Miracle-dz/UniFAR-FTUs huggingface dataset:
DMRT1 Is Upregulated in the Gonads During Female-to-Male Sex Reversal in ZW Chicken Embryos1

Abstract Sex in birds is chomosomally based (ZZ male, ZW female), but the mechanism underlying sex determination remains unknown. An unresolved question is whether Z gene dosage plays a role in avian sex determination. DMRT1 is an avian Z-linked gene that shows higher expression in male gonads during embryogenesis and has been proposed as a putative testis-determining gene in birds. The Z-linkage of this gene makes it an ideal candidate for testing the question of gene dosage in avian testis determination. A higher level of DMRT1 expression in male (ZZ) versus female (ZW) embryonic gonads may reflect the presence of two Z-linked copies in the male, or it may be due to specific and active upregulation of DMRT1 during testis formation. A functional interventionist strategy was used to distinguish between these two possibilities. DMRT1 expression was analyzed in chicken embryos during experimentally induced female-to-male sex reversal, using the aromatase enzyme inhibitor fadrozole. DMRT1 expression was analyzed by whole mount in situ hybridization and reverse transcription polymerase chain reaction (for mRNA) and indirect immunofluorescence (for protein). Female-to-male sex-reversed embryos (genetically ZW) showed elevated levels of DMRT1 expression similar to those of normal males (with two copies of the Z chromosome). Elevated levels of DMRT1 are therefore associated with testis development, both in normal males (ZZ) and in sex-reversed females (ZW). SOX9 expression was also activated during female-to-male sex reversal but appeared delayed relative to DMRT1 upregulation. These results show that testis development does not require two Z-linked copies of DMRT1, but it does involve active upregulation of the gene. Higher levels of DMRT1 expression during testis differentiation therefore do not simply reflect a gene dosage difference between the two sexes but imply active involvement in male development.
Matrix Multiplication on Heterogeneous Platforms

We address the issue of implementing matrix multiplication on heterogeneous platforms. We target two different classes of heterogeneous computing resources: heterogeneous networks of workstations and collections of heterogeneous clusters. Intuitively, the problem is to load balance the work with different speed resources while minimizing the communication volume. We formally state this problem in a geometric framework and prove its NP-completeness. Next, we introduce a (polynomial) column-based heuristic, which turns out to be very satisfactory: We derive a theoretical performance guarantee for the heuristic and we assess its practical usefulness through MPI experiments.
Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting.

UNLABELLED The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions. SIGNIFICANCE We found that the number of CRISPR/Cas9-induced DNA breaks dictates a gene-independent antiproliferative response in cells. These observations have practical implications for using CRISPR/Cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies. Cancer Discov; 6(8); 914-29. ©2016 AACR.See related commentary by Sheel and Xue, p. 824See related article by Munoz et al., p. 900This article is highlighted in the In This Issue feature, p. 803.
Reliability of grating couplers incorporated on integrated interferometric biosensors

Sub-micronic grating couplers have been integrated on optical waveguides for efficient light in-coupling into interferometric biosensors. Design and fabrication processes are presented as well as the results of the optical characterization and the sensing evaluation. Keywords-Grating couplers; interferometers; biosensors; integrated optics.
Imaging Epidermal Growth Factor Receptor Expression In vivo: Pharmacokinetic and Biodistribution Characterization of a Bioconjugated Quantum Dot Nanoprobe

Purpose: To develop and validate an optical imaging nanoprobe for the discrimination of epidermal growth factor (EGF) receptor (EGFR)–overexpressing tumors from surrounding normal tissues that also expresses EGFR. Experimental Design: Near-infrared (NIR) quantum dots (QD) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. In vitro binding affinity of these nanoprobes and unconjugated QDs was evaluated in a panel of cell lines, with and without anti-EGFR antibody pretreatment. Serial optical imaging of HCT116 xenograft tumors was done after systemic injection of QD and EGF-QD. Results: EGF-QD showed EGFR-specific binding in vitro. In vivo imaging showed three distinct phases, tumor influx (∼3 min), clearance (∼60 min), and accumulation (1-6 h), of EGF-QD nanoprobes. Both QD and EGF-QD showed comparable nonspecific rapid tumor influx and clearance followed by attainment of an apparent dynamic equilibrium at ∼60 min. Subsequently (1-6 h), whereas QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. On delayed imaging at 24 h, tumor fluorescence decreased to near-baseline levels for both QD and EGF-QD. Ex vivo whole-organ fluorescence, tissue homogenate fluorescence, and confocal microscopic analyses confirmed tumor-specific accumulation of EGF-QD at 4 h. Immunofluorescence images showed diffuse colocalization of EGF-QD fluorescence within EGFR-expressing tumor parenchyma compared with patchy perivascular sequestration of QD. Conclusion: These results represent the first pharmacokinetic characterization of a robust EGFR imaging nanoprobe. The measurable contrast enhancement of tumors 4 h after systemic administration of EGF-QD and its subsequent normalization at 24 h imply that this nanoprobe may permit quantifiable and repetitive imaging of EGFR expression.
Genetics of Human Obesity: An Overview

Abstract Obesity is a complex, heterogeneous group of disorders that is determined by genes, environmental factors and interaction between genes and environment. Body Mass Index (BMI) is a proxy measure for obesity and is the most commonly studied marker for it. Obesity is becoming an increasingly important clinical and public health challenge through out the world. It is associated not only with an increased burden of non-insulin diabetes, hypertension, cardiovascular diseases, some types of cancers and premature mortality but also with the social and psychological effects of excess weight. Because of its larger population size, the developing world has faced with larger burden of overweight and obesity. Several studies have shown that changes in dietary patterns, physical activity levels and life styles associated with diet and urbanization are related to increasing incidence of obesity in India. The risk of obesity is about two to three times higher for an individual with a family history of obesity and it increases with the severity of obesity. In this paper, we present a broad historical overview of the studies on the genetic etiology of human obesity, including the recent studies involving candidate gene and whole genome scan approaches using case-control and family samples. The uniqueness of Indian population structure and its relevance to understanding and/or for disentangling the genetic etiology of complex genetic disorders in general and particularly of human obesity has been emphasized.
Volume, rates, source and types of add-on pathology test requests across five hospitals

Abstract Background: Add-on test requests, where a clinician requests further test assays on an existing specimen, contribute disproportionately to pathology service workload. However, little research has quantified the volume, rates, source or types of add-on tests. This study provides a descriptive analysis of add-on testing within a pathology service serving five hospitals. Methods: We analyzed 6 months of test data extracted from a pathology service in metropolitan Sydney, Australia. Add-on requests were analyzed in terms of total volume and as a proportion of all test requests and test assays; ten most frequently requested add-on test types for clinical chemistry and hematology; by patient registration category; and proportions of add-on requests received within 1-, 4-, 8-, and 24-h of specimen collection. Results: Add-on test requests constituted 3.7% (n=19,541) of the total 529,361 test requests. Clinical chemistry and hematology add-on requests accounted for 76.9% of all add-on requests. The add-on request rate was higher in the clinical chemistry (5.4%) than in hematology (1.3%). Patients who entered hospital via the emergency department had the highest rates of add-on requests. A total of 79.5% of add-on requests across the pathology service were made within 24-h of specimen collection. Conclusions: The volume of add-on requests is substantial and varies considerably by test type and patient registration category thus impacting differentially upon pathology service departments. While some add-on requests are unavoidable in clinical practice, others are precipitated by inadequate information at the point of care. Improving appropriate utilization of add-on testing will reduce their burden on pathology services.
Negotiating the ‘real’ in ‘reality shows’: production side discourses between deconstruction and reconstruction

In this study, we set out to elaborate configurations of the ‘real’ and ‘authentic’ in the discourses of program makers and participants of ‘reality shows’. This production side perspective has more often been the object, rather than the subject, in the debate. We develop our argument through a theoretically informed discussion at the intersection of cultural and documentary studies. Our analysis proceeds through a thematic content analysis of 39 semi-structured, in-depth interviews with 14 television professionals and 25 participants involved in the production of formats belonging to various subgenres, all with a border-crossing circulation. The analysis demonstrates that when gauging ‘the real’ in ‘reality shows’, participants and program makers do not subscribe to a ‘naïve realistic’ celebration, as the ‘reality TV’ denominator may suggest, yet, nonetheless still strongly invest in a sense of the ‘real’ or ‘authentic’. As such, they engage in a sophisticated, dynamic and, so it could be argued, strategic shifting to-and-fro deconstructive and reconstructive positions. What ensues from this dialog between deconstruction and reconstruction is a conception of the ‘reality show’ as a nodal point of the multiple and ever-evolving configurations of the ‘real’ and the ‘authentic’ in a reflexive, media-savvy culture.
Excitation of motoneurons by the Mauthner axon in goldfish: complexities in a "simple" reticulospinal pathway.

1. The Mauthner cell in fish and amphibians initiates an escape behavior that has served as a model system for studies of the reticulospinal control of movement. This behavior consists of a very rapid bend of the body and tail that is thought to arise from the monosynaptic excitation of large primary motoneurons by the Mauthner cell. Recent work suggests that the excitation of primary motoneurons might be more complex than a solely monosynaptic connection. To examine this possibility, I used intracellular recording and staining to study the excitation of primary motoneurons by the M cell. 2. Simultaneous intracellular recordings from the M axon and ipsilateral primary motoneurons show that firing the M cell leads to complex postsynaptic potentials (PSPs) in the motoneurons. These PSPs usually have three components: an early, small, slow depolarization (component 1), a later, large, fast depolarization (component 2), and an even later, large, long-lasting depolarization (component 3). The first component has a latency of 0.52 +/- 0.15 (SD) ms, (n = 27) and most probably is a monosynaptic input from the M cell. This study focused on the two subsequent, less-understood parts of the PSP. Motoneurons typically fire off the second part of the PSP. This is usually (27 of 33 cells) the largest component, and it has a mean amplitude of 6.24 +/- 3.33 (SD) mV (n = 33) and a half-decay time of 0.44 +/- 0.18 (SD) ms (n = 27). The mean amplitude of the third component is 3.20 +/- 1.7 (SD) mV (n = 35), and its half-decay is 6.73 +/- 2.66 (SD) ms (n = 35). The latency of the second component averages 0.66 +/- 0.21 (SD) ms (n = 32), indicating that there are few synapses in the pathway mediating it. 3. One candidate pathway for the second component of the PSP involves a class of descending interneurons (DIs) that are monosynaptically, chemically excited by the M cell and appear in light microscopy to contact motoneurons. Simultaneous intracellular recordings from the M axon, a DI, and a primary motoneuron show that the interneurons are electrotonically coupled to motoneurons and produce the fast, second component of the PSP. Direct excitation of an interneuron leads to a very short-latency (less than 0.2 ms), fast PSP in a motoneuron similar to the second component of the PSP produced by the M axon. The short latency and fatigue resistance of this connection indicate it is electrotonic, and this is supported by evidence for DC coupling between the two cells. (ABSTRACT TRUNCATED AT 400 WORDS)
Haemoptysis with a normal chest radiograph: how concerned should we be?

In this issue of Thorax ( see page 854 ), Thirumaran and colleagues describe their experience with a consecutive group of patients evaluated for haemoptysis who had a normal chest radiograph.1 Over a 4-year period these investigators identified 270 patients who were evaluated for this problem. They made two important observations. First, they found that 26 of the 270 patients (9.6%) had respiratory tract malignancies as the cause of the haemoptysis. Of these 26 respiratory tract malignancies, 20 were non-small cell lung cancer (NSCLC) and 2 were small cell lung cancer. Secondly, they performed both fibreoptic bronchoscopy (FOB) and chest CT on the majority of the 270 patients evaluated. Overall, at least 269 FOBs and 257 CTs were performed to diagnose these 22 lung cancers. These observations lead to a series of fundamentally important questions for doctors to consider. Why should haemoptysis with a normal chest radiograph be a concern? Haemoptysis can be massive and life-threatening, by causing either airway compromise or haemodynamic insufficiency. Fortunately, haemoptysis is rarely massive. I work in a busy Intensive Care Unit (ICU; 19 beds and >1500 admissions per year) in a large urban hospital (907 beds and about 47 000 admissions per year) and we see probably only 1–2 cases of massive, life-threatening haemoptysis per year. In the study by Thirumaran et al , of the 275 episodes of haemoptysis, none was massive; the majority were described as simply streaks of bleeding. Although doctors should be aware of the risk of massive haemoptysis, most cases of haemoptysis represent minor bleeding which stops spontaneously. The real concern about haemoptysis with a normal chest radiograph is understanding the cause. As Thirumaran and colleagues point out, haemoptysis should be considered a possible signal of an underlying serious illness, particularly lung cancer. Doctors should not be lulled into believing that …
Mechanism of Action of l-arginine on the Vitality of Spermatozoa is Primarily Through Increased Biosynthesis of Nitric Oxide

Abstract The ability of sperm to fertilize the egg is primarily dependent on sperm motility and membrane integrity. Nitric oxide (NO) plays a decisive role in regulating multiple functions within the male reproductive system. The aim of the present study is to determine the mechanism by which l-arginine confers a protective action on spermatozoa obtained from the goat epididymis. NO is synthesized from l-arginine by the enzyme nitric oxide-synthase (NOS) present in spermatozoa. A possible participation of NO and NOS in arginine action has been suggested.
The Naked Truth: Appearance Discrimination, Employment, and the Law

Physical beauty elicits benefits that are more than skin deep. In every aspect of our lives we are reminded that appearance matters. Evidence suggests that society tends to attribute to those who are physically attractive the added qualities of sociability, friendliness, and competence. ' The appropriate standards for appearance are measured and dictated by societal norms, for which white culture often serves as a reference. Those who do not measure up to society's norms of aesthetics, appearance, and grooming are often perceived as lazy, incompetent, and less productive. Not only do these implicit biases affect social interactions, they also affect one's ability to obtain employment. Employers often use appearance as a signal of an employee's qualifications,2 and even after hiring decisions are made, employers continue to regulate the appearance of their employees through dressing and grooming policies. While such appearance-based decisions are pervasive in the employment context, under current law it is not illegal for an employer to consider appearance when making hiring or other employment decisions. Generally, the only way an aggrieved employee can secure her day in court is by tying her appearance-based complaint to a category protected by Title VII, the Age Discrimination in Employment Act, or the Americans with Disabilities Act. However, because of the manner in which courts currently examine such claims, these statutes are unlikely to provide adequate relief for employees who have experienced appearance-based discrimination. The law's failure to address appearance-based discrimination is problematic
Nondaily smokers: who are they?

OBJECTIVE We sought to understand who constitutes the sizable population of nondaily, or some-day (SD), smokers. METHODS We analyzed descriptive statistics and regression results using the 1998-1999 Current Population Survey Tobacco Use Supplement to determine the prevalence of SD smokers, their sociodemographic characteristics, and the smoking patterns and histories of groups differentiated by the length and stability of their SD smoking. RESULTS SD smokers make up 19.2% of all current smokers. Among SD smokers, 44.6% have smoked less than daily for at least 1 year, no more than 14.4% are just starting to smoke, and the rest are likely in transition. Overall, SD smokers smoked a mean of 102 cigarettes per month (compared to 566.4 for daily smokers), on an average of 14.5 days out of the past 30. CONCLUSIONS SD smokers make up a substantial segment of the smoking population. They are not just beginning to smoke nor trying to quit. Many have developed a long-standing pattern of nondaily smoking, smoking relatively few cigarettes on the days when they do smoke. They are not substantially younger than daily smokers, as one might expect.
Where Deforestation Leads to Urbanization: How Resource Extraction Is Leading to Urban Growth in the Brazilian Amazon

Developing the Amazon into a major provider of internationally traded mineral and food commodities has dramatically transformed broad expanses of tropical forests to farm and pasturelands and to mining sites. The environmental impacts of this transformation, as well as the drivers underlying the process, have already been well documented. In this article we turn our analytical lenses to another, less examined effect of Amazon land use and environmental change, namely, the creation and development of new urban areas. Here we argue that urban growth in the Amazon is a direct residual of international interest in the production of traded commodities and of the capacity of local urban residents to capture capital and value before it is extracted from the region. Specifically, we suggest that urban growth is occurring fastest where cities have access to both rural export commodities and export corridors. We also show correlations between urban growth and lower rural population density and cities' capacities to draw migrants from beyond their immediate rural surroundings. More broadly, we argue that urbanization in the Amazon is better interpreted as a symptom rather than a driver of the region's land use and land cover change.
Activation of nuclear factor κB in inflammatory bowel disease

Background—Expression of pro-inflammatory cytokines is increased in the intestinal lamina propria of patients with inflammatory bowel disease (IBD). Nuclear factor κB (NFκB) controls transcription of inflammation genes. On activation, NFκB is rapidly released from its cytoplasmic inhibitor (IκB), transmigrates into the nucleus, and binds to DNA response elements in gene promoter regions. Aims—To investigate whether increased activation of NFκB is important in IBD and may be down-regulated by anti-inflammatory treatment. Methods—Activation of NFκB was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells. Results—Nuclear levels of NFκB p65 are increased in lamina propria biopsy specimens from patients with Crohn’s disease in comparison with patients with ulcerative colitis and controls. Increased activation of NFκB was detected in lamina propria mononuclear cells from patients with active IBD. Corticosteroids strongly inhibit intestinal NFκB activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor IκBα against activation induced degradation. Conclusions—In both IBDs, but particularly Crohn’s disease, increased activation of NFκB may be involved in the regulation of the inflammatory response. Inhibition of NFκB activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD.