bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Central Vision Loss Impair Visual Search Performance of Adults More than Children?
Authors: Satgunam PremNandhini , Luo Gang
Published: April 2018

SIGNIFICANCE

In general, young adults with normal vision show the best visual search performance when compared with children and older adults. Through our study, we show that this trend is not observed in individuals with vision impairment. An interaction effect of vision impairment with visual development and aging is observed.

PURPOSE

Performance in many visual tasks typically shows improvement with age until young adulthood and then declines with aging. Using a visual search task, this study investigated whether a similar age effect on performance is present in people with central vision loss.

METHODS

A total of 98 participants, 37 with normal sight (NS) and 61 with visual impairment (VI) searched for targets in 150 real-world digital images. Search performance was quantified by an integrated measure combining speed and accuracy. Participant ages ranged from 5 to 74 years, visual acuity from −0.14 (20/14.5) to 1.16 logMAR (20/290), and log contrast sensitivity (CS) from 0.48 to 2.0. Data analysis was performed with participants divided into three age groups: children (aged <14 years, n = 25), young adults (aged 14 to 45 years, n = 47), and older adults (aged >45 years, n = 26).

RESULTS

Regression (r
2 = 0.7) revealed CS (P < .001) and age (P = .003) were significant predictors of search performance. Performance of VI participants was normalized to the age-matched average performance of the NS group. In the VI group, it was found that children's normalized performance (52%) was better than both young (39%, P = .05) and older (40%, P = .048) adults.

CONCLUSIONS

Unlike NS participants, young adults in the VI group may not have search ability superior to children with VI, despite having the same level of visual functions (quantified by visual acuity and CS). This could be because of vision impairment limiting the developmental acquisition of the age dividend for peak performance. Older adults in the VI group had the worst performance, indicating an interaction of aging.
People with Hemianopia Report Difficulty with TV, Computer, Cinema Use, and Photography
Authors: Costela Francisco M. , Sheldon Sarah S. , Walker Bethany , Woods Russell L.
Published: April 2018

SIGNIFICANCE

Our survey found that participants with hemianopia report more difficulties watching video in various formats, including television (TV), on computers, and in a movie theater, compared with participants with normal vision (NV). These reported difficulties were not as marked as those reported by people with central vision loss.

PURPOSE

The aim of this study was to survey the viewing experience (e.g., frequency, difficulty) of viewing video on TV, computers and portable visual display devices, and at the cinema of people with hemianopia and NV. This information may guide vision rehabilitation.

METHODS

We administered a cross-sectional survey to investigate the viewing habits of people with hemianopia (n = 91) or NV (n = 192). The survey, consisting of 22 items, was administered either in person or in a telephone interview. Descriptive statistics are reported.

RESULTS

There were five major differences between the hemianopia and NV groups. Many participants with hemianopia reported (1) at least “some” difficulty watching TV (39/82); (2) at least “some” difficulty watching video on a computer (16/62); (3) never attending the cinema (30/87); (4) at least some difficulty watching movies in the cinema (20/56), among those who did attend the cinema; and (5) never taking photographs (24/80). Some people with hemianopia reported methods that they used to help them watch video, including video playback and head turn.

CONCLUSIONS

Although people with hemianopia report more difficulty with viewing video on TV and at the cinema, we are not aware of any rehabilitation methods specifically designed to assist people with hemianopia to watch video. The results of this survey may guide future vision rehabilitation.
Evidence of the Homeostatic Regulation With the Combination of Transcranial Direct Current Stimulation and Physical Activity
Authors: Baltar Adriana , Nogueira Fernanda , Marques Déborah , Carneiro Maíra , Monte-Silva Kátia
Published: April 2018

Background

Transcranial direct current stimulation (tDCS) can optimize beneficial effects induced by motor practice in patients with neurological disorders. However, possibly because of homeostatic regulation, the conditioning effects of tDCS are often imprecise and variable, limiting its therapeutic application.

Objective

The aim of the study was to explore the magnitude and direction of the after effects induced by physical activity (PA) on tDCS-preconditioned cortical excitability (CE).

Design

First, a crossover experiment was performed with 12 subjects to determine whether a single session of low-, moderate-, and high-intensity PA on a treadmill modulates the motor CE measured by transcranial magnetic stimulation. In a second crossover experiment, we investigated long-lasting changes (until 90 mins) of the effects induced by PA (with intensities defined by the first experiment) on motor CE after the subject had been preconditioned by tDCS (using different polarities).

Results and Conclusions

In experiment 1, we found that high- and moderate-intensity PA modulate the CE. Experiment 2 demonstrated that preconditioning the CE using tDCS homeostatically changes the direction and magnitude of after effects induced by subsequent PA plasticity caused by motor activity. In conclusion, the results suggest that the direction of after effects induced by the combination of physical exercise with tDCS on the CE is regulated within a physiologically defined range.
Pancreaticojejunostomy Versus Pancreaticogastrostomy After Pancreaticoduodenectomy: An Up-to-date Meta-analysis of RCTs Applying the ISGPS (2016) Criteria
Authors: Lyu Yunxiao , Li Ting , Cheng Yunxiao , Wang Bin , Chen Liang , Zhao Sicong
Published: April 2018

The goal of our study was to compare the impact of pancreaticogastrostomy (PG) versus pancreaticojejunostomy (PJ) on the incidence of complications after pancreaticoduodenectomy. A systematic search was performed using RevMan 5.3 software. A meta-analysis showed that PG was not superior to PJ in terms of postoperative pancreatic fistula (POPF). In multicenter randomized controlled trials, the incidence of POPF was lower in patients undergoing PG than in those undergoing PJ. However, PG was associated with an increased risk of postoperative intraluminal hemorrhage, but no significant difference was observed between 2-layer PG and PJ. No significant differences were found in the rate of overall delayed gastric emptying, biliary fistula, reoperation, mortality, and morbidity. PG and PJ have similar incidences of POPF, but PG could be slightly superior to PJ in multicenter trials. However, this analysis verifies that PG has a higher rate of postpancreatectomy hemorrhage. Of note, a 2-layer anastomosis could reduce the occurrence of postpancreatectomy hemorrhage.
A Modern Comparison of Urodynamic Findings in Diabetic Versus Nondiabetic Women
Authors: Malik Rena D. , Cohn Joshua A. , Volsky Jessica , Garvey Sarah , Chang Charles , Bales Gregory T. , Chung Doreen E.
Published: April 2018

Objectives

Few contemporary studies exist regarding urodynamic (UDS) findings in patients with diabetes mellitus (DM), and data are conflicting. Our aim was to compare UDS findings in women with and without DM.

Methods

Data from female patients in a prospectively maintained UDS database (2010–2014) were reviewed. Studies were performed according to International Continence Society standards. Clinical data, presenting symptoms, and UDS findings were compared in women with and without DM, controlling for demographic and pertinent variables.

Results

There were 384 patients who met the inclusion criteria, of whom 88 (26%) had DM. Symptoms at presentation were not statistically different in women with and without DM. Women with DM had larger bladder capacity (mean, 493 mL vs 409 mL; P = 0.005) and had more detrusor underactivity (30% vs 18%, P = 0.042) when compared with nondiabetic women. Diabetic women were more frequently diagnosed as having impaired sensation, or lack of desire to void, at 75% of capacity (17% vs 5%, P = 0.001). In women with diabetes, a serum hemoglobin A1c level of at least 7.5% was associated with delayed first sensation and first urge. Diagnosis of DM of more than 10 years was associated with greater volume at first urge, and maximal capacity, lower detrusor pressures, and higher postvoid residual.

Conclusions

In this contemporary series, women with DM demonstrated similar presenting complaints to women without DM but had significantly altered UDS findings. Among diabetic female patients, diabetes control and duration of diabetes seem to impact bladder sensation and contractility. Urodynamics may be helpful in diabetic female patients to diagnose underlying concealed bladder dysfunction before initiation of treatment.
Association of Anticholinergic Risk Score With Functional Status in Patients Preparing for Pelvic Reconstructive Surgery
Authors: Brueseke Taylor J. , de la Luz Nieto Maria , Pulliam Samantha , Wu Jennifer M.
Published: April 2018

Objectives

Anticholinergic medication use has been associated with cognitive impairment and other functional limitations, particularly in older patients. The anticholinergic risk score (ARS) can be used to measure a patient’s cumulative exposure to medications with anticholinergic properties. Our primary objective was to evaluate the correlation between ARS and functional status, as measured by instrumental activities of daily living (IADL), in patients preparing to undergo urogynecologic surgery. The secondary objective was to examine the correlation between ARS and physical function in this same cohort.

Methods

This was a planned cross-sectional analysis of a prospective cohort study to evaluate the impact of urogynecologic surgery on functional status. The ARS was calculated by summing the ARSs of each patient’s medications and classified as high (ARS > 5) or low (ARS ≤ 5). A patient’s ability to live independently was determined using the IADL questionnaire. The patient’s physical function status was determined using the functional comorbidity index.

Results

One hundred twenty-two patients were evaluated. A total of 89.3% of subjects had a low and 10.7% had a high ARS score. For our primary outcome, high ARS was associated with low IADL in logistic regression controlling for age and formal education level (odds ratio, 8.0; 95% confidence interval, 1.4–46.9). For our secondary outcome, ARS was not associated with the functional comorbidity index (P = 0.24).

Conclusions

These data support recognition of ARS as a potential risk factor for low functional status in patients planning urogynecologic surgery.
Therapeutic Outcomes of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Severe Aplastic Anemia: A Multicenter Study
Authors: Li Yonghua , Duan Fengqi , Xiao Haowen , Wu Xiaoxiong , Wang Shunqing , Xu Duorong , Liu Qifa , Fan Zhiping , Nie Danian , Lai Yongrong , Wu Bingyi , Lin Dongjun , Du Xin , Weng Jianyu , Jiang Zujun , Pang Yan , Ouyang Ling , Liu Zenghui , Zhang Leqin , Han Na , Chen Lixuan , Xiao Yang
Published: April 2018

Background

Haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (HSCT) is an alternative curative treatment for patients with severe aplastic anemia (SAA) who do not have suitable matched related donors (MRD). The aim of this study was to compare the therapeutic outcomes of HID-HSCT with those of MRD-HSCT for SAA.

Methods

A total of 235 SAA patients who underwent HID-HSCT (116) or MRD-HSCT (119) at 11 transplantation centers from January 2007 to January 2016 were included. Complications and survival outcomes were evaluated and compared between the 2 groups.

Results

The HID group had a lower incidence of secondary graft failure but higher incidences of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). However, the incidence of severe aGVHD (grades III-IV), poor graft function, and infections was comparable between groups. Patients in the HID group had a significantly lower survival and overall survival rates than those in the MRD group. The estimated 3-year survival rates for the MRD and HID groups were 82.82% and 75.00%, respectively. Ferritin levels, graft failure, poor graft function, severe aGVHD, and infections were the significant risk factors for survival.

Conclusions

The overall survival rate is acceptable for patients who underwent HID-HSCT, making it a feasible treatment choice for SAA patients.
One Hundred Fifteen Cases of Pure Laparoscopic Living Donor Right Hepatectomy at a Single Center
Authors: Lee Kwang-Woong , Hong Suk Kyun , Suh Kyung-Suk , Kim Hyo-Sin , Ahn Sung-Woo , Yoon Kyung Chul , Lee Jeong-Moo , Cho Jae-Hyung , Kim Hyeyoung , Yi Nam-Joon
Published: April 2018

Background

The pure laparoscopic approach to donor hepatectomy is being taken more often. However, few centers perform pure laparoscopic donor right hepatectomy (PLDRH) because it requires a high level of surgical skill. Studies reporting initial outcomes of PLDRH may prompt further implementation of the technique and help reduce initial learning curves at other transplant centers. This study reports performance of PLDRH at a single center with extensive experience of adult living donor liver transplantation.

Methods

Data from 115 donors (and recipients) who underwent PLDRH between November 2015 and June 2017 were analyzed retrospectively. Subgroup analysis was performed to compare outcomes between the initial (November 2015 to October 2016) and more recent (November 2016 to June 2017) periods.

Results

During the initial period, 3 (2.6%) donors experienced complications greater than grade III on the Clavien-Dindo scale. By contrast, no donors developed complications during the recent period. The operative time (293.6 minutes vs 344.4 minutes; P < 0.001) and hospital stay (7.3 days vs 8.3 days; P = 0.002) were significantly shorter during the more recent period. Also, Δhemoglobin (Hb)%, calculated as ΔHb% = [(preoperative Hb − postoperative Hb)/preoperative Hb] × 100 (14.9% vs 17.5%; P = 0.042), and Δaspartate aminotransferase (AST)%, calculated as ΔAST% = [(peak AST − preoperative AST)/preoperative AST] × 100 (1048.9% vs 1316.6%; P = 0.009), were significantly lower during the recent period.

Conclusions

Pure laparoscopic donor right hepatectomy is both feasible and safe when performed at a center experienced in adult living donor liver transplantation. Performance of about 60 PLDRHs over 1 year is sufficient to standardize the procedure.
Multifunctional chitosan–magnetic graphene quantum dot nanocomposites for the release of therapeutics from detachable and non-detachable biodegradable microneedle arrays
Authors: Justin Richard , Chen Biqiong
Published: April 2018

Biodegradable chitosan–magnetic graphene quantum dot (MGQD) nanocomposites were prepared and investigated for the release of small and large molecular weight (MWt) therapeutics from detachable and non-detachable biodegradable microneedle arrays. The presence of MGQDs in chitosan increased the electrical conductivity and biodegradation rate of chitosan while maintaining its mechanical properties. The detachable microneedle arrays were created by including a water-soluble ring of poly(ethylene glycol) (PEG) at the base of the microneedle, which enabled the rapid detachment of the microneedle shaft from the base. The PEG ring did not impede the microneedle array performance, with mechanical properties and a drug release profile of low MWt lidocaine hydrochloride similar to microneedle arrays without the ring. Without the PEG ring, the chitosan–MGQD microneedles were electrically conductive and allowed for electrically stimulated release of large MWt therapeutics which was challenging without the stimulation. These results demonstrate that chitosan nanocomposites containing MGQDs with intrinsic photoluminescent and supermagnetic properties are promising materials for developing multifunctional microneedles for targeted and tracked transdermal drug delivery.
Ultrananocrystalline diamond-coated nanoporous membranes support SK-N-SH neuroblastoma endothelial cell attachment
Authors: Yang Kai-Hung , Nguyen Alexander K. , Goering Peter L. , Sumant Anirudha V. , Narayan Roger J.
Published: April 2018

Ultrananocrystalline diamond (UNCD) has been demonstrated to have attractive features for biomedical applications and can be combined with nanoporous membranes for applications in drug delivery systems, biosensing, immunoisolation and single molecule analysis. In this study, free-standing nanoporous UNCD membranes with pore sizes of 100 or 400 nm were fabricated by directly depositing ultrathin UNCD films on nanoporous silicon nitride membranes and then etching away silicon nitride using reactive ion etching. Successful deposition of UNCD on the substrate with a novel process was confirmed with Raman spectroscopy, X-ray photoelectron spectroscopy, cross-section scanning electron microscopy (SEM) and transmission electron microscopy. Both sample types exhibited uniform geometry and maintained a clear hexagonal pore arrangement. Cellular attachment of SK-N-SH neuroblastoma endothelial cells was examined using confocal microscopy and SEM. Attachment of SK-N-SH cells onto UNCD membranes on both porous regions and solid surfaces was shown, indicating the potential use of UNCD membranes in biomedical applications such as biosensors and tissue engineering scaffolds.
Detection of Candida species in pregnant Chinese women with a molecular beacon method
Authors: Zhai Yanhong , Liu Jing , Zhou Li , Ji Tongzhen , Meng Lingxin , Gao Yang , Liu Ran , Wang Xiao , Li Lin , Lu Binghuai , Cao Zheng
Published: April 2018

Purpose.
Candida pathogens are commonly found in women and can cause vulvovaginal candidiasis (VVC), whose infection rate is further increased during pregnancy. We aimed to study the Candida prevalence and strain distribution in pregnant Chinese women with a molecular beacon assay.

Methodology. From March 2016 to February 2017, a total of 993 pregnant women attending routine antenatal visits at the Beijing Obstetrics and Gynecology Hospital were enrolled. For Candida detection and identification, a unique molecular beacon assay was presented and compared with a traditional phenotypic method. Antifungal susceptibility was tested with the following agents: 5-flucytosine, amphotericin B, fluconazole, itraconazole and voriconazole.

Results. The prevalence of Candida was found to be 21.8 % when using the molecular method and 15.0 % when using the phenotypic method. The distribution of the Candida spp. was listed in order of decreasing prevalence: Candida albicans (79.8 %), Candida glabrata (13.5 %), Candida parapsilosis (3.7 %), Candida krusei (2.2 %) and Candida tropicalis (1.1 %). We found that 90.7 % of the Candida detection results were consistent between the molecular and the phenotypic methods. In the cases where the sequencing analyses for the Candida isolates resulted in inconsistent identification, the molecular method showed higher sensitivity than the phenotypic method (96.0 vs 64.6 %). C. albicans, C. glabrata and C. parapsilosis were essentially susceptible to all five antifungal agents tested, whereas C. tropicalis and C. krusei were susceptible to voriconazole and amphotericin B.

Conclusion. By exhibiting good sensitivity and specificity, the molecular assay may offer a fast and accurate Candida screening platform for pregnant women.
Seed predation increases from the Arctic to the Equator and from high to low elevations
Authors: Hargreaves A.L. , Suárez Esteban , Mehltreter Klaus , Myers-Smith Isla , Vanderplank Sula E. , Slinn Heather L. , Vargas-Rodriguez Yalma L. , Haeussler Sybille , David Santiago , Muñoz Jenny , Almazán Núñez Roberto Carlos , Loughnan Deirdre , Benning John W. , Moeller David A. , Brodie Jedediah F. , Thomas Haydn J.D. , Morales M.P.A.
Published: April 2018

Species interactions have long been predicted to increase in intensity towards the tropics and low elevations, due to gradients in climate, productivity, or biodiversity. Despite their importance for understanding global ecological and evolutionary processes, plant-animal interaction gradients are particularly difficult to test systematically across large geographic gradients, and evidence from smaller, disparate studies is inconclusive. By systematically measuring post-dispersal seed predation using 6980 standardized seed depots along 18 mountains in the Pacific cordillera, we found that seed predation increases 18% from the Arctic to Equator and 16% from 4000 masl to sea level. Clines in total predation, likely driven by invertebrates, were consistent across tree-line ecotones and in continuous forest, and were better explained by climate seasonality than by productivity, biodiversity, or latitude. These results suggest that species interactions play predictably greater ecological and evolutionary roles in tropical, lowland, and other less seasonal ecosystems.

One Sentence Summary

Post-dispersal seed predation increases from the Arctic to the Equator and from high elevations to sea level.
Hepatocyte Nuclear Factor 4 alpha (HNF4α) Activation is Essential for Termination of Liver Regeneration
Authors: Huck Ian , Gunewardena Sumedha , Espanol-Suner Regina , Willenbring Holger , Apte Udayan
Published: April 2018

Hepatocyte Nuclear Factor 4 alpha (HNF4α) is critical for hepatic differentiation. Recent studies have highlighted its role in inhibition of hepatocyte proliferation and tumor suppression. However, the role of HNF4α in liver regeneration is not known. We hypothesized that hepatocytes modulate HNF4α activity when navigating between differentiated and proliferative states during liver regeneration. Western blot analysis revealed a rapid decline in nuclear and cytoplasmic HNF4α protein levels accompanied with decreased target gene expression within 1 hour after 2/3 partial hepatectomy (post-PH) in C57BL/6J mice. HNF4α protein expression did not recover to the pre-PH levels until day 3. Hepatocyte-specific deletion of HNF4α (HNF4α-KO) in mice resulted in 100% mortality post-PH despite increased proliferative marker expression throughout regeneration. Sustained loss of HNF4α target gene expression throughout regeneration indicated HNF4α-KO mice were unable to compensate for loss of HNF4α transcriptional activity. Deletion of HNF4α resulted in sustained proliferation accompanied by c-myc and cyclin D1 over expression and a complete deficiency of hepatocyte function after PH. Interestingly, overexpression of degradation-resistant HNF4α in hepatocytes did not prevent initiation of regeneration after PH. Finally, AAV8-mediated reexpression of HNF4α in hepatocytes of HNF4α-KO mice post-PH restored HNF4α protein levels, induced target gene expression and improved survival of HNF4α-KO mice post-PH. In conclusion, these data indicate that HNF4α reexpression following initial decrease is critical for hepatocytes to exit from cell cycle and resume function during the termination phase of liver regeneration. These results reveal the role of HNF4α in liver regeneration and have implications for therapy of liver failure.
Development of the P300 from childhood to adulthood: a multimodal EEG and MRI study
Authors: Overbye Knut , Huster Rene J. , Walhovd Kristine B. , Fjell Anders M. , Tamnes Christian K.
Published: April 2018

Maturation of attentional processes is central to cognitive development. The electrophysiological P300 is associated with rapid allocation of attention, and bridges stimulus and response processing. P300 is among the most studied and robust electrophysiological components, but how different subcomponents of the P300 develop from childhood to adulthood and relate to structural properties of the cerebral cortex is not well understood. We investigated age-related differences in both early visual and P300 components, and how individual differences in these components related to cortical structure in a cross-sectional sample of participants 8-19 years (n=86). Participants completed a three-stimulus visual oddball task while high-density EEG was recorded. Cortical surface area and thickness were estimated from T1-weighthed MRI. Group-level blind source separation of the EEG data identified two P300-like components, a fronto-central P300 and a parietal P300, as well as a component reflecting N1 and P2. Differences in activity across age were found for the parietal P300, N1 and P2, with the parietal P300 showing stronger activity for older participants, while N1 and P2 were stronger for younger participants. Stronger P300 components were positively associated with task performance, independently of age, while negative associations were found for P2 strength. Parietal P300 strength was age-independently associated with larger surface area in a region in left lateral inferior temporal cortex. We suggest that the age differences in component strength reflect development of attentional mechanisms, with increased brain responses to task-relevant stimuli representing an increasing ability to focus on relevant information and to respond accurately and efficiently.
Motor nuclei innervating eye muscles spared in mouse model of SOD1-linked ALS
Authors: Thomas Eleanor V. , Nagy Maria , Zhao Hongyu , Fenton Wayne A. , Horwich Arthur L.
Published: April 2018

The eye muscles of humans with either inherited or sporadic forms of ALS are relatively unaffected during disease progression, a function of sparing of the cranial nerve motor neurons supplying them. Here we observe that cranial nerve nuclei are also spared in a mouse model of inherited SOD1-linked ALS. We examined the cranial nerve motor nuclei in a mouse strain, G85R SOD1YFP, which carries a high copy transgene encoding a mutant human SOD1-YFP fusion protein, that exhibits florid YFP-fluorescent aggregates in spinal cord motor neurons and paralyzes by 6 months of age. We observed in the cranial nerve nuclei that innervate the eye, 3N (oculomotor), 4N (trochlear), and 6N (abducens), that there was little (4N, 6N) or no (3N) aggregation, in comparison with other motor nuclei, 5N (trigeminal), 7N (facial), and 12N (hypoglossal), in the latter two of which florid aggregation was observed. Correspondingly, the number of ChAT positive motor neurons in 3N of G85R SOD1YFP relative to that in 3N of ChAT-EGFP mice showed that there was no loss of motor neurons over time, whereas in 12N there was progressive loss of motor neurons, amounting to a loss of ∼30% from G85R SOD1YFP by end-stage. Thus, the sparing of extraocular motor neurons as occurs in humans with ALS appears to be replicated in our SOD1-linked ALS mouse strain, supporting the validity of the mouse model for studying this aspect of selective motor system loss in ALS. Comparisons of extraocular motor neurons (e.g., from 3N), resistant to ALS pathology, with other cranial motor neurons (e.g., from 12N), sensitive to such pathology, may thus be of value in understanding mechanisms of protection vs. susceptibility of motor neurons.
Robust predictions of specialized metabolism genes through machine learning
Authors: Moore Bethany M. , Wang Peipei , Fan Pengxiang , Leong Bryan , Schenck Craig A. , Lloyd John P. , Lehti-Shiu Melissa D. , Last Robert L. , Pichersky Eran , Shiu Shin-Han
Published: April 2018

Plant specialized metabolism (SM) enzymes produce lineage-specific metabolites with important ecological, evolutionary, and biotechnological implications. UsingArabidopsis thalianaas a model, we identified distinguishing characteristics of SM and GM (general metabolism, traditionally referred to as primary metabolism) genes through a detailed study of features including duplication pattern, sequence conservation, transcription, protein domain content, and gene network properties. Analysis of multiple sets of benchmark genes revealed that SM genes tend to be tandemly duplicated, co-expressed with their paralogs, narrowly expressed at lower levels, less conserved, and less well connected in gene networks relative to GM genes. Although the values of each of these features significantly differed between SM and GM genes, any single feature was ineffective at predicting SM from GM genes. Using machine learning methods to integrate all features, a well performing prediction model was established with a true positive rate of 0.87 and a true negative rate of 0.71. In addition, 86% of known SM genes not used to create the machine learning model were predicted as SM genes, further demonstrating its accuracy. We also demonstrated that the model could be further improved when we distinguished between SM, GM, and junction genes responsible for reactions shared by SM and GM pathways. Application of the prediction model led to the identification of 1,217A. thalianagenes with previously unknown functions, providing a global, high-confidence estimate of SM gene content in a plant genome.

Significance

Specialized metabolites are critical for plant-environment interactions, e.g., attracting pollinators or defending against herbivores, and are important sources of plant-based pharmaceuticals. However, it is unclear what proportion of enzyme-encoding genes play roles in specialized metabolism (SM) as opposed to general metabolism (GM) in any plant species. This is because of the diversity of specialized metabolites and the considerable number of incompletely characterized pathways responsible for their production. In addition, SM gene ancestors frequently played roles in GM. We evaluate features distinguishing SM and GM genes and build a computational model that accurately predicts SM genes. Our predictions provide candidates for experimental studies, and our modeling approach can be applied to other species that produce medicinally or industrially useful compounds.
Particle-templated emulsification for microfluidics-free digital biology
Authors: Hatori Makiko N. , Kim Samuel C. , Abate Adam R.
Published: April 2018

The compartmentalization of reactions in monodispersed droplets is valuable for applications across biology. However, the requirement of microfluidics to partition the sample into monodispersed droplets is a significant barrier that impedes implementation. Here, we introduce particle-templated emulsification, a method to encapsulate samples in monodispersed emulsions without microfluidics. By vortexing a mixture of hydrogel particles and sample solution, we encapsulate the sample in monodispersed emulsions that are useful for most droplet applications. We illustrate the method with ddPCR and single cell culture. The ability to encapsulate samples in monodispersed droplets without microfluidics should facilitate the implementation of compartmentalized reactions in biology.
Transient kinetic analysis of SWR1C-catalyzed H2A.Z deposition unravels the impact of nucleosome dynamics and the asymmetry of stepwise histone exchange
Authors: Singh Raushan K. , Watanabe Shinya , Bilsel Osman , Peterson Craig L.
Published: April 2018

The SWR1C chromatin remodeling enzyme catalyzes an ATP-dependent replacement of nucleosomal H2A with the H2A.Z variant, regulating key DNA-mediated processes, such as transcription and DNA repair. Here we investigate the transient kinetic mechanism of the histone exchange reaction employing ensemble FRET, fluorescence correlation spectroscopy (FCS), and the steady state kinetics of ATP hydrolysis. Our studies indicate that SWR1C modulates nucleosome dynamics on both the millisecond and microsecond timescales, poising the nucleosome for the dimer exchange reaction. The transient kinetic analysis of the remodeling reaction performed under single turnover conditions unraveled a striking asymmetry in the ATP-dependent replacement of nucleosomal dimers, promoted by localized DNA translocation. Taken together, our transient kinetic studies identify new intermediates and provide crucial insights into the SWR1C-catalyzed dimer exchange reaction, as well as shedding light on how the mechanics of H2A.Z deposition might contribute to transcriptional regulation in vivo.
Impact of DNA sequencing and analysis methods on 16S rRNA gene bacterial community analysis in dairy products
Authors: Xue Zhengyao , Kable Mary E , Marco Maria L
Published: April 2018

DNA sequencing and analysis methods were compared for 16S rRNA V4 PCR amplicon and gDNA mock communities encompassing nine bacterial species commonly found in milk and dairy products. The communities were examined using Illumina MiSeq and Ion Torrent PGM DNA sequencing methods followed by the QIIME 1 (UCLUST) and Divisive Amplicon Denoising Algorithm 2 (DADA2) data analysis pipelines including taxonomic comparisons to the Greengenes and Ribosomal Database Project (RDP) databases. Examination of the PCR amplicon mock community with these methods resulted in Operation Taxonomy Units (OTUs) and Amplicon Sequence Variants (ASVs) that ranged from a low of 13 to high of 118 and were dependent on the DNA sequencing method and read assembly step. The elevated numbers of OTUs and ASVs included assignments to spurious taxa as well as sequence variants of the nine species included in the mock community. Comparisons between the gDNA and PCR amplicon mock communities showed that combining gDNA from the different strains prior to PCR resulted in up to 8.9-fold greater numbers of spurious OTUs and ASVs. However, the DNA sequencing method and initial data assembly steps conferred the largest effects on predictions of bacterial diversity, independent of the mock community type (PCR amplicon or gDNA; Bray-Curtis R2 = 0.88 and weighted Unifrac, R2 = 0.32). Overall, DNA sequencing performed with the Ion Torrent PGM and analyzed with DADA2 and the Greengenes database resulted in the most accurate predictions of the mock community phylogeny, taxonomy, and diversity.

Importance

Validated methods are urgently needed to improve DNA-sequence based assessments of complex bacterial communities. In this study, we used 16S rRNA PCR amplicon and gDNA mock community standards, consisting of nine, dairy-associated bacterial species, to evaluate the most commonly applied 16S rRNA marker gene DNA sequencing and analysis platforms used in evaluating dairy and other bacterial habitats. Our results show that bacterial metataxonomic assessments are largely dependent on the DNA sequencing platform and read curation method used. DADA2 improved sequence annotation compared with QIIME 1, and when combined with the Ion Torrent PGM DNA sequencing platform and the Greengenes database for taxonomic assignment, the most accurate representation of the dairy mock community standards was reached. This approach will be useful for validating sample collection and DNA extraction methods and ultimately investigating bacterial population dynamics in milk and dairy-associated environments.
Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation
Authors: Brinkman Arie B. , Nik-Zainal Serena , Simmer Femke , Rodríguez-González F. Germán , Smid Marcel , Alexandrov Ludmil B. , Butler Adam , Martin Sancha , Davies Helen , Glodzik Dominik , Zou Xueqing , Ramakrishna Manasa , Staaf Johan , Ringnér Markus , Sieuwerts Anieta , Ferrari Anthony , Morganella Sandro , Fleischer Thomas , Kristensen Vessela , Gut Marta , van de Vijver Marc J. , Børresen-Dale Anne-Lise , Richardson Andrea L. , Thomas Gilles , Gut Ivo G. , Martens John W.M. , Foekens John A. , Stratton Mike , Stunnenberg Hendrik G.
Published: April 2018

Global loss of DNA methylation and CpG island (CGI) hypermethylation are regarded as key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which can extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. Using whole genome bisulfite sequencing (WGBS) of breast cancers, we comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of variation in DNA methylation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). However, significant repression effects on cancer-genes are negligible as tumor suppressor genes are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin of different cancers and may represent tissue-specific ‘silent’ regions of the genome, which tolerate instability at the epigenetic, transcriptomic and genetic level.
Replicative cellular age distributions in compartmentalised tissues
Authors: Böttcher Marvin A. , Werner Benjamin , Dingli David , Traulsen Arne
Published: April 2018

The cellular age distribution of hierarchically organized tissues can reveal important insights into the dynamics of cell differentiation and self-renewal and associated cancer risks. Here, we examine theoretically the effect of progenitor compartments with varying differentiation and self-renewal capacities on the resulting observable distributions of replicative cellular ages. We find that strongly amplifying progenitor compartments, i.e. compartments with high self-renewal capacities, substantially broaden the age distributions which become skewed towards younger cells with a long tail of few old cells. However, since mutations predominantly accumulate during cell division, a few old cells may considerably increase cancer risk. In contrast, if tissues are organised into many downstream compartments with low self-renewal capacity, the shape of the replicative cell distributions in more differentiated compartments are dominated by stem cell dynamics with little added variation. In the limiting case of a strict binary differentiation tree without self-renewal, the shape of the output distribution becomes indistinguishable from the shape of the input distribution. Our results suggest that a comparison of cellular age distributions between healthy and cancerous tissues may inform about dynamical changes within the hierarchical tissue structure, i.e. an acquired increased self-renewal capacity in certain tumours.
Hematopoietic Stem Cell Dynamics are Regulated by Progenitor Demand: Lessons from a Quantitative Modeling Approach
Authors: Klose Markus , Florian Maria Carolina , Geiger Hartmut , Glauche Ingmar
Published: April 2018

The prevailing view on murine hematopoiesis and on hematopoietic stem cells (HSC) in particular derives from experiments that are related to regeneration after irradiation and HSC transplantation. However, over the past years, different experimental techniques have been developed to investigate hematopoiesis under homeostatic conditions, thereby providing access to proliferation and differentiation rates of hematopoietic stem and progenitor cells in the unperturbed situation. Moreover, it has become clear that hematopoiesis undergoes distinct changes during aging with large effects on HSC abundance, lineage contribution, asymmetry of division and self-renewal potential. However, it is currently not fully resolved how stem and progenitor cells interact to respond to varying demands and how this balance is altered by an aging-induced shift in HSC polarity.

Here, we present anin-silicomodel to investigate the dynamics of HSC response to varying demand. By introducing an internal feedback between stem and progenitor cells, the model is suited to consistently describe both hematopoietic homeostasis and regeneration, including the limited regulation of HSCs in the homeostatic situation. The model further explains the age-dependent increase in phenotypic HSCs as a consequence of the cells’ inability to preserve divisional asymmetry.

Our model suggests a dynamically regulated population of intrinsically asymmetrically dividing HSCs as suitable control mechanism that adheres with many qualitative and quantitative findings on hematopoietic recovery after stress and aging. The modeling approach thereby illustrates how a mathematical formalism can support the conceptual and the quantitative understanding of regulatory principles in HSC biology.
The Receptor-Like Kinase AtVRLK1 Regulates Secondary Cell Wall Thickening
Authors: Huang Cheng , Zhang Rui , Gui Jinshan , Zhong Yu , Li Laigeng
Published: April 2018

During the growth and development of land plants, some specialized cells, such as tracheary elements, undergo secondary cell wall thickening. Secondary cell walls contain additional lignin, compared with primary cell walls, thus providing mechanical strength and potentially improving defenses against pathogens. However, the molecular mechanisms that initiate wall thickening are unknown. In this study, we identified an Arabidopsis (Arabidopsis thaliana) leucine-rich repeat receptor-like kinase, encoded by AtVRLK1 (Vascular-Related Receptor-Like Kinase1), that is expressed specifically in cells undergoing secondary cell wall thickening. Suppression of AtVRLK1 expression resulted in a range of phenotypes that included retarded early elongation of the inflorescence stem, shorter fibers, slower root growth, and shorter flower filaments. In contrast, up-regulation of AtVRLK1 led to longer fiber cells, reduced secondary cell wall thickening in fiber and vessel cells, and defects in anther dehiscence. Molecular and cellular analyses showed that down-regulation of AtVRLK1 promoted secondary cell wall thickening and up-regulation of AtVRLK1 enhanced cell elongation and inhibited secondary cell wall thickening. We propose that AtVRLK1 functions as a signaling component in coordinating cell elongation and cell wall thickening during growth and development.
The Tomato Mitogen-Activated Protein Kinase SlMPK1 Is as a Negative Regulator of the High-Temperature Stress Response
Authors: Ding Haidong , He Jie , Wu Yuan , Wu Xiaoxia , Ge Cailin , Wang Yijun , Zhong Silin , Peiter Edgar , Liang Jiansheng , Xu Weifeng
Published: April 2018

High-temperature (HT) stress is a major environmental stress that limits plant growth and development. MAPK cascades play key roles in plant growth and stress signaling, but their involvement in the HT stress response is poorly understood. Here, we describe a 47-kD MBP-phosphorylated protein (p47-MBPK) activated in tomato (Solanum lycopersicum) leaves under HT and identify it as SlMPK1 by tandem mass spectrometry analysis. Silencing of SlMPK1 in transgenic tomato plants resulted in enhanced tolerance to HT, while overexpression resulted in reduced tolerance. Proteomic analysis identified a set of proteins involved in antioxidant defense that are significantly more abundant in RNA interference-SlMPK1 plants than nontransgenic plants under HT stress. RNA interference-SlMPK1 plants also showed changes in membrane lipid peroxidation and antioxidant enzyme activities. Furthermore, using yeast two-hybrid screening, we identified a serine-proline-rich protein homolog, SlSPRH1, which interacts with SlMPK1 in yeast, in plant cells, and in vitro. We demonstrate that SlMPK1 can directly phosphorylate SlSPRH1. Furthermore, the serine residue serine-44 of SlSPRH1 is a crucial phosphorylation site in the SlMPK1-mediated antioxidant defense mechanism activated during HT stress. We also demonstrate that heterologous expression of SlSPRH1 in Arabidopsis (Arabidopsis thaliana) led to a decrease in thermotolerance and lower antioxidant capacity. Taken together, our results suggest that SlMPK1 is a negative regulator of thermotolerance in tomato plants. SlMPK1 acts by regulating antioxidant defense, and its substrate SlSPRH1 is involved in this pathway.
Influence of microstructure on symmetry determination of piezoceramics
Authors: Hinterstein M. , Mgbemere H. E. , Hoelzel M. , Rheinheimer W. , Adabifiroozjaei E. , Koshy P. , Sorrell C. C. , Hoffman M.
Published: April 2018

The origin of the complex reflection splitting in potassium sodium niobate doped with lithium and manganese was investigated using temperature-dependent high-resolution X-ray and neutron diffraction as well as electron probe microanalysis and scanning electron microscopy. Two structural models were developed from the diffraction data. A single-phase monoclinicPmmodel is known from the literature and is able to reproduce the diffraction patterns perfectly. However, a model with phase coexistence of two classical orthorhombicAmm2 phases can also reproduce the diffraction data with equal accuracy. Scanning electron microscopy in combination with electron probe microanalysis revealed segregation of theA-site substituents potassium and sodium. This favours the model with phase coexistence and confirms the need for comprehensive analyses with complementary methods to cover a broad range of length scales as well as to assess both average and local structure.
Identification of a secondary phase Ga2O3(ZnO)
m
in Ga-doped ZnO thermoelectric materials by a (3 + 1)-dimensional superspace model
Authors: Michiue Yuichi , Mori Takao
Published: April 2018

A unified structure model for the homologous compounds Ga2O3(ZnO)
m
in (3 + 1)-dimensional superspace was modified by refinements for samples of Ga2O3:ZnO = 1:n (n = 15, 23, 28, 33, 38). The first-order sine terms in the modulation functions decreased with increasing phase index m. The diffraction intensities of the thermoelectric material Ga2O3:ZnO = 1:98 were best fitted by a two-phase model containing the wurtzite structure (Ga-doped ZnO) and the homologous compound Ga2O3(ZnO)
s
, where s = 38.
From the source: student-centred guest lecturing in a chemical crystallography class
Authors: Zheng Shao-Liang , Chen Yu-Sheng , Wang Xiaoping , Hoffmann Christina , Volkov Anatoliy
Published: April 2018

Guest lecturing is an underutilized teaching strategy that provides depth and richness in college-level chemistry courses. The authors have found that student-centred guest lecturing that combines themed guest presentations, hands-on workshops (whenever possible) and small group conversations has yielded tremendous benefits. As a result, students have developed a lasting interest in chemical crystallography and have employed advanced experiments in their own research. The authors report on their experience in planning student-centred guest lecturing, advise on best practices, and demonstrate the long lasting positive impact on student learning and engagement.