bluuebunny/crossref_metadata_2025 huggingface dataset:
Fission yeast TRP channel Pkd2p localizes to the cleavage furrow and regulates cell separation during cytokinesis
Authors: Morris Zachary , Sinha Debatrayee , Poddar Abhishek , Morris Brittni , Chen Qian
Published: May 2019

Force plays a central role in separating daughter cells during cytokinesis, the last stage of cell division. However, the mechanism of force sensing during cytokinesis remains unknown. Here we discovered that Pkd2p, a putative force-sensing transient receptor potential channel, localizes to the cleavage furrow during cytokinesis of the fission yeast, Schizosaccharomyces pombe. Pkd2p, whose human homologues are associated with autosomal polycystic kidney disease, is an essential protein whose localization depends on the contractile ring and the secretory pathway. We identified and characterized a novel pkd2 mutant pkd2-81KD. The pkd2 mutant cells show signs of osmotic stress, including temporary shrinking, paused turnover of the cytoskeletal structures, and hyperactivated mitogen-activated protein kinase signaling. During cytokinesis, although the contractile ring constricts more rapidly in the pkd2 mutant than the wild-type cells (50% higher), the cell separation in the mutant is slower and often incomplete. These cytokinesis defects are also consistent with misregulated turgor pressure. Finally, the pkd2 mutant exhibits strong genetic interactions with two mutants of the septation initiation network pathway, a signaling cascade essential for cytokinesis. We propose that Pkd2p modulates osmotic homeostasis and is potentially a novel regulator of cytokinesis.
PACRG and FAP20 form the inner junction of axonemal doublet microtubules and regulate ciliary motility
Authors: Dymek Erin E. , Lin Jianfeng , Fu Gang , Porter Mary E. , Nicastro Daniela , Smith Elizabeth F.
Published: May 2019

We previously demonstrated that PACRG plays a role in regulating dynein-driven microtubule sliding in motile cilia. To expand our understanding of the role of PACRG in ciliary assembly and motility, we used a combination of functional and structural studies, including newly identified Chlamydomonas pacrg mutants. Using cryo-electron tomography we show that PACRG and FAP20 form the inner junction between the A- and B-tubule along the length of all nine ciliary doublet microtubules. The lack of PACRG and FAP20 also results in reduced assembly of inner-arm dynein IDA b and the beak-MIP structures. In addition, our functional studies reveal that loss of PACRG and/or FAP20 causes severe cell motility defects and reduced in vitro microtubule sliding velocities. Interestingly, the addition of exogenous PACRG and/or FAP20 protein to isolated mutant axonemes restores microtubule sliding velocities, but not ciliary beating. Taken together, these studies show that PACRG and FAP20 comprise the inner junction bridge that serves as a hub for both directly modulating dynein-driven microtubule sliding, as well as for the assembly of additional ciliary components that play essential roles in generating coordinated ciliary beating.
Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma
Authors: Huang Fengbo , Xiang Xueping , Hong Bo , Min Jie , Li Jinfan
Published: May 2019

Objectives

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLGNPPA) is a relatively rare nasopharyngeal tumor. We performed morphological characterization, immunohistochemical profiling, and investigated gene mutations. We also provide clinical follow-up data and brief review of the literature.

Methods

Immunohistochemistry was used to evaluate the expression of TTF-1, CK19, CK7, EMA, TG, Pax-8, CK5/6, S100, and Ki-67. Additionally, in situ hybridization was utilized to identify the presence of EBV. We investigated mutations in hot-spot exons of KRAS/NRAS/BRAF to rule out common mutations seen in thyroid tumors.

Results

Histopathologic examination of four cases identified tumors that were mainly occupied by papillary architectures. One case had a predominantly glandular structure. The tumors expressed TTF-1 and CK19, while TG and Pax-8 were negative. S100 was moderately expressed focally in three cases.

Conclusions

While TLLGNPPA displays a morphological resemblance to papillary thyroid carcinoma (PTC), it is vital to differentiate nasopharyngeal metastasis from PTC for appropriate treatment.
Association Between Serum β-Alanine and Risk of Dementia
Authors: Hata Jun , Ohara Tomoyuki , Katakura Yoshinori , Shimizu Kuniyoshi , Yamashita Shuntaro , Yoshida Daigo , Honda Takanori , Hirakawa Yoichiro , Shibata Mao , Sakata Satoko , Kitazono Takanari , Kuhara Satoru , Ninomiya Toshiharu
Published: May 2019

We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60–79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia.
Evaluation of Intussusception After Oral Monovalent Rotavirus Vaccination in South Africa
Authors: Groome Michelle J , Tate Jacqueline E , Arnold Marion , Chitnis Milind , Cox Sharon , de Vos Corné , Kirsten Mari , le Grange Susanna M , Loveland Jerome , Machaea Sello , Maharaj Ashwini , Andrews Nick , Madhi Shabir A , Parashar Umesh D
Published: May 2019

Background

Postlicensure studies have shown an association between rotavirus vaccination and intussusception. We assessed the risk of intussusception associated with Rotarix (RV1) administration, at 6 and 14 weeks of age, in an upper-middle-income country, South Africa.

Methods

Active prospective surveillance for intussusception was conducted in 8 hospitals from September 2013 through December 2017. Retrospective case enrollment was done at 1 hospital from July 2012 through August 2013. Demographic characteristics, symptom onset, and rotavirus vaccine status were ascertained. Using the self-controlled case-series method, we estimated age-adjusted incidence rate ratios within 1–7, 8–21, and 1–21 days of rotavirus vaccination in children aged 28–275 days at onset of symptoms. In addition, age-matched controls were enrolled for a subset of cases (n = 169), and a secondary analysis was performed.

Results

Three hundred forty-six cases were included in the case-series analysis. Post–dose 1, there were zero intussusception cases within 1–7 days, and 5 cases within 8–21 days of vaccination. Post–dose 2, 15 cases occurred within 1–7 days, and 18 cases within 8–21 days of vaccination. There was no increased risk of intussusception 1–7 days after dose 1 (no cases observed) or dose 2 (relative incidence [RI], 1.71 [95% confidence interval {CI} .83–3.01]). Similarly, there was no increased risk 8–21 days after the first (RI, 4.01 [95% CI, .87–10.56]) or second dose (RI, .96 [95% CI, .52–1.60]). Results were similar for the case-control analysis.

Conclusions

The risk of intussusception in the 21 days after the first or second dose of RV1 was not higher than the background risk among South Africa infants.

Clinical Trials Registration

South African National Clinical Trial Register (DOH-27-0913-4183).
Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin
Authors: Hall Kathryn T , Kessler Thorsten , Buring Julie E , Passow Dani , Sesso Howard D , Zee Robert Y L , Ridker Paul M , Chasman Daniel I , Schunkert Heribert
Published: May 2019

Aims

Efficacy of aspirin in primary prevention of cardiovascular disease (CVD) may be influenced by a common allele in guanylate cyclase GUCY1A3, which has been shown to modify platelet function and increase CVD risk.

Methods and results

We investigated whether homozygotes of the GUCY1A3 rs7692387 risk (G) allele benefited from aspirin in two long-term, randomized placebo-controlled trials of aspirin in primary CVD prevention: the Women’s Genome Health Study (WGHS, N = 23 294) and a myocardial infarction (MI, N = 550) and stroke (N = 382) case–control set from the Physician’s Health Study (PHS, N = 22 071). Bleeding risk was evaluated in the WGHS. In the placebo group of the WGHS, the GUCY1A3 risk (G) allele was confirmed to increase CVD risk [hazard ratio 1.38; 95% confidence interval (CI) 1.08–1.78; P = 0.01]. Random-effects meta-analysis of the WGHS and PHS revealed that aspirin reduced CVD events among risk allele homozygotes [G/G: odds ratio (OR) 0.79; 95% CI 0.65–0.97; P = 0.03] but increased CVD events among non-risk allele carriers (e.g. G/A: OR 1.39; 95% CI 1.03–1.87; P = 0.03) thus implying an interaction between genotype stratum and aspirin intake (P  interaction = 0.01). Bleeding associated with aspirin increased in all genotype groups, with higher risks in heterozygotes.

Conclusion

In two randomized placebo-controlled trials in the setting of primary prevention, aspirin reduced the incidence of CVD events in individuals homozygous for the GUCY1A3 risk (G) allele, whereas heterozygote individuals had more events when taking aspirin.
Weight and weight change and risk of atrial fibrillation: the HUNT study
Authors: Feng Tingting , Vegard Malmo , Strand Linn B , Laugsand Lars E , Mørkedal Bjørn , Aune Dagfinn , Vatten Lars , Ellekjær Hanne , Loennechen Jan P , Mukamal Kenneth , Janszky Imre
Published: May 2019

Aims

Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain.

Methods and results

An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0–1.4) for average BMI 25.0–29.9 kg/m2 and 1.6 (1.2–2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened.

Conclusion

Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.
Induction of Senescence in Cancer Cells by a Novel Combination of Cucurbitacin B and Withanone: Molecular Mechanism and Therapeutic Potential
Authors: Garg Sukant , Huifu He , Kumari Anjani , Sundar Durai , Kaul Sunil C , Wadhwa Renu
Published: May 2019

Cancer, an uncontrolled proliferation syndrome, is treated with synthetic chemotherapeutic drugs that are associated with severe adverse effects. Development and application of new natural compounds is warranted to deal with the exponentially increasing incidence of cancer worldwide. Keeping selective toxicity to cancer cells as a priority criterion, we developed a combination of Cucurbitacin B and Withanone, and analyzed its anticancer potential using non-small cell lung cancer cells. We demonstrate that the selective cytotoxicity of the combination, called CucWi-N, to cancer cells is mediated by induction of cellular senescence that was characterized by decrease in Lamin A/C, CDK2, CDK4, Cyclin D, Cyclin E, phosphorylated RB, mortalin and increase in p53 and CARF proteins. It compromised cancer cell migration that was mediated by decrease in mortalin, hnRNP-K, vascular endothelial growth factor, matrix metalloproteinase 2, and fibronectin. We provide in silico, molecular dynamics and experimental data to support that CucWi-N (i) possesses high capability to target mortalin–p53 interaction and hnRNP-K proteins, (ii) triggers replicative senescence and inhibits metastatic potential of the cancer cells, and (iii) inhibits tumor progression and metastasis in vivo. We propose that CucWi-N is a potential natural anticancer drug that warrants further mechanistic and clinical studies.
CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease
Authors: Magg Thomas , Shcherbina Anna , Arslan Duran , Desai Mukesh M , Wall Sarah , Mitsialis Vanessa , Conca Raffaele , Unal Ekrem , Karacabey Neslihan , Mukhina Anna , Rodina Yulia , Taur Prasad D , Illig David , Marquardt Benjamin , Hollizeck Sebastian , Jeske Tim , Gothe Florian , Schober Tilmann , Rohlfs Meino , Koletzko Sibylle , Lurz Eberhard , Muise Aleixo M , Snapper Scott B , Hauck Fabian , Klein Christoph , Kotlarz Daniel
Published: May 2019

Background

Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes.

Methods

To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID.

Results

Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency.

Conclusion

Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.
Diverse Developmental Responses to Warming Temperatures Underlie Changes in Flowering Phenologies
Authors: Diggle Pamela K , Mulder Christa P H
Published: May 2019

Climate change has resulted in increased temperature means across the globe. Many angiosperms flower earlier in response to rising temperature and the phenologies of these species are reasonably well predicted by models that account for spring (early growing season) and winter temperatures. Surprisingly, however, exceptions to the general pattern of precocious flowering are common. Many species either do not appear to respond or even delay flowering in, or following, warm growing seasons. Existing phenological models have not fully addressed such exceptions to the common association of advancing phenologies with warming temperatures. The phenological events that are typically recorded (e.g., onset of flowering) are but one phase in a complex developmental process that often begins one or more years previously, and flowering time may be strongly influenced by temperature over the entire multi-year course of flower development. We propose a series of models that explore effects of growing-season temperature increase on the multiple processes of flower development and how changes in development may impact the timing of anthesis. We focus on temperate forest trees, which are characterized by preformation, the initiation of flower primordia one or more years prior to anthesis. We then synthesize the literature on flower development to evaluate the models. Although fragmentary, the existing data suggest the potential for temperature to affect all aspects of flower development in woody perennials. But, even for relatively well studied taxa, the critical developmental responses that underlie phenological patterns are difficult to identify. Our proposed models explain the seemingly counter-intuitive observations that warmer growing-season temperatures delay flowering in many species. Future research might concentrate on taxa that do not appear to respond to temperature, or delay flowering in response to warm temperatures, to understand what processes contribute to this pattern.
Temporary disengagement and re-engagement in human immunodeficiency virus care in a rural county serving pastoralist communities in Kenya: a retrospective cohort study
Authors: Yonga Paul , Kalya Stephen , Lynen Lutgarde , Decroo Tom
Published: May 2019

Background

Pastoralist communities are known to be hard to reach. The magnitude of temporary disengagement from human immunodeficiency virus (HIV) care is understudied.

Methods

We conducted a retrospective cohort study of temporary disengagement (2 weeks late for a next appointment), virologic response, lost to follow-up (6 months late) and re-engagement in care among patients who started antiretroviral therapy between 2014 and 2016 in Baringo County, Kenya. Predictors of re-engagement after disengagement were estimated using logistic regression.

Results

Of 342 patients, 76.9% disengaged at least once (range 0–7). Of 218 patients with a viral load (VL), 78.0% had a suppressed VL. Those with a history of temporary disengagement from care were less likely to suppress their VL (p=0.002). Six patients had treatment failure (two consecutive VLs >1000 copies/mm3) and all had disengaged at least once. After disengagement from care, male patients (adjusted odds ratio [aOR] 0.3 [95% confidence interval {CI} 0.2 to 0.6]; p<0.001) and patients with World Health Organization stage III–IV (aOR 0.3 [95% CI 0.1 to 0.5; p<0.001) were less likely to re-engage in care.

Conclusions

Temporary disengagement was frequent in this pastoralist setting. This indicator is often overlooked, as most studies only report binary outcomes, such as retention in care. Innovative strategies are required to achieve HIV control in rural settings like this pastoralist setting.
Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer
Authors: Chari Nikhil S , Ivan Cristina , Le Xiandong , Li Jinzhong , Mijiti Ainiwaer , Patel Ameeta A , Osman Abdullah A , Peterson Christine B , Williams Michelle D , Pickering Curtis R , Caulin Carlos , Myers Jeffrey N , Calin George A , Lai Stephen Y
Published: May 2019

Background

Alterations in the epidermal growth factor receptor and PI3K pathways in head and neck squamous cell carcinomas (HNSCCs) are frequent events that promote tumor progression. Ectopic expression of the epidermal growth factor receptor–targeting microRNA (miR), miR-27a* (miR-27a-5p), inhibits tumor growth. We sought to identify mechanisms mediating repression of miR-27a* in HNSCC, which have not been previously identified.

Methods

We quantified miR-27a* in 47 oral cavity squamous cell carcinoma patient samples along with analysis of miR-27a* in 73 oropharyngeal and 66 human papillomavirus–positive (HPV+) samples from The Cancer Genome Atlas. In vivo and in vitro TP53 models engineered to express mutant TP53, along with promoter analysis using chromatin immunoprecipitation and luciferase assays, were used to identify the role of TP53 and TP63 in miR-27a* transcription. An HNSCC cell line engineered to conditionally express miR-27a* was used in vitro to determine effects of miR-27a* on target genes and tumor cells.

Results

miR-27a* expression was repressed in 47 oral cavity tumor samples vs matched normal tissue (mean log2 difference = −0.023, 95% confidence interval = −0.044 to −0.002; two-sided paired t test, P = .03), and low miR-27a* levels were associated with poor survival in HPV+ and oropharyngeal HNSCC samples. Binding of ΔNp63α to the promoter led to an upregulation of miR-27a*. In vitro and in vivo findings showed that mutant TP53 represses the miR-27a* promoter, downregulating miR-27a* levels. ΔNp63α and nucleoporin 62, a protein involved in ΔNP63α transport, were validated as novel targets of miR-27a*.

Conclusion

Our results characterize a negative feedback loop between TP63 and miR-27a*. Genetic alterations in TP53, a frequent event in HNSCC, disrupt this regulatory loop by repressing miR-27a* expression, promoting tumor survival.
Annual Report to the Nation on the Status of Cancer, Featuring Cancer in Men and Women Age 20–49 Years
Authors: Ward Elizabeth M , Sherman Recinda L , Henley S Jane , Jemal Ahmedin , Siegel David A , Feuer Eric J , Firth Albert U , Kohler Betsy A , Scott Susan , Ma Jiemin , Anderson Robert N , Benard Vicki , Cronin Kathleen A
Published: May 2019

Background

The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries provide annual updates on cancer occurrence and trends by cancer type, sex, race, ethnicity, and age in the United States. This year’s report highlights the cancer burden among men and women age 20–49 years.

Methods

Incidence data for the years 1999 to 2015 from the Centers for Disease Control and Prevention- and National Cancer Institute–funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries and death data for the years 1999 to 2016 from the National Vital Statistics System were used. Trends in age-standardized incidence and death rates, estimated by joinpoint, were expressed as average annual percent change.

Results

Overall cancer incidence rates (per 100 000) for all ages during 2011–2015 were 494.3 among male patients and 420.5 among female patients; during the same time period, incidence rates decreased 2.1% (95% confidence interval [CI] = −2.6% to −1.6%) per year in men and were stable in females. Overall cancer death rates (per 100 000) for all ages during 2012–2016 were 193.1 among male patients and 137.7 among female patients. During 2012–2016, overall cancer death rates for all ages decreased 1.8% (95% CI = −1.8% to −1.8%) per year in male patients and 1.4% (95% CI = −1.4% to −1.4%) per year in females. Important changes in trends were stabilization of thyroid cancer incidence rates in women and rapid declines in death rates for melanoma of the skin (both sexes). Among adults age 20–49 years, overall cancer incidence rates were substantially lower among men (115.3 per 100 000) than among women (203.3 per 100 000); cancers with the highest incidence rates (per 100 000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8), and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1). During 2011 to 2015, the incidence of all invasive cancers combined among adults age 20–49 years decreased −0.7% (95% CI = −1.0% to −0.4%) among men and increased among women (1.3%, 95% CI = 0.7% to 1.9%). The death rate for (per 100 000) adults age 20–49 years for all cancer sites combined during 2012 to 2016 was 22.8 among men and 27.1 among women; during the same time period, death rates decreased 2.3% (95% CI = −2.4% to −2.2%) per year among men and 1.7% (95% CI = −1.8% to −1.6%) per year among women.

Conclusions

Among people of all ages and ages 20–49 years, favorable as well as unfavorable trends in site-specific cancer incidence were observed, whereas trends in death rates were generally favorable. Characterizing the cancer burden may inform research and cancer-control efforts.
The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters – XIX. A chemical tagging of the multiple stellar populations over the chromosome maps
Authors: Marino A F , Milone A P , Renzini A , D’Antona F , Anderson J , Bedin L R , Bellini A , Cordoni G , Lagioia E P , Piotto G , Tailo M
Published: May 2019

The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters (GCs) has investigated GCs and their stellar populations. In previous papers of this series we have introduced a pseudo two-colour diagram, or ‘chromosome map’ (ChM) that maximizes the separation between the multiple populations. We have identified two main classes of GCs: Type I, including ∼83 per cent of the objects, and Type II clusters. Both classes host two main groups of stars, referred to in this series as first (1G) and second generation (2G). Type II clusters host more complex ChMs, exhibiting two or more parallel sequences of 1G and 2G stars. We exploit spectroscopic elemental abundances from the literature to assign the chemical composition to the distinct populations as identified on the ChMs of 29 GCs. We find that stars in different regions of the ChM have different compositions: 1G stars share the same light-element content as field stars, while 2G stars are enhanced in N and Na and depleted in O. Stars with enhanced Al, as well as stars with depleted Mg, populate the extreme regions of the ChM. We investigate the intriguing colour spread among 1G stars observed in many Type I GCs, and find no evidence for internal variations in light elements among these stars, whereas either a ∼0.1 dex iron spread or a variation in He among 1G stars remains to be verified. In the attempt of analysing the global properties of the multiple-population phenomenon, we have constructed a universal ChM, which highlights that, though very variegate, the phenomenon has some common pattern among all the analysed GCs. The universal ChM reveals a tight connection with Na abundances, for which we have provided an empirical relation. The additional ChM sequences observed in Type II GCs are enhanced in metallicity and, in some cases, s-process elements. Omega Centauri can be classified as an extreme Type II GC, with a ChM displaying three main extended ‘streams’, each with its own variations in chemical abundances. One of the most noticeable differences is found between the lower and upper streams, with the latter, associated with higher He, being also shifted towards higher Fe and lower Li abundances. We publicly release the ChMs.
Transcriptional supercoiling boosts topoisomerase II-mediated knotting of intracellular DNA
Authors: Valdés Antonio , Coronel Lucia , Martínez-García Belén , Segura Joana , Dyson Sílvia , Díaz-Ingelmo Ofelia , Micheletti Cristian , Roca Joaquim
Published: May 2019

Recent studies have revealed that the DNA cross-inversion mechanism of topoisomerase II (topo II) not only removes DNA supercoils and DNA replication intertwines, but also produces small amounts of DNA knots within the clusters of nucleosomes that conform to eukaryotic chromatin. Here, we examine how transcriptional supercoiling of intracellular DNA affects the occurrence of these knots. We show that although (−) supercoiling does not change the basal DNA knotting probability, (+) supercoiling of DNA generated in front of the transcribing complexes increases DNA knot formation over 25-fold. The increase of topo II-mediated DNA knotting occurs both upon accumulation of (+) supercoiling in topoisomerase-deficient cells and during normal transcriptional supercoiling of DNA in TOP1 TOP2 cells. We also show that the high knotting probability (Pkn ≥ 0.5) of (+) supercoiled DNA reflects a 5-fold volume compaction of the nucleosomal fibers in vivo. Our findings indicate that topo II-mediated DNA knotting could be inherent to transcriptional supercoiling of DNA and other chromatin condensation processes and establish, therefore, a new crucial role of topoisomerase II in resetting the knotting–unknotting homeostasis of DNA during chromatin dynamics.
Trust in national health information sources in the United States: comparing predictors and levels of trust across three health domains
Authors: Peterson Emily B , Chou Wen-Ying Sylvia , Kelley Dannielle E , Hesse Brad
Published: May 2019

Public trust in traditional sources of health information is essential for public health agencies and organizations to perform necessary public health functions. Little research has examined levels and predictors of trust in government health agencies and national health organizations. Additionally, few studies have simultaneously analyzed trust in multiple health topics. The major aim of this study was to compare levels and factors associated with trust in national health sources across three health topics: information about tobacco, electronic cigarettes, and general health. Data from two cycles of the National Cancer Institute’s Health Information National Trends Survey collected in 2015 and 2017 were merged and analyzed for this study (n = 5,474). A series of weighted multivariable logistic regression models calculated odds of high trust in government health agencies and health organizations for each health topic. More respondents reported high trust in health organizations than for government health agencies across all topics. More participants reported high trust in these sources tobacco information, as compared to general health or e-cigarette information. Logistic models found that those higher in information seeking confidence were more likely to report high trust across all models. Other demographic variables were inconsistent predictors of trust across topics. This study highlights inconsistent sociodemographic predictors of trust across multiple health topics and national health sources. Researchers, practitioners, and policymakers should consider the unique context of specific health topics in health promotion campaigns, partner with existing community-based organizations, and encourage and enable health information seeking.
Estimating intervention dose of the multilevel multisite children’s healthy living program intervention
Authors: Butel Jean , Braun Kathryn L , Nigg Claudio R , Leon Guerrero Rachael , Fleming Travis , Bersamin Andrea , Coleman Patricia , Novotny Rachel
Published: May 2019

Increased community collective efficacy (CE), defined as social cohesion among neighbors and their willingness to intervene for common good, is associated with improved community health outcomes. However, processes to increase CE and estimate its dose within an intervention are not well understood. The 2 year Children’s Healthy Living (CHL) intervention aimed to improve child behaviors known to affect obesity. We used data from CHL to estimate CE dose and examine its association with a successful outcome from CHL—reduction in children’s recreational screen time. Monthly reports from nine intervention communities were quantified, and CE dose was calculated for each community overall, at 4 time intervals (6, 12, 18, and 24 months), and for each CE building block—social bonding, social bridging, social leveraging, empowerment, and civic engagement. CE dose at each time interval and change in screen time was correlated using Spearman’s rho. Next, communities were categorized as having a high CE dose or a low CE dose, and differences between four high-dose and five low-dose communities were compared using a two-tailed t-test. The correlation between change in screen time and CE dose was significant (rs = 0.83, p = .003). Significantly more activities facilitating empowerment and civic engagement were conducted in high-dose communities, which were more likely to show improvements in screen time, than in low-dose communities. This method of estimating an intervention’s CE dose and examining change over time and effect of CE and its building blocks on intervention outcomes shows promise.
Plant water content integrates hydraulics and carbon depletion to predict drought-induced seedling mortality
Authors: Sapes Gerard , Roskilly Beth , Dobrowski Solomon , Maneta Marco , Anderegg William R L , Martinez-Vilalta Jordi , Sala Anna
Published: May 2019

Widespread drought-induced forest mortality (DIM) is expected to increase with climate change and drought, and is expected to have major impacts on carbon and water cycles. For large-scale assessment and management, it is critical to identify variables that integrate the physiological mechanisms of DIM and signal risk of DIM. We tested whether plant water content, a variable that can be remotely sensed at large scales, is a useful indicator of DIM risk at the population level. We subjected Pinus ponderosa Douglas ex C. Lawson seedlings to experimental drought using a point of no return experimental design. Periodically during the drought, independent sets of seedlings were sampled to measure physiological state (volumetric water content (VWC), percent loss of conductivity (PLC) and non-structural carbohydrates) and to estimate population-level probability of mortality through re-watering. We show that plant VWC is a good predictor of population-level DIM risk and exhibits a threshold-type response that distinguishes plants at no risk from those at increasing risk of mortality. We also show that plant VWC integrates the mechanisms involved in individual tree death: hydraulic failure (PLC), carbon depletion across organs and their interaction. Our results are promising for landscape-level monitoring of DIM risk.
Disease Incidence–Severity Relationships on Leaflets, Leaves, and Fruit in the Pecan–Venturia effusaPathosystem
Authors: Bock Clive H. , Chiang Kuo-Szu
Published: May 2019

The most destructive disease of pecan in the southeastern United States is scab, caused by Venturia effusa. Incidence (I)-severity (S) relationships have not previously been characterized in this pathosystem, but incidence measures can save time and should have higher accuracy compared with estimates of severity. Ten scab-susceptible cultivars and seedling trees were assessed for I and S of scab on fruit (1,972 trees) and foliage (compound leaves and leaflets, 1,129 trees) between 2010 and 2014. Samples were assessed on a tree basis, and sample size ranged from 10 to 100 specimens per tree. The range in mean I and S was different depending on the organ (fruit I = 0 to 100%, S = 0 to 100%; compound leaves and leaflets, I = 0 to 100%, S = 0–10.1%, respectively). However, mean I could be 100% at a mean S < 2.0% for fruit, compound leaves, and leaflets. Both I and S data were transformed by complementary log-log prior to linear regression analysis. A linear regression model described the relationship between transformed I and S per tree for fruit (P ≤ 0.0001, R2= 0.61), compound leaves (P ≤ 0.0001, R2= 0.82), and leaflets (P ≤ 0.0001, R2= 0.91) for all cultivars. The regression analysis showed significant effects of cultivar and year on the relationship between I and S; therefore, separate analyses were performed for each cultivar and year. Back-transformed predicted severity values showed that the differences among cultivars and years were negligible at severity <80%, and were generally numerically small at severity >80%. The observation that low severity persists until a high incidence of scab is achieved may limit the ability of incidence data to clearly differentiate treatment effects, even when based on the CLL transformation. But if found to be effective, and if used, it would reduce the labor requirements and result in more accurate data being obtained, as incidence estimates do not tend to suffer from the same subjective biases as do visual estimates of severity.
Chocolate Under Threat from Old and New Cacao Diseases
Authors: Marelli Jean-Philippe , Guest David I. , Bailey Bryan A. , Evans Harry C. , Brown Judith K. , Junaid Muhammad , Barreto Robert W. , Lisboa Daniela O. , Puig Alina S.
Published: May 2019

Theobroma cacao, the source of chocolate, is affected by destructive diseases wherever it is grown. Some diseases are endemic; however, as cacao was disseminated from the Amazon rain forest to new cultivation sites it encountered new pathogens. Two well-established diseases cause the greatest losses: black pod rot, caused by several species of Phytophthora, and witches’ broom of cacao, caused by Moniliophthora perniciosa. Phytophthora megakarya causes the severest damage in the main cacao producing countries in West Africa, while P. palmivora causes significant losses globally. M. perniciosa is related to a sister basidiomycete species, M. roreri which causes frosty pod rot. These Moniliophthora species only occur in South and Central America, where they have significantly limited production since the beginnings of cacao cultivation. The basidiomycete Ceratobasidium theobromae causing vascular-streak dieback occurs only in South-East Asia and remains poorly understood. Cacao swollen shoot disease caused by Cacao swollen shoot virus is rapidly spreading in West Africa. This review presents contemporary research on the biology, taxonomy and genomics of what are often new-encounter pathogens, as well as the management of the diseases they cause.
Brexanolone Injection in Postpartum Depression: 2 Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trials
Authors: Meltzer-Brody S. , Colquhoun H. , Riesenberg R. , Epperson C.N. , Deligiannidis K.M. , Rubinow D.R. , Li H. , Sankoh A.J. , Clemson C. , Schacterle A. , Jonas J. , Kanes S.
Published: May 2019

(Lancet. 2018;392:1058–1070)

Postpartum depression is a common problem, with an overall prevalence in the United States of ∼11.5%. It is associated with impaired mother-infant attachment, increased maternal morbidity and poor outcomes for infants later in life, including lower academic achievement and an increased risk of depression. There is a need for improved pharmacological treatment options for mothers suffering from postpartum depression. Brexanolone is a soluble, intravenous, positive allosteric modulator of y-aminobutyric-acid type A (GABAA) receptors. In a previous phase 2 clinical trial, this medication was found to have rapid and sustained antidepressant effects. The current article reports on 2 randomized double-blind phase 3 studies that aimed to assess the efficacy of brexanolone injection in women with moderate to severe postpartum depression.
Maternal-fetal Transmission and Adverse Perinatal Outcomes in Pregnant Women Infected With Zika Virus: A Prospective Cohort Study in French Guiana
Authors: Pomar L. , Vouga M. , Lambert V. , Pomar C. , Hcini N. , Jolivet A. , Benoist G. , Rousset D. , Matheus S.
Published: May 2019

(BMJ. 2018;363:k4431)

While Zika virus has been confirmed to be vertically transmitted from mothers to infants, and associated with congenital anomalies, the risk of congenital Zika virus syndrome (CZS) is unclear due to a lack of fetal and neonatal testing. The risk of CZS with its associated fetal abnormalities had been reported to be as high as 40% based on the outbreak in Brazil, but more recent reports from the United States suggest a 4% to 8% risk of birth defects in babies born to mothers with confirmed infection. This study aimed to estimate the risk of maternal-fetal transmission of infection as well as the percentage of neonates with clear signs of infection or complications related to CZS within 1 week after birth.
Total Talus Replacement for Traumatic Bone Loss or Idiopathic Avascular Necrosis of the Talus
Authors: Lachman James R. , Parekh Selene G.
Published: May 2019

More than a dozen surgical techniques have been described for management of avascular necrosis or traumatic loss of large portions of the talus. The smaller the area of necrosis, the better the outcomes. Procedures to induce revascularization (core decompression/drilling, vascularized bone grafts) have been reported with variable success. Patients with avascular necrosis of large portions of the talus present unique treatment difficulties. These techniques largely focus on pantalar or tibiotalar-calcaneal arthrodesis with large bone blocks. These surgeries eliminate motion, lead to high levels of patient dissatisfaction, and risk the possibility of multiple surgeries with nonunions. Total talus replacement, first described in Southeast Asia, used traditional manufacturing techniques to try to replicate a patient’s anatomy while preserving motion and eliminating pain. Modern techniques involve 3D printing technology to identically recreate the patient’s native anatomy and preserve tibiotalar, subtalar and talonavicular joint motion. The surgery is reliable, relatively simple technically, and provides another option for treatment of this very difficult problem.

Level of Evidence: Diagnostic Level 5. See Instructions for Authors for a complete description of levels of evidence.
Semaphorin-5A downregulation is associated with enhanced migration and invasion of BRAF-positive melanoma cells under vemurafenib treatment in melanomas with heterogeneous BRAF status
Authors: Komina Anna V. , Palkina Nadezhda V. , Aksenenko Mariya B. , Lavrentev Semyon N. , Moshev Anton V. , Savchenko Andrey A. , Averchuk Anton S. , Rybnikov Yuri A. , Ruksha Tatiana G.
Published: May 2019

Tumor heterogeneity affects the efficacy of anticancer treatment as tumor subclones with distinct molecular patterns may be present within one tumor, leading to differing sensitivities to chemotherapeutic agents. In the present study, six melanoma tissue fragments were obtained from different parts of tumor of four patients and then the effect of vemurafenib treatment on biological characteristics and molecular processes of cell cultures was estimated by using MTT-test, apoptosis, migration and invasion assays, PCR real time. There was different BRAF status determined between cells derived from the central and peripheral regions of primary melanoma tumors. BRAF-positive melanoma cells showed an increased apoptotic rate under vemurafenib treatment, as well as increased migration and invasion rates, whereas BRAF-negative melanoma cells did not exhibit such tendency. Furthermore, semaphorin-5A levels were diminished in BRAF-positive cells, but not in BRAF-negative ones, which could be related to increased migration and invasion. Melanoma cells derived from different regions of the same tumor may differ by mutations status, molecular processes and biological response to target therapy. The downregulation of semaphorin-5A may be involved in divergent effects of anticancer agents on tumor cell biology.
Long-term exposure to fine particulate matter and natural-cause and cause-specific mortality in Japan
Authors: Yorifuji Takashi , Kashima Saori , Tani Yasunari , Yamakawa Junji , Doi Hiroyuki
Published: May 2019

Background:

A number of studies have linked long-term exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) with mortality, but most of these studies were conducted in Europe and North America. Studies in Asian countries had been conducted at relatively high exposures. We evaluated the association of long-term exposure to PM2.5 and natural-cause and cause-specific mortality in Japan, where PM2.5 levels are relatively low compared with levels in other Asian countries.

Methods:

A cohort of 75,531 participants underwent basic health checkups in Okayama City in 2006 or 2007. We followed the participants until the end of 2016. Average PM2.5 levels from 2006 to 2010 were obtained and assigned to the participants by geographical location. We used the Cox proportional hazard models to estimate hazard ratios for a 5-μg/m3 increase in PM2.5 levels for natural-cause or cause-specific mortality, adjusting for potential confounders.

Results:

PM2.5 exposure was associated with increased risk of mortality; the hazard ratios were 1.29 (95% confidence interval = 1.18, 1.41) for mortality from natural causes, 1.16 (1.02, 1.32) for cardiorespiratory mortality, and 1.63 (1.13, 2.34) for lung cancer mortality. PM2.5 exposure was more strongly associated with cardiorespiratory mortality from hypertension, pneumonia and influenza, and chronic obstructive pulmonary disease than with ischemic heart disease or cerebrovascular disease. Elderly participants and smokers tended to have higher effect estimates.

Conclusion:

Long-term exposure to PM2.5 can increase the risk of natural-cause, cardiorespiratory, and lung cancer mortality in Japan.
Commercial Sexual Exploitation of Children: An Update for the Forensic Nurse
Authors: Hornor Gail , Quinones Saribel Garcia , Bretl Deborah , Courtney Audrey B. , Herendeen Pamela Ann , Lewin Linda , Loyke Julie A. , Morris Kristen , Schapiro Naomi A. , Williams Sheona
Published: May 2019

Commercial sexual exploitation of children (CSEC) is the sexual abuse of children through buying, selling, or trading their sexual services. This may involve engaging a child under the age of 18 years in prostitution, pornography, stripping, exotic dancing, escort services, or other sexual services. CSEC is a problem of epidemic proportions throughout the world including the United States; however, the actual number of CSEC victims in the United States is unknown. Studies indicate that most child victims are seen by a healthcare provider while being trafficked and that many victims receive care at a pediatric hospital within 1 year of their identification as a victim. CSEC is a significant pediatric healthcare problem. It is vital that forensic nurses possess a thorough understanding of the problem and be poised to better identify, intervene, and prevent CSEC. In this article, we focus on risk factors commonly experienced by victims, recruitment strategies used by traffickers, indicators to identify child victims, and intervention and educational strategies of relevance to forensic nurses.
European Society of Emergency Medicine position paper on the 1-hour sepsis bundle of the Surviving Sepsis Campaign: expression of concern
Authors: Freund Yonathan , Khoury Abdo , Möckel Martin , Karamercan Mehmet , Dodt Christoph , Leach Robert , Bloom Ben , Garcia-Castrillo Luis
Published: May 2019

In 2018 the Surviving Sepsis Campaign issued new guidance with a revised version of their sepsis bundle. Instead of the 2016 3-hour sepsis bundle, the Surviving Sepsis Campaign now recommends that blood cultures, lactate measurement, broad-spectrum antibiotic therapy and 30 ml/kg crystalloid fluid administration should be initiated within 1 hour after triage. The European Society of Emergency Medicine wishes to express its concerns regarding the low level of evidence that underlies this guidance, and the potential implications from an emergency physician point of view.