bluuebunny/crossref_metadata_2025 huggingface dataset:
Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers
Authors: Corlier Juliana , Tadayonnejad Reza , Wilson Andrew C , Lee Jonathan C , Marder Katharine G , Ginder Nathaniel D , Wilke Scott A , Levitt Jennifer , Krantz David , Leuchter Andrew F
Published: June 2021

Background

Major depressive disorder (MDD) and chronic pain are highly comorbid, and pain symptoms are associated with a poorer response to antidepressant medication treatment. It is unclear whether comorbid pain also is associated with a poorer response to treatment with repetitive transcranial magnetic stimulation (rTMS).

Methods

162 MDD subjects received 30 sessions of 10 Hz rTMS treatment administered to the left dorsolateral prefrontal cortex (DLPFC) with depression and pain symptoms measured before and after treatment. For a subset of 96 patients, a resting-state electroencephalogram (EEG) was recorded at baseline. Clinical outcome was compared between subjects with and without comorbid pain, and the relationships among outcome, pain severity, individual peak alpha frequency (PAF), and PAF phase-coherence in the EEG were examined.

Results

64.8% of all subjects reported pain, and both depressive and pain symptoms were significantly reduced after rTMS treatment, irrespective of age or gender. Patients with severe pain were 27% less likely to respond to MDD treatment than pain-free individuals. PAF was positively associated with pain severity. PAF phase-coherence in the somatosensory and default mode networks was significantly lower for MDD subjects with pain who failed to respond to MDD treatment.

Conclusions

Pain symptoms improved after rTMS to left DLPFC in MDD irrespective of age or gender, although the presence of chronic pain symptoms reduced the likelihood of treatment response. Individual PAF and baseline phase-coherence in the sensorimotor and midline regions may represent predictors of rTMS treatment outcome in comorbid pain and MDD.
World Trade Center responders in their own words: predicting PTSD symptom trajectories with AI-based language analyses of interviews
Authors: Son Youngseo , Clouston Sean A. P. , Kotov Roman , Eichstaedt Johannes C. , Bromet Evelyn J. , Luft Benjamin J. , Schwartz H. Andrew
Published: June 2021

Background

Oral histories from 9/11 responders to the World Trade Center (WTC) attacks provide rich narratives about distress and resilience. Artificial Intelligence (AI) models promise to detect psychopathology in natural language, but they have been evaluated primarily in non-clinical settings using social media. This study sought to test the ability of AI-based language assessments to predict PTSD symptom trajectories among responders.

Methods

Participants were 124 responders whose health was monitored at the Stony Brook WTC Health and Wellness Program who completed oral history interviews about their initial WTC experiences. PTSD symptom severity was measured longitudinally using the PTSD Checklist (PCL) for up to 7 years post-interview. AI-based indicators were computed for depression, anxiety, neuroticism, and extraversion along with dictionary-based measures of linguistic and interpersonal style. Linear regression and multilevel models estimated associations of AI indicators with concurrent and subsequent PTSD symptom severity (significance adjusted by false discovery rate).

Results

Cross-sectionally, greater depressive language (β = 0.32; p = 0.049) and first-person singular usage (β = 0.31; p = 0.049) were associated with increased symptom severity. Longitudinally, anxious language predicted future worsening in PCL scores (β = 0.30; p = 0.049), whereas first-person plural usage (β = −0.36; p = 0.014) and longer words usage (β = −0.35; p = 0.014) predicted improvement.

Conclusions

This is the first study to demonstrate the value of AI in understanding PTSD in a vulnerable population. Future studies should extend this application to other trauma exposures and to other demographic groups, especially under-represented minorities.
Three-variable systems: An integrative moderation and mediation framework for developmental psychopathology
Authors: Goldstein Brandon L. , Finsaas Megan C. , Olino Thomas M. , Kotov Roman , Grasso Damion J. , Klein Daniel N.
Published: June 2021

In this article, we consider an often overlooked model that combines mediation and moderation to explain how a third variable can relate to a risk factor–psychopathology relationship. We refer to it as moderation and mediation in a three-variable system. We describe how this model is relevant to studying vulnerability factors and how it may advance developmental psychopathology research. To illustrate the value of this approach, we provide several examples where this model may be applicable, such as the relationships among parental externalizing pathology, harsh parenting, and offspring psychopathology as well as between neuroticism, stressful life events, and depression. We discuss possible reasons why this model has not gained traction and attempt to clarify and dispel those concerns. We provide guidance and recommendations for when to consider this model for a given data set and point toward existing resources for testing this model that have been developed by statisticians and other methodologists. Lastly, we describe important caveats, limitations, and considerations for making this approach most useful for developmental research. Overall, our goal in presenting this information to developmental psychopathology researchers is to encourage testing moderation and mediation in a three-variable system with the aim of advancing analytic strategies for studying vulnerability factors.
A cryoprotectant supplemented with pentoxifylline can improve the effect of freezing on the motility of human testicular sperm
Authors: Xian Yang , Jiang Min , Liu Bo , Zhao Wenrui , Zhou Bin , Liu Xiao , Liu Shasha , Li Fuping
Published: June 2021

This study examined the effect of a cryoprotectant with and without pentoxifylline supplementation on the motility and viability of human testicular sperm, both before and after freezing. Testicular samples were obtained from 68 patients with azoospermia who came to the Andrology Service of West China Second University Hospital, Sichuan University, for testicular biopsies from December 2019 to April 2020. All patients were assigned randomly to two groups: experimental, whose testicular sperm were added to the cryoprotectant with pentoxifylline, and the control, whose testicular sperm were added to the cryoprotectant without pentoxifylline. Both groups used the same freezing and thawing methods. Testicular sperm motility in the experimental group was significantly higher than that of the control group, both before and after cryopreservation. The recovery rate of sperm motility in the experimental group was significantly higher than that of the control group. The percentage of samples with motile testicular sperm in the experimental group was significantly higher than that of the control group after thawing. Sperm viability was unchanged between the experimental and control groups, both before and after freezing. Overall, a pentoxifylline-supplemented cryoprotectant can significantly improve the motility of testicular sperm before and after cryopreservation.
Palliative care among adult cancer survivors: Knowledge, attitudes, and correlates
Authors: Stal Julia , Nelson Mary Baron , Mobley Erin M. , Ochoa Carol Y. , Milam Joel E. , Freyer David R. , Miller Kimberly A.
Published: June 2021

Objective

Palliative care (PC) is patient and family-centered supportive care intended to improve symptom management, reduce caregiver burden, coordinate care, and improve quality of life for patients diagnosed with serious illness. Optimally, PC is begun close to initial diagnosis and delivered in synchrony with disease-specific treatment until symptom relief or patient death. The purpose of this study was to examine cancer survivors’ knowledge and perceptions of PC using a nationally representative sample of US adults from the Health Information National Trends Survey (HINTS).

Method

A total of 593 HINTS respondents reported a personal history of cancer and were included in the sample (55.56% female; mean age of 65.88 years, SD = 18.21; mean time from diagnosis 13.83 years, SD = 18.21). Weighted logistic regression models were conducted to identify correlates of PC knowledge.

Results

Of the 593 cancer survivors in the sample, 66% (N = 378) reported that they had never heard of PC, 18% (N = 112) reported knowing a little bit about PC, and 17% (N = 95) reported knowing what PC is and could explain it to someone else. In multivariable analysis, survivors of color (Hispanic/Latino, Black, Asian, American Indian, and Pacific Islander), males, and those less educated were significantly less likely to report knowledge of PC. Among survivors who did report knowledge of PC, a lack of distinction between differing modes of supportive care exists.

Significance of results

These findings suggest a need to increase PC knowledge among cancer survivors with the ultimate goal of addressing disparities in PC acceptance and utilization.
The federal government and Canada's COVID-19 responses: from ‘we're ready, we're prepared’ to ‘fires are burning’
Authors: Allin Sara , Fitzpatrick Tiffany , Marchildon Gregory P. , Quesnel-Vallée Amélie
Published: June 2021

Canada's experience with the coronavirus disease-2019 (COVID-19) pandemic has been characterized by considerable regional variation, as would be expected in a highly decentralized federation. Yet, the country has been beset by challenges, similar to many of those documented in the severe acute respiratory syndrome outbreak of 2003. Despite a high degree of pandemic preparedness, the relative success with flattening the curve during the first wave of the pandemic was not matched in much of Canada during the second wave. This paper critically reviews Canada's response to the COVID-19 pandemic with a focus on the role of the federal government in this public health emergency, considering areas within its jurisdiction (international borders), areas where an increased federal role may be warranted (long-term care), as well as its technical role in terms of generating evidence and supporting public health surveillance, and its convening role to support collaboration across the country. This accounting of the first 12 months of the pandemic highlights opportunities for a strengthened federal role in the short term, and some important lessons to be applied in preparing for future pandemics.
Influence of the Kuroshio Intrusion on Deep Flow Intraseasonal Variability in the Northern South China Sea
Authors: Quan Qi , Liu Zhiqiang , Sun Shantong , Cai Zhongya , Yang Yang , Jin Guangzhen , Li Zhibing , Liang X. San
Published: June 2021

Interactions between the open ocean and marginal seas have been suggested to be critical to the redistribution and dissipation of global energy. Here, we propose a mechanism for the upper open ocean influencing the deep flow in marginal seas that hinges on the formation and propagation of topographic Rossby waves (TRWs). Observations and high‐resolution simulations suggest substantial intraseasonal variability with periods of 5–60 days associated with the deep flow over continental slopes of the northern South China Sea (NSCS). These fluctuations generally account for over 40% of the total deep kinetic energy variability and the number can reach 70% over the slopes to the west of the Luzon Strait, southwest of the Dongsha Islands, and northeast of the Xisha Islands. By examining the spatiotemporal features of the fluctuations, we demonstrate that the intraseasonal variability of the deep flow in the NSCS is closely associated with TRWs. Using a recently developed multiscale energetics analysis in combination with a ray tracing model, we show that the energy sources of TRWs can be traced back to the east of the Dongsha Islands, where the Kuroshio intrusion and related eddies energize the TRWs primarily through pressure work. These waves propagate westward across the NSCS and drive the intraseasonal variability of the deep flow over continental slopes. Our findings highlight an energy pathway from the open ocean western boundary current to the abyssal marginal sea that could modulate regional circulation as well as exchanges between major ocean basins.
New Global Meteoric Smoke Observations From SOFIE: Insight Regarding Chemical Composition, Meteoric Influx, and Hemispheric Asymmetry
Authors: Hervig Mark E. , Plane John M. C. , Siskind David E. , Feng Wuhu , Bardeen Charles G. , Bailey Scott M.
Published: June 2021

Measurements from the Solar Occultation For Ice Experiment (SOFIE) in both hemispheres are used to characterize meteoric smoke in the mesosphere and to estimate the meteoric flux into Earth's atmosphere. New smoke extinction retrievals from sunrise measurements in the Northern Hemisphere (NH) are presented, which complement the previously reported sunset observations in the Southern Hemisphere (SH). The sunrise observations are in good agreement with simulations from the Whole Atmosphere Community Climate Model (WACCM), for both the seasonal and height dependence of smoke in the mesosphere. The SOFIE‐WACCM comparisons assumed that smoke in the mesosphere exists purely as Fe‐rich olivine. This is justified because olivine is detected optically by SOFIE, meteoric ablation is predicted to inject similar quantities of the most abundant elements (Fe, Mg, and Si) into the mesosphere, and olivine is anticipated by theory and laboratory experiments. In addition, the ablated meteoric influx (AMI) and total meteoric influx determined from SOFIE assuming Fe‐rich olivine is in agreement with a recent and independent investigation based on models and observations. SOFIE observations from 2007 to 2021 indicate a global AMI of 7.3 ± 2.2 metric tons per day (t d−1), which corresponds to a total influx (ablated plus surviving material) of 24.7 ± 7.3 t d−1. Finally, the results indicate stronger descent in the NH polar winter mesosphere than in the SH winter. This hemispheric asymmetry at polar latitudes is indicated by smoke and water vapor results from both SOFIE and WACCM.
WISP-1 induced by mechanical stress contributes to fibrosis and hypertrophy of the ligamentum flavum through Hedgehog-Gli1 signaling
Authors: Sun Chao , Ma Qinghong , Yin Jian , Zhang Han , Liu Xinhui
Published: June 2021

Ongoing chronic fibrosis and hypertrophy of the ligamentum flavum (LF) is an important cause of lumbar spinal canal stenosis (LSCS). Our previous work showed that WNT1-inducible signaling pathway protein 1 (WISP-1) is a critical driver of LF fibrosis. However, the potential mechanism has not been explored. Here, we found that Gli1 was upregulated in hypertrophic LF tissues and required for fibrogenesis in fibroblasts. Moreover, mechanical stretching increased the expression of WISP-1 in LF fibroblasts. Furthermore, WISP-1 induced fibrogenesis in vitro through the Hedgehog-Gli1 pathway. This conclusion was supported by the fact that WISP-1 activated the Hedgehog-Gli1 pathway in LF fibroblasts and that cyclopamine attenuated the effect of WISP-1-induced fibrogenesis. WISP-1 also promoted the transition of fibroblasts into myofibroblasts via the Hedgehog pathway. Importantly, a hypertrophic LF rabbit model induced by mechanical stress also showed pathological changes in fibrosis and elevated expression of WISP-1, Gli1, and α-SMA. Therapeutic administration of cyclopamine reduced collagen expression, fibroblast proliferation, and myofibroblast differentiation and ameliorated fibrosis in the mechanical stress-induced rabbit model. Collectively, our findings show mechanical stress/WISP-1/Hedgehog signaling as a new fibrotic axis contributing to LF hypertrophy and identify Hedgehog signaling as a therapeutic target for the prevention and treatment of LF fibrosis.
Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents
Authors: Usman Moonisah , Woloshynowych Maria , Britto Jessica Carrilho , Bilkevic Ivona , Glassar Bethany , Chapman Simon , Ford-Adams Martha E. , Desai Ashish , Bain Murray , Tewfik Ihab , Volpi Emanuela V.
Published: June 2021

Background/objectives

Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status.

Subjects/methods

We carried out a cross-sectional study with 132 participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2′-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay.

Results

As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability.

Conclusions

Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.
Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing
Authors: Fabbri Chiara , Pain Oliver , Hagenaars Saskia P. , Lewis Cathryn M. , Serretti Alessandro
Published: June 2021

Major depressive disorder (MDD) is the single largest contributor to global disability and up to 20–30% of patients do not respond to at least two antidepressants (treatment-resistant depression, TRD). This study leveraged imputed gene expression in TRD to perform a drug repurposing analysis. Among those with MDD, we defined TRD as having at least two antidepressant switches according to primary care records in UK Biobank (UKB). We performed a transcriptome-wide association study (TWAS) of TRD (n = 2165) vs healthy controls (n = 11,188) using FUSION and gene expression levels from 21 tissues. We identified compounds with opposite gene expression signatures (ConnectivityMap data) compared to our TWAS results using the Kolmogorov-Smirnov test, Spearman and Pearson correlation. As symptom patterns are routinely assessed in clinical practice and could be used to provide targeted treatments, we identified MDD subtypes associated with TRD in UKB and analysed them using the same pipeline described for TRD. Anxious MDD (n = 14,954) and MDD with weight gain (n = 4697) were associated with TRD. In the TWAS, two genes were significantly dysregulated (TMEM106B and ATP2A1 for anxious and weight gain MDD, respectively). A muscarinic receptor antagonist was identified as top candidate for repurposing in TRD; inhibition of heat shock protein 90 was the main mechanism of action identified for anxious MDD, while modulators of metabolism such as troglitazone showed promising results for MDD with weight gain. This was the first TWAS of TRD and associated MDD subtypes. Our results shed light on possible pharmacological approaches in individuals with difficult-to-treat depression.
Robustification of GWAS to explore effective SNPs addressing the challenges of hidden population stratification and polygenic effects
Authors: Akond Zobaer , Ahsan Md. Asif , Alam Munirul , Mollah Md. Nurul Haque
Published: June 2021

Genome-wide association studies (GWAS) play a vital role in identifying important genes those is associated with the phenotypic variations of living organisms. There are several statistical methods for GWAS including the linear mixed model (LMM) which is popular for addressing the challenges of hidden population stratification and polygenic effects. However, most of these methods including LMM are sensitive to phenotypic outliers that may lead the misleading results. To overcome this problem, in this paper, we proposed a way to robustify the LMM approach for reducing the influence of outlying observations using the β-divergence method. The performance of the proposed method was investigated using both synthetic and real data analysis. Simulation results showed that the proposed method performs better than both linear regression model (LRM) and LMM approaches in terms of powers and false discovery rates in presence of phenotypic outliers. On the other hand, the proposed method performed almost similar to LMM approach but much better than LRM approach in absence of outliers. In the case of real data analysis, our proposed method identified 11 SNPs that are significantly associated with the rice flowering time. Among the identified candidate SNPs, some were involved in seed development and flowering time pathways, and some were connected with flower and other developmental processes. These identified candidate SNPs could assist rice breeding programs effectively. Thus, our findings highlighted the importance of robust GWAS in identifying candidate genes.
Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways
Authors: Contant Camille , Rouabhia Mahmoud , Loubaki Lionel , Chandad Fatiha , Semlali Abdelhabib
Published: June 2021

Oral cancer is one of the major public health problems. The aim of this study was to evaluate the effects of anethole, 1-methoxy-4-[(E)-1-propenyl]-benzene, on growth and apoptosis of oral tumor cells, and to identify the signaling pathways involved in its interaction with these cancer cells. Cancer gingival cells (Ca9-22) were treated with different concentrations of anethole. Cell proliferation and cytotoxic effects were measured by MTT and LDH assays. Cell death, autophagy and oxidative stress markers were assessed by flow cytometry while cell migration was determined by a healing capacity assay. The effect of anethole on apoptotic and pro-carcinogenic signaling pathways proteins was assessed by immunoblotting. Our results showed that anethole selectively and in a dose-dependent manner decreases the cell proliferation rate, and conversely induces toxicity and apoptosis in oral cancer cells. This killing effect was mediated mainly through NF-κB, MAPKinases, Wnt, caspase 3, 9 and PARP1 pathways. Anethole showed an ability to induce autophagy, decrease reactive oxygen species (ROS) production and increased intracellular glutathione (GSH) activity. Finally, anethole treatment inhibits the expression of oncogenes (cyclin D1) and up-regulated cyclin-dependent kinase inhibitor (p21WAF1), increases the expression of p53 gene, but inhibits the epithelial-mesenchymal transition markers. These results indicate that anethole could be a potential molecule for the therapy of oral cancer.
Terrestrial snail-mucus mediated green synthesis of silver nanoparticles and in vitro investigations on their antimicrobial and anticancer activities
Authors: Mane Pramod C. , Sayyed Shabnam A. R. , Kadam Deepali D. , D.Shinde Manish , Fatehmulla Amanullah , Aldhafiri Abdullah M. , Alghamdi Eman A. , Amalnerkar Dinesh P. , Chaudhari Ravindra D.
Published: June 2021

Over the past few years, biogenic methods for designing silver nanocomposites are in limelight due to their ability to generate semi-healthcare and para-pharmaceutical consumer goods. The present study reports the eco-friendly synthesis of silver nanoparticles from the hitherto unexplored mucus of territorial snail Achatina fulica by the facile, clean and easily scalable method. The detailed characterization of the resultant samples by UV–Visible Spectroscopy, FESEM-EDS, XRD and FTIR Spectroscopy techniques corroborated the formation of silver nanoparticles in snail mucus matrix. The resultant samples were tested against a broad range of Gram positive and Gram negative bacteria like Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and a fungal strain Aspergillus fumigatus by well diffusion method. The results indicate that silver nanoparticles in mucus matrix exhibit strong antibacterial as well as antifungal activity. The pertinent experiments were also performed to determine the inhibitory concentration against both bacterial and fungal strains. Anticancer activity was executed by in vitro method using cervical cancer cell lines. Curiously, our biogenically synthesized Ag nanoparticles in biocompatible mucus revealed anticancer activity and demonstrated more than 15% inhibition of Hela cells. We suggest an interesting possibility of formulating antimicrobial and possibly anticancer creams/gels for topical applications in skin ailments.
Inorganic nanomaterials with rapid clearance for biomedical applications
Authors: Wang Xianwen , Zhong Xiaoyan , Li Jianxiang , Liu Zhuang , Cheng Liang
Published: June 2021

Inorganic nanomaterials with inherently exceptional physicochemical properties and rapid clearance behavior would find wide biomedical applications.
A computational study of the properties of low- and high-index Pd, Cu and Zn surfaces
Authors: Kabalan Lara , Kowalec Igor , Catlow C. Richard A. , Logsdail Andrew J.
Published: June 2021

Surface energies and nano-particle structures from DFT modelling.
Mechanical characterization of base analogue modified nucleic acids by force spectroscopy
Authors: Sundar Rajan Vinoth , Viader-Godoy Xavier , Lin Yii-Lih , Dutta Uttama , Ritort Felix , Westerlund Fredrik , Wilhelmsson L. Marcus
Published: June 2021

Investigating the forces in nucleic acids using single base-pair level modifications and optical tweezers.
Warm white-light emitting silica films prepared using lead-free double perovskite QDs
Authors: Li Zexin , Sun Fenglei , Song Haining , Zhou Haifeng , zhou Yifei , Yuan Zhenlei , Guo Peng , Zhou Guangjun , Zhuang Qianqian , Yu Xiaoqiang
Published: June 2021

Bi-doped Cs2AgxNa1−xInCl6 quantum dots with a wide luminescence domain were prepared by a heat injection method, and warm white light emitting films with good photostability and thermal stability were prepared by SiO2 coating.
Divergent α-functionalization of cyclic amines via ring construction by molecular O2 oxidized dearomatization and ring deconstruction by aromatization-driven C–C σ-bond cleavage
Authors: Hu Fangzhi , Wang Liang , Ge Chunyan , Li Xinyao , Ding Zhanshuai , Xu Lubin , Li Shuai-Shuai
Published: June 2021

An efficient approach to achieve the divergent α-C(sp3)–H functionalization of cyclic amines through an O2 oxidized dearomatization/ring construction and aromatization-driven ring deconstruction/intermolecular functionalization strategy was developed.
α-Arylation of (hetero)aryl ketones in aqueous surfactant media
Authors: Wood Alex B. , Roa Daniel E. , Gallou Fabrice , Lipshutz Bruce H.
Published: June 2021

α-Arylations can be run under micellar catalysis conditions using a Pd(i) pre-catalyst together with KO-t-Bu as base. Sequences using this coupling along with as many as four additional steps can be carried out in a 1-pot fashion, all in water.
The surfactant effect on electrorheological performance and colloidal stability
Authors: Xu Hanqi , Wu Jinbo , Hong Yaying , Wen Weijia
Published: June 2021

The enhancement of the electrorheological properties and suspension stability can be achieved by adding a certain amount of Span surfactant in the electrorheological fluid.
The MLL3/4 H3K4 methyltransferase complex in establishing an active enhancer landscape
Authors: Wang Lan-Hsin , Aberin Marvin Angelo E. , Wu Sean , Wang Shu-Ping
Published: June 2021

Enhancers are cis-regulatory elements that play essential roles in tissue-specific gene expression during development. Enhancer function in the expression of developmental genes requires precise regulation, while deregulation of enhancer function could be the main cause of tissue-specific cancer development. MLL3/KMT2C and MLL4/KMT2D are two paralogous histone modifiers that belong to the SET1/MLL (also named COMPASS) family of lysine methyltransferases and play critical roles in enhancer-regulated gene activation. Importantly, large-scale DNA sequencing studies have revealed that they are amongst the most frequently mutated genes associated with human cancers. MLL3 and MLL4 form identical multi-protein complexes for modifying mono-methylation of histone H3 lysine 4 (H3K4) at enhancers, which together with the p300/CBP-mediated H3K27 acetylation can generate an active enhancer landscape for long-range target gene activation. Recent studies have provided a better understanding of the possible mechanisms underlying the roles of MLL3/MLL4 complexes in enhancer regulation. Moreover, accumulating studies offer new insights into our knowledge of the potential role of MLL3/MLL4 in cancer development. In this review, we summarize recent evidence on the molecular mechanisms of MLL3/MLL4 in the regulation of active enhancer landscape and long-range gene expression, and discuss their clinical implications in human cancers.
Sequence determinants, function, and evolution of CpG islands
Authors: Angeloni Allegra , Bogdanovic Ozren
Published: June 2021

In vertebrates, cytosine-guanine (CpG) dinucleotides are predominantly methylated, with ∼80% of all CpG sites containing 5-methylcytosine (5mC), a repressive mark associated with long-term gene silencing. The exceptions to such a globally hypermethylated state are CpG-rich DNA sequences called CpG islands (CGIs), which are mostly hypomethylated relative to the bulk genome. CGIs overlap promoters from the earliest vertebrates to humans, indicating a concerted evolutionary drive compatible with CGI retention. CGIs are characterised by DNA sequence features that include DNA hypomethylation, elevated CpG and GC content and the presence of transcription factor binding sites. These sequence characteristics are congruous with the recruitment of transcription factors and chromatin modifying enzymes, and transcriptional activation in general. CGIs colocalize with sites of transcriptional initiation in hypermethylated vertebrate genomes, however, a growing body of evidence indicates that CGIs might exert their gene regulatory function in other genomic contexts. In this review, we discuss the diverse regulatory features of CGIs, their functional readout, and the evolutionary implications associated with CGI retention in vertebrates and possibly in invertebrates.
The cellular pathways and potential therapeutics of Polycystic Kidney Disease
Authors: Richards Taylor , Modarage Kavindiya , Malik Soniya A. , Goggolidou Paraskevi
Published: June 2021

Polycystic Kidney Disease (PKD) refers to a group of disorders, driven by the formation of cysts in renal tubular cells and is currently one of the leading causes of end-stage renal disease. The range of symptoms observed in PKD is due to mutations in cilia-localising genes, resulting in changes in cellular signalling. As such, compounds that are currently in preclinical and clinical trials target some of these signalling pathways that are dysregulated in PKD. In this review, we highlight these pathways including cAMP, EGF and AMPK signalling and drugs that target them and may show promise in lessening the disease burden of PKD patients. At present, tolvaptan is the only approved therapy for ADPKD, however, it carries several adverse side effects whilst comparatively, no pharmacological drug is approved for ARPKD treatment. Aside from this, drugs that have been the subject of multiple clinical trials such as metformin, which targets AMPK signalling and somatostatins, which target cAMP signalling have shown great promise in reducing cyst formation and cellular proliferation. This review also discusses other potential and novel targets that can be used for future interventions, such as β-catenin and TAZ, where research has shown that a reduction in the overexpression of these signalling components results in amelioration of disease phenotype. Thus, it becomes apparent that well-designed preclinical investigations and future clinical trials into these pathways and other potential signalling targets are crucial in bettering disease prognosis for PKD patients and could lead to personalised therapy approaches.
Protein-fragment complementation assays for large-scale analysis of protein–protein interactions
Authors: Blaszczak Ewa , Lazarewicz Natalia , Sudevan Aswani , Wysocki Robert , Rabut Gwenaël
Published: June 2021

Protein–protein interactions (PPIs) orchestrate nearly all biological processes. They are also considered attractive drug targets for treating many human diseases, including cancers and neurodegenerative disorders. Protein-fragment complementation assays (PCAs) provide a direct and straightforward way to study PPIs in living cells or multicellular organisms. Importantly, PCAs can be used to detect the interaction of proteins expressed at endogenous levels in their native cellular environment. In this review, we present the principle of PCAs and discuss some of their advantages and limitations. We describe their application in large-scale experiments to investigate PPI networks and to screen or profile PPI targeting compounds.
Utilizing magnetic resonance techniques to study membrane interactions of amyloid peptides
Authors: Rajput Sunnia , Sani Marc-Antoine , Keizer David W. , Separovic Frances
Published: June 2021

Alzheimer's disease (AD) is a common neurodegenerative condition that involves the extracellular accumulation of amyloid plaques predominantly consisting of Aβ peptide aggregates. The amyloid plaques and soluble oligomeric species of Aβ are believed to be the major cause of synaptic dysfunction in AD brain and their cytotoxic mechanisms have been proposed to involve interactions with cell membranes. In this review, we discuss our solid-state nuclear magnetic resonance (ssNMR) studies of Aβ interactions with model membranes.
Uncertainties in the18F(p,α)15O reaction rate in classical novae
Authors: Kahl D. , José J. , Woods P. J.
Published: June 2021

Context.Direct observation ofγ-ray emission from the decay of18F ejected in classical nova outbursts remains a major focus of the nuclear astrophysics community. However, modeling the abundance of ejected18F, and thus the predicted detectability distance of aγ-ray signal near 511 keV emitted from these transient thermonuclear episodes, is hampered by significant uncertainties in our knowledge of the key18F(p,α) reaction rate.

Aims.We analyze uncertainties in the most recent nuclear physics experimental results employed to calculate the18F(p,α) reaction rate. Our goal is to determine which uncertainties have the most profound influence on the predicted abundance of18F ejected from novae in order to guide future experimental works.

Methods.We calculated a wide range of18F(p,α) reaction rates using theR-Matrix formalism, which allowed us to take all interference effects into account. Using a selection of 16 evenly spaced rates over the full range, we performed 16 new hydrodynamic nova simulations.

Results.We have performed one of the most thorough theoretical studies of the impact of the18F(p,α) reaction in classical novae to date. The18F(p,α) rate remains highly uncertain at nova temperatures, resulting in a factor of ∼10 uncertainty in the predicted abundance of18F ejected from nova explosions. We also found that the abundance of18F may be strongly correlated with that of19F.

Conclusions.Despite numerous nuclear physics uncertainties affecting the determination of the18F(p,α) reaction rate, dominated by unknown interference signs between 1/2+and 3/2+resonances, future experimental work should focus on firmly and precisely determining the directly measurable quantum properties of the subthreshold states in the compound nucleus19Ne near 6.13 and 6.29 MeV.
Observability of the vertical shear instability in protoplanetary disk CO kinematics
Authors: Barraza-Alfaro Marcelo , Flock Mario , Marino Sebastian , Pérez Sebastián
Published: June 2021

Context. Dynamical and turbulent motions of gas in a protoplanetary disk are crucial for their evolution and are thought to affect planet formation. Recent (sub-)millimeter observations show evidence of weak turbulence in the disk’s outer regions. However, the detailed physical mechanism of turbulence in these outer regions remains uncertain. The vertical shear instability (VSI) is a promising candidate mechanism to produce turbulence in the outer parts of the disk.

Aims. Our objective is to study the observability of the gas velocity structure produced by the VSI via CO kinematics with the Atacama Large Millimetre/submillimetre Array (ALMA).

Methods. We performed global 3D hydrodynamical simulations of an inviscid and locally isothermal VSI-unstable disk. We post-processed the simulation results with radiative transfer calculations and produced synthetic predictions of CO rotational emission lines. Next, we computed the line of sight velocity map and its deviations from a sub-Keplerian equilibrium solution. We explored the detectability of the VSI by identifying kinematic signatures using realistic simulated observations using the CASA package.

Results. Our 3D hydrodynamical simulations of the VSI show the steady state dynamics of the gas in great detail. From the velocity structure, we infer a turbulent stress value of αrϕ = 1.4 × 10−4. On large scales, we observe clear velocity deviations of the order of 50 m s−1 as axisymmetric rings with radially interspersed signs. By comparing synthetic observations at different inclinations we find optimal conditions at i ≲ 20° to trace for the kinematic structures of the VSI. We found that current diagnostics to constrain gas turbulence from nonthermal broadening of the molecular line emission are not applicable to anisotropic VSI turbulence.

Conclusions. We conclude that the detection of kinematic signatures produced by the VSI is possible with ALMA’s current capabilities. Observations including an extended antenna configuration are required to resolve the structure (beam sizes below ~10 au). The highest spectral resolution available is needed (~0.05 km s−1 with ALMA Band 6) for a robust detection. The characterization of the large-scale velocity perturbations is required to constrain the turbulence level produced by the VSI from gas observations.
Sunspot tilt angles revisited: Dependence on the solar cycle strength
Authors: Jiao Qirong , Jiang Jie , Wang Zi-Fan
Published: June 2021

Context. The tilt angle of sunspot groups is crucial in the Babcock-Leighton (BL) type dynamo for the generation of the poloidal magnetic field. Some studies have shown that the tilt coefficient, which excludes the latitudinal dependence of the tilt angles, is anti-correlated with the cycle strength. If the anti-correlation exists, it will be shown to act as an effective nonlinearity of the BL-type dynamo to modulate the solar cycle. However, some studies have shown that the anti-correlation has no statistical significance.

Aims. We aim to investigate the causes behind the controversial results of tilt angle studies and to establish whether the tilt coefficient is indeed anti-correlated with the cycle strength.

Methods. We first analyzed the tilt angles from Debrecen Photoheliographic Database (DPD). Based on the methods applied in previous studies, we took two criteria (with or without angular separation constraint Δs > 2.​​°5) to select the data, along with the linear and square-root functions to describe Joy’s law, and three methods (normalization, binned fitting, and unbinned fitting) to derive the tilt coefficients for cycles 21–24. This allowed us to evaluate different methods based on comparisons of the differences among the tilt coefficients and the tilt coefficient uncertainties. Then we utilized Monte Carlo experiments to verify the results. Finally, we extended these methods to analyze the separate hemispheric DPD data and the tilt angle data from Kodaikanal and Mount Wilson.

Results. The tilt angles exhibit an extremely wide scatter due to both the intrinsic mechanism for its generation and measurement errors, for instance, the unipolar regions included in data sets. Different methods to deal with the uncertainties are mainly responsible for the controversial character of the previous results. The linear fit to the tilt-latitude relation of sunspot groups with Δs > 2.​​°5 of a cycle carried out without binning the data can minimize the effect of the tilt scatter on the uncertainty of the tilt coefficient. Based on this method the tilt angle coefficient is anti-correlated with the cycle strength with strong statistical significance (r = −0.85 at 99% confidence level). Furthermore, we find that tilts tend to be more saturated at high latitudes for stronger cycles. The tilts tend to show a linear dependence on the latitudes for weak cycles and a square-root dependence for strong cycles.

Conclusions. This study disentangles the cycle dependence of sunspot group tilt angles from the previous results that were shown to be controversial, spurring confusion in the field.
The effect of mineral fertilizers on the yield of vegetable beans, depending on the competition between plants in crops
Authors: Varfolomeyeva Natalya , Blagorodova Elena , Zvyagina Anastasiya , Nepshekueva Tamara
Published: June 2021

The sources of nutrient accumulation in beans and bean seeds are the process of photosynthesis, root nutrition during the seed filling period, as well as the reutilization of substances accumulated in the vegetative organs in the previous period. The close dependence of the competition intensity on the number of plants per unit area of sowing is revealed. It was found that although increased nitrogen doses significantly reduce the competitive mutual inhibition of plants, it begins earlier than with a low nitrogen nutrition level. The main factor for which bean plants compete during the emergence-beginning of flowering phase under normal cultivation conditions is the available soil nitrogen. Therefore, the nitrogen fertilizers rational use leads to a more complete phenotypic manifestation of the vegetable beans genetically determined productivity.
Analysis of environmental problems of crop production and ways to solve them
Authors: Shirokov Yuri , Tikhnenko Valery
Published: June 2021

The article deals with engineering and technological problems of improving the environmental safety of crop production as a complex biotechnical system, for the environment, consumers of crop production and machine operators who ensure production in the field. It is noted that the impact of agriculture on the environment and humans is not only promoting global warming, participation in environmental pollution by pesticides and undigested remnants of mineral and organic fertilizers, the pollution of the production of field crops with residual amounts of pesticides and food is not absorbed nitrogen, toxic threat environment in the area of the machine, but unsustainable use of non-renewable resources, the availability of which depend on agricultural technologies. The main directions of minimizing environmental pollution and reducing dependence on non-renewable resources as a result of agricultural activities are shown.
Evaluation of histochemical and molecular markers in the placenta of sows during pregnancy complicated by isoimmunization
Authors: Agarkov Alexander , Grudeva Elena , Agarkov Nikolay , Pisarenko Natalia , Belugin Nikolay
Published: June 2021

It is known that the pathological course of pregnancy is associated with a disturbance in the interdependent “mother-fetus” complex and leads to specific clinical consequences at the molecular-cellular, tissue, organ, organismal and population levels of organization. In case of violation of placentation (placental barrier), a state of immune conflict occurs, characterized by an antigen-antibody reaction, carried out through the placenta (in relation to the fetus), or through colostrum after birth (in relation to the newborn offspring). Therefore, immunological relations at the population level should be considered both the consequences of the action of the maternal organism’s antigens on the fetus, and the effects of the allogeneic action of the fetus on the mother’s body. According to the results of the experiment, the placentas of 10 sows of Large White breed were used as the material, which showed signs of isoimmunization to the resulting offspring. For histological examination, immediately after delivery, pieces of placenta up to 0.5 cm thick were selected, which were fixed in a 10% aqueous solution of neutral formalin. The fixed material after wiring through alcohols of increasing concentration, xylene, xylene-paraffin, was poured into paraffin. The obtained preparations were stained with conventional methods-hematoxylin and eosin. d (fibrinoid masses).
Changes in morphological composition of blood in rats under intragastric load with walnut meal
Authors: Leonov Victor , Pavlova Olga , Gulenko Olga , Kislov Maxim , Boriskin Pavel
Published: June 2021

The basis for the existence of all living organisms is homeostasis. Any living organism is an open dynamic self-regulating system and self-regulation is based on the feedback principle. The use of biologically active substances, for example, plant meal, opens up great possibilities for modulation of physiological processes in the body. Walnut fruit meal also has a rich composition, contains almost all microelements, large amounts of protein as well as carotene, quinones, lecithin, water-soluble vitamins and flavonoids. The aim of the work was to study the adaptive changes in the morphological composition of rat blood to intragastric loading with walnut meal in the form of suspension on distilled water. The experiment was carried out on 60 white laboratory rats. Conclusion: intragastric loading with distilled water suspension of walnut meal in a concentration of 15 mg/100 g body weight of clinically healthy rats was accompanied by an increase in erythrocyte count, hemoglobin concentration and leukocyte count by 6.8%, 7.0% and 9.6%, respectively, compared with the control group animals.