bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis
Authors: Chen Junhong , Pan Weicong , Chen Yongjin , Wen Lijia , Tu Jihao , Liu Kai
Published: January 2020

Background

Aldehyde dehydrogenase 2 (ALDH2) and cytochrome p450 2E1 (CYP2E1) are important alcohol-metabolizing enzymes. The aim of this meta-analysis was to evaluate the association of ALDH2 rs671 and CYP2E1 rs2031920 polymorphisms with hepatocellular carcinoma (HCC) susceptibility in East Asians.

Methods

A systematic search strategy was implemented in MEDLINE, PubMed, Scopus, Embase, and China Academic Journals databases. Nineteen case-control studies were selected for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through random-effects or fixed-effects models. Subgroup analysis, meta-regression, sensitivity analysis, cumulative meta-analysis, and evaluation of publication bias were performed.

Results

The overall meta-analysis did not find a significant association of ALDH2 rs671 and CYP2E1 rs2031920 genotypes with HCC susceptibility in East Asians. In addition, stratified analysis by country, Hardy-Weinberg equilibrium status, and source of controls also did not identify any association.

Conclusion

The ALDH2 rs671 and CYP2E1 rs2031920 polymorphisms are not associated with HCC susceptibility in East Asians.
The role of the redox/miR-6855-3p/PRDX5A axis in reversing SLUG-mediated BRCA2 silencing in breast cancer cells
Authors: Ellison Marshall , Mittal Mukul , Chaudhuri Minu , Chaudhuri Gautam , Misra Smita
Published: January 2020

Background

We have previously shown that the zinc finger transcription repressor SNAI2 (SLUG) represses tumor suppressor BRCA2-expression in non-dividing cells by binding to the E2-box upstream of the transcription start site. However, it is unclear how proliferating breast cancer (BC) cells that has higher oxidation state, overcome this repression. In this study, we provide insight into the mechanism of de-silencing of BRCA2 gene expression by PRDX5A, which is the longest member of the peroxiredoxin5 family, in proliferating breast cancer cells.

Methods

We used cell synchronization and DNA affinity pulldown to analyze PRDX5A binding to the BRCA2 silencer. We used oxidative stress and microRNA (miRNA) treatments to study nuclear localization of PRDX5A and its impact on BRCA2-expression. We validated our findings using mutational, reporter assay, and immunofluorescence analyses.

Results

Under oxidative stress, proliferating BC cells express PRDX5 isoform A (PRDX5A). In the nucleus, PRDX5A binds to the BRCA2 silencer near the E2-box, displacing SLUG and enhancing BRCA2-expression. Nuclear PRDX5A is translated from the second AUG codon in frame to the first AUG codon in the PRDX5A transcript that retains all exons. Mutation of the first AUG increases nuclear localization of PRDX5A in MDA-MB-231 cells, but mutation of the second AUG decreases it. Increased mitronic hsa-miRNA-6855-3p levels under oxidative stress renders translation from the second AUG preferable. Mutational analysis using reporter assay uncovered a miR-6855-3p binding site between the first and second AUG codon in the PRDX5A transcript. miR-6855-3p mimic increases accumulation of nuclear PRDX5A and inhibits reporter gene translation.

Conclusion

Oxidative stress increases miR-6855-3p expression and binding to the inter-AUG sequence of the PRDX5A transcript, promoting translation of nuclear PRDX5A. Nuclear PRDX5A relieves SLUG-mediated BRCA2 silencing, resulting in increased BRCA2-expression.

Graphical abstract
The role of CSDE1 in translational reprogramming and human diseases
Authors: Guo Ao-Xiang , Cui Jia-Jia , Wang Lei-Yun , Yin Ji-Ye
Published: January 2020

CSDE1 (cold shock domain containing E1) plays a key role in translational reprogramming, which determines the fate of a number of RNAs during biological processes. Interestingly, the role of CSDE1 is bidirectional. It not only promotes and represses the translation of RNAs but also increases and decreases the abundance of RNAs. However, the mechanisms underlying this phenomenon are still unknown. In this review, we propose a “protein-RNA connector” model to explain this bidirectional role and depict its three versions: sequential connection, mutual connection and facilitating connection. As described in this molecular model, CSDE1 binds to RNAs and cooperates with other protein regulators. CSDE1 connects with different RNAs and their regulators for different purposes. The triple complex of CSDE1, a regulator and an RNA reprograms translation in different directions for each transcript. Meanwhile, a number of recent studies have found important roles for CSDE1 in human diseases. This model will help us to understand the role of CSDE1 in translational reprogramming and human diseases.

Graphical abstract
Correction to: The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression
Authors: Zhu Lei , Xi Pei-Wen , Li Xiao-Xia , Sun Xi , Zhou Wen-Bin , Xia Tian-Song , Shi Liang , Hu Yue , Ding Qiang , Wei Ji-Fu
Published: January 2020

In the original publication of this article [1], the molecular weight of RBMS3 was incorrectly noted as 38 KDa within Fig 1A, Fig 2A and Fig 2B. The figures have been updated to list the correct molecular weight of RBMS3 as 41 KDa.
Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer
Authors: Yang Dan , He Yang , Wu Bo , Deng Yan , Wang Nan , Li Menglin , Liu Yang
Published: January 2020

Background

Ovarian cancer (OC) ranks fifth as a cause of gynecological cancer-associated death globally. Until now, the molecular mechanisms underlying the tumorigenesis and prognosis of OC have not been fully understood. This study aims to identify hub genes and therapeutic drugs involved in OC.

Methods

Four gene expression profiles (GSE54388, GSE69428, GSE36668, and GSE40595) were downloaded from the Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) in OC tissues and normal tissues with an adjusted P-value < 0.05 and a |log fold change (FC)| > 1.0 were first identified by GEO2R and FunRich software. Next, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed for functional enrichment analysis of these DEGs. Then, the hub genes were identified by the cytoHubba plugin and the other bioinformatics approaches including protein-protein interaction (PPI) network analysis, module analysis, survival analysis, and miRNA-hub gene network construction was also performed. Finally, the GEPIA2 and DGIdb databases were utilized to verify the expression levels of hub genes and to select the candidate drugs for OC, respectively.

Results

A total of 171 DEGs were identified, including 114 upregulated and 57 downregulated DEGs. The results of the GO analysis indicated that the upregulated DEGs were mainly involved in cell division, nucleus, and protein binding, whereas the biological functions showing enrichment in the downregulated DEGs were mainly negative regulation of transcription from RNA polymerase II promoter, protein complex and apicolateral plasma membrane, and glycosaminoglycan binding. As for the KEGG-pathway, the upregulated DEGs were mainly associated with metabolic pathways, biosynthesis of antibiotics, biosynthesis of amino acids, cell cycle, and HTLV-I infection. Additionally, 10 hub genes (KIF4A, CDC20, CCNB2, TOP2A, RRM2, TYMS, KIF11, BIRC5, BUB1B, and FOXM1) were identified and survival analysis of these hub genes showed that OC patients with the high-expression of CCNB2, TYMS, KIF11, KIF4A, BIRC5, BUB1B, FOXM1, and CDC20 were statistically more likely to have poorer progression free survival. Meanwhile, the expression levels of the hub genes based on GEPIA2 were in accordance with those based on GEO. Finally, DGIdb database was used to identify 62 small molecules as the potentially targeted drugs for OC treatment.

Conclusions

In summary, the data may produce new insights regarding OC pathogenesis and treatment. Hub genes and candidate drugs may improve individualized diagnosis and therapy for OC in future.
Studying the evolution of exception handling anti-patterns in a long-lived large-scale project
Authors: de Sousa Dêmora B C , Maia Paulo Henrique M. , Rocha Lincoln S , Viana Windson
Published: January 2020

Exception handling is a well-known technique used to improve software robustness. However, recent studies report that developers typically neglect exception handling (mostly novice ones). We believe the quality of exception handling code in a software project is directly affected (i) by the absence, or lack of awareness, of an explicit exception handling policy and guidelines and (ii) by a silent rising of exception handling anti-patterns. In this paper, we investigate this phenomenon in a case study of a long-lived large-scale Java Web system in a Public Education Institution, trying to better understand the relationship between (i) and (ii), and the impact of developers’ turnover, skills, and guidance in (ii). Our case study takes into account the technical and human aspects. As a first step, we surveyed 21 developers regarding their perception of exception handling in the system’s institution. Next, we analysed the evolution of exception handling anti-patterns across 15 releases of the target system. We conducted a semi-structured interview with three senior software engineers, representatives of the development team, to present partial results of the case and raise possible causes for the found problems. The interviewed professionals and a second analysis of the code identified the high team turnover as the source of this phenomenon, since the public procurement process for hiring new developers has mostly attracted novice ones. These findings suggest that the absence of an explicit exception handling policy impacts negatively in the developers’ perception and implementation of exception handling. Furthermore, the absence of such policy has been leading developers to replicate existing anti-patterns and spread them through new features added during system evolution. We also observed that most developers have low skills regarding exception handling in general and low knowledge regarding the design and implementation of exception handling in the system. The system maintainer now has a diagnosis of the major causes of the quality problems in the exception handling code and was able to lead the required measures to repair this technical debt.
Does political risk matter for economic and financial risks in Venezuela?
Authors: Kirikkaleli Dervis
Published: January 2020

In this paper, the time–frequency dependency of political risk as well as economic and financial risks is explored in Venezuela using quarterly data from 1984Q1 to 2018Q4. The present study uses the wavelet coherence technique, which allows the investigation of both the long and short-term causal relationships between political risk and economic and financial risks in Venezuela. The findings of this study indicate that: (i) significant vulnerabilities in political risk, economic risk, and financial risk are observed at different time periods and different frequency levels; (ii) political risk has a strong power for explaining economic risk from 1995 to 2005 in the long run, while between 1984 and 2010, economic risk and political risk are positively correlated at different frequency levels; (iii) in the long run, changes in political risk significantly lead to changes in financial risk in Venezuela.
Epistatic interaction between PKD2 and ABCG2 influences the pathogenesis of hyperuricemia and gout
Authors: Dong Zheng , Zhou Jingru , Jiang Shuai , Li Yuan , Zhao Dongbao , Yang Chengde , Ma Yanyun , He Hongjun , Ji Hengdong , Jin Li , Zou Hejian , Wang Jiucun
Published: January 2020

Background

Genetic background affects serum urate concentration and gout risk, especially regarding these variants in the urate-transporter gene ABCG2. However, the role of epistasis between PKD2 and ABCG2 on the pathogenesis of gout is poorly understood. Here we assess this epistatic interaction in the progression from elevated serum urate to gout.

Results

We identified two epistatic interaction pairs (rs2728121: rs1481012 and rs2728121: rs2231137) were associated with urate levels in 4914 Chinese individuals (Pint = 0.018 and 0.004, respectively). Using subgroup analysis for gender and BMI, we found the degree of associations was varied by gender and BMI. The SNP pair rs2728121:rs1481012 influenced urate levels in females and overweight subjects (Pint = 0.006 and 0.022, respectively), but rs2728121:rs2231137 did in males, overweight and normal-weight subjects (Pint = 0.017, 0.047 and 0.013, respectively). Consistent results were also observed in associations between these epistatic interactions with hyperuricemia. Next, the SNP pair rs2728121:rs2231137 was identified to influence the development of gout from both hyperuricemia and healthy (Pint = 0.035 and 0.001, respectively), especially in males (Pint = 0.030 and 0.001, respectively). Furthermore, we demonstrated that interacting regions were enriched by regulatory elements. Finally, we observed a strong gene co-expression pattern between PKD2 and ABCG2 (r = 0.743, P = 5.83E-06).

Conclusion

Our findings indicate epistasis between PKD2 and ABCG2 influence serum urate concentrations, hyperuricemia and gout risk, thus providing insight into the pathogenesis of gout.
Aboveground biomass, growth and yield for some selected introduced tree species, namely Cupressus lusitanica, Eucalyptus saligna, and Pinus patula in Central Highlands of Ethiopia
Authors: Tesfaye Mehari Alebachew , Gardi Oliver , Anbessa Tesfaye Bekele , Blaser Jurgen
Published: January 2020

Background

Species of the generaEucalyptus,Cupressus, andPinusare the most widely planted tree species in the country in general and in Chilimo dry Afromontane forest in particular. Eucalyptus covers 90% of the total planted forest area in the country. However, only limited information exists in the country regarding aboveground biomass (AGB), belowground biomass (BGB), growth, and yield. This study was conducted to assess the variables on 25 and 30 years of age for three planted species:Cupressus lusitanica,Eucalyptus saligna, andPinus patulain Chilimo plantation forest, in the Central Highlands of Ethiopia. A two-times inventory was conducted in 2012 and 2017. A total of nine square sampled plots of 400 m2each, three plots underCupressus lusitanica, 3Eucalyptus saligna, and 3Pinus patulawere used for data collection. Data on height, diameter, soil, and tree stumps were collected. Percent C, % N, and bulk density was performed following chemical procedure.

Results

The aboveground biomass ranged from 125.76 to 228.67 t C ha−1and the basal area and number of stems from 3.76 to 25.50 m2 ha−1and 483 to 1175 N ha−1, respectively. The mean annual basal area and volume increment were between 0.97 and 1.20 m2 ha−1 year−1and 10.79 and 16.22 m3 ha−1 year−1. Both carbon and nitrogen stock of the planted forest was non-significant among the tree species.

Conclusion

The aboveground biomass, growth, and yield significantly varied among the species.Cupressus lusitanicahad the highest aboveground biomass, volume, and basal area, whileEucalyptus salignahad the lowest value .To a depth of 1 m, total carbon stored ranged from 130.13 to 234.26 t C ha−1. The total annual carbon sequestration potential was 12,575.18 t CO2eq.Eucalyptus has the highest carbon stock density and growth rate than other species.
Changing wildfire, changing forests: the effects of climate change on fire regimes and vegetation in the Pacific Northwest, USA
Authors: Halofsky Jessica E. , Peterson David L. , Harvey Brian J.
Published: January 2020

Background

Wildfires in the Pacific Northwest (Washington, Oregon, Idaho, and western Montana, USA) have been immense in recent years, capturing the attention of resource managers, fire scientists, and the general public. This paper synthesizes understanding of the potential effects of changing climate and fire regimes on Pacific Northwest forests, including effects on disturbance and stress interactions, forest structure and composition, and post-fire ecological processes. We frame this information in a risk assessment context, and conclude with management implications and future research needs.

Results

Large and severe fires in the Pacific Northwest are associated with warm and dry conditions, and such conditions will likely occur with increasing frequency in a warming climate. According to projections based on historical records, current trends, and simulation modeling, protracted warmer and drier conditions will drive lower fuel moisture and longer fire seasons in the future, likely increasing the frequency and extent of fires compared to the twentieth century. Interactions between fire and other disturbances, such as drought and insect outbreaks, are likely to be the primary drivers of ecosystem change in a warming climate. Reburns are also likely to occur more frequently with warming and drought, with potential effects on tree regeneration and species composition. Hotter, drier sites may be particularly at risk for regeneration failures.

Conclusion

Resource managers will likely be unable to affect the total area burned by fire, as this trend is driven strongly by climate. However, fuel treatments, when implemented in a spatially strategic manner, can help to decrease fire intensity and severity and improve forest resilience to fire, insects, and drought. Where fuel treatments are less effective (wetter, high-elevation, and coastal forests), managers may consider implementing fuel breaks around high-value resources. When and where post-fire planting is an option, planting different genetic stock than has been used in the past may increase seedling survival. Planting seedlings on cooler, wetter microsites may also help to increase survival. In the driest topographic locations, managers may need to consider where they will try to forestall change and where they will allow conversions to vegetation other than what is currently dominant.
Pathologic assessment of tumor-associated macrophages and their histologic localization in invasive breast carcinoma
Authors: Mwafy Shorouk E. , El-Guindy Dina M.
Published: January 2020

Background

Tumor-associated macrophages (TAMs) are important in regulating cross-talk between tumor cells and tumor microenvironment. TAMs are involved in multiple steps of tumor progression and invasion. This study aimed to compare CD163 expression with the widely used CD68 pan-macrophage marker in invasive breast carcinoma. Furthermore, it focused on assessing the significance of TAMs localization in relation to clinicopathological parameters.

Results

CD68 and CD163 immunohistochemical expressions within TAMs infiltrating both tumor nest (TN) and tumor stroma (TS) were evaluated in 60 specimens with invasive breast carcinoma. High CD68-positive stromal TAMs was significantly related to larger tumor, nodal metastasis and vascular invasion (p = 0.003, 0.037, 0.032, respectively), whereas high CD163-positive stromal TAMs was significantly related to larger tumors, nodal metastasis, stage III tumors, vascular invasion, estrogen receptor (ER) negativity, and triple-negative subtype (p = 0.023, < 0.001, 0.001, 0.022, 0.002, 0.017, respectively). On multivariate analysis, high CD68-positive TAMs infiltrating TS was significantly associated with larger tumor and positive nodal metastasis (p = 0.006 and 0.016, respectively), whereas high CD163 TAMs density within TS was significantly associated with positive vascular invasion, nodal metastasis, and molecular subtypes (p = 0.003, 0.001, and 0.009, respectively).

Conclusion

TAMs within tumor stroma and tumor nest have different levels of association with poor prognostic parameters. So, it is of great importance to consider the histologic localization of TAMs in addition to the degree of TAMs infiltration.
Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline
Authors: Konstantinopoulos Panagiotis A. , Norquist Barbara , Lacchetti Christina , Armstrong Deborah , Grisham Rachel N. , Goodfellow Paul J. , Kohn Elise C. , Levine Douglas A. , Liu Joyce F. , Lu Karen H. , Sparacio Dorinda , Annunziata Christina M.
Published: January 2020

PURPOSE

To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus.

METHODS

A literature search and prospectively defined study selection criteria sought systematic reviews, meta-analyses, randomized controlled trials (RCTs), and comparative observational studies published from 2007 through 2019. Guideline recommendations were based on the review of the evidence.

RESULTS

The systematic review identified 19 eligible studies. The evidence consisted of systematic reviews of observational data, consensus guidelines, and RCTs.

RECOMMENDATIONS

All women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes. In women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants should be performed. Women with identified germline or somatic pathogenic or likely pathogenic variants in BRCA1/2 genes should be offered treatments that are US Food and Drug Administration (FDA) approved in the upfront and the recurrent setting. Women diagnosed with clear cell, endometrioid, or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. First- or second-degree blood relatives of a patient with ovarian cancer with a known germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation, counseling, and genetic testing. Clinical decision making should not be made based on a variant of uncertain significance. Women with epithelial ovarian cancer should have testing at the time of diagnosis.
Anesthetic Management of Posterior Sternoclavicular Joint Dislocations: A Report of 2 Cases
Authors: Weinberg Roniel , Chazen J. Levi , Lichtman Adam D.
Published: January 2020

Posterior sternoclavicular joint (SCJ) dislocation is a rare cause of shoulder injury that can present with life-threatening mediastinal complications. This injury most commonly occurs in adolescents and young adults, and there is a lack of anesthesia literature addressing its anesthetic implications. We present 2 cases of posterior SCJ dislocations and discuss the anesthetic management and the potential for mediastinal injuries.
Treaty 6 Cree Annuity Spending in the Territorial Economy of Western Canada, 1873–1905
Authors: Colpitts George
Published: January 2020

Before mass settlement occurred in Western Canada at the turn of the twentieth century, Indigenous people used treaty monetization and town spending to subvert the very forces of liberalism encouraged with the expansion of a colonial market economy. After 1880, the Cree of Treaty 6, in particular, chose to collectively spend their annuities in new towns to support traditional dances and ceremonies and, especially, to join together in large multiband gatherings. Despite increasingly restrictive government policies, particularly the pass system that limited Indigenous movement beyond reserves, town “Treaty Days” spending only declined in prevalence in the late 1890s when treaty annuities began quickly losing their extraordinary spending power.
A Comparison of Historical Evidence for Droughts in the Pre-Columbian Maya Codices with Climatological Evidence for Droughts during the Early and Late Classic Periods
Authors: Bricker Harvey M. , Bricker Victoria R.
Published: January 2020

An examination of several historical texts in the Maya codices reveals that droughts were a significant concern to the pre-Columbian Maya that ultimately resulted in the collapse of their civilization. The effects of such droughts mentioned in those texts include damage to crops, famine, and wildfires. The dates assigned to five droughts in the codical texts agree with dates obtained from the analysis of lacustrine cores and stalagmites in caves by climatologists.
Optic cup morphogenesis requires neural crest-mediated basement membrane assembly
Authors: Bryan Chase D. , Casey Macaulie A. , Pfeiffer Rebecca L. , Jones Bryan W. , Kwan Kristen M.
Published: January 2020

Organogenesis requires precise interactions between a developing tissue and its environment. In vertebrates, the developing eye is surrounded by a complex extracellular matrix as well as multiple mesenchymal cell populations. Disruptions to either the matrix or periocular mesenchyme can cause defects in early eye development, yet in many cases, the underlying mechanism is unknown. Here, using multidimensional imaging and computational analyses in zebrafish, we establish that cell movements in the developing optic cup require neural crest. Ultrastructural analysis reveals that basement membrane formation around the developing eye is also dependent on neural crest, but only specifically around the retinal pigment epithelium. Neural crest cells produce the extracellular matrix protein nidogen: impairing nidogen function disrupts eye development, and strikingly, expression of nidogen in the absence of neural crest partially restores optic cup morphogenesis. These results demonstrate that eye formation is regulated in part by extrinsic control of extracellular matrix assembly.
A genetic system for tissue-specific inhibition of cell proliferation
Authors: Pu Wenjuan , Han Ximeng , He Lingjuan , Li Yan , Huang Xiuzhen , Zhang Mingjun , Lv Zan , Yu Wei , Wang Qing-Dong , Cai Dongqing , Wang Jinjin , Sun Ruilin , Fei Jian , Ji Yong , Nie Yu , Zhou Bin
Published: January 2020

Cellular proliferation is a basic process during organ development, tissue homeostasis, and/or disease progression. Likewise, after injury typically multiple cell lineages respond to various cues and proliferate to initiate repair and/or remodeling of the injured tissue. Unravelling the specific role of proliferation of one cell type and its lineage in the context of the whole organism during tissue regeneration and/or disease progression would provide valuable information on these processes. Here we reported a new genetic system to inhibit cell proliferation in a tissue-specific manner. We generated Cre- or Dre-inducible p21-GFP (ip21-GFP) transgenic mice that allow for the experimentally-induced permanent cell cycle arrest of specific cell lineages of interest, while genetically marking these cells. This system allows for the inhibition of pathogenic cell proliferation. We found that cardiac fibroblast proliferation inhibition significantly reduced scar formation, and promoted neovascularization and cardiomyocyte survival. Additionally, we found that inhibition of one type of cell proliferation (namely, hepatocytes) induces the lineage conversion of another type cells (ie, ductal cells) during tissue regeneration. These results validate the use of ip21-GFP mice as a new genetic tool for cell lineage-specific inhibition of cell proliferation in vivo.
Lamin A/C modulates spatial organization and function of the Hsp70 gene locus via nuclear myosin I
Authors: Pradhan Roopali , Nallappa Muhunden Jayakrishnan , Sengupta Kundan
Published: January 2020

The structure–function relationship of the nucleus is tightly regulated, especially during heat shock. Typically, heat shock activates molecular chaperones that prevent protein misfolding and preserve genome integrity. However, the molecular mechanisms that regulate nuclear structure–function relationships during heat shock remain unclear. Here, we show that lamin A and C (hereafter lamin A/C; both lamin A and C are encoded by LMNA) are required for heat-shock-mediated transcriptional induction of the Hsp70 gene locus (HSPA genes). Interestingly, lamin A/C regulates redistribution of nuclear myosin I (NM1) into the nucleus upon heat shock, and depletion of either lamin A/C or NM1 abrogates heat-shock-induced repositioning of Hsp70 gene locus away from the nuclear envelope. Lamins and NM1 also regulate spatial positioning of the SC35 (also known as SRSF2) speckles – important nuclear landmarks that modulates Hsp70 gene locus expression upon heat shock. This suggests an intricate crosstalk between nuclear lamins, NM1 and SC35 organization in modulating transcriptional responses of the Hsp70 gene locus during heat shock. Taken together, this study unravels a novel role for lamin A/C in the regulation of the spatial dynamics and function of the Hsp70 gene locus upon heat shock, via the nuclear motor protein NM1.

This article has an associated First Person interview with the first author of the paper.
Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles
Authors: Tahir Uzma , Monroy Jenna A. , Rice Nicole A. , Nishikawa Kiisa C.
Published: January 2020

The active isometric force produced by muscles varies with muscle length in accordance with the force–length relationship. Compared with isometric contractions at the same final length, force increases after active lengthening (force enhancement) and decreases after active shortening (force depression). In addition to cross-bridges, titin has been suggested to contribute to force enhancement and depression. Although titin is too compliant in passive muscles to contribute to active tension at short sarcomere lengths on the ascending limb and plateau of the force–length relationship, recent evidence suggests that activation increases titin stiffness. To test the hypothesis that titin plays a role in force enhancement and depression, we investigated isovelocity stretching and shortening in active and passive wild-type and mdm (muscular dystrophy with myositis) soleus muscles. Skeletal muscles from mdm mice have a small deletion in the N2A region of titin and show no increase in titin stiffness during active stretch. We found that: (1) force enhancement and depression were reduced in mdm soleus compared with wild-type muscles relative to passive force after stretch or shortening to the same final length; (2) force enhancement and force depression increased with amplitude of stretch across all activation levels in wild-type muscles; and (3) maximum shortening velocity of wild-type and mdm muscles estimated from isovelocity experiments was similar, although active stress was reduced in mdm compared with wild-type muscles. The results of this study suggest a role for titin in force enhancement and depression, which contribute importantly to muscle force during natural movements.
Medium compensation in a spring-actuated system
Authors: Feller Kathryn D. , Sutton Gregory P. , Gonzalez-Bellido Paloma T.
Published: January 2020

Mantis shrimp strikes are one of the fastest animal movements, despite their occurrence in a water medium with viscous drag. Since the strike is produced by a latch-mediated spring-actuated system and not directly driven by muscle action, we predicted that strikes performed in air would be faster than underwater due to reduction in the medium's drag. Using high-speed video analysis of stereotyped strikes elicited from Squilla mantis, we found the exact opposite: strikes are much slower and less powerful in air than in water. S. mantis strikes in air have a similar mass and performance to latch-mediated spring-actuated jumps in locusts, suggesting a potential threshold for the energetics of a 1-2 g limb rotating in air. Drag forces induced by the media may be a key feature in the evolution of mantis shrimp strikes and provide a potential target for probing the braking system of these extremely fast movements.
Dual-Task Gait Recovery after Concussion among Female and Male Collegiate Athletes
Authors: HOWELL DAVID R. , OLDHAM JESSIE , LANOIS COREY , KOERTE INGA , LIN ALEXANDER P. , BERKSTRESSER BRANT , WANG FRANCIS , MEEHAN WILLIAM P.
Published: January 2020

Purpose

Few studies have investigated recovery between sexes using objective outcome measures. Our purpose was to examine the independent association between biological sex and recovery of postconcussion gait among collegiate athletes.

Methods

We evaluated participants with a diagnosed concussion <7 d postinjury, and approximately 1.5 months and 3.5 months postinjury. Participants completed a single/dual-task gait evaluation and symptom inventory. During dual-task trials, they completed a mental task (backward subtraction, spelling, or month recitation). The primary outcome measure was height-adjusted gait velocity recovery, defined as achieving normal gait velocity using established values: >0.56 and >0.50 gait velocity (m·s−1)/height (m) under single and dual-task conditions, respectively. We used a multivariable Cox proportional hazard model to identify associations between sex and dual-task recovery, controlling for age, concussion history, symptom severity, and loss of consciousness at the time of injury.

Results

Ninety-four individuals participated in the study: 47 (50%) were female athletes (mean age = 20.1, SD = 1.3 yr) and 47 (50%) were male athletes (mean age = 20.3, SD = 1.3 yr). Sex was not independently associated with height-adjusted single-task gait velocity recovery after controlling for potential confounders (hazard ratio = 1.62, 95% confidence interval = 0.87–3.01). However, male sex was independently associated with longer dual-task gait recovery time after controlling for potential confounders (hazard ratio = 2.43, 95% confidence interval = 1.11–5.35).

Conclusion

Male athletes required a longer duration of time after concussion to achieve dual-task gait recovery than female athletes. Thus, functional dual-task abilities after concussion may be affected differentially by sex and should be accounted for within individualized concussion management strategies.
Comparison of Tibial Shock during Treadmill and Real-World Running
Authors: JOHNSON CALEB D. , OUTERLEYS JEREME , JAMISON STEVE T. , TENFORDE ADAM S. , RUDER MATTHEW , DAVIS IRENE S.
Published: January 2020

The degree to which standard laboratory gait assessments accurately reflect impact loading in an outdoor running environment is currently unknown.

Purpose

To compare tibial shock between treadmill and road marathon conditions.

Methods

One hundred ninety-two runners (men/women, 105/87; age, 44.9 ± 10.8 yr) completed a treadmill gait assessment while wearing a tibial-mounted inertial measurement unit, several days before completing a marathon race. Participants ran at 90% of their projected race speed and 30 s of tibial shock data were collected. Participants then wore the sensors during the race and tibial shock was averaged over the 12th, 23rd, and 40th kilometers. One-way analysis of covariance and correlation coefficients were used to compare vertical/resultant tibial shock between treadmill and marathon conditions. Analyses were adjusted for differences in running speed between conditions.

Results

A significant main effect of condition was found for mean vertical and resultant tibial shock (P < 0.001). Early in the marathon (12-km point), runners demonstrated higher mean tibial shock adjusted for speed compared with the treadmill data (vertical = +24.3% and resultant = +30.3%). Mean differences decreased across the course of the marathon. Vertical tibial shock at the 40th kilometer of the race was similar to treadmill data, and resultant shock remained higher. Vertical and resultant tibial shock were significantly correlated between treadmill and the 12th kilometer of the race (r
s = 0.64–0.65, P < 0.001), with only 40% to 42% of the variance in outdoor tibial shock explained by treadmill measures. Correlations for tibial shock showed minimal changes across stages of the marathon.

Conclusions

These results demonstrate that measures of impact loading in an outdoor running environment are not fully captured on a treadmill.
scRepertoire: An R-based toolkit for single-cell immune receptor analysis
Authors: Borcherding Nicholas , Bormann Nicholas L.
Published: January 2020

Single-cell sequencing is an emerging technology in the field of immunology and oncology that allows researchers to couple RNA quantification and other modalities, like immune cell receptor profiling at the level of an individual cell. A number of workflows and software packages have been created to process and analyze single-cell transcriptomic data. These packages allow users to take the vast dimensionality of the data generated in single-cell-based experiments and distill the data into novel insights. Unlike the transcriptomic field, there is a lack of options for software that allow for single-cell immune receptor profiling. Enabling users to easily combine mRNA and immune profiling, scRepertoire was built to process data derived from 10x Genomics Chromium Immune Profiling for both T-cell receptor (TCR) and immunoglobulin (Ig) enrichment workflows and subsequently interacts with the popular Seurat R package. The scRepertoire R package and processed data are open source and available on GitHub and provides in-depth tutorials on the capability of the package.
Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target
Authors: Veljkovic Veljko , Vergara-Alert Júlia , Segalés Joaquim , Paessler Slobodan
Published: January 2020

A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.
A grid-based sample design framework for household surveys
Authors: Boo Gianluca , Darin Edith , Thomson Dana R. , Tatem Andrew J.
Published: January 2020

Traditional sample designs for household surveys are contingent upon the availability of a representative primary sampling frame. This is defined using enumeration units and population counts retrieved from decennial national censuses that can become rapidly inaccurate in highly dynamic demographic settings. To tackle the need for representative sampling frames, we propose an original grid-based sample design framework introducing essential concepts of spatial sampling in household surveys. In this framework, the sampling frame is defined based on gridded population estimates and formalized as a bi-dimensional random field, characterized by spatial trends, spatial autocorrelation, and stratification. The sampling design reflects the characteristics of the random field by combining contextual stratification and proportional to population size sampling. A nonparametric estimator is applied to evaluate the sampling design and inform sample size estimation. We demonstrate an application of the proposed framework through a case study developed in two provinces located in the western part of the Democratic Republic of the Congo. We define a sampling frame consisting of settled cells with associated population estimates. We then perform a contextual stratification by applying a principal component analysis (PCA) and k-means clustering to a set of gridded geospatial covariates, and sample settled cells proportionally to population size. Lastly, we evaluate the sampling design by contrasting the empirical cumulative distribution function for the entire population of interest and its weighted counterpart across different sample sizes and identify an adequate sample size using the Kolmogorov-Smirnov distance between the two functions. The results of the case study underscore the strengths and limitations of the proposed grid-based sample design framework and foster further research into the application of spatial sampling concepts in household surveys.
MODERN VIEW ON THE PROBLEM OF OSTEOPOROSIS IN ANKYLOSING SPONDYLITIS
Authors: Raskina Tat'yana , Malyshenko O. , Pirigova M. , Letaeva M. , Averkieva Yu.
Published: January 2020

The study included 72 men with a reliable diagnosis of AS, mean age – 43,2±9,1 years. X-ray examination of the axial skeleton and peripheral joints was carried out, HLA-B27 was determined. Disease activity was assessed using the index ВАSDАI, functional disorders with the help of the BASFI index. BMD was determined by two-energy x-ray absorptiometry. The control group consisted of 74 healthy men, mean age – 46,7±0,9 years. Given the chronic nature and asymptomatic course of osteoporosis, the task of doctors working with this group of patients is an active search for osteoporosis using all available diagnostic techniques for the early detection of this condition and subsequent correction of the drug treatment.
COTTONWEED MARSH (MARSH). CHEMICAL COMPOSITION OF ETHANOL EXTRACT
Authors: Platonov V. , Dunaev V. , Suhih G. , Shatskiy M. , Volochaeva M.
Published: January 2020

For the first time, a detailed study of the chemical composition of ethanol extract of dried marsh (swamp), a product obtained after preliminary exhaustive last ex-traction with n-hexane, toluene, chloroform and acetone was performed. Chromatography-mass spectrometry made it possible to identify 119 individual compounds in this extract with the determination of their quantitative content, mass spectra and structural formulas, and the calculation of the structural-group composition was performed. A characteristic feature of the extract is the presence of significant amounts of nitrogen and sulfur-containing compounds (20.04), esters (21.47), sterols (18.54), carboxylic acids (8.15) and hydrocarbons (7.15) (wt. % of the extract). In addition, the extract contains phenols, ketones, aldehydes, alcohols and glycosides: 5.01; 4.34; 4.88; 3.16 and 3.12 (wt. % of the extract), respectively. Dominance in the extract of nitrogen-sulfur-containing and compounds; environment of sterols-betulin and its derivatives, esters, as well as the presence of different structure of phenols, glycosides, aldehydes and alcohols makes it possible to assume a wide range of pharmacological activity of drugs based on ethanol extract of dried marsh (marsh).
DYNAMICS OF INCIDENCE AND ITS CHRONIZATION IN GIRLS-TEENAGERS IN THE RUSSIAN FEDERATION
Authors: Bant'eva M. , Manoshkina E. , Matveev E.
Published: January 2020

The health condition of the Russian Federation children, including adolescents, has been characterized by negative trends in the past thirty years. The aim of the study is to identify the main trends in the total and for the first time in the life registered incidence in girls 15-17 years old in the Russian Federation, as well as to track the quantity and dynamics of the indicator of chronicity of diseases. The data of form N12 of the federal statistical observation for the period 2000-2017 are analyzed, using the method of descriptive statistics. A significant increase was revealed both in the total incidence of girls (by 56.9%) and for the first time in the life registered incidence (by 63.0%). The maximum increase in total incidence is observed for the most classes of diseases, for example: neoplasms (2.4 times), injuries, poisoning and some other consequences of external causes (2.4 times), congenital anomalies (malformations) (2.3 times), cardiovascular system diseases (2 times), diseases of the musculoskeletal system and connective tissue (2 times). The growth for the first time in life registered incidence was revealed for the overwhelming majority of classes of diseases, for example: injuries, poisoning and some other consequences of exposure to external causes (2.5 times), diseases of the nervous system (2.2 times), cardiovascular system diseases (2 times), neoplasms (2 times), diseases of the ear and mastoid process (2 times), diseases of the musculoskeletal system and connective tissue (1.9 times). High figures of the chronicity index aggregative for all classes of diseases reflect the initially high level of chronic pathology in girls 15-17 years old, what is an unfavorable characteristic of their health condition. An analysis of the chronization index of the diseases among girls aged 15–17 years over the study period revealed its maximum growth for classes of congenital anomalies (malformations) (by 31.1%) and tumors (for 23.0%), and for certain nosologies: menstrual disorders (5.8 times) and renal failure (4.2 times). The health of children, and especially adolescents, determines the health of the nation in the nearest future; therefore, the issues of its preservation and improvement require thorough attention.
PARAMETERS OF CARDIO-INTERVALS OF WOMEN OF THE NORTH RUSSIAN FEDERATION FOR DOSED LOADS
Authors: Filatova O. , Bashkatova Yuliya , Mel'nikova E. , Chempalova L.
Published: January 2020

The study of the effect of physical activity on the parameters of the human cardiovascular system in the North of the Russian Federation is an urgent problem of age-related physiology. The purpose of this research is to study the parameters of the pseudoattractors of the cardiointervals of the subjects at rest and after exercise. Object and methods: a group of 15 women in a calm state (sitting) and after 30 squats were examined using the «Elox-01C» instrument. 15 samples of cardio-intervals for each subject were recorded (in 5 minutes), and then 225 phase portraits of the subjects before the load and 225 phase portraits after the load were calculated. The mezhattraktorny distances Ri were calculated for each subject (before and after the load). Significant differences were found across the entire group of area parameters S for pseudoattractors of cardiointervals and for parameters of mezhattraktorny distances R. It is shown that the areas of pseudoattractors S and mezhattraktorny distances can be used to identify individual characteristics of the parameters of the cardiovascular system of the subjects (for example, before and after the load) and for group comparison. At the same time, traditional statistics practically do not give results due to the Eskov-Zinchenko effect.
SWEET SAWBERRY (Comarum Palustre L.) IN MEDICAL PRACTICE (literature review)
Authors: Platonov V. , Hadarcev Aleksandr , Belyaeva Elena
Published: January 2020

The review substantiates the use of biologically active substances of plant origin, derived from marsh saber, common on the territory of Russia – in various sections of clinical medicine. The General description and zones of its distribution, possibilities of extraction of Sabel-nick rhizomes are given. The chemical composition was charac-terized and the role of proanthocyanidins in the anti-inflammatory effects of sabelnik was clarified. The possibility of obtaining various medicinal forms of drugs from the rhizomes of sabelnik is shown. A well-known range of applications in medical practice for lesions of the musculoskeletal system, arthrosis and arthritis, nephropathy, after transurethral resection of the prostate, etc.