bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different sensitivities of photosystem II in green algae and cyanobacteria to phenylurea and phenol-type herbicides: effect on electron donor side
Authors: Yotsova Ekaterina K. , Stefanov Martin A. , Dobrikova Anelia G. , Apostolova Emilia L. 
Published: March 2017

Abstract
The effects of short-term treatment with phenylurea (DCMU, isoproturon) and phenol-type (ioxynil) herbicides on the green alga Chlorella kessleri and the cyanobacterium Synechocystis salina with different organizations of photosystem II (PSII) were investigated using pulse amplitude modulated (PAM) chlorophyll fluorescence and photosynthetic oxygen evolution measured by polarographic oxygen electrodes (Clark-type and Joliot-type). The photosynthetic oxygen evolution showed stronger inhibition than the PSII photochemistry. The effects of the studied herbicides on both algal and cyanobacterial cells decreased in the following order: DCMU>isoproturon>ioxynil. Furthermore, we observed that the number of blocked PSII centers increased significantly after DCMU treatment (204–250 times) and slightly after ioxynil treatment (19–35 times) in comparison with the control cells. This study suggests that the herbicides affect not only the acceptor side but also the donor side of PSII by modifications of the Mn cluster of the oxygen-evolving complex. We propose that one of the reasons for the different PSII inhibitions caused by herbicides is their influence, in different extents, on the kinetic parameters of the oxygen-evolving reactions (the initial S0−S1 state distribution, the number of blocked centers SB, the turnover time of Si states, misses and double hits). The relationship between the herbicide-induced inhibition and the changes in the kinetic parameters is discussed.
Parallel Specification of Visuomotor Feedback Gains during Bimanual Reaching to Independent Goals
Authors: de Brouwer Anouk J. , Jarvis Tayler , Gallivan Jason P. , Flanagan J. Randall 
Published: March 2017

AbstractDuring goal-directed reaching, rapid visuomotor feedback processes enable the human motor system to quickly correct for errors in the trajectory of the hand that arise from motor noise and, in some cases, external perturbations. To date, these visuomotor responses, the gain of which is sensitive to features of the task and environment, have primarily been examined in the context of unimanual reaching movements toward a single target. However, many natural tasks involve moving both hands together, often to separate targets, such that errors can occur in parallel and at different spatial locations. Here, we examined the resource capacity of automatic visuomotor corrective mechanisms by comparing feedback gains during bimanual reaches, toward two targets, to feedback gains during unimanual reaches toward single targets. To investigate the sensitivity of the feedback gains and their relation to visual-spatial processing, we manipulated the widths of the targets and participants’ gaze location. We found that the gain of corrective responses to cursor displacements, while strongly modulated by target width and gaze position, were only slightly reduced during bimanual control. Our results show that automatic visuomotor corrective mechanisms can efficiently operate in parallel across multiple spatial locations.
Inhibition of L-Type Ca2+Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons
Authors: Sun Yuyang , Zhang Haopeng , Selvaraj Senthil , Sukumaran Pramod , Lei Saobo , Birnbaumer Lutz , Singh Brij B. 
Published: March 2017

Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca2+channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1−/−, mice. Similarly, TRPC1−/−substantia nigra neurons showed increased L-type Ca2+currents, decreased stimulation-dependent STIM1-Cav1.3 interaction, and decreased DA neurons. L-type Ca2+currents and the open channel probability of Cav1.3 channels were also reduced upon TRPC1 activation, whereas increased Cav1.3 currents were observed upon STIM1 or TRPC1 silencing. Increased interaction between Cav1.3-TRPC1-STIM1 was observed upon store depletion and the loss of either TRPC1 or STIM1 led to DA cell death, which was prevented by inhibiting L-type Ca2+channels. Neurotoxins that mimic Parkinson's disease increased Cav1.3 function, decreased TRPC1 expression, inhibited Tg-mediated STIM1-Cav1.3 interaction, and induced caspase activation. Importantly, restoration of TRPC1 expression not only inhibited Cav1.3 function but increased cell survival. Together, we provide evidence that TRPC1 suppresses Cav1.3 activity by providing an STIM1-based scaffold, which is essential for DA neuron survival.SIGNIFICANCE STATEMENTCa2+entry serves critical cellular functions in virtually every cell type, and appropriate regulation of Ca2+in neurons is essential for proper function. In Parkinson's disease, DA neurons are specifically degenerated, but the mechanism is not known. Unlike other neurons, DA neurons depend on Cav1.3 channels for their rhythmic activity. Our studies show that, in normal conditions, the pacemaking activity in DA neurons is inhibited by the TRPC1-STIM1 complex. Neurotoxins that mimic Parkinson's disease target TRPC1 expression, which leads to an abnormal increase in Cav1.3 activity, thereby causing degeneration of DA neurons. These findings link TRPC1 to Cav1.3 regulation and provide important indications about how disrupting Ca2+balance could have a direct implication in the treatment of Parkinson's patients.
EphA4 Regulates Neuroblast and Astrocyte Organization in a Neurogenic Niche
Authors: Todd Krysti L. , Baker Kasey L. , Eastman Matthew B. , Kolling Frederick W. , Trausch Alexandra G. , Nelson Craig E. , Conover Joanne C. 
Published: March 2017

Significant migration cues are required to guide and contain newly generated rodent subventricular zone (SVZ) neuroblasts as they transit along the lateral ventricles and then through the anterior forebrain to their ultimate site of differentiation in the olfactory bulbs (OBs). These cues enforce strict neuroblast spatial boundaries within the dense astroglial meshwork of the SVZ and rostral migratory stream (RMS), yet are permissive to large-scale neuroblast migration. Therefore, the molecular mechanisms that define these cues and control dynamic interactions between migratory neuroblasts and surrounding astrocytes are of particular interest. We found that deletion of EphA4 and specifically ablation of EphA4 kinase activity resulted in misaligned neuroblasts and disorganized astrocytes in the RMS/SVZ, linking EphA4 forward signaling to SVZ and RMS spatial organization, orientation, and regulation. In addition, within a 3 week period, there was a significant reduction in the number of neuroblasts that reached the OB and integrated into the periglomerular layer, revealing a crucial role for EphA4 in facilitating efficient neuroblast migration to the OB. Single-cell analysis revealed thatEPHA4and itsEFNbinding partners are expressed by subpopulations of neuroblasts and astrocytes within the SVZ/RMS/OB system resulting in a cell-specific mosaic, suggesting complex EphA4 signaling involving both homotypic and heterotypic cell–cell interactions. Together, our studies reveal a novel molecular mechanism involving EphA4 signaling that functions in stem cell niche organization and ultimately neuroblast migration in the anterior forebrain.SIGNIFICANCE STATEMENTThe subventricular zone neurogenic stem cell niche generates highly migratory neuroblasts that transit the anterior forebrain along a defined pathway to the olfactory bulb. Postnatal and adult brain organization dictates strict adherence to a narrow migration corridor. Subventricular zone neuroblasts are aligned in tightly bundled chains within a meshwork of astrocytes; however, the cell–cell cues that organize this unique, cell-dense migration pathway are largely unknown. Our studies show that forward signaling through the EphA4 tyrosine kinase receptor, mediated by ephrins expressed by subpopulations of neuroblasts and astrocytes, is required for compact, directional organization of neuroblasts and astrocytes within the pathway and efficient transit of neuroblasts through the anterior forebrain to the olfactory bulb.
Locomotion Induces Stimulus-Specific Response Enhancement in Adult Visual Cortex
Authors: Kaneko Megumi , Fu Yu , Stryker Michael P. 
Published: March 2017

The responses of neurons in the visual cortex (V1) of adult mammals have long been thought to be stable over long periods. Here, we investigated whether repeated exposure to specific stimuli would enhance V1 visual responses in mice using intrinsic signal imaging through the intact skull and two-photon imaging of calcium signals in single neurons. Mice ran on Styrofoam balls floating on air while viewing one of three different, high-contrast visual stimuli. V1 responses to the stimuli that were viewed by the animal were specifically enhanced, while responses to other stimuli were unaffected. Similar exposure in stationary mice or in mice in which NMDA receptors were partially blocked did not significantly enhance responses. These findings indicate that stimulus-specific plasticity in the adult visual cortex depends on concurrent locomotion, presumably as a result of the high-gain state of the visual cortex induced by locomotion.SIGNIFICANCE STATEMENTWe report a rapid and persistent increase in visual cortical responses to visual stimuli presented during locomotion in intact mice. We first used a method that is completely noninvasive to image intrinsic signals through the intact skull. We then measured the same effects on single neurons using two-photon calcium imaging and found that the increase in response to a particular stimulus produced by locomotion depends on how well the neuron is initially driven by the stimulus. To our knowledge, this is the first time such enhancement has been described in single neurons or using noninvasive measurements.
Uncoupling of neurogenesis and differentiation during retinal development
Authors: Engerer Peter , Suzuki Sachihiro C , Yoshimatsu Takeshi , Chapouton Prisca , Obeng Nancy , Odermatt Benjamin , Williams Philip R , Misgeld Thomas , Godinho Leanne 
Published: March 2017

AbstractConventionally, neuronal development is regarded to follow a stereotypic sequence of neurogenesis, migration, and differentiation. We demonstrate that this notion is not a general principle of neuronal development by documenting the timing of mitosis in relation to multiple differentiation events for bipolar cells (BCs) in the zebrafish retina using in vivo imaging. We found that BC progenitors undergo terminal neurogenic divisions while in markedly disparate stages of neuronal differentiation. Remarkably, the differentiation state of individual BC progenitors at mitosis is not arbitrary but matches the differentiation state of post‐mitotic BCs in their surround. By experimentally shifting the relative timing of progenitor division and differentiation, we provide evidence that neurogenesis and differentiation can occur independently of each other. We propose that the uncoupling of neurogenesis and differentiation could provide neurogenic programs with flexibility, while allowing for synchronous neuronal development within a continuously expanding cell pool.
The linear ubiquitin chain assembly complex regulates TRAIL‐induced gene activation and cell death
Authors: Lafont Elodie , Kantari‐Mimoun Chahrazade , Draber Peter , De Miguel Diego , Hartwig Torsten , Reichert Matthias , Kupka Sebastian , Shimizu Yutaka , Taraborrelli Lucia , Spit Maureen , Sprick Martin R , Walczak Henning 
Published: March 2017

AbstractThe linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo. LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL‐R‐associated complex I as well as of the cytoplasmic TRAIL‐induced complex II. In both of these complexes, HOIP limits caspase‐8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase‐8‐dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL‐containing complex, LUBAC also restricts TRAIL‐induced necroptosis. We identify RIPK1 and caspase‐8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL‐induced RIPK1‐independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL‐induced activation of NF‐κB and, consequently, the production of cytokines, downstream of FADD, caspase‐8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation.
Mortality in Graves’ orbitopathy is increased and influenced by gender, age and pre-existing morbidity: a nationwide Danish register study
Authors: Schwensen Charlotte F , Brandt Frans , Hegedüs Laszlo , Brix Thomas H 
Published: March 2017

Introduction
It is unclear whether the excess mortality associated with Graves’ disease differs between individuals with Graves’ orbitopathy (GO) or without (GD).

Subjects and methods
A nationwide, register-based cohort study in which all adult Danes diagnosed with GD (n = 28 461) and GO (n = 3965) between 1995 and 2012 were matched for age and gender with four control subjects. Median follow-up time was 7.9 years (range 0–17.5). Mortality risk in GO patients compared to the control population and compared to GD patients was calculated using Cox regression analyses, adjusting for pre-existing morbidity using the Charlson score.

Results
Adjusted mortality in Graves’ disease overall (GD + GO) was significantly increased compared to that in the background population (HR = 1.18 (95% confidence interval: 1.15–1.21)). In GD and GO separately, adjusted mortality was also significantly higher than that in their respective control populations (HR: 1.19 (1.16–1.22) and HR: 1.23 (1.12–1.35) respectively). However, mortality in GO compared to that in GD was decreased (HR: 0.64 (0.59–0.69)), although this difference attenuated after adjustment for pre-existing morbidity, age and gender. Both GD and GO males had a significantly higher mortality than those in females. For GO, but not for GD, mortality risk was the highest in the youngest and decreased with increasing age.

Conclusions
GD and GO were associated with increased mortality, especially in males. In GO, but not in GD patients, there was an inverse relationship between age and mortality. Surprisingly, and in need of further study, mortality was not higher in GO than that in GD individuals.
A Whole-Transcriptome Approach to Evaluating Reference Genes for Quantitative Gene Expression Studies: A Case Study in Mimulus
Authors: Stanton Kimmy A , Edger Patrick P , Puzey Joshua R , Kinser Taliesin , Cheng Philip , Vernon Daniel M , Forsthoefel Nancy R , Cooley Arielle M 
Published: March 2017

Abstract
While quantitative PCR (qPCR) is widely recognized as being among the most accurate methods for quantifying gene expression, it is highly dependent on the use of reliable, stably expressed reference genes. With the increased availability of high-throughput methods for measuring gene expression, whole-transcriptome approaches may be increasingly utilized for reference gene selection and validation. In this study, RNA-seq was used to identify a set of novel qPCR reference genes and evaluate a panel of traditional “housekeeping” reference genes in two species of the evolutionary model plant genus Mimulus. More broadly, the methods proposed in this study can be used to harness the power of transcriptomes to identify appropriate reference genes for qPCR in any study organism, including emerging and nonmodel systems. We find that RNA-seq accurately estimates gene expression means in comparison to qPCR, and that expression means are robust to moderate environmental and genetic variation. However, measures of expression variability were only in agreement with qPCR for samples obtained from a shared environment. This result, along with transcriptome-wide comparisons, suggests that environmental changes have greater impacts on expression variability than on expression means. We discuss how this issue can be addressed through experimental design, and suggest that the ever-expanding pool of published transcriptomes represents a rich and low-cost resource for developing better reference genes for qPCR.
Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP
Authors: Wang Ying , Naturale Victor F , Adler Paul N 
Published: March 2017

AbstractThe Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled. PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (inPD). We found that mild overexpression of Fritz partially rescued inPD, indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritzmNeonGreen provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains (“puncta”). Surprisingly, we found it in stripes in developing bristles.
Automated Phenotyping Indicates Pupal Size in Drosophila Is a Highly Heritable Trait with an Apparent Polygenic Basis
Authors: Reeves R Guy , Tautz Diethard 
Published: March 2017

Abstract
The intense focus on studying human height has done more than any other genetic analysis to advance our understanding of the heritability of highly complex phenotypes. Here, we describe in detail the properties of a previously unexplored trait in Drosophila melanogaster that shares many salient properties with human height. The total length of the pupal case varies between 2.8 and 3.9 mm among natural variants, and we report that it is among the most heritable traits reported in this species. We have developed a simple semiautomatic phenotyping system with which a single operator can reliably score &gt;5000 individuals in a day. The precision of the automated system is 0.042 mm (± 0.030 SD). All phenotyped individuals are available to be mated in subsequent generations or uniquely archived for future molecular work. We report both broad sense and narrow sense heritability estimates for two biologically distinct data sets. Narrow sense heritability (h2) ranged from 0.44 to 0.50, and broad sense heritability (H2) ranged from 0.58 to 0.61. We present results for mapping the trait in 195 recombinant inbred lines, which suggests that there are no loci with &gt;10% effect size in this panel. We propose that pupal size genetics in Drosophila could represent a model complex trait amenable to deep genetic dissection using the automated system described.
Dynamic Notch Signaling Specifies Each Cell Fate inDrosophilaSpermathecal Lineage
Authors: Shen Wei , Sun Jianjun 
Published: March 2017

AbstractSpermathecae are glandular organs in the insect female reproductive tract that play essential roles in insect reproduction; however, the molecular mechanism involved in their development is largely unknown. Drosophila spermathecae consist of class-III secretory units, in which each secretory cell (SC) discharges its products to the central lumen through an end-apparatus and a canal. Secretory unit formation in Drosophila spermathecae utilizes a fixed cell lineage, in which each secretory unit precursor (SUP) divides to produce one pIIb cell and one pIIa cell. The former differentiates into an apical cell (AC), whereas the latter divides again to produce an SC and a basal cell (BC). It is unclear how each cell acquires its identity and contributes to secretory unit formation. Here, we demonstrate that Notch signaling is required and sufficient for the specification of lumen epithelial precursors (LEPs; vs. SUPs), pIIb (vs. pIIa), and SCs (vs. BCs) sequentially. To our surprise, Notch activation in LEPs and SCs apparently utilizes different ligand mechanisms. In addition, Notch signaling both suppresses and activates transcription factors Hindsight (Hnt) and Cut during spermathecal lineage specification, supporting the notion that Notch signaling can have opposite biological outcomes in different cellular environments. Furthermore, LEP-derived epithelial cells (ECs) and ACs show distinct cellular morphology and are essential for securing secretory units to the epithelial lumen. Our work demonstrates, for the first time, the dynamic role of Notch signaling in binary cell fate determination in Drosophila spermathecae and the role of ECs and ACs in secretory unit formation.
pnp4aIs the Causal Gene of the Medaka Iridophore Mutantguanineless
Authors: Kimura Tetsuaki , Takehana Yusuke , Naruse Kiyoshi 
Published: March 2017

AbstractSee-through medaka lines are suitable for observing internal organs throughout life. They were bred by crossing multiple color mutants. However, some of the causal genes for these mutants have not been identified. The medaka has four pigment cell types: black melanophores, yellow xanthophores, white leucophores, and silvery iridophores. The causal genes of melanophore, xanthophore, and leucophore mutants have been elucidated, but the causal gene for the iridophore mutant remains unknown. Here, we describe the iridophore mutant, guanineless (gu), which exhibits a strong reduction in visible iridophores throughout its larval to adult stages. The gu locus was previously mapped to chromosome 5, but was located near the telomeric region, making it difficult to integrate into the chromosome. We sought the causal gene of gu using synteny analysis with the zebrafish genome and found a strong candidate, purine nucleoside phosphorylase 4a (pnp4a). Gene targeting and complementation testing showed that pnp4a is the causal gene of gu. This result will allow the establishment of inbred medaka strains or other useful strains with see-through phenotypes without major disruption in the genetic background of each strain.