bluuebunny/crossref_metadata_2025 huggingface dataset:
Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report
Authors: Emmons Gregory S , Steingart Richard H , Stewart James A , Mertens Wilson C
Published: October 2012

Introduction

In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels.

Case presentation

A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing.

Conclusion

Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.
Health-related quality of life in women with endometriosis: a systematic review
Authors: Jia Shuang-zheng , Leng Jin-hua , Shi Jing-hua , Sun Peng-ran , Lang Jing-he
Published: October 2012

Endometriosis has critical implications for women’s quality of life. However, an overview of the current knowledge of this issue is limited. The objective of this systematic review was to determine the extent of endometriosis and its treatment upon women’s health-related quality of life (HRQoL). PubMed, Embase, PsycoINFO, CINAHL and the Cochrane Clinical Trials were searched up to May 2012, and only studies using standardized instruments to evaluate HRQoL in women with endometriosis were selected. Our electronic searches identified 591 citations, of which 39 studies satisfied the inclusion criteria including nine qualitative studies and 30 treatment-related studies. Findings showed that endometriosis impaired women’s HRQoL. Pain was strongly related to a poor HRQoL, and medical or surgical treatment could partially restore this impairment. No conclusive evidence was available on whether endometriosis imposed an additional impairment in HRQoL per se, apart from the decrease caused by chronic pelvic pain, or on the superiority of various hormonal suppression agents. The impacts of disease extent, duration and fertility status upon HRQoL were inconsistent. In summary, HRQoL was impaired in women with endometriosis, and medical or surgical treatment to alleviate pain could partially restore this impairment.
Glucagon-Like Peptide-1 Counteracts Oxidative Stress-Dependent Apoptosis of Human Cardiac Progenitor Cells by Inhibiting the Activation of the c-Jun N-terminal Protein Kinase Signaling Pathway
Authors: Laviola L. , Leonardini A. , Melchiorre M. , Orlando M. R. , Peschechera A. , Bortone A. , Paparella D. , Natalicchio A. , Perrini S. , Giorgino F.
Published: October 2012

Increased apoptosis of cardiac progenitor cells (CPCs) has been proposed as a mechanism of myocardial damage and dysfunction. Glucagon-like peptide-1 (GLP-1) has been shown to improve heart recovery and function after ischemia and to promote cell survival. The protective effects of GLP-1 on oxidative stress-induced apoptosis were investigated in human CPCs isolated from human heart biopsies. Mesenchymal-type cells were isolated from human heart biopsies, exhibited the marker profile of CPCs, differentiated toward the myocardiocyte, adipocyte, chondrocyte, and osteocyte lineages under appropriate culture conditions, and expressed functional GLP-1 receptors. CPCs were incubated with GLP-1 with or without hydrogen peroxide (H2O2). Phospho- and total proteins were detected by immunoblotting and immunofluorescence analysis. Gene expression was evaluated by quantitative RT-PCR. The role of the canonical GLP-1 receptor was assessed by using the receptor antagonist exendin(9–39) and receptor-specific silencer small interfering RNAs. Cell apoptosis was quantified by an ELISA assay and by flow cytometry-detected Annexin V. Exposure of CPCs to H2O2 induced a 2-fold increase in cell apoptosis, mediated by activation of the c-Jun N-terminal protein kinase (JNK) pathway. Preincubation of CPCs with GLP-1 avoided H2O2-triggered JNK phosphorylation and nuclear localization, and protected CPCs from apoptosis. The GLP-1 effects were markedly reduced by coincubation with the receptor antagonist exendin(9–39), small interfering RNA-mediated silencing of the GLP-1 receptor, and pretreatment with the protein kinase A inhibitor H89. In conclusion, activation of GLP-1 receptors prevents oxidative stress-mediated apoptosis in human CPCs by interfering with JNK activation and may represent an important mechanism for the cardioprotective effects of GLP-1.
Adiponectin Deficit During the Precarious Glucose Economy of Early Lactation in Dairy Cows
Authors: Giesy Sarah L. , Yoon Bohyung , Currie W. Bruce , Kim Jin Wook , Boisclair Yves R.
Published: October 2012

In rodents and primates, insulin resistance develops during pregnancy and fades after parturition. In contrast, dairy cows and other ruminants maintain insulin resistance in early lactation (EL). This adaptation favors mammary glucose uptake, an insulin-independent process, at a time when the glucose supply is scarce. Reduction in circulating levels of the insulin-sensitizing hormone adiponectin promotes insulin resistance in other species, but whether it contributes to insulin resistance in EL dairy cows is unknown. To address this question, plasma adiponectin was measured in high-yielding dairy cows during the transition from late pregnancy (LP) to EL. Plasma adiponectin varied in quadratic fashion with the highest levels in LP, a maximal reduction of 45% on the day after parturition and a progressive return to LP values over the next 8 wk. Adiponectin circulated nearly exclusively in high molecular weight complexes in LP, and this distribution remained unaffected in EL. The reduction of plasma adiponectin in EL occurred without changes in adiponectin mRNA in adipose tissue but was associated with repression of the expression of proteins associated with the endoplasmic reticulum and involved in assembly of adiponectin oligomers. Finally, EL increased the expression of the adiponectin receptor 1 in muscle and adiponectin receptor 2 in liver but had no effect on the expression of these receptors in adipose tissue and in the mammary gland. These data suggest that reduced plasma adiponectin belongs to the subset of hormonal adaptations in EL dairy cows facilitating mammary glucose uptake via promotion of insulin resistance.
Dual Effect of 17β-Estradiol on NMDA-Induced Neuronal Death: Involvement of Metabotropic Glutamate Receptor 1
Authors: Spampinato Simona Federica , Merlo Sara , Molinaro Gemma , Battaglia Giuseppe , Bruno Valeria , Nicoletti Ferdinando , Sortino Maria Angela
Published: October 2012

Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.
Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells
Authors: Jung Oisun , Choi Suyong , Jang Sun-Bok , Lee Sin-Ae , Lim Ssang-Taek , Choi Yoon-Ju , Kim Hye-Jin , Kim Do-Hee , Kwak Tae Kyoung , Kim Hyeonjung , Kang Minkyung , Lee Mi-Sook , Park Sook Young , Ryu Jihye , Jeong Doyoung , Cheong Hae-Kap , Kim Hyun Jeong , Park Ki Hun , Lee Bong-Jin , Schlaepfer David D. , Lee Jung Weon
Published: October 2012

Transmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesion-dependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer.
Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency
Authors: Pasque Vincent , Radzisheuskaya Aliaksandra , Gillich Astrid , Halley-Stott Richard P. , Panamarova Maryna , Zernicka-Goetz Magdalena , Surani M. Azim , Silva José C. R.
Published: October 2012

How cell fate becomes restricted during somatic cell differentiation is a long-lasting question in biology. Epigenetic mechanisms not present in pluripotent cells and acquired during embryonic development are expected to stabilize the differentiated state of somatic cells and thereby restrict their ability to convert to another fate. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development. Here we show that macroH2A marks the differentiated cell state during mouse embryogenesis. MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. Removal of macroH2A.1, macroH2A.2 or both increased the efficiency of induced pluripotency up to 25-fold. The obtained induced pluripotent stem cells reactivated pluripotency genes, silenced retroviral transgenes and contributed to chimeras. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. In summary, our study identifies for the first time a link between an epigenetic mark and cell fate restriction during somatic cell differentiation, which helps to maintain cell identity and antagonizes induction of a pluripotent stem cell state.
Mechanisms of transepithelial ammonia excretion and luminal alkalinization in the gut of an intestinal air-breathing fish, Misgurnus anguilliacaudatus
Authors: Wilson Jonathan M. , Moreira-Silva Joana C. , Delgado Inês L. S. , Ebanks Sue C. , Vijayan Mathilakath M. , Coimbra João , Grosell Martin
Published: October 2012

The weatherloach, Misgurnus angulliacaudatus, is an intestinal air-breathing, freshwater fish that has the unique ability to excrete ammonia through gut volatilization when branchial and cutaneous routes are compromised during high environmental ammonia or air exposure. We hypothesized that transepithelial gut NH4+ transport is facilitated by an apical Na+/H+ (NH4+) exchanger (NHE) and basolateral Na+/K+(NH4+)-ATPase, and that gut boundary layer alkalinization (NH4+ => NH3 + H+) is facilitated by apical HCO3- secretion through a Cl-/HCO3- anion exchanger. This was tested using a pharmacological approach with anterior (digestive) and posterior (respiratory) intestine preparations mounted in pH-stat equipped Ussing chambers. The anterior intestine had a markedly higher conductance, short circuit current and net base (Jbase) and ammonia excretions rates (Jamm) than posterior intestine. In anterior intestine, HCO3- accounted for 70% Jbase. In the presence of an imposed serosal-mucosal ammonia gradient, both NHE and Na+/K+-ATPase inhibitors EIPA (0.1mM) and ouabain (0.1mM) significantly inhibit Jamm in the anterior intestine, although only the former in the posterior intestine. In addition, the anion exchange inhibitor DIDS significantly reduced Jbase in anterior intestine although only at a high dose (1mM). Carbonic anhydrase does not appear to be associated with gut alkalization under these conditions since etoxzolamide was without effect on Jbase. Membrane fluidity of the posterior intestine was low suggesting low permeability, which was also reflected in a lower mucosal-serosal Jamm in the presence of an imposed gradient in contrast to the anterior intestine. To conclude although the posterior intestine is highly modified for gas exchange, it is the anterior intestine that is the likely site of ammonia excretion and alkalinization leading to ammonia volatilization in the gut.
Context-dependent correlation between resting metabolic rate and daily energy expenditure in wild chipmunks
Authors: Careau Vincent , Réale Denis , Garant Dany , Pelletier Fanie , Speakman John R. , Humphries Murray M.
Published: October 2012

Several empirical studies have shown that variation in daily energy expenditure (DEE) and resting metabolic rate (RMR) is influenced by environmental and individual factors, but whether these shared influences are responsible for, or independent of, relationships between DEE and RMR remains unknown. The objectives of this study were to i) simultaneously evaluate the effects of environmental and individual variables on DEE and RMR in free-ranging eastern chipmunks (Tamias striatus) and ii) quantify the correlation between DEE and RMR before and after controlling for common sources of variation. We found that the influence of individual factors on DEE and RMR are most often shared, whereas the influence of environmental factors tends to be distinct. Both raw and mass-adjusted DEE and RMR were significantly correlated, but this correlation vanished after accounting for the shared effect of reproduction on both traits. However, within reproductive individuals, DEE and RMR remained positively correlated after accounting for all other significant covariates. The ratio of DEE to RMR was significantly higher during reproduction than at other times of the year and was negatively correlated with ambient temperature. DEE and RMR appear to be inherently correlated during reproduction, but this correlation does not persist during other, less energy-demanding periods of the annual cycle.
Pronounced heritable variation and limited phenotypic plasticity in visual pigments and opsin expression of threespine stickleback photoreceptors
Authors: Novales Flamarique Iñigo , Cheng Christiana , Bergstrom Carolyn , Reimchen Tom
Published: October 2012

Vertebrate colour vision is mediated by the differential expression of visual pigment proteins (opsins) in retinal cone photoreceptors. Many species alter opsin expression during life, either as part of development or as a result of changes in habitat. The latter, a result of phenotypic plasticity, appears common among fishes, but its cellular origin and ecological significance are unknown. Here, we used adult threespine stickleback fish from different photic regimes to investigate heritable variability and phenotypic plasticity in opsin expression. Fish from clear waters had double cones that expressed long (LWS) and middle (RH2) wavelength opsins, one per member. In contrast, fish from red light-shifted lakes had double cones that were >95% LWS/LWS pairs. All fish had single cones that predominantly expressed a short wavelength (SWS2) opsin but ultraviolet cones, expressing a SWS1 opsin, were present throughout the retina. Fish from red light-shifted lakes, when transferred to clear waters, had a ~2% increase in RH2/LWS double cones, though double cone density remained constant. Comparison of visual pigment absorbance and light transmission in the environment indicated that the opsin complements of double cones maximized sensitivity to the background light, whereas single cones had visual pigments that were spectrally offset from the dominant background wavelengths. Our results indicate that phenotypic plasticity in opsin expression is minor in sticklebacks and may be functionally inconsequential.
Oral nifedipine versus intravenous labetalol in hypertensive urgencies and emergencies of pregnancy: a randomized clinical trial
Authors: Sathya Lakshmi B , Dasari Papa
Published: October 2012

Background:

Hypertensive crisis is an important cause of maternal and perinatal morbidity and mortality.

Aim:

To compare the efficacy of oral nifedipine and intravenous labetalol.

Materials and methods:

One hundred women with hypertensive crisis were randomized to receive either oral nifedipine 10 mg or intravenous labetalol 20 mg. Oral nifedipine was given 10 mg stat followed by 10 mg every 30 minutes up to a maximum of 50 mg. Intravenous labetalol was given 20 mg stat followed by 40 mg 30 minutes later then two more doses of 80 mg every 30 minutes up to a maximum of 220 mg. The primary outcome was the number of doses required to achieve target blood pressure (BP) and time required to reduce the mean arterial pressure by 25%. Secondary outcomes analysed included additional drugs required, resurgence of hypertensive crisis. Data were analysed using repeated measures analysis of variance (ANOVA), mixed ANOVA, unpaired t-test and chi square test and P value ≤0.05 was considered significant.

Results:

Systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) were lower than baseline at all time points of follow-up in both nifedipine and labetalol groups ( P < 0.01). P < 0.05 by repeated measures ANOVA for overall trend of changes in SBP, DBP and MAP for within-group effects in both nifedipine and labetalol groups and P < 0.05 by mixed ANOVA for between-group effects during entire observation period. The magnitude of fall in SBP, DBP and MAP was greater in the labetalol group compared with the nifedipine group ( P < 0.05). Target BP was achieved in 90% in the nifedipine group and 92% in the labetalol group. Maternal and fetal adverse effects were infrequent.

Conclusion:

Both oral nifedipine and intravenous labetalol are effective in the treatment of hypertensive crisis. Intravenous labetalol may have benefits because it is more effective in reducing the SBP, DBP and MAP to target levels with a lower number of doses.
Extending the theatre experience: The potential for wearable and onstage cameras
Authors: Stenton Phil , Geelhoed Erik , Pollard Stephen , Porter Gary , Bellaar-Spruijt Vanessa
Published: October 2012

The National Theatre has led the way in the delivery of live theatre experiences to audiences in cinemas. Audience data suggests that the programme has introduced the theatre experience to a broader audience beyond theatre-goers unable to get tickets for sell-out shows. The success
of NT Live led NESTA to conclude that a better understanding of what works for audiences and what does not with respect to digital innovation is ‘crucial for the competitiveness of the Creative Industries in the UK’.

This study presents the analysis of the Extended Theatre Experience
project and compares the reactions to a performance captured using camera locations and one that incorporates views from cameras worn by the actors and in the stage props. Home and cinema screenings are compared. Statistical analysis of the data collected is presented and conclusions are drawn
regarding the effectiveness of onstage shots to create a sense of the immediacy of the live performance.
Synaptic Refinement of an Inhibitory Topographic Map in the Auditory Brainstem Requires Functional CaV1.3 Calcium Channels
Authors: Hirtz Jan J. , Braun Nadine , Griesemer Désirée , Hannes Christian , Janz Katrin , Löhrke Stefan , Müller Britta , Friauf Eckhard
Published: October 2012

Synaptic refinement via the elimination of inappropriate synapses and strengthening of appropriate ones is crucially important for the establishment of specific, topographic neural circuits. The mechanisms driving these processes are poorly understood, particularly concerning inhibitory projections. Here, we address the refinement of an inhibitory topographic projection in the auditory brainstem in functional and anatomical mapping studies involving patch-clamp recordings in combination with minimal and maximal stimulation, caged glutamate photolysis, and single axon tracing. We demonstrate a crucial dependency of the refinement on CaV1.3 calcium channels:CaV1.3−/−mice displayed virtually no elimination of projections up to hearing onset. Furthermore, strengthening was strongly impaired, in line with a reduced number of axonal boutons. The mediolateral topography was less precise and the shift from a mixed GABA/glycinergic to a purely glycinergic transmission before hearing onset did not occur. Together, our findings provide evidence for a CaV1.3-dependent mechanism through which both inhibitory circuit formation and determination of the neurotransmitter phenotype are achieved.
Serotonergic Integration of Circadian Clock and Ultradian Sleep–Wake Cycles
Authors: Miyamoto Hiroyuki , Nakamaru-Ogiso Eiko , Hamada Kozo , Hensch Takao K.
Published: October 2012

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus generates a 24 h rhythm of sleep and arousal. While neuronal spiking activity in the SCN provides a functional circadian oscillator that propagates throughout the brain, the ultradian sleep–wake state is regulated by the basal forebrain/preoptic area (BF/POA). How this SCN circadian oscillation is integrated into the shorter sleep–wake cycles remains unclear. We examined the temporal patterns of neuronal activity in these key brain regions in freely behaving rats. Neuronal activity in various brain regions presented diurnal rhythmicity and/or sleep–wake state dependence. We identified a diurnal rhythm in the BF/POA that was selectively degraded when diurnal arousal patterns were disrupted by acute brain serotonin depletion despite robust circadian spiking activity in the SCN. Local blockade of serotonergic transmission in the BF/POA was sufficient to disrupt the diurnal sleep–wake rhythm of mice. These results suggest that the serotonergic system enables the BF/POA to couple the SCN circadian signal to ultradian sleep–wake cycles, thereby providing a potential link between circadian rhythms and psychiatric disorders.
Fast Scan Cyclic Voltammetry as a Novel Method for Detection of Real-Time Gonadotropin-Releasing Hormone Release in Mouse Brain Slices
Authors: Glanowska Katarzyna M. , Venton B. Jill , Moenter Suzanne M.
Published: October 2012

Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detectionin vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber–fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME ofhpgmice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.
The Retinoblastoma Protein Is Essential for Survival of Postmitotic Neurons
Authors: Andrusiak Matthew G. , Vandenbosch Renaud , Park David S. , Slack Ruth S.
Published: October 2012

The retinoblastoma protein (Rb) family members are essential regulators of cell cycle progression, principally through regulation of the E2f transcription factors. Growing evidence indicates that abnormal cell cycle signals can participate in neuronal death. In this regard, the role of Rb (p105) itself has been controversial. Germline Rb deletion leads to massive neuronal loss, but initial reports argue that death is non-cell autonomous. To more definitively resolve this question, we generated acute murine knock-out models of Rb in terminally differentiated neuronsin vitroandin vivo. Surprisingly, we report that acute inactivation of Rb in postmitotic neurons results in ectopic cell cycle protein expression and neuronal loss without concurrent induction of classical E2f-mediated apoptotic genes, such as Apaf1 or Puma. These results suggest that terminally differentiated neurons require Rb for continuous cell cycle repression and survival.
Digital Morphometry of Rat Cerebellar Climbing Fibers Reveals Distinct Branch and Bouton Types
Authors: Brown Kerry M. , Sugihara Izumi , Shinoda Yoshikazu , Ascoli Giorgio A.
Published: October 2012

Cerebellar climbing fibers (CFs) provide powerful excitatory input to Purkinje cells (PCs), which represent the sole output of the cerebellar cortex. Recent discoveries suggest that CFs have information-rich signaling properties important for cerebellar function, beyond eliciting the well known all-or-none PC complex spike. CF morphology has not been quantitatively analyzed at the same level of detail as its biophysical properties. Because morphology can greatly influence function, including the capacity for information processing, it is important to understand CF branching structure in detail, as well as its variability across and within arbors. We have digitally reconstructed 68 rat CFs labeled using biotinylated dextran amine injected into the inferior olive and comprehensively quantified their morphology. CF structure was considerably diverse even within the same anatomical regions. Distinctly identifiable primary, tendril, and distal branches could be operationally differentiated by the relative size of the subtrees at their initial bifurcations. Additionally, primary branches were more directed toward the cortical surface and had fewer and less pronounced synaptic boutons, suggesting they prioritize efficient and reliable signal propagation. Tendril and distal branches were spatially segregated and bouton dense, indicating specialization in signal transmission. Furthermore, CFs systematically targeted molecular layer interneuron cell bodies, especially at terminal boutons, potentially instantiating feedforward inhibition on PCs. This study offers the most detailed and comprehensive characterization of CF morphology to date. The reconstruction files and metadata are publicly distributed atNeuroMorpho.org.
Overcoming Motor “Forgetting” Through Reinforcement Of Learned Actions
Authors: Shmuelof Lior , Huang Vincent S. , Haith Adrian M. , Delnicki Raymond J. , Mazzoni Pietro , Krakauer John W.
Published: October 2012

The human motor system rapidly adapts to systematic perturbations but the adapted behavior seems to be forgotten equally rapidly. The reason for this forgetting is unclear, as is how to overcome it to promote long-term learning. Here we show that adapted behavior can be stabilized by a period of binary feedback about success and failure in the absence of vector error feedback. We examined the time course of decay after adaptation to a visuomotor rotation through a visual error-clamp condition—trials in which subjects received false visual feedback showing perfect directional performance, regardless of the movements they actually made. Exposure to this error-clamp following initial visuomotor adaptation led to a rapid reversion to baseline behavior. In contrast, exposure to binary feedback after initial adaptation turned the adapted state into a new baseline, to which subjects reverted after transient exposure to another visuomotor rotation. When both binary feedback and vector error were present, some subjects exhibited rapid decay to the original baseline, while others persisted in the new baseline. We propose that learning can be decomposed into two components—a fast-learning, fast-forgetting adaptation process that is sensitive to vector errors and insensitive to task success, and a second process driven by success that learns more slowly but is less susceptible to forgetting. These two learning systems may be recruited to different degrees across individuals. Understanding this competitive balance and exploiting the long-term retention properties of learning through reinforcement is likely to be essential for successful neuro-rehabilitation.
Glucocorticoid Suppresses Dendritic Spine Development Mediated by Down-Regulation of Caldesmon Expression
Authors: Tanokashira Daisuke , Morita Tsuyoshi , Hayashi Ken'ichiro , Mayanagi Taira , Fukumoto Kentaro , Kubota Yoshiko , Yamashita Toshihide , Sobue Kenji
Published: October 2012

Glucocorticoids (GCs) mediate the effects of stress to cause structural plasticity in brain regions such as the hippocampus, including simplification of dendrites and shrinkage of dendritic spines. However, the molecular mechanics linking stress and GCs to these effects remain largely unclear. Here, we demonstrated that corticosterone (CORT) reduces the expression levels of caldesmon (CaD), causing dendritic spines to become vulnerable. CaD regulates cell motility by modulating the actin-myosin system and actin filament stability. In cultured rat hippocampal neurons, CaD localized to dendritic spines by binding to filamentous actin (F-actin), and CaD expression levels increased during spine development. CaD stabilized the F-actin dynamics in spines, thereby enlarging the spine heads, whereas CaD knockdown decreased the spine-head size via destabilization of the F-actin dynamics. CaD was also required for chemical LTP-induced actin stabilization. The CaD expression levels were markedly decreased by exposure to CORT mediated by suppression of serum response factor-dependent transcription. High CORT levels reduced both the spine-head size and F-actin stability similarly to CaD knockdown, and overexpressing CaD abolished the detrimental effect of CORT on dendritic spine development. These results indicate that CaD enlarges the spine-head size by stabilizing F-actin dynamics, and that CaD is a critical target in the GC-induced detrimental effects on dendritic spine development.
Neural Correlates of Sensory Substitution in Vestibular Pathways following Complete Vestibular Loss
Authors: Sadeghi Soroush G. , Minor Lloyd B. , Cullen Kathleen E.
Published: October 2012

Sensory substitution is the term typically used in reference to sensory prosthetic devices designed to replace input from one defective modality with input from another modality. Such devices allow an alternative encoding of sensory information that is no longer directly provided by the defective modality in a purposeful and goal-directed manner. The behavioral recovery that follows complete vestibular loss is impressive and has long been thought to take advantage of a natural form of sensory substitution in which head motion information is no longer provided by vestibular inputs, but instead by extravestibular inputs such as proprioceptive and motor efference copy signals. Here we examined the neuronal correlates of this behavioral recovery after complete vestibular loss in alert behaving monkeys (Macaca mulatta). We show for the first time that extravestibular inputs substitute for the vestibular inputs to stabilize gaze at the level of single neurons in the vestibulo-ocular reflex premotor circuitry. The summed weighting of neck proprioceptive and efference copy information was sufficient to explain simultaneously observed behavioral improvements in gaze stability. Furthermore, by altering correspondence between intended and actual head movement we revealed a fourfold increase in the weight of neck motor efference copy signals consistent with the enhanced behavioral recovery observed when head movements are voluntary versus unexpected. Thus, together our results provide direct evidence that the substitution by extravestibular inputs in vestibular pathways provides a neural correlate for the improvements in gaze stability that are observed following the total loss of vestibular inputs.
Mechanisms of Itch Evoked by β-Alanine
Authors: Liu Qin , Sikand Parul , Ma Chao , Tang Zongxiang , Han Liang , Li Zhe , Sun Shuohao , LaMotte Robert H. , Dong Xinzhong
Published: October 2012

β-alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, β-alanine elicited itch-associated behavior that requires MrgprD, a G-protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to β-alanine, heat, and mechanical noxious stimuli but do not respond to histamine. In humans, intradermally injected β-alanine induced itch but neither wheal nor flare, suggesting that the itch was not mediated by histamine. Thus, the primary sensory neurons responsive to β-alanine are likely part of a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines.
Tracing the Emperor: Photography, Famous Places, and the Imperial Progresses in Prewar Japan
Authors: Kim Gyewon
Published: October 2012

This essay examines the relations between two distinctive photographic projects in prewar Japan: the photographic records of the imperial progresses from 1872 to 1886 and the photographic commemoration of the emperor’s sacred trace during the subsequent half-century. Together, these photographic projects re-present and re-make local landscapes through the mediation of the emperor’s sacred gaze, thereby providing a ground for new knowledge and political subjectivity in early twentieth-century Japan.
Blue Roses and Yellow Violets: Flowers and the Cultivation of Color in Nineteenth-Century France
Authors: Kalba Laura Anne
Published: October 2012

In the second half of the nineteenth century, the flowers and gardens visible in France became increasingly defined by the imperatives of commodity capitalism, in particular by the perpetual quest for variety and novelty that characterized the fashion industry. Focusing on the important role that color played in this process, this article shows how floriculture disrupted not only the relationship between the natural and the artificial and the real and the imaginary but also contemporary aesthetic standards and practices of signification.
Generalized glucocorticoid resistance caused by a novel two-nucleotide deletion in the hormone-binding domain of the glucocorticoid receptor gene NR3C1
Authors: Donner Kati M , Hiltunen Timo P , Jänne Olli A , Sane Timo , Kontula Kimmo
Published: October 2012

Objective

Generalized glucocorticoid resistance is characterized by impaired cortisol signaling, resulting from mutations of the glucocorticoid receptor (GR) geneNR3C1. The objective of our study was to identify the causative mutation in a patient with clinical manifestations compatible with generalized glucocorticoid resistance and to determine the functional consequences of the mutation. The possible occurrence ofNR3C1mutations in a selected group of hypertensive subjects with low plasma renin and aldosterone levels was also explored.

Patients

The proband, a male athlete, was diagnosed with hypertension associated with low plasma renin activity and low serum aldosterone concentration at the age of 27 years. Liddle's syndrome was suspected and the patient was treated with amiloride with initial success. Subsequent examinations revealed elevated serum cortisol and ACTH levels, with resistance to suppression with low doses of dexamethasone. After identification of anNR3C1mutation in the proband, the available family members and 51 nonrelated hypertensive subjects with low plasma renin and aldosterone concentrations were also studied.

Results

A two-nucleotide deletion in exon 9α, predicted to cause a frameshift mutation (p.L773VfsX25) in the hormone-binding domain of the GR, was identified in the patient in a heterozygous form. Affected brother and father died of premature coronary heart disease. Functional studies in COS-1 cells showed that this mutation eliminates both ligand-binding and transactivation ability of the receptor. No pathogenicNR3C1mutations were identified in 51 unrelated hypertensive patients with low plasma renin and aldosterone levels.

Conclusion

We identified a novel frameshift mutation inNR3C1as the cause of glucocorticoid resistance. The mutation eliminates the functional activity of the GR, as studied byin vitroexperiments. Mutations inNR3C1do not seem to be common causes for hypertension with low renin and aldosterone levels.
Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause
Authors: Markopoulos Marios C , Valsamakis George , Kouskouni Evangelia , Boutsiadis Anastassios , Papassotiriou Ioannis , Creatsas George , Mastorakos George
Published: October 2012

Objective

Hyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.

Subjects and methods

Blood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI).

Results

PCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS.

Conclusions

Early postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.
Influence of Winter Annual Weed Management and Crop Rotation on Soybean Cyst Nematode (Heterodera glycines) and Winter Annual Weeds: Years Four and Five
Authors: Mock Valerie A. , Creech J. Earl , Ferris Virginia R. , Faghihi Jamal , Westphal Andreas , Santini Judith B. , Johnson William G.
Published: October 2012

Certain winter annual weeds have been documented as alternative hosts to soybean cyst nematode (SCN), and infestations by such species are common in no-till production fields in the midwestern United States of Indiana, Ohio, and Illinois. The objective of this research was to determine the influence of crop rotation and winter annual weed management on winter weed growth, SCN population density, and crop yield. Two crop rotations (SS and soybean–corn rotation) and six winter annual weed-management systems (autumn-applied herbicide, spring-applied herbicide, autumn + spring applied herbicides, autumn-seeded Italian ryegrass, autumn-seeded wheat, and a nontreated check) were evaluated in long-term, no-tillage systems at West Lafayette, IN, and Vincennes, IN. In the fourth and fifth years of these experiments, the 2-yr corn–soybean rotation generally resulted in increased soybean yield, decreased winter annual weed growth, and reduced SCN population density compared with SS. Autumn or spring herbicide applications or both were a more effective option than cover crops at reducing winter annual weed density. Cover-crop systems generally did not differ from the nontreated check in winter weed density. Between years three and five, winter annual weed SCN hosts in nontreated check plots increased approximately threefold to levels as high as 102 and 245 plants m−2 at West Lafayette, IN, and Vincennes, IN, respectively, which are infestation levels at or above those commonly observed in production fields. However, controlling winter annual weeds did not influence crop yields or SCN population density. The results of these studies suggest that winter weed management, even at the high levels of weed infestation present in these studies, appears to have little value as a tool for SCN management in corn and soybean production systems in the midwestern United States.
Molecular Techniques for Discrimination of Late Watergrass (Echinochloa oryzicola) and Early Watergrass (Echinochloa oryzoides) Species in Turkish Rice Production
Authors: Mennan Husrev , Kaya-Altop Emine
Published: October 2012

Molecular techniques are useful tools for solving taxonomic confusion among species. Polymerase chain reaction (PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods were applied for the identification of barnyardgrass, early watergrass, and late watergrass. Total DNA was extracted from 266 accessions, which were collected from different rice growing areas of Turkey. The two primer sets (trn-a and trn-b1, and trn-c and trn-d) specific to a target region of the intergenic spacer between trnT (UGU) and trnL (UAA) and the entire intron region of trnL (UAA), respectively, were used in PCR amplifications. Of the 266 accessions of Echinochloa spp., only eight accessions gave a similar fragment size, which was slightly shorter than 495 bp. The PCR product obtained with the primers trn-a and trn-b1 gave two fragments when EcoRI restriction enzyme was used in barnyardgrass and early watergrass. However, not all accessions of late watergrass were digested with this enzyme. In contrast to EcoRI, the PCR product obtained using the trn-c and trn-d primer set was digested into two fragments by using AluI restriction enzyme in all accessions of late watergrass; whereas, it was not digested in barnyardgrass and early watergrass. This molecular differentiation among barnyardgrass, early watergrass, and late watergrass supports the hypothesis that late watergrass is not a synonym of early watergrass in Turkish accessions.
Benghal Dayflower (Commelina benghalensis) Seed Viability in Soil
Authors: Riar Mandeep K. , Webster Theodore M. , Brecke Barry J. , Jordan David L. , Burton Michael G. , Telenko Darcy P. , Rufty Thomas W.
Published: October 2012

Benghal dayflower is an exotic weed species in the United States that is a challenge to manage in agricultural fields. Research was conducted in North Carolina, Georgia, and Florida to evaluate the longevity of buried Benghal dayflower seeds. Seeds were buried in the field for 2 to 60 mo at a depth of 20 cm in mesh bags containing soil native to each area. In North Carolina, decline of Benghal dayflower seed viability was described by a sigmoidal regression model, with seed size having no effect on viability. Seed viability at the initiation of the study was 81%. After burial, viability declined to 51% after 24 mo, 27% after 36 mo, and < 1% after 42 mo. In Georgia, initial seed viability averaged 86% and declined to 63 and 33% at 12 and 24 mo, respectively. Burial of 36 mo or longer reduced seed viability to < 2%. The relationship between Benghal dayflower seed viability and burial time was described by a sigmoidal regression model. In Florida, there was greater variability in Benghal dayflower seed viability than there was at the other locations. Seed viability at the first sampling date after 2 mo of burial was 63%. Although there were fluctuations during the first 24 mo, the regression model indicated approximately 60% of seed remained viable. After 34 mo of burial, seed viability was reduced to 46% and then rapidly fell to 7% at 39 mo, which was consistent with the decrease in seed viability at the other locations. Although there is a physical dormancy imposed by the seed coat of Benghal dayflower, which has been detected in previous studies, it appears that a decline in buried seed viability to minimal levels occurs within 39 to 48 mo in the southeastern United States, suggesting that management programs must prevent seed production for at least four growing seasons to severely reduce the Benghal dayflower soil seedbank.