bluuebunny/crossref_metadata_2025 huggingface dataset:
Corneal hysteresis as a risk factor for optic nerve head surface depression and retinal nerve fiber layer thinning in glaucoma patients
Authors: Xu Guihua , Chen Zilin
Published: June 2021

To evaluate the role of corneal hysteresis (CH) as a risk factor for progressive ONH surface depression and RNFL thinning measured by confocal scanning laser ophthalmoscopy (CSLO) and spectral-domain optical coherence tomography (SD-OCT), respectively in glaucoma patients. Prospective study. A total of 146 eyes of 90 patients with glaucoma were recruited consecutively. The CH measurements were acquired at baseline and 4-months interval using the Ocular Response Analyzer (Reichert Instruments, Depew, NY). Eyes were imaged by CSLO (Heidelberg Retinal Tomograph [HRT]; Heidelberg Engineering, GmbH, Dossenheim, Germany) and SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec AG, Dublin, CA) at approximately 4-month intervals for measurement of ONH surface topography and RNFL thickness, respectively. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA) with HRT and Guided Progression Analysis (GPA) with Cirrus HD-OCT, respectively. Multivariate cox proportional hazards models were used to investigate whether CH is a risk factor for ONH surface depression and RNFL progression after adjusting potential confounding factors. All patients with glaucoma were followed for an average of 6.76 years (range, 4.56–7.61 years). Sixty-five glaucomatous eyes (44.5%) of 49 patients showed ONH surface depression, 55 eyes (37.7%) of 43 patients had progressive RNFL thinning and 20 eyes (13.7%) of 17 patients had visual field progression. In the cox proportional hazards model, after adjusting baseline diastolic IOP, CCT, age, baseline disc area and baseline MD, baseline CH was significantly associated with ONH surface depression and visual field progression (HR = 0.71, P = 0.014 and HR = 0.54, P = 0.018, respectively), but not with RNFL thinning (HR = 1.03, P = 0.836). For each 1-mmHg decrease in baseline CH, the hazards for ONH surface depression increase by 29%, and the hazards for visual field progression increase by 46%. The CH measurements were significantly associated with risk of glaucoma progression. Eyes with a lower CH were significantly associated with an increased risk of ONH surface depression and visual field progression in glaucoma patients.
Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn’s disease
Authors: Vuyyuru Sudheer K. , Kante Bhaskar , Kumar Peeyush , Sahu Pabitra , Kedia Saurabh , Ranjan Mukesh Kumar , Sharma Raju , Panwar Rajesh , Makharia Govind , Ahuja Vineet
Published: June 2021

Crohn’s disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30–396) months; median follow-up duration-42 (range 8–180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2–96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.
Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension
Authors: Kolifarhood Goodarz , Sabour Siamak , Akbarzadeh Mahdi , Sedaghati-khayat Bahareh , Guity Kamran , Rasekhi Dehkordi Saeid , Amiri Roudbar Mahmoud , Hadaegh Farzad , Azizi Fereidoun , Daneshpour Maryam S.
Published: June 2021

High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.
The relationship between the plasma proinflammatory cytokine levels of depressed/anxious children and their parents
Authors: Mevorach Tomer , Taler Michal , Dar Shira , Lebow Maya , Sapir Irit Schorr , Rotkopf Ron , Apter Alan , Fennig Silvana , Chen Alon , Weizman Abraham , Amitai Maya
Published: June 2021

Recent studies suggest immune function dysregulation in depression and anxiety disorders. Elevated pro-inflammatory cytokines may be a marker for immune system dysregulation. No study assessed the correlation between the levels of cytokines in children and adolescents with depression/anxiety disorders and their parents. In this study, 92 children and adolescents (mean age 13.90 ± 2.41 years) with depression and/or anxiety disorders were treated with fluoxetine. Blood samples were collected before initiation of treatment. One hundred and sixty-four of their parents (mean age 50.6 ± 6.2 years) and 25 parents of healthy children (mean age 38.5 ± 6.2 years) also gave blood samples. Plasma levels of three pro-inflammatory cytokine (TNF-α, IL-6, IL-1β) were measured by enzyme linked immunosorbent assays (ELISA) and compared between depressed/anxious children and their parents. We also compared cytokine levels between parents of children with depression/anxiety and control parents. Mothers of depressed children had higher TNF-α levels than mothers of controls. No significant difference was detected in the fathers. A positive correlation was found between the IL-1β levels of the depressed/anxious boys and their mothers. No such correlation was observed in the fathers. Our conclusions are that higher levels of proinflammatory cytokines may indicate immune system activation in mothers in response to the distress associated with having depressed/anxious offspring. The correlation between IL-1β levels in the mothers and their depressed/anxious children may indicate familial vulnerability to depression and anxiety. Our observation highlights the need for a better understanding of sexual dimorphism in inflammatory responses to stress.
Novel duck reovirus exhibits pathogenicity to specific pathogen-free chickens by the subcutaneous route
Authors: Yu Kexiang , Ti Jinfeng , Lu Xiao , Pan Li , Liu Liping , Gao Yuehua , Guo Xiaozhen , Hu Feng , Liu Cunxia , Ma Xiuli , Li Yufeng , Huang Bing , Song Minxun
Published: June 2021

To study the pathogenicity of new duck reovirus (NDRV) to chickens, eighty 3-day-old SPF chickens were equally divided into two groups. The experimental group was inoculated with a NDRV challenge strain of 100 μL (10–5.00 ELD50/0.1 mL) by the subcutaneous (s.c.) route, and the control group was inoculated with 100 μL of sterile phosphate-buffered saline (PBS) by the same route. In the experimental group, chickens exhibited introflexion of claws, performing of splits, stunting syndrome, weight loss and death. Gross lesions such as enlargement and yellowish-white focal necroses were observed in the liver and spleen. Microscopic changes were typical including varying degrees of hepatocyte steatosis and necrosis, splenic lymphocyte necrosis, interstitial pneumonia. Viral loads were detected in lung, liver, heart, spleen, duodenum, burse and kidney. The liver and spleen viral loads remained a much higher level and maintained for a longer time, suggesting that these tissues might be the target organs. In summary, NDRV can cause systemic infections and death in chickens, which indicated that chickens may be infected by NDRV in poultry production.
The impact of second-hand smoke on nitrogen oxides concentrations in a small interior
Authors: Braun Markus , Klingelhöfer Doris , Müller Ruth , Groneberg David A.
Published: June 2021

Nitrogen oxides (NOx), especially nitrogen dioxide (NO2), are among the most hazardous forms of air pollution. Tobacco smoke is a main indoor source of NOx, but little information is available about their concentrations in second-hand smoke (SHS), particularly in small indoors. This study presents data of NOx and its main components nitric oxide (NO) and NO2 in SHS emitted by ten different cigarette brands measured in a closed test chamber with a volume of 2.88 m3, similar to the volume of vehicle cabins. The results show substantial increases in NOx concentrations when smoking only one cigarette. The NO2 mean concentrations ranged between 105 and 293 µg/m3, the NO2 peak concentrations between 126 and 357 µg/m3. That means the one-hour mean guideline of 200 µg/m3 for NO2 of the World Health Organization was exceeded up to 47%, respectively 79%. The measured NO2 values show positive correlations with the values for tar, nicotine, and carbon monoxide stated by the cigarette manufacturers. This study provides NO2 concentrations in SHS at health hazard levels. These data give rise to the necessity of health authorities’ measures to inform about and caution against NOx exposure by smoking in indoor rooms.
Ultra-wideband, wide angle, asymmetric transmission based chiral metasurface for C and X band applications
Authors: Bokhari Syed Hussain Ali , Cheema Hammad M.
Published: June 2021

A multi-layered chiral device manifesting asymmetric transmission (AT) facilitating one-way channeling of electromagnetic (EM) waves, based on the inherent polarization is presented. The designed metasurface depicts a high transmission contrast with an efficiency above 80% for an ultra-wide operational range of 6.3–12.3 GHz, constituting a fractional bandwidth of 64%. As an additional feature, the reported metasurface yields robustness against oblique incidences up to 45$$^\circ $$

∘

while maintaining high transmission efficiency. This report also introduces a unique analogy of the AT based communication system with logic-gates by formulating its truth-table and logic circuit. Furthermore, new insights of AT magnitude’s dependence to oblique incidences are presented on the account of surface impedance mismatch due to TE and TM polarization with varying incidence angle. Moreover, avoidance of grating lobes and the associated transmission deterioration through utilization of electrically small periodic metasurface is presented. The results have been numerically and practically validated yielding state-of-the-art features. Operating within C and X band, the reported work is an ideal candidate for practical AT applications.
Establishment of an integrated automated embryonic manipulation system for producing genetically modified mice
Authors: Eto Tomoo , Ueda Hiroki , Ito Ryoji , Takahashi Tsukasa , Watanabe Toshiaki , Goto Motohito , Sotomaru Yusuke , Tanaka Nobuaki , Takahashi Riichi
Published: June 2021

Genetically modified mice are commonly used in biologic, medical, and drug discovery research, but conventional microinjection methods used for genetic modification require extensive training and practical experience. Here we present a fully automated system for microinjection into the pronucleus to facilitate genetic modification. We first developed software that automatically controls the microinjection system hardware. The software permits automatic rotation of the zygote to move the pronucleus to the injection pipette insertion position. We also developed software that recognizes the pronucleus in 3-dimensional coordinates so that the injection pipette can be automatically inserted into the pronucleus, and achieved a 94% insertion rate by linking the 2 pieces of software. Next, we determined the optimal solution injection conditions (30 hPa, 0.8–2.0 s) by examining the survival rate of injected zygotes. Finally, we produced transgenic (traditional DNA injection and piggyBac Transposon system) and knock-in (genomic editing) mice using our newly developed Integrated Automated Embryo Manipulation System (IAEMS). We propose that the IAEMS will simplify highly reproducible pronuclear stage zygote microinjection procedures.
Role of insulin/glucagon ratio and cell redox state in the hyperglycaemia induced by exposure to a 60-Hz magnetic field in rats
Authors: Martiñón-Gutiérrez Gabriel , Luna-Castro María , Hernández-Muñoz Rolando
Published: June 2021

The exposure to extremely low-frequency electromagnetic fields (EMFs) could adversely affect the endocrine system and cellular proliferative response. Nonetheless, the use of 60-Hz EMFs in the form of magneto-therapy exerts beneficial actions on human health but can also induce hyperglycaemia. Therefore, the present study was aimed to search for metabolic responses of fed or fasted male rats to a single EMF exposure. We performed a 15 min-single exposure to 60-Hz (3.8 mT, intensity) EMF, and determined serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to a 60-Hz EMF induced hyperglycaemia in both animal groups, and an attenuated second serum insulin peak. The 60-Hz EMF also decreased free fatty acids and lactate serum levels, oppositely increasing pyruvate and acetoacetate levels. Significant increases in blood glucose level and rat’s glucose metabolism were related to a more oxidized cellular redox state and variations in insulin and glucagon secretion. The 60-Hz EMF’s effects were not modified in animals previously subjected to chronic EMFs exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by a single 60-Hz EMF exposure were closely related to the cellular redox state and the insulin/glucagon ratio.
Energy constraints on brain network formation
Authors: Takagi Kosuke
Published: June 2021

Energy constraints are a fundamental limitation of the brain, which is physically embedded in a restricted space. The collective dynamics of neurons through connections enable the brain to achieve rich functionality, but building connections and maintaining activity come at a high cost. The effects of reducing these costs can be found in the characteristic structures of the brain network. Nevertheless, the mechanism by which energy constraints affect the organization and formation of the neuronal network in the brain is unclear. Here, it is shown that a simple model based on cost minimization can reproduce structures characteristic of the brain network. With reference to the behavior of neurons in real brains, the cost function was introduced in an activity-dependent form correlating the activity cost and the wiring cost as a simple ratio. Cost reduction of this ratio resulted in strengthening connections, especially at highly activated nodes, and induced the formation of large clusters. Regarding these network features, statistical similarity was confirmed by comparison to connectome datasets from various real brains. The findings indicate that these networks share an efficient structure maintained with low costs, both for activity and for wiring. These results imply the crucial role of energy constraints in regulating the network activity and structure of the brain.
Author Correction: Tailings facility disclosures reveal stability risks
Authors: Franks Daniel M. , Stringer Martin , Torres-Cruz Luis A. , Baker Elaine , Valenta Rick , Thygesen Kristina , Matthews Adam , Howchin John , Barrie Stephen
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A randomized trial examining the effect of predictive analytics and tailored interventions on the cost of care
Authors: Nikolova-Simons Mariana , Golas Sara Bersche , den Buijs Jorn op , Palacholla Ramya S. , Garberg Gary , Orenstein Allison , Kvedar Joseph
Published: June 2021

This two-arm randomized controlled trial evaluated the impact of a Stepped-Care intervention (predictive analytics combined with tailored interventions) on the healthcare costs of older adults using a Personal Emergency Response System (PERS). A total of 370 patients aged 65 and over with healthcare costs in the middle segment of the cost pyramid for the fiscal year prior to their enrollment were enrolled for the study. During a 180-day intervention period, control group (CG) received standard care, while intervention group (IG) received the Stepped-Care intervention. The IG had 31% lower annualized inpatient cost per patient compared with the CG (3.7 K, $8.1 K vs. $11.8 K, p = 0.02). Both groups had similar annualized outpatient costs per patient ($6.1 K vs. $5.8 K, p = 0.10). The annualized total cost reduction per patient in the IG vs. CG was 20% (3.5 K, $17.7 K vs. $14.2 K, p = 0.04). Predictive analytics coupled with tailored interventions has great potential to reduce healthcare costs in older adults, thereby supporting population health management in home or community settings.
Patient-specific COVID-19 resource utilization prediction using fusion AI model
Authors: Tariq Amara , Celi Leo Anthony , Newsome Janice M. , Purkayastha Saptarshi , Bhatia Neal Kumar , Trivedi Hari , Gichoya Judy Wawira , Banerjee Imon
Published: June 2021

The strain on healthcare resources brought forth by the recent COVID-19 pandemic has highlighted the need for efficient resource planning and allocation through the prediction of future consumption. Machine learning can predict resource utilization such as the need for hospitalization based on past medical data stored in electronic medical records (EMR). We conducted this study on 3194 patients (46% male with mean age 56.7 (±16.8), 56% African American, 7% Hispanic) flagged as COVID-19 positive cases in 12 centers under Emory Healthcare network from February 2020 to September 2020, to assess whether a COVID-19 positive patient’s need for hospitalization can be predicted at the time of RT-PCR test using the EMR data prior to the test. Five main modalities of EMR, i.e., demographics, medication, past medical procedures, comorbidities, and laboratory results, were used as features for predictive modeling, both individually and fused together using late, middle, and early fusion. Models were evaluated in terms of precision, recall, F1-score (within 95% confidence interval). The early fusion model is the most effective predictor with 84% overall F1-score [CI 82.1–86.1]. The predictive performance of the model drops by 6 % when using recent clinical data while omitting the long-term medical history. Feature importance analysis indicates that history of cardiovascular disease, emergency room visits in the past year prior to testing, and demographic factors are predictive of the disease trajectory. We conclude that fusion modeling using medical history and current treatment data can forecast the need for hospitalization for patients infected with COVID-19 at the time of the RT-PCR test.
Evaluation of biases in remote photoplethysmography methods
Authors: Dasari Ananyananda , Prakash Sakthi Kumar Arul , Jeni László A. , Tucker Conrad S.
Published: June 2021

This work investigates the estimation biases of remote photoplethysmography (rPPG) methods for pulse rate measurement across diverse demographics. Advances in photoplethysmography (PPG) and rPPG methods have enabled the development of contact and noncontact approaches for continuous monitoring and collection of patient health data. The contagious nature of viruses such as COVID-19 warrants noncontact methods for physiological signal estimation. However, these approaches are subject to estimation biases due to variations in environmental conditions and subject demographics. The performance of contact-based wearable sensors has been evaluated, using off-the-shelf devices across demographics. However, the measurement uncertainty of rPPG methods that estimate pulse rate has not been sufficiently tested across diverse demographic populations or environments. Quantifying the efficacy of rPPG methods in real-world conditions is critical in determining their potential viability as health monitoring solutions. Currently, publicly available face datasets accompanied by physiological measurements are typically captured in controlled laboratory settings, lacking diversity in subject skin tones, age, and cultural artifacts (e.g, bindi worn by Indian women). In this study, we collect pulse rate and facial video data from human subjects in India and Sierra Leone, in order to quantify the uncertainty in noncontact pulse rate estimation methods. The video data are used to estimate pulse rate using state-of-the-art rPPG camera-based methods, and compared against ground truth measurements captured using an FDA-approved contact-based pulse rate measurement device. Our study reveals that rPPG methods exhibit similar biases when compared with a contact-based device across demographic groups and environmental conditions. The mean difference between pulse rates measured by rPPG methods and the ground truth is found to be ~2% (1 beats per minute (b.p.m.)), signifying agreement of rPPG methods with the ground truth. We also find that rPPG methods show pulse rate variability of ~15% (11 b.p.m.), as compared to the ground truth. We investigate factors impacting rPPG methods and discuss solutions aimed at mitigating variance.
Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
Authors: Rayford Walter , Beksac Alp Tuna , Alger Jordan , Alshalalfa Mohammed , Ahmed Mohsen , Khan Irtaza , Falagario Ugo G. , Liu Yang , Davicioni Elai , Spratt Daniel E. , Schaeffer Edward M. , Feng Felix Y. , Mahal Brandon , Nguyen Paul L. , Den Robert B. , Greenberger Mark D. , Bradley Randy , Watson Justin M. , Beamer Matthew , Stamatakis Lambros , Carmen Darrell J. , Awasthi Shivanshu , Hwang Jonathan , Weil Rachel , Merisaari Harri , Mohamed Nihal , Deane Leslie A. , Chakravarty Dimple , Yadav Kamlesh K. , Yamoah Kosj , Nair Sujit S. , Tewari Ashutosh K.
Published: June 2021

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.
Wolfberry genomes and the evolution of Lycium (Solanaceae)
Authors: Cao You-Long , Li Yan-long , Fan Yun-Fang , Li Zhen , Yoshida Kouki , Wang Jie-Yu , Ma Xiao-Kai , Wang Ning , Mitsuda Nobutaka , Kotake Toshihisa , Ishimizu Takeshi , Tsai Kun-Chan , Niu Shan-Ce , Zhang Diyang , Sun Wei-Hong , Luo Qing , Zhao Jian-Hua , Yin Yue , Zhang Bo , Wang Jun-Yi , Qin Ken , An Wei , He Jun , Dai Guo-Li , Wang Ya-Jun , Shi Zhi-Gang , Jiao En-Ning , Wu Peng-Ju , Liu Xuedie , Liu Bin , Liao Xing-Yu , Jiang Yu-Ting , Yu Xia , Hao Yang , Xu Xin-Yu , Zou Shuang-Quan , Li Ming-He , Hsiao Yu-Yun , Lin Yu-Fu , Liang Chieh-Kai , Chen You-Yi , Wu Wan-Lin , Lu Hsiang-Chai , Lan Si-Ren , Wang Zhi-Wen , Zhao Xiang , Zhong Wen-Ying , Yeh Chuan-Ming , Tsai Wen-Chieh , Van de Peer Yves , Liu Zhong-Jian
Published: June 2021

Wolfberry Lycium, an economically important genus of the Solanaceae family, contains approximately 80 species and shows a fragmented distribution pattern among the Northern and Southern Hemispheres. Although several herbaceous species of Solanaceae have been subjected to genome sequencing, thus far, no genome sequences of woody representatives have been available. Here, we sequenced the genomes of 13 perennial woody species of Lycium, with a focus on Lycium barbarum. Integration with other genomes provides clear evidence supporting a whole-genome triplication (WGT) event shared by all hitherto sequenced solanaceous plants, which occurred shortly after the divergence of Solanaceae and Convolvulaceae. We identified new gene families and gene family expansions and contractions that first appeared in Solanaceae. Based on the identification of self-incompatibility related-gene families, we inferred that hybridization hotspots are enriched for genes that might be functioning in gametophytic self-incompatibility pathways in wolfberry. Extremely low expression of LOCULE NUBER (LC) and COLORLESS NON-RIPENING (CNR) orthologous genes during Lycium fruit development and ripening processes suggests functional diversification of these two genes between Lycium and tomato. The existence of additional flowering locus C-like MADS-box genes might correlate with the perennial flowering cycle of Lycium. Differential gene expression involved in the lignin biosynthetic pathway between Lycium and tomato likely illustrates woody and herbaceous differentiation. We also provide evidence that Lycium migrated from Africa into Asia, and subsequently from Asia into North America. Our results provide functional insights into Solanaceae origins, evolution and diversification.
Comparative analysis of mite genomes reveals positive selection for diet adaptation
Authors: Liu Qiong , Deng Yuhua , Song An , Xiang Yifan , Chen De , Wei Lai
Published: June 2021

Diet is a powerful evolutionary force for species adaptation and diversification. Acari is one of the most abundant clades of Arachnida, exhibiting diverse dietary types, while the underlying genetic adaptive mechanisms are not fully understood. Based on comparative analyses of 15 Acari genomes, we found genetic bases for three specialized diets. Herbivores experienced stronger selection pressure than other groups; the olfactory genes and gene families involving metabolizing toxins showed strong adaptive signals. Genes and gene families related to anticoagulation, detoxification, and haemoglobin digestion were found to be under strong selection pressure or significantly expanded in the blood-feeding species. Lipid metabolism genes have a faster evolutionary rate and been subjected to greater selection pressures in fat-feeding species; one positively selected site in the fatty-acid amide hydrolases 2 gene was identified. Our research provides a new perspective for the evolution of Acari and offers potential target loci for novel pesticide development.
The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function
Authors: Oftedal Bergithe E. , Maio Stefano , Handel Adam E. , White Madeleine P. J. , Howie Duncan , Davis Simon , Prevot Nicolas , Rota Ioanna A. , Deadman Mary E. , Kessler Benedikt M. , Fischer Roman , Trede Nikolaus S. , Sezgin Erdinc , Maizels Rick M. , Holländer Georg A.
Published: June 2021

T cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. In the absence of CCT-controlled protein folding, Th2 polarization diverges from normal differentiation with paradoxical continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.
Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes
Authors: Wang Hong , Duan Aiping , Zhang Jing , Wang Qi , Xing Yuexian , Qin Zhaohui , Liu Zhihong , Yang Jingping
Published: June 2021

Elucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.
Zinc isotopes from archaeological bones provide reliable trophic level information for marine mammals
Authors: McCormack Jeremy , Szpak Paul , Bourgon Nicolas , Richards Michael , Hyland Corrie , Méjean Pauline , Hublin Jean-Jacques , Jaouen Klervia
Published: June 2021

In marine ecology, dietary interpretations of faunal assemblages often rely on nitrogen isotopes as the main or only applicable trophic level tracer. We investigate the geographic variability and trophic level isotopic discrimination factors of bone zinc 66Zn/64Zn ratios (δ66Zn value) and compared it to collagen nitrogen and carbon stable isotope (δ15N and δ13C) values. Focusing on ringed seals (Pusa hispida) and polar bears (Ursus maritimus) from multiple Arctic archaeological sites, we investigate trophic interactions between predator and prey over a broad geographic area. All proxies show variability among sites, influenced by the regional food web baselines. However, δ66Zn shows a significantly higher homogeneity among different sites. We observe a clear trophic spacing for δ15N and δ66Zn values in all locations, yet δ66Zn analysis allows a more direct dietary comparability between spatially and temporally distinct locations than what is possible by δ15N and δ13C analysis alone. When combining all three proxies, a more detailed and refined dietary analysis is possible.
Phenotypic analysis of catastrophic childhood epilepsy genes
Authors: Griffin Aliesha , Carpenter Colleen , Liu Jing , Paterno Rosalia , Grone Brian , Hamling Kyla , Moog Maia , Dinday Matthew T. , Figueroa Francisco , Anvar Mana , Ononuju Chinwendu , Qu Tony , Baraban Scott C.
Published: June 2021

Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Local field potential recordings (LFP) were used to screen ∼3300 larvae. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.
Templated interfacial synthesis of metal-organic framework (MOF) nano- and micro-structures with precisely controlled shapes and sizes
Authors: Meng Lingyao , Yu Binyu , Qin Yang
Published: June 2021

Metal-organic frameworks (MOF) are an emerging class of microporous materials with promising applications. MOF nanocrystals, and their assembled super-structures, can display unique properties and reactivities when compared with their bulk analogues. MOF nanostructures of 0-D, 2-D, and 3-D dimensions can be routinely obtained by controlling reaction conditions and ligand additives, while formation of 1-D MOF nanocrystals (nanowires and nanorods) and super-structures has been relatively rare. We report here a facile templated interfacial synthesis methodology for the preparation of a series of 1-D MOF nano- and micro-structures with precisely controlled shapes and sizes. Specifically, by applying track-etched polycarbonate (PCTE) membranes as the templates and at the oil/water interface, we rapidly and reproducibly synthesize zeolitic imidazolate framework-8 (ZIF-8) and ZIF-67 nano- and micro structures of sizes ranging from 10 nm to 20 μm. We also identify a size confinement effect on MOF crystal growth, which leads to single crystals under the most restricted conditions and inter-grown polycrystals at larger template pore sizes, as well as surface directing effects that influence the crystallographic preferred orientation. Our findings provide a potentially generalizable method for controlling the size, morphology, and crystal orientations of MOF nanomaterials, as well as offering fundamental understanding into MOF crystal growth mechanisms.
Merohedral disorder and impurity impacts on superconductivity of fullerenes
Authors: Wang Shu-Ze , Ren Ming-Qiang , Han Sha , Cheng Fang-Jun , Ma Xu-Cun , Xue Qi-Kun , Song Can-Li
Published: June 2021

Local quasiparticle states around impurities provide essential insight into the mechanism of unconventional superconductivity, especially when the candidate materials are proximate to an antiferromagnetic Mott-insulating phase. While such states have been reported in atom-based cuprates and iron-based compounds, they are unexplored in organic superconductors which feature tunable molecular orientation. Here we employ scanning tunneling microscopy and spectroscopy to reveal multiple forms of robustness of an exotic s-wave superconductivity in epitaxial Rb3C60 films against merohedral disorder, non-magnetic single impurities and step edges at the atomic scale. Yu-Shiba-Rusinov (YSR) states, induced by deliberately incurred Fe adatoms that act as magnetic scatterers, have also been observed. The YSR bound states show abrupt spatial decay and vary in energy with the Fe adatom registry. These results and a doping-dependent study of superconductivity point towards local electron pairing in which the multiorbital electronic correlations and intramolecular phonons together drive the high-temperature superconductivity of doped fullerenes.
Tunable polarization-induced Fano resonances in stacked wire-grid metasurfaces
Authors: Romain Xavier , Degl’Innocenti Riccardo , Baida Fadi I. , Boyer Philippe
Published: June 2021

Stacked metasurfaces are being investigated in light of exploring exotic optical effects that cannot be achieved with single-layered metasurfaces. In this article, we theoretically demonstrate that metallic wire-grid metasurfaces with specific polarization properties have the ability to induce tunable Fano resonances when they are stacked. The developed original model—combining a circulating field approach together with an extended Jones formalism—reveals the underlying principle that gives rise to the polarization-induced Fano resonances. The theoretical frame is validated in an experimental proof of concept using commercially available wire-grids and a terahertz time domain spectrometer. This unexplored possibility opens an alternative path to the realization and control of Fano resonances by using stacked metallic metasurfaces. Furthermore, these findings suggest that the polarization can be used as an additional degree of freedom for the design of optical resonators with enhanced and tunable properties.
Biosignatures of ancient microbial life are present across the igneous crust of the Fennoscandian shield
Authors: Drake Henrik , Roberts Nick M. W. , Reinhardt Manuel , Whitehouse Martin , Ivarsson Magnus , Karlsson Andreas , Kooijman Ellen , Kielman-Schmitt Melanie
Published: June 2021

Earth’s crust contains a substantial proportion of global biomass, hosting microbial life up to several kilometers depth. Yet, knowledge of the evolution and extent of life in this environment remains elusive and patchy. Here we present isotopic, molecular and morphological signatures for deep ancient life in vein mineral specimens from mines distributed across the Precambrian Fennoscandian shield. Stable carbon isotopic signatures of calcite indicate microbial methanogenesis. In addition, sulfur isotope variability in pyrite, supported by stable carbon isotopic signatures of methyl-branched fatty acids, suggest subsequent bacterial sulfate reduction. Carbonate geochronology constrains the timing of these processes to the Cenozoic. We suggest that signatures of an ancient deep biosphere and long-term microbial activity are present throughout this shield. We suggest that microbes may have been active in the continental igneous crust over geological timescales, and that subsurface investigations may be valuable in the search for extra-terrestrial life.
Central Asian modulation of Northern Hemisphere moisture transfer over the Late Cenozoic
Authors: Prud’homme Charlotte , Scardia Giancarlo , Vonhof Hubert , Guinoiseau Damien , Nigmatova Saida , Fiebig Jens , Gerdes Axel , Janssen Renee , Fitzsimmons Kathryn E.
Published: June 2021

Earth’s climatic evolution over the last 5 million years is primarily understood from the perspective of marine mechanisms, however, the role of terrestrial feedbacks remains largely unexplored. Here we reconstruct the last 5 million years of soil moisture variability in Central Asia using paleomagnetism data and isotope geochemistry of an 80 m-thick sedimentary succession at Charyn Canyon, Kazakhstan. We identify a long-term trend of increasing aridification throughout the period, along with shorter-term variability related to the interaction between mid-latitude westerlies and the Siberian high-pressure system. This record highlights the long-term contribution of mid-latitude Eurasian terrestrial systems to the modulation of moisture transfer into the Northern Hemisphere oceans and back onto land via westerly air flow. The response of Earth-surface dynamics to Plio-Pleistocene climatic change in Central Asia likely generated terrestrial feedbacks affecting ocean and atmospheric circulation. This missing terrestrial link elucidates the significance of land-water feedbacks for long-term global climate.
What's all the phos about? Insights into the phosphorylation state of the RNA polymerase II C-terminal domainviamass spectrometry
Authors: LeBlanc Blase M. , Moreno R. Yvette , Escobar Edwin E. , Venkat Ramani Mukesh Kumar , Brodbelt Jennifer S. , Zhang Yan
Published: June 2021

Mass spectrometry techniques allow us to investigate the phosphorylation state of the C-terminal domain of RNA polymerase II with high resolution. Here, we review mass spectrometry in this capacity and discuss technical advancements that provide critical opportunities in understanding the dynamic transcriptional assembly.
Out of stoichiometry CuCrO2 films as a promising p-type TCO for transparent electronics
Authors: Bottiglieri Lorenzo , Resende João , Weber Matthieu , Chaix-Pluchery Odette , Jiménez Carmen , Deschanvres Jean-Luc
Published: June 2021

Optimal deposition conditions to synthesize highly conductive and transparent CuCrO2 films out of stoichiometry and Cu2O + CuCrO2 nanocomposite films by AA-MOCVD at a low temperature and atmospheric pressure.
Nanostructural analysis of distinct nucleation sites in pathological mineralization
Authors: Hara Emilio Satoshi , Oozawa Susumu , Nagaoka Noriyuki , Okada Masahiro , Kasahara Shingo , Matsumoto Takuya
Published: June 2021

Vesicular and non-vesicular phospholipids were the nucleation sites in atherosclerotic calcification. Mineralization in vitro showed that LDL, PS and PC mineralized in 2 days. PS mineralized more than PC.
A more effective catalysis of the CO2 fixation with aziridines: computational screening of metal-substituted HKUST-1
Authors: Jiang Yan , Hu Tian-ding , Yu Li-ying , Ding Yi-hong
Published: June 2021

By performing the first computational screening on the cycloaddition of CO2 with aziridines under 18 metal-substituted HKUST-1 MOFs and TBAB as a co-catalyst, up to 11 M-HKUST-1 systems possess superior catalytic ability to the original Cu-HKUST-1.
Silk fibroin microspheres as optical resonators for wide-range humidity sensing and biodegradable lasers
Authors: Heah Wey Yih , Yamagishi Hiroshi , Fujita Keitaro , Sumitani Megumi , Mikami Yuya , Yoshioka Hiroaki , Oki Yuji , Yamamoto Yohei
Published: June 2021

Silk fibroin, a naturally abundant and eco-friendly material, is successfully transformed into discrete, well-defined microspherical particles that function as an active optical resonator for precise moisture sensing over a wide humidity range.
Indolizine synthesis via radical cyclization and demethylation of sulfoxonium ylides and 2-(pyridin-2-yl)acetate derivatives
Authors: Su Kexin , Guo Xin , Zhu Liangwei , Liu Yafeng , Lu Yixuan , Chen Baohua
Published: June 2021

A novel radical cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and sulfoxonium ylides is developed, which provides a straightforward access to structurally diverse methylthio-substituted indolizine.
Organocatalytic domino annulation of in situ generated tert-butyl 2-hydroxybenzylidenecarbamates with 2-isothiocyanato-1-indanones for synthesis of bridged and fused ring heterocycles
Authors: Hou Xi-Qiang , Lin Ye , Du Da-Ming
Published: June 2021

An asymmetric domino annulation of 2-isothiocyanato-1-indanones with tert-butyl 2-hydroxybenzylidenecarbamates was developed for the enantioselective construction of bridged and fused ring hererocycles in high yields with excellent stereoselectivities.
Improving the efficiency of electrokinetic conversion in nanofluidics with graphene-engineered surface
Authors: Pei Junxian , Chen Bo , Liu Xiaowei , Huang Jun , Hu Xuejiao , Liu Kang
Published: June 2021

We demonstrate decoupling of the flow boundary and surface electrical charging with single-layer graphene, which promotes the energy efficiency of a streaming generator by a factor of 20–100.
Effects of cosolvent partitioning on conformational transitions and tethered chain flexibility in spherical polymer brushes
Authors: Zhu Peng Wei
Published: June 2021

Based on the framework of the preferential adsorption concept and analytical self-consistent field theory, a model is proposed to investigate the reentrant transition of a thermoresponsive spherical brush in a series of aqueous alcohol solutions.
Creating a Path for Systematic Investigation of Children With Cortical Visual Impairment Who Use Augmentative and Alternative Communication
Authors: Boster Jamie B. , McCarthy John W. , Brown Kathryn , Spitzley Alyson M. , Blackstone Sarah W.
Published: June 2021

Purpose

There is limited information about how to support children with cortical visual impairment (CVI) who require augmentative and alternative communication (AAC). An initial review designed to explore the available evidence was used to outline critical needs in moving research and intervention forward for children who use AAC and have CVI.

Method

Previous systematic reviews, six databases, and theses and dissertations were systematically searched, along with reviews of the resulting works cited. An initial yield of 575 articles was narrowed to 10, which discussed AAC interventions that included children with CVI.

Results

Three interventions were technology based, and seven were instructional based. The use of textured microswitches was the most frequent form of technology intervention, with the frequency of switch activations being the most frequently coded outcome. Overall, the studies represent explorations in the area rather than systematic lines of inquiry.

Conclusions

While evidence shows at least some children with CVI have been included in AAC research to date, the inclusion is more incidental than deliberate. Issues such as clear descriptions of the vision capabilities and needs of participants may have impacted study results.
High efficiency low thermal resistance semiconductor laser with novel insulating layer and coating film
Authors: Wang Yuancheng , Qi Aiyi , Wang Yufei , Qu Hongwei , Zheng Wanhua
Published: June 2021

Thermal effect of semiconductor lasers is the biggest challenge to the development of semiconductor lasers. This problem limits the life and performance of high‐power laser diode. In this letter, we have reduced the thermal resistance of laser to enhance its heat dissipation capability. For this, we choose aluminium nitride (AlN) to replace traditional materials as insulating layer, as well as a passivation film for facet coating. The impact of insulation layer and facet coating on the thermal rollover process is analyzed. Finite element method simulations are compared with the experimental result. The comparison shows that the thermal resistance of the laser with the new insulating layer is reduced compared with normal laser diodes (LD). Eventually, the maximum conversion efficiency is 67.5% at room temperature and thermal resistance is 1.81C° W–1.