bluuebunny/crossref_metadata_2025 huggingface dataset:
Silver Sulfadiazine Cream Treatment Results in More Wound Contraction and More Itch in a Standardized Porcine Scald Model
Authors: van den Brand Carlien S , van der Steen Lydia P E , Boekema Bouke , Paauw Nanne J , Ulrich Magda M W , Middelkoop Esther , Beelen Robert H J , Richters Cornelia D
Published: February 2021

A variety of dressings is available for the treatment of partial-thickness wounds, but none has strong evidence supporting their beneficial effect on healing. This may be due to variation in the type and depth of wounds in clinical studies. The aim of this study was to use a standardized porcine wound model to compare three dressings commonly used in burn centers for partial-thickness burns. Partial-thickness scalds were made on the flanks of pigs. Wounds were treated with silver sulfadiazine (SSD, flammazine), a hydrofiber dressing, or glycerol-preserved allogeneic (pig) skin. The healing process was monitored for 8 weeks. Macroscopic parameters were the itching behavior, the cosmetic appearance of the scars, and contraction. Microscopic parameters were the inflammatory response, myofibroblast influx, and the numbers of nerves. All wounds were closed on day 14 and wound infection did not occur. Treatment with SSD resulted in significantly more wound contraction compared to treatment with glycerol-preserved pig skin. Animals treated with SSD suffered more from itching (scratching) during the first 2 weeks after wounding. The number of nerves in healing wounds of these animals was significantly higher compared to wounds treated with hydrofiber dressing or allogeneic skin. In our standardized porcine partial-thickness wound model, treatment with SSD resulted in less favorable wound healing. Compared to treatment with glycerol-preserved allogeneic skin, SSD resulted in more contraction.
Spatially Targeted Biological Control of Mile-a-Minute Weed Using Rhinoncomimus latipes (Coleoptera: Curculionidae) and an Unmanned Aircraft System
Authors: Kim Jaewon , Huebner Cynthia D , Reardon Richard , Park Yong-Lak
Published: February 2021

Rhinoncomimus latipes Korotyaev is a specialist biocontrol agent of mile-a-minute weed, Persicaria perfoliata (L.) H. Gross (Caryophyllales: Polygonaceae). Currently, R. latipes is released by hand where the presence of the weed is readily detected. However, the hand-release method is not applicable to weed patches spread in hard-to-access areas. This study was conducted to develop a spatially targeted biocontrol strategy by using an unmanned aircraft system (UAS, a.k.a. drone) for the detection of P. perfoliata and aerial release of R. latipes. A ground survey was performed to locate P. perfoliata patches and then a rotary-wing UAS was flown at 15 different altitudes to determine the detectability of P. perfoliata patches. We developed an insect-release system including a pod that housed R. latipes for aerial release. The pod was 3D printed with biodegradable polyvinyl alcohol (PVA), and field tests were conducted to determine the ability of R. latipes to escape the pod and assess their post-release mortality and feeding ability. The results of this study showed that P. perfoliata patches were readily detectable on the aerial images taken at ≤15 m above the ground. More than 98% of R. latipes (n = 118) successfully escaped from the pod within 24 h after aerial deployment. There were no significant (P > 0.05) effects of PVA exposure on the mortality and feeding ability of R. latipes. These results indicate that aerial detection of P. perfoliata and deployment of R. latipes for spatially targeted biological control in hard-to-access areas can be accomplished using a rotary-wing UAS.
Colonization of Trees by Ambrosia Beetles (Coleoptera: Curculionidae: Scolytinae) Is Influenced by Duration of Flood Stress
Authors: Reding Michael E , Ranger Christopher M , Schultz Peter B
Published: February 2021

The ambrosia beetles Xylosandrus germanus (Blandford) and Xylosandrus crassiusculus (Motschulsky) bore into flood-stressed trees to establish colonies, but the influence of flooding duration on colonization is unknown. This relationship was examined by flooding trees for various time periods and evaluating colonization. In one experiment, X. germanus bored into 20 dogwood (Cornus florida L.) trees during a 3-d flood treatment. Ten trees dissected that season had no offspring present in tunnels; the remaining trees appeared healthy and bloomed the following spring. In another experiment, dogwood trees were flooded for 3 or 7 d and then dissected to assess colonization. The incidence of superficial (short unbranched) and healed (callus tissue in entrance) tunnels was greater in the 3-d trees, while the incidence of tunnels with X. germanus or offspring was greater in the 7-d trees. Four experiments (three in Ohio and one in Virginia) had flood treatments of 0 (nonflooded), 3, 5, 7, and 10 d. Numbers of tunnel entrances, tunnels with X. germanus, and incidence of tunnels with offspring or live foundresses tended to increase as flood duration increased on apple (Malus × domestica Borkh.), dogwood, and redbud (Cercis canadensis L.) in Ohio and redbud in Virginia. Nonflooded trees in Ohio had no boring activity, but ambrosia beetles bored into three nonflooded trees in Virginia. Indicators of unsuccessful colonization, such as superficial tunnels and healing, decreased as flood duration increased. These results suggest tree crops may recover from boring by ambrosia beetles following short-duration flood events, and not necessarily require culling.
Efficient Harvesting of Safe Edible Grasshoppers: Evaluation of Modified Drums and Light-Emitting Diode Bulbs for Harvesting Ruspolia differens (Orthoptera: Tettigoniidae) in Uganda
Authors: Sengendo F , Subramanian S , Chemurot M , Tanga C M , Egonyu J P
Published: February 2021

Ruspolia differens (Serville) (Orthoptera: Tettigoniidae) is a delicacy in many African countries. It is commonly mass-harvested from the wild using light traps consisting of energy-intensive mercury bulbs which pollute the environment when poorly disposed. The catch is collected using open-ended drums which are inefficient in retaining the insects. The drums also collect nontarget insects including those that produce toxic chemicals (such as pederin) that cause severe burns to human skin. To prevent escape of trapped R. differens, trappers apply potentially hazardous substances like waste cooking oil on the walls of drums. Here, we modified the collection drum by fitting a funnel to retain R. differens; and partitioned it into three compartments with wire meshes of variable sizes to filter nontarget insects. Additionally, we replaced mercury bulbs with light-emitting diode (LED) bulbs which are energy-efficient. We evaluated the performance of the modified R. differens trap (modified drums and LED bulbs) compared to the current collection drums and mercury bulbs. The catch of R. differens in the modified drums was comparable to that of current drums. Nontarget insects were significantly filtered from the catch collected in modified drums compared to the current drums. Further, LED bulbs of 400 W trapped a comparable quantity of R. differens as 400 W mercury bulbs, but with less than half the consumption of electricity compared to the mercury bulbs. We concluded that modified R. differens light traps have better energy-use efficiency and ensure safety to collectors, processors, and consumers.
Brown Stink Bug (Hemiptera: Pentatomidae) Damage to Seedling Corn and Impact on Grain Yield
Authors: Bryant Tim B , Babu Arun , Reisig Dominic D
Published: February 2021

Brown stink bugs, Euschistus servus, are an important early-season pest of field corn in the southeastern United States. Feeding in the early stages of corn development can lead to a number of growth deformities and deficiencies and, ultimately, a reduction in yield. An observational and two experimentally manipulated trials were conducted in 2017 and 2018 to 1) determine optimal timing for assessing brown stink bug damage, 2) assess the level of damage from which yield compensation can occur, and 3) examine the relationship between brown stink bug density and early-season damage and yield. Fields were identified with infestations of brown stink bugs and a damage rating system for early stages of corn was established. Varying rates of brown stink bug densities were introduced using field cages and damage was assessed throughout the season. The density and duration of stink bug infestations were critical factors for damage potential, with each day of active feeding per plant resulting in a loss of ~14 kg/ha in yield. The level of damage in early stages of corn was categorized into easily identifiable groups, with only the most severe damage leading to a reduction in yield. Moderate and minimal feeding damage did not result in yield loss. This study emphasizes the need for early and frequent scouting of corn to determine the risk of damage and yield loss from brown stink bugs. Results from this study can be used to help develop management programs for brown stink bugs in the early vegetative stages of field corn.
Dopamine Receptor Antagonists, Radiation, and Cholesterol Biosynthesis in Mouse Models of Glioblastoma
Authors: Bhat Kruttika , Saki Mohammad , Cheng Fei , He Ling , Zhang Le , Ioannidis Angeliki , Nathanson David , Tsang Jonathan , Bensinger Steven J , Nghiemphu Phioanh Leia , Cloughesy Timothy F , Liau Linda M , Kornblum Harley I , Pajonk Frank
Published: February 2021

Background

Glioblastoma is the deadliest brain tumor in adults, and the standard of care consists of surgery followed by radiation and treatment with temozolomide. Overall survival times for patients suffering from glioblastoma are unacceptably low indicating an unmet need for novel treatment options.

Methods

Using patient-derived HK-157, HK-308, HK-374, and HK-382 glioblastoma lines, the GL261 orthotopic mouse models of glioblastoma, and HK-374 patient-derived orthotopic xenografts, we tested the effect of radiation and the dopamine receptor antagonist quetiapine on glioblastoma self-renewal in vitro and survival in vivo. A possible resistance mechanism was investigated using RNA-sequencing. The blood-brain-barrier–penetrating statin atorvastatin was used to overcome this resistance mechanism. All statistical tests were 2-sided.

Results

Treatment of glioma cells with the dopamine receptor antagonist quetiapine reduced glioma cell self-renewal in vitro, and combined treatment of mice with quetiapine and radiation prolonged the survival of glioma-bearing mice. The combined treatment induced the expression of genes involved in cholesterol biosynthesis. This rendered GL261 and HK-374 orthotopic tumors vulnerable to simultaneous treatment with atorvastatin and further statistically significantly prolonged the survival of C57BL/6 (n = 10 to 16 mice per group; median survival not reached; log-rank test, P < .001) and NOD Scid gamma mice (n = 8 to 21 mice per group; hazard ratio = 3.96, 95% confidence interval = 0.29 to 12.40; log-rank test, P < .001), respectively.

Conclusions

Our results indicate promising therapeutic efficacy with the triple combination of quetiapine, atorvastatin, and radiation treatment against glioblastoma without increasing the toxicity of radiation. With both drugs readily available for clinical use, our study could be rapidly translated into a clinical trial.
Screening for Depression in Younger Breast Cancer Survivors: Outcomes From Use of the 9-item Patient Health Questionnaire
Authors: Ganz Patricia A , Bower Julienne E , Partridge Ann H , Wolff Antonio C , Thorner Elissa D , Joffe Hadine , Irwin Michael R , Petersen Laura , Crespi Catherine M
Published: February 2021

Background

Major cancer organizations recommend depression screening in patients and survivors. The 9-item Patient Health Questionnaire (PHQ-9) is often suggested, with limited information about its use.

Methods

Enrollment data collected from younger breast cancer survivors participating in a behavioral intervention trial were used to examine the relationship between PHQ-9 scores (range = 0-27), patient characteristics, and responses to standardized psychosocial assessment tools. Major depressive disorder criterion was met if responses to the first 2 PHQ-9 items (range = 0-6) were 3 or greater. The sample was categorized by total PHQ-9 scores: less than 5 (minimal depressive symptoms), 5-9 (mild to moderate depressive symptoms), and 10 or greater (moderate to severe depression). PHQ-9 category associations with medical, demographic, psychosocial, and behavioral characteristics were examined using analysis of variance for continuous variables and χ2 tests for categorical variables.

Results

A total of 231 women met the study prescreening eligibility criterion of mild depressive symptoms and enrolled in the study. On average, they were 45.2 years old and 2.6 years since diagnosis. At enrollment, 22.1% met the screening criterion for possible major depressive disorder; among those with PHQ-9 scores of 10 or greater, 58.3% met this criterion. Anxiety, fatigue, insomnia, and intrusive thoughts about cancer were frequent and were associated with depressive symptom severity (all P < .001). In contrast, neither demographic nor cancer treatment characteristics were associated with depressive symptoms.

Conclusions

Depressive symptoms in this selected sample of younger breast cancer survivors were independent of demographic characteristics or cancer treatment history, suggesting that depression screening is necessary to detect uncontrolled depressive symptoms.
Insulinotropic and antidiabetic properties of Eucalyptus citriodora leaves and isolation of bioactive phytomolecules
Authors: Ansari Prawej , Flatt Peter R , Harriott Patrick , Abdel-Wahab Yasser H A
Published: February 2021

Objective

The aim of this study was to delineate the mechanisms of action of the plant Eucalyptus citriodora used traditionally for the treatment of type 2 diabetes.

Methods

Insulin secretion and signal transduction were measured using clonal pancreatic β-cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation and phytoconstituents were identified by RP-HPLC followed by LC-MS.

Key findings

Eucalyptus citriodora stimulated 1.2–4.6-fold insulin release that was inhibited by the Ca2+-channel blocker, verapamil, KATP-channel opener, diazoxide and Ca2+ free conditions. The effect was potentiated by IBMX and preserved in presence of tolbutamide or 30 mM KCl. The action mechanism involved membrane depolarization and elevation of intracellular Ca2+. Eucalyptus citriodora also significantly increased glucose uptake by 3T3-L1 cells and inhibited digestion of starch, glucose absorption, DPP-IV enzyme and glycation of protein. Administration of E. citriodora (250 mg/5 ml/kg) for 9 days to HFF obese-diabetic rats improved glycaemic control and β-cell function. The isolated phytoconstituents responsible for the β-cell actions included quercitrin, isoquercitrin and rhodomyrtosone E.

Conclusions

Eucalyptus citriodora improves glycaemic control via multiple mechanisms. Further studies are required to assess the utility of the plant or active constituents in the therapy of type 2 diabetes.
A comparative study of high-dose-rate brachytherapy boost combined with external beam radiation therapy versus external beam radiation therapy alone for high-risk prostate cancer
Authors: Oshikane Tomoya , Kaidu Motoki , Abe Eisuke , Ohta Atsushi , Saito Hirotake , Nakano Toshimichi , Honda Moe , Tanabe Satoshi , Utsunomiya Satoru , Sasamoto Ryuta , Ishizaki Fumio , Kasahara Takashi , Nishiyama Tsutomu , Tomita Yoshihiko , Aoyama Hidefumi , Ishikawa Hiroyuki
Published: February 2021

We aimed to compare the outcomes of high-dose-rate brachytherapy (HDR-BT) boost and external beam radiation therapy (EBRT) alone for high-risk prostate cancer. This was a single-center, retrospective and observational study. Consecutive patients who underwent initial radical treatment by HDR-BT boost or EBRT alone from June 2009 to May 2016 at the Niigata University Medical and Dental Hospital, Japan were included. A total of 96 patients underwent HDR-BT boost, and 61 underwent EBRT alone. The prescription dose of HDR-BT boost was set to 18 Gy twice a day with EBRT 39 Gy/13 fractions. The dose for EBRT alone was mostly 70 Gy/28 fractions. The high-risk group received >6 months of prior androgen deprivation therapy. Overall survival, biochemical-free survival, local control and distant metastasis-free survival rates at 5 years were analyzed. The incidence of urological and gastrointestinal late adverse events of Grade 2 and above was also summarized. In the National Comprehensive Cancer Network (NCCN) high-risk calssification, HDR-BT boost had a significantly higher biochemical-free survival rate at 5 years (98.9% versus 90.7%, P = 0.04). Urethral strictures were more common in the HDR-BT boost group. We will continuously observe the progress of the study patients and determine the longer term results.
Forced Migration and the Quest for Normality: Post-Migratory Experiences of Traumatized Iraqi Refugees in Norway
Authors: Sarpong Sarah P , Opaas Marianne
Published: February 2021

The study investigates how a clinical sample of Iraqi refugee men speak about their lives in Norway, specifically on their experiences related to factors known to be influential in the restoration of normality in exile. Using thematic analysis (TA), the major themes extracted in this study relate to employment, finances and social support. These themes were all found to be influential in the lives of the participants, encouraging a sense of normality when in place. Drawing from Conservation of resources theory and The resource-based model of refugee adaptation, the key-findings suggest that (1) access to resources are regulated by social and political conditions and that (2) resource spirals perpetuate positive and negative cycles in the lives of the participants. We also engage in discussions on social inequality, discuss implications of the findings for service providers, and finally we make suggestions for future research.
Functional testicular torsion secondary to an incarcerated inguinal hernia in a 4-month old: complete recovery at 18-hours
Authors: Taylor Gregory M , Strachan Christian C
Published: February 2021

One of the most common urological emergencies encountered in pediatric patients in the emergency department (ED) is the acute scrotum. We present the case of a 4-month-old male that presented to our community ED with scrotal swelling and vomiting of 16-hours duration. He was diagnosed with a functional testicular torsion from an incarcerated inguinal hernia, transferred to a hospital with pediatric urological capabilities and was taken to the operating room ~2 hours later. His hospital course was unremarkable, and he was discharged on day 3, having made a full recovery without any loss of bowel or testicle. There have only been a handful of cases in the literature of a pediatric patient presenting with a functional testicular torsion as a result of spermatic cord compression from an indirect inguinal hernia, with no reported cases of complete salvage at nearly 18 hours since symptom onset.
A case of a retained chest drain
Authors: Waqanivavalagi Steve W F R , Chaudhuri Krish
Published: February 2021

Retention of an intercostal drain segment is an uncommon and infrequently reported complication of underwater seal drain use. We report the case of a 66-year-old New Zealand European male who underwent bilateral lung transplantation for severe chronic obstructive pulmonary disease and bronchiectasis. The patient required a return to the operating room for exploratory surgery after an intercostal drain severed during its attempted removal and became retained within the chest cavity. A deep suture had inadvertently been passed around the chest drain intraoperatively. In the event of such a complication, prompt recognition and removal of the retained segment is required. This novel case is reported to highlight the possibility of an entrapped suture as a cause of resistance when attempting to remove an intercostal drain. Kinking on a chest X-ray may also point to this problem, and senior input should be sought early if radiographic findings are coupled with clinical difficulties.
Quantitative analysis of character networks in Polish 19th- and 20th-century novels
Authors: Kubis Marek
Published: February 2021

This article presents a study on induction and quantitative analysis of character networks inferred from Polish novels. The corpus compiled  for this study includes both 19th- and 20th-century literary works in the form of electronic editions of novels and OCR-derived texts obtained from publicly available sources. The natural language processing pipeline developed for the purpose of inducing character networks from novels is described. The structural properties of the inferred character networks are investigated, and significant differences between the properties of networks induced from 19th- to 20th-century novels are demonstrated.
The sensitivity of stellar feedback to IMF averaging versus IMF sampling in galaxy formation simulations
Authors: Smith Matthew C
Published: February 2021

Galaxy formation simulations frequently use initial mass function (IMF) averaged feedback prescriptions, where star particles are assumed to represent single stellar populations that fully sample the IMF. This approximation breaks down at high mass resolution, where stochastic variations in stellar populations become important. We discuss various schemes to populate star particles with stellar masses explicitly sampled from the IMF. We use Monte Carlo numerical experiments to examine the ability of the schemes to reproduce an input IMF in an unbiased manner while conserving mass. We present our preferred scheme which can easily be added to pre-existing star formation prescriptions. We then carry out a series of high-resolution isolated simulations of dwarf galaxies with supernovae (SNe), photoionization, and photoelectric heating to compare the differences between using IMF averaged feedback and explicitly sampling the IMF. We find that if SNe are the only form of feedback, triggering individual SNe from IMF averaged rates gives identical results to IMF sampling. However, we find that photoionization is more effective at regulating star formation when IMF averaged rates are used, creating more, smaller H ii regions than the rare, bright sources produced by IMF sampling. We note that the increased efficiency of the IMF averaged feedback versus IMF sampling is not necessarily a general trend and may be reversed depending on feedback channel, resolution and other details. However, IMF sampling is always the more physically motivated approach. We conservatively suggest that it should be used for star particles less massive than $\sim 500\, \mathrm{M_\odot }$.
A circular polarization survey for radio stars with the Australian SKA Pathfinder
Authors: Pritchard Joshua , Murphy Tara , Zic Andrew , Lynch Christene , Heald George , Kaplan David L , Anderson Craig , Banfield Julie , Hale Catherine , Hotan Aidan , Lenc Emil , Leung James K , McConnell David , Moss Vanessa A , Raja Wasim , Stewart Adam J , Whiting Matthew
Published: February 2021

We present results from a circular polarization survey for radio stars in the Rapid ASKAP Continuum Survey (RACS). RACS is a survey of the entire sky south of δ = +41○ being conducted with the Australian Square Kilometre Array Pathfinder telescope (ASKAP) over a 288 MHz wide band centred on 887.5 MHz. The data we analyse include Stokes I and V polarization products to an RMS sensitivity of 250 μJy PSF−1. We searched RACS for sources with fractional circular polarization above 6 per cent, and after excluding imaging artefacts, polarization leakage, and known pulsars we identified radio emission coincident with 33 known stars. These range from M-dwarfs through to magnetic, chemically peculiar A- and B-type stars. Some of these are well-known radio stars such as YZ CMi and CU Vir, but 23 have no previous radio detections. We report the flux density and derived brightness temperature of these detections and discuss the nature of the radio emission. We also discuss the implications of our results for the population statistics of radio stars in the context of future ASKAP and Square Kilometre Array surveys.
Field linkage and magnetic helicity density
Authors: Lund K , Jardine M , Russell A J B , Donati J-F , Fares R , Folsom C P , Jeffers S V , Marsden S C , Morin J , Petit P , See V
Published: February 2021

The helicity of a magnetic field is a fundamental property that is conserved in ideal MHD. It can be explored in the stellar context by mapping large-scale magnetic fields across stellar surfaces using Zeeman–Doppler imaging. A recent study of 51 stars in the mass range 0.1–1.34 M⊙ showed that the photospheric magnetic helicity density follows a single power law when plotted against the toroidal field energy, but splits into two branches when plotted against the poloidal field energy. These two branches divide stars above and below ∼0.5 M⊙. We present here a novel method of visualizing the helicity density in terms of the linkage of the toroidal and poloidal fields that are mapped across the stellar surface. This approach allows us to classify the field linkages that provide the helicity density for stars of different masses and rotation rates. We find that stars on the lower mass branch tend to have toroidal fields that are non-axisymmetric and so link through regions of positive and negative poloidal field. A lower mass star may have the same helicity density as a higher mass star, despite having a stronger poloidal field. Lower mass stars are therefore less efficient at generating large-scale helicity.
Size Variation of the Nonrecombining Region on the Mating-Type Chromosomes in the Fungal Podospora anserina Species Complex
Authors: Hartmann Fanny E , Ament-Velásquez Sandra Lorena , Vogan Aaron A , Gautier Valérie , Le Prieur Stephanie , Berramdane Myriam , Snirc Alodie , Johannesson Hanna , Grognet Pierre , Malagnac Fabienne , Silar Philippe , Giraud Tatiana
Published: February 2021

Sex chromosomes often carry large nonrecombining regions that can extend progressively over time, generating evolutionary strata of sequence divergence. However, some sex chromosomes display an incomplete suppression of recombination. Large genomic regions without recombination and evolutionary strata have also been documented around fungal mating-type loci, but have been studied in only a few fungal systems. In the model fungus Podospora anserina (Ascomycota, Sordariomycetes), the reference S strain lacks recombination across a 0.8-Mb region around the mating-type locus. The lack of recombination in this region ensures that nuclei of opposite mating types are packaged into a single ascospore (pseudohomothallic lifecycle). We found evidence for a lack of recombination around the mating-type locus in the genomes of ten P. anserina strains and six closely related pseudohomothallic Podospora species. Importantly, the size of the nonrecombining region differed between strains and species, as indicated by the heterozygosity levels around the mating-type locus and experimental selfing. The nonrecombining region is probably labile and polymorphic, differing in size and precise location within and between species, resulting in occasional, but infrequent, recombination at a given base pair. This view is also supported by the low divergence between mating types, and the lack of strong linkage disequilibrium, chromosomal rearrangements, transspecific polymorphism and genomic degeneration. We found a pattern suggestive of evolutionary strata in P. pseudocomata. The observed heterozygosity levels indicate low but nonnull outcrossing rates in nature in these pseudohomothallic fungi. This study adds to our understanding of mating-type chromosome evolution and its relationship to mating systems.
Hawk-Seq™ differentiates between various mutations in Salmonella typhimurium TA100 strain caused by exposure to Ames test-positive mutagens
Authors: Otsubo Yuki , Matsumura Shoji , Ikeda Naohiro , Morita Osamu
Published: February 2021

A precise understanding of differences in genomic mutations according to the mutagenic mechanisms detected in mutagenicity data is required to evaluate the carcinogenicity of environmental mutagens. Recently, we developed a highly accurate genome sequencing method, ‘Hawk-Seq™’, that enables the detection of mutagen-induced genome-wide mutations. However, its applicability to detect various mutagens and identify differences in mutational profiles is not well understood. Thus, we evaluated DNA samples from Salmonella typhimurium TA100 exposed to 11 mutagens, including alkylating agents, aldehydes, an aromatic nitro compound, epoxides, aromatic amines and polycyclic aromatic hydrocarbons (PAHs). We extensively analysed mutagen-induced mutational profiles and studied their association with the mechanisms of mutagens. Hawk-Seq™ sensitively detected mutations induced by all 11 mutagens, including one that increased the number of revertants by approximately 2-fold in the Ames test. Although the sensitivity for less water-soluble mutagens was relatively low, we increased the sensitivity to obtain high-resolution spectra by modifying the exposure protocol. Moreover, two epoxides indicated similar 6- or 96-dimensional mutational patterns; likewise, three SN1-type alkylating agents indicated similar mutational patterns, suggesting that the mutational patterns are compound category specific. Meanwhile, an SN2 type alkylating agent exhibited unique mutational patterns compared to those of the SN1 type alkylating agents. Although the mutational patterns induced by aldehydes, the aromatic nitro compound, aromatic amines and PAHs did not differ substantially from each other, the maximum total base substitution frequencies (MTSFs) were similar among mutagens in the same structural groups. Furthermore, the MTSF was found to be associated with the carcinogenic potency of some direct-acting mutagens. These results indicate that our method can generate high-resolution mutational profiles to identify characteristic features of each mutagen. The detailed mutational data obtained by Hawk-Seq™ can provide useful information regarding mutagenic mechanisms and help identify its association with the carcinogenicity of mutagens without requiring carcinogenicity data.
Discovery of molecular features underlying the morphological landscape by integrating spatial transcriptomic data with deep features of tissue images
Authors: Bae Sungwoo , Choi Hongyoon , Lee Dong Soo
Published: February 2021

Profiling molecular features associated with the morphological landscape of tissue is crucial for investigating the structural and spatial patterns that underlie the biological function of tissues. In this study, we present a new method, spatial gene expression patterns by deep learning of tissue images (SPADE), to identify important genes associated with morphological contexts by combining spatial transcriptomic data with coregistered images. SPADE incorporates deep learning-derived image patterns with spatially resolved gene expression data to extract morphological context markers. Morphological features that correspond to spatial maps of the transcriptome were extracted by image patches surrounding each spot and were subsequently represented by image latent features. The molecular profiles correlated with the image latent features were identified. The extracted genes could be further analyzed to discover functional terms and exploited to extract clusters maintaining morphological contexts. We apply our approach to spatial transcriptomic data from different tissues, platforms and types of images to demonstrate an unbiased method that is capable of obtaining image-integrated gene expression trends.
Increased dishevelled associated activator of morphogenesis 2, a new podocyte-associated protein, in diabetic nephropathy
Authors: Qi Chenyang , Alsomali Faten , Zhong Jinyong , Harris Raymond C , Kon Valentina , Yang Haichun , Fogo Agnes B
Published: February 2021

Background

Previously, by using proteomic analysis and RNA sequencing in isolated glomeruli, we identified several novel differentially expressed proteins in human and mouse diabetic nephropathy (DN) versus controls, including dishevelled associated activator of morphogenesis 2 (DAAM2). DAAM2 binds the Wnt effector Dvl. We aimed to study possible contributions of DAAM2 to DN.

Methods

We assessed DAAM2 by immunostaining in non-cancer regions of human nephrectomy (Nx), DN and normal donor kidney tissues. We also examined DAAM2 in DN mice (db/db eNOS−/−) and Nx mice. DN mice treated with angiotensin-converting enzyme inhibitor (ACEI), dipeptidyl peptidase 4 inhibitor (DPP4I) or vehicle were compared. DAAM2 was knocked down in primary cultured podocytes by small interfering RNA to study its effects on cell function.

Results

In normal human glomeruli, DAAM2 was expressed only on podocytes. DAAM2 expression was increased in both Nx and DN versus normal donors. Podocyte DAAM2 expression was increased in DN and Nx mouse models. Glomerular DAAM2 expression correlated with glomerular size and was decreased significantly by ACEI while DPP4I only numerically reduced DAAM2. In primary cultured podocytes, knockdown of DAAM2 enhanced adhesion, slowed migration, activated Wnt–β-catenin signaling and downregulated mammalian target of rapamycin complex 1 (mTORC1) and Rho activity.

Conclusions

Podocyte DAAM2 is upregulated in both Nx and DN, which could be contributed to by glomerular hypertrophy. We hypothesize that DAAM2 regulates podocyte function through the mTORC1, Wnt/β-catenin and Rho signaling pathways.
On the potential of wearable bioimpedance for longitudinal fluid monitoring in end-stage kidney disease
Authors: Lindeboom Lucas , Lee Seulki , Wieringa Fokko , Groenendaal Willemijn , Basile Carlo , van der Sande Frank , Kooman Jeroen
Published: February 2021

Bioimpedance spectroscopy (BIS) has proven to be a promising non-invasive technique for fluid monitoring in haemodialysis (HD) patients. While current BIS-based monitoring of pre- and post-dialysis fluid status utilizes benchtop devices, designed for intramural use, advancements in micro-electronics have enabled the development of wearable bioimpedance systems. Wearable systems meanwhile can offer a similar frequency range for current injection as commercially available benchtop devices. This opens opportunities for unobtrusive longitudinal fluid status monitoring, including transcellular fluid shifts, with the ultimate goal of improving fluid management, thereby lowering mortality and improving quality of life for HD patients. Ultra-miniaturized wearable devices can also offer simultaneous acquisition of multiple other parameters, including haemodynamic parameters. Combination of wearable BIS and additional longitudinal multiparametric data may aid in the prevention of both haemodynamic instability as well as fluid overload. The opportunity to also acquire data during interdialytic periods using wearable devices likely will give novel pathophysiological insights and the development of smart (predicting) algorithms could contribute to personalizing dialysis schemes and ultimately to autonomous (nocturnal) home dialysis. This review provides an overview of current research regarding wearable bioimpedance, with special attention to applications in end-stage kidney disease patients. Furthermore, we present an outlook on the future use of wearable bioimpedance within dialysis practice.
The Medicago truncatula Sugar Transport Protein 13 and Its Lr67res-Like Variant Confer Powdery Mildew Resistance in Legumes via Defense Modulation
Authors: Gupta Megha , Dubey Shubham , Jain Deepti , Chandran Divya
Published: February 2021

Obligate biotrophic pathogens like the pea powdery mildew© (PM) Erysiphe pisi establish long-term feeding relationships with their host, during which they siphon sugars from host cells through haustoria. Plants in turn deploy sugar transporters to restrict carbon allocation toward pathogens, as a defense mechanism. Studies in Arabidopsis have shown that sugar transport protein 13 (STP13), a proton-hexose symporter involved in apoplasmic hexose retrieval, contributes to bacterial and necrotrophic fungal resistance by limiting sugar flux toward these pathogens. By contrast, expression of Lr67res,a transport-deficient wheat STP13 variant harboring two amino acid substitutions (G144R and V387L), conferred resistance against biotrophic fungi in wheat and barley, indicating its broad applicability in disease management. Here, we investigated the role of STP13 and STP13G144R in legume–PM interactions. We show that Medicago truncatula STP13.1 is a proton-hexose symporter involved in basal resistance against PM and indirectly show that Lr67res-mediated PM resistance, so far reported only in monocots, is transferable to legumes. Among the 30 MtSTPs, STP13.1 exhibited the highest fold induction in PM-challenged leaves and was also responsive to chitosan, ABA and sugar treatment. Functional assays in yeast showed that introduction of the G144R mutation but not V388L abolished MtSTP13.1’s hexose uptake ability. Virus-induced gene silencing of MtSTP13 repressed pathogenesis-related (PR) gene expression and enhanced PM susceptibility in M. truncatula whereas transient overexpression of MtSTP13.1 or MtSTP13.1G144R in pea induced PR and isoflavonoid pathway genes and enhanced PM resistance. We propose a model in which STP13.1-mediated sugar signaling triggers defense responses against PM in legumes.
TOR coordinates nucleotide availability with ribosome biogenesis in plants
Authors: Busche Michael , Scarpin M Regina , Hnasko Robert , Brunkard Jacob O
Published: February 2021

TARGET OF RAPAMYCIN (TOR) is a conserved eukaryotic Ser/Thr protein kinase that coordinates growth and metabolism with nutrient availability. We conducted a medium-throughput functional genetic screen to discover essential genes that promote TOR activity in plants, and identified a critical regulatory enzyme, cytosolic phosphoribosyl pyrophosphate (PRPP) synthetase (PRS4). PRS4 synthesizes cytosolic PRPP, a key upstream metabolite in nucleotide synthesis and salvage pathways. We found that prs4 knockouts are embryo-lethal in Arabidopsis thaliana, and that silencing PRS4 expression in Nicotiana benthamiana causes pleiotropic developmental phenotypes, including dwarfism, aberrant leaf shape, and delayed flowering. Transcriptomic analysis revealed that ribosome biogenesis is among the most strongly repressed processes in prs4 knockdowns. Building on these results, we discovered that TOR activity is inhibited by chemical or genetic disruption of nucleotide biosynthesis, but that this effect can be reversed by supplying plants with nucleobases. Finally, we show that TOR transcriptionally promotes nucleotide biosynthesis to support the demands of ribosomal RNA synthesis. We propose that TOR coordinates ribosome biogenesis with nucleotide availability in plants to maintain metabolic homeostasis and support growth.
Rice and Arabidopsis homologs of yeast CHROMOSOME TRANSMISSION FIDELITY PROTEIN 4 commonly interact with Polycomb complexes but exert divergent regulatory functions
Authors: Zhang Pingxian , Zhu Chunmei , Geng Yuke , Wang Yifan , Yang Ying , Liu Qing , Guo Weijun , Chachar Sadaruddin , Riaz Adeel , Yan Shuangyong , Yang Liwen , Yi Keke , Wu Changyin , Gu Xiaofeng
Published: February 2021

Both genetic and epigenetic information must be transferred from mother to daughter cells during cell division. The mechanisms through which information about chromatin states and epigenetic marks like histone 3 lysine 27 trimethylation (H3K27me3) are transferred have been characterized in animals; these processes are less well understood in plants. Here, based on characterization of a dwarf rice (Oryza sativa) mutant (dwarf-related wd40 protein 1, drw1) deficient for yeast CTF4 (CHROMOSOME TRANSMISSION FIDELITY PROTEIN 4), we discovered that CTF4 orthologs in plants use common cellular machinery yet accomplish divergent functional outcomes. Specifically, drw1 exhibited no flowering-related phenotypes (as in the putatively orthologous Arabidopsis thaliana eol1 mutant), but displayed cell cycle arrest and DNA damage responses. Mechanistically, we demonstrate that DRW1 sustains normal cell cycle progression by modulating the expression of cell cycle inhibitors KIP-RELATED PROTEIN 1 (KRP1) and KRP5, and show that these effects are mediated by DRW1 binding their promoters and increasing H3K27me3 levels. Thus, although CTF4 orthologs ENHANCER OF LHP1 1 (EOL1) in Arabidopsis and DRW1 in rice are both expressed uniquely in dividing cells, commonly interact with several Polycomb complex subunits, and promote H3K27me3 deposition, we now know that their regulatory functions diverged substantially during plant evolution. Moreover, our work experimentally illustrates specific targets of CTF4/EOL1/DRW1, their protein–proteininteraction partners, and their chromatin/epigenetic effects in plants.
Current progress in Striga management
Authors: Jamil Muhammad , Kountche Boubacar A , Al-Babili Salim
Published: February 2021

The Striga, particularly S. he rmonthica, problem has become a major threat to food security, exacerbating hunger and poverty in many African countries. A number of Striga control strategies have been proposed and tested during the past decade, however, further research efforts are still needed to provide sustainable and effective solutions to the Striga problem. In this paper, we provide an update on the recent progress and the approaches used in Striga management, and highlight emerging opportunities for developing new technologies to control this enigmatic parasite.
YSL3-mediated copper distribution is required for fertility, seed size and protein accumulation in Brachypodium
Authors: Sheng Huajin , Jiang Yulin , Rahmati Maryam , Chia Ju-Chen , Dokuchayeva Tatyana , Kavulych Yana , Zavodna Tetiana-Olena , Mendoza Patrick N , Huang Rong , Smieshka Louisa M , Miller Julia , Woll Arthur R , Terek Olga I , Romanyuk Nataliya D , Piñeros Miguel , Zhou Yonghong , Vatamaniuk Olena K
Published: February 2021

Addressing the looming global food security crisis requires the development of high-yielding crops. In agricultural soils, deficiency in the micronutrient copper significantly decreases grain yield in wheat (Triticum aestivum), a globally important crop. In cereals, grain yield is determined by inflorescence architecture, flower fertility, grain size, and weight. Whether copper is involved in these processes, and how it is delivered to the reproductive organs is not well understood. We show that copper deficiency alters not only the grain set but also flower development in both wheat and its recognized model, Brachypodium distachyon. We then show that the Brachypodium yellow stripe-like 3 (YSL3) transporter localizes to the phloem, transports copper in frog (Xenopus laevis) oocytes, and facilitates copper delivery to reproductive organs and grains. Failure to deliver copper, but not iron, zinc, or manganese to these structures in the ysl3 CRISPR-Cas9 mutant results in delayed flowering, altered inflorescence architecture, reduced floret fertility, grain size, weight, and protein accumulation. These defects are rescued by copper supplementation and are complemented by YSL3 cDNA. This knowledge will help to devise sustainable approaches for improving grain yield in regions where soil quality is a major obstacle for crop production. Copper distribution by a phloem-localized transporter is essential for the transition to flowering, inflorescence architecture, floret fertility, size, weight, and protein accumulation in seeds.
Consistency of M-Theory on Non-Orientable Manifolds
Authors: Freed Daniel S , Hopkins Michael J
Published: February 2021

We prove that there is no parity anomaly in M-theory in the low-energy field theory approximation. Our approach is computational. We determine the generators for the 12-dimensional bordism group of pin manifolds with a w1-twisted integer lift of w4; these are the manifolds on which Wick-rotated M-theory exists. The anomaly cancellation comes down to computing a specific η-invariant and cubic form on these manifolds. Of interest beyond this specific problem are our expositions of computational techniques for η-invariants, the algebraic theory of cubic forms, Adams spectral sequence techniques and anomalies for spinor fields and Rarita–Schwinger fields.
Second Moment Of Dirichlet L-Functions, Character Sums Over Subgroups And Upper Bounds On Relative Class Numbers
Authors: Louboutin Stéphane R , Munsch Marc
Published: February 2021

We prove an asymptotic formula for the mean-square average of L-functions associated with subgroups of characters of sufficiently large size. Our proof relies on the study of certain character sums ${\mathcal{A}}(p,d)$ recently introduced by E. Elma, where p ≥ 3 is prime and d ≥ 1 is any odd divisor of p − 1. We obtain an asymptotic formula for ${\mathcal{A}}(p,d),$ which holds true for any odd divisor d of p − 1, thus removing E. Elma’s restrictions on the size of d. This answers a question raised in Elma’s paper. Our proof relies on both estimates on the frequency of large character sums and techniques from the theory of uniform distribution. As an application, in the range $1\leq d\leq\frac{\log p}{3\log\log p}$, we obtain a significant improvement $h_{p,d}^- \leq 2(\frac{(1+o(1))p}{24})^{m/4}$ over the trivial bound $h_{p,d}^- \ll (\frac{dp}{24} )^{m/4}$ on the relative class numbers of the imaginary number fields of conductor $p\equiv 1\mod{2d}$ and degree $m=(p-1)/d$, where d ≥ 1 is odd.
Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis
Authors: Wang Yuanyuan , Meng Tao , Ruan Guangfeng , Zheng Shuang , Zhu Jimin , Cen Han , Antony Benny , Wluka Anita E , Cicuttini Flavia , Winzenberg Tania , Pelletier Jean-Pierre , Martel-Pelletier Johanne , Ding Changhai
Published: February 2021

Objective

To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA.

Methods

A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations.

Results

Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral β −6.23, medial β −5.14, total β −11.35 mm3/mmHg; diastolic: lateral β −10.25, medial β −11.29, total β −21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral β −17.35, total β −28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial β −8.24, total β −19.13 mm3/%; femoral: lateral β −23.70, medial β −26.42, total β −50.12 mm3/%).

Conclusions

Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.