bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient
Authors: Nantsupawat Teerapat , Wongcharoen Wanwarang , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: November 2020

Metformin has been shown to have various cardiovascular benefits beyond its antihyperglycemic effects, including a reduction in stroke, heart failure, myocardial infarction, cardiovascular death, and all-cause mortality. However, the roles of metformin in cardiac arrhythmias are still unclear. It has been shown that metformin was associated with decreased incidence of atrial fibrillation in diabetic patients with and without myocardial infarction. This could be due to the effects of metformin on preventing the structural and electrical remodeling of left atrium via attenuating intracellular reactive oxygen species, activating 5′ adenosine monophosphate-activated protein kinase, improving calcium homeostasis, attenuating inflammation, increasing connexin-43 gap junction expression, and restoring small conductance calcium-activated potassium channels current. For ventricular arrhythmias, in vivo reports demonstrated that activation of 5′ adenosine monophosphate-activated protein kinase and phosphorylated connexin-43 by metformin played a key role in ischemic ventricular arrhythmias reduction. However, metformin failed to show anti-ventricular arrhythmia benefits in clinical trials. In this review, in vitro and in vivo reports regarding the effects of metformin on both atrial arrhythmias and ventricular arrhythmias are comprehensively summarized and presented. Consistent and controversial findings from clinical trials are also summarized and discussed. Due to limited numbers of reports, further studies are needed to elucidate the mechanisms and effects of metformin on cardiac arrhythmias. Furthermore, randomized controlled trials are needed to clarify effects of metformin on cardiac arrhythmias in human.
Recent advances in the management of anaplastic thyroid cancer
Authors: De Leo Simone , Trevisan Matteo , Fugazzola Laura
Published: November 2020

Anaplastic thyroid cancer (ATC) is undoubtedly the thyroid cancer histotype with the poorest prognosis. The conventional treatment includes surgery, radiotherapy, and conventional chemotherapy. Surgery should be as complete as possible, securing the airway and ensuring access for nutritional support; the current standard of care of radiotherapy is the intensity-modulated radiation therapy; chemotherapy includes the use of doxorubicin or taxanes (paclitaxel or docetaxel) generally with platin (cisplatin or carboplatin). However, frequently, these treatments are not sufficient and a systemic treatment with kinase inhibitors is necessary. These include multitarget tyrosine kinase inhibitors (Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Axitinib, Pazopanib, Pyrazolo-pyrimidine compounds), single target tyrosine kinase inhibitors (Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, PPARγ ligands (e.g. Efatutazone), Everolimus against mTOR, vascular disruptors (e.g. Fosbretabulin), and immunotherapy (e.g. Spartalizumab and Pembrolizumab, which are anti PD-1/PD-L1 molecules). Therapy should be tailored to the patients and to the tumor genetic profile. A BRAF mutation analysis is mandatory, but a wider evaluation of tumor mutational status (e.g. by next-generation sequencing) is desirable. When a BRAFV600E mutation is detected, treatment with Dabrafenib and Trametinib should be preferred: this combination has been approved by the Food and Drug Administration for the treatment of patients with locally advanced or metastatic ATC with BRAFV600E mutation and with no satisfactory locoregional treatment options. Alternatively, Lenvatinib, regardless of mutational status, reported good results and was approved in Japan for treating unresectable tumors. Other single target mutation agents with fair results are Everolimus when a mutation involving the PI3K/mTOR pathway is detected, Imatinib in case of PDGF-receptors overexpression, and Spartalizumab in case of PD-L1 positive tumors. Several trials are currently evaluating the possible beneficial role of a combinatorial therapy in ATC. Since in this tumor several genetic alterations are usually found, the aim is to inhibit or disrupt several pathways: these combination strategies use therapy targeting angiogenesis, survival, proliferation, and may act against both MAPK and PI3K pathways. Investigating new treatment options is eagerly awaited since, to date, even the molecules with the best radiological results have not been able to provide a durable disease control.
Incidence, clinical features, and outcomes of COVID-19 in Canada: impact of sex and age
Authors: O’Brien Jacob , Du Kevin Y. , Peng Chun
Published: November 2020

Male sex and older age have been reported to be associated with worse outcomes from COVID-19. It was postulated that estrogens may play a role in reducing the severity of the disease and may therefore offer a treatment option for COVID-19 patients. However, more female cases and deaths from COVID-19 have been recorded in Canada. To determine the potential role of estrogens, we analyzed COVID-19 data from Canada, focusing on the impact of sex and age. Although the overall incidence rate is higher in females than in males, when several high risk groups, including health care workers and long-term care residences, which are predominantly females, were excluded, we found that females had a lower incidence rate than males between the ages of 20s to 70s. Interestingly, this sex-based difference is more evident in females of the reproductive ages (20–49) than in postmenopausal patients (60s or older). Males have significantly higher hospitalization, ICU admission, and case fatality rates; however, a greater difference was observed in the older age groups. Finally, symptom manifestation varied between sexes. Some of the symptoms, which were more frequently observed in patients who recovered than patients who died, were more commonly observed in females of the reproductive age compared to their male counterparts. Since only females of the reproductive age have much higher circulating estrogens than males, these findings suggest that estrogens may play a role in reducing COVID-19 incidence and in the development of symptoms, especially those related to better survival.
Simultaneous diagnosis of liver PEComa in a family with known Li–Fraumeni syndrome: a case report
Authors: Galera López María del Mar , Márquez Rodas Iván , Agra Pujol Carolina , García Pérez Ángela , Velasco Sánchez Enrique , Álvarez Álvarez Rosa
Published: November 2020

Background

Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary disease. It is associated with the loss of function of the p53 protein and an increased risk of malignant tumor development at early age. The most frequently detected tumors include breast cancer, sarcomas, leukemia, brain tumors, and adrenocortical carcinomas. While sarcomas account for only 1% of solid tumors, they are more frequently detected in these families.

Case presentation

We report a simultaneous diagnosis of hepatic perivascular epithelioid cell tumor (PEComa), a very rare subtype of sarcoma, in two siblings with a LFS.

Conclusions

The simultaneous diagnosis of PEComa in two siblings presented in this case allowed us to review the frequency of PEComa in this genetic syndrome previously reported, which was very little. Despite its rarity, PEComa must be considered in the differential diagnosis of new-onset liver lesions in patients who were previously diagnosed with LFS.
Teratogenic and developmental toxic effects of etridiazole on zebrafish (Danio rerio) embryos
Authors: Vasamsetti Bala Murali Krishna , Kim Nam-Seok , Chon Kyongmi , Park Hong-Hyun
Published: November 2020

Etridiazole (EDZ), a thiadiazole-containing toxic chemical, is widely used as a fungicide. Regular usage of EDZ may reach and contaminate water bodies, but its adverse effects on aquatic vertebrates have not been well studied. Therefore, the present study aimed to evaluate the harmful effects of EDZ using zebrafish (ZF) (Danio rerio) embryos. ZF embryos were treated with 3.75, 7.5, 15, 30, and 60 mg/L of EDZ. Subsequently, mortality and developmental toxicities were quantified at 24, 48, 72, and 96 h post fertilization (hpf). The results showed that embryo mortality was concentration- and time-dependent. The median lethal concentration (LC50) of EDZ at 96-h was 25.58 ± 1.49 mg/L. Besides, EDZ induced a series of morphological deformities, including abnormal somite formation, abnormal eye pigmentation, abnormal tail morphology, tail kinks, skeletal malformations (lordosis, kyphosis, and scoliosis), and yolk sac edema in a concentration-dependent manner. Among the deformities, the most significant were reduced heartbeat and increased incidence of pericardial edema. The median effective concentration (EC50) of EDZ at 96-h was 17.93 ± 2.22 mg/L and the 96-h teratogenic index (TI) value was 1.52. Taken together, these results indicate that EDZ is a teratogen, and primarily affects the cardiovascular system of ZF.
Soil organic carbon stock and retention rate among land uses along Didessa toposequence in humid Western Ethiopia
Authors: Deressa Abdenna , Yli-Halla Markku , Mohamed Muktar
Published: November 2020

Background

There is scarcity of scientific information on stocks and retention rate of soil organic carbon (SOC) among mixed farming systems in humid Western Ethiopia. The objectives of study were to determine the SOC stocks and retention rates along a 53-km long toposequence of Didessa watershed. The study was conducted in mixed farming systems (annual arable cropping, grazing, fallow, grassland, coffee agroforestry, eucalyptus agroforestry and mechanized irrigated sugarcane production) within an elevation range of 1273 to 2543 m above sea level.

Results

The results revealed that land use types greatly affected SOC stocks and retention rates in the upper 20 cm soil depth. The SOC stocks ranged from 9.27 to 13.5 Mg C ha−1 (0–20 cm) while the retention rates were 0.11, 0.20, 0.28, 0.31 and 1.14 Mg C ha−1 year−1 for coffee agroforestry, fallow, grazing, eucalyptus agroforestry and irrigated sugarcane production systems, respectively.

Conclusion

The retention rates demonstrated that the different farming systems are potential source of C sinks. The study indicated that the farming systems are efficient in sequestering SOC and their benefits can be further adopted for their economic values, social significance, restoration of degraded land, and sequestration of carbon (C) in humid tropical Western Ethiopia.
Self-esteem instability and affective instability in everyday life after remission from borderline personality disorder
Authors: Santangelo Philip S. , Kockler Tobias D. , Zeitler Marie-Luise , Knies Rebekka , Kleindienst Nikolaus , Bohus Martin , Ebner-Priemer Ulrich W.
Published: November 2020

Background

Borderline personality disorder (BPD) is defined by a pervasive pattern of instability. According to prior findings and clinical theories, self-esteem instability and affective instability are key features of BPD. Previous e-diary studies showed that instability in self-esteem is heightened and that it is highly intertwined with affective instability in BPD in comparison to healthy controls (HC). The present study sought to extend these findings by adding symptomatologically remitted BPD patients (BPD-REM), i.e. former patients with BPD who met four or fewer BPD criteria within the past year, as a comparison group.

Methods

To examine differences regarding self-esteem instability and affective instability, we used e-diaries for repeatedly collecting data on self-esteem, valence, and tense arousal 12 times a day for four consecutive days while participants underwent their daily life activities. Determining three different state-of-the-art instability indices and applying multilevel analyses, we compared 35 BPD-REM participants with previously reported 60 acute BPD patients (BPD-ACU) and 60 HC.

Results

Our results revealed that self-esteem instability was significantly lower in the BPD-REM compared to the BPD-ACU group, irrespective of the instability index. In contrast, there were no significant differences regarding affective instability between the BPD-REM participants and those in the BPD-ACU group. The comparison between the BPD-REM with the HC indicated both a significantly higher instability in self-esteem as well as significantly heightened affective instability in the BPD-REM participants. Moreover, even though the associations were not significant, we found tentative support for the assumption that affective changes that are accompanied by changes in self-esteem are experienced as more burdensome and negatively impact the quality of life of remitted BPD participants.

Conclusions

This study builds on growing evidence for the importance of self-esteem instability in BPD. Whereas affective instability has been reported in various psychiatric disorders and might indeed constitute a transdiagnostic marker of affective dysregulation, our results indicate that self-esteem instability might be a specific symptom that construes the unique pathology in BPD.
Hydrological functioning of forested catchments, Central Himalayan Region, India
Authors: Qazi Nuzhat
Published: November 2020

Background

Central Himalayan forested catchments provide fresh water supply and innumerable ecosystem services to millions of people. Hence, the understanding of linkages between forests and water is very crucial for availability and quality of water at catchment scale. Therefore, the present study aims to understand the hydrological response of two forested catchments (namely, Arnigad and Bansigad) in the Central Himalayan Region.

Methods

Three-years’ data (March, 2008 to February, 2011) were collected from meteorological and hydrological stations in Arnigad and Bansigad catchments. The present paper describes the mean hydrological response of these forested catchments investigated through detailed field investigation.

Results

The annual hyetograph analysis revealed that the rainfall at both the catchments was highly seasonal, and wet-period (June–September) plays a key role in catchment functioning. Exceedance of rainfall threshold of ~ 200 mm (~ 10% of annual rainfall) significantly increased streamflow generation in both catchments. In Arnigad, the stream was perennial with a mean baseflow of ~ 83 mm per month (~ 6% of annual baseflow) whereas, Bansigad had greater seasonality due to lack of streamflow during the pre-wet-period (March–May). Separation of hydrographs in Arnigad and Bansigad catchments i.e. stormflow (6% and 31%, respectively) and baseflow (50% and 32%, respectively) helped to understand the probability of flooding during wet-period and drought during dry-period. The forest ecosystem in Arnigad displayed healthier hydrological functioning in terms of reduced stormflow (82%), and enhanced baseflow (52%), soil moisture (13%), steady infiltration rate (22%) and lag time (~ 15 min) relative to Bansigad. These enhanced values indicated soil capability to store water in the forested catchment (Arnigad) and helped to understand the volume of water (discharge) that was available during dry-period. The lower denudation rate at Arnigad by 41% resulted in decreased suspended sediment (18%) and bed load (75%) compared to Bansigad. Further, the enhanced dissolved solids in the Arnigad stream resulted from the higher organic matter generated in the forest floor.

Conclusion

This study shows that rainfall during the wet-period was the main driver of hydrological functioning, whereas, forests provided substantial services by regulating water balance, soil moisture and sediment budget through different mechanisms of forest components at catchment-scale in the Central Himalayan Region.
Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss
Authors: Yu Jing , Jiang Wei , Cao Li , Na Xiaoxue , Yang Jiyun
Published: November 2020

Mutations in HARS2 are one of the genetic causes of Perrault syndrome, characterized by sensorineural hearing loss (SNHL) and ovarian dysfunction. Here, we identified two novel putative pathogenic variants of HARS2 in a Chinese family with sensorineural hearing loss including two affected male siblings, c.349G > A (p.Asp117Asn) and c.908 T > C (p.Leu303Pro), through targeted next-generation sequencing methods. The two affected siblings (13 and 11 years old) presented with early-onset, rapidly progressive SNHL. The affected siblings did not have any inner ear malformations or delays in gross motor development. Combined with preexisting clinical reports, Perrault syndrome may be latent in some families with non-syndromic deafness associated with HARS2 mutations. The definitive diagnosis of Perrault syndrome based on clinical features alone is a challenge in sporadic males, and preadolescent females with no signs of POI. Our findings further expanded the existing spectrum of HARS2 variants and Perrault syndrome phenotypes, which will assist in molecular diagnosis and genetic counselling of patients with HARS2 mutations.
NOACs: an emerging class of oral anticoagulants-a review article
Authors: Paul Chithra , Baby Mable , Anthraper Alfet Raju , K Krishnakumar
Published: November 2020

Background

NOACs, commonly known as novel oral anticoagulants, are the non-vitamin K antagonist oral anticoagulants which are relatively newer in the market. It has displaced vitamin K antagonists, notably warfarin, for many indications. These agents are dabigatran, rivaroxaban, apixaban, and edoxaban.

Main body

The drugs are licenced to prevent stroke and also systemic embolism in patients on treatment for atrial fibrillation and prevent venous thromboembolism. Rivaroxaban and apixaban are approved for prophylaxis of thrombus following surgical hip or knee arthroplasty. The recent surveys reveal that use of NOACs has steeply increased due to its safety profile and convenience to use. Also, the studies have shown that NOACs have lesser bleeding complications and associated mortality in contrast to traditional anticoagulants. The upcoming years are known to be NOACs’ age due to the significant findings in this area.

Conclusion

Therefore, a basic understanding on these drugs is highly recommended to provide a better service to the patients. This article aims to provide quick and brief information on the novel class of drugs. It equips an overview of NOAC and deals with the following areas: (i) pharmacology, (ii) laboratory methods, (iii) peri-operative management, (iv) advantages, (v) challenges, and (vi) future.
Acoustic fields for monopole logging while drilling with an eccentric collar
Authors: Ji Yunjia , He Xiao , Chen Hao , Wang Xiuming , Zhang Hailan
Published: November 2020

The acoustic problem of an eccentric drill collar in a fluid-filled borehole has been of interest in the field of acoustic logging while drilling (ALWD) in recent years. To reduce the effects of tool eccentricity on ALWD measurements, studies on acoustic responses under such conditions are essential. This study therefore has developed an analytical method to investigate borehole wavefields with an off-center monopole ALWD tool in fast and slow formations. By evaluating the contributions of compressional and shear branch points, the effects of the tool eccentricity on individual formation primary and shear head waves are investigated. Results illustrate that tool eccentricity only affects the excitation properties and has almost no effect on the extracted velocities. The joint analysis of synthetic full waveforms and dispersion diagrams with varying eccentricity degrees indicates that multipole modes are excited when the tool is off center, and their excitation amplitudes gradually increase with the increasing eccentricity, especially in the direction of tool movement. Moreover, the dispersion analysis reveals that the two modes with intersections in the centered case are coupled when the tool becomes eccentric. In particular, the coupling performance between the Stoneley and flexural modes is the most prominent. Furthermore, the effects of tool eccentricity on the monopole acquisition method, that is, the sum of waveforms received at four orthogonal azimuths, are evaluated. Results show that the above summation method can effectively reduce the effects of slight or moderate eccentricity. However, for large or extreme eccentricity, reducing or eliminating the effects of eccentricity on the Stoneley wave is a challenge for this method. Based on the above analyses, measurements may not be reliable for formation evaluation in the case of extreme eccentricity, especially for Stoneley wave applications.
Reciprocity-gap misfit functional for distributed acoustic sensing, combining data from passive and active sources
Authors: Faucher Florian , de Hoop Maarten V. , Scherzer Otmar
Published: November 2020

Quantitative imaging of subsurface earth properties in elastic media is performed from distributed acoustic sensing data. A new misfit functional based upon the reciprocity gap is designed, taking crosscorrelations of displacement and strain, and these products further associate an observation with a simulation. In comparison with other misfit functionals, this functional has the advantage of only requiring little a priori information on the exciting sources. In particular, the misfit criterion enables the use of data from regional earthquakes (teleseismic events can be included as well), followed by exploration data to perform a multiresolution reconstruction. The data from regional earthquakes contain the low-frequency content that is missing in the exploration data, allowing for the recovery of the long spatial wavelength, even with very few sources. These data are used to build prior models for the subsequent reconstruction from the higher frequency exploration data. This results in the elastic full reciprocity-gap waveform inversion method, and we illustrate its performance with a pilot experiment for elastic isotropic reconstruction.
Mechanical properties of grain contacts in unconsolidated sands
Authors: Sayers Colin M.
Published: November 2020

Unconsolidated sands provide zones of high porosity and permeability important for freshwater aquifers, hydrocarbon production, and CO2 sequestration. An understanding of the acoustics of unconsolidated sands enables the characterization of such formations using ultrasonics, borehole acoustics, and seismic methods. Inversion of ultrasonic compressional and shear velocities measured for unloading as a function of confining pressure for room-dry unconsolidated sands allows information on the mechanical properties of the grain contacts to be obtained using an approach based on the divergence theorem. This allows the effective compliance of sand to be written as the sum of the compliance of the pores and of the grain contacts, and it does not assume that the grains are identical spheres, in contrast to previous approaches. Grain contacts are found to be more compliant under shear than under normal compression, and the ratio of the normal-to-shear compliance decreases with decreasing confining pressure, implying that the shear compliance increases faster with decreasing confining pressure than the normal compliance. This is of importance in understanding the role of shear in the failure of unconsolidated sands, such as occurs in shallow water flow, sanding, and failure around injectors, where the change in stress is a function of the normal-to-shear compliance ratio of the grain contacts.
Investigation of fluid effects on seismic responses through a physical modeling experiment
Authors: Xu Chao , Ding Pinbo , Di Bangrang , Wei Jianxin
Published: November 2020

We have investigated fluid effects on seismic responses using seismic data from a physical modeling experiment. Eight cubic samples with cavities quantitatively filled with air, oil, and water and 16 nonfluid samples were set within a physical model. The pre- and poststack seismic responses of the samples were analyzed to quantitatively investigate the fluid effect on the seismic response. We determined that fluids could cause detectable changes in pre- and poststack seismic responses for tight rocks. At first, fluids filled within samples caused changes in prestack seismic responses. Visible differences could be detected between angle gathers of the samples filled with air, oil, and water. For the base reflections, the amplitudes at large angles of the air- and oil-filled samples are obviously stronger than those of the water-filled sample. In addition, the presence of fluids within samples led to significant changes in poststack seismic reflections. For samples with similar P-wave impedances to the background, we found strong seismic reflections for the fluid samples and weak or even no reflections for the nonfluid samples. There was notable interference between the top and base reflections for the fluid samples, whereas there was none for the nonfluid samples. Seismic velocities were estimated using the two-way traveltimes between the top and base reflections. The estimated seismic velocity gently declined with increasing water saturation until 90%. When the water saturation was more than 90%, the seismic velocity showed a steep increase.
Brittleness evaluation of the Lower Silurian marine shale reservoirs: A case study of Longmaxi shale in Fenggang block, southern China
Authors: Gu Yang , Xu Sheng , Fang Chao , Zhang Wei , Zhang Bairen , Zhao Xiangkuan , Jiang Chongxin
Published: November 2020

The brittleness of shale determines the fracturability of the shale reservoir and has a great influence on the exploration and development of shale gas. Therefore, prediction of brittleness and evaluation of fracturability of shale are very important in finding favorable areas for shale gas. We have used the mineral composition, rock-mechanics experiment, logging evaluation, 2D seismic data inversion, and fracture development degree to evaluate and analyze the vertical and plane brittleness characteristics and the main controlling factors of Longmaxi shale. In addition, we established the fracturability index of shale based on the brittleness index, critical strain energy release rate, and fracture toughness. The results indicate that the brittle mineral content of Longmaxi shale in the Fenggang block is between 69% and 90%, and shale samples are prone to brittle deformation by microscopic observation. Brittle deformation has a positive effect on the porosity and percolation ability of shale; the fractures in the upper and lower parts of the Longmaxi shale are relatively developed, and the degree of core fracture development is consistent with rock brittleness. The brittleness distribution of 2D seismic data inversion is in good agreement with the brittleness predicted by well logging; shale reservoirs with low fracture toughness, low critical strain energy release rate, and high brittleness index have high fracturability. Therefore, the research on shale brittleness and fracturability of Lower Silurian Longmaxi shale is expected to have important guiding significance for shale-gas exploration and development in southern China.
Harmine enhances the activity of the HIV-1 latency-reversing agents ingenol A and SAHA
Authors: Taylor Jared P. , Armitage Lucas H. , Aldridge Daniel L. , Cash Melanie N. , Wallet Mark A.
Published: November 2020

Infection of HIV-1 remains incurable because long-lived, latently-infected cells persist during prolonged antiretroviral therapy. Attempts to pharmacologically reactivate and purge the latent reservoir with latency reactivating agents (LRAs) such as protein kinase C (PKC) agonists (e.g. ingenol A) or histone deacetylase (HDAC) inhibitors (e.g. SAHA) have shown promising but incomplete efficacy. Using the J-Lat T cell model of HIV latency, we found that the plant-derived compound harmine enhanced the efficacy of existing PKC agonist LRAs in reactivating latently-infected cells. Treatment with harmine increased not only the number of reactivated cells but also increased HIV transcription and protein expression on a per-cell basis. Importantly, we observed a synergistic effect when harmine was used in combination with ingenol A and the HDAC inhibitor SAHA. An investigation into the mechanism revealed that harmine, when used with LRAs, increased the activity of NFκB, MAPK p38, and ERK1/2. Harmine treatment also resulted in reduced expression of HEXIM1, a negative regulator of transcriptional elongation. Thus, harmine enhanced the effects of LRAs by increasing the availability of transcription factors needed for HIV reactivation and promoting transcriptional elongation. Combination therapies with harmine and LRAs could benefit patients by achieving deeper reactivation of the latent pool of HIV provirus.
A developmental stage specific network approach for studying dynamic transcription factor-microRNA co-regulation during craniofacial development
Authors: Yan Fangfang , Jia Peilin , Yoshioka Hiroki , Suzuki Akiko , Iwata Junichi , Zhao Zhongming
Published: November 2020

Craniofacial development is regulated through dynamic and complex mechanisms that involve various signaling cascades and gene regulations. Disruption of such regulations may result in craniofacial birth defects. Here, we propose the first developmental stage-specific network approach by integrating two critical regulators, transcription factor (TF) and microRNA (miRNA), to study their co-regulation during craniofacial development. Specifically, we used TFs, miRNAs, and non-TF genes to form Feed-forward Loops (FFLs) using genomic data covering mouse embryonic days E10.5 to E14.5. We identified key novel regulators (TFs: Foxm1, Hif1a, Zbtb16, Myog, Myod1, and Tcf7, and miRNAs: miR-340-5p and miR-129-5p) and target genes (Col1a1, Sgms2, and Slc8a3) whose expression changed in a developmental stage-dependent manner. We found Wnt-FoxO-Hippo pathway (from E10.5 to E11.5), tissue remodeling (from E12.5 to E13.5), and miR-129-5p-mediated Col1a1 regulation (from E10.5 to E14.5) might play crucial roles in craniofacial development. Enrichment analyses further suggested their functions. Our experiments validated the regulatory roles of miR-340-5p and Foxm1 in Wnt-FoxO-Hippo subnetwork, as well as the role of miR-129-5p in the miR-129-5p-Col1a1 subnetwork. Thus, our study helps understand comprehensive regulatory mechanisms for craniofacial development.
Ccn2a/Ctgfa is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish
Authors: Mukherjee Debanjan , Wagh Ganesh , Mokalled Mayssa H. , Kontarakis Zacharias , Dickson Amy L. , Rayrikar Amey , Günther Stefan , Poss Kenneth D. , Stainier Didier Y. R. , Patra Chinmoy
Published: November 2020

The ability of zebrafish to heal their heart after injury makes them an attractive model to investigate mechanisms governing the regenerative process. In this study, we show that the gene cellular communication network factor 2a (ccn2a), previously known as ctgfa, is induced in endocardial cells in the injured tissue and regulates CM proliferation and repopulation of the damaged tissue. We find that whereas in wild-type animals, CMs track along the newly formed blood vessels that revascularize the injured tissue, in ccn2a mutants CM proliferation and repopulation are disrupted despite apparently unaffected revascularization. In addition, we find that ccn2a overexpression enhances CM proliferation and improves the resolution of transient collagen deposition. Through loss- and gain-of-function as well as pharmacological approaches, we provide evidence that Ccn2a is necessary for and promotes heart regeneration by enhancing the expression of pro-regenerative extracellular matrix genes, and by inhibiting the chemokine receptor gene cxcr3.1 through a mechanism involving Tgfβ/pSmad3 signaling. Thus, Ccn2a positively modulates the innate regenerative response of the adult zebrafish heart.
Interpreting the pathogenicity of Joubert syndrome missense variants in Caenorhabditis elegans
Authors: Lange Karen I. , Tsiropoulou Sofia , Kucharska Katarzyna , Blacque Oliver E.
Published: November 2020

Ciliopathies are inherited disorders caused by defects in motile and non-motile (primary) cilia. Ciliopathy syndromes and associated gene variants are often highly pleiotropic and represent exemplars for interrogating genotype-phenotype correlations. Towards understanding disease mechanisms in the context of ciliopathy mutations, we have used a leading model organism for cilia and ciliopathy research, Caenorhabditis elegans, together with gene editing, to characterise two missense variants (P74S and G155S) in mksr-2/B9D2 associated with Joubert syndrome (JBTS). B9D2 functions within the Meckel syndrome (MKS) module at the ciliary base transition zone (TZ) compartment and regulates the molecular composition and sensory/signalling functions of the cilium. Quantitative assays of cilium/TZ structure and function, together with knock-in reporters, confirm that both variant alleles are pathogenic in worms. G155S causes a more severe overall phenotype and disrupts endogenous MKSR-2 organisation at the TZ. Recapitulation of the patient biallelic genotype shows that compound heterozygous worms phenocopy worms homozygous for P74S. The P74S and G155S alleles also reveal evidence of a very close functional association between the B9D2-associated B9 complex and MKS-2/TMEM216. Together, these data establish C. elegans as a model for interpreting JBTS mutations and provide further insight into MKS module organisation.

This article has an associated First Person interview with the first author of the paper.
Impaired muscle morphology in a Drosophila model of myosin storage myopathy was suppressed by overexpression of an E3 ubiquitin ligase
Authors: Dahl-Halvarsson Martin , Olive Montse , Pokrzywa Malgorzata , Norum Michaela , Ejeskär Katarina , Tajsharghi Homa
Published: November 2020

Myosin is vital for body movement and heart contractility. Mutations in MYH7, encoding slow/β-cardiac myosin heavy chain, are an important cause of hypertrophic and dilated cardiomyopathy, as well as skeletal muscle disease. A dominant missense mutation (R1845W) in MYH7 has been reported in several unrelated cases of myosin storage myopathy. We have developed a Drosophila model for a myosin storage myopathy in order to investigate the dose-dependent mechanisms underlying the pathological roles of the R1845W mutation. This study shows that a higher expression level of the mutated allele is concomitant with severe impairment of muscle function and progressively disrupted muscle morphology. The impaired muscle morphology associated with the mutant allele was suppressed by expression of Thin (herein referred to as Abba), an E3 ubiquitin ligase. This Drosophila model recapitulates pathological features seen in myopathy patients with the R1845W mutation and severe ultrastructural abnormalities, including extensive loss of thick filaments with selective A-band loss, and preservation of I-band and Z-disks were observed in indirect flight muscles of flies with exclusive expression of mutant myosin. Furthermore, the impaired muscle morphology associated with the mutant allele was suppressed by expression of Abba. These findings suggest that modification of the ubiquitin proteasome system may be beneficial in myosin storage myopathy by reducing the impact of MYH7 mutation in patients.
Interplays between pre- and post-natal environments affect early-life mortality, body mass and telomere dynamics in the wild
Authors: Kärkkäinen Tiia , Teerikorpi Pauliina , Schuett Wiebke , Stier Antoine , Laaksonen Toni
Published: November 2020

Early-life conditions are crucial determinants of phenotype and fitness. The effects of pre- and postnatal conditions on fitness prospects have been widely studied but their interactive effects have received less attention. In birds, asynchronous hatching creates challenging developmental conditions for the last-hatched chicks, but differential allocation in last-laid eggs might help to compensate this initial handicap. The relative importance and potential interaction between pre- and post-hatching developmental conditions for different fitness components remains mostly unknown. We manipulated hatching order in wild pied flycatchers (Ficedula hypoleuca), creating three groups: Natural asynchrony (last-laid eggs hatching last), Reversed asynchrony (last-laid eggs hatching first) and Hatching synchrony (all eggs hatching at once). We examined the effects of these manipulations on early-life survival, growth and telomere length, a potential cellular biomarker of fitness prospects. Mortality was mostly affected by hatching order, with last-hatched chicks being more likely to die. Early-life telomere dynamics and growth were influenced by the interplays between laying and hatching order. Last-laid but first-hatched chicks were heavier but had shorter telomeres 5 days after hatching than their siblings, indicating rapid early growth with potential adverse consequences on telomere length. Synchronous chicks did not suffer any apparent cost of hatching synchronously. Impaired phenotypes only occurred when reversing the natural hatching order (i.e. developmental mismatch), suggesting that maternal investment in last-laid eggs might indeed counterbalance the initial handicap of last-hatched chicks. Our experimental study thus highlights that potential interplays between pre- and post-natal environments are likely to shape fitness prospects in the wild.
Assembly and Active Control of Nanoparticles using Polymer Brushes as a Scaffold
Authors: Nakamura Satoshi , Mitomo Hideyuki , Ijiro Kuniharu
Published: November 2020

Inorganic nanoparticles are an attractive material that shows unique properties that differ from their bulk counterparts. Assembly of nanoparticles with soft materials is an effective approach to leverage their unusual properties for the fabrication of functional devices. Among the various soft materials, polymer brushes are expected to offer exciting opportunities due to their unique conformational properties. Here, we review research progress in the assembly and active control of gold nanoparticles with polymer brushes as a scaffold.
The Mineralogical Composition of Samos Zeoliitic Rocks and their potential use as Feed Additives and Nutrition Supplements
Authors: Filippidis Anestis , Mytiglaki Christina , Kantiranis Nikolaos , Tsirambides Ananias
Published: November 2020

Fifteen (15) zeolitic rocks from Karlovassi-Marathokampos basin of Samos Island (Greece) were investigated for their mineralogical composition by X-Ray Diffraction (XRD) method. According to EU Regulation No 651/2013, clinoptilolite of sedimentary origin with ≥80 wt% clinoptilolite, ≤20 wt% clay minerals, free of fibres and quartz, can be used as feed additive for all animal species. Depending on the zeolites, the zeolitic rocks are grouped to those containing: Clinoptilolite (33-86 wt%), clinoptilolite (59 wt%) + mordenite (20-21 wt%), clinoptilolite (22 wt%) + analcime (29 wt%), clinoptilolite (17 wt%) + phillipsite (27 wt%), analcime (29-70 wt%), mordenite (62%) and chabazite (63 wt%). None of the clinoptilolite-containing rocks (10 samples) meet the requirements of the EU Regulation No 651/2013, and thus cannot be used as feed additives for all animal species and consequently as nutrition supplements, since all of them contain 2-5 wt% quartz, two of them 20-21 wt% mordenite (fibrous zeolite), nine of them <80 wt% clinoptilolite (17-73 wt%) and two of them >20 wt% clay minerals (27-42 wt%). Although the EU Regulation No 651/2013 refers to clinoptilolite of sedimentary origin, using the presence or absence of quartz and fibrous minerals, none of the five mordenite, analcime and chabazite containing zeolitic rocks, can be used as feed additives and nutrition supplements, since all of them contain 2-6 wt% quartz and one of them contains 62 wt% mordenite (fibrous zeolite).
COMPARATIVE STUDY OF THE CESIUM UPTAKE ABILITY BETWEEN HEU-TYPE (CLINOPTILOLITE-HEULANDITE) ZEOLITIC TUFF AND PURE HEULANDITE
Authors: Mytiglaki Christina , Kantiranis Nikolaos , Misaelides Panagiotis , Noli Fotini , Filippidis Anestis
Published: November 2020

Specific continuous layers of zeolitic tuff in Ntrista stream location of Petrota area of Evros region (NA11) and pure natural crystals of heulandite (HEU1) from the collection of the Department of Mineralogy-Petrology-Economic Geology, School of Geology, Aristotle University of Thessaloniki, have been investigated. The X-Ray Diffraction analyses showed that the sample NA11 consists of 86 wt% HEU-type zeolite, 4 wt% micas+ clay-minerals, 4 wt% quartz, 2 wt% christobalite and 4 wt% feldspars, while the sample HEU1 is pure heulandite crystal. The mineral-chemistry was determined by SEM-EDS microanalyses. The zeolite of the NA11 sample is Ca-rich clinoptilolite and its chemical formulae is Ca1.8K1.0Mg0.7Na0.5Al6.4 Si29.5O72·21H2O, while the zeolite of the sample HEU1 is heulandite and its chemical formulae is Ca3.6Na1.0Κ0.2Sr0.2Ba0.1Al8.1Si27.6O72·21H2O. The uptake ability of the samples was measured by the AMAS method (Ammonium Acetate Saturation). The two examined materials show high uptake ability. The measured value for the zeolitic tuff NA11 is 231 meq/100g, while for the heulandite crystal (HEU1) is 296 meq/100g. For the determination of the cesium sorption a CsNO3 solution (concentration 500 mg/L), labelled with small activity of 137Cs, and pH 2-12 was used. The sorption of the cesium by the two materials, was determined by measuring the gamma radiation emitted by the 137Cs tracer. The zeolitic tuff presents higher uptake ability of radioactive cesium than the pure heulandite crystal, whereas the sorption of radioactive cesium is not significantly affected by the pH values of the initial solutions in the range pH 2-12.The clinoptilolitic zeolitic tuff NA11 is suitable material for various environmental, agricultural and industrial applications.
Hydrochemical characteristics of the Oropos coastal aquifers, Attica, Greece
Authors: Hermides Demetrios , Zaxariadis Dimitrios , Stamatis George
Published: November 2020

This article deals with the hydrochemistry of coastal aquifers of the Oropos plain, Attica, Greece. It is the first study which presents hydrochemical data of the Oropos plain groundwater. Groundwater samples from 34 wells were collected and analyzed for major and heavy metal constituents. Groundwater was differentiated between the Pleistocene confined aquifer and the group of the Holocene, the Miocene and the Mesozoic aquifers based on the electrical conductivity (EC) values and the chlorides content. Groundwater in the Pleistocene sediments presented EC values ranging between 766 and 971μS/cm and chlorides between 95-163mg/l. The group of the rest aquifers presented EC values up to 3770 μS/cm and chlorides up to 993mg/l. The Pleistocene aquifer seems to be protected from seawater intrusion, although, it is located adjacent to the shoreline. In addition, most of the heavy metal concentration exceeded the EU limits. Cd, Fe, Pb, Ni have been determined at 82, 2500, 817, 217 μg/lit respectively. Groundwater was, also, categorized into 2 main water types that of Ca-Mg-HCO3 type indicating recharge of fresh water and that of Ca-Mg-Cl type indicating reverse cation exchange of old Na-Cl waters.
Mineralogical and Geochemical Study of the Zeolitized Volcaniclastic Rocks of Petrota region, Evros Prefecture, Northeastern Greece
Authors: Michailidou Eleni , Vavelidis Michael , Papadopoulou Lambrini , Kantiranis Nikolaos
Published: November 2020

The present work studies the tuffs associated with the volcanic area of the Paleogene Sheinovets caldera, located on the southeastern part of the Rhodope massif, in Bulgaria. Its purpose is to describe the mineralogical and geochemical composition of the zeolitized volcaniclastic deposits in the broader area of Petrota village, in the northwesternmost part of the Greek regional unit of Evros, in northeast Greece. The samples studied in this work were collected from seven (7) different locations, covering an area of almost 4 km in length and 2 km in width. Macroscopically, the samples display a greyish-green hue and they are widespread in the area of study. They often contain fragments of the crystalline metamorphic basement (mica-schists, phyllites, amphibolites, quartzites) and/or rhyolitic clasts. A rhyolitic outcrop of greyish-pink hue is observed in the Mavri Petra region, probably related to the Rupelian acid volcanism that occurred in the Sheinovets caldera. The mineralogy of the tuffs was studied under light polarizing microscope and using Scanning Electron Microscopy (SEM), and it was further confirmed by X-ray powder diffraction (XRPD) method. The initial matrix of the tuffs consisted predominantly of glass shards that are now partly or fully altered into zeolites and clay minerals, such as celadonite, displaying characteristic pseudomorphic structures. The dominant zeolite is clinoptilolite, while in some areas the presence of mordenite is also noticed. Feldspar phenocrysts are abundant, and they are represented by plagioclase and sanidine. Although quartz crystals can be observed under light-polarizing microscope solely in metamorphic fragments, the presence of silica polymorphs was also confirmed through SEM and XRPD analysis, with quartz and cristobalite prevailing. The mineralogical assemblage includes phenocrysts of biotite and in some cases amphiboles, while pyroxene, epidote, garnet, titanite, apatite, zircon, ilmenite, magnetite and rutile are additional minerals which have been identified locally in accessory quantities. Chemical analysis was carried out for major and trace elements, using the X-ray fluorescence (XRF) method and 4 Acid digestion ICP-MS analysis, respectively. The samples of Mavri Petra region, exhibit high concentrations in Cu, Pb, Mn, V, P and W. The analyzed concentrations of U in the area of Palaeokklisi are relatively high in comparison to the rest due to its proximity to a fault. Towards the northwestern study area, close to the Greek-Bulgarian border, the concentrations of Sr appear to be particularly high, probably because the area is closer to the volcanic centre.
Rock-Eval analysis and organic petrographical characterization of the Upper Jurassic Naokelekan Formation, northern Mesopotamian basin, Kurdistan Region-Iraq
Authors: Abdula Rzger , Kolo Kamal , Damoulianou Maria-Elli , Raftopoulou Victoria , Khanaqa Polla , Kalaitzidis Stavros
Published: November 2020

The aim of this study is to assess the type, thermal maturity and the petroleum generation potential of the Upper Jurassic Naokelekan Formation, occurring across the Kurdistan Region of Iraq, by applying organic petrographical methods and Rock-Eval analysis. The Rock-Eval data would indicate the presence of kerogen types III, IV and II as the main constituents. However, the qualitative petrographical evaluation revealed that the main organic constituents are solid hydrocarbons, in the form of microgranular migrabitumens, with minor amounts of pyrobitumens. These secondary particles have affected the results of the Rock-Eval analysis and would have led to misinterpretation of organic matter typification based on pyrolysis results only. The combined results of petrography and pyrolysis indicate an active petroleum system within the Upper Jurassic sequence, where hydrocarbons are generated and reservoired within suitable lithologies.