bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic Variation in Outcomes After Burn Injury
Authors: Espinoza Leda F. , Friedstat Jonathan , Faoro Nicholas , Chang Philip H. , McMullen Kara A. , Simko Laura C. , Esselman Peter , Holavanahalli Radha , Ryan Colleen M. , Schneider Jeffrey C. 
Published: February 2020

Background
Geography is an important yet underexplored factor that may influence the care and outcomes of burn survivors. This study aims to examine the impact of geography on physical and psychosocial function after burn injury.

Methods
Data from the Burn Model Systems National Database (1997–2015) were analyzed. Individuals 18 years and older who were alive at discharge were included. Physical and psychosocial functions were assessed at 6, 12, and 24 months postinjury using the following patient-reported outcome measures: Community Integration Questionnaire, Physical Composite Scale and Mental Composite Scale of the 12-Item Short Form Health Survey, Satisfaction with Appearance Scale, and Satisfaction with Life Scale. Descriptive statistics were generated for demographic and medical data, and mixed regression models were used to assess the impact of geography on long-term outcomes.

Results
The study included 469 burn survivors from the Centers for Medicare and Medicaid Services regions 10, 31 from region 8, 477 from region 6, 267 from region 3, and 41 from region 1. Participants differed significantly by region in terms of race/ethnicity, burn size, burn etiology, and acute care length of stay (P < 0.001). In adjusted mixed model regression analyses, scores of all 5 evaluated outcome measures were found to differ significantly by region (P < 0.05).

Conclusions
Several long-term physical and psychosocial outcomes of burn survivors vary significantly by region. This variation is not completely explained by differences in population characteristics. Understanding these geographical differences may improve care for burn survivors and inform future policy and resource allocation.
Urbanization, urbanicity, and depression: a review of the recent global literature
Authors: Sampson Laura , Ettman Catherine K. , Galea Sandro 
Published: February 2020

Purpose of review
One of the defining trends of population movement in the last half century has been global urbanization. Depression is the most common mental disorder in the world, but it is unclear how urbanization and urban living affect depression outcomes. Grounded in a previously articulated conceptual framework, we systematically reviewed recently published studies on urbanization, urbanicity, and depression.

Recent findings
Eleven articles were included in this review. Four studies found that living in urban areas was associated with elevated odds or more symptoms of depression. Three studies – all done in China – estimated protective effects of urbanization or urbanicity on depression. Two studies concluded no overall clear association. The remaining two articles stratified by urbanicity and found that greenspace was inversely associated with depression in more densely populated areas relative to rural areas. Other themes discussed included global and national trends such as aging, immigration, and planned urbanization in China, as well as urban living conditions such as traffic noise, air pollution, proximity to roadways, neighborhood social capital, and social cohesion.

Summary
Urbanization may affect depression differentially across geographic regions and income levels. More research is needed, particularly in low-income and middle-income countries, and on intersections between urbanization and other emerging global trends.
The importance of faith-based mental healthcare in African urbanized sites
Authors: Ojagbemi Akin , Gureje Oye 
Published: February 2020

Purpose of review
This review highlights what current research says about how local beliefs and norms can facilitate expansion of mental healthcare to meet the large unmet need for services in Africa.

Recent findings
In contemporary Africa, religious beliefs exert important influences on mental health as well as the way people with mental illnesses are viewed and cared for. Mental healthcare practices based on traditional and other religious beliefs, and offered by complementary and alternative health providers (CAPs), reflect the people's culture and are often preferentially sought by a majority of the population. Despite important differences in the worldviews of CAPs and biomedical mental healthcare practitioners in regard to causal explanations, there are nevertheless overlaps in the approaches of both sectors to the management of mental health conditions. These overlaps may provide a platform for collaboration and facilitate the scaling-up of evidence-based mental health services to underserved African populations, especially those residing in ever-expanding urban centres.

Summary
Faith-based mental healthcare is an important but informal component of the mental health system in much of Africa. Collaboration between its practitioners and biomedical practice may help to bridge the large treatment gap for mental health conditions on the continent.
Transposable elements have contributed human regulatory regions that are activated upon bacterial infection
Authors: Bogdan Lucia , Barreiro Luis , Bourque Guillaume 
Published: February 2020

Transposable elements (TEs) are increasingly recognized as important contributors to mammalian regulatory systems. For instance, they have been shown to play a role in the human interferon response, but their involvement in other mechanisms of immune cell activation remains poorly understood. Here, we investigated the profile of accessible chromatin enhanced in stimulated human macrophages using ATAC-seq to assess the role of different TE subfamilies in regulating gene expression following an immune response. We found that both previously identified and new repeats belonging to the MER44, THE1, Tigger3 and MLT1 families provide 14 subfamilies that are enriched in differentially accessible chromatin and found near differentially expressed genes. These TEs also harbour binding motifs for several candidate transcription factors, including important immune regulators AP-1 and NF-κB, present in 96% of accessible MER44B and 83% of THE1C instances, respectively. To more directly assess their regulatory potential, we evaluated the presence of these TEs in regions putatively affecting gene expression, as defined by quantitative trait locus (QTL) analysis, and found that repeats are also contributing to accessible elements near QTLs. Together, these results suggest that a number of TE families have contributed to the regulation of gene expression in the context of the immune response to infection in humans.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
Widespread correlation of KRAB zinc finger protein binding with brain-developmental gene expression patterns
Authors: Farmiloe Grace , Lodewijk Gerrald A. , Robben Stijn F. , van Bree Elisabeth J. , Jacobs Frank M. J. 
Published: February 2020

The large family of KRAB zinc finger (KZNF) genes are transcription factors implicated in recognizing and repressing repetitive sequences such as transposable elements (TEs) in our genome. Through successive waves of retrotransposition-mediated insertions, various classes of TEs have invaded mammalian genomes at multiple timepoints throughout evolution. Even though most of the TE classes in our genome lost the capability to retrotranspose millions of years ago, it remains elusive why the KZNFs that evolved to repress them are still retained in our genome. One hypothesis is that KZNFs become repurposed for other regulatory roles. Here, we find evidence that evolutionary changes in KZNFs provide them not only with the ability to repress TEs, but also to bind to gene promoters independent of TEs. Using KZNF binding site data in conjunction with gene expression values from the Allen Brain Atlas, we show that KZNFs have the ability to regulate gene expression in the human brain in a region-specific manner. Our analysis shows that the expression of KZNFs shows correlation with the expression of their target genes, suggesting that KZNFs have a direct influence on gene expression in the developing human brain. The extent of this regulation and the impact it has on primate brain evolution are still to be determined, but our results imply that KZNFs have become widely integrated into neuronal gene regulatory networks. Our analysis predicts that gene expression networks have been repeatedly innovated throughout primate evolution, continuously gaining new layers of gene regulation mediated by both TEs and KZNFs in our genome.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity
Authors: Kauzlaric Annamaria , Jang Suk Min , Morchikh Mehdi , Cassano Marco , Planet Evarist , Benkirane Monsef , Trono Didier 
Published: February 2020

KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation, notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in the human K562 erythro-leukaemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodellers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited at actively transcribed polymerase II promoters, where its depletion resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
On transposons and totipotency
Authors: Torres-Padilla Maria-Elena 
Published: February 2020

Our perception of the role of the previously considered ‘selfish’ or ‘junk’ DNA has been dramatically altered in the past 20 years or so. A large proportion of this non-coding part of mammalian genomes is repetitive in nature, classified as either satellites or transposons. While repetitive elements can be termed selfish in terms of their amplification, such events have surely been co-opted by the host, suggesting by itself a likely altruistic function for the organism at the subject of such natural selection. Indeed numerous examples of transposons regulating the functional output of the host genome have been documented. Transposons provide a powerful framework for large-scale relatively rapid concerted regulatory activities with the ability to drive evolution. Mammalian totipotency has emerged as one key stage of development in which transposon-mediated regulation of gene expression has taken centre stage in the past few years. During this period, large-scale (epigenetic) reprogramming must be accomplished in order to activate the host genome. In mice and men, one particular element murine endogenous retrovirus with leucine tRNA primer (MERVL) (and its counterpart human ERVL (HERVL)) appears to have acquired roles as a key driving force in this process. Here, I will discuss and interpret the current knowledge and its implications regarding the role of transposons, particularly of long interspersed nuclear elements (LINE-1s) and endogenous retroviruses (ERVs), in the regulation of totipotency.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
sRNA/L1 retrotransposition: using siRNAs and miRNAs to expand the applications of the cell culture-based LINE-1 retrotransposition assay
Authors: Tristan-Ramos Pablo , Morell Santiago , Sanchez Laura , Toledo Belen , Garcia-Perez Jose L. , Heras Sara R. 
Published: February 2020

The cell culture-based retrotransposition reporter assay has been (and is) an essential tool for the study of vertebrate Long INterspersed Elements (LINEs). Developed more than 20 years ago, this assay has been instrumental in characterizing the role of LINE-encoded proteins in retrotransposition, understanding how ribonucleoprotein particles are formed, how host factors regulate LINE mobilization, etc. Moreover, variations of the conventional assay have been developed to investigate the biology of other currently active human retrotransposons, such as Alu and SVA. Here, we describe a protocol that allows combination of the conventional cell culture-based LINE-1 retrotransposition reporter assay with short interfering RNAs (siRNAs) and microRNA (miRNAs) mimics or inhibitors, which has allowed us to uncover specific miRNAs and host factors that regulate retrotransposition. The protocol described here is highly reproducible, quantitative, robust and flexible, and allows the study of several small RNA classes and various retrotransposons. To illustrate its utility, here we show that siRNAs to Fanconi anaemia proteins (FANC-A and FANC-C) and an inhibitor of miRNA-20 upregulate and downregulate human L1 retrotransposition, respectively.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
Arabidopsis
RNA Polymerase IV generates 21–22 nucleotide small RNAs that can participate in RNA-directed DNA methylation and may regulate genes
Authors: Panda Kaushik , McCue Andrea D. , Slotkin R. Keith 
Published: February 2020

The plant-specific RNA Polymerase IV (Pol IV) transcribes heterochromatic regions, including many transposable elements (TEs), with the well-described role of generating 24 nucleotide (nt) small interfering RNAs (siRNAs). These siRNAs target DNA methylation back to TEs to reinforce the boundary between heterochromatin and euchromatin. In the male gametophytic phase of the plant life cycle, pollen, Pol IV switches to generating primarily 21–22 nt siRNAs, but the biogenesis and function of these siRNAs have been enigmatic. In contrast to being pollen-specific, we identified that Pol IV generates these 21–22 nt siRNAs in sporophytic tissues, likely from the same transcripts that are processed into the more abundant 24 nt siRNAs. The 21–22 nt forms are specifically generated by the combined activities of DICER proteins DCL2/DCL4 and can participate in RNA-directed DNA methylation. These 21–22 nt siRNAs are also loaded into ARGONAUTE1 (AGO1), which is known to function in post-transcriptional gene regulation. Like other plant siRNAs and microRNAs incorporated into AGO1, we find a signature of genic mRNA cleavage at the predicted target site of these siRNAs, suggesting that Pol IV-generated 21–22 nt siRNAs may function to regulate gene transcript abundance. Our data provide support for the existing model that in pollen Pol IV functions in gene regulation.
This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.
Developing bio-technical reliability among future researchers and industrial work-force in developing countries: a success story
Authors: Acharya Kshitish K 
Published: February 2020

AbstractA common problem in the biotech sector of developing countries is that a large portion of students attain a poor conceptual understanding of the basic theory and/or lack proficiency in basic laboratory skills even as they complete higher studies such as a master’s degree. A small scale solution was developed in the form of a unique post-graduate diploma program that imparted reliable skills in students with good theoretical knowledge. The course of 6 to 8 months duration, with an optional 6 months internship, was successfully conducted for 8 batches. Most students of this course inculcated the right laboratory practices. This was evident by safe operations, and precise as well as accurate results of quantitative experiments conducted by them. They learned to work independently as well as in teams. They could create and follow standard operating procedures, and contribute to general laboratory maintenance. Every student also designed, prepared and conducted routine molecular biology experiments. The following aspects are suggested for successfully dealing with the patchy and varied capacities of life science students during higher (post bachelor’s) studies: a) careful selection of students, b) training with prioritized objectives, c) attention to basic lab-practices, d) opportunities to self-learn, e) structured group discussions, f) teacher(s) with genuine interest and passion, g) reasonable infrastructure, and h) maintaining a good student-instructor ratio. The course objectives, structure, teaching methods, and experiences are presented here along with some of the relevant data, including statistics about improvement in the precision and accuracy in experimental results by students. Limitations in this course and a general critical perspective of the routine higher education have also been discussed briefly.
Divide et Impera: Identification of Small-Molecule Inhibitors of HCMV Replication Interfering with Dimerization of DNA Polymerase Processivity Factor UL44
Authors: Ghassabian Hanieh , Falchi Federico , Antonio Veronica Di , Timmoneri Martina , Mercorelli Beatrice , Loregian Arianna , Palù Giorgio , Alvisi Gualtiero 
Published: February 2020

ABSTRACTHuman cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS and transplanted patients, and in congenitally infected newborns. Despite the availability of several antiviral drugs, their utility is limited by poor bioavailability, toxicity, and resistant strains emergence. Therefore, it is crucial to identify new targets of therapeutic intervention. The dimerization of HCMV DNA polymerase processivity factor UL44 plays an essential role in the viral life cycle being required fororiLyt-dependent DNA replication. We validated the existence of UL44 homodimers bothin vitroand in living cells by a variety of approaches, including GST pulldown, thermal shift, FRET and BRET assays. Dimerization occurred with an affinity comparable to that of the UL54/UL44 interaction, and was impaired by amino acid substitutions at the dimerization interface. Subsequently, we performed anin-silicoscreening to select 18 small molecules (SMs) potentially interfering with UL44 homodimerization. Antiviral assays using recombinant HCMV TB4-UL83-YFP in the presence of the 18 selected SMs led to the identification of four active SMs. The most active one also inhibited AD169 in plaque reduction assays, and impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extent. As assessed by Western blotting experiments, treatment of infected cells specifically reduced viral gene expression starting from 48 h post infection, consistent with activity on viral DNA synthesis. Therefore, SMs inhibitors of UL44 dimerization could represent a new class of HCMV inhibitors, alternative to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.IMPORTANCEHCMV is a ubiquitous infectious agent causing life-lasting infections in humans. HCMV primary infections and reactivation in non-immunocompetent individuals often result in life-threatening conditions. Antiviral therapy mainly targets the DNA polymerase catalytic subunit UL54 and is often limited by toxicity and selection of drug-resistant viral strains, making the identification of new targets of therapeutic intervention crucial for a successful management of HCMV infections. The significance of our work is in identifying the dimerization of the DNA polymerase processivity factor UL44 as an alternative antiviral target. We could show that full length UL44 dimerizes in a cellular context with high affinity and that such interaction could be targeted by small molecules, thus inhibiting the replication of several HCMV strains, including a drug-resistant mutant. Thus, our work could pave the way to the development of a new class of anti-HCMV compounds that act by targeting UL44 dimerization.
Comparison between conventional electrodes and ultrasound monitoring to measure TMS evoked muscle contraction
Authors: Kaczmarczyk Isabella , Rawji Vishal , Rothwell John C. , Hodson-Tole Emma , Sharma Nikhil 
Published: February 2020

AbstractBackgroundTranscranial Magnetic stimulation (TMS) is a non-invasive cortical stimulation method that has been widely employed to explore cortical physiology in health and a range of diseases. At the core of many TMS protocols is the measurement of evoked muscle contractions using surface electromyography (sEMG). While sEMG is appropriate for many superficial muscles such as abductor pollicis brevis (ABP) and first dorsal interosseous (FDI), there are situations where the study of less accessible muscles may be of interest. Peripheral ultrasound is a non-invasive method that could provide a solution. We explore the relationship between TMS evoked sMEP and TMS evoked muscle contractions measured with muscle ultrasound. We hypothesise that in a healthy population, we expect a positive correlation between EMG and ultrasound measures.MethodsIn 10 participants we performed a standard TMS recruitment curve and simultaneously measured MEP and peripheral muscle ultrasound (pUS). We targeted the following muscles: biceps (BI), first dorsal interosseous (FDI), tibialis anterior (TA) and the tongue (TO).ResultsWe report a very close relationship between the MEP and pUS contraction. Resting motor threshold (RMT) measurements and recruitment curves are consistent in sEMG and pUS. A key aspect of this work is the ability to examine clinically relevant muscles that are difficult to probe using surface EMG electrodes, such as the tongue.ConclusionWe find that TMS muscle contractions can be measured with muscle ultrasound in superficial and deep muscles, enable additional, previously hard to study muscles, to be investigated. This could be valuable for allowing TMS to be used to explore a new range of muscles in disorders such as ALS. In muscles less accessible by sEMG, such as the tongue, it may be possible to use pUS as an alternative output. This may be useful in conditions such as ALS and stroke that can differentially affect the tongue.