bluuebunny/crossref_metadata_2025 huggingface dataset:
New techniques for mobility spectrum analysis
Authors: Beck W. A.
Published: April 2021

Mobility spectrum analysis (MSA) is a process of recovering the spectrum of carrier mobilities in an electronic material from a magnetic-field-dependent Hall measurement. This paper first presents a set of useful general properties of MSA that are true for all MSA methods. One such property is that Hall data can be classified as either “physical,” with at least one spectrum of carrier mobilities that exactly fits the data, or “unphysical,” where no mobility spectra exactly fit the data and the analysis must find approximate solutions. Almost all experimental Hall data collected at seven or more magnetic fields are slightly unphysical. The closest approximate solution for such unphysical data is always a set of discrete-carrier mobilities. A new method for multicarrier MSA is presented to display the likely properties of the discrete carriers as two-dimensional spectra vs both mobility and carrier density instead of one-dimensional spectra vs only mobility, as in previous methods. Measurement uncertainties are included as a fundamental part of the analysis so that the user can easily view the resultant uncertainty in the derived carrier properties. A separate method is also presented for reliably determining a smooth, high-entropy spectrum of carrier mobilities, which is constructed as the maximum-entropy linear combination of discrete-carrier solutions to the Hall data. An example using calculated Hall data corresponding to acoustic phonon scattering shows that the technique could potentially be used to measure the continuous mobility distributions that result from different scattering mechanisms.
High resolution infrared spectroscopy of (HCl)2 and (DCl)2 isolated in solid parahydrogen: Interchange-tunneling in a quantum solid
Authors: Anderson David T. , Fajardo Mario E. , Lindsay C. Michael
Published: April 2021

Infrared spectroscopic studies of weakly bound clusters isolated in solid parahydrogen (pH2) that exhibit large-amplitude tunneling motions are needed to probe how quantum solvation perturbs these types of coherent dynamics. We report high resolution Fourier transform infrared absorption spectra of (HCl)2, HCl–DCl, and (DCl)2 isolated in solid pH2 in the 2.4–4.8 K temperature range. The (HCl)2 spectra show a remarkable amount of fine structures that can be rigorously assigned to vibration–rotation–tunneling transitions of (HCl)2 trapped in double substitution sites in the pH2 matrix where end-over-end rotation of the cluster is quenched. The spectra are assigned using a combination of isotopically (H/D and 35Cl/37Cl) enriched samples, polarized IR absorption measurements, and four-line combination differences. The interchange-tunneling (IT) splitting in the ground vibrational state for in-plane and out-of-plane H35Cl–H37Cl dimers is 6.026(1) and 6.950(1) cm−1, respectively, which are factors of 2.565 and 2.224 smaller than in the gas phase dimer. In contrast, the (DCl)2 results show larger perturbations where the ground vibrational state IT splitting in D35Cl–D37Cl is 1.141(1) cm−1, which is a factor of 5.223 smaller than in the gas phase, and the tunneling motion is quenched in excited intramolecular vibrational states. The results are compared to similar measurements on (HCl)2 made in liquid helium nanodroplets to illustrate the similarities and differences in how both these quantum solvents interact with large amplitude tunneling motions of an embedded chromophore.
Queensland Rural Generalist Pathway: why do trainees separate without achieving a Rural Generalist end point?
Authors: Kitchener Scott , Douyere John , Bond Deanne
Published: April 2021

The aim of this study was to learn from trainees separating from the Queensland Rural Generalist Pathway (QRGP) the reasons and circumstances around their decision so as to improve the efficiency of the program and experience of trainees. Forty-one QRGP trainees who separated without achieving a Rural Generalist (RG) end point to training were interviewed regarding their reasons for separation and thoughts on improving the program. The mean period of time enrolled in the QRGP was 2.87 years. Broadly, the cohort divided into those separating for specialist training, those moving into non-RG general practice and those undecided. Separation for specialist training tended to occur during prevocational years and that to general practice later in the program before trainees had completed advanced skill training. Female trainees were over-represented among trainees separating without completing training. This cohort provided their opinions on the strengths of the QRGP and possible improvements. Understanding and addressing the reasons for early separation suggested several strategies to improve the efficiency of the QRGP in selecting and retaining trainees. Lessons learned included the value of employer-provided coordinated prevocational placements and training, potential benefits of guiding rural-interested medical graduates who ultimately enter other specialist training and the need for greater liaison with external Australian General Practice Training administration organisations to coordinate transition of trainees. There is a need to further address accessibility of advanced training for all trainees. What is known about the topic? Policies to generate RG medicine programs are now present in most state jurisdictions and nationally in Australia, with reports of successes appearing. However, little information is available regarding non-completion of trainees selected. What does this paper add? As programs grow in number and throughput, lessons learned from those choosing not to complete will inform the selection and management of trainees to improve the efficiency of these programs. This paper provides lessons learned by the QRGP regarding trainees not completing the program to inform the selection and management of trainees to make the program more efficient. What are the implications for practitioners? RG programs may facilitate retention or efficient separation of trainees by addressing potential reasons for separation at relevant times in the program.
ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1
Authors: Umeda Masataka , Yoshida Nobuya , Hisada Ryo , Burbano Catalina , Orite Seo Yeon K. , Kono Michihito , Kyttaris Vasileios C. , Krishfield Suzanne , Owen Caroline A. , Tsokos George C.
Published: April 2021

Significance

Members of the ADAM family of proteinases are expressed by immune cells and have been postulated to contribute to the development of autoimmune pathology. The current report provides evidence that ADAM9 drives the development of Th17 cells by producing bioactive TGF-β1. ADAM9 deficiency mitigates experimental autoimmune encephalomyelitis in mice, while T cells from patients with systemic lupus erythematosus express increased amounts of ADAM9, which, when suppressed, mitigates the generation of Th17 cells. The findings of this study identify the pivotal role of ADAM9 in the development of Th17 cells, and its targeting should ameliorate pathology in Th17-dependent diseases.
Oidium anacardii (cashew powdery mildew).
Authors: Swart Wijnand J.
Published: April 2021

In some African countries such as Tanzania crop losses of 50 and 70% were recorded from experimental blocks (Sijaona and Shomari, 1987; Shomari and Kennedy, 1999).
Anastrepha fraterculus (South American fruit fly).
Authors: Norrbom Allen
Published: April 2021

A. fraterculus has a broad host range, particularly in the family Myrtaceae, but it is also a pest of citrus and apples [Malus domestica] in some areas. It is the most important pest species of Anastrepha in subtropical areas of South America, thus it and Anastrepha ludens may be more of a threat of introduction to other subtropical areas of the world than other species of Anastrepha. It is invasive in the Galapagos Islands. As it is probably a complex of cryptic species whose ranges and delimitation remain unresolved, there is also the threat of introduction of particular cryptic species to other areas within the range of the complex. It is considered an A1 quarantine pest by EPPO.
Source term method for binary neutron stars initial data
Authors: Tsao Bing-Jyun , Haas Roland , Tsokaros Antonios
Published: April 2021

The initial condition problem for a binary neutron star system requires a Poisson equation solver for the velocity potential with a Neumann-like boundary condition on the surface of the star. Difficulties that arise in this boundary value problem are: (a) the boundary is not known a priori, but constitutes part of the solution of the problem; (b) various terms become singular at the boundary. In this work, we present a new method to solve the fluid Poisson equation for irrotational/spinning binary neutron stars. The advantage of the new method is that it does not require complex fluid surface fitted coordinates and it can be implemented in a Cartesian grid, which is a standard choice in numerical relativity calculations. This is accomplished by employing the source term method proposed by Towers, where the boundary condition is treated as a jump condition and is incorporated as additional source terms in the Poisson equation, which is then solved iteratively. The issue of singular terms caused by vanishing density on the surface is resolved with an additional separation that shifts the computation boundary to the interior of the star. We present two-dimensional tests to show the convergence of the source term method, and we further apply this solver to a realistic three-dimensional binary neutron star problem. By comparing our solution with the one coming from the initial data solver cocal, we demonstrate agreement to approximately 1%. Our method can be used in other problems with non-smooth solutions like in magnetized neutron stars.
Euclidean LQG dynamics: an electric shift in perspective
Authors: Varadarajan Madhavan
Published: April 2021

Loop quantum gravity (LQG) is a non-perturbative attempt at quantization of a classical phase space description of gravity in terms of SU(2) connections and electric fields. As emphasized recently Ashtekar and Varadarajan (2020 arXiv:2012.12094 [gr-qc]), on this phase space, classical gravitational evolution in time can be understood in terms of certain gauge covariant generalizations of Lie derivatives with respect to a spatial
SU(2) Lie algebra valued vector field called the electric shift. We present a derivation of a quantum dynamics for Euclidean LQG which is informed by this understanding. In addition to the physically motivated nature of the action of the Euclidean Hamiltonian constraint so derived, the derivation implies that the spin labels of regulating holonomies are determined by corresponding labels of the spin network state being acted upon thus eliminating the ‘spin j-ambiguity’ pointed out by Perez. By virtue of Thiemann’s seminal work, the Euclidean quantum dynamics plays a crucial role in the construction of the Lorentzian quantum dynamics so that our considerations also have application to Lorentzian LQG.
Center-of-mass ambiguity for Bondi–Metzner–Sachs charges
Authors: Helfer Adam D
Published: April 2021

Dray and Streubel proposed a definition of angular momentum in general relativity based on ‘Bondi–Metzner–Sachs charges’. I show here that the natural definition of center of mass in this program has an infinite-dimensional ambiguity. (This seems not to have been noticed before because previous work has tacitly carried over a special-relativistic assumption.) A related point is that the natural definition of spin in this context is translation-, but not supertranslation-, invariant.
Relation of the fragility and heat capacity jump in the supercooled liquid region with the shear modulus relaxation in metallic glasses
Authors: Makarov A S , Qiao J C , Kobelev N P , Aronin A S , Khonik V A
Published: April 2021

Fragility constitutes a major parameter of supercooled liquids. The phenomenological definition of this quantity is related to the rate of a change of the shear viscosity η at the glass transition temperature. Although a large number of correlations of the fragility with different properties of metallic glasses were reported, an adequate understanding of its physical nature is still lacking. Attempting to uncover this nature, we performed the calculation of the fragility within the framework of the interstitialcy theory (IT) combined with the elastic shoving model. We derived an analytical expression for the fragility, which shows its relation with the high-frequency shear modulus G in the supercooled liquid state. To verify this result, specially designed measurements of η and G were performed on seven Zr-, Cu- and Pd-based metallic glasses. It was found that the fragility calculated from shear modulus relaxation data is in excellent agreement with the fragility derived directly from shear viscosity measurements. We also calculated the heat capacity jump ΔC
sql at the glass transition and showed that it is related to the fragility and, consequently, to shear modulus relaxation. The ΔC
sql-value thus derived is in a good agreement with experimental data. It is concluded that the fragility and heat capacity jump in the supercooled liquid state can be determined by the evolution of the system of interstitial-type defects frozen-in from the melt upon glass production, as suggested by the IT. This connection is mediated by the high-frequency shear modulus.
Artemisinin co-delivery system based on manganese oxide for precise diagnosis and treatment of breast cancer
Authors: Zhang Huijuan , Li Mengting , Zhu Xing , Zhang Zhenzhong , Huang Heqing , Hou Lin
Published: April 2021

Tumor microenvironment (TME) responsive intelligent system can realize the specific release and uniform distribution of chemotherapy drugs in tumor tissues, to achieve high-efficiency and low-toxic treatment of tumors. In this paper, drug delivery system TKD@RBCm-Mn2O3-ART with the above characteristics was constructed. We synthesized hollow mesoporous manganese trioxide (Mn2O3) nanoparticles and firstly found that they owned time-dependent size transformation feature in simulated TME. The particle size decreased from 318 nm to 50 nm and 6 nm at 1 h and 4 h in simulated TME, respectively. Then artemisinin (ART) was loaded into Mn2O3 to realize the co-delivery of Mn2+ and ART. The modification of homologous red cell membrane (RBCm) and TKD peptide was aimed at long circulation and tumor targeting in the body. In vitro results demonstrated that in the presence of GSH, the cumulative drug release percentage could achieve 97.5%. Meanwhile, Mn2O3 exhibited a good imaging capability in tumor, with the relaxation rate of 6.3113 mM−1 s−1. After entering into MCF-7 cells, TKD@RBCm-Mn2O3/ART synchronously released Mn2+ and ART to generate large amount of ROS and induce DNA damage. In vivo results proved TKD@RBCm-Mn2O3/ART could arrive the deep area of solid tumors and achieve accurate diagnosis and treatment of breast cancer.
Synergistic function of doping and ligand engineering to enhance the photostability and electroluminescence performance of CsPbBr3 quantum dots
Authors: Chen Junfei , Shen Zhaohui , Liu Pengbo , Sun Zhengyang , Liu Jay Guoxu , Shen Chongyu , Song Dandan , Zhao Suling , Xu Zheng
Published: April 2021

The photostability issue of CsPbX3 (X = Cl, Br, I) quantum dots (QDs) is one of the key origins for the degradation of their luminescence performance, which hinders their application in lighting and displays. Herein, we report a new method combining doping and ligand engineering, which effectively improves the photostability of CsPbBr3 QDs and the performance of QD light-emitting diodes (QLEDs). In this method, ZnBr2 is doped into CsPbBr3 QDs to reduce surface anion defects; didodecyldimethyl ammonium bromide (DDAB) and tetraoctylammonium bromide (TOAB) hybrid ligands, which have strong adsorption with QDs, are employed to protect the surface and enhance the conductivity of QD layer in QLEDs. The photoluminescence (PL) and transmission electron microscopy measurements prove the effectively improved photostability of CsPbX3 QDs. Moreover, reduced defects and improved conductivity by doping and hybrid ligands treatment also enable the improved electroluminescence performance of CsPbX3 QDs. The maximum luminance and external quantum efficiency of the QLED with optimized CsPbX3 QDs are 3518.9 cd m−2 and 5.07%, which are 3.6 and 2.1 times than that of the control device, respectively. Combining doping and hybrid ligands makes perovskite QDs have an extremely promising prospect in future applications of high-definition displays, high-quality lighting, as well as solar cells.
Influence of thermal growth of Au nanoparticles in the coupling efficiency of Au/SiO2 nanocomposite grating coupler
Authors: Wang Gang , Wang Jun , Dai Haitao , Liu Changlong
Published: April 2021

The Au/SiO2 nanocomposite grating coupler with a period of 600 nm was fabricated by implantation of 140 keV Au ions at a fluence of 6 × 1016 ions·cm−2 in combination with subsequent electron-beam lithography and ion beam etching. The thermal evolution of Au nanoparticles and its influence on the vertical coupling efficiency of the prepared grating coupler has been investigated in detail. The results clearly show that the coupling efficiency of the nanocomposite grating coupler could be affected by the thermal evolution of Au nanoparticles, which increases in the annealing temperature range up to 800 °C, and then decreases at 900 °C and above. Theoretical calculation demonstrates that the change of the coupling efficiency should be closely related to the synergistic effect of the scattering effect and the variation in the volume fraction of Au nanoparticles due to the thermal growth.
Newton’s cradle: using a smartphone sound sensor to extract g from the sound of impacts
Authors: Pili Unofre B
Published: April 2021

The sound of impacts made by the two outermost balls in a Newton’s cradle were recorded with a smartphone sound sensor. As a time series of sound pressure levels, the data made it possible to obtain the period of the identical pendulums. Hence the determination of the acceleration due to gravity. The result, on average, g = 9.99 m s−2, is close enough to the locally accepted value of 9.78 m s−2 for instructional purposes.
VR modernism: the newest technological solutions for urban development and preservation of cultural heritage
Authors: Fadeeva T E , Staruseva-Persheeva A D , Davidov D G
Published: April 2021

Modern urban studies are developing in an inextricable connection with sociology and economic theory, since the city is thought of as a “machine” that summarizes all the processes taking place in society and, accordingly, through the development of cities, it is possible to solve such pressing issues as inequality, growth of crime, etc. However, no less important is the issue of the “organic integrity” of cities, which implies a careful treatment of a variety of buildings, including those that seem technologically and aesthetically outdated. This article highlights the basic contradiction between two approaches to urban planning: the pursuit of constant innovation and the desire to preserve the diversity of urban development. Virtual reality is becoming one of the most effective tools for solving issues of the city care today. The article will analyze international experience, demonstrating how the design of new buildings is carried out with the help of VR technologies and the work is carried out to preserve the cultural and historical heritage.
Mediterranean city: constructing a social attractor (the example of Barcelona)
Authors: Chikharev I A , Tikunova I N , Fedorova E A
Published: April 2021

The paper analyzes the experience of Barcelona in constructing a city as a social attractor, an area to which the global socio-economic system gravitates. The role of positive changes in the urban environment, the introduction of intelligent technologies of urban management, linking the city with global flows in ensuring the attractiveness of the Mediterranean city are consistently analyzed. The authors define the fundamental structure of the Mediterranean urban attractor, including openness and accessibility of the sea, internal and external transport accessibility, comfortable urban environment, introduction of smart city technologies and connectivity with the global economy.
Social risk management in nuclear cities: ROSATOM experience
Authors: Polosin A V , Chikharev I A , Ganat S A , Rzhepishevskaya A B
Published: April 2021

The article examines the activities of the State Atomic Energy Corporation “Rosatom” on the implementation of social projects in the cities where nuclear facilities are located and improving the quality of territory management. The factors of social and political risk for the implementation of the programs of the State Corporation “Rosatom” for the development of nuclear cities are given. Possible methods for managing political risks in nuclear cities are presented.
Transformation of the scientific, technical and industrial complex of municipalities as a factor in ensuring the technological sovereignty of Russia
Authors: Polosin A V , Chikharev I A , Samoilova E S , Medvedev V V
Published: April 2021

The country’s economic stability and security, overcoming the consequences of the economic crisis, as well as comprehensive regional development are closely related to the preservation and further development of our own industrial, scientific and technical complexes. The introduction of the concept of technological sovereignty, as well as the definition of a set of measures to achieve it, are necessary steps towards sustainable development and security of the state. In scientific research, much attention has been paid to the problem of modernizing industrial production through the introduction of advanced innovative and technical innovations, but at the same time, the issue of ensuring the technological and component independence of domestic production has not been sufficiently studied. The practical significance of the results of the work lies in the possibility of applying the formulated conclusions and recommendations in the practical activities of the subjects of regional infrastructure, as well as in the possibility of their application by the authorities in the formation of regional economic policy for the development of the scientific, technical and industrial complex in the context of all its components in order to ensure the sustainability of the economic growth of each territory.
The role of external focusing in spectral enrichment under mid-IR laser filamentation in dielectrics
Authors: Lvov Kirill , Stremoukhov Sergey , Potemkin Fedor
Published: April 2021

We report on the numerical investigation of spectral enrichment under mid-infrared (4.4 μm) laser filamentation in CaF2 and the influence of the external focusing on this nonlinear phenomenon. It is shown that the supercontinuum generation is related to the rapid free-electron increase and appears when nonlinear and diffraction lengths are practically the same. With further pulse propagation, the anti-Stokes wing (ASW) is formed which is caused by the pulse splitting. Looser focusing leads to pulse splitting be closer to the point of supercontinuum formation along the propagation axis. The ASW experiences a red-shift when external focusing is applied due to increased free-electron density.
Impact of COVID-19 on care-home mortality and life expectancy in Scotland
Authors: Burton Jennifer K , Reid Martin , Gribben Ciara , Caldwell David , Clark David N , Hanlon Peter , Quinn Terence J , Fischbacher Colin , Knight Peter , Guthrie Bruce , McAllister David A
Published: April 2021

Background

COVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified.

Methods

Care-home residency was identified via a national primary care registration database linked to mortality data. Life expectancy was estimated using Makeham–Gompertz models to (i) describe yearly life expectancy from November 2015 to October 2020 (ii) compare life expectancy (during 2016–18) between care-home residents and the wider population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL).

Results

Among care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3 years for women and 2.3 to 1.8 years for men. Age–sex-specific life expectancy in 2016–18 in care-home residents was lower than in the Scottish population (10 and 2.5 years in those aged 70 and 90, respectively). Applying care home-specific life expectancies to COVID-19 deaths yield mean YLLs for care-home residents of 2.6 and 2.2 for women and men, respectively. In total YLL care-home residents have lost 3,560 years in women and 2,046 years in men. Approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents.

Conclusion

COVID-19 infection has led to the loss of substantial years of life in care-home residents aged 70 years and over in Scotland. Prioritising the 5% of older adults who are care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of YLL.
Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot
Authors: Witham Miles D , Heslop Philip , Dodds Richard M , Clegg Andrew P , Hope Suzy V , McDonald Claire , Smithard David , Storey Bryony , Tan Ai Lyn , Thornhill Anna , Sayer Avan A
Published: April 2021

Background

sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.

Methods

six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.

Results

sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval −1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.

Conclusion

recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.
Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers–reaching the frontiers of individual risk prediction
Authors: Verstraelen Tom E , van Lint Freyja H M , Bosman Laurens P , de Brouwer Remco , Proost Virginnio M , Abeln Bob G S , Taha Karim , Zwinderman Aeilko H , Dickhoff Cathelijne , Oomen Toon , Schoonderwoerd Bas A , Kimman Gerardus P , Houweling Arjan C , Gimeno-Blanes Juan R , Asselbergs Folkert W , van der Zwaag Paul A , de Boer Rudolf A , van den Berg Maarten P , van Tintelen J Peter , Wilde Arthur A M
Published: April 2021

Aims

This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model.

Methods and results

Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27–55]. During a median follow-up of 4.3 years (IQR 1.7–7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78–0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61–0.75).

Conclusion

This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach.
Conversion-Type and Restoration-Type Repair of DNA Mismatches Formed During Meiotic Recombination in Saccharomyces cerevisiae
Authors: Kirkpatrick David T , Dominska Margaret , Petes Thomas D
Published: April 2021

Meiotic recombination in yeast is associated with heteroduplex formation. Heteroduplexes formed between nonidentical DNA strands contain DNA mismatches, and most DNA mismatches in wild-type strains are efficiently corrected. Although some patterns of mismatch correction result in non-Mendelian segregation of the heterozygous marker (gene conversion), one predicted pattern of correction (restoration-type repair) results in normal Mendelian segregation. Using a yeast strain in which a marker leading to a well-repaired mismatch is flanked by markers that lead to poorly repaired mismatches, we present direct evidence for restoration-type repair in yeast. In addition, we find that the frequency of tetrads with conversion-type repair is higher for a marker at the 5′ end of the HIS4 gene than for a marker in the middle of the gene. These results suggest that the ratio of conversion-type to restoration-type repair may be important in generating gradients of gene conversion (polarity gradients).
Molecular Analysis of pcc1, a Gene That Leads to A-Regulated Sexual Morphogenesis in Coprinus cinereus
Authors: Murata Yukio , Fujii Motohiro , Zolan Miriam E , Kamada Takashi
Published: April 2021

A homokaryotic strain (5337) in our culture stock of Coprinus cinereus produced fertile fruit bodies after prolonged culture. Microscopic examination revealed that hyphae dedifferentiated from the tissues of one of the fruit bodies, as well as all basidiospore derivatives from the fruit body, exhibited pseudoclamps, whereas vegetative hyphae of 5337, from which the fruit body developed, had no clamp connections. Genetic analysis showed that the formation of pseudoclamps results from a recessive mutation in a gene designated pcc1 (pseudoclamp connection formation), which is distinct from the A and B mating type genes. Cloning and sequencing of the pcc1 gene and cDNA identified an ORF of 1683 bp interrupted by one intron. Database searches revealed that pcc1 encodes an SRY-type HMG protein. The HMG box shared 44, 41, and 29% sequence identities (>80 amino acids) to those of FPR1 of Podospora anserina, MAT-Mc of Schizosaccharomyces pombe, and prf1 of Ustilago maydis, respectively. Northern analysis revealed that the level of pcc1 expression is higher in the dikaryon, in homokaryons in which the A and B mating type developmental sequences are individually activated, than in the homokaryon in which these sequences are not active. Sequencing of the pcc1-1 mutant allele revealed that the mutant carries a nonsense mutation at serine 211, a residue located between the HMG box and the C terminus. Based on these results, possible roles of the pcc1 gene in the sexual development of homobasidiomycetes are discussed.
Wolbachia Transfer from Drosophila melanogaster into D. simulans: Host Effect and Cytoplasmic Incompatibility Relationships
Authors: Poinsot Denis , Bourtzis Kostas , Markakis George , Savakis Charalambos , Merçot Hervé
Published: April 2021

Wolbachia are maternally transmitted endocellular bacteria causing a reproductive incompatibility called cytoplasmic incompatibility (CI) in several arthropod species, including Drosophila. CI results in embryonic mortality in incompatible crosses. The only bacterial strain known to infect Drosophila melanogaster (wDm) was transferred from a D. melanogaster isofemale line into uninfected D. simulans isofemale lines by embryo microinjections. Males from the resulting transinfected lines induce >98% embryonic mortality when crossed with uninfected D. simulans females. In contrast, males from the donor D. melanogaster line induce only 18–32% CI on average when crossed with uninfected D. melanogaster females. Transinfected D. simulans lines do not differ from the D. melanogaster donor line in the Wolbachia load found in the embryo or in the total bacterial load of young males. However, >80% of cysts are infected by Wolbachia in the testes of young transinfected males, whereas only 8% of cysts are infected in young males from the D. melanogaster donor isofemale line. This difference might be caused by physiological differences between hosts, but it might also involve tissue-specific control of Wolbachia density by D. melanogaster. The wDm-transinfected D. simulans lines are unidirectionally incompatible with strains infected by the non-CI expressor Wolbachia strains wKi, wMau, or wAu, and they are bidirectionally incompatible with strains infected by the CI-expressor Wolbachia strains wHa or wNo. However, wDm-infected males do not induce CI toward females infected by the CI-expressor strain wRi, which is found in D. simulans continental populations, while wRi-infected males induce partial CI toward wDm-infected females. This peculiar asymmetrical pattern could reflect an ongoing divergence between the CI mechanisms of wRi and wDm. It would also confirm other results indicating that the factor responsible for CI induction in males is distinct from the factor responsible for CI rescue in females.
Overexpression Beadex Mutations and Loss-of-Function heldup-a Mutations in Drosophila Affect the 3′ Regulatory and Coding Components, Respectively, of the Dlmo Gene
Authors: Shoresh Michal , Orgad Sara , Shmueli Orit , Werczberger Ruth , Gelbaum Dana , Abiri Shirly , Segal Daniel
Published: April 2021

LIM domains function as bridging modules between different members of multiprotein complexes. We report the cloning of a LIM-containing gene from Drosophila, termed Dlmo, which is highly homologous to the vertebrate LIM-only (LMO) genes. The 3′ untranslated (UTR) of Dlmo contains multiple motifs implicated in negative post-transcriptional regulation, including AT-rich elements and Brd-like boxes. Dlmo resides in polytene band 17C1-2, where Beadex (Bx) and heldup-a (hdp-a) mutations map. We demonstrate that Bx mutations disrupt the 3′UTR of Dlmo, and thereby abrogate the putative negative control elements. This results in overexpression of Dlmo, which causes the wing scalloping that is typical of Bx mutants. We show that the erect wing phenotype of hdp-a results from disruption of the coding region of Dlmo. This provides molecular grounds for the suppression of the Bx phenotype by hdp-a mutations. Finally, we demonstrate phenotypic interaction between the LMO gene Dlmo, the LIM homeodomain gene apterous, and the Chip gene, which encodes a homolog of the vertebrate LIM-interacting protein NLI/Ldb1. We propose that in analogy to their vertebrate counterparts, these proteins form a DNA-binding complex that regulates wing development.
Regulation of Gene Expression During the Vegetative Incompatibility Reaction in Podospora anserina: Characterization of Three Induced Genes
Authors: Bourges Nathalie , Groppi Alexis , Barreau Christian , Clavé Corinne , Bégueret Joël
Published: April 2021

Vegetative incompatibility in fungi limits the formation of viable heterokaryons. It results from the coexpression of incompatible genes in the heterokaryotic cells and leads to a cell death reaction. In Podospora anserina, a modification of gene expression takes place during this reaction, including a strong decrease of total RNA synthesis and the appearance of a new set of proteins. Using in vitro translation of mRNA and separation of protein products by two-dimensional gel electrophoresis, we have shown that the mRNA content of cells is qualitatively modified during the progress of the incompatibility reaction. Thus, gene expression during vegetative incompatibility is regulated, at least in part, by variation of the mRNA content of specific genes. A subtractive cDNA library enriched in sequences preferentially expressed during incompatibility was constructed. This library was used to identify genomic loci corresponding to genes whose mRNA is induced during incompatibility. Three such genes were characterized and named idi genes for genes induced during incompatibility. Their expression profiles suggest that they may be involved in different steps of the incompatibility reaction. The putative IDI proteins encoded by these genes are small proteins with signal peptides. IDI-2 protein is a cysteine-rich protein. IDI-2 and IDI-3 proteins display some similarity in a tryptophan-rich region.
The Male-Determining Activity on the Y Chromosome of the Housefly (Musca domestica L.) Consists of Separable Elements
Authors: Hediger Monika , Minet Ariane Denise , Niessen Markus , Schmidt Regula , Hilfiker-Kleiner Denise , Çakır Şükran , Nöthiger Rolf , Dübendorfer Andreas
Published: April 2021

In the common housefly, the presence or absence of a male-determining factor, M, is responsible for sex determination. In different strains, M has been found on the Y, on the X, or on any of the five autosomes. By analyzing a Y-autosomal translocation and a ring-shaped, truncated Y chromosome, we could show that M on the Y consists of at least two regions with M activity: One of them can be assigned to the short arm of the Y chromosome (MYS), which is largely C-banding negative, the other region lies on the C-banding positive long arm of the Y, including the centromeric part (MYL). Each region alone behaves as a hypomorphic M factor, causing many carriers to develop as intersexes of the mosaic type instead of as males. When introduced into the female germ line by transplantation of progenitor germ cells (pole cells), the MYS shows an almost complete maternal effect that predetermines 96% of the genotypic female (NoM) animals to develop as males. In contrast, the MYL has largely lost its maternal effect, and most of the NoM animals develop as females. Increasing the amount of product made by either of the two hypomorphic M factors (by combining the MYS and MYL or two MYS) leads to complete male development in almost every case. We thus assume that the Y chromosome carries at least two copies of M, and that these are functionally equivalent.
Relative Paucity of Genes Causing Inviability in Hybrids Between Drosophila melanogaster and D. simulans
Authors: Coyne Jerry A , Simeonidis Simos , Rooney Peggy
Published: April 2021

Using deficiencies from Drosophila melanogaster, we looked for genomic regions in the sister species D. simulans that could cause lethality when hemizygous on a hybrid genetic background. Such genotypes allow hemizygous genes from one species to interact with heterozygous genes from other species and may correspond to the kinds of genotypes causing Haldane’s rule, the observation that if only one gender is sterile or inviable in species hybrids, it is nearly always the heterogametic sex. A survey of roughly 50% of the D. simulans genome (114 chromosome regions) revealed only four regions causing hybrid lethality and five causing severe reductions in hybrid viability. However, the viability of all of these genotypes was at least partially restored by rearing hybrids at lower temperature or using different genetic backgrounds from D. simulans. We therefore detected no D. simulans chromosome regions causing unconditional hybrid lethality, although several regions were shown to be deleterious under most tested temperatures and genetic backgrounds. The relative paucity of “inviability genes” supports the idea, suggested by work on other species, that hybrid inviability between closely related species might be caused by interactions among relatively few genes, while hybrid sterility may involve many more loci.
Embryonic Lethality and Tumorigenesis Caused by Segmental Aneuploidy on Mouse Chromosome 11
Authors: Liu Pentao , Zhang Heju , McLellan Andrew , Vogel Hannes , Bradley Allan
Published: April 2021

Chromosome engineering in mice enables the construction of models of human chromosomal diseases and provides key reagents for genetic studies. To begin to define functional information for a small portion of chromosome 11, deficiencies, duplications, and inversions were constructed in embryonic stem cells with sizes ranging from 1 Mb to 22 cM. Two deficiencies and three duplications were established in the mouse germline. Mice with a 1-Mb duplication developed corneal hyperplasia and thymic tumors, while two different 3- to 4-cM deficiencies were embryonically lethal in heterozygous mice. A duplication corresponding to one of these two deficiencies was able to rescue its haplolethality.
Dominant Defects in Drosophila Eye Pigmentation Resulting From a Euchromatin-Heterochromatin Fusion Gene
Authors: Rong Yikang S , Golic Kent G
Published: April 2021

We have isolated a dominant mutation, pugilistDominant (pug D), that causes variegated reductions in pteridine and ommochrome pigmentation of the Drosophila eye. The effect of pugD on pteridine pigmentation is most dramatic: the only remaining pigment consists of a thin ring of pigment around the periphery of the eye with a few scattered spots in the center. The pugD mutation disrupts a gene that encodes a Drosophila homolog of the trifunctional enzyme methylenetetrahydrofolate dehydrogenase (MTHFD; E.C.1.5.1.5, E.C.3.5.4.9, E.C.6.3.4.3). This enzyme produces a cofactor that is utilized in purine biosynthesis. Because pteridines are derived from GTP, the pigment defect may result from an impairment in the production of purines. The mutant allele consists of a portion of the MTHFD coding region fused to ∼1 kb of highly repetitive DNA. Transcription and translation of both parts are required for the phenotype. The repetitive DNA consists of ∼140 nearly perfect repeats of the sequence AGAGAGA, a significant component of centric heterochromatin. The unusual nature of the protein produced by this gene may be responsible for its dominance. The repetitive DNA may also account for the variegated aspect of the phenotype. It may promote occasional association of the pugD locus with centric heterochromatin, accompanied by inactivation of pugD, in a manner similar to the proposed mode of action for brownDominant.
Molecular Consequences of Ds Insertion Into and Excision From the Helix-Loop-Helix Domain of the Maize R Gene
Authors: Liu Yanhong , Wang Liangjiang , Kermicle Jerry L , Wessler Susan R
Published: April 2021

The R and B proteins of maize are required to activate the transcription of several genes in the anthocyanin biosynthetic pathway. To determine the structural requirements for R function in vivo, we are exploiting its sensitive mutant phenotype to identify transposon (Ds) insertions that disrupt critical domains. Here we report that the ability of the r-m1 allele to activate transcription of at least three structural genes is reduced to only 2% of wild-type activity because of a 396-bp Ds element in helix 2 of the basic helix-loop-helix (bHLH) motif. Residual activity likely results from the synthesis of a mutant protein that contains seven additional amino acids in helix 2. This protein is encoded by a transcript where most of the Ds sequence has been spliced from pre-mRNA. Two phenotypic classes of stable derivative alleles, very pale and extremely pale, condition <1% of wild-type activity as a result of the presence of two- and three-amino-acid insertions, respectively, at the site of Ds excision. Localization of these mutant proteins to the nucleus indicates a requirement for an intact bHLH domain after nuclear import. The fact that deletion of the entire bHLH domain has only a minor effect on R protein activity while these small insertions virtually abolish activity suggests that deletion of the bHLH domain may bypass a requirement for bHLH-mediated protein-protein interactions in the activation of the structural genes in the anthocyanin biosynthetic pathway.
The Role of Evolutionarily Conserved Sequences in Alternative Splicing at the 3′ End of Drosophila melanogaster Myosin Heavy Chain RNA
Authors: Hodges Dianne , Cripps Richard M , O'Connor Martin E , Bernstein Sanford I
Published: April 2021

Exon 18 of the muscle myosin heavy chain gene (Mhc) of Drosophila melanogaster is excluded from larval transcripts but included in most adult transcripts. To identify cis-acting elements regulating this alternative RNA splicing, we sequenced the 3′ end of Mhc from the distantly related species D. virilis. Three noncoding regions are conserved: (1) the nonconsensus splice junctions at either end of exon 18; (2) exon 18 itself; and (3) a 30-nucleotide, pyrimidine-rich sequence located about 40 nt upstream of the 3′ splice site of exon 18. We generated transgenic flies expressing Mhc mini-genes designed to test the function of these regions. Improvement of both splice sites of adult-specific exon 18 toward the consensus sequence switches the splicing pattern to include exon 18 in all larval transcripts. Thus nonconsensus splice junctions are critical to stage-specific exclusion of this exon. Deletion of nearly all of exon 18 does not affect stage-specific utilization. However, splicing of transcripts lacking the conserved pyrimidine sequence is severely disrupted in adults. Disruption is not rescued by insertion of a different polypyrimidine tract, suggesting that the conserved pyrimidine-rich sequence interacts with tissue-specific splicing factors to activate utilization of the poor splice sites of exon 18 in adult muscle.
Aspergillus nidulans swo Mutants Show Defects in Polarity Establishment, Polarity Maintenance and Hyphal Morphogenesis
Authors: Momany Michelle , Westfall Patrick J , Abramowsky Gretel
Published: April 2021

When the spores of filamentous fungi break dormancy, they grow isotropically, adding cell wall material uniformly in every direction. Later they switch to polarized growth, with new material added to the tip of an emerging germ tube. To identify genes involved in the synthesis and localization of cell wall material in filamentous fungi, we screened a collection of temperature-sensitive Aspergillus nidulans mutants for swollen cells. We have isolated mutants representing eight genes involved in polarity establishment, polarity maintenance, and hyphal morphogenesis. On the basis of the results of temperature-shift experiments, swo C, D, and F are required to establish polarity, while swoA is required to maintain polarity. swo B, E, G, and H are involved in later hyphal morphogenesis. Our results suggest that polarity establishment and polarity maintenance are genetically separate events and that a persistent signal is required for apical extension in A. nidulans.