bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic enclave or transcultural edge? Reassessing the Prato district through digital mapping
Authors: Ricatti Francesco , Dutto Matteo , Wilson Rita
Published: September 2019

Relations between Italy and other countries – such as China – are often imagined within a binary frame that essentialises national and ethnic communities and fails to recognise the complex transcultural ramifications of an increasingly globalising world. This is particularly problematic when studying those social and cultural spaces that Ilaria Vanni (2016) has described as transcultural edges. These are marginal spaces of transition and encounters between different cultures and societies, which have the potential to create new, innovative and productive ecosystems. We argue that one such space is Prato, an industrial town near Florence, well known for its textile district, and host to one of the largest Chinese communities in Europe. Significant academic attention has been devoted to the Chinese community in Prato, including studies of its social and economic impact on the host local community and the textile industry. Most of these studies tend to isolate the Chinese community from the ethnic complexity of the area, within a binary frame that fails to acknowledge the large presence of other migrant groups and the reciprocal permeability and transculturation between the Chinese community, the Italian community, and other ethnic groups. As part of a larger project, a group of scholars is currently digitally remapping Prato, to include quantitative and qualitative geolocalised information collected through a multidisciplinary method that includes ethnography, media analysis, translation studies, transcultural studies, and digital participatory action research. Through a brief description of the aims and characteristics of this research project, the paper will discuss the importance of rethinking the relationship between Italy and China, and between Italians and Chinese, within a more complex and nuanced transcultural frame.
Evaluating Devonian bioregionalization: quantifying biogeographic areas
Authors: Dowding Elizabeth M. , Ebach Malte C.
Published: September 2019

The work of Arthur J. Boucot (vale, 1924–2017) is foundational to Devonian biogeography. Cited more than 1000 times and mentioned in excess of 105,000 times, his classification of the Old World, Eastern Americas, and Malvinokaffric realms has become the framework for Devonian biogeographic and faunal studies. This study is the first to test and quantify the biotic area classification using the distributional data of trilobite, brachiopod, and fish taxa across the Lower, Middle, and Late Devonian. The biotic similarity analysis of 676 genera (ca. 30,000 occurrences) of late Silurian (Ludlow–Pridoli) and Devonian taxa represents the largest quantification of distributional data undertaken in Devonian biogeography. The temporal area approach (TAAp), applied here for the first time, failed to recover in the area phenogram many of the realms and regions used by Devonian biogeographers, excepting the Malvinokaffric realm, across the entirety of the Devonian. The Old World and Western Gondwana realms are found to be artificial and in need of revision. Without natural areas, bioregionalizations (area classifications) become unstable and unusable, resulting in authors creating further artificial regions and provinces. This study offers a better solution, namely, to identify artificial areas in existing area classifications using TAAp and biotic similarity analysis and revise them. Area classifications are modeled on taxonomic process (Wilson and Brown 1953; Starrett 1958) and the movement toward revision is necessary to break the cycle of reinvention of realms and regions within bioregionalization.
Input–output relations in Hebrew verb acquisition at the morpho-lexical interface
Authors: ASHKENAZI Orit , GILLIS Steven , RAVID Dorit
Published: September 2019

This study examined early Hebrew verb acquisition, highlighting CDS–CS relations across inflectional and derivational verb learning. It was carried out on a corpus of longitudinal dense dyadic interactions of two Hebrew-speaking toddlers aged 1;8–2;2 and their parents. Findings revealed correlated patterns within and between CDS and CS corpora in terms of verbs, structural root categories, and their components (roots,binyanconjugations, and derivational verb families), and clear relations between lexical-derivational development and inflectional growth in input–output relations, measured by MSP. It also showed that both corpora had few, yet highly semantically coherent, derivational families. Lexical learning in Hebrew was shown to be morphologically oriented, with both inflectional and derivational learning supporting and being supported by the development of the verb lexicon. These findings support findings in the general literature regarding the close relationship between parental input and child speech, and the affinity between lexical and grammatical growth.
Comparing environmental and socioeconomic drivers of illegal capture of wild birds in Brazil
Authors: Destro Guilherme Fernando Gomes , De Marco Paulo , Terribile Levi Carina
Published: September 2019

In order to conserve species exploited by trafficking, governmental actions should be directed to source areas, aiming to reduce or eliminate illegal and indiscriminate trapping. However, few studies have diagnosed and prioritized the most relevant drivers of the illegal capture of wild animals. In this study, we aimed to evaluate the main drivers of the illegal capture of wild birds in Brazil. A literature review and a multivariate modelling approach indicated the economic, social and environmental factors that display the greatest influence in boosting this illicit activity worldwide. Our search revealed seven drivers of illegal wildlife capture addressed by researchers in studies carried out in source countries. This is the first broad-scale study in Brazil showing that higher native vegetation coverage and greater proximity to protected areas were the main drivers of illegal wild bird capture for trafficking. Thus, actions that aim to protect species threatened by trafficking require a multidisciplinary approach encompassing social, economic and environmental factors.
Assessment of population susceptibility to upcoming seasonal influenza epidemic strain using interepidemic emerging influenza virus strains
Authors: Chen Lin-Lei , Wu Wai-Lan , Chan Wan-Mui , Fong Carol H. Y. , Ng Anthony C. K. , Ip Jonathan D. , Lu Lu , Dissanayake Thrimendra K. , Ding Xixia , Cai Jian-Piao , Zhang Anna J. X. , Tam Sidney , Hung Ivan F. N. , Chan Kwok-Hung , Yuen Kwok-Yung , To Kelvin K. W.
Published: September 2019

Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
Suicidal ideation in patients with cancer: A systematic review of prevalence, risk factors, intervention and assessment
Authors: Kolva Elissa , Hoffecker Lilian , Cox-Martin Emily
Published: September 2019

Objectives

Suicidal ideation (SI) underlies risk of death by suicide. It is well established that patients with cancer are at increased risk of death by suicide. Therefore, understanding SI in patients with cancer is critically important. The goal of this systematic review was to investigate the prevalence, risk factors, intervention, and assessment of SI in patients with cancer.

Methods

This systematic review was registered with the PROSPERO database (CRD42018115405) and was guided by the PRISMA statement. We searched Medline, PsycInfo, Embase, CINAHL, the Cochrane Database of Systematic Reviews, and Cochrane Central. Two reviewers independently screened abstracts and assessed for quality assurance using a revised Newcastle-Ottawa Scale.

Results

We identified 439 studies to screen for eligibility. Eligible studies included adults with cancer diagnoses and listed SI as an outcome. Ultimately, 44 studies were included in the analyses. Prevalence of SI ranged greatly from 0.7% to 46.3%. Single items drawn from validated measures were the most frequent method of assessing SI (n = 20, 45.5%); additional methods included validated measures and psychological interviews. Commonly identified risk factors for SI included age, sex, and disease/treatment-related characteristics, as well as psychological constructs including depression, anxiety, hopelessness, existential distress, and social support.

Significance of Results

Assessment of SI in patients with cancer is the concern of researchers worldwide. Prevalence of SI varied with study population and was likely influenced by the method of assessment. Psychological distress consistently predicted SI. Increasing awareness of demographic, clinical, and psychological associations is critical for risk assessment and intervention development.
Effects of a multidisciplinary quality of life intervention on sleep quality in patients with advanced cancer receiving radiation therapy
Authors: Gentry Melanie T. , Atherton Pamela J. , Lapid Maria , Rosen Preetha Sharone , Kung Simon , Richardson Jarrett , Niazi Shehzad K. , Bobo William V. , Clark Matthew M. , Rummans Teresa A.
Published: September 2019

Objectives

Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer.

Method

This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52.

Results

The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03).

Significance of results

A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.
Distribution of herbicide-resistant waterhemp (Amaranthus tuberculatus) across row crop production systems in Texas
Authors: Singh Vijay , Garetson Russ , McGinty Josh , Dotray Peter , Morgan Gaylon , Nolte Scott , Bagavathiannan Muthukumar
Published: September 2019

We conducted a survey in the major row-crop production regions of Texas to determine the response of waterhemp to glyphosate (5-enolpyruvylshikimate-3-phosphate synthase [EPSPS] inhibitor), atrazine (photosystem II [PSII] inhibitor), pyrithiobac (acetolactate synthase [ALS] inhibitor), tembotrione (hydroxyphenylpyruvate dioxygenase [HPPD] inhibitor), fomesafen (protoporphyrinogen oxidase [PPO] inhibitor), and dicamba (synthetic auxin). We evaluated 127 accessions for these herbicides. Resistance was confirmed on the basis of plant survival within an accession, and the injury ratings of surviving plants were used to categorize each accession as resistant (<50% injury) or less sensitive (50% to 89% injury). For glyphosate, approximately 27% of all tested accessions were resistant and 20% were less sensitive. The Gulf Coast region had the most glyphosate-resistant accessions (46% of the accessions from this region), followed by the Blacklands region (9%). A dose-response assay of the most resistant waterhemp accession (TX-25) exhibited 17-fold resistance to glyphosate when compared with a susceptible standard. Waterhemp resistance to atrazine also was common in the Gulf Coast region. The accession with the greatest atrazine resistance (TX-31) exhibited 47- and 68-fold resistance to this herbicide when applied POST and PRE, respectively. Widespread resistance to pyrithiobac was observed in waterhemp accessions throughout the Blacklands and Gulf Coast regions. The most resistant accession identified in this study was 61-fold resistant compared with a susceptible standard. No high-level resistance was detected for tembotrione, dicamba, or fomesafen, but high variability in sensitivity to tembotrione and dicamba was observed. One waterhemp accession exhibited reduced sensitivity to fomesafen; the rest were sensitive. Overall, at least two accessions exhibited resistance or reduced sensitivity to herbicides with five different sites of action. The study illustrates the prevalence of multiple herbicide resistance in waterhemp accessions in Texas and emphasizes the need to implement diversified management tactics.
Sugarcane response and fall panicum (Panicum dichotomiflorum) control with topramezone and triazine herbicides
Authors: Negrisoli Raphael M. , Odero D. Calvin , MacDonald Gregory E. , Sellers Brent A. , Laughinghouse H. Dail
Published: September 2019

Field studies were conducted on organic soils in Belle Glade, FL, in 2016 to 2017 to evaluate sugarcane tolerance and fall panicum control with topramezone applied alone or in combination with triazine herbicides (atrazine, metribuzin, ametryn). Treatments included topramezone (25 and 50 g ai ha−1) applied alone or in combination with atrazine (2,240 g ai ha−1), metribuzin (2,240 g ai ha−1), and ametryn (440 g ha−1) on four plant cane varieties to evaluate tolerance, and on second ratoon fields to determine efficacy on fall panicum control. Topramezone applied alone had no effect on sugarcane chlorophyll fluorescence (i.e., the ratio of variable fluorescence to maximum fluorescence), total chlorophyll, and carotenoid 7 to 28 d after treatment (DAT), suggesting sugarcane tolerance. Significant reduction of these parameters occured 7 to 14 DAT when topramezone (50 g ai ha−1) was applied with ametryn or metribuzin; however, reductions were not detected thereafter, indicating recovery. Sugarcane yield was not affected by topramezone applied alone or in combination with the triazine herbicides. Topramezone (50 g ai ha−1) plus metribuzin resulted in acceptable control of fall panicum (84%) with limited to no regrowth of meristematic tissue at sugarcane canopy closure, equivalent to 56 to 70 DAT. These results indicate that when sequential applications of topramezone, applied alone or in combination with these triazine herbicides, are required for efficacious weed control, topramezone applications alone can be made after 7 d, whereas the combinations can be made after 14 or 21 d, depending on sugarcane sensitivity.
Artificial Intelligence May Help Predict El Ni�o
Authors: Duncombe Jenessa
Published: September 2019

Deep learning techniques give scientists the longest–lead time forecasts yet.
Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)
Authors:   for the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE), Sharrack Basil , Saccardi Riccardo , Alexander Tobias , Badoglio Manuela , Burman Joachim , Farge Dominique , Greco Raffaella , Jessop Helen , Kazmi Majid , Kirgizov Kirill , Labopin Myriam , Mancardi Gianluigi , Martin Roland , Moore John , Muraro Paolo A. , Rovira Montserrat , Sormani Maria Pia , Snowden John A.
Published: September 2019

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.
Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer
Authors: Joseph Chitra , Al-Izzi Sara , Alsaleem Mansour , Kurozumi Sasagu , Toss Michael S , Arshad Maariya , Goh Fang Qin , Alshankyty Ibraheem M. , Aleskandarany Mohammed A. , Ali Simak , Ellis Ian O. , Mongan Nigel P. , Green Andrew R. , Rakha Emad A.
Published: September 2019

Background

Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer.

Methods

Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome.

Results

Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade(p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (allp < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts,RXRGexpression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005).

Conclusion

This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.
T-cell receptor signal strength and epigenetic control of Bim predict memory CD8+ T-cell fate
Authors: Li Kun-Po , Ladle Brian H. , Kurtulus Sema , Sholl Allyson , Shanmuganad Sharmila , Hildeman David A.
Published: September 2019

Most effector CD8+T cells die, while some persist and become either “effector” (TEM) or “central” (TCM) memory T cells. Paradoxically, effector CD8+T cells with greater memory potential have higher levels of the pro-apoptotic molecule Bim. Here, we report, using a novel Bim-mCherry knock-in mouse, that cells with high levels of Bim preferentially develop into TCMcells. Bim levels remained stable and were regulated by DNA methylation at the Bim promoter. Notably, high levels of Bcl-2 were required for Bimhicells to survive. Using Nur77-GFP mice as an indicator of TCR signal strength, Nur77 levels correlated with Bim expression and Nur77hicells also selectively developed into TCMcells. Altogether, these data show that Bim levels and TCR signal strength are predictive of TEM- vs. TCM-cell fate. Further, given the many other biologic functions of Bim, these mice will have broad utility beyond CD8+T-cell fate.
Correction: In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects
Authors: Jiang Tongmeng , Xu Guojie , Wang Qiuyan , Yang Lihui , Zheng Li , Zhao Jinmin , Zhang Xingdong
Published: September 2019

Following the publication of this article, the authors noticed that Fig. 5c in the original manuscript is incorrect due to an error in image handling during the creation of the figure. Specifically, the image for the group P3 BMSCs of time point 21d and the image in the group BMMNCs of time point 14d were incorrect. These linked to the group for BMMNCs of time point 21d, which was also, as a result, incorrect.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The stem cell-associated transcription co-factor, ZNF521, interacts with GLI1 and GLI2 and enhances the activity of the Sonic hedgehog pathway
Authors: Scicchitano Stefania , Giordano Marco , Lucchino Valeria , Montalcini Ylenia , Chiarella Emanuela , Aloisio Annamaria , Codispoti Bruna , Zoppoli Pietro , Melocchi Valentina , Bianchi Fabrizio , De Smaele Enrico , Mesuraca Maria , Morrone Giovanni , Bond Heather M.
Published: September 2019

ZNF521 is a transcription co-factor with recognized regulatory functions in haematopoietic, osteo-adipogenic and neural progenitor cells. Among its diverse activities, ZNF521 has been implicated in the regulation of medulloblastoma (MB) cells, where the Hedgehog (HH) pathway, has a key role in the development of normal cerebellum and of a substantial fraction of MBs. Here a functional cross-talk is shown for ZNF521 with the HH pathway, where it interacts with GLI1 and GLI2, the major HH transcriptional effectors and enhances the activity of HH signalling. In particular, ZNF521 cooperates with GLI1 and GLI2 in the transcriptional activation of GLI (glioma-associated transcription factor)-responsive promoters. This synergism is dependent on the presence of the N-terminal, NuRD-binding motif in ZNF521, and is sensitive to HDAC (histone deacetylase) and GLI inhibitors. Taken together, these results highlight the role of ZNF521, and its interaction with the NuRD complex, in determining the HH response at the level of transcription. This may be of particular relevance in HH-driven diseases, especially regarding the MBs belonging to the SHH (sonic HH) subgroup where a high expression of ZNF521 is correlated with that of HH pathway components.
microRNA-17 functions as an oncogene by downregulating Smad3 expression in hepatocellular carcinoma
Authors: Lu Zhufeng , Li Xiuhua , Xu Yongfeng , Chen Miaomiao , Chen Wei , Chen Tao , Tang Qinghe , He Zhiying
Published: September 2019

The sekelsky mothers against dpp3 (Smad3) functions as a transcriptional modulator activated by transforming growth factor-β (TGF-β). Accumulated evidences indicated that Smad3 played the important roles in carcinogenesis and progression of hepatocellular carcinoma (HCC). Up to now, the regulatory mechanism of Smad3 in HCC still remains unclear. It has been known that some particular microRNAs (miRNAs) involve in carcinogenesis through the regulation of gene expressions with targeting mRNAs. In our study, the unknown candidates of miRNAs that target Smad3 mRNA were searched by using a newly established in vivo approach, the miRNA in vivo precipitation (miRIP). Using a loss-of-function assay, we demonstrated that miR-17 directly targeted Smad3 in HCC cells and inhibition on miR-17 increased Smad3 expression. Furthermore, we found that downregulation on Smad3 expression was consistent with high level of miR-17 in HCC tissues of patients when compared with around normal liver tissues. The manipulated miR-17 silence in HCC cells suppressed their growth of both in vitro and in vivo. Such suppression on cell growth could be recovered through downregulating Smad3. In addition, miR-17 affected cell proliferation through arresting cell cycle in G1 phase. The negative correlation between levels of miR-17 and protein levels of Smad3 was supported by the results of analysis with HCC tissue chip. In summary, for the first time, we confirmed that miR-17 directly targeted Smad3 mRNA and downregulated Smad3 protein expression in HCC. Our results indicated that the increased expression of miR-17 promoted carcinogenesis of HCC through down-regulations of Smad3, suggesting miR-17 might serve as the potential diagnostic and therapeutic targets for clinical HCC.
Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population
Authors: Sakaue Saori , Akiyama Masato , Hirata Makoto , Matsuda Koichi , Murakami Yoshinori , Kubo Michiaki , Kamatani Yoichiro , Okada Yukinori
Published: September 2019

The functional variants involved in alcohol metabolism, the A allele of rs1229984:A > G in ADH1B and the A allele of rs671:G > A in ALDH2, are specifically prevalent among East Asian population. They are shown to be under recent positive selection, but the reasons for the selection are unknown. To test whether these positively selected variants have beneficial effects on survival in modern population, we performed the survival analyses using the large-scale Japanese cohort (n = 135,974) with genotype and follow-up survival data. The rs671-A allele was significantly associated with the better survival in the additive model (HR for mortality = 0.960, P = 1.7 × 10−5), and the rs1229984-A had both additive and non-additive effects (HR = 0.962, P = 0.0016 and HR = 0.958, P = 0.0066, respectively), which was consistent with the positive selection. The favorable effects of these alleles on survival were independent of the habit of alcohol consumption itself. The heterogenous combinatory effect between rs1229984 and rs671 genotype was also observed (HRs for AA genotype at rs671 were 1.03, 0.80, and 0.90 for GG, GA, and AA genotype at rs1229984, respectively), supposedly reflecting the synergistic effects on survival.
Severe neurodevelopmental disease caused by a homozygous TLK2 variant
Authors: Töpf Ana , Oktay Yavuz , Balaraju Sunitha , Yilmaz Elmasnur , Sonmezler Ece , Yis Uluc , Laurie Steven , Thompson Rachel , Roos Andreas , MacArthur Daniel G. , Yaramis Ahmet , Güngör Serdal , Lochmüller Hanns , Hiz Semra , Horvath Rita
Published: September 2019

A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism.
Relating retinal blood flow and vessel morphology in sickle cell retinopathy
Authors: Cano Jennifer , Farzad Shayan , Khansari Maziyar M. , Tan Ou , Huang David , Lim Jennifer I. , Shahidi Mahnaz
Published: September 2019

Purpose

The purpose of the current study was to determine associations between retinal blood flow and vessel morphology metrics in sickle cell retinopathy (SCR) and healthy normal control (NC) subjects.

Methods

Optical coherence tomography angiography (OCTA) and Doppler OCT imaging were performed in 12 SCR (15 eyes) and 19 NC (26 eyes) subjects. Vessel tortuosity was measured using a dedicated image analysis algorithm applied to OCTA images. Vessel density and spacing between vessels were determined from OCTA images by a fractal dimension analysis method. Retinal blood flow was quantified using a phase-resolved technique applied to en face Doppler OCT images.

Results

There was a significant association between increased retinal blood flow and increased vessel tortuosity (P = 0.03). Furthermore, increased retinal blood flow was associated with increased vessel density (P = 0.03) and decreased spacing between small vessels (P = 0.01). There was no significant association between retinal blood flow and spacing between large vessels (P = 0.11). Vessel tortuosity and blood flow were increased, whereas spacing between small vessels was decreased in SCR compared to NC group (P ≤ 0.03). There were no significant differences in vessel density or spacing between large vessels between the SCR and NC groups (P ≥ 0.31).

Conclusions

Associations between retinal hemodynamics and vessel morphology were reported, providing better understanding of retinal pathophysiology and insight into potential quantitative biomarkers to evaluate SCR.
The hidden structure of human enamel
Authors: Beniash Elia , Stifler Cayla A. , Sun Chang-Yu , Jung Gang Seob , Qin Zhao , Buehler Markus J. , Gilbert Pupa U. P. A.
Published: September 2019

Enamel is the hardest and most resilient tissue in the human body. Enamel includes morphologically aligned, parallel, ∼50 nm wide, microns-long nanocrystals, bundled either into 5-μm-wide rods or their space-filling interrod. The orientation of enamel crystals, however, is poorly understood. Here we show that the crystalline c-axes are homogenously oriented in interrod crystals across most of the enamel layer thickness. Within each rod crystals are not co-oriented with one another or with the long axis of the rod, as previously assumed: the c-axes of adjacent nanocrystals are most frequently mis-oriented by 1°–30°, and this orientation within each rod gradually changes, with an overall angle spread that is never zero, but varies between 30°–90° within one rod. Molecular dynamics simulations demonstrate that the observed mis-orientations of adjacent crystals induce crack deflection. This toughening mechanism contributes to the unique resilience of enamel, which lasts a lifetime under extreme physical and chemical challenges.
Possible role of L-form switching in recurrent urinary tract infection
Authors: Mickiewicz Katarzyna M. , Kawai Yoshikazu , Drage Lauren , Gomes Margarida C. , Davison Frances , Pickard Robert , Hall Judith , Mostowy Serge , Aldridge Phillip D. , Errington Jeff
Published: September 2019

Recurrent urinary tract infection (rUTI) is a major medical problem, especially in the elderly and infirm, but the nature of the reservoir of organisms responsible for survival and recolonisation after antibiotic treatment in humans is unclear. Here, we demonstrate the presence of cell-wall deficient (L-form) bacteria in fresh urine from 29 out of 30 older patients with rUTI. In urine, E. coli strains from patient samples readily transition from the walled state to L-form during challenge with a cell wall targeting antibiotic. Following antibiotic withdrawal, they then efficiently transition back to the walled state. E. coli switches between walled and L-form states in a zebrafish larva infection model. The results suggest that L-form switching is a physiologically relevant phenomenon that may contribute to the recurrence of infection in older patients with rUTI, and potentially other infections.
Multiplexed and high-throughput neuronal fluorescence imaging with diffusible probes
Authors: Guo Syuan-Ming , Veneziano Remi , Gordonov Simon , Li Li , Danielson Eric , Perez de Arce Karen , Park Demian , Kulesa Anthony B. , Wamhoff Eike-Christian , Blainey Paul C. , Boyden Edward S. , Cottrell Jeffrey R. , Bathe Mark
Published: September 2019

Synapses contain hundreds of distinct proteins whose heterogeneous expression levels are determinants of synaptic plasticity and signal transmission relevant to a range of diseases. Here, we use diffusible nucleic acid imaging probes to profile neuronal synapses using multiplexed confocal and super-resolution microscopy. Confocal imaging is performed using high-affinity locked nucleic acid imaging probes that stably yet reversibly bind to oligonucleotides conjugated to antibodies and peptides. Super-resolution PAINT imaging of the same targets is performed using low-affinity DNA imaging probes to resolve nanometer-scale synaptic protein organization across nine distinct protein targets. Our approach enables the quantitative analysis of thousands of synapses in neuronal culture to identify putative synaptic sub-types and co-localization patterns from one dozen proteins. Application to characterize synaptic reorganization following neuronal activity blockade reveals coordinated upregulation of the post-synaptic proteins PSD-95, SHANK3 and Homer-1b/c, as well as increased correlation between synaptic markers in the active and synaptic vesicle zones.
The Chinese public’s awareness and attitudes toward genetically modified foods with different labeling
Authors: Zhao Yawei , Deng Haiyan , Yu Changxin , Hu Ruifa
Published: September 2019

Abstracts

This paper analyzes the awareness and attitudes of the Chinese public toward genetically modified (GM) foods with different types of labeling and evaluates the impact of public confidence in the government management of GM food labeling has on their attitude. From 2015 to 2016, we conducted a series of surveys to collect data from 1730 respondents, which included consumers, farmers, media, and local agricultural officials in agricultural departments. The results show ~60% of the Chinese public do not know that they usually consume or purchase GM products or products containing GM ingredients. Nearly 80% of the Chinese public are accepting foods labeled as not containing GM ingredients, 57% are accepting foods without labeling, and ~40% are accepting GM-labeled foods. The respondents with a lack of confidence in the government are less likely to embrace GM foods. Those that are more aware of GM products are more likely to accept GM labeled foods. The group having the most positive attitude toward GM-labeled foods is the media, followed by agricultural officials, while the group having the most negative attitude toward GM labeled foods is farmers. Our findings provide an empirical basis to inform GM food labeling policy discussions and possible revisions, which may promote the development of GM foods in China.
Oxytocin modulates the temporal dynamics of resting EEG networks
Authors: Schiller Bastian , Koenig Thomas , Heinrichs Markus
Published: September 2019

Oxytocin is a key modulator of social interaction, but we possess little knowledge of its underlying effects on neuropsychological processes. We used a spatio-temporal EEG microstates analysis to reveal oxytocin’s effects on the temporal dynamics of intrinsically generated activity in neural networks. Given oxytocin’s known anxiolytic effects, we hypothesized that it increases the temporal stability of the four archetypal EEG resting networks. Eighty-six male participants had received oxytocin or placebo intranasally before we recorded their resting EEG. As hypothesized, oxytocin globally increased the average duration of the four archetypal resting networks and specifically decreased the occurrence and coverage of an autonomic processing-related network to benefit greater coverage of an attention-related network. Moreover, these neurophysiological changes were more pronounced in participants with high anxiety levels and strong subjectively experienced effects of the oxytocin administration. In sum, our study shows that oxytocin reduces rapid switching among neural resting networks by increasing their temporal stability. Specifically, it seems to reduce the brain’s need for preparing the internally-oriented processing of autonomic information, thus enabling the externally-oriented processing of social information. Changes in the temporal dynamics of resting networks might underlie oxytocin’s anxiolytic effects - potentially informing innovative psychobiological treatment strategies.
RNAseq analysis reveals drought-responsive molecular pathways with candidate genes and putative molecular markers in root tissue of wheat
Authors: Iquebal Mir Asif , Sharma Pradeep , Jasrotia Rahul Singh , Jaiswal Sarika , Kaur Amandeep , Saroha Monika , Angadi U. B. , Sheoran Sonia , Singh Rajender , Singh G. P. , Rai Anil , Tiwari Ratan , Kumar Dinesh
Published: September 2019

Drought is one of the major impediments in wheat productivity. Traditional breeding and marker assisted QTL introgression had limited success. Available wheat genomic and RNA-seq data can decipher novel drought tolerance mechanisms with putative candidate gene and marker discovery. Drought is first sensed by root tissue but limited information is available about how roots respond to drought stress. In this view, two contrasting genotypes, namely, NI5439 41 (drought tolerant) and WL711 (drought susceptible) were used to generate ~78.2 GB data for the responses of wheat roots to drought. A total of 45139 DEGs, 13820 TF, 288 miRNAs, 640 pathways and 435829 putative markers were obtained. Study reveals use of such data in QTL to QTN refinement by analysis on two model drought-responsive QTLs on chromosome 3B in wheat roots possessing 18 differentially regulated genes with 190 sequence variants (173 SNPs and 17 InDels). Gene regulatory networks showed 69 hub-genes integrating ABA dependent and independent pathways controlling sensing of drought, root growth, uptake regulation, purine metabolism, thiamine metabolism and antibiotics pathways, stomatal closure and senescence. Eleven SSR markers were validated in a panel of 18 diverse wheat varieties. For effective future use of findings, web genomic resources were developed. We report RNA-Seq approach on wheat roots describing the drought response mechanisms under field drought conditions along with genomic resources, warranted in endeavour of wheat productivity.
Network-based Responses to the Psychomotor Vigilance Task during Lapses in Adolescents after Short and Extended Sleep
Authors: DiFrancesco M. W. , Van Dyk T. , Altaye M. , Drummond S. P. A. , Beebe D. W.
Published: September 2019

Neuroimaging studies of the Psychomotor Vigilance Task (PVT) have revealed brain regions involved in attention lapses in sleep-deprived and well-rested adults. Those studies have focused on individual brain regions, rather than integrated brain networks, and have overlooked adolescence, a period of ongoing brain development and endemic short sleep. This study used functional MRI (fMRI) and a contemporary analytic approach to assess time-resolved peri-stimulus response of key brain networks when adolescents complete the PVT, and test for differences across attentive versus inattentive periods and after short sleep versus well-rested states. Healthy 14–17-year-olds underwent a within-subjects randomized protocol including 5-night spans of extended versus short sleep. PVT was performed during fMRI the morning after each sleep condition. Event-related independent component analysis (eICA) identified coactivating functional networks and corresponding time courses. Analysis of salient time course characteristics tested the effects of sleep condition, lapses, and their interaction. Seven eICA networks were identified supporting attention, executive control, motor, visual, and default-mode functions. Attention lapses, after either sleep manipulation, were accompanied by broadly increased response magnitudes post-stimulus and delayed peak responses in some networks. Well-circumscribed networks respond during the PVT in adolescents, with timing and intensity impacted by attentional lapses regardless of experimentally shortened or extended sleep.
Systematic Analysis of Pigeons’ Discrimination of Pixelated Stimuli: A Hierarchical Pattern Recognition System Is Not Identifiable
Authors: Delius Juan D. , Delius Julia A. M.
Published: September 2019

Pigeons learned to discriminate two different patterns displayed with miniature light-emitting diode arrays. They were then tested with 84 interspersed, non-reinforced degraded pattern pairs. Choices ranged between 100% and 50% for one or other of the patterns. Stimuli consisting of few pixels yielded low choice scores whereas those consisting of many pixels yielded a broad range of scores. Those patterns with a high number of pixels coinciding with those of the rewarded training stimulus were preferred and those with a high number of pixels coinciding with the non-rewarded training pattern were avoided; a discrimination index based on this correlated 0.74 with the pattern choices. Pixels common to both training patterns had a minimal influence. A pixel-by-pixel analysis revealed that eight pixels of one pattern and six pixels of the other pattern played a prominent role in the pigeons’ choices. These pixels were disposed in four and two clusters of neighbouring locations. A summary index calculated on this basis still only yielded a weak 0.73 correlation. The individual pigeons’ data furthermore showed that these clusters were a mere averaging mirage. The pigeons’ performance depends on deep learning in a midbrain-based multimillion synapse neuronal network. Pixelated visual patterns should be helpful when simulating perception of patterns with artificial networks.
Migratory strategies of juvenile northern fur seals (Callorhinus ursinus): bridging the gap between pups and adults
Authors: Zeppelin Tonya , Pelland Noel , Sterling Jeremy , Brost Brian , Melin Sharon , Johnson Devin , Lea Mary-Anne , Ream Rolf
Published: September 2019

In species exhibiting differential migration by sex and age, understanding what differences exist, and the adaptive reasons for these differences is critical for determining how demographic groups will respond to environmental variability and anthropogenic perturbations. We used satellite-telemetered movement and diving data to investigate differential migration and its ontogeny in a highly migratory North Pacific Ocean predator, the northern fur seal (Callorhinus ursinus; NFS), with a focus on understudied juvenile (1- to 2-year-old) animals. We instrumented 71 juvenile NFS in two years (2006–07 and 2007–08) at three major North American breeding sites and compared their migratory strategies with pups and adults. Although sexual dimorphism is strong in adult NFS, only weak differences in body mass between sexes were found in juveniles, which had similar body mass to pups (~3–4 months). However, unlike widely-dispersed pups, juvenile male and female NFS dispersed in different directions, and used different habitats characterized by distinct hydrography and prey assemblages during migration, similar to breeding adults. Juvenile diving behavior differed only modestly among habitats and between sexes, consistent with weak differences in body mass. Evidence of habitat sexual segregation by juvenile NFS contradicts previous hypotheses that physiological differences predominantly drive the ontogeny of differential migration.
Vegetation dynamics in Alpine glacier forelands tackled from space
Authors: Fischer Andrea , Fickert Thomas , Schwaizer Gabriele , Patzelt Gernot , Groß Günther
Published: September 2019

Monitoring of plant succession in glacier forelands has so far been restricted to field sampling. In this study, in situ vegetation sampling along a chronosequence between Little Ice Age (LIA) maximum extent and the recent glacier terminus at Jamtalferner in the Austrian Alps is compared to time series of the Normalized Difference Vegetation Index (NDVI) calculated from 13 Landsat scenes (1985–2016). The glacier terminus positions at 16 dates between the LIA maximum and 2015 were analysed from historical maps, orthophotos and LiDAR images. We sampled plots of different ages since deglaciation, from very recent to approx. 150 years: after 100 years, roughly 80% of the ground is covered by plants and ground cover does not increase significantly thereafter. The number of species increases from 10–20 species on young sites to 40–50 species after 100 years. The NDVI increases with the time of exposure from a mean of 0.11 for 1985–1991 to 0.20 in 2009 and 0.27 in 2016. As the increase in ground cover is clearly reproduced by the NDVI (R² ground cover/NDVI 0.84) – even for sparsely vegetated areas –, we see a great potential of satellite-borne NDVI to perform regional characterizations of glacier forelands for hydrological, ecological and hazard management-related applications.
Responses of neurons in the rat’s inferior colliculus to a sound are affected by another sound in a space-dependent manner
Authors: Chot Mathiang G. , Tran Sarah , Zhang Huiming
Published: September 2019

The perception of a sound can be influenced by another sound in a space-dependent manner. An understanding of this perceptual phenomenon depends on knowledge about how the spatial relationship between two sounds affects neural responses to the sounds. We used the rat as a model system and equal-probability two-tone sequences as stimuli to evaluate how spatial separation between two asynchronously recurring sounds affected responses to the sounds in midbrain auditory neurons. We found that responses elicited by two tone bursts when they were colocalized at the ear contralateral to the neuron were different from the responses elicited by the same sounds when they were separated with one at the contralateral ear while the other at another location. For neurons with transient sound-driven firing and not responsive to stimulation presented at the ipsilateral ear, the response to a sound with a fixed location at the contralateral ear was enhanced when the second sound was separated. These neurons were likely important for detecting a sound in the presence of a spatially separated competing sound. Our results suggest that mechanisms underlying effects of spatial separation on neural responses to sounds may include adaptation and long-lasting binaural excitatory/inhibitory interaction.