bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired proteasomal degradation enhances autophagy via hypoxia signaling in Drosophila
Authors: Lőw Péter , Varga Ágnes , Pircs Karolina , Nagy Péter , Szatmári Zsuzsanna , Sass Miklós , Juhász Gábor 
Published: June 2013

Abstract

Background
Two pathways are responsible for the majority of regulated protein catabolism in eukaryotic cells: the ubiquitin-proteasome system (UPS) and lysosomal self-degradation through autophagy. Both processes are necessary for cellular homeostasis by ensuring continuous turnover and quality control of most intracellular proteins. Recent studies established that both UPS and autophagy are capable of selectively eliminating ubiquitinated proteins and that autophagy may partially compensate for the lack of proteasomal degradation, but the molecular links between these pathways are poorly characterized.

Results
Here we show that autophagy is enhanced by the silencing of genes encoding various proteasome subunits (α, β or regulatory) in larval fat body cells. Proteasome inactivation induces canonical autophagy, as it depends on core autophagy genes Atg1, Vps34, Atg9, Atg4 and Atg12. Large-scale accumulation of aggregates containing p62 and ubiquitinated proteins is observed in proteasome RNAi cells. Importantly, overexpressed Atg8a reporters are captured into the cytoplasmic aggregates, but these do not represent autophagosomes. Loss of p62 does not block autophagy upregulation upon proteasome impairment, suggesting that compensatory autophagy is not simply due to the buildup of excess cargo. One of the best characterized substrates of UPS is the α subunit of hypoxia-inducible transcription factor 1 (HIF-1α), which is continuously degraded by the proteasome during normoxic conditions. Hypoxia is a known trigger of autophagy in mammalian cells, and we show that genetic activation of hypoxia signaling also induces autophagy in Drosophila. Moreover, we find that proteasome inactivation-induced autophagy requires sima, the Drosophila ortholog of HIF-1α.

Conclusions
We have characterized proteasome inactivation- and hypoxia signaling-induced autophagy in the commonly used larval Drosophila fat body model. Activation of both autophagy and hypoxia signaling was implicated in various cancers, and mutations affecting genes encoding UPS enzymes have recently been suggested to cause renal cancer. Our studies identify a novel genetic link that may play an important role in that context, as HIF-1α/sima may contribute to upregulation of autophagy by impaired proteasomal activity.
Genetic variation in four maturity genes affects photoperiod insensitivity and PHYA-regulated post-flowering responses of soybean
Authors: Xu Meilan , Xu Zeheng , Liu Baohui , Kong Fanjiang , Tsubokura Yasutaka , Watanabe Satoshi , Xia Zhengjun , Harada Kyuya , Kanazawa Akira , Yamada Testuya , Abe Jun 
Published: June 2013

Abstract

Background
Absence of or low sensitivity to photoperiod is necessary for short-day crops, such as rice and soybean, to adapt to high latitudes. Photoperiod insensitivity in soybeans is controlled by two genetic systems and involves three important maturity genes: E1, a repressor for two soybean orthologs of Arabidopsis FLOWERING LOCUS T (GmFT2a and GmFT5a), and E3 and E4, which are phytochrome A genes. To elucidate the diverse mechanisms underlying photoperiod insensitivity in soybean, we assessed the genotypes of four maturity genes (E1 through E4) in early-flowering photoperiod-insensitive cultivars and their association with post-flowering responses.

Results
We found two novel dysfunctional alleles in accessions originally considered to have a dominant E3 allele according to known DNA markers. The E3 locus, together with E1 and E4, contained multiple dysfunctional alleles. We identified 15 multi-locus genotypes, which we subdivided into 6 genotypic groups by classifying their alleles by function. Of these, the e1-as/e3/E4 genotypic group required an additional novel gene (different from E1, E3, and E4) to condition photoperiod insensitivity. Despite their common pre-flowering photoperiod insensitivity, accessions with different multi-locus genotypes responded differently to the post-flowering photoperiod. Cultivars carrying E3 or E4 were sensitive to photoperiod for post-flowering characteristics, such as reproductive period and stem growth after flowering. The phytochrome A–regulated expression of the determinate growth habit gene Dt1, an ortholog of Arabidopsis TERMINAL FLOWER1, was involved in the persistence of the vegetative activity at the stem apical meristem of flower-induced plants under long-day conditions.

Conclusions
Diverse genetic mechanisms underlie photoperiod insensitivity in soybean. At least three multi-locus genotypes consisting of various allelic combinations at E1, E3, and E4 conferred pre-flowering photoperiod insensitivity to soybean cultivars but led to different responses to photoperiod during post-flowering vegetative and reproductive development. The phyA genes E3 and E4 are major controllers underlying not only pre-flowering but also post-flowering photoperiod responses. The current findings improve our understanding of genetic diversity in pre-flowering photoperiod insensitivity and mechanisms of post-flowering photoperiod responses in soybean.
In-plane optical anisotropy of InAs/GaSb superlattices with alternate interfaces
Authors: Wu Shujie , Chen Yonghai , Yu Jinling , Gao Hansong , Jiang Chongyun , Huang Jianliang , Zhang Yanhua , Wei Yang , Ma Wenquan 
Published: June 2013

Abstract
The in-plane optical anisotropy (IPOA) in InAs/GaSb superlattices has been studied by reflectance difference spectroscopy (RDS) at different temperatures ranging from 80 to 300 K. We introduce alternate GaAs- and InSb-like interfaces (IFs), which cause the symmetry reduced from D
2d
to C
2v
. IPOA has been observed in the (001) plane along [110] and [1

1

¯

0] axes. RDS measurement results show strong anisotropy resonance near critical point (CP) energies of InAs and GaSb. The energy positions show red shift and RDS intensity decreases with the increasing temperature. For the superlattice sample with the thicker InSb-like IFs, energy positions show red shift, and the spectra exhibit stronger IPOA. The excitonic effect is clearly observed by RDS at low temperatures. It demonstrates that biaxial strain results in the shift of the CP energies and IPOA is enhanced by the further localization of the carriers in InSb-like IFs.

PACS

78.67.Pt, 78.66.Fd, 78.40.Fy
Assessing the effectiveness and cost effectiveness of subcutaneous nerve stimulation in patients with predominant back pain due to failed back surgery syndrome (SubQStim study): study protocol for a multicenter randomized controlled trial
Authors: Eldabe Sam , Kern Michael , Peul Wilco , Green Colin , Winterfeldt Kristi , Taylor Rod S 
Published: June 2013

Abstract

Background
Chronic radicular pain can be effectively treated with spinal cord stimulation, but this therapy is not always sufficient for chronic back pain. Subcutaneous nerve stimulation (SQS) refers to the placement of percutaneous leads in the subcutaneous tissue within the area of pain. Case series data show that failed back surgery syndrome (FBSS) patients experience clinically important levels of pain relief following SQS and may also reduce their levels of analgesic therapy and experience functional well-being. However, to date, there is no randomized controlled trial evidence to support the use of SQS in FBSS.

Methods/Design
The SubQStim study is a multicenter randomized controlled trial comparing SQS plus optimized medical management (‘SQS arm’) versus optimized medical management alone (‘OMM arm’) in patients with predominant back pain due to FBSS. Up to 400 patients will be recruited from approximately 33 centers in Europe and Australia and will be randomized 1:1 to the SQS or OMM arms. After 9 months, patients who fail to reach the primary outcome will be allowed to switch treatments. Patients will be evaluated at baseline (prior to randomization) and at 1, 3, 6, 9, 12, 18, 24, and 36 months after randomization. The primary outcome is the proportion of patients at 9 months with a ≥50% reduction in back pain intensity compared to baseline. The secondary outcomes are: back and leg pain intensity score, functional disability, health-related quality of life, patient satisfaction, patient global impression of change, healthcare resource utilization/costs, cost-effectiveness analysis and adverse events. Outcomes arms will be compared between SQS and OMM arms at all evaluation points up to and including 9 months. After the 9-month assessment visit, the main analytic focus will be to compare within patient changes in outcomes relative to baseline.

Discussion
The SubQStim trial began patient recruitment in November 2012. Recruitment is expected to close in late 2014.

Trial registration
ClinicalTrials.gov NCT01711619
Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation
Authors: Hock Sabrina , Ng Yen-Kar , Hasenauer Jan , Wittmann Dominik , Lutter Dominik , Trümbach Dietrich , Wurst Wolfgang , Prakash Nilima , Theis Fabian J 
Published: June 2013

Abstract

Background
The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context.

Results
We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays.

Conclusion
In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses.
Seroprevalence and risk factors of toxoplasmosis in cattle from extensive and semi-intensive rearing systems at Zona da Mata, Minas Gerais state, Southern Brazil
Authors: Fajardo Hugo Vieira , D’ávila Sthefane , Bastos Ronaldo Rocha , Cyrino Carolina Dutra , de Lima Detoni Michelle , Garcia João Luis , das Neves Leandro Batista , Nicolau José Leonardo , Amendoeira Maria Regina Reis 
Published: June 2013

AbstractBackgroundConcerning the infection of humans byT. gondii,limited efforts have been directed to the elucidation of the role of horizontal transmission between hosts. One of the main routes of transmission from animals to humans occurs through the ingestion of raw or insufficiently cooked meat. However, even though the detection ofT. gondiiin meat constitutes an important short-term measure, control strategies can only be accomplished by a deeper understanding of the epidemiology of toxoplasmosis. The present study aimed to investigate the seroprevalence of toxoplasmosis in cattle from Zona da Mata, Minas Gerais, Brazil, and to identify associated risk factors, through an epidemiological investigation.MethodsThe animals studied (Bos indicus,breed Nelore or Gir) were reared in the Zona da Mata micro-region and killed at a commercial slaughterhouse at Juiz de Fora, Minas Gerais state. The animals came from 53 cattle farms with extensive (predominantly pasture feeding management) or semi-intensive (food management based on grazing, salt mineral and feed supplementation) rearing systems. Blood samples were collected from 1200 animals, and assigned toIndirect Fluorescent Antibody Test.ResultsWhen analyzing IgG anti-T.gondiiwe found an overall seroprevalence of 2.68%. In Brazil prevalences vary from 1.03% to 60%. Although in the present study, the seroprevalence per animal is considered low compared to those observed in other studies, we found out that of the 53 farms analyzed, 17 (34.69%) had one or more positive cattle. It is a considerable percentage, suggesting that the infection is well distributed through the Zona da Mata region. The results of the epidemiological investigation showed that the main risk factors ofToxoplasma gondiiinfection are related to animal management and to the definive host. There was a relationship between the number of seropositive cattle and the presence and number of resident cats, presence and number of stray cats, presence of cats walking freely, rat control by using cats and feed storage.ConclusionThese results may contribute to the development of preventive strategies in Brazil and other developing countries were extensive and semi-intensive cattle rearing systems are very widespread and the efforts to control this important zoonotic disease have attained little success.
Early microvascular dysfunction in cerebral small vessel disease is not detectable on 3.0 Tesla magnetic resonance imaging: a longitudinal study in spontaneously hypertensive stroke-prone rats
Authors: Mencl Stine , Garz Cornelia , Niklass Solveig , Braun Holger , Göb Eva , Homola György , Heinze Hans-Jochen , Reymann Klaus G , Kleinschnitz Christoph , Schreiber Stefanie 
Published: June 2013

Abstract

Background
Human cerebral small vessel disease (CSVD) has distinct histopathologic and imaging findings in its advanced stages. In spontaneously hypertensive stroke-prone rats (SHRSP), a well-established animal model of CSVD, we recently demonstrated that cerebral microangiopathy is initiated by early microvascular dysfunction leading to the breakdown of the blood–brain barrier and an activated coagulatory state resulting in capillary and arteriolar erythrocyte accumulations (stases). In the present study, we investigated whether initial microvascular dysfunction and other stages of the pathologic CSVD cascade can be detected by serial magnetic resonance imaging (MRI).

Findings
Fourteen SHRSP and three control (Wistar) rats (aged 26–44 weeks) were investigated biweekly by 3.0 Tesla (3 T) MRI. After perfusion, brains were stained with hematoxylin–eosin and histology was correlated with MRI data. Three SHRSP developed terminal CSVD stages including cortical, hippocampal, and striatal infarcts and macrohemorrhages, which could be detected consistently by MRI. Corresponding histology showed small vessel thromboses and increased numbers of small perivascular bleeds in the infarcted areas. However, 3 T MRI failed to visualize intravascular erythrocyte accumulations, even in those brain regions with the highest densities of affected vessels and the largest vessels affected by stases, as well as failing to detect small perivascular bleeds.

Conclusion
Serial MRI at a field strength of 3 T failed to detect the initial microvascular dysfunction and subsequent small perivascular bleeds in SHRSP; only terminal stages of cerebral microangiopathy were reliably detected. Further investigations at higher magnetic field strengths (7 T) using blood- and flow-sensitive sequences are currently underway.
Missing women in the United Kingdom
Authors: Adamou Adamos , Drakos Christina , Iyer Sriya 
Published: June 2013

Abstract

Abstract
This paper investigates the gender-selection decisions of immigrants in the United Kingdom, using data from the 1971–2006 General Household Survey. We examine sex-selection in the UK among immigrant families and the gender composition of previous births, conditional on socio-economic characteristics. Our key result is that better-educated immigrants balance their family after the birth of two sons, by having a daughter thereafter. Our study also is the first to estimate the number of missing women among Asian immigrants in a European country, contributing to research on the US and Canada that missing women are also a phenomenon of the developed world.

JEL codes
J13, J15, O52, Z13
Thermal stress effects on grain yield in Brachypodium distachyon occur via H2A.Z-nucleosomes
Authors: Boden Scott A , Kavanová Monika , Finnegan E Jean , Wigge Philip A 
Published: June 2013

Abstract
Background
Crop plants are highly sensitive to ambient temperature, with a 1 ºC difference in temperature sufficient to affect development and yield. Monocot crop plants are particularly vulnerable to higher temperatures during the reproductive and grain-filling phases. The molecular mechanisms by which temperature influences grain development are, however, unknown. In Arabidopsis thaliana, H2A.Z-nucleosomes coordinate transcriptional responses to higher temperature. We therefore investigated whether the effects of high temperature on grain development are mediated by H2A.Z-nucleosomes.

Results
We have analyzed the thermal responses of the Pooid grass, Brachypodium distachyon, a model system for crops. We find that H2A.Z-nucleosome occupancy is more responsive to increases in ambient temperature in the reproductive tissue of developing grains compared withvegetative seedlings. This difference correlates with strong phenotypic responses of developing grain to increased temperature, including early maturity and reduced yield. Conversely, temperature has limited impact on the timing of transition from the vegetative to generative stage, with increased temperature unable to substitute for long photoperiod induction of flowering. RNAi silencing of components necessary for H2A.Z-nucleosome deposition is sufficient to phenocopythe effects of warmer temperature on grain development.

Conclusions
H2A.Z-nucleosomes are important in coordinating the sensitivity of temperate grasses to increased temperature during grain development. Perturbing H2A.Z occupancy, through higher temperature or genetically, strongly reduces yield. Thus, we provide a molecular understanding of the pathways through which high temperature impacts on yield. These findings may be useful for breeding crops resilient to thermal stress.
Mapping gene activity of Arabidopsis root hairs
Authors: Lan Ping , Li Wenfeng , Lin Wen-Dar , Santi Simonetta , Schmidt Wolfgang 
Published: June 2013

Abstract
Background
Quantitative information on gene activity at single cell-type resolution is essential for the understanding of how cells work and interact. Root hairs, or trichoblasts, tubular-shaped outgrowths of specialized cells in the epidermis, represent an ideal model for cell fate acquisition and differentiation in plants.

Results
Here, we provide an atlas of gene and protein expression in Arabidopsis root hair cells, generated by paired-end RNA sequencing and LC/MS-MS analysis of protoplasts from plants containing a pEXP7-GFP reporter construct. In total, transcripts of 23,034 genes were detected in root hairs. High-resolution proteome analysis led to the reliable identification of 2,447 proteins, 129 of which were differentially expressed between root hairs and non-root hair tissue. Dissection of pre-mRNA splicing patterns showed that all types of alternative splicing were cell type-dependent, and less complex in EXP7-expressing cells when compared to non-root hair cells. Intron retention was repressed in several transcripts functionally related to root hair morphogenesis, indicative of a cell type-specific control of gene expression by alternative splicing of pre-mRNA. Concordance between mRNA and protein expression was generally high, but in many cases mRNA expression was not predictive for protein abundance.

Conclusions
The integrated analysis shows that gene activity in root hairs is dictated by orchestrated, multilayered regulatory mechanisms that allow for a cell type-specific composition of functional components.
Revised International Prognostic Scoring System (IPSS) Predicts Survival and Leukemic Evolution of Myelodysplastic Syndromes Significantly Better Than IPSS and WHO Prognostic Scoring System: Validation by the Gruppo Romano Mielodisplasie Italian Regional Database
Authors: Voso Maria Teresa , Fenu Susanna , Latagliata Roberto , Buccisano Francesco , Piciocchi Alfonso , Aloe-Spiriti Maria Antonietta , Breccia Massimo , Criscuolo Marianna , Andriani Alessandro , Mancini Stefano , Niscola Pasquale , Naso Virginia , Nobile Carolina , Piccioni Anna Lina , D'Andrea Mariella , D'Addosio Ada , Leone Giuseppe , Venditti Adriano 
Published: June 2013

Purpose The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. Patients and Methods We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. Results We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. Conclusion Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.