bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live imaging of muscle histolysis in Drosophila metamorphosis
Authors: Kuleesha Yadav , Puah Wee Choo , Wasser Martin 
Published: May 2016

Abstract
Background
The contribution of programmed cell death (PCD) to muscle wasting disorders remains a matter of debate. Drosophila melanogaster metamorphosis offers the opportunity to study muscle cell death in the context of development. Using live cell imaging of the abdomen, two groups of larval muscles can be observed, doomed muscles that undergo histolysis and persistent muscles that are remodelled and survive into adulthood.

Method
To identify and characterize genes that control the decision between survival and cell death of muscles, we developed a method comprising in vivo imaging, targeted gene perturbation and time-lapse image analysis. Our approach enabled us to study the cytological and temporal aspects of abnormal cell death phenotypes.

Results
In a previous genetic screen for genes controlling muscle size and cell death in metamorphosis, we identified gene perturbations that induced cell death of persistent or inhibit histolysis of doomed larval muscles. RNA interference (RNAi) of the genes encoding the helicase Rm62 and the lysosomal Cathepsin-L homolog Cysteine proteinase 1 (Cp1) caused premature cell death of persistent muscle in early and mid-pupation, respectively. Silencing of the transcriptional co-repressor Atrophin inhibited histolysis of doomed muscles. Overexpression of dominant-negative Target of Rapamycin (TOR) delayed the histolysis of a subset of doomed and induced ablation of all persistent muscles. RNAi of AMPKα, which encodes a subunit of the AMPK protein complex that senses AMP and promotes ATP formation, led to loss of attachment and a spherical morphology. None of the perturbations affected the survival of newly formed adult muscles, suggesting that the method is useful to find genes that are crucial for the survival of metabolically challenged muscles, like those undergoing atrophy. The ablation of persistent muscles did not affect eclosion of adult flies.

Conclusions
Live imaging is a versatile approach to uncover gene functions that are required for the survival of muscle undergoing remodelling, yet are dispensable for other adult muscles. Our approach promises to identify molecular mechanisms that can explain the resilience of muscles to PCD.
Longitudinal Associations of Phospholipid and Cholesteryl Ester Fatty Acids With Disorders Underlying Diabetes
Authors: Johnston Luke W. , Harris Stewart B. , Retnakaran Ravi , Zinman Bernard , Giacca Adria , Liu Zhen , Bazinet Richard P. , Hanley Anthony J. 
Published: May 2016

AbstractContext:Specific serum fatty acid (FA) profiles predict the development of incident type 2 diabetes; however, limited longitudinal data exist exploring their role in the progression of insulin sensitivity (IS) and β-cell function.Objective:To examine the longitudinal associations of the FA composition of serum phospholipid (PL) and cholesteryl ester (CE) fractions with IS and β-cell function over 6 years.Design:The Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort is a longitudinal observational study, with clinic visits occurring every 3 years. Three visits have been completed, totaling 6 years of follow-up.Setting:Individuals (n = 477) at risk for diabetes recruited from the general population in London and Toronto, Canada.Main Outcome Measures:Values from an oral glucose tolerance test were used to compute 1/HOMA-IR and the Matsuda index for IS, the insulinogenic index over HOMA-IR, and the insulin secretion-sensitivity index-2 for β-cell function. Thin-layer chromatograph and gas chromatograph quantified FA. Generalized estimating equations were used for the analysis.Results:IS and β-cell function declined by 8.3–19.4% over 6 years. In fully adjusted generalized estimating equation models, PL cis-vaccenate (18:1n-7) was positively associated with all outcomes, whereas γ-linolenate (GLA; 18:3n-6) and stearate (18:0) were negatively associated with IS. Tests for time interactions revealed that PL eicosadienoate (20:2n-6) and palmitate (16:0) and CE dihomo-γ-linolenate (20:3n-6), GLA, and palmitate had stronger associations with the outcomes after longer follow-up.Conclusions:In a Canadian population at risk for diabetes, we found that higher PL stearate and GLA and lower cis-vaccenic acid predicted consistently lower IS and β-cell function over 6 years.
Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey
Authors: Akinci Baris , Onay Huseyin , Demir Tevfik , Ozen Samim , Kayserili Hulya , Akinci Gulcin , Nur Banu , Tuysuz Beyhan , Nuri Ozbek Mehmet , Gungor Adem , Yildirim Simsir Ilgin , Altay Canan , Demir Leyla , Simsek Enver , Atmaca Murat , Topaloglu Haluk , Bilen Habib , Atmaca Hulusi , Atik Tahir , Cavdar Umit , Altunoglu Umut , Aslanger Ayca , Mihci Ercan , Secil Mustafa , Saygili Fusun , Comlekci Abdurrahman , Garg Abhimanyu 
Published: May 2016

Context:
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat.

Objective:
We aimed to study natural history and disease burden of various subtypes of CGL.

Design:
We attempted to ascertain nearly all patients with CGL in Turkey.

Setting:
This was a nationwide study.

Patients or Other Participants:
Participants included 33 patients (22 families) with CGL and 30 healthy controls.

Main Outcome Measure(s):
We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up.

Results:
Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C&gt;A, c.667_705delinsCTGCG, c.268delC, and c.316+1G&gt;T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C&gt;T, c.631delG, c.62A&gt;T, and c.465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c.259C&gt;T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events.

Conclusions:
CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.
DNA Methylation Biphasically Regulates 3T3-L1 Preadipocyte Differentiation
Authors: Yang Xiaosong , Wu Rui , Shan Weiguang , Yu Liqing , Xue Bingzhong , Shi Hang 
Published: May 2016

Abstract
Better understanding the mechanisms underlying adipogenesis may provide novel therapeutic targets in the treatment of obesity. Most studies investigating the mechanisms underlying adipogenesis focus on highly regulated transcriptional pathways; little is known about the epigenetic mechanisms in this process. Here, we determined the role of DNA methylation in regulating 3T3-L1 adipogenesis in early and late stage of differentiation. We found that inhibiting DNA methylation pharmacologically by 5-aza-2′-deoxycytidine (5-aza-dC) at early stage of 3T3-L1 differentiation markedly suppressed adipogenesis. This inhibition of adipogenesis by 5-aza-dC was associated with up-regulation of Wnt10a, an antiadipogenic factor, and down-regulation of Wnt10a promoter methylation. In contrast, inhibiting DNA methylation by 5-aza-dC at late stage of differentiation enhanced the lipogenic program. The differential effects of 5-aza-dC on adipogenesis were confirmed by gain or loss of function of DNA methyltransferase 1 using genetic approaches. We further explored the molecular mechanism underlying the enhanced lipogenesis by inhibition of DNA methylation at late stage of differentiation. The Srebp1c promoter is enriched with CpG sites. Chromatin immunoprecipitation assays showed that DNA methyltransferase 1 bound to the methylation region at the Srebp1c promoter. Pyrosequencing analysis revealed that the DNA methylation at the key cis-elements of the Srebp1c promoter was down-regulated in adipogenesis. Further, luciferase reporter assays showed that the Srebp1c promoter activity was dramatically up-regulated by the unmethylated promoter compared with the fully methylated promoter. Thus DNA methylation appears to exert a biphasic regulatory role in adipogenesis, promoting differentiation at early stage while inhibiting lipogenesis at late stage of 3T3-L1 preadipocyte differentiation.
Lessons Learned from Latin America
Authors: Sommer Doris 
Published: May 2016

AbstractDuring the US Cold War boom in area studies, scholars would sometimes innocently support homeland economic and political interests. In Latin America and elsewhere, the fact-finding focus often morphed into the look of love, as objects of investigation turned out to be more charming than alarming. Inevitably, interrogations led to lessons in sociability and wit to derail some missions promoted by private and public Cold Warriors. Ethical quandaries would soon turn new North American lovers of Latin America toward ironies related to the metaphor of cannibalism that Brazil’s Oswald de Andrade formulated in his 1928 “Manifesto antropófago.” “Who eats whom?” they asked. And, “Is it bad?” For humanists, thanks to theoretical contributions in literary studies by Jorge Luis Borges, and for the range of arts by Luis Camnitzer, scholars north and south have been learning that the vital processes of ingestion and appropriation give flesh and blood to art and to life in general. Reformulating ethical questions, scholars now ask about levels of collaboration and mutual admiration. Interest need not disappear when love arrives. That’s why teachers today (through Pre-Texts, for example) can appropriate the art processes they love in the hope of developing student skills and civility.
Disruption of a cystine transporter downregulates expression of genes involved in sulfur regulation and cellular respiration
Authors: Simpkins Jessica A. , Rickel Kirby E. , Madeo Marianna , Ahlers Bethany A. , Carlisle Gabriel B. , Nelson Heidi J. , Cardillo Andrew L. , Weber Emily A. , Vitiello Peter F. , Pearce David A. , Vitiello Seasson P. 
Published: May 2016

ABSTRACT
Cystine and cysteine are important molecules for pathways such as redox signaling and regulation, and thus identifying cellular deficits upon deletion of the Saccharomyces cerevisiae cystine transporter Ers1p allows for a further understanding of cystine homeostasis. Previous complementation studies using the human ortholog suggest yeast Ers1p is a cystine transporter. Human CTNS encodes the protein Cystinosin, a cystine transporter that is embedded in the lysosomal membrane and facilitates the export of cystine from the lysosome. When CTNS is mutated, cystine transport is disrupted, leading to cystine accumulation, the diagnostic hallmark of the lysosomal storage disorder cystinosis. Here, we provide biochemical evidence for Ers1p-dependent cystine transport. However, the accumulation of intracellular cystine is not observed when the ERS1 gene is deleted from ers1-Δ yeast, supporting the existence of modifier genes that provide a mechanism in ers1-Δ yeast that prevents or corrects cystine accumulation. Upon comparison of the transcriptomes of isogenic ERS1+ and ers1-Δ strains of S. cerevisiae by DNA microarray followed by targeted qPCR, sixteen genes were identified as being differentially expressed between the two genotypes. Genes that encode proteins functioning in sulfur regulation, cellular respiration, and general transport were enriched in our screen, demonstrating pleiotropic effects of ers1-Δ. These results give insight into yeast cystine regulation and the multiple, seemingly distal, pathways that involve proper cystine recycling.
The challenges of big data
Authors: Mardis Elaine R. 
Published: May 2016

ABSTRACT
The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest.
Morphological, anatomical and isozyme variation among giant taro
Authors: SURATMAN SURATMAN , PITOYO ARI , KURNIASARI SEPTIANA , SURANTO SURANTO 
Published: May 2016

Suratman, Pitoyo A, Kurniasari S, Suranto. 2016. Morphological, anatomical and isozyme variation among giant taroÂ (Alocasia macrorrhizos) accessions from Central Java, Indonesia. Biodiversitas 17: 422-429. The objective of this study was to evaluateÂ morphological, anatomical and isozyme variation among giant taroÂ (Alocasia macrorrhizos (L.) G.Don) accessions from Central Java. Identification of morphological characters was done by direct observation of roots, leaves, stems, and corms. Anatomical characters were observed from both paradermal and transverse sections of leaf. Identification of biochemical markers was done by using peroxidase and esterase isozyme system. The genetic similarity among giant taro accessions was measured by using Group Average Clustering. The results of the analysis of variance revealed highly significant differences for majority of the tested morphological and anatomical characters suggesting that there was a high degree of diversity among the giant taro accessions. Isozyme polymorphism was observed in giant taroÂ accessions using peroxidase (two banding patterns)Â and esterase (four banding patterns).Â Based on the dendogram, giant taro accessions were segregated into two major clusters. In Cluster I, the closest relationship were showed in KTN 2 and WNG 1 accessions from Klaten and Wonogiri that had 80.95% of similarity coefficient. The five accessions (SKA, SKH, WNG 4, KRA 3, KRA 4)Â fromÂ Surakarta, Sukoharjo, Wonogiri and some parts of Karanganyar were clustered separately as Cluster II with similarity coefficient of 50%.
Culture jamming (and tucking): RuPaul’s Drag Race and unconventional reality
Authors: Gudelunas David 
Published: May 2016

Abstract
Reality television is rarely subversive, but occasionally a programme enters the popular culture Zeitgeist that not just contributes to the genre, but rather exposes it. Launched in 2009, Logo’s RuPaul’s Drag Race presents a case study on how occasionally even commercial television can serve as a type of culture jamming. This article offers a critical analysis of RuPaul’s Drag Race and argues that the typical reality competition format is both exploited and exposed as a type of culture jamming that is uniquely queer. Through interviews with queer audiences, this article also looks at how audiences understand and react to promotional realities.
Synthesis and characterization of amorphous Al2O3 and γ-Al2O3 by spray pyrolysis
Authors: Wang Zhenfeng , Wu Wenyuan , Bian Xue , Wu Yongfu 
Published: May 2016

Abstract
As an environmentally friendly method, spray pyrolysis has been widely used to produce a variety of metal oxides and composite metal oxides. Spray pyrolysis is used to synthesize amorphous Al2O3 and γ-Al2O3. A pyrolysis temperature ranging from 1073 to 1273 K and a collector temperature ranging from 273 to 283 K result in amorphous Al2O3. To strengthen the stability of the amorphous Al2O3, La3+ was added to modify amorphous Al2O3 with different La3+ concentrations. With a particle residence time of 2.6–3.0 s in the calciner, the pyrolysis temperature of γ-Al2O3 was obtained at 1373 and 1273 K, respectively. Microstructural and morphological analyses conducted by using X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, and infrared absorption spectrum showed that the obtained alumina are amorphous or γ crystalline forms flake.
Oligodendroglial TNFR2 Mediates Membrane TNF-Dependent Repair in Experimental Autoimmune Encephalomyelitis by Promoting Oligodendrocyte Differentiation and Remyelination
Authors: Madsen Pernille M. , Motti Dario , Karmally Shaffiat , Szymkowski David E. , Lambertsen Kate Lykke , Bethea John R. , Brambilla Roberta 
Published: May 2016

Tumor necrosis factor (TNF) is associated with the pathophysiology of various neurological disorders, including multiple sclerosis. It exists as a transmembrane form tmTNF, signaling via TNF receptor 2 (TNFR2) and TNFR1, and a soluble form, solTNF, signaling via TNFR1. Multiple sclerosis is associated with the detrimental effects of solTNF acting through TNFR1, while tmTNF promotes repair and remyelination. Here we demonstrate that oligodendroglial TNFR2 is a key mediator of tmTNF-dependent protection in experimental autoimmune encephalomyelitis (EAE). CNP-cre:TNFR2fl/flmice with TNFR2 ablation in oligodendrocytes show exacerbation of the disease with increased axon and myelin pathology, reduced remyelination, and increased loss of oligodendrocyte precursor cells and mature oligodendrocytes. The clinical course of EAE is not improved by the solTNF inhibitor XPro1595 in CNP-cre:TNFR2fl/flmice, indicating that for tmTNF to promote recovery TNFR2 in oligodendrocytes is required. We show that TNFR2 drives differentiation of oligodendrocyte precursor cells, but not proliferation or survival. TNFR2 ablation leads to dysregulated expression of microRNAs, among which are regulators of oligodendrocyte differentiation and inflammation, including miR-7a. Our data provide the first directin vivoevidence that TNFR2 in oligodendrocytes is important for oligodendrocyte differentiation, thereby sustaining tmTNF-dependent repair in neuroimmune disease. Our studies identify TNFR2 in the CNS as a molecular target for the development of remyelinating agents, addressing the most pressing need in multiple sclerosis therapy nowadays.SIGNIFICANCE STATEMENTOur study, using novel TNF receptor 2 (TNFR2) conditional KO mice with selective TNFR2 ablation in oligodendrocytes, provides the first direct evidence that TNFR2 is an important signal for oligodendrocyte differentiation. Following activation by transmembrane TNF, TNFR2 initiates pathways that drive oligodendrocytes into a reparative mode contributing to remyelination following disease. This identifies TNFR2 as a new molecular target for the development of therapeutic agents in multiple sclerosis.
Glutamatergic Preoptic Area Neurons That Express Leptin Receptors Drive Temperature-Dependent Body Weight Homeostasis
Authors: Yu Sangho , Qualls-Creekmore Emily , Rezai-Zadeh Kavon , Jiang Yanyan , Berthoud Hans-Rudolf , Morrison Christopher D. , Derbenev Andrei V. , Zsombok Andrea , Münzberg Heike 
Published: May 2016

The preoptic area (POA) regulates body temperature, but is not considered a site for body weight control. A subpopulation of POA neurons express leptin receptors (LepRbPOAneurons) and modulate reproductive function. However, LepRbPOAneurons project to sympathetic premotor neurons that control brown adipose tissue (BAT) thermogenesis, suggesting an additional role in energy homeostasis and body weight regulation. We determined the role of LepRbPOAneurons in energy homeostasis usingcre-dependent viral vectors to selectively activate these neurons and analyzed functional outcomes in mice. We show that LepRbPOAneurons mediate homeostatic adaptations to ambient temperature changes, and their pharmacogenetic activation drives robust suppression of energy expenditure and food intake, which lowers body temperature and body weight. Surprisingly, our data show that hypothermia-inducing LepRbPOAneurons are glutamatergic, while GABAergic POA neurons, originally thought to mediate warm-induced inhibition of sympathetic premotor neurons, have no effect on energy expenditure. Our data suggest a new view into the neurochemical and functional properties of BAT-related POA circuits and highlight their additional role in modulating food intake and body weight.SIGNIFICANCE STATEMENTBrown adipose tissue (BAT)-induced thermogenesis is a promising therapeutic target to treat obesity and metabolic diseases. The preoptic area (POA) controls body temperature by modulating BAT activity, but its role in body weight homeostasis has not been addressed. LepRbPOAneurons are BAT-related neurons and we show that they are sufficient to inhibit energy expenditure. We further show that LepRbPOAneurons modulate food intake and body weight, which is mediated by temperature-dependent homeostatic responses. We further found that LepRbPOAneurons are stimulatory glutamatergic neurons, contrary to prevalent models, providing a new view on thermoregulatory neural circuits. In summary, our study significantly expands our current understanding of central circuits and mechanisms that modulate energy homeostasis.
Conversion of Synthetic Aβ toIn VivoActive Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model
Authors: Novotny Renata , Langer Franziska , Mahler Jasmin , Skodras Angelos , Vlachos Andreas , Wegenast-Braun Bettina M. , Kaeser Stephan A. , Neher Jonas J. , Eisele Yvonne S. , Pietrowski Marie J. , Nilsson K. Peter R. , Deller Thomas , Staufenbiel Matthias , Heimrich Bernd , Jucker Mathias 
Published: May 2016

The aggregation of amyloid-β peptide (Aβ) in brain is an early event and hallmark of Alzheimer's disease (AD). We combined the advantages ofin vitroandin vivoapproaches to study cerebral β-amyloidosis by establishing a long-term hippocampal slice culture (HSC) model. While no Aβ deposition was noted in untreated HSCs of postnatal Aβ precursor protein transgenic (APP tg) mice, Aβ deposition emerged in HSCs when cultures were treated once with brain extract from aged APP tg mice and the culture medium was continuously supplemented with synthetic Aβ. Seeded Aβ deposition was also observed under the same conditions in HSCs derived from wild-type orApp-null mice but in no comparable way when HSCs were fixed before cultivation. Both the nature of the brain extract and the synthetic Aβ species determined the conformational characteristics of HSC Aβ deposition. HSC Aβ deposits induced a microglia response, spine loss, and neuritic dystrophy but no obvious neuron loss. Remarkably, in contrast toin vitroaggregated synthetic Aβ, homogenates of Aβ deposits containing HSCs induced cerebral β-amyloidosis upon intracerebral inoculation into young APP tg mice. Our results demonstrate that a living cellular environment promotes the seeded conversion of synthetic Aβ into a potentin vivoseeding-active form.SIGNIFICANCE STATEMENTIn this study, we report the seeded induction of Aβ aggregation and deposition in long-term hippocampal slice cultures. Remarkably, we find that the biological activities of the largely synthetic Aβ aggregates in the culture are very similar to those observedin vivo. This observation is the first to show that potentin vivoseeding-active Aβ aggregates can be obtained by seeded conversion of synthetic Aβ in a living (wild-type) cellular environment.