319 research outputs found
RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins
The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning
The Vehicle, Fall 1986
Table of Contents
Selling Poetry: Honesty with the InvestorPatrick Peterspage 2
Father\u27s Book, Jan. 1984 (A Fictional Autobiography)James T. Finneganpage 3
Pet Day in Afternoon KindergartenDan Von Holtenpage 7
Dental Dreams in the Bathroom MirrorDan Von Holtenpage 7
PhotographStephanie Eihlpage 8
SilenceJoe Hortonpage 8
SkullMichael Salempage 9
The TunnelJim Harrispage 10
Lindenwood CemeteryJean Chandlerpage 12
Into the SeaDan Seltzerpage 13
PhotographStephanie Eihlpage 13
WindowsJim Harrispage 14
Little Pieces of YouStuart Albertpage 18
Slicing the AppleAmy Callpage 19
Winter WalkLarry Mitchellpage 19
Komical KellyJohn Fehrmannpage 20
Thermal SueJohn Fehrmannpage 20
Death PoemBob Zordanipage 21
Venice, ItalySherry L. Clinepage 22
RoadkillPhil Simpsonpage 24
I Hate CowsLori Delzer, Joe Crites, Becky Michaelpage 32
Telephone Operators: 1942Jim Harrispage 33
Expiration Date 3/8/65Edward Schellpage 34
Desert FloorPatrick Peterspage 35
PhotographLawrence McGownpage 36
PhotographStephanie Eihlpage 37
Coping with NightStuart Albertpage 38
PhotographDan Mountpage 38
One On OnePatrick Peterspage 39
An Acquired TasteTina Wrightpage 40
PhotographStephanie Eihlpage 40
PhotographStephanie Eihlpage 41
When Children Are Alone, The Devil SpeaksTom Greenpage 41
BobChristy Denphypage 42
Gut & ScissorsDane Buczkowskipage 42
This Old HouseAmy Callpage 43
MortgageTina Wrightpage 43https://thekeep.eiu.edu/vehicle/1048/thumbnail.jp
The Vehicle, Fall 1986
Table of Contents
Selling Poetry: Honesty with the InvestorPatrick Peterspage 2
Father\u27s Book, Jan. 1984 (A Fictional Autobiography)James T. Finneganpage 3
Pet Day in Afternoon KindergartenDan Von Holtenpage 7
Dental Dreams in the Bathroom MirrorDan Von Holtenpage 7
PhotographStephanie Eihlpage 8
SilenceJoe Hortonpage 8
SkullMichael Salempage 9
The TunnelJim Harrispage 10
Lindenwood CemeteryJean Chandlerpage 12
Into the SeaDan Seltzerpage 13
PhotographStephanie Eihlpage 13
WindowsJim Harrispage 14
Little Pieces of YouStuart Albertpage 18
Slicing the AppleAmy Callpage 19
Winter WalkLarry Mitchellpage 19
Komical KellyJohn Fehrmannpage 20
Thermal SueJohn Fehrmannpage 20
Death PoemBob Zordanipage 21
Venice, ItalySherry L. Clinepage 22
RoadkillPhil Simpsonpage 24
I Hate CowsLori Delzer, Joe Crites, Becky Michaelpage 32
Telephone Operators: 1942Jim Harrispage 33
Expiration Date 3/8/65Edward Schellpage 34
Desert FloorPatrick Peterspage 35
PhotographLawrence McGownpage 36
PhotographStephanie Eihlpage 37
Coping with NightStuart Albertpage 38
PhotographDan Mountpage 38
One On OnePatrick Peterspage 39
An Acquired TasteTina Wrightpage 40
PhotographStephanie Eihlpage 40
PhotographStephanie Eihlpage 41
When Children Are Alone, The Devil SpeaksTom Greenpage 41
BobChristy Denphypage 42
Gut & ScissorsDane Buczkowskipage 42
This Old HouseAmy Callpage 43
MortgageTina Wrightpage 43https://thekeep.eiu.edu/vehicle/1048/thumbnail.jp
Characterisation and expression of calpain family members in relation to nutritional status, diet composition and flesh texture in gilthead sea bream (Sparus aurata).
Calpains are non-lysosomal calcium-activated neutral proteases involved in a wide range of cellular processes including muscle proteolysis linked to post-mortem flesh softening. The aims of this study were (a) to characterise several members of the calpain system in gilthead sea bream and (b) to examine their expression in relation to nutritional status and muscle tenderisation. We identified the complete open reading frame of gilthead sea bream calpains1-3, sacapn1, sacapn2, sacapn3, and two paralogs of the calpain small subunit1, sacapns1a and sacapns1b. Proteins showed 63-90% sequence identity compared with sequences from mammals and other teleost fishes, and the characteristic domain structure of vertebrate calpains. Transcripts of sacapn1, sacapn2, sacapns1a and sacapns1b had a wide tissue distribution, whereas sacapn3 was almost exclusively detected in skeletal muscle. Next, we assessed transcript expression in skeletal muscle following alteration of nutritional status by (a) fasting and re-feeding or (b) feeding four experimental diets with different carbohydrate-to-protein ratios. Fasting significantly reduced plasma glucose and increased free fatty acids and triglycerides, together with a significant increase in sacapns1b expression. Following 7 days of re-feeding, plasma parameters returned to fed values and sacapn1, sacapn2, sacapns1a and sacapns1b expression was significantly reduced. Furthermore, an increase in dietary carbohydrate content (11 to 39%) diminished growth but increased muscle texture, which showed a significant correlation with decreased sacapn1 and sacapns1a expression, whilst the other calpains remained unaffected. This study has demonstrated that calpain expression is modulated by nutritional status and diet composition in gilthead sea bream, and that the expression of several calpain members is correlated with muscle texture, indicating their potential use as molecular markers for flesh quality in aquaculture production
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
Naturally Occurring Genetic Variants in Human Chromogranin A (CHGA) Associated with Hypertension as well as Hypertensive Renal Disease
Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 3′-UTR. In chromaffin cell-transfected CHGA 3′-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3′-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 3′-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects
Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017
Background
Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout.
Methods
The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function.
Findings
Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function.
Interpretation
Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI
Violent masculinities: Gendered dynamics of policing in Rio de Janeiro
Historically, policing in Rio de Janeiro has been shaped by the equation of racialized violence and masculinity. Attempts to reform the police have paradoxically drawn on forms of male violence that are centered on the rational and professional use of force and on “softer” practices, such as dialogue and collaboration, symbolically coded as feminine. The failure of police reform reflects the cultural salience of understandings of masculinity centered around violence within the police, historical patterns of policing in Rio, and political actors’ strategic cultivation of male violence. Through Rio de Janeiro's failed attempt at police reform, we theorize the relation between racialized state violence, authoritarian political projects, and transgressive forms of male violence, arguing that an important appeal of authoritarianism lies in its promise to carve out a space for performing what we call wild masculinity. [masculinity, race, police, violence, gender, politics, favela, Rio de Janeiro, Brazil]publishedVersio
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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