bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organism-like formation of Schistosoma hemozoin and its function suggest a mechanism for anti-malarial action of artemisinin
Authors: Sun Jun , Li Chen , Wang Suwen 
Published: October 2016

AbstractThe current theories of antimalarial mechanism of artemisinin are inadequate to fully explain the observed effects. In our study, “organism-like” formation of Schistosoma hemozoin granules by attaching to and utilizing erythrocytes to form new ones was observed. This indicates that heme iron is transferred from erythrocytes to hemozoin granules during their formation. However, as a disposal product of heme detoxification, these granules are not completely expelled from the Schistosoma gut, but decomposed again between microvilli in the posterior portion of the gut to transfer iron to eggs. Based on the function of iron transport supported by our observation of the unique process of Schistosoma hemozoin formation, here we propose a new viewpoint of antimalarial mechanism of artemisinin, which emphasizes the final outcome, i.e., interference of iron utilization in parasites by artemisinin, instead of focusing on the mode of interaction between artemisinin and heme or hemozoin. This suggests that artemisinin and its endoperoxides derivatives likely hit the Achilles’ heel of hemozoin-producing and iron-dependent organisms.
Effective pinning energy landscape perturbations for propagating magnetic domain walls
Authors: Burn D. M. , Atkinson D. 
Published: October 2016

AbstractThe interaction between a magnetic domain wall and a pinning site is explored in a planar nanowire using micromagnetics to reveal perturbations of the pinning energetics for propagating domain walls. Numerical simulations in the high damping ’quasi-static’ and low damping ’dynamic’ regimes are compared and show clear differences in de-pinning fields, indicating that dynamical micromagnetic models, which incorporate precessionally limited magnetization processes, are needed to understand domain wall pinning. Differences in the micromagnetic domain wall structure strongly influence the pinning and show periodic behaviour with increasing applied field associated with Walker breakdown. In the propagating regime pinning is complicated.
Monosodium urate crystal-induced pro-interleukin-1β production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes
Authors: Chung Yeon-Ho , Kim Dong-Hyun , Lee Won-Woo 
Published: October 2016

AbstractIL-1β is a key mediator of sterile inflammation in response to endogenous particulates, a type of damage-associated molecular pattern (DAMPs) molecule derived from damaged cells. Despite the well-known role of sterile particulates such as monosodium urate (MSU) crystals as inflammasome inducers in monocytes/macrophages, little is known regarding how pro-IL-1β synthesis is induced under sterile inflammatory conditions. We provide evidence that MSU crystals post-transcriptionally induce the rapid production of pro-IL-1β in human primary monocytes. Metabolic labeling and pull-down assays for newly-synthesized proteins clearly showed that MSU crystals rapidly, within 30 min, induce the synthesis of pro-IL-1β as well as global proteins. Notably, MSU crystal-induced pro-IL-1β synthesis is selectively dependent on the p38 MAPK pathway, whereas global protein synthesis is mediated via the mTOR, ERK1/2, and p38 pathways. Furthermore, inhibition of Mnk1, a substrate of p38, blocked MSU crystal-induced pro-IL-1β synthesis downstream of eIF4E phosphorylation. In addition, the p38 MAPK pathway leading to phosphorylation of MK2 was also critical for stabilization of pro-IL-1β mRNA following MSU stimulation. Our findings demonstrate that post-transcriptional regulation via p38 MAPK plays a central role in the rapid synthesis of pro-IL-1β in response to MSU crystals, which is an essential step for IL-1β production in human monocytes.
Novel optical gyroscope: proof of principle demonstration and future scope
Authors: Srivastava Shailesh , Rao D. S. Shreesha , Nandakumar Hari 
Published: October 2016

AbstractWe report the first proof-of-principle demonstration of the resonant optical gyroscope with reflector that we have recently proposed. The device is very different from traditional optical gyroscopes since it uses the inherent coupling between the clockwise and counterclockwise propagating waves to sense the rotation. Our demonstration confirms our theoretical analysis and simulations. We also demonstrate a novel method of biasing the gyroscope using orthogonal polarization states. The simplicity of the structure and the readout method, the theoretically predicted high sensitivities (better than 0.001 deg/hr), and the possibility of further performance enhancement using a related laser based active device, all have immense potential for attracting fresh research and technological initiatives.
The trafficking of bacterial type rhodopsins into the Chlamydomonas eyespot and flagella is IFT mediated
Authors: Awasthi Mayanka , Ranjan Peeyush , Sharma Komal , Veetil Sindhu Kandoth , Kateriya Suneel 
Published: October 2016

AbstractThe bacterial type rhodopsins are present in all the three domains of life. In contrast to the animal type rhodopsin that performs mainly sensory functions in higher eukaryotes, the bacterial type rhodopsin could function as ion channel, pumps and as sensory proteins. The functioning of rhodopsin in higher eukaryotes requires the transport of rhodopsin from its site of synthesis to the ciliated outer segment of the photoreceptive cells. However, the trafficking of bacterial type rhodopsin from its site of synthesis to the position of action is not characterized. Here we present the first report for the existence of an IFT-interactome mediated trafficking of the bacterial type rhodopsins into eyespot and flagella of the Chlamydomonas. We show that there is a light-dependent, dynamic localization of rhodopsins between flagella and eyespot of Chlamydomonas. The involvement of IFT components in the rhodopsin trafficking was elucidated by the use of conditional IFT mutants. We found that rhodopsin can be co-immunoprecipitated with the components of IFT machinery and with other protein components required for the IFT-cargo complex formation. These findings show that light-regulated localization of rhodopsin is not restricted to animals thereby suggesting that rhodopsin trafficking is an IFT dependent ancient process.
Chemical chaperone TUDCA prevents apoptosis and improves survival during polymicrobial sepsis in mice
Authors: Doerflinger Marcel , Glab Jason , Nedeva Christina , Jose Irvin , Lin Ann , O’Reilly Lorraine , Allison Cody , Pellegrini Marc , Hotchkiss Richard S. , Puthalakath Hamsa 
Published: October 2016

AbstractSepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice. Furthermore, in a ‘two-hit’ pneumonia model in mice, we have been able to demonstrate that administration of the chemical chaperone TUDCA helped to maintain lymphocyte homeostasis by significantly reducing lymphocyte apoptosis and this correlated with four-fold improvement in survival. Our results demonstrate a novel therapeutic opportunity for treating sepsis-induced lymphopenia in humans.
In vitro germ cell differentiation from embryonic stem cells of mice: induction control by BMP4 signalling
Authors: Makoolati Zohreh , Movahedin Mansoureh , Forouzandeh-Moghadam Mehdi 
Published: October 2016

The present study aims to confirm and analyse germ cell-related patterns and specific gene expressions at a very early stage of cell commitment. Following the XY cytogenetic confirmation of the CCE mouse embryonic stem cells (mESCs) line, cells were cultured to form embryoid bodies (EBs). Expression pattern assessment of the mouse vasa homologue (Mvh), Stra8, α6 and β1 integrin genes in ESC and 1–3-day-old EB showed that all genes except α6 integrin were expressed in the ESC. The mean calibration of Mvh, Stra8 and α6 integrin expression significantly increased upon EB formation compared with the ESCs. During mouse embryogenesis, the signalling of bone morphogenetic protein (BMP) is essential for germ-line formation. To investigate its role in germ-line induction in vitro, mESCs were cultured as 1-day-old EB aggregates with BMP4 for 4 days in STO co-culture systems, in the presence and absence of 5 ng/ml BMP4. At the end of the culture period, colony assay (number and diameter) was performed and the viability percentage and proliferation rate was determined. There were no significant statistical differences in the abovementioned criteria between these two groups. Moreover, the expression of Mvh, α6 and β1 integrins, Stra8 and Piwil2 genes was evaluated in co-culture groups. The molecular results of co-culture groups showed higher–but insignificant–Piwil2 and significant α6 integrin expressions in BMP4 treated co-culture systems. These results confirmed that the EB system and the presence of BMP4 in a STO co-culture system improve the differentiation of ESCs to germ cell.
Modified Elmslie–Trillat Procedure for Recurrent Dislocation of the Patella
Authors: Mitani Genya , Maeda Takashi , Takagaki Tomonori , Hamahashi Kosuke , Serigano Kenji , Nakamura Yutaka , Mochida Joji , Sato Masato 
Published: October 2016

AbstractMany groups have reported good to excellent clinical outcomes of the Elmslie–Trillat (ET) procedure for recurrent dislocation of the patella. However, the mean follow-up period of these studies was no more than 5 years. We hypothesized that the long-term postoperative outcomes of the modified ET procedure for recurrent dislocation of the patella would be acceptable compared with those of other procedures. The long-term postoperative outcomes of patients treated with the modified ET procedure were examined. A total of 31 knees in 27 patients with recurrent dislocation of the patella who underwent a modified ET procedure (without medial capsular plication) were evaluated. The mean follow-up period was 13.0 years. Pre- and postoperative radiographs were examined to determine the Q-angle, tilting angle, lateral shift ratio, sulcus angle, congruence angle, and Insall–Salvati index. Clinical outcomes were evaluated based on the Fulkerson patellofemoral joint evaluation score, Kujala score, and the presence of the apprehension sign. Radiological evaluation revealed significant postoperative improvements in the Q-angle, tilting angle, lateral shift ratio, congruence angle, Kujala score, and Fulkerson score (p < 0.001). Sixty-eight percent of all patients had a “good” or “excellent” Fulkerson score. The apprehension sign continued to be shown for six knees. Progression of osteoarthritic changes was observed in three knees, and one knee was symptomatic. The modified ET procedure provided satisfactory outcomes based on radiological and clinical evaluations. These results show the long-term effectiveness and safety of the modified ET procedure for recurrent patellar dislocation.
Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach
Authors: Marín de Mas Igor , Fanchon Eric , Papp Balázs , Kalko Susana , Roca Josep , Cascante Marta 
Published: October 2016

Abstract

Motivation
Skeletal muscle dysfunction is a systemic effect in one-third of patients with chronic obstructive pulmonary disease (COPD), characterized by high reactive-oxygen-species (ROS) production and abnormal endurance training-induced adaptive changes. However, the role of ROS in COPD remains unclear, not least because of the lack of appropriate tools to study multifactorial diseases.

Results
We describe a discrete model-driven method combining mechanistic and probabilistic approaches to decipher the role of ROS on the activity state of skeletal muscle regulatory network, assessed before and after an 8-week endurance training program in COPD patients and healthy subjects. In COPD, our computational analysis indicates abnormal training-induced regulatory responses leading to defective tissue remodeling and abnormal energy metabolism. Moreover, we identified tnf, insr, inha and myc as key regulators of abnormal training-induced adaptations in COPD. The tnf-insr pair was identified as a promising target for therapeutic interventions. Our work sheds new light on skeletal muscle dysfunction in COPD, opening new avenues for cost-effective therapies. It overcomes limitations of previous computational approaches showing high potential for the study of other multi-factorial diseases such as diabetes or cancer.

Supplementary information
Supplementary data are available at Bioinformatics online.
AUV-based acoustic observations of the distribution and patchiness of pelagic scattering layers during midnight sun†
Authors: Geoffroy Maxime , Cottier Finlo R , Berge Jørgen , Inall Mark E 
Published: October 2016

Abstract
An autonomous underwater vehicle (AUV) carrying 614 kHz RDI acoustic doppler current profilers (ADCPs) was deployed at four locations over the West Spitsbergen outer shelf in July 2010. The backscatter signal recorded by the ADCPs was extracted and analysed to investigate the vertical distribution and patchiness of pelagic organisms during midnight sun. At the northernmost locations (Norskebanken and Woodfjorden), fresher and colder water prevailed in the surface layer (0–20 m) and scatterers (interpreted as zooplankton and micronekton) were mainly distributed below the pycnocline. In contrast, more saline and warmer Atlantic Water dominated the surface layer at Kongsfjordbanken and Isfjordbanken and scatterers were concentrated in the top 20 m, above the pycnocline. Pelagic scatterers formed patchy aggregations at all locations, but patchiness generally increased with the density of organisms and decreased at depths &gt;80 m. This study contributes to our understanding of the vertical distribution of pelagic organisms in the Arctic, and the spatial coverage of the AUV has extended early acoustic studies limited to Arctic fjords from 1D observations to a broader offshore coverage. Neither synchronized nor unsynchronized vertical migrations were detected, but autonomous vehicles with limited autonomy (&lt;1 day) may not be as effective as long-term mooring deployments or long-range AUVs to study vertical migrations. Short-term AUV-based acoustic surveys of the pelagic communities are nonetheless highly complementary to Eulerian studies, in particular by providing spatial measurements of patchiness. Compared with ship-based or moored acoustic instruments, the 3D trajectory of AUVs also allows using acoustic instruments with higher frequencies and better size resolution, as well as the detection of organisms closer to the surface.
SENP1 regulates IFN-γ−STAT1 signaling through STAT3−SOCS3 negative feedback loop
Authors: Yu Tingting , Zuo Yong , Cai Rong , Huang Xian , Wu Shuai , Zhang Chenxi , Chin Y Eugene , Li Dongdong , Zhang Zhenning , Xia Nansong , Wang Qi , Shen Hao , Yao Xuebiao , Zhang Zhong-Yin , Xue Song , Shen Lei , Cheng Jinke 
Published: October 2016

Abstract
Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK−STAT1 signaling. Suppressor of cytokine signaling 1 (SOCS1) and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3−SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B), in IFN-γ signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macrophages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listeria monocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in macrophage polarization.
Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma
Authors: Yahara Katsuya , Ohguri Takayuki , Udono Hiroki , Yamamoto Junkoh , Tomura Kyosuke , Onoda Toshihiro , Imada Hajime , Nishizawa Shigeru , Korogi Yukunori 
Published: October 2016

Abstract
The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5–2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3–5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.
Optimal Time-Consistent Government Debt Maturity*
Authors: Debortoli Davide , Nunes Ricardo , Yared Pierre 
Published: October 2016

Abstract
This article develops a model of optimal government debt maturity in which the government cannot issue state-contingent bonds and cannot commit to fiscal policy. If the government can perfectly commit, it fully insulates the economy against government spending shocks by purchasing short-term assets and issuing long-term debt. These positions are quantitatively very large relative to GDP and do not need to be actively managed by the government. Our main result is that these conclusions are not robust to the introduction of lack of commitment. Under lack of commitment, large and tilted debt positions are very expensive to finance ex ante since they exacerbate the problem of lack of commitment ex post. In contrast, a flat maturity structure minimizes the cost of lack of commitment, though it also limits insurance and increases the volatility of fiscal policy distortions. We show that the optimal time-consistent maturity structure is nearly flat because reducing average borrowing costs is quantitatively more important for welfare than reducing fiscal policy volatility. Thus, under lack of commitment, the government actively manages its debt positions and can approximate optimal policy by confining its debt instruments to consols.
Comparison of efficacy of methyl prednisolone and triamcinolone in wrist ganglion using double dart technique and its application in an Indian population
Authors: Kumar Kuljit , Sharma Dhruv 
Published: October 2016

Background:
Ganglion cysts are benign soft-tissue tumors most commonly encountered in the wrist. Treatment modalities described for ganglion cysts include conservative therapy, aspiration, steroid injection, and surgical excision. The purpose of the study was to compare the efficacy of methyl prednisolone and triamcinolone in wrist ganglia using the double dart technique in an Indian population.

Methods:
All wrist ganglia (dorsal and volar) were included in the study. Patients with diabetes mellitus, tuberculosis, or rheumatoid arthritis were not included in the study. The patients included in the study were randomly divided in two groups: in one group (n=24), aspiration and methyl prednisolone acetate, 1 mL (40 mg) was injected, and in the other group (n=24) aspiration and triamcinolone acetonide, 1 mL (40 mg) was injected using the double dart technique.

Results:
Of the 48 patients included in the study, 36 (75%) were women and 12 (25%) were men, showing a female preponderance. The mean age of the patients was 37.18±6.38 yr. There was no significant difference between the methyl prednisolone group and the triamcinolone group in terms of recurrence (Fisher’s exact test, P=1.6). There were no complications in either group, but the triamcinolone group reported more pain at the injection site.

Conclusions:
Injection with methyl prednisolone is as effective as injection with triamcinolone and avoids post-injection pain.
Extensor tendon splitting versus extensor tendon sparing approach for miniplate fixation of extraarticular proximal phalangeal fractures
Authors: Abubeih Hossam M.A. , Saleh Waleed Riad , Thabet Mostafa A. , Ibrahim Abdel-Khalek H. 
Published: October 2016

Background:
Unstable phalangeal fractures constitute a challenge for surgeons with many options for operative treatment. Miniplate fixation of these fractures has the advantages of stability and neutralization of bending, rotational, and shear forces. To our knowledge, this is the first study to compare the functional results of an extensor tendon splitting approach with an extensor tendon sparing approach in extraarticular proximal phalangeal fractures fixed with a miniplate and screws.

Methods:
In a randomized prospective study we compared two groups of patients: group A, patients treated with an extensor tendon splitting approach (24 fractures in 21 patients with average age 31.9 yr) and group B, patients treated with an extensor tendon sparing approach (26 fractures in 19 patients with average age 30.8 yr). The final results were assessed with total active range of motion (TAM), grade of TAM, grip strength and Quick Disability of the Arm, Shoulder, and Hand (DASH) Score.

Results:
A TAM of 220 degrees or more was achieved in 79.2% (19/24) and 84.6% (22/26) of fractures in group A and B, respectively. There was a significant reduction in grip strength in group A compared to group B (45.9±8.4 kg vs. 51.7±7.3 kg; P<0.025). Other parameters showed slightly better results in group B compared with group A but the differences were statistically insignificant in regard to time to union (5.3+1 wk vs. 5.6+1.1 wk), TAM (226.8+18.4 degrees vs. 233.2+17.5 degrees), grading of TAM (excellent score 75% vs. 80.8%) and QuickDASH score (12±9.2 vs. 11.5±8.3).

Conclusions:
Meticulous surgical dissection, anatomical closure of layers, and early active mobilization are the keys to success in fixation of phalangeal fractures, regardless of the approach chosen.