bluuebunny/crossref_metadata_2025 huggingface dataset:
Second Opinions in Psychiatry: A Review
Authors: HEUSS SABINA C. , SCHWARTZ BRUCE J. , SCHNEEBERGER ANDRES R.
Published: January 2019

Background:

Although second opinions are rather restricted to the surgical disciplines, they have become more and more important to the health system in the last 20 years. The demand has been triggered by rising health costs and the economization of the field. The Internet has also made a considerable contribution to the demand for patient-initiated second opinions. Given these developments, it is surprising that second opinions have not become more important in the field of psychiatry. This article highlights the special situation of second opinions in psychiatry, discusses possible barriers to the adoption of second opinions in psychiatry, and the potential for greater use of second opinions in this field.

Objective:

In psychiatry, second opinions have been neglected by the typical drivers of innovations in health care, including insurers and other commercial drivers as well as psychiatrists and patients themselves. This review identifies current barriers to widespread adoption of second opinions in psychiatric practice, discusses the benefits of second opinions that have been demonstrated in other disciplines, and outlines the potential gains to be realized through use of second opinions in psychiatry.

Methods:

Literature in the area was reviewed through a search of the main medical databases. This literature review was supported by in-depth interviews with health care personnel and insurers.

Conclusions:

Second opinions are rarely obtained in psychiatry and there is little literature on this subject. The stigmatization of psychiatric disorders and patients and the uniqueness of the patient-doctor relationship in psychiatry, especially in psychotherapeutic care, may pose considerable obstacles to the use of second opinions in this field. In addition, more stakeholders, such as social workers, government agencies and regulators, health care and disability insurers, and social security agencies, are involved in the mental health compared with the somatic health sector, which may make it more difficult to achieve a coordinated approach in psychiatric care. However, we have found no convincingly good reason why second opinions have not been at least discussed in psychiatry. Psychiatry could benefit from ongoing discussions concerning the outcomes of second opinions in other medical disciplines.
Recognizing Fournier's Gangrene in the Emergency Department
Authors: Gadler Tracie , Huey Sally , Hunt Kelly
Published: January 2019

Fournier's gangrene is a rare disease with a significant mortality rate. The potentially fatal disease stems from both aerobic and anaerobic bacteria and primarily occurs in men. The majority of Fournier's gangrene cases are idiopathic or derived from perineal and genital skin infections. Comorbid risk factors include diabetes mellitus, alcohol misuse, and immunosuppression (Benjelloun et al., 2013). The infection initially presents as a cellulitis in the perineum or perianal area. As Fournier's gangrene progresses, the infected tissue becomes swollen, significantly painful, and necrotic. The progression of infection can lead to systemic symptoms, sepsis, and death. Early intervention is a key component in the treatment plan for Fournier's gangrene. The primary intervention is surgical debridement of the necrotic tissue. If an abscess is present, incision and drainage are indicated. In addition to surgical debridement, the administration of broad-spectrum antibiotics and hemodynamic stabilization are required (Cottrill, 2013). Complications after treatment include chronic pain, sexual dysfunction, decreased sensation of the penile skin, and scarring (Benjelloun et al., 2013).
Oral Diclofenac Potassium Versus Intravenous Acetaminophen in Acute, Isolated, Closed-Limb Trauma
Authors: Momeni Mehdi , Vahidi Elnaz , Badrizadeh Mohsen , Naderpour Zeinab , Saeedi Morteza
Published: January 2019

Pain control is an important concern in limb trauma. The most ideal agent for this purpose varies among different hospitals. The objective of this study was to compare the analgesic effect of oral diclofenac potassium versus intravenous acetaminophen in patients with limb trauma. This was a double-blind randomized clinical trial conducted on 60 adult patients. Oral diclofenac potassium (50 mg) was given in Group D, and intravenous acetaminophen (1 g in 500 ml normal saline over 20 min) was administered in Group A. Patients' pain scores (visual analogue scale) were recorded and compared at baseline, 5, 15, 30, 60 min, and 4 hr after drug administration. The mean age was 42.62 ± 15.42 and 38.04 ± 17.48 years in Group A and Group D, respectively. No significant change was observed between the 2 groups (p = 0.11). In this study, both drugs could decrease the pain score effectively and safely in isolated limb trauma.
Word Catheter Placement for Bartholin's Gland Abscess
Authors: Lannen Amy , Destephano Christopher , Wilbeck Jennifer
Published: January 2019

For women who present with Bartholin's abscesses, placement of a Word catheter offers a minimally invasive approach for effective management in urgent care and emergency department settings. Although the procedure is relatively simple, the frequency of placement in the ED setting varies. Provider familiarity with both the device and the procedure can be enhanced using simulation techniques. This article presents the diagnostic and treatment approaches to Bartholin's abscesses and describes in detail both low- and high-fidelity simulations for Word catheter placements.
Alcohol Use and Sexual Assault Among College Students
Authors: Sheridan Trisha , Evans Dian Dowling
Published: January 2019

The Research to Practice column is designed to provide advanced practice nurses (APRNs) with an analysis of a current research topic with implications for practice change within emergency care settings. This review examines a recent study conducted by Tadros, Sharon, Hoffman, and Davidov (2018), titled “Emergency Department Visits for Sexual Assault by Emerging Adults: Is Alcohol a Factor?” The authors conducted a retrospective chart review of emergency department (ED) visits for sexual assault among a college-age population and found most patients were female (98%) and 70% were younger than 21 years. Additionaly, among those younger than 21 years, 74% reported alcohol use at the time of their assault and 62.3% delayed presenting to the ED for care for 24 hr or more. These and other associated findings have implications for APRN practice, including reporting and documentation of these events, and risk reduction educational strategies.
Genome analysis-based reclassification of Lelliottia aquatilis as a later heterotypic synonym of Lelliottia jeotgali
Authors: Wu Wenjing , Zong Zhiyong
Published: January 2019

The aim of this study was to further clarify the taxonomic relationship between the two recently described bacterial species,

Lelliottia jeotgali

sp. nov. and

Lelliottia aquatilis

sp. nov. Whole genome sequences of types strains of the two species are available for analysis. Average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) values between the two type strains were determined. The ANI and isDDH values between type strains of the two species are 98.7 and 91.0 %, respectively, which are higher than cut-offs to define a bacterial species. It is therefore clear that the two species actually belong to the same species. The name of L.aquatilis was published at an earlier date than that of

L. aquatilis

. We therefore propose that

L. aquatilis

is a later heterotypic synonym of

L. jeotgali

.
Genomic analysis of bacteria in the Acute Oak Decline pathobiome
Authors: Doonan James , Denman Sandra , Pachebat Justin A. , McDonald James E.
Published: January 2019

The UK’s native oak is under serious threat from Acute Oak Decline (AOD). Stem tissue necrosis is a primary symptom of AOD and several bacteria are associated with necrotic lesions. Two members of the lesion pathobiome,

Brenneria goodwinii

and

Gibbsiella quercinecans

, have been identified as causative agents of tissue necrosis. However, additional bacteria including

Lonsdalea britannica

and

Rahnella

species have been detected in the lesion microbiome, but their role in tissue degradation is unclear. Consequently, information on potential genome-encoded mechanisms for tissue necrosis is critical to understand the role and mechanisms used by bacterial members of the lesion pathobiome in the aetiology of AOD. Here, the whole genomes of bacteria isolated from AOD-affected trees were sequenced, annotated and compared against canonical bacterial phytopathogens and non-pathogenic symbionts. Using orthologous gene inference methods, shared virulence genes that retain the same function were identified. Furthermore, functional annotation of phytopathogenic virulence genes demonstrated that all studied members of the AOD lesion microbiota possessed genes associated with phytopathogens. However, the genome of

B. goodwinii

was the most characteristic of a necrogenic phytopathogen, corroborating previous pathological and metatranscriptomic studies that implicate it as the key causal agent of AOD lesions. Furthermore, we investigated the genome sequences of other AOD lesion microbiota to understand the potential ability of microbes to cause disease or contribute to pathogenic potential of organisms isolated from this complex pathobiome. The role of these members remains uncertain but some such as

G. quercinecans

may contribute to tissue necrosis through the release of necrotizing enzymes and may help more dangerous pathogens activate and realize their pathogenic potential or they may contribute as secondary/opportunistic pathogens with the potential to act as accessory species for

B. goodwinii

. We demonstrate that in combination with ecological data, whole genome sequencing provides key insights into the pathogenic potential of bacterial species whether they be phytopathogens, part-contributors or stimulators of the pathobiome.
Selection, succession and stabilization of soil microbial consortia
Authors: Zegeye Elias K. , Brislawn Colin J. , Farris Yuliya , Fansler Sarah J. , Hofmockel Kirsten S. , Jansson Janet K. , Wright Aaron T. , Graham Emily B. , Naylor Dan , McClure Ryan S. , Bernstein Hans C.
Published: January 2019

Soil microorganisms play fundamental roles in cycling of soil carbon, nitrogen and other nutrients, yet we have a poor understanding of how soil microbiomes are shaped by their nutritional and physical environment. Here we investigated the successional dynamics of a soil microbiome during 21-weeks of enrichment on chitin and its monomer,N-acetylglucosamine. We examined succession of the soil communities in a physically heterogeneous soil matrix as well as a highly mixed liquid medium. The guiding hypothesis was that the initial species richness would influence the tendency for the selected consortia to stabilize and maintain relatively constant community structure over time. We also hypothesized that long term, substrate-driven growth would result in consortia with reduced species richness as compared to the parent microbiome and that this process would be deterministic with relatively little variation between replicates. We found that the initial species richness does influence the long-term community stability in both liquid media and soil and that lower initial richness results in a more rapid convergence to stability. Despite use of the same soil inoculum and access to the same major substrate, the resulting community composition differed greatly in soil compared to liquid medium. Hence, distinct selective pressures in soils relative to homogenous liquid media exist and can control community succession dynamics. This difference is likely related to the fact that soil microbiomes are more likely to thrive, with fewer compositional changes, in a soil matrix compared to liquid environments.

IMPORTANCE

The soil microbiome carries out important ecosystem functions, but interactions between soil microbial communities have been difficult to study due to the high microbial diversity and complexity of the soil habitat. Here we successfully obtained stable consortia with reduced complexity that contained species found in the original source soil. These consortia and the methods used to obtain them can be a valuable resource for exploration of specific mechanisms underlying soil microbial community ecology. The results of this study also provide new experimental context to better inform how soil microbial communities are shaped by new environments and how a combination of initial taxonomic structure and physical environment influences stability.
Increased Replication of Dissimilatory Nitrate-Reducing Bacteria Leads to Decreased Anammox Bioreactor Performance
Authors: Keren Ray , Lawrence Jennifer E. , Zhuang Weiqin , Jenkins David , Banfield Jillian F. , Alvarez-Cohen Lisa , Zhou Lijie , Yu Ke
Published: January 2019

Background

Anaerobic ammonium oxidation (anammox) is a biological process employed to remove reactive nitrogen from wastewater. While a substantial body of literature describes the performance of anammox bioreactors under various operational conditions and perturbations, few studies have resolved the metabolic roles of their core microbial community members.

Results

Here, we used metagenomics to study the microbial community of a laboratory-scale anammox bioreactor from inoculation, through a performance destabilization event, to robust steady-state performance. Metabolic analyses revealed that nutrient acquisition from the environment is selected for in the anammox community. Dissimilatory nitrate reduction to ammonium (DNRA) was the primary nitrogen removal pathway that competed with anammox. Increased replication of bacteria capable of DNRA led to the out-competition of annamox bacteria, and the loss of the bioreactor’s nitrogen removal capacity. These bacteria were highly associated with the anammox bacterium and considered part of the core microbial community.

Conclusions

Our findings highlight the importance of metabolic interdependencies related to nitrogen- and carbon-cycling within anammox bioreactors and the potentially detrimental effects of bacteria that are otherwise considered core microbial community members.
Biological Impact of a Large Scale Genomic Inversion that Grossly Disrupts the Relative Positions of the Origin and Terminus Loci of the Streptococcus pyogenes Chromosome
Authors: Savic Dragutin J. , Nguyen Scott V. , McCullor Kimberly , McShan W. Michael
Published: January 2019

A large-scale genomic inversion encompassing 0.79 Mb of the 1.816 Mb-longStreptococcus pyogenesserotype M49 strain NZ131 chromosome spontaneously occurs in a minor subpopulation of cells, and in this report genetic selection was used to obtain a stable lineage with this chromosomal rearrangement. This inversion, which drastically displaces theorisite, changes the relative length of the replication arms so that one replichore is approximately 0.41 Mb while the other is about 1.40 Mb in length. Genomic reversion to the original chromosome constellation is not observed in PCR-monitored analyses after 180 generations of growth in rich medium. As compared to the parental strain, the inversion surprisingly demonstrates a nearly identical growth pattern in exponential phase. Similarly, when cultured separately in rich medium during prolong stationary phase or in an experimental acute infection animal model (Galleria mellonella), the survival rate of both the parental strain and the invertant is equivalent. However, when co-incubated together, both in vitro and in vivo, the survival of the invertant declines relative to the parental strain. The accompanying aspect of the study suggests that inversions taking place nearbyoriC, always happen to secure the linkage oforiC to DNA sequences responsible for chromosome partition. The biological relevance of large scale inversions is also discussed.

IMPORTANCE

Based on our previous work, we created to our knowledge the largest asymmetric inversion covering 43.5% of theS. pyogenesgenome. In spite of a drastic replacement of origin of replication and the unbalanced size of replichores (1.4 Mb vs 0.41 Mb), the invertant, when not challenged with its progenitor, showed impressive vitality for growthin vitroand pathogenesis assays. The mutant supports the existing idea that slightly deleterious mutations can provide the setting for secondary adaptive changes. Furthermore, comparative analysis of the mutant with previously published data strongly indicate that even large genomic rearrangements survive provided that the integrity of theoriC and the chromosome partition cluster is preserved.
The strikingflower-in-flowerphenotype ofArabidopsis thalianaNossen (No-0) is caused by a novelLEAFYallele
Authors: Mohrholz Anne , Sun Hequan , Glöckner Nina , Hummel Sabine , Kolukisaoglu Üner , Schneeberger Korbinian , Harter Klaus
Published: January 2019

The transition to reproduction is a crucial step in the life cycle of any organism. InArabidopsis thalianathe establishment of reproductive growth can be divided into two phases: In the first phase, cauline leaves with axillary meristems are formed and internode elongation begins. In the second phase, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe aDstransposon insertion mutant in the Nossen (No-0) accession with severe defects in floral development and flower morphology. The most striking aspect is the outgrowth of stems from the axillary bracts of the primary flower carrying terminal secondary flowers. Therefore, we named this mutantflower-in-flower(fif). However, the insertion of the transposon in the annotated gene is not responsible for thefifphenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for thefifphenotype was found to be in theLEAFY(LFY) gene. The mutation, a G-to-A exchange in the second exon ofLFY, creates a novellfyallele and causes a cysteine-to-tyrosine exchange in the α1-helix of the LFY DNA-binding domain. Whereas subcellular localization and homomerization are not affected, the DNA-binding of LFYFIFis abolished. We propose that the amino acid exchange interferes with the cooperative binding of LFY to its target DNA. To generate the strongfifphenotype, LFYFIFmay act dominant-negatively by either forming non-binding LFY/LFYFIFheteromers or by titrating out the interaction partners, required for LFY function as transcription factor.

Significant Statement:

Thefifphenotype ofArabidopsis thalianaNo-0 is caused by a novel allele of theLEAFYgene
DeePaC: Predicting pathogenic potential of novel DNA with a universal framework for reverse-complement neural networks
Authors: Bartoszewicz Jakub M. , Seidel Anja , Rentzsch Robert , Renard Bernhard Y.
Published: January 2019

Motivation:

We expect novel pathogens to arise due to their fast-paced evolution, and new species to be discovered thanks to advances in DNA sequencing and metagenomics. What is more, recent developments in synthetic biology raise concerns that some strains of bacteria could be modified for malicious purposes. Traditional approaches to open-view pathogen detection depend on databases of known organisms, limiting their performance on unknown, unrecognized, and unmapped sequences. In contrast, machine learning methods can infer pathogenic phenotypes from single NGS reads even though the biological context is unavailable. However, modern neural architectures treat DNA as a simple character string and may predict conflicting labels for a given sequence and its reverse-complement. This undesirable property may impact model performance.

Results:

We present DeePaC, a Deep Learning Approach to Pathogenicity Classification. It includes a universal, extensible framework for neural architectures ensuring identical predictions for any given DNA sequence and its reverse-complement. We implement reverse-complement convolutional neural networks and LSTMs, which outperform the state-of-the-art methods based on both sequence homology and machine learning. Combining a reverse-complement architecture with integrating the predictions for both mates in a read pair results in cutting the error rate almost in half in comparison to the previous state-of-the-art.

Availability:

The code and the models are available at:https://gitlab.com/rki_bioinformatics/DeePaC
Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan
Authors: Zhang Lei , Dong Xiao , Lee Moonsook , Maslov Alexander Y. , Wang Tao , Vijg Jan
Published: January 2019

Introductory paragraph

The accumulation of mutations in somatic cells have been implicated as a cause of ageing since the 1950s1,2. Yet, attempts to establish a causal relationship between somatic mutations and ageing have been constrained by the lack of methods to directly identify mutational events in primary human tissues. Here we provide detailed, genome-wide mutation frequencies and spectra of human B lymphocytes from healthy individuals across the entire human lifespan, from newborns to centenarians, using a recently developed, highly accurate single-cell whole-genome sequencing method3. We found that the number of somatic mutations increases from <500 per cell in newborns to >3,000 per cell in centenarians. We discovered mutational hotspot regions, some of which, as expected, located at immunoglobulin genes associated with somatic hypermutation. B cell-specific mutation signatures were observed associated with development, ageing or somatic hypermutation (SHM). The SHM signature strongly correlated with the signature found in human chronic lymphocytic leukemia and malignant B-cell lymphomas4, indicating that even in B cells of healthy individuals the potential cancer-causing events are already present. We also identified multiple mutations in sequence features relevant to cellular function, i.e., transcribed genes and gene regulatory regions. Such mutations increased significantly during ageing, but only at approximately half the rate of the genome average, indicating selection against mutations that impact B cell function. This first full characterization of the landscape of somatic mutations in human B lymphocytes indicates that spontaneous somatic mutations accumulating with age can be deleterious and may contribute to both the increased risk for leukemia and the functional decline of B lymphocytes in the elderly.
DnaJB6 is a RanGTP-regulated protein involved in dynein-dependent microtubule organization during mitosis
Authors: M. Rosas-Salvans , Vernos Isabelle
Published: January 2019

Bipolar spindle organization is essential for the faithful segregation of chromosomes during cell division. This organization relies on the collective activities of motor proteins. The minus-end directed dynein motor complex generates spindle inward forces and plays a major role in spindle pole focusing. The dynactin complex regulates many dynein functions increasing its processivity and force production.

Here we show that DnaJB6 is a novel RanGTP regulated protein. It interacts with dynactin p150Glued in a RanGTP-dependent manner specifically in M-phase and promotes spindle pole focusing and dynein force generation. Our data suggest a novel mechanism by which RanGTP regulates dynein activity during M-phase.

Summary statement

We describe DnaJB6 as a novel RanGTP-regulated protein important for spindle assembly. Our data suggest that RanGTP regulates dynein-dependent inward spindle force generation and pole focusing through DnaJB6
Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
Authors: Acquaviva Laurent , Boekhout Michiel , Karasu Mehmet E. , Brick Kevin , Pratto Florencia , Overbeek Megan van , Kauppi Liisa , Camerini-Otero R. Daniel , Jasin Maria , Keeney Scott
Published: January 2019

Sex chromosomes in males share only a diminutive homologous segment, the pseudoautosomal region (PAR), wherein meiotic double-strand breaks (DSBs), pairing, and crossing over must occur for correct segregation. How cells ensure PAR recombination is unknown. Here we delineate cis-and trans-acting factors that control PAR ultrastructure and make the PAR the hottest area of DSB formation in the male mouse genome. Prior to DSB formation, PAR chromosome axes elongate, sister chromatids separate, and DSB-promoting factors hyperaccumulate. These phenomena are linked to mo-2 minisatellite arrays and require ANKRD31 protein. We propose that the repetitive PAR sequence confers unique chromatin and higher order structures crucial for DSB formation, X–Y pairing, and recombination. Our findings establish a mechanistic paradigm of mammalian sex chromosome segregation during spermatogenesis.
The enigmatic role of fungal annexins: the case of Cryptococcus neoformans
Authors: Maryam Maria , Fu Man Shun , Alanio Alexandre , Camacho Emma , Goncalves Diego S. , Faneuff Eden E. , Grossman Nina T. , Casadevall Arturo , Coelho Carolina
Published: January 2019

Annexins are multifunctional proteins that bind to phospholipid membranes in a calcium-dependent manner. Annexins play a myriad of critical and well-characterized roles in mammals, ranging from membrane repair to vesicular secretion. The role of annexins in the kingdoms of bacteria, protozoa and fungi have been largely overlooked. The fact that there is no known homologue of annexins in the model organism may contribute to this gap in knowledge. However, annexins are found in most medically important fungal pathogens, with the notable exception of Candida albicans. In this study we evaluated the function of the one annexin gene in Cryptococcus neoformans, a causative agent of cryptococcosis. This gene CNAG_02415, is annotated in the C. neoformans genome as a target of calcineurin through its transcription factor Crz1, and we propose to update its name to cryptococcal annexin, AnnexinC1. C. neoformans strains deleted for AnnexinC1 revealed no difference in survival after exposure to various chemical stressor relative the wild type, as well as no major alteration in virulence or mating. The only alteration observed in strains deleted for AnnexinC1 was a small increase in the titan cells formation in vitro. The preservation of annexins in many different fungal species suggests an important function, and therefore the lack of a strong phenotype for annexin-deficient C. neoformans is suggestive of either redundant genes that can compensate for the absence of AnnexinC1 function or novel functions not revealed by standard assays of cell function and pathogenicity.

Importance

Cryptococcus neoformans is the deadliest human fungal pathogen, causing almost 200,000 deaths each year. Treatment of this lethal infection is lengthy, and in some patients therapy is not curative and patients require lifelong therapy. Fundamental research in this yeast is needed so that we can understand mechanisms of infection and disease and ultimately devise better therapies. In this work we investigated a fungal representative of the annexin family of proteins, specifically in the context of virulence and mating. We find that the cryptococcal annexin does not seem to be involved in virulence or mating but affects generation of titan cells, enlarged yeast cells that are detected in the lungs of mammalian hosts. Our data provides new knowledge in an unexplored area of fungal biology.
A novel mesocosm set-up reveals strong methane emission reduction in submerged peat moss Sphagnum cuspidatum by tightly associated methanotrophs
Authors: Kox Martine A. R. , Smolders Alfons J. P. , Speth Daan R. , Lamers Leon P. M. , Op den Camp Huub J. M. , Jetten Mike S. M. , van Kessel Maartje A. H. J.
Published: January 2019

Wetlands present the largest natural sources of methane (CH4) and their potential CH4 emissions greatly vary due to the activity of CH4-oxidizing bacteria associated with wetland plant species. In this study, the association of CH4-oxidizing bacteria with submerged Sphagnum peat mosses was studied, followed by the development of a novel mesocosm set-up. This set-up enabled the precise control of CH4 input and allowed for monitoring the dissolved CH4 in a Sphagnum moss layer while mimicking natural conditions. Two mesocosm set-ups were used in parallel: one containing a Sphagnum moss layer in peat water, and a control only containing peat water. Moss-associated CH4 oxidizers in the field could reduce net CH4 emission up to 93%, and in the mesocosm set-up up to 31%. Furthermore, CH4 oxidation was only associated with Sphagnum, and did not occur in peat water. Especially methanotrophs containing a soluble methane monooxygenase enzyme were significantly enriched during the 32 day mesocosm incubations. Together these findings showed the new mesocosm setup is very suited to study CH4 cycling in submerged Sphagnum moss community under controlled conditions. Furthermore, the tight associated between Sphagnum peat mosses and methanotrophs can significantly reduce CH4 emissions in submerged peatlands.
Molecular Dynamics simulations of Alzheimer’s variants, R47H and R62H, in TREM2 provide evidence for structural alterations behind functional changes
Authors: Menzies Georgina E , Sims Rebecca , Williams Julie
Published: January 2019

There is strong evidence supporting the association between Alzheimer’s disease (AD) and protein-coding variants, R47H and R62H in TREM2. The TREM2 protein is an immune receptor found in brain microglia. A structural alteration could therefore have a large effect on the protein. Crystallised structures were used as a base for both WT and mutated proteins. These subjected to 300ns of molecular dynamic simulation (MD). Results suggest structural alterations in both mutated forms of TREM2. A large change was noted in the R47H simulation in the complementarity-determining region two (CDR2) binding loop, a proposed binding sites for ligands such as APOE, a smaller change was observed in the R62H model. These differing levels of structural impact could explain the in vitro observed differences in TREM2-ligand binding.

Author Summary

A number of mutations have been found in the TREM2 protein in populations of people with Alzheimer’s and other dementias. Two of these mutations are similar in that the both cause the same coding change in the same domain of the protein. However, they both cause a very different result in terms of risk and in vitro observed changes. Why these two similar mutations are so different is largely unknown. Here we have used a in silico, simulation, approach to understanding the structural changes which occur in both of the mutations. Our results suggest that the mutation which carries a higher risk, but it less commonly observed, has a much larger impact on the protein structure than the mutation which is thought to be less damaging. This structural change is observed at a part of the protein which is thought to code for a binding loop and a change here could have a big impact on the proteins function. Further studies to investigate this binding loop could help not only a better understanding of TREM2’s role in the onset of dementia but also possibly provide a target for therapeutics.
Higher seroprevalence ofEntamoeba histolyticathan that of HIV-1 at a voluntary counselling and testing centre in Tokyo
Authors: Yanagawa Yasuaki , Nagashima Mami , Gatanaga Hiroyuki , Kikuchi Yoshimi , Oka Shinichi , Yokoyama Keiko , Shinkai Takayuki , Sadamasu Kenji , Watanabe Koji
Published: January 2019

Background

Amebiasis, which is caused byEntamoeba histolytica, is a re-emerging public health issue owing to sexually transmitted infection (STI) in Japan. However, epidemiological data are quite limited.

Methodology

To reveal the relative prevalence of sexually transmittedE. histolyticainfection to other STIs, we conducted a cross-sectional study at a voluntary counselling and testing (VCT) centre in Tokyo. Seroprevalence ofE. histolyticawas assessed according to positivity with an enzyme-linked immunosorbent assay forE. histolytica-specific IgG in serum samples collected from anonymous VCT clients.

Principal Findings

Among 2,083 samples, seropositivity forE. histolyticawas 2.64%, which was higher than that for HIV-1 (0.34%, p < 0.001) and comparable to that for syphilis (rapid plasma reagin (RPR) 2.11%, p = 0.31). Positivity forChlamydia trachomatisin urine by transcription-mediated amplification (TMA) was 4.59%. Seropositivity forE. histolyticawas high among RPR-orTreponema pallidumhemagglutination (TPHA)-positive individuals and it was not different between clients with and without other STIs. Both seropositivity ofE. histolyticaand RPR were high among male clients. The seropositive rate for anti-E. histolyticaantibody was positively correlated with age. TMA positivity for urineC. trachomatiswas high among female clients and negatively correlated with age. Regression analysis identified that male sex, older age, and TPHA-positive results are independent risk factors ofE. histolyticaseropositivity.

Conclusions

Seroprevalence ofE. histolyticawas 7.9 times higher than that of HIV-1 at a VCT centre in Tokyo, with a tendency to be higher among people at risk for syphilis infection.

Author summary

Amebiasis caused byEntamoeba histolyticais an increasingly prevalent sexually transmitted infection (STI) in Japan; however, relative to other STIs, the prevalence ofE. histolyticahas not been fully assessed. We investigated the seropositivity ofE. histolyticausing serum samples from 2,083 clients of a voluntary counselling and testing centre in Tokyo.E. histolyticaseroprevalence (2.64%) was 7.9 times higher than that of HIV-1 (0.31%) and the same as that of syphilis (rapid plasma reagin: 2.11%). Logistic regression analysis showed thatE. histolyticaseroprevalence tended to be higher among individuals who were male, older, and positive inTreponema pallidumhemagglutination. These results strongly suggest that public health interventions should be considered to control sexual transmission ofE. histolyticainfection, which is currently neglected in Japan.
Transgeneratonal inheritance of ethanol preference is caused by maternal NPF repression
Authors: Bozler Julianna , Kacsoh Balint Z , Bosco Giovanni
Published: January 2019

Rapid or even anticipatory adaptation to environmental conditions can provide a decisive fitness advantage to an organism. The memory of recurring conditions could also benefit future generations, however neuronally-encoded behavior isn’t thought to be inherited across generations. We tested the possibility that environmentally triggered modifications could allow “memory” of parental experiences to be inherited. In Drosophila melanogaster, exposure to predatory wasps leads to inheritance of a predisposition for ethanol-rich food for five generations. Inhibition of Neuropeptide-F (NPF) activates germline caspases required for transgenerational ethanol preference. Further, inheritance of low NPF expression in specific regions of F1 brains is required for the transmission of this food preference: A maternally derived NPF locus is necessary for this phenomenon, implicating a maternal epigenetic mechanism of NPF-repression. Given the conserved signaling functions of NPF and its mammalian NPY homolog in drug and alcohol disorders, these observations raise the intriguing possibility of NPY-related transgenerational effects in humans.
mTOR suppresses macroautophagy during postnatal development of the striatum
Authors: Lieberman Ori J. , Pigulevskiy Irena , Post Michael R , Sulzer David , Santini Emanuela
Published: January 2019

Macroautophagy (hereafter referred to as autophagy) plays a critical role in neuronal function related to development and degeneration. Here, we investigated whether autophagy is developmentally regulated in the striatum, a brain region implicated in neurodevelopmental disease. We demonstrate that autophagic flux is suppressed during striatal postnatal development, reaching adult levels around postnatal day 28 (P28). We also find that mTOR signaling, a key regulator of autophagy, increases during the same developmental period. We further show that mTOR signaling is responsible for suppressing autophagy, via regulation of Beclin-1 and VPS34 activity. These results demonstrate that neurons coopt metabolic signaling cascades to developmentally regulate autophagy and establish mTOR as a central node in the regulation of neuronal autophagy.
Geometric Sketching Compactly Summarizes the Single-Cell Transcriptomic Landscape
Authors: Hie Brian , Cho Hyunghoon , DeMeo Benjamin , Bryson Bryan , Berger Bonnie
Published: January 2019

Large-scale single-cell RNA-sequencing (scRNA-seq) studies that profile hundreds of thousands of cells are becoming increasingly common, overwhelming existing analysis pipelines. Here, we describe how to enhance and accelerate single-cell data analysis by summarizing the transcriptomic heterogeneity within a data set using a small subset of cells, which we refer to as a geometric sketch. Our sketches provide more comprehensive visualization of transcriptional diversity, capture rare cell types with high sensitivity, and accurately reveal biological cell types via clustering. Our sketch of umbilical cord blood cells uncovers a rare subpopulation of inflammatory macrophages, which we experimentally validatedin vitro. The construction of our sketches is extremely fast, which enabled us to accelerate other crucial resource-intensive tasks such as scRNA-seq data integration. We anticipate that our algorithm will become an increasingly essential step when sharing and analyzing the rapidly-growing volume of scRNA-seq data and help enable the democratization of single-cell omics.
Regulation of CHD2 expression by the Chaserr long noncoding RNA is essential for viability
Authors: Rom Aviv , Melamed Liliya , Goldrich Micah Jonathan , Kadir Rotem , Golan Matan , Biton Inbal , Perry Rotem Ben-Tov , Ulitsky Igor
Published: January 2019

Genomic loci adjacent to genes encoding for transcription factors and chromatin remodelers are enriched for long non-coding RNAs (lncRNAs), but the functional importance of this enrichment is largely unclear. Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller with various reported functions in cell differentiation and DNA damage response. Heterozygous mutations in human CHD2 have been implicated in epilepsy, neurodevelopmental delay, and intellectual disability. Here we show that Chaserr, a highly conserved lncRNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to increased transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potentially viable strategy for increasing CHD2 levels in haploinsufficient individuals.
A series of two-dimensional lanthanide coordination polymers: synthesis, structures, magnetism and selective luminescence detection for heavy metal ions and toxic solvents
Authors: Hao Hongguo , Liu Hongyan , Wang Yuchen , Yuan Suxian , Xu Han , Zhang Jingyue , Wang Ying , Li Dacheng , Sun Junshan
Published: January 2019

A series of two-dimensional (2D) coordination polymers (CPs), namely poly[[bis(μ-acetato)diaqua(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)bis(N,N-dimethylacetamide)digadolinium(III)] N,N-dimethylacetamide monosolvate], {[Gd2(C16H6O8)(C2H3O2)2(C4H9NO)2(H2O)2]·C4H9NO}
n
(CP1), poly[[bis(μ-acetato)diaqua(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)bis(N,N-dimethylacetamide)didysprosium(III)] N,N-dimethylacetamide monosolvate], {[Dy2(C16H6O8)(C2H3O2)2(C4H9NO)2(H2O)2]·C4H9NO}
n
(CP2), poly[bis(μ-acetato)diaqua(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)bis(N,N-dimethylacetamide)dineodymium(III)], [Nd2(C16H6O8)(C2H3O2)2(C4H9NO)2(H2O)2]
n
(CP3), poly[bis(μ-acetato)diaqua(μ6-biphenyl-3,3′,5,5′-tetracarboxylato)bis(N,N-dimethylacetamide)disamarium(III)], [Sm2(C16H6O8)(C2H3O2)2(C4H9NO)2(H2O)2]
n
(CP4), has been synthesized from rigid biphenyl-3,3′,5,5′-tetracarboxylic acid under solvothermal conditions. Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction and thermogravimetric analyses, and CP1–CP4 crystallize in the monoclinic space group P21/n. CP1–CP4 are isomorphous and feature similar 2D double layers, which are further extended via interlayer hydrogen-bonding interactions into a three-dimensional (3D) supramolecular structure. Hydrogen-bonding interactions between N,N-dimethylacetamide molecules and carboxylate O atoms strengthen the packing of the layers. The organic ligands interconnect with metal ions to generate 2D layered structures with a (4,4)-connected net having {44.62} topology. CP1 has been investigated for its magnetic properties and magnetic susceptibility measurements were carried out in the range 2.0–300 K. The results of the magnetic measurements show weak antiferromagnetic coupling between the GdIII ions in CP1. Moreover, the strong luminescence of CP2 and CP4 can be selectively quenched by the Fe3+ ion and toxic solvents (e.g. acetone).
Co-crystallization of 3,5-dinitrobenzoic acid with two antipsychotic agents: a simple 1:1 salt with trihexyphenidyl and a 1:2 acid salt containing a very short O—H...O hydrogen bond with chlorprothixene
Authors: Shaibah Mohammed A. E. , Yathirajan Hemmige S. , Rathore Ravindranath S. , Furuya Tetsundo , Haraguchi Tomoyuki , Akitsu Takashiro , Glidewell Christopher
Published: January 2019

Co-crystallization of racemic 1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol (trihexyphenidyl) with 3,5-dinitrobenzoic acid gives a simple 1:1 salt, namely 1-(3-cyclohexyl-3-hydroxy-3-phenylpropyl)piperidin-1-ium 3,5-dinitrobenzoate, C20H32NO+·C7H3N2O6
−, (I), whereas a similar co-crystallization using (Z)-3-(2-chloro-9H-thioxanthen-9-yl)-N,N-dimethylpropan-1-amine (chlorprothixene) gives a 1:2 acid salt, namely (Z)-3-(2-chloro-9H-thioxanthen-9-yl)-N,N-dimethylpropan-1-aminium hydrogen bis(3,5-dinitrobenzoate), C18H19ClNS+·[H(C7H3N2O6)2]−, (II), the anion of which contains a very short O—H...O hydrogen bond, with dimensions O—H = 1.04 (3) Å, H...O = 1.41 (3) Å, O...O = 2.4197 (15) Å and O—H...O = 161 (3)°. In the cation of (I), the cyclohexyl and piperidyl rings both adopt chair conformations, whereas in the cation of (II), the central heterocyclic ring adopts a boat conformation, so that the dihedral angle between the two aryl rings is 41.56 (4)°. A combination of O—H...O, N—H...O and C—H...O hydrogen bonds links the ions of (I) into a complex chain of rings, and these chains are linked into sheets by π–π stacking interactions between inversion-related pairs of anions. In compound (II), a different combination of O—H...O, N—H...O and C—H...O hydrogen bonds links the ions into sheets. Comparisons are made with some related structures.
Crystal structure of bis(4-benzoylpyridine-κN)bis(methanol-κO)bis(thiocyanato-κN)nickel(II) methanol monosolvate
Authors: Wellm Carsten , Näther Christian
Published: January 2019

The asymmetric unit of the title compound, [Ni(NCS)2(C12H9NO)2(CH3OH)2]·CH3OH, comprises one NiII cation, two thiocyanate anions, two 4-benzoylpyridine coligands, two coordinating, as well as one non-coordinating methanol molecule. The NiII cation is coordinated by two terminally N-bonded thiocyanate anions, the N atoms of two 4-benzoylpyridine coligands and the O atoms of two methanol ligands within a slightly distorted octahedron. Individual complexes are linked by intermolecular O—H...S hydrogen bonding into chains parallel to [010] that are further connected into layers parallel to (10\overline{1}) by C—H...S hydrogen bonds. Additional C—H...O hydrogen-bonding interactions lead to the formation of a three-dimensional network that limits channels extending parallel to [010] in which the non-coordinating methanol molecules are located. They are hydrogen-bonded to the coordinating methanol molecules. X-ray powder diffraction revealed that the compound could not be prepared as a pure phase.
Choosing your (Friedel) mates wisely: grouping data sets to improve anomalous signal
Authors: Foos Nicolas , Cianci Michele , Nanao Max H.
Published: January 2019

Single-wavelength anomalous diffraction (SAD) phasing from multiple crystals can be especially challenging in samples with weak anomalous signals and/or strong non-isomorphism. Here, advantage is taken of the combinatorial diversity possible in such experiments to study the relationship between merging statistics and downstream metrics of phasing signals. It is furthermore shown that a genetic algorithm (GA) can be used to optimize the grouping of data sets to enhance weak anomalous signals based on these merging statistics.
N′-[5-Acetyl-3-(4-chlorophenyl)-2,3-dihydro-1,3,4-thiadiazol-2-ylidene]-5-(1H-indol-3-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide dimethylformamide monosolvate
Authors: El-Hiti Gamal A. , Abdel-Wahab Bakr F. , Yousif Emad , Alotaibi Mohammad Hayal , Hegazy Amany S. , Kariuki Benson M.
Published: January 2019

In the title solvate, C28H20ClN7O2S·C3H7NO, the main molecule consists of chlorophenyl (A), thiadiazolyl (B), pyrazolyl (C), phenyl (D) and indolyl (E) rings, with twist angles between neighbouring rings A/B, B/C, C/D and D/E of 32.6 (1), 14.8 (1), 60.8 (1) and 20.1 (1)°, respectively. The dimethylformamide solvent molecule accepts an N—H...O hydrogen bond from the indole group. In the extended structure, molecules related by 21 screw axes are stacked in the [001] direction to form columns linked by weak C—H...O interactions.
Communication, coordination, decision-making and knowledge-sharing: a case study in construction management
Authors: Al Nahyan Moza Tahnoon , Sohal Amrik , Hawas Yaser , Fildes Brian
Published: January 2019

Purpose

This paper aims to examine four key management processes, namely, communication, coordination, decision-making and knowledge-sharing, to determine how these impact on transportation infrastructure project success. The context for this study is the construction of a major highway in the United Arab Emirates.

Design/methodology/approach

Multiple sources of data are used in this case study that include the following: examination of various documents relating to the project in question; interviews with ten key stakeholders involved with the construction of the project; observations made during the site visit and interviews conducted with four site engineers; a focus group conducted with six key stakeholders involved in the project; and finally interviews conducted with the Minister of Public Works and the Director-General of the Ministry of Public Works. Analysis was conducted using NVivo.

Findings

Identification and involvement of key stakeholders, particularly in the early phases of a construction project, is found to be highly critical. Managers must develop detailed understanding of stakeholders’ influence in terms of their legitimacy, power and urgency in achieving effectiveness of the management processes.

Originality/value

The study highlights how different stakeholders influence communication, coordination, decision-making and knowledge-sharing at different stages of the construction project. Hence, understanding stakeholder’s level of legitimacy, power and urgency across the different stages of a project is highly critical.