bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancies complicated by preeclampsia and non-preeclampsia-related nephrotic range proteinuria
Authors: Brown RA , Kemp GJ , Walkinshaw SA , Howse MLP
Published: August 2013

Objective

To examine the impact of nephrotic range proteinuria during pregnancy on renal, maternal and fetal outcomes.

Methods

A retrospective study of pregnant women with proteinuria greater than 3 g/24 h. Outcome measures included: gestation and mode of delivery, maternal high dependency unit admission, birth weight, maternal blood pressure and proteinuria at time of last follow-up, renal biopsy.

Results

Two hundred and sixty four pregnancies in 262 women were reviewed. Postnatal data were available in 180; of these 104 (57%) had urinary protein quantified postnatally. Sixty three (60%) were pure preeclampsia and nine (9%) super-imposed preeclampsia. Biopsy-proven renal disease was newly diagnosed in nine (9%). Sixty three per cent required caesarean section and 34% required high dependency unit admission. There were no maternal deaths. Birth weight corrected for gestation was below the fifth centile in 33%.

Conclusions

The incidence of underlying renal pathology in this cohort is significant and highlights the importance of careful follow-up.
A Pilot Study to Establish Better Eating Practices Using an Exam Room–Based Educational Video
Authors: Sirota Dana , Hametz Patricia
Published: August 2013

Objective. To evaluate whether the introduction of an exam room–based educational video in a busy clinic setting can improve Hispanic caregiver knowledge, attitudes, and children’s eating practices. Results. Between June and September of 2010, 80 caregivers enrolled in the study and a total of 37 completed the entire study. The majority of caregivers were female (90%) and Hispanic (89.9%) with a mean age of 36.9 years (±10.9). At 1-month posttesting, compared with pretesting, caregivers report their child’s consumption of “any” vegetables increased (34% to 70%, P = .01) as did self-efficacy to control portions (55.6% to 81.1%, P = .01). On multivariable analysis, older caregivers were more likely to report improvement of vegetable consumption (adjusted odds ratio = 1.28; 95% confidence interval = 1.01-1.62, P = .04). Conclusion. There may be value in providing nutrition education to caregivers during routine child care using exam room–based educational videos.
Should we think about wrist extensor after flexor tendon repair?
Authors: Ferreira Aline M , Fonseca Marisa CR , Tanaka Denise M , Barbosa Rafael I , Marcolino Alexandre M , Elui Valeria MC , Mazzer Nilton
Published: August 2013

Objective:

To evaluate the activity of wrist extensor muscle, correlating with wrist motion during gripping after flexor tendon repair.

Design:

Cross-sectional clinical measurement study.

Setting:

Laboratory for biomechanics and rehabilitation.

Subjects:

A total of 11 patients submitted to rehabilitation by early passive motion of the fingers with wrist flexion position were evaluated after 8 weeks of fingers flexor tendon repair and 11 healthy volunteers, all ranging from 20 to 37 years of age.

Intervention:

Volunteers performed an isometric standardized gripping task.

Main measures:

We used electrogoniometry to analyze wrist range of motion and surface electromyography, considering 100% maximum voluntary contraction to represent the amplitude of electromyographic activity of the extensor carpi radialis and flexor digitorum superficialis.

Results:

Patients with flexor tendon repair showed co-activation deficit between wrist extensor (extensor carpi radialis) and flexor finger muscles (flexor digitorum superficialis) during gripping in the intermediate phase of rehabilitation, despite some recovering mobility for wrist extension ( p ≤ 0.05). A moderate correlation between range of motion and extensor carpi radialis was present only for injured group ( r = 0.32). Total active motion score, which represents finger active excursion, was regular or poor in 65% of cases, all with nerve repair associated.

Conclusion:

Wrist extensors have an important synergist role at handgrip, although some imbalance can be present after flexor tendon repair. These preliminary findings suggest that emphasis could be directed to add synergistic wrist motion in rehabilitation protocols after flexor tendon repair. Future studies with early active rehabilitation are necessary.
Marital Dissolution and Major Depression in Midlife
Authors: Sbarra David A. , Emery Robert E. , Beam Christopher R. , Ocker Bailey L.
Published: August 2013

Marital dissolution is commonly assumed to cause increased depression among adults, but causality can be questioned based on directionality and third-variable concerns. The present study improves on past research by using a propensity score matching algorithm to identify a subsample of continuously married participants equivalent in divorce risk to participants who actually experienced separation/divorce between two waves of the nationally representative Midlife Development in the United States (MIDUS) study. After correcting for participants’ propensity to separate/divorce, we observed increased rates of depression at the second MIDUS assessment only among participants who (a) were depressed at the initial MIDUS assessment and (b) experienced a separation/divorce. Participants who were not depressed at the initial assessment but who experienced a separation/divorce were not at increased risk for a later major depressive disorder. Thus, both social selection and social causation contribute to the increased risk for a major depressive disorder found among separated/divorced adults.
BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells
Authors: Beurlet Stephanie , Omidvar Nader , Gorombei Petra , Krief Patricia , Le Pogam Carole , Setterblad Niclas , de la Grange Pierre , Leboeuf Christophe , Janin Anne , Noguera Maria-Elena , Hervatin Florence , Sarda-Mantel Laure , Konopleva Marina , Andreeff Michael , Tu Andrea W. , Fan Alice C. , Felsher Dean W. , Whetton Anthony , Pla Marika , West Robert , Fenaux Pierre , Chomienne Christine , Padua Rose Ann
Published: August 2013

Key Points

BCL-2 homology domain 3 mimetic inhibitor ABT-737 targets leukemia initiating cells and progenitors. Dephosphorylates RAS signaling proteins and regulates proliferation and differentiation genes detected by gene expression profiling.
Diminutive somatic deletions in the 5q region lead to a phenotype atypical of classical 5q− syndrome
Authors: Vlachos Adrianna , Farrar Jason E. , Atsidaftos Eva , Muir Ellen , Narla Anupama , Markello Thomas C. , Singh Sharon A. , Landowski Michael , Gazda Hanna T. , Blanc Lionel , Liu Johnson M. , Ellis Steven R. , Arceci Robert J. , Ebert Benjamin L. , Bodine David M. , Lipton Jeffrey M.
Published: August 2013

Key Points

Small deletions in the RPS14 region of 5q must be considered in atypical 5q− syndrome and nonclassical Diamond Blackfan anemia.
Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies
Authors: Swanson Lucas , Robertson Gordon , Mungall Karen L , Butterfield Yaron S , Chiu Readman , Corbett Richard D , Docking T Roderick , Hogge Donna , Jackman Shaun D , Moore Richard A , Mungall Andrew J , Nip Ka Ming , Parker Jeremy DK , Qian Jenny Qing , Raymond Anthony , Sung Sandy , Tam Angela , Thiessen Nina , Varhol Richard , Wang Sherry , Yorukoglu Deniz , Zhao YongJun , Hoodless Pamela A , Sahinalp S Cenk , Karsan Aly , Birol Inanc
Published: August 2013

Background

Chimeric transcripts, including partial and internal tandem duplications (PTDs, ITDs) and gene fusions, are important in the detection, prognosis, and treatment of human cancers.

Results

We describe Barnacle, a production-grade analysis tool that detects such chimeras in de novo assemblies of RNA-seq data, and supports prioritizing them for review and validation by reporting the relative coverage of co-occurring chimeric and wild-type transcripts. We demonstrate applications in large-scale disease studies, by identifying PTDs in MLL, ITDs in FLT3, and reciprocal fusions between PML and RARA, in two deeply sequenced acute myeloid leukemia (AML) RNA-seq datasets.

Conclusions

Our analyses of real and simulated data sets show that, with appropriate filter settings, Barnacle makes highly specific predictions for three types of chimeric transcripts that are important in a range of cancers: PTDs, ITDs, and fusions. High specificity makes manual review and validation efficient, which is necessary in large-scale disease studies. Characterizing an extended range of chimera types will help generate insights into progression, treatment, and outcomes for complex diseases.
The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus
Authors: Gottschalk Sanne , Ifrah Dan , Lerche Sandra , Gottlieb Caroline T , Cohn Marianne T , Hiasa Hiroshi , Hansen Paul R , Gram Lone , Ingmer Hanne , Thomsen Line E
Published: August 2013

Background

The increase in antibiotic resistant bacteria has led to renewed interest in development of alternative antimicrobial compounds such as antimicrobial peptides (AMPs), either naturally-occurring or synthetically-derived. Knowledge of the mode of action (MOA) of synthetic compounds mimicking the function of AMPs is highly valuable both when developing new types of antimicrobials and when predicting resistance development. Despite many functional studies of AMPs, only a few of the synthetic peptides have been studied in detail.

Results

We investigated the MOA of the lysine-peptoid hybrid, LP5, which previously has been shown to display antimicrobial activity against Staphylococcus aureus. At concentrations of LP5 above the minimal inhibitory concentration (MIC), the peptoid caused ATP leakage from bacterial cells. However, at concentrations close to the MIC, LP5 inhibited the growth of S. aureus without ATP leakage. Instead, LP5 bound DNA and inhibited macromolecular synthesis. The binding to DNA also led to inhibition of DNA gyrase and topoisomerase IV and caused induction of the SOS response.

Conclusions

Our data demonstrate that LP5 may have a dual mode of action against S. aureus. At MIC concentrations, LP5 binds DNA and inhibits macromolecular synthesis and growth, whereas at concentrations above the MIC, LP5 targets the bacterial membrane leading to disruption of the membrane. These results add new information about the MOA of a new synthetic AMP and aid in the future design of synthetic peptides with increased therapeutic potential.
Novel open-source electronic medical records system for palliative care in low-resource settings
Authors: Shah Kamal G , Slough Tara Lyn , Yeh Ping Teresa , Gombwa Suave , Kiromera Athanase , Oden Z Maria , Richards-Kortum Rebecca R
Published: August 2013

Background

The need for palliative care in sub-Saharan Africa is staggering: this region shoulders over 67% of the global burden of HIV/AIDS and cancer. However, provisions for these essential services remain limited and poorly integrated with national health systems in most nations. Moreover, the evidence base for palliative care in the region remains scarce. This study chronicles the development and evaluation of DataPall, an open-source electronic medical records system that can be used to track patients, manage data, and generate reports for palliative care providers in these settings.

DataPall was developed using design criteria encompassing both functional and technical objectives articulated by hospital leaders and palliative care staff at a leading palliative care center in Malawi. The database can be used with computers that run Windows XP SP 2 or newer, and does not require an internet connection for use. Subsequent to its development and implementation in two hospitals, DataPall was tested among both trained and untrained hospital staff populations on the basis of its usability with comparison to existing paper records systems as well as on the speed at which users could perform basic database functions. Additionally, all participants evaluated this program on a standard system usability scale.

Results

In a study of health professionals in a Malawian hospital, DataPall enabled palliative care providers to find patients’ appointments, on average, in less than half the time required to locate the same record in current paper records. Moreover, participants generated customizable reports documenting patient records and comprehensive reports on providers’ activities with little training necessary. Participants affirmed this ease of use on the system usability scale.

Conclusions

DataPall is a simple, effective electronic medical records system that can assist in developing an evidence base of clinical data for palliative care in low resource settings. The system is available at no cost, is specifically designed to chronicle care in the region, and is catered to meet the technical needs and user specifications of such facilities.
Comparative study of an externship program versus a corporate-academic cooperation program for enhancing nursing competence of graduating students
Authors: Tseng Chien-Ning , Hsieh Chia-Ju , Chen Kee-Hsin , Lou Meei-Fang
Published: August 2013

Background

New graduates report intense stress during the transition from school to their first work settings. Managing this transition is important to reduce turnover rates. This study compared the effects of an externship program and a corporate-academic cooperation program on enhancing junior college students’ nursing competence and retention rates in the first 3 months and 1 year of initial employment.

Methods

This two-phase study adopted a pretest and posttest quasi-experimental design. All participants were graduating students drawn from a 5-year junior nursing college in Taiwan. There were 19 and 24 students who participated in the phase I externship program and phase II corporate-academic cooperation program, respectively. The nursing competence of the students had to be evaluated by mentors within 48 hours of practicum training and after practicum training. The retention rate was also surveyed at 3 months and 1 year after beginning employment.

Results

Students who participated in the corporate-academic cooperation program achieved a statistically significant improvement in nursing competence and retention rates relative to those who participated in the externship program (p <0.01 andp <0.05, respectively).

Conclusions

The corporate-academic cooperation program facilitates the transition of junior college nursing students into independent staff nurses, enhances their nursing competence, and boosts retention rates.
Recurrence after skin-sparing mastectomy and immediate transverse rectus abdominis musculocutaneous flap reconstruction for invasive breast cancer
Authors: Liang Tsung-Jung , Wang Being-Whey , Liu Shiuh-Inn , Yeh Ming-Hsin , Chen Yu-Chia , Chen Jin-Shyr , Mok King-Tong , Chang Hong-Tai
Published: August 2013

Background

The aim of this study was to evaluate the recurrence pattern after skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) using transverse rectus abdominis musculocutaneous (TRAM) flap in patients with invasive breast cancer.

Methods

From 1995 to 2010, patients with invasive breast cancer who underwent SSM followed by IBR using TRAM flap were retrospectively reviewed. The pattern of the first recurrence event was recorded.

Results

We identified 249 consecutive patients with invasive breast cancer, two-thirds of whom (67.1%) were diagnosed with stage II or stage III disease. During a median follow-up period of 53 months, three (1.2%) local, 13 (5.2%) regional, 34 (13.7%) distant, and five (2.0%) concurrent locoregional and distant recurrences were observed. The median time to recurrences was 26 months (range, 2 to 70 months) for all recurrences, 23 months (range, 2 to 64 months) for locoregional recurrences, and 26 months (range, 8 to 70 months) for distant recurrences. All local recurrent lesions were detectable by careful physical examination, and detection of local recurrence suggested the presence of distant metastasis (60.0%). In contrast to distant metastasis, the risk of locoregional recurrence did not increase significantly with an increase in disease stage. The 5-year overall, locoregional relapse-free, and distant relapse-free survival rates were 89.7%, 90.8%, and 81.6%, respectively.

Conclusions

SSM followed by immediate reconstruction using TRAM flap is an oncologically safe procedure even in patients with advanced-stage disease. Detection of local recurrence is crucial and can be aided by a thorough physical examination.
Circulating levels and subcutaneous adipose tissue gene expression of pigment epithelium-derived factor in polycystic ovary syndrome and normal women: a case control study
Authors: Lecke Sheila B , Morsch Debora , Spritzer Poli M
Published: August 2013

Background

Polycystic ovary syndrome (PCOS) has been recognized as a metabolic disorder, manifested by abdominal obesity, insulin resistance, dyslipidemia and hypertension. Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor family, is a pleiotropic protein known for its antiangiogenic, antioxidant, and neuroprotective properties and has been shown to induce insulin resistance and play a role in glucose metabolism. Recent studies investigating circulating PEDF levels show elevated serum PEDF in association with insulin resistance in normal-weight women with PCOS, but not in obese PCOS patients. The aims of this study were 1) to assess PEDF gene expression in subcutaneous adipose tissue (scAT) from women with PCOS and nonhirsute, ovulatory controls, and 2) to determine the circulating levels of PEDF in these groups.

Methods

Total RNA was extracted from adipose tissue biopsy samples and reverse-transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels.

Results

The 22 women with PCOS and 14 non-PCOS controls included in the study had similar age, BMI, and fasting glucose, triglycerides, and HDL-cholesterol levels. Participants with PCOS exhibited higher 2 h oral glucose tolerance test levels (p = 0.006), total (p = 0.026) and LDL-cholesterol (p = 0.036), Ferriman-Gallwey score (p = 0.003) and total testosterone (p = 0.001) as compared to controls. BMI-adjusted PEDF serum levels and scAT gene expression were similar in the PCOS and control groups (p = 0.622 and p = 0.509, respectively). Circulating PEDF levels were not associated with scAT PEDF gene expression. Multiple regression analysis revealed that, in women with PCOS, insulin contributed positively and significantly to serum PEDF (p = 0.027), independently of testosterone.

Conclusion

Serum PEDF levels and scAT gene expression were associated with metabolic risk factors, but did not differ between women with PCOS and age- and BMI-matched controls. Circulating levels and scAT gene expression of PEDF were not associated in the study subjects, suggesting additional sources for PEDF in addition to or instead of fat tissue.
Transport Response is a filial-specific behavioral response to maternal carrying in C57BL/6 mice
Authors: Yoshida Sachine , Esposito Gianluca , Ohnishi Ryuko , Tsuneoka Yousuke , Okabe Shota , Kikusui Takefumi , Kato Tadafumi , Kuroda Kumi O
Published: August 2013

Background

A mother carries her young in many altricial mammals, such as cats, lions, rats and mice. During maternal carrying, the transported young assume a compact posture. We have recently shown that, in both humans and mice, the carried infants immediately calmed down and showed reductions in heart rate, distress vocalizations, and voluntary movement. The loss of the calming response in mouse pups hindered maternal retrieval efficacy. These findings suggested that the infant calming response functioned to reduce the maternal burden of carrying and was therefore conserved in a variety of mammalian species. However, it remains unclear how and when each component of this calming response develops and whether it is a filial-specific behavior.

Results

We dissected various components of the carrying-induced responses in mouse pups, collectively called the “Transport Response” herein. We showed that during the second postnatal week, pups exhibited characteristic compact posture with limb ventroflexion. The body trunk remained paradoxically pliable, suggesting complex neural regulation throughout the body. Pups also showed an increased pain tolerance to a tail pinch during the Transport Response. Analyses of the developmental courses of distinct components of the Transport Response revealed the independent regulation of each component: in the first postnatal week, the cessation of ultrasonic vocalizations was exhibited prominently; in the second postnatal week, immobilization reached its peak; and toward the third postnatal week, the postural component became fully matured. At the end of the third postnatal week, when the pups are able to transport by themselves, the pups no longer exhibited the Transport Response.

Conclusions

This study has revealed the mouse Transport Response as a complex set of behavioral and physiological components, each of which has a specific postnatal time window but is orchestrated in a well-matched manner with the maturation of ambulatory ability in the pups. These findings collectively indicate that the Transport Response is a filial-specific, innate behavioral reaction and is distinct from a simple reflex or defensive freezing response. The Transport Response could be a novel index of primitive filial attachment behaviors, acting to smooth mother-infant interaction.
Apical root resorption during orthodontic treatment with aligners? A retrospective radiometric study
Authors: Krieger Elena , Drechsler Thomas , Schmidtmann Irene , Jacobs Collin , Haag Simeon , Wehrbein Heinrich
Published: August 2013

Introduction

Objective of this study was to investigate the incidence and severity of apical root resorptions (ARR) during orthodontic treatment with aligners.

Materials and methods

The sample comprised 100 patients (17–75 years of age) with a class I occlusion and anterior crowding before treatment, treated exclusively with aligners (Invisalign®, Align Technologies, Santa Clara, CA, USA). The following teeth were assessed: upper and lower anterior teeth and first molars. Root and crown lengths of a total of 1600 teeth were measured twice in pre- and post-treatment panoramic radiographs. Afterwards, relative changes of the root length during treatment were calculated by a root-crown-ratio taking pre- and post-treatment root and crown lengths into consideration. A reduction of this ratio was considered as a shortening of the initial root length. Additionally, tooth movements of the front teeth were assessed by lateral cephalograms and the 3-dimensonal set up of each patient.

Results

All patients had a reduction of the pre-treatment root length with a minimum of two teeth. On average 7.36 teeth per patient were affected. 54% of 1600 measured teeth showed no measurable root reduction. A reduction of >0%-10% of the pre-treatment root length was found in 27.75%, a distinct reduction of >10%-20% in 11.94%. 6.31% of all teeth were affected with a considerable reduction of >20%. We found no statistically significant correlation between relative root length changes and the individual tooth, gender, age or sagittal and vertical orthodontic tooth movement; except for extrusion of upper front teeth, which was considered as not clinical relevant due to the small amount of mean 4% ARR.

Conclusions

The present study is the first analyzing ARR in patients with a fully implemented orthodontic treatment with aligners (i.e. resolving anterior crowding). The variety was high and no clinical relevant influence factor could be detected. A minimum of two teeth with a root length reduction was found in every patient. On average, 7.36 teeth per patient were affected.
Studies of ab initio and Monte Carlo simulation on interaction of fluorouracil anticancer drug with carbon nanotube
Authors: Zare Karim , Najafi Fahimeh , Sadegh Hamidreza , ghoshekandi Ramin Shahryari
Published: August 2013

In this study, we have carried out the calculation for the interaction of fluorouracil anticancer drug with carbon nanotube using Hartree-Fock theory with 3-21G basis set and molecular mechanic/Monte Carlo simulation (with MM+, AMBER, and OPLS force field) in the gas phase, methanol, and water solvents at various temperatures (298 up to 312 K). The obtained results of potential energy, Gibbs free energy, enthalpy, entropy, and dipole moment value changes are compared in gas phase, methanol, and water, and the temperature effects on the stability of the interaction between fluorouracil anticancer drug and carbon nanotube in gas phase, methanol, and water solvents.
Ca2+ and calpain control membrane expansion during rapid cell spreading of neutrophils
Authors: Dewitt S. , Francis R. J. , Hallett M. B.
Published: August 2013

Following adherence of neutrophils to the endothelium, neutrophils undergo a major morphological change which is a necessary prelude to their extravasation. We show here that this shape change is triggered by an elevation of cytosolic IP3, to provoke physiological Ca2+ influx through a store-operated mechanism. This transition from a spherical to “flattened” neutrophil morphology is rapid (about 100 s) and is accompanied by an apparent rapid expansion of the area of the plasma membrane. However, no new membrane is added into the plasma membrane. Pharmacological inhibition of calpain-activation, which is triggered by Ca2+ influx during neutrophil spreading, prevents normal cell flattening. In calpain-suppressed cells, an aberrant form of cell spreading can occur where an uncoordinated and localised expansion of the plasma membrane is evident. These data show that rapid neutrophil spreading is triggered by Ca2+ influx which causes activation of calpain, and release of furled plasma membrane to allow its apparent “expansion”.
EGFR endocytosis requires its kinase activity and N-terminal transmembrane dimerization motif
Authors: Heukers Raimond , Vermeulen Jeroen F. , Fereidouni Farzad , Bader Arjen N. , Voortman Jarno , Roovers Rob C. , Gerritsen Hans C. , van Bergen en Henegouwen Paul M. P.
Published: August 2013

EGFR signaling is attenuated by endocytosis and degradation of receptor/ligand complexes in lysosomes. Endocytosis of EGFR is known to be regulated by multiple posttranslational modifications. The observation that prevention of these modifications does not block endocytosis completely, suggests the involvement of other mechanism(s). Recently, receptor clustering has been suggested to induce internalization of multiple types of membrane receptors. However, the mechanism of clustering-induced internalization remains unknown. We have used biparatopic antibody fragments from llama (VHHs) to induce EGFR clustering without stimulating tyrosine kinase activity. Using this approach, we have found an essential role for the N-terminal GG4-like dimerization motif in the transmembrane domain (TMD) for clustering-induced internalization. Moreover, conventional EGF-induced receptor internalization depends exclusively on this TMD dimerization and kinase activity. Mutations in this dimerization motif eventually lead to reduced EGFR degradation and sustained signaling. We propose a novel role for the TMD dimerization motif in the negative feedback control of EGFR. The widely conserved nature of GG4-like dimerization motifs in transmembrane proteins suggests a general role for these motifs in clustering-induced internalization.
Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein
Authors: Lin Wan-Hsin , Hurley Joshua T. , Raines Alexander N. , Cheney Richard E. , Webb Donna J.
Published: August 2013

Myosin X (Myo10) is an unconventional myosin with two known isoforms: full-length (FL)-Myo10 that has motor activity, and a recently identified brain-expressed isoform, headless (Hdl)-Myo10, which lacks most of the motor domain. FL-Myo10 is involved in the regulation of filopodia formation in non-neuronal cells; however, the biological function of Hdl-Myo10 remains largely unknown. Here, we show that FL- and Hdl-Myo10 have important, but distinct, roles in the development of dendritic spines and synapses in hippocampal neurons. FL-Myo10 induces dendritic filopodia formation and modulates filopodia dynamics by trafficking the actin-binding protein vasodilator-stimulated phosphoprotein (VASP) to the tips of filopodia. In contrast, Hdl-Myo10 acts on dendritic spines to enhance spine and synaptic density as well as spine head expansion by increasing the retention of VASP in spines. Thus, this study shows a novel biological function for Hdl-Myo10, and an important new role for both Myo10 isoforms in the development of dendritic spines and synapses.
Amino-terminus oligomerization regulates cardiac ryanodine receptor function
Authors: Zissimopoulos Spyros , Viero Cedric , Seidel Monika , Cumbes Bevan , White Judith , Cheung Iris , Stewart Richard , Jeyakumar Loice H. , Fleischer Sidney , Mukherjee Saptarshi , Thomas N. Lowri , Williams Alan J. , Lai F. Anthony
Published: August 2013

The ryanodine receptor (RyR) is an ion channel composed of four identical subunits mediating calcium efflux from the endo/sarcoplasmic reticulum of excitable and non-excitable cells. We present several lines of evidence indicating that the RyR2 amino-terminus is capable of self-association. A combination of yeast two-hybrid screens, co-immunoprecipitation analysis, chemical cross-linking and gel filtration assays collectively demonstrate that an RyR2 N-terminal fragment possesses the intrinsic ability to oligomerize, enabling apparent tetramer formation. Interestingly, N-terminus tetramerization mediated by endogenous disulfide bond formation occurs in native RyR2, but notably not in RyR1. Disruption of N-terminal inter-subunit interactions within RyR2 results in dysregulation of channel activation at diastolic Ca2+ concentrations from ryanodine binding and single channel measurements. Our findings suggest that the N-terminus interactions mediating tetramer assembly are involved in RyR channel closure, identifying a critical role for this structural association in the dynamic regulation of intracellular Ca2+ release.
Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells
Authors: Lidsky Peter V. , Sprenger Frank , Lehner Christian F.
Published: August 2013

Centromeres are specified epigenetically in animal cells. Therefore, faithful chromosome inheritance depends critically on the accurate maintenance of epigenetic centromere marks during progression through the cell cycle. Clarification of the mechanisms that control centromere protein behavior during the cell cycle should profit from the relative simplicity of the protein cast at Drosophila centromeres. Thus we have analyzed the dynamics of the three key players Cid/Cenp-A, Cenp-C and Cal1 in S2R+ cells using quantitative microscopy and fluorescence recovery after photobleaching in combination with novel fluorescent cell cycle markers. As revealed by the observed protein abundances and mobilities, centromeres proceed through at least five distinct states during the cell cycle, distinguished in part by unexpected Cid behavior. In addition to the predominant Cid loading onto centromeres during G1, a considerable but transient increase was detected during early mitosis. Low level of Cid loading was detected in late S and G2, starting at the reported time of centromere DNA replication. Our results disclose the complexities of Drosophila centromere protein dynamics and its intricate coordination with cell cycle progression.
Regulation of Cancerous inhibitor of PP2A (CIP2A) by small molecule inhibitor for c-Jun NH2-Terminal Kinases (JNKs), SP600125, in Human Fibrosarcoma (HT1080) cells
Authors: Khanna Anchit
Published: August 2013

Background: Protein phosphatase 2A inhibition is one of the pre-requisites for human cell transformation. Previously, we have identified an endogenous inhibitor of PP2A, CIP2A (Cancerous Inhibitor of Protein Phosphatase 2A) in human fibrosarcoma cells (HT1080) using tandem affinity purification. CIP2A over expression has been demonstrated in almost every tumour type studied so far. However, our understanding on the mechanisms regulating CIP2A expression in human cancers, especially in sarcomas, is still emerging. 

Methods:  Human fibrosarcoma (HT1080) cells were treated with small molecule inhibitors against the three major signalling pathways, namely p38, MEK and JNK pathways to identify the pathway regulating CIP2A expression in the sarcoma cells. This was followed by verification of the results using small interfering RNAs (siRNA) for the kinases. 

Results:  In line with previous observations, small molecule inhibitor for MEK pathway (PD98059) decreased CIP2A mRNA and protein expression. Interestingly, small molecule inhibitor for the JNK pathway, SP600125 decreased mRNA and protein levels of CIP2A oncoprotein with negligible effect of SB203580 (p38 kinase) inhibitor on CIP2A expression in HT1080 cells. However, siRNAs specific to either JNK1 or JNK2 kinases did not result in decrease in CIP2A expression. Contrarily, two different CIP2A siRNAs, which were used as positive controls, decreased JNK2 expression in HT1080 cells. 

Conclusion: Although it is well established that SP600125 inhibits JNK kinases, it has also been shown to inhibit a spectra of other kinases. SP600125 inhibits CIP2A protein expression both in time and concentration dependent manner. However, depletion of both JNK1 and JNK2 kinases using specific siRNAs fails to decrease CIP2A protein expression levels, thereby indicating the need to verify the results obtained by treatment with small molecular inhibitors of kinases by independent approaches like two different target specific siRNAs. Finally, fortuitously we identify JNK2 as a CIP2A downstream target in HT1080 cells.
Tamanho e Número Ideal de Amostras para Coleta de Gafanhotos na Região Depressão Central do Rio Grande do Sul
Authors: Carvalho Nathália Leal , Costa Ervandil Correa , Souza Danilo Boanerges , Garlet Juliana
Published: August 2013

Objetivando observar a viabilidade de um novo método para amostragem de acridóideos (conhecidos vulgarmente por gafanhotos), bem como a distancia percorrida e número ideal de amostras para amostragem foi proposto o estudo. Os levantamentos foram conduzidos em duas áreas de campo nativo no município de São Sepé, localizado na região Depressão Central no RS. As coletas foram realizadas durante o verão de 2009 com o auxilio de uma rede de coleta adaptada. As distâncias avaliadas foram de 5, 10, 15, 20 e 25m, com oito repetições cada, sendo 40 coletas por área, a amostragem foi ao acaso. As variáveis respostas foram: adultos, ninfas, espécies e número total de insetos. Foram calculadas as estatísticas descritivas, o teste Qui-quadrado a 5% de probabilidade de erro e à relação mediana/pseudo-sigma, aliada a metodologia de reamostragem Jackknife. Foram coletados 969 espécimes distribuídos em 22 espécies, 17 Gêneros, três Famílias distintas Acrididae, Proscopiidae e Romaleidae, e duas Superfamílias (Acridoidea e Eumastacoidea). Evidenciou-se relativa eficiência do método proposto. A distancia percorrida de 25 m aliada ao número de sete amostras mostrou-se ideal para coleta de acridóideos.

Ideal Size and Number of Samples to Collect Grasshoppers in the Central Depression in Rio Grande do Sul

Abstract. Aiming to observe the viability of a new method for sampling acridoideos (by commonly known locusts) and the ideal distance and number of samples for the study sample was proposed. The surveys were conducted in two areas of native grassland in Sao Sepe, in Central Depression, Rio Grande do Sul State. Samples were collected during the summer of 2009 with the help of a network of collection adapted. The distances were measured 5, 10, 15, 20 and 25m, with eight repetitions each, of which 40 samples per area, sampling was random. The response variables were: adults, nymphs, and total number of species of insects. Descriptive statistics were calculated, Chi-square test and used the median ratio/pseudo-sigma methodology combined with Jackknife resampling. We collected 969 specimens representing 22 species, 17 Genres and three distinct families Acrididae, Proscopiidae and Romaleidae, and also two Superfamilies (Acridoidea and Eumastacoidea). It was evident relative efficiency of the proposed method. The distance traveled of 25 m coupled with the number seven samples proved to be ideal for collecting of grasshoppers.
Asymptotics of the Yang–Mills
flow for holomorphic vector bundles over Kähler manifolds: The canonical
structure of the limit
Authors: Sibley Benjamin
Published: August 2013

In the following article we study the limiting properties of the Yang–Mills
flow associated to a holomorphic vector bundle E over an arbitrary compact
Kähler manifold (X,ω). In particular we show that the flow is
determined at infinity by the holomorphic structure of E. Namely, if we
fix an integrable unitary reference connection A
0 defining the
holomorphic structure, then the Yang–Mills flow with initial condition A
0 converges (away from an appropriately defined singular set) in the
sense of the Uhlenbeck compactness theorem to a holomorphic vector bundle E
∞, which is isomorphic to the associated graded object of the
Harder–Narasimhan–Seshadri filtration of (E,A
0). Moreover, E
∞
extends as a reflexive sheaf over the singular set as the double dual of the
associated graded object. This is an extension of previous work in the cases
of one and two complex dimensions and proves the general case of a
conjecture of Bando and Siu.
Modeling the influence of thermal modification on the electrical conductivity of wood
Authors: Brischke Christian , Sachse Kathrin A. , Welzbacher Christian R.
Published: August 2013

A model has been developed aiming at the description of the effect of thermal modification on the electrical conductivity of wood. The intention was to calculate the moisture content (MC) of thermally modified timber (TMT) through the parameters electrical resistance R, wood temperature T, and CIE L*a*b* color data, which are known to correlate well with the intensity of a heat treatment. Samples of Norway spruce (Picea abies Karst.) and beech (Fagus sylvatica L.) samples were thermally modified in laboratory scale at 11 different heat treatment intensities and the resistance characteristics of the samples were determined. Within the hygroscopic range, a linear relationship between the resistance characteristics and the mass loss (ML) through the heat treatment was established. Based on this, a model was developed to calculate MC from R, T, and ML. To validate this model, color values of 15 different TMTs from industrial production were determined for estimation of their ML and fed into the model. MC of the 15 arbitrarily heat-treated TMTs was calculated with an accuracy of ±3.5% within the hygroscopic range. The material-specific resistance characteristics based on experimental data led to an accuracy of ±2.5%.
Apparent hot and cold spots of acceleration along the Atlantic and Pacific coasts of the United States
Authors: Parker Albert
Published: August 2013

While sea levels are known to oscillate with
multi-decadal periodicities worldwide up to quasi-60 years,
the most part of the literature on sea levels computes apparent
rates of rise of sea levels much larger than the legitimate
by using short time windows covering only part of a valleyto-
peak quasi-60 year multi-decadal oscillation. It is shown
that along the North Atlantic coast of the United States the
sea levels oscillate closely to the AMO index, and the rate
of rise of sea levels computed by linear fitting of the last
30-36 years of data is much higher than the true value. It is
also shown that similar minimum requirement of 60 years
of recording is needed along the North Pacific coast of the
US, where the longer periodicity of the oscillations is not
clearly defined; possibly for the strong ENSO signal covering
a quasi-60 years oscillation.
The miR-223/Nuclear Factor I-A Axis Regulates Glial Precursor Proliferation and Tumorigenesis in the CNS
Authors: Glasgow Stacey M. , Laug Dylan , Brawley Vita S. , Zhang Zhiyuan , Corder Amanda , Yin Zheng , Wong Stephen T. C. , Li Xiao-Nan , Foster Aaron E. , Ahmed Nabil , Deneen Benjamin
Published: August 2013

Contemporary views of tumorigenesis regard its inception as a convergence of genetic mutation and developmental context. Glioma is the most common and deadly malignancy in the CNS; therefore, understanding how regulators of glial development contribute to its formation remains a key question. Previously we identified nuclear factor I-A (NFIA) as a key regulator of developmental gliogenesis, while miR-223 has been shown to repress NFIA expression in other systems. Using this relationship as a starting point, we found that miR-223 can suppress glial precursor proliferation via repression of NFIA during chick spinal cord development. This relationship is conserved in glioma, as miR-223 and NFIA expression is negatively correlated in human glioma tumors, and the miR-223/NFIA axis suppresses tumorigenesis in a human glioma cell line. Subsequent analysis of NFIA function revealed that it directly represses p21 and is required for tumorigenesis in a mouse neural stem cell model of glioma. These studies represent the first characterization of miR-223/NFIA axis function in glioma and demonstrate that it is a conserved proliferative mechanism across CNS development and tumorigenesis.
Loss of NR1 Subunit of NMDARs in Primary Sensory Neurons Leads to Hyperexcitability and Pain Hypersensitivity: Involvement of Ca2+-Activated Small Conductance Potassium Channels
Authors: Pagadala Promila , Park Chul-Kyu , Bang Sangsu , Xu Zheng-Zhong , Xie Rou-Gang , Liu Tong , Han Bao-Xia , Tracey W. Daniel , Wang Fan , Ji Ru-Rong
Published: August 2013

It is well established that activation of NMDARs plays an essential role in spinal cord synaptic plasticity (i.e., central sensitization) and pain hypersensitivity after tissue injury. Despite prominent expression of NMDARs in DRG primary sensory neurons, the unique role of peripheral NMDARs in regulating intrinsic neuronal excitability and pain sensitivity is not well understood, in part due to the lack of selective molecular tools. To address this problem, we used Advillin-Cre driver to delete the NR1 subunit of NMDARs selectively in DRG neurons. In NR1 conditional knock-out (NR1-cKO) mice, NR1 expression is absent in DRG neurons but remains normal in spinal cord neurons; NMDA-induced currents are also eliminated in DRG neurons of these mice. Surprisingly, NR1-cKO mice displayed mechanical and thermal hypersensitivity compared with wild-type littermates. NR1-deficient DRG neurons show increased excitability, as indicated by increased frequency of action potentials, and enhanced excitatory synaptic transmission in spinal cord slices, as indicated by increased frequency of miniature EPSCs. This hyperexcitability can be reproduced by the NMDAR antagonist APV and by Ca2+-activated slow conductance K+(SK) channel blocker apamin. Furthermore, NR1-positive DRG neurons coexpress SK1/SK2 and apamin-sensitive afterhyperpolarization currents are elevated by NMDA and suppressed by APV in these neurons. Our findings reveal the hitherto unsuspected role of NMDARs in controlling the intrinsic excitability of primary sensory neurons possibly via Ca2+-activated SK channels. Our results also call attention to potential opposing effects of NMDAR antagonists as a treatment for pain and other neurological disorders.
Laterality Effect for Faces in Chimpanzees (Pan troglodytes)
Authors: Dahl Christoph D. , Rasch Malte J. , Tomonaga Masaki , Adachi Ikuma
Published: August 2013

Face perception in humans is governed more by right-hemispheric than left-hemispheric neural correlate. Some but not all neurophysiological studies depict a right-side dominance for face responsive neurons in the brains of macaques. Hence, it is an open question whether and to what extent a right-hemisphere preference of processing faces exists across primate brains. We investigated chimpanzees discriminating chimeric faces of chimpanzees and humans, i.e., the combination of either left or right sides of a face vertically flipped and merged into a whole face. We found an effect of choosing the left-chimeric face more often than the right-chimeric face as being the one of the two that is closer to the original face, reflecting an advantage for the right side of the brain to process faces, as reported in humans. Moreover, we found a modulation by age of the participants, suggesting that the exposure history with a particular category shapes the right-hemispheric neural correlate to a configural/holistic processing strategy. In other words, the findings in chimpanzee participants parallel those in human participants and are suggestive for similar neural machineries in the occipital-temporal cortices in both species.
Distance-Dependent Scaling of AMPARs Is Cell-Autonomous and GluA2 Dependent
Authors: Shipman Seth L. , Herring Bruce E. , Suh Young Ho , Roche Katherine W. , Nicoll Roger A.
Published: August 2013

The extensive dendritic arbor of a pyramidal cell introduces considerable complexity to the integration of synaptic potentials. Propagation of dendritic potentials is largely passive, in contrast to regenerative axonal potentials that are maintained by voltage-gated sodium channels, leading to a declination in amplitude as dendritic potentials travel toward the soma in a manner that disproportionally affects distal synaptic inputs. To counteract this amplitude filtering, Schaffer collateral synapses onto CA1 pyramidal cells contain a varying number of AMPA receptors (AMPARs) per synapse that increases with distance from the soma, a phenomenon known as distance-dependent scaling. Here, we undertake an investigation into the molecular mechanisms of distance-dependent scaling. Using dendritic recordings from rat pyramidal neurons, we confirm the basic scaling phenomenon and find that it is expressed and can be manipulated cell autonomously. Finally, we show that it depends on the presence of both a reserve pool of AMPARs and the AMPAR subunit GluA2.
Reversal of Neurofibrillary Tangles and Tau-Associated Phenotype in the rTgTauEC Model of Early Alzheimer's Disease
Authors: Polydoro Manuela , de Calignon Alix , Suárez-Calvet Marc , Sanchez Laura , Kay Kevin R. , Nicholls Samantha B. , Roe Allyson D. , Pitstick Rose , Carlson George A. , Gómez-Isla Teresa , Spires-Jones Tara L. , Hyman Bradley T.
Published: August 2013

Neurofibrillary tangles (NFTs), a marker of neuronal alterations in Alzheimer's disease (AD) and other tauopathies, are comprised of aggregates of hyperphosphorylated tau protein. We recently studied the formation of NFTs in the entorhinal cortex (EC) and their subsequent propagation through neural circuits in the rTgTauEC mouse model (de Calignon et al., 2012). We now examine the consequences of suppressing transgene expression with doxycycline on the NFT-associated pathological features of neuronal system deafferentation, NFT progression and propagation, and neuronal loss. At 21 months of age we observe that EC axonal lesions are associated with an abnormal sprouting response of acetylcholinesterase (AChE)-positive fibers, a phenotype reminiscent of human AD. At 24 months, NFTs progress, tau inclusions propagate to the dentate gyrus, and neuronal loss is evident. Suppression of the transgene expression from 18 to 24 months led to reversal of AChE sprouting, resolution of Gallyas-positive and Alz50-positive NFTs, and abrogation of progressive neuronal loss. These data suggest that propagation of NFTs, as well as some of the neural system consequences of NFTs, can be reversed in an animal model of NFT-associated toxicity, providing proof in principle that these lesions can be halted, even in established disease.