CpG‐oligonucleotide (CpG‐ODN), B7 molecule expression was upregulated on pre‐pDC, however the ratio between coinhibitory (B7‐H1) and costimulatory (B7‐1/B7‐2) signals was much higher (five‐ to six‐fold) on pre‐pDC than MDC. Blockade of B7‐H1 expression on pDC increased their T‐cell allostimulatory capacity significantly. A single preoperative infusion of C3H hosts with pre‐pDC prolonged B10 heart graft survival significantly but nonspecifically compared with untreated mice (median survival times 22 vs. 9 days, respectively). Thus, pre‐pDC of donor origin have potential to regulate T‐cell responses to alloantigens and can prolong organ graft survival.
Differential depression of myocardial function and metabolism by lactate and H 1

MICHELE SAMAJA,1 SONIA ALLIBARDI,1 GIUSEPPINA MILANO,1 GABRIELLA NERI,1 BRUNO GRASSI,2 L. BRUCE GLADDEN,3 AND MICHAEL C. HOGAN4 1Dipartimento di Scienze e Tecnologie Biomediche, University of Milan, I-20090 Milan, Italy; 2Istituto di Tecnologie Biomediche Avanzate, CNR, I-20090 Milan, Italy; 3Department of Health and Human Performance, Auburn University, Alabama 36849-5323; and 4Department of Medicine, University of California, San Diego 92093-0623