bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST‐HCV cohort
Authors: Calvaruso Vincenza , Petta Salvatore , Cacciola Irene , Cabibbo Giuseppe , Cartabellotta Fabio , Distefano Marco , Scifo Gaetano , Di Rosolini Maria Antonietta , Russello Maurizio , Prestileo Tullio , Madonia Salvatore , Malizia Giuseppe , Montineri Arturo , Digiacomo Antonio , Licata Anna , Benanti Francesco , Bertino Gaetano , Enea Marco , Battaglia Salvatore , Squadrito Giovanni , Raimondo Giovanni , Cammà Calogero , Craxì Antonio , Di Marco Vito ,   Rete Sicilia Selezione Terapia ‐ HCV (RESIST‐HCV)
Published: April 2021

Real‐world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct‐acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post‐treatment survival of 4307 patients in the RESIST‐HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child‐Pugh A cirrhosis and 8.4% Child‐Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause‐specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA‐positive at last follow‐up. Sixty‐three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta −2.37, p < .001). Also, platelet count (HR 0.99, beta‐0.01, p = .007) and albumin value (HR 0.26, beta −1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta‐2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.
Sustained and cumulative impact of an electronic medical record‐based alert on a hepatitis C birth cohort screening programme
Authors: Fimmel Claus J. , Khan Mohammad Q. , Belopolsky Yuliya , Imas Polina , Gampa Anuhya , Sonnenberg Amnon
Published: April 2021

The study aimed to assess the effect of an electronic medical record‐embedded best practice alert (BPA) on HCV age cohort screening in primary care clinics. HCV testing by primary care physicians was monitored prior and subsequent to the implantation of the BPA. Four intervals of 9 months duration were analysed in detail, including a pre‐BPA baseline analysis and three annual post‐BPA assessments. Pre‐ and post‐BPA orders consistently followed a power law distribution, characterized by small groups of physicians placing the majority of test orders. Significant correlations were present between the numbers of tests orders by each physician, suggesting that ‘high’ and ‘low’ screening performances tended to be physician‐specific. Testing rates increased markedly in response to the BPA, resulting in completion of screening in 56.8% (50,468 of 88,914%) of the entire age cohort within less than 3 years. In conclusion, HCV age cohort testing by primary care physicians follows a power‐law distribution, with high‐performing physicians contributing disproportionately to the overall effort. A simple BPA resulted in a sufficient increase in testing to allow testing of the entire target population within a reasonable time frame.
Parental care does not compensate for the effects of bad years on reproductive success of a vagile bird
Authors: Stojanovic D. , McEvoy J. , Alves F. , Rayner L. , Heinsohn R. , Saunders D. , Webb M.
Published: April 2021

Life history theory predicts that long‐lived animals trade off the costs of reproduction against individual survival. If the costs of reproduction are too high, animals should prioritize their own survival. During bad times, mobile animals may be able to compensate for local food shortages by travelling further to provision their offspring. But, whether inherent mobility alleviates individual fitness costs of this parental strategy is not known. We studied parental investment and breeding success of long‐lived, nomadic, migratory swift parrots Lathamus discolor over two successive years at the same site where food abundance went from locally low to high. We hypothesize that in a bad year, swift parrots should adjust their parental strategy by foregoing breeding altogether, producing smaller clutches/broods or reducing provisioning investment. Fewer swift parrots bred locally when food was scarce. In the bad year, clutch and brood sizes were smaller and nestlings were >20 g lighter (approximately 28% of mean body mass) than in the good year. Compared with the good year, fathers spent longer foraging, less time at the nest and travelled further during provisioning trips in the bad year. Although limited to only 2 years, our results suggest that mobile species may attempt to mitigate the effects of a bad year on their reproductive success by rearing fewer offspring and investing more in provisioning behaviour, but this strategy may not necessarily compensate for environmental conditions.
Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2
Authors: Yamada Tsuyoshi , Yaguchi Takashi , Tamura Takashi , Pich Christine , Salamin Karine , Feuermann Marc , Monod Michel
Published: April 2021

Background

Dermatophytes showing reduced sensitivity to antifungal agents have emerged in several countries. One terbinafine resistant strain of Trichophyton rubrum, TIMM20092, also showed reduced sensitivity to itraconazole (ITC) and voriconazole (VRC). The expression of two genes (TruMDR2 and TruMDR3) encoding multidrug transporters of the ABC family was found to be highly up‐regulated in this strain. Deletion of TruMDR3 in TIMM20092 abolished its resistance to VRC but only slightly reduced its resistance to ITC.

Objectives

We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.

Methods

The deletion of TruMDR2 by gene replacement was performed in TIMM20092 and one TruMDR3‐lacking mutant (∆TruMDR3) previously generated from TIMM20092. TruMDR2 single and TruMDR2/TruMDR3 double mutants (∆TruMDR2 and ∆TruMDR2/3) were successfully obtained, respectively.

Results

The suppression of TruMDR2 was shown to abolish resistance to ITC in TIMM20092 and the TruMDR3‐lacking mutant, strongly suggesting that TruMDR2 is a major contributor to ITC resistance in TIMM20092.

Conclusions

Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
The influence of CYP2C19 polymorphisms on voriconazole trough concentrations: Systematic review and meta‐analysis
Authors: Zhang Ying , Hou Kelu , Liu Fang , Luo Xingxian , He Shiyu , Hu Lei , Yang Changqing , Huang Lin , Feng Yufei
Published: April 2021

Background

Voriconazole primary metabolism is catalysed by CYP2C19. A large variability of trough concentrations in patients with invasive fungal infection treated with voriconazole has been observed in clinical practice. It remains controversial whether the CYP2C19 polymorphisms are responsible for voriconazole metabolism in the individual variation.

Objectives

The primary aim of this study was to assess the effect of CYP2C19 polymorphisms on voriconazole trough concentrations.

Methods

Following a systematic literature review, we performed a meta‐analysis for mean differences (MD) of voriconazole trough concentrations (Cmin), voriconazole dosage adjusted trough concentrations (Cmin/D) and for risk ratio (RR) of the proportion of patients in the target therapeutic range between pairwise comparisons of CYP2C19 phenotypes.

Results

Compared with normal metabolisers (NMs), intermediate metabolisers (IMs) (MD: 0.82, 95% CI: 0.57 to 1.07, I2 = 44%, p < .00001) or poor metabolisers (PMs) (MD: 1.59, 95% CI: 1.14 to 2.05, I2 = 46%, p < .00001) had significantly higher voriconazole Cmin (μg·ml−1), while rapid metabolisers (RMs) had significantly lower voriconazole Cmin (MD: −0,87, 95% CI: −1.35 to −0.38, I2 = 0%, p = .0004). In addition, IMs had significantly lower Cmin than PMs (MD: −0.59, 95% CI: −0.97 to −0.20, I2 = 22%, p = .003). Similarly, the Cmin/D (μg·kg·ml−1·mg−1) was significantly higher in IMs (MD: 0.13, 95% CI: 0.05 to 0.22, I2 = 0%, p = .002) and PMs (MD: 0.20, 95% CI: 0.07 to 0.34, I2 = 0%, p = .003) than that in NMs, and also, IMs had significantly lower Cmin/D than PMs (MD: −0.11, 95% CI: −0.14 to −0.08, I2 = 0%, p < .00001). Furthermore, PMs had a significantly higher proportion of the target therapeutic range than NMs (RR: 1.34, 95% CI: 1.09 to 1.64, I2 = 50%, p = .005).

Conclusions

Compared to NMs, IMs and PMs had higher voriconazole trough concentrations, especially in Asians, while RMs had lower voriconazole trough concentrations. In addition, PMs had a higher proportion of the target therapeutic range than NMs, especially in Asians. CYP2C19 genotyping is expected to be used to preemptively guide the individualisation of voriconazole in clinical practice.
What drives the energy consumption mix in Nigeria? The role of financial development, population age groups, urbanization and international trade: insight from ARDL Analysis
Authors: Okere Kingsley Ikechukwu , Ogbulu Onyemachi Maxwell , Onuoha Favour Chidinma , Ogbodo Izuchukwu
Published: April 2021

Abstract

This study aims to investigate the influence and the direct causal relationship between energy consumption and the selected explanatory variables in the Nigerian economic system. Using ARDL‐VECM over the period of 1972–2014, the results are that financial development exerts negative and significant influence on energy consumption. Trade openness and urbanisation exert positive and significant effect on energy consumption both in the short and long run, the active age (15–64) and old age (65 and >) have different effects on energy consumption. Although the number of the older population (age 65 and above) causes the energy consumption level to fall, the size of the working/active population (age 15–64) causes the energy consumption level to increase. Further results revealed (i) unidirectional causality runs from working population to energy consumption, (ii) uni‐directional causality runs from energy consumption to credit to private sector, (iii) uni‐directional from trade openness to real GDP per capita, (iv) bi‐directional causal relationship is observed between urbanisation and energy consumption, (v) bi‐directional relationship between trade openness and energy consumption. These findings may be a guide to policymakers in evaluating Nigerian economy's energy needs and effective energy policies needed to address environmental issues related to fossil fuel use.
Magnesium sulfate reduces postoperative pain in women with cesarean section: A meta‐analysis of randomized controlled trials
Authors: Ma Siguang , Zhang Yanju , Li Qian
Published: April 2021

Objectives

The use of magnesium sulfate (MgSO4) as an adjunct in different anesthetic regimens for cesarean section (CS) delivery often reports conflicting results. This study aimed to review the effectiveness of MgSO4 on improving postoperative analgesia after CS systematically.

Methods

PubMed, Embase, and the Cochrane library were searched for randomized controlled trials (RCTs) published from inception to February 2020.

Results

A total of 880 women were included (440 in each group). MgSO4 had a statistically significant effect compared to the control group on the highest VAS (weighted mean difference [WMD] = −0.74, 95% confidence interval [CI] = −1.03 to −0.46, p < 0.001, I2 = 91.7%, pheterogeneity < 0.001) and the last VAS (WMD = −0.47, 95% CI = −0.71 to −0.23, p < 0.001, I2 = 95.0%, pheterogeneity < 0.001). MgSO4 prolonged the time to the first use of analgesia compared to the control group (standardized mean difference [SMD] = −3.03 min, 95% CI = −4.32 to −1.74, p < 0.001, I2 = 96.3%, pheterogeneity < 0.001). MgSO4 decreased the consumption of analgesia compared to the control group (SMD = −3.20 mg of IV morphine equivalent, 95% CI: −5.45 to −0.95, p = 0.005, I2 = 97.6%, pheterogeneity < 0.001).

Discussion

MgSO4 decreases the highest VAS in women who underwent general anesthesia, spinal anesthesia, or epidural for CS (all p < 0.05). Additional MgSO4 significantly reduces postoperative pain in women undergoing CS.
The influence of HLA genotype on the severity of COVID‐19 infection
Authors: Langton David J. , Bourke Stephen C. , Lie Benedicte A. , Reiff Gabrielle , Natu Shonali , Darlay Rebecca , Burn John , Echevarria Carlos
Published: April 2021

The impact of COVID‐19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in HLA genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID‐19 infection. Forty‐nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre‐existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA‐DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01‐DQB1*05:01‐DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID‐19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID‐19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.
THE SIMULATION OF MECHANICAL STIMULATION EFFECT ON BONE ELASTICITY LIMIT BASED ON FINITE ELEMENT METHOD (FEM)
Authors: Yakin Khusnul , Setyaningsih Ita , Rusmana Nurani Indha , Tirono Mohammad , Umam Rofiqul
Published: April 2021

Osteoporosis is a disease  affecting bones which is characterized by decreased bone density;  bones become porous and  susceptible to fractures. Osteoporosis occurs because of an imbalance during bone remodeling phase between resorption and formation processes. This study aims to simulate the effects of mechanical stimulations on the femoral bone elasticity limit. It is hoped that these mechanical stimuli can provide information on bone elasticity limits. Initially, we constructed the femur in two layers using triangular elements. Then we entered the bone properties (Young’s modulus and Poisson’s ratio) based on the age of the femur. After that we  calculated the value of the stress, strain, and strain rate in the reversal phase. Next, we calculated the  bone density using the thermodynamic equation and calculation of the bone elasticity limit using particle swarm optimization (PSO) methods. The value of stress and strain caused by walking is higher than the value of stress and strain when standing still. In this case, the difference in activity results an increase in stress by 33.82% and an increase in strain and strain rate by 34.57%. Based on these simulation results, it can be concluded that mechanical stimulation can increase the limit of bone elasticity to 2.99% in cortical bone and 0.975% in trabecular bone. Bone elasticity limit can be used to determine the level of osteoporosis that occurs. The higher value of the bone elasticity, the smaller the possibility of osteoporosis.
EVALUATION ON THE REDUCED GRAPHENE OXIDE THERMAL INTERFACE MATERIAL AND HEAT SPREADER FOR THERMAL MANAGEMENT IN HIGH-TEMPERATURE POWER DEVICE
Authors: Abdullah Mohd Faizol , Mohamad Badaruddin Siti Aishah , Mat Hussin Mohd Rofei , Syono Mohd Ismahadi
Published: April 2021

Thermally conductive reduced graphene oxide (rGO) is desirable for removing generated heat during the operation of a power device. Excessive heat accumulation results in device failure. In this article, the performance of rGO as a thermal interface material (TIM) and heat spreader on Si substrate was evaluated using a custom build thermal test setup. By a simple drop-casting of graphene oxide (GO) on Si followed by 700 oC thermal reduction, a hybrid film of GO (electrical insulator) and rGO (thermal conductor) was obtained. This was verified by Raman spectra and surface morphological image. Approximately 300 nm-thick rGO film prepared from 4-times drop-casting of GO exhibited the highest performance as a TIM and heat spreader. The heating rate of Si increased from 14.85 oC/W to 18.37 oC/W due to the improved heat transfer from the heater into the Si substrate. The experimental results endorsed the effectiveness of rGO as a thermal solution and verified the capability of the thermal test setup as a thermal simulation of a high-power device.
Regimes of motion of magnetocapillary swimmers
Authors: Sukhov Alexander , Hubert Maxime , Grosjean Galien , Trosman Oleg , Ziegler Sebastian , Collard Ylona , Vandewalle Nicolas , Smith Ana-Sunčana , Harting Jens
Published: April 2021

The dynamics of a triangular magnetocapillary swimmer is studied using the lattice Boltzmann method. We extend on our previous work, which deals with the self-assembly and a specific type of the swimmer motion characterized by the swimmer’s maximum velocity centred around the particle’s inverse viscous time. Here, we identify additional regimes of motion. First, modifying the ratio of surface tension and magnetic forces allows to study the swimmer propagation in the regime of significantly lower frequencies mainly defined by the strength of the magnetocapillary potential. Second, introducing a constant magnetic contribution in each of the particles in addition to their magnetic moment induced by external fields leads to another regime characterized by strong in-plane swimmer reorientations that resemble experimental observations.

Graphic Abstract
Design of high-resolution flow sensor used in cold gas micro propulsion system
Authors: Zhu Xiaocheng , Chen Yan , Lin Huang , Guo Bin , Guo Xiaoliang ,   On behalf of The Taiji Scientific Collaboration
Published: April 2021

Cold Gas Micro Propulsion (CGMP) is a reliable technology for spacecraft attitude and orbit control used in drag-free control system to compensate the environmental disturbance from the aerospace. The CGMP requiring a very fine control resolution and low noise is desired to be used on TAIJI mission for gravitational wave detection which is supported by Chinese Academy of Science (CAS). One of CGMP’s key technologies is high-resolution Gas Mass Flow Sensor (GMFS). In this paper, calorimetric thermal flow sensor characterized with miniaturization, high sensitivity and low noise is studied by simulation method and manufacturing process. By simulating the influence of heating power, electrode distance, temperature, etc. on sensor response, the methods on optimizing sensitivity and accuracy have been proposed. The sensitivity is about 2.53 mV/(m/s)/mW. An amplifier circuit with ultra-low noise of 7.29 nV/[Formula: see text]Hz for reading out has been designed, which is essential for high resolution. The sensor was fabricated and preliminary tests have been conducted. The sensitivity of the sensor is about 100 mV/(m/s).
QoS‐Oriented Optimal Relay Selection in Cognitive Radio Networks
Authors: Alvi Shakeel A. , Hussain Riaz , Shakeel Atif , Javed Muhammad Awais , Hasan Qadeer Ul , Lee Byung Moo , Malik Shahzad A.
Published: April 2021

A cognitive radio network can be employed in any wireless communication systems, including military communications, public safety, emergency networks, aeronautical communications, and wireless‐based Internet of Things, to enhance spectral efficiency. The performance of a cognitive radio network (CRN) can be enhanced through the use of cooperative relays with buffers; however, this incurs additional delays which can be reduced by using virtual duplex relaying that requires selection of a suitable relay pair. In a virtual duplex mode, we mimic full‐duplex links by using simultaneous two half‐duplex links, one transmitting and the other one receiving, in such a way that the overall effect of duplex mode is achieved. The relays are generally selected based on signal‐to‐interference‐plus‐noise ratio (SINR). However, other factors such as power consumption and buffer capacity can also have a significant impact on relay selection. In this work, a multiobjective relay selection scheme is proposed that simultaneously takes into account throughput, delay performance, battery power, and buffer status (i.e., both occupied and available) at the relay nodes while maintaining the required SINR. The proposed scheme involves the formulation of four objective functions to, respectively, maximize throughput and buffer space availability while minimizing the delay and battery power consumption. The weighted sum approach is then used to combine these objective functions to form the multiobjective optimization problem and an optimal solution is obtained. The assignments of weights to objectives have been done using the rank sum (RS) method, and several quality‐of‐service (QoS) profiles have been considered by varying the assignment of weights. The results gathered through simulations demonstrate that the proposed scheme efficiently determines the optimal solution for each application scenario and selects the best relay for the respective QoS profile. The results are further verified by using the genetic algorithm (GA) and particle swarm optimization (PSO) techniques. Both techniques gave identical solutions, thus validating our claim.
Clinical Diagnosis has a High Negative Predictive Value in Evaluation of Malignant Skin Lesions
Authors: Seyed Ahadi Maral , Firooz Alireza , Rahimi Hoda , Jafari Mehrdad , Tehranchinia Zohreh
Published: April 2021

Background. The increasing incidence of skin cancers in fair-skinned population and its relatively good response to treatment make its accurate diagnosis of great importance. We evaluated the accuracy of clinical diagnosis of malignant skin lesions by comparing the clinical diagnosis with histological diagnosis as the gold standard. Materials and Methods. In this retrospective study, we assessed all the pathology reports from specimens sent to a university hospital laboratory in 3 consecutive years from March 2008 to March 2010. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios were calculated for clinical diagnosis of malignant skin lesions stratified by their histological subtype. Results. A total 4,123 specimen were evaluated. The sensitivity and specificity for clinical diagnosis of malignancy were 90.48% and 82.85%, respectively, whereas the negative predictive value was shown to be 99.06%. The positive and negative likelihood ratios were 5.23 and 0.11, respectively. Conclusion. Pathological assessment of skin lesions remains the cornerstone of skin cancer diagnosis. The high NPV and the relatively low PPV indicate that clinical diagnosis is more efficient in ruling out malignancies rather than diagnosing them.
The Jewish–Tat Relations and the Issue of Mountain Jews Identity (Part I)
Authors: Adamczewski Przemysław
Published: April 2021

The aim of this article is to present mainly those aspects of the interviews that concerned the relationship of Mountain Jews to the Tats. In addition, issues regarding the language, identity, and relations of Mountain Jews with other ethnic groups are discussed. The article is based on interviews that were conducted as part of a research project “Between the Caucasus and Jerusalem: Mountain Jews in the Dialogue of Cultures” carried out by the “Sefer” Center for University Teaching of Jewish Civilization. This project aims to explore the history, culture, and identity of Mountain Jews. So far, two scientific expeditions have taken place—one in August 2018 and another in August 2019, both to southern Dagestan. Participants of the expedition were divided into two groups—epigraphic and ethnographic. The task of the ethnographic group was to conduct interviews with representatives of the Mountain Jew community living in southern Dagestan. In 2018, these were conducted in Derbent and Nyugdi. In 2019, interviews were conducted with Mountain Jews living in Derbent, in Nyugdi and with inhabitants of Dzhalgan.
Indo-Iranian *mastr̥ghan- / *mastr̥ǰhan- ‘Brain, Skull’ and its Etymology
Authors: Lubotsky Alexander
Published: April 2021

The purpose of this short note is to clarify the meaning, the original inflection and the etymology of the Indo-Iranian word *mastr̥ghan- / *mastr̥ǰhan- ‘brain, skull’.
A Triangle of Interests: Azerbaijan, Iran and Israel
Authors: Cohen, Tzvi Lev Ronen A.
Published: April 2021

In the world of Realpolitik, Israel and Azerbaijan seem to have closer relations than just pragmatic ones. This article intends to shed light on the strategic and regional interests of Israel and Azerbaijan, while considering Iran’s efforts to maintain an alliance with Azerbaijan. From the Israeli side, these relations have multi-dimensional components that enable Israel to keep an eye on Iran without dragging Azerbaijan into the conflict. Azerbaijan and Iran, for their part, sharing a common religion and, partly, culture, both use Realpolitik in order to retain the Caucasus balance of power.
汉语方言中源于连接词的句末先行义助词及语法化问题
Authors: 李 桂兰
Published: April 2021

汉语方言中句末先行义助词“正、再、至、□（[sa5]）”和“可”等兼具连接功能，文章考察其功能后，认为上述先行义助词源于祈愿句中相应连接词省略后项内容后的重新分析，是语法化而非征派（/移位）的结果。文章第四部分讨论了连接词发展为句末助词的相关问题，补充了连接词的语义来源类别。
Political Dynasties and Economic Development: Evidence using Nighttime Light in the Philippines
Authors: Garces Ludigil , Jandoc Karl , Lu Mary Grace
Published: April 2021

Political dynasties, by limiting political competition, are thought to exacerbate corruption, poverty, and abuse of power. This paper examines the economic effects of the presence of political dynasties in Philippine cities and municipalities, taking into account possible channels in the local dynastic cycle – the framework in which politicians try to balance their goals to perform well for their constituents, to divert resources for personal gain, and to continue to be in power. Due to the lack of extensive income accounts or other economic indicators in finer geographical units (i.e., city or municipality level), we use the Defense Meteorological Satellite Program-Operational Linescan System (DMSP-OLS) nighttime light data as our proxy for economic activity. Using a panel of Philippine municipalities and cities, we find that, in general, the relationship of political dynasties on economic performance is weak. However, we find that a higher share of economic expenditures leads to lower economic development in municipalities where the mayor, governor, and congressman belong to the same clan. We see this as an indication of weak institutions of checks and balances in localities with dynasties.
Integrated transcriptome and proteome analysis reveals complex regulatory mechanism of cotton in response to salt stress
Authors: CHEN Lin , SUN Heng , KONG Jie , XU Haijiang , YANG Xiyan
Published: April 2021

Background

Soil salt stress seriously restricts the yield and quality of cotton worldwide. To investigate the molecular mechanism of cotton response to salt stress, a main cultivated variety Gossypium hirsutum L. acc. Xinluzhong 54 was used to perform transcriptome and proteome integrated analysis.

Results

Through transcriptome analysis in cotton leaves under salt stress for 0 h (T0), 3 h (T3) and 12 h (T12), we identified 8 436, 11 628 and 6 311 differentially expressed genes (DEGs) in T3 vs. T0, T12 vs. T0 and T12 vs. T3, respectively. A total of 459 differentially expressed proteins (DEPs) were identified by proteomic analysis, of which 273, 99 and 260 DEPs were identified in T3 vs. T0, T12 vs. T0 and T12 vs. T3, respectively. Metabolic pathways, biosynthesis of secondary metabolites, photosynthesis and plant hormone signal transduction were enriched among the identified DEGs or DEPs. Detail analysis of the DEGs or DEPs revealed that complex signaling pathways, such as abscisic acid (ABA) and jasmonic acid (JA) signaling, calcium signaling, mitogen-activated protein kinase (MAPK) signaling cascade, transcription factors, activation of antioxidant and ion transporters, were participated in regulating salt response in cotton.

Conclusions

Our research not only contributed to understand the mechanism of cotton response to salt stress, but also identified nine candidate genes, which might be useful for molecular breeding to improve salt-tolerance in cotton.
Inductive signal and tissue responsiveness defining the tectum and the cerebellum
Authors: Sato Tatsuya , Araki Isato , Nakamura Harukazu
Published: April 2021

The mes/metencephalic boundary (isthmus) has an organizing activity for mesencephalon and metencephalon. The candidate signaling molecule is Fgf8 whose mRNA is localized in the region where the cerebellum differentiates. Responding to this signal, the cerebellum differentiates in the metencephalon and the tectum differentiates in the mesencephalon. Based on the assumption that strong Fgf8 signal induces the cerebellum and that the Fgf8b signal is stronger than that of Fgf8a, we carried out experiments to misexpress Fgf8b and Fgf8a in chick embryos. Fgf8a did not affect the expression pattern of Otx2, Gbx2 or Irx2. En2 expression was upregulated in the mesencephalon and in the diencephalon by Fgf8a. Consequently, Fgf8a misexpression resulted in the transformation of the presumptive diencephalon to the fate of the mesencephalon. In contrast, Fgf8b repressed Otx2 expression, but upregulated Gbx2 and Irx2 expression in the mesencephalon. As a result, Fgf8b completely changed the fate of the mesencephalic alar plate to cerebellum. Quantitative analysis showed that Fgf8b signal is 100 times stronger than Fgf8a signal. Co-transfection of Fgf8b with Otx2 indicates that Otx2 is a key molecule in mesencephalic generation. We have shown by RT-PCR that both Fgf8a and Fgf8b are expressed, Fgf8b expression prevailing in the isthmic region. The results all support our working hypothesis that the strong Fgf8 signal induces the neural tissue around the isthmus to differentiate into the cerebellum.
The role of an endogenous PKA inhibitor, PKIα, in organizing left-right axis formation
Authors: Kawakami Minoru , Nakanishi Nobuki
Published: April 2021

Protein kinase inhibitor (PKI) is an endogenous inhibitor of cAMP-dependent protein kinase A (PKA). We have found that the α-isoform of PKI (PKIα) is asymmetrically expressed along the left-right (L-R) axis in chick embryos. At stage 6, PKIα is expressed on the right side of the node, and this asymmetric expression continues until stage 7+. After stage 8, PKIα expression returns symmetric. Treatment of embryos with antisense PKIα oligonucleotides increased the incidence of reversed heart looping. Antisense oligonucleotides also induced ectopic expression of the left-specific genes Nodal and Pitx2, and suppressed the expression of the right-specific gene SnR in the right lateral plate mesoderm. Similarly, treatment with PKA activators forskolin and Sp-cAMPs resulted in both reversed heart looping and bilateral expression of Nodal. Ectopic activin induced PKIα on the left side of the node, while ectopic Shh and anti-Shh antibody had no effect on PKIα expression. Taken together, these data suggest that PKIα induced by an activin-like molecule, through the inhibition of PKA activity, suppresses the Nodal-Pitx2 pathway on the right side of the body.
Extranuclear sequestration of phospho-Jun N-terminal kinase and distorted villi produced by activated Rac1 in the intestinal epithelium of chimeric mice
Authors: Stappenbeck Thaddeus S. , Gordon Jeffrey I.
Published: April 2021

Previously, we used a genetic mosaic system to conduct an in vivo analysis of the effects of Rac1 activation on the developing intestinal epithelium (Stappenbeck, T. S. and Gordon, J. I. (2000) Development127, 2629-2642). Expression of a constitutively active human Rac1 (Rac1Leu61) in the 129/Sv-derived small intestinal epithelium of C57Bl/6-ROSA26↔129/Sv chimeric mice led to precocious differentiation of some lineages with accompanying alterations in their apical actin. We have now explored the underlying mechanisms. Rac1Leu61 leads to accumulation of the 46 kDa form of phosphorylated Jun N-terminal kinase (p-Jnk) in the apical cytoplasm, but not in the nucleus of E18.5 proliferating and differentiating intestinal epithelial cells. The effect is cell-autonomous, selective for this mitogen-activated protein kinase family member, and accompanied by apical cytoplasmic accumulation of p21-activated kinase. c-Jun, a downstream nuclear target of p-Jnk, does not show evidence of enhanced phosphorylation, providing functional evidence for cytoplasmic sequestration of p-Jnk in Rac1Leu61-expressing epithelium. In adult chimeras, Rac1 activation augments cell proliferation in crypts of Lieberkühn, without a compensatory change in basal apoptosis and produces a dramatic, very unusual widening of villi. These results reveal a novel in vivo paradigm for Rac1 activation involving p-Jnk-mediated signaling at a distinctive extra-nuclear site, with associated alterations in the actin cytoskeleton. They also provide a new perspective about the determinants of small intestinal villus morphogenesis.
Morphogenetic pattern formation during ascidian notochord formation is regulative and highly robust
Authors: Munro Edwin M. , Odell Garrett
Published: April 2021

The ascidian notochord forms through simultaneous invagination and convergent extension of a monolayer epithelial plate. Here we combine micromanipulation with time lapse and confocal microscopy to examine how notochord-intrinsic morphogenetic behaviors and interactions with surrounding tissues, determine these global patterns of movement. We show that notochord rudiments isolated at the 64-cell stage divide and become motile with normal timing; but, in the absence of interactions with non-notochordal tissues, they neither invaginate nor converge and extend. We find that notochord formation is robust in the sense that no particular neighboring tissue is required for notochord formation. Basal contact with either neural plate or anterior endoderm/lateral mesenchyme or posterior mesoderm are each alone sufficient to ensure that the notochord plate forms and extends a cylindrical rod. Surprisingly, the axis of convergent extension depends on the specific tissues that contact the notochord, as do other patterns of cell shape change, movement and tissue deformation that accompany notochord formation. We characterize one case in detail, namely, embryos lacking neural plates, in which a normal notochord forms but by an entirely different trajectory. Our results show ascidian notochord formation to be regulative in a fashion and to a degree never before appreciated. They suggest this regulative behavior depends on a complex interplay between morphogenetic tendencies intrinsic to the notochord plate and instructive and permissive interactions with surrounding tissues. We discuss mechanisms that could account for these data and what they imply about notochord morphogenesis and its evolution within the chordate phylum.
Specification and determination of limb identity: evidence for inhibitory regulation ofTbxgene expression
Authors: Saito Daisuke , Yonei-Tamura Sayuri , Kano Kohko , Ide Hiroyuki , Tamura Koji
Published: April 2021

Limb-type-specific expression of Tbx5/Tbx4 plays a key role in drawing distinction between a forelimb and a hindlimb. Here, we show insights into specification and determination during commitment of limb-type identity, in particular that median tissues regulate Tbx expressions. By using the RT-PCR technique on chick embryos, the onset of specific Tbx5/Tbx4 expression in the wing/leg region was estimated to be stage 13. Specification of the limb-type identity is thought to occur before stage 9, since all explants from stage 9 through 14 expressed the intrinsic Tbx gene autonomously in a simple culture medium. The results of transplantation experiments revealed that axial structures medial to the lateral plate mesoderm at the level of the wing region are capable of transforming leg identity to wing identity, suggesting that a factor(s) from the median tissues is involved in the limb-type determination. Nevertheless, the transplanted wing region was not converted to leg identity. The results of the transplantation experiments also suggested that wing-type identity is determined much earlier than is leg-type identity. Finally, we also found that inhibitory effects of median tissues mediate the specific expression of Tbx5/Tbx4 in the presumptive wing/leg region. We propose a model for limb-type identification in which inhibitory regulation is involved in restricting one Tbx gene expression by masking the other Tbx expression there.
Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression
Authors: Stühmer Thorsten , Anderson Stewart A. , Ekker Marc , Rubenstein John L. R.
Published: April 2021

The expression of the Dlx homeobox genes is closely associated with neurons that express γ-aminobutyric acid (GABA) in the embryonic rostral forebrain. To test whether the Dlx genes are sufficient to induce some aspects of the phenotype of GABAergic neurons, we adapted the electroporation method to ectopically express DLX proteins in slice cultures of the mouse embryonic cerebral cortex. This approach showed that ectopic expression of Dlx2 and Dlx5 induced the expression of glutamic acid decarboxylases (GADs), the enzymes that synthesize GABA. We also used this method to show cross-regulation between different Dlx family members. We find that Dlx2 can induce Dlx5 expression, and that Dlx1, Dlx2 and Dlx5 can induce expression from a Dlx5/6-lacZ enhancer/”reporter construct.
Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo
Authors: Mailleux Arnaud André , Spencer-Dene Bradley , Dillon Christian , Ndiaye Delphine , Savona-Baron Catherine , Itoh Nobuyuki , Kato Shigeaki , Dickson Clive , Thiery Jean Paul , Bellusci Saverio
Published: April 2021

The mouse develops five pairs of mammary glands that arise during mid-gestation from five pairs of placodes of ectodermal origin. We have investigated the molecular mechanisms of mammary placode development using Lef1 as a marker for the epithelial component of the placode, and mice deficient for Fgf10 or Fgfr2b, both of which fail to develop normal mammary glands. Mammary placode induction involves two different signaling pathways, a FGF10/FGFR2b-dependent pathway for placodes 1, 2, 3 and 5 and a FGF10/FGFR2b-independent pathway for placode 4. Our results also suggest that FGF signaling is involved in the maintenance of mammary bud 4, and that Fgf10 deficient epithelium can undergo branching morphogenesis into the mammary fat pad precursor.
Specific heparan sulfate structures involved in retinal axon targeting
Authors: Irie Atsushi , Yates Edwin A. , Turnbull Jeremy E. , Holt Christine E.
Published: April 2021

Heparan sulfate (HS), a structurally diverse molecule comprising distinct sequences of sulfated disaccharide units, is abundant in the developing brain and binds to axon guidance molecules. Addition of HS to the developing Xenopus optic pathway causes severe targeting errors yet it is not known how the structural diversity of this molecule relates to its role in axon guidance. We have used an in vivo brain assay to identify the structural characteristics of HS that induce aberrant axon targeting. Inhibiting sulfation of endogenous HS with chlorate causes axons to bypass their target, the tectum, and treatment with chemically modified heparins reveals that 2-O- and 6-O-sulfate groups have potent bypass-inducing activity. Experiments with purified heparin saccharides show that bypass-inducing activity correlates with distinct structures, particularly those containing a combination of 2-O- and 6-O-sulfate groups. Taken together the results indicate that specific sequences, rather than gross structural composition, are critical for activity. In situ hybridisation revealed that HS 6-O-sulfotransferase is regionally expressed along the border of the dorsal optic tract whereas 2-O-sulfotransferase is expressed broadly. Our results demonstrate that specific HS sequences are essential for regulating retinotectal axon targeting and suggest that regionalised biosynthesis of specific HS structures is important for guiding axons into the tectum.
MASK, a large ankyrin repeat and KH domain-containing protein involved inDrosophilareceptor tyrosine kinase signaling
Authors: Smith Rachel K. , Carroll Pamela M. , Allard John D. , Simon Michael A.
Published: April 2021

The receptor tyrosine kinases Sevenless (SEV) and the Epidermal growth factor receptor (EGFR) are required for the proper development of the Drosophila eye. The protein tyrosine phosphatase Corkscrew (CSW) is a common component of many RTK signaling pathways, and is required for signaling downstream of SEV and EGFR. In order to identify additional components of these signaling pathways, mutations that enhanced the phenotype of a dominant negative form of Corkscrew were isolated. This genetic screen identified the novel signaling molecule MASK, a large protein that contains two blocks of ankyrin repeats as well as a KH domain. MASK genetically interacts with known components of these RTK signaling pathways. In the developing eye imaginal disc, loss of MASK function generates phenotypes similar to those generated by loss of other components of the SEV and EGFR pathways. These phenotypes include compromised photoreceptor differentiation, cell survival and proliferation. Although MASK is localized predominantly in the cellular cytoplasm, it is not absolutely required for MAPK activation or nuclear translocation. Based on our results, we propose that MASK is a novel mediator of RTK signaling, and may act either downstream of MAPK or transduce signaling through a parallel branch of the RTK pathway.
Repression of organizer genes in dorsal and ventralXenopuscells mediated by maternal XTcf3
Authors: Houston Douglas W. , Kofron Matt , Resnik Ernesto , Langland Rachel , Destree Olivier , Wylie Christopher , Heasman Janet
Published: April 2021

In the early Xenopus embryo, the dorsal axis is specified by a Wnt signal transduction pathway, involving the movement of β-catenin into dorsal cell nuclei and its functional association with the LEF-type transcription factor XTcf3. The subsequent function of XTcf3 is uncertain. Overexpression data has suggested that it can be both an activator and repressor of downstream genes. XTcf3 mRNA is synthesized during oogenesis in Xenopus and is stored in the egg. To identify its role in dorsal axis specification, we depleted this maternal store in full-grown oocytes using antisense deoxyoligonucleotides, and fertilized them. The developmental effects of XTcf3 depletion, both on morphogenesis and the expression of marker genes, show that primarily, XTcf3 is an inhibitor, preventing both dorsal and ventral cells of the late blastula from expressing dorsal genes. We also show that simple relief from the repression is not the only factor required for dorsal gene expression. To demonstrate this, we fertilized eggs that had been depleted of both XTcf3 and the maternal transcription factor VegT. Dorsal genes normally repressed by XTcf3 are not activated in these embryos. These data show that normal dorsal gene expression in the embryo requires the transcriptional activator VegT, whilst XTcf3 prevents their inappropriate expression on the ventral side of the embryo.
The roles of three signaling pathways in the formation and function of the Spemann Organizer
Authors: Xanthos Jennifer B. , Kofron Matthew , Tao Qinghua , Schaible Kyle , Wylie Christopher , Heasman Janet
Published: April 2021

Since the three main pathways (the Wnt, VegT and BMP pathways) involved in organizer and axis formation in the Xenopus embryo are now characterized, the challenge is to understand their interactions. Here three comparisons were made. Firstly, we made a systematic comparison of the expression of zygotic genes in sibling wild-type, VegT-depleted (VegT–), β-catenin-depleted (β-catenin–) and double depleted (VegT–/β-catenin–) embryos and placed early zygotic genes into specific groups. In the first group some organizer genes, including chordin, noggin and cerberus, required the activity of both the Wnt pathway and the VegT pathway to be expressed. A second group including Xnr1, 2, 4 and Xlim1 were initiated by the VegT pathway but their dorsoventral pattern and amount of their expression was regulated by the Wnt pathway. Secondly, we compared the roles of the Wnt and VegT pathways in producing dorsal signals. Explant co-culture experiments showed that the Wnt pathway did not cause the release of a dorsal signal from the vegetal mass independent from the VegT pathway. Finally we compared the extent to which inhibiting Smad 1 phosphorylation in one area of VegT–, or β-catenin– embryos would rescue organizer and axis formation. We found that BMP inhibition with cm-BMP7 mRNA had no rescuing effects on VegT– embryos, while cm-BMP7 and noggin mRNA caused a complete rescue of the trunk, but not of the anterior pattern in β-catenin– embryos.
Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells
Authors: Nemer Georges , Nemer Mona
Published: April 2021

In vertebrates, heart development is a complex process requiring proper differentiation and interaction between myocardial and endocardial cells. Significant progress has been made in elucidating the molecular events underlying myocardial cell differentiation. In contrast, little is known about the development of the endocardial lineage that gives rise to cardiac valves and septa. We have used a novel in vitro model to identify the molecular hierarchy of endocardial differentiation and the role of transcription factor GATA5 in endocardial development. The results indicate that GATA5 is induced at an early stage of endothelial-endocardial differentiation prior to expression of such early endocardial markers as Tie2 and ErbB3. Inhibition of either GATA5 expression or NF-ATc activation, blocks terminal differentiation at a pre-endocardial stage and GATA5 and NF-ATc synergistically activate endocardial transcription. The data reveal that transcription factor GATA5 is required for differentiation of cardiogenic precursors into endothelial endocardial cells. This, in turn, suggests that the GATA5 pathway may be relevant to early stages of valvuloseptal development, defects of which account for the majority of human birth malformations.