bluuebunny/crossref_metadata_2025 huggingface dataset:
A CRISPR-Cas9–engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions
Authors: Rodríguez de los Santos Miguel , Rivalan Marion , David Friederike S. , Stumpf Alexander , Pitsch Julika , Tsortouktzidis Despina , Velasquez Laura Moreno , Voigt Anne , Schilling Karl , Mattei Daniele , Long Melissa , Vogt Guido , Knaus Alexej , Fischer-Zirnsak Björn , Wittler Lars , Timmermann Bernd , Robinson Peter N. , Horn Denise , Mundlos Stefan , Kornak Uwe , Becker Albert J. , Schmitz Dietmar , Winter York , Krawitz Peter M.
Published: January 2021

Significance

Inherited GPI-anchor biosynthesis deficiencies (IGDs) explain many cases of syndromic intellectual disability. Although diagnostic methods are improving, the pathophysiology underlying the disease remains unclear. Furthermore, we lack rodent models suitable for characterizing cognitive and social disabilities. To address this issue, we generated a viable mouse model for an IGD that mirrors the condition in human patients with a behavioral phenotype and susceptibility to epilepsy. Using this model, we obtained neurological insights such as deficits in synaptic transmission that will facilitate understanding of the pathophysiology of IGDs.
In silico dynamics of COVID-19 phenotypes for optimizing clinical management
Authors: Voutouri Chrysovalantis , Nikmaneshi Mohammad Reza , Hardin C. Corey , Patel Ankit B. , Verma Ashish , Khandekar Melin J. , Dutta Sayon , Stylianopoulos Triantafyllos , Munn Lance L. , Jain Rakesh K.
Published: January 2021

Significance

A distinctive feature of COVID-19 is its extreme heterogeneity—illness ranges from minimally symptomatic to life threatening. Heterogeneity results from a poorly understood combination of patient factors, viral dynamics, antiviral and immune modulating therapies, and dynamics of the innate and adaptive immune responses. In order to better understand clinical heterogeneity and optimal treatment, we developed a comprehensive mathematical model incorporating elements of the innate and adaptive immune responses, the renin−angiotensin system (which the virus exploits for cellular entry), rates of viral replication, inflammatory cytokines, and the coagulation cascade. Our model reveals divergent treatment responses and clinical outcomes as a function of comorbidities, age, and details of the innate and adaptive immune responses which can provide a framework for understanding individual patients’ trajectories.
The syntactic tradition in the Spanish linguistic atlases
Authors: García Mouton Pilar
Published: January 2021

This chapter studies the methodology of
traditional Spanish linguistic atlases to obtain syntactic data.
After setting the background, from the notes of Tomás Navarro Tomás
in his questionnaires, the way of asking syntax in the Atlas
Lingüístico de la Península Ibérica is reconstructed.
To what extent the subsequent atlases followed that method is also
traced and we can see how the recent ones, besides assuming this
tradition, choose to complement it with more spontaneous syntactic
materials.
Syntactic features and dialect areas in European Spanish
Authors: Camus Bergareche Bruno , Gutiérrez Edita
Published: January 2021

Traditional Dialectology has focused on phonetic,
morphological and lexical variation and has paid less attention to
syntactic variation. Consequently, dialectal boundaries are usually
drawn employing mainly phonetic, morphological or lexical traits. In
the case of Spanish this bias can easily be confirmed by the main
contents of the regional linguistic atlases of Spain. The present
chapter is aimed to be a complete review of the syntactic
information present in these atlases. We will evaluate its actual
usefulness as to the purpose of defining dialect areas inside
European Spanish. Finally, after examining the main syntactic
features subject to variation in Peninsular Spanish, we will also
make a tentative proposal of dialect areas based on syntactic
differences.
The Corpus del español del siglo XXI
(CORPES XXI)
Authors: Buenafuentes de la Mata Cristina , Sanchez Lancis Carlos
Published: January 2021

In this work we review the multiple uses of the
Corpus del español del siglo XXI
(CORPES XXI) to facilitate the study of
syntactic variation in Spanish. We present different kinds of
searches and data sorting available from the corpus and we provide
some examples of syntactic phenomena, most of them characteristic of
American Spanish areas. In sum, we show that CORPES
XXI can become an extremely useful tool to describe the
syntactic variation of Spanish.
Impact of a double sphere dropped vertically onto a horizontal surface
Authors: Cross Rod
Published: January 2021

A simple experiment is described concerning the vertical bounce of a nonspherical object. The object consisted of two golf balls joined together. The balls were dropped onto a heavy, rigid horizontal surface and were filmed with a video camera to measure the coefficient of restitution (COR). For spherical objects, the COR is usually defined in terms of the vertical speed of the centre of mass and can vary between zero and unity depending on the elastic properties of the object and the surface on which it bounces. For nonspherical objects, the COR is best defined in terms of the vertical speed of the contact point. For the two golf balls, the centre of mass COR was found to vary between −4 and +2 depending on the incident spin and the angle of inclination of the long axis. The contact point COR was found to be 0.8 ± 0.2, regardless of the incident spin and angle of inclination.
Chiral Bloch–Zener oscillations of spin–orbit coupled cold atoms in an optical superlattice
Authors: Li Zhe-Han , Zhou Lu , Li Yan
Published: January 2021

We study the Bloch oscillation (BO) dynamics of spin–orbit coupled cold atoms in a one-dimensional Su–Schrieffer–Heeger optical lattice. The Hamiltonian of our system can be mapped into a tilted SSH ladder pierced by an effective magnetic flux. Based on the calculation of Wannier–Stark states, we investigate dynamical properties of BOs with the chiral character of spin-momentum locking. Importantly, the chiral Bloch–Zener oscillations can be induced by adjusting system parameters. The corresponding Landau–Zener (LZ) tunneling probability is analytically derived by the LZ model and we found a good agreement with the numerical simulation.
Precise locomotion controller design for a novel magnetorheological fluid robot based on improved gray wolf optimization algorithm
Authors: Hua Dezheng , Liu Xinhua , Sun Shuaishuai , Li Zengqiang , Li Zhixiong , Li Weihua
Published: January 2021

Spherical magnetorheological fluid (MRF) robots are capable to move in narrow space, which can be used for drug releasing to human stomach; however, the magnetic-controlled rolling movement often generates a large displacement error, which greatly hinders the practical applications of the MRF robots. In order to bridge this research gap, this paper introduces a new MRF robot with a precise locomotion controller. In this control system, a data acquisition system is designed for the MRF robot and an optimal proportion integration differentiation (PID) controller is proposed based on an improved grey wolf optimization algorithm (IGWO). Both simulations and experiments have been performed to verify the performance of the locomotion controller. The simulation results show that the proposed IGWO-PID controller is superior to the conventional PID and GWO PID controller, with faster response output and smaller overshoot. Experimental analysis results demonstrate the proposed MRF robot can move in a complex trace with a speed fluctuation rate below 5.4%. As a result, precise locomotion has been achieved to make the new MRF robot ready for medicine delivery in narrow space.
Pedestal collapse by resonant magnetic perturbations
Authors: Nazikian R. , Hu Q. , Ashourvan A. , Eldon D. , Evans T.E. , Grierson B.A. , Logan N.C. , Orlov D.M. , Park J.-K. , Paz-Soldan C. , Poli F.M. , Yu Q.
Published: January 2021

Pedestal collapse (i.e., the complete loss of the edge transport barrier (ETB)) in DIII-D H-mode plasmas occurs when resonant magnetic perturbations (RMPs) penetrate the steep gradient region at the plasma edge. Normally, RMP driven magnetic islands can occur at the top and bottom of the H-mode pedestal and these islands generate conditions consistent with edge-localized-mode (ELM) suppression and density pump-out, respectively, based on nonlinear two-fluid MHD simulations. In contrast, MHD simulations show that the steep pressure gradient region between the top and bottom of the DIII-D pedestal is generally immune to resonant field penetration due to large local E × B and diamagnetic flows. By this fortuitous circumstance, the edge-transport-barrier and H-mode confinement can be maintained while achieving ELM suppression. However, pedestal collapse can occur in DIII-D when the screening flows are inadequate to prevent field penetration in the steep gradient region of the pedestal. Non-linear two-fluid MHD simulations support the role of resonant field penetration in pedestal collapse for DIII-D H-mode plasmas with weak edge E × B and diamagnetic screening flows. ITER will likely have weaker edge screening flows than present experiments due to its much larger size, making it more susceptible to resonant field penetration in the steep gradient region of the pedestal. Analysis of model ITER equilibria demonstrates that resonant field penetration in the steep pressure gradient region is possible for RMP levels of the order required for ELM suppression. The effect of such penetration on the ITER pedestal will depend sensitively on the resulting degree of island overlap.
Understanding photoluminescence in semiconductor Bragg-reflection waveguides
Authors: Auchter S , Schlager A , Thiel H , Laiho K , Pressl B , Suchomel H , Kamp M , Höfling S , Schneider C , Weihs G
Published: January 2021

Compared to traditional non-linear optical crystals, like BaB2O4, KTiOPO4 or LiNbO3, semiconductor integrated sources of photon pairs may operate at pump wavelengths much closer to the bandgap of the materials. This is also the case for Bragg-reflection waveguides (BRWs) targeting parametric down-conversion (PDC) to the telecom C-band. The large non-linear coefficient of the AlGaAs alloy and the strong confinement of the light enable extremely bright integrated photon pair sources. However, under certain circumstances, a significant amount of detrimental broadband photoluminescence has been observed in BRWs. We show that this is mainly a result of linear absorption near the core and subsequent radiative recombination of electron–hole pairs at deep impurity levels in the semiconductor. For PDC with BRWs, we conclude that devices operating near the long wavelength end of the S-band or the short C-band require temporal filtering shorter than 1 ns. We predict that shifting the operating wavelengths to the L-band reduces the amount of photoluminescence by 70% and making small adjustments in the material composition results in its total reduction of 90%. Such measures enable us to increase the average pump power and/or the repetition rate, which makes integrated photon pair sources with on-chip multi-gigahertz pair rates feasible for future devices.
Effect of solid loading on properties of zirconia ceramic by direct ink writing
Authors: Xia Xiaoguang , Duan Guolin
Published: January 2021

High solid loading water-based zirconia slurries for direct ink writing had been successfully prepared in this paper. The water-soluble epoxy resin and sodium polyacrylate were used as the binder and dispersant, respectively. The effect of solid loading on the rheological properties of zirconia slurries was systematically investigated. The 54–58 vol.% zirconia slurries exhibited suitable printability for direct ink writing. After sintering at 1550 °C for 2 h, the properties of sintered zirconia ceramic specimens including linear shrinkage, relative density, flexural strength, tensile strength and microstructure were examined by a series of test methods. Further, the intrinsic relationships between the solid loading and physical and mechanical properties of zirconia ceramic specimens were explored. The experimental results showed that the densification and strength of sintered zirconia ceramic could be significantly improved by increasing the solid loading of zirconia due to the less content of organic matter and water. The maximum relative density, flexural strength and tensile strength of the sintered specimens were 98.8% ,676 ± 10 MPa and 92 ± 5 MPa, respectively, when the zirconia solid loading was 58 vol.%.
Preparation of micron–sized polystyrene/silver core–shell microspheres by ultrasonic assisted electroless plating
Authors: Cheng Junhua , Gan Guoyou , Li Junpeng , Yu Xianglei , Tang Lin , Liu Chengbin
Published: January 2021

In the study, PS/Ag composite microspheres with polystyrene (PS) core and silver shell were synthesized by ultrasonic electroless plating. The samples were characterized by SEM, FTIR and XRD. The effects of times of sensitization and silver plating, mass ratio of AgNO3 to PS microspheres and stirring method on the preparation and dispersion of PS/Ag microspheres were studied. The results show that the more times of sensitization and silver plating, the more uniform the silver deposition on the surface of microspheres. When the mass ratio of AgNO3 to PS microspheres is 2: 1, it can promote the uniform coating of silver shell and reduce the content of free silver. Ultrasonic assisted electroless plating for 10 min can prevent PS/Ag microspheres from agglomerating and improve the speed of electroless plating. The thickness of the silver shell on the surface of the PS microsphere is about 200 nm.
Effect of multi-pass deformation on microstructure and flow behavior of Ti-6Al-4V alloy fabricated through hot isostatic pressing
Authors: Zhang Jishi , Liu Haijun , Xu Kaihua , Zhang Zhimin , Wang Qiang , Xue Yong
Published: January 2021

Ti-6Al-4V titanium alloy specimens fabricated through hot isostatic pressing (HIP) were made by multi-pass thermal deformation. The temperature was 950 °C, 850 °C and 900 °C for one pass, two passes and three passes, respectively, and each pass corresponded to three strain rate (i.e. 0.01 s−1, 0.1 s−1 and 1 s−1), in addition, the total reduction in height was 70%. When the true strain was greater than 0.51 and the strain rate was 1 s−1, the stress-strain curves showed the phenomenon of flow softening. X-ray diffraction (XRD) patterns indicated that the diffraction peak of α lattice plane of (0002) increased first and then declined with the strain under the strain rate of 0.1 s−1. Besides, the Vickers hardness increased with the strain at the same strain rate and was not sensitive to strain rate. Moreover, when the strain rate was 0.1 s−1, the fraction of LAGBs decreased from two passes to three passes and the microstructure results showed that the fraction of equiaxed α phases increased with the passes increasing. This is due to the strain energy increased as the increasing passes which could provide driving force for dynamic recrystallization (DRX). At the same amount of deformation, increasing the strain rate, the slender lamellar α bended and the equiaxed α grains gradually took place of the discontinuous lamellar α. Additionally, the spheroidization mechanism of lamellar α phase was mainly through grain boundaries bulging. After completing three passes deformation, the average grain size was approximately 12 μm.
Improved glucose oxidation catalytic current generation by an FAD-dependent glucose dehydrogenase-modified hydrogel electrode, in accordance with the Hofmeister effect
Authors: Yoshida Aimi , Tsujimura Seiya
Published: January 2021

Herein, we describe the effect of varying anions in an electrolyte solution on current generation by a redox hydrogel electrode. The electrode surface is coated with a thin film of hydrogel matrix, consisting of an osmium (Os) redox polymer including tethered Os complexes, polymer backbone, and a redox enzyme. In this case, the enzymes employed are flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH), which catalyzes glucose oxidation, and the result was compared with that reported earlier for glucose oxidase (GOx). The hydrogel matrix facilitates efficient electron transfer from glucose to the electrode via collision of the Os complexes and thus acts as a mediator. The degree of impact of anions on current generation is characteristic of the Hofmeister series. Chaotropic anions, such as nitrate and chloride, increase and decrease the catalytic current produced by FAD-GDH and GOx hydrogel electrodes, respectively. Such anions can adsorb onto the cationic region of the FAD-GDH surface and induce a negative charge, which enhances electrostatic interactions between the enzyme and the positively charged Os polymer. Kosmotropic anions, such as sulphate and phosphate increase the catalytic current due to hydrogel shrinkage, which increases the relative concentrations of both enzyme and mediator within the hydrogel architecture due to an increase in density. High-performance electrode design depends on understanding the impact of ion identity on catalytic current responses of redox hydrogel electrodes.
Characterisation of CVD diamond with high concentrations of nitrogen for magnetic-field sensing applications
Authors: Edmonds Andrew M , Hart Connor A , Turner Matthew J , Colard Pierre-Olivier , Schloss Jennifer M , Olsson Kevin S , Trubko Raisa , Markham Matthew L , Rathmill Adam , Horne-Smith Ben , Lew Wilbur , Manickam Arul , Bruce Scott , Kaup Peter G , Russo Jon C , DiMario Michael J , South Joseph T , Hansen Jay T , Twitchen Daniel J , Walsworth Ronald L
Published: January 2021

Ensembles of nitrogen-vacancy (NV) centres in diamond are a leading platform for practical quantum sensors. Reproducible and scalable fabrication of NV-ensembles with desired properties is crucial, as is an understanding of how those properties influence performance. This work addresses these issues by characterising nitrogen-doped diamond produced by the chemical vapour deposition (CVD) method across a range of synthesis conditions. This is shown to produce material with widely differing absorption characteristics, which is linked to the level of defects other than substitutional nitrogen (NS) and NV. In such material, the achievable concentration of NV− ([NV−]) is found to be influenced by the as-grown properties. At the 10–20 ppm level for [NS], the production of CVD-grown material with strain levels sufficient not to limit achievable device sensitivity is demonstrated and a favourable product of [NV−] and

T

2

*

is obtained. Additionally, reproducible properties over a batch of 23 samples from a single synthesis run are achieved, which appears promising for the scalability efforts underway in this area of research.
Adopting an adaptation‑mitigation‑resilience framework to ageing
Authors: Gietel-Basten Stuart
Published: January 2021

Population ageing is presented as one of the ‘grand challenges’ of the 21st century. Yet, policies designed to offset these challenges seem to be a jumbled, disjointed mix with no clear, overarching narrative. One of the successes of climate change science is the development of a clear, distinguishable framework to plan action: adaptation, mitigation and resilience. This framework can be applied to designing better policy for ageing: adapting to support people in need today; mitigating future challenges by ensuring that people and institutions ‘age better’; and building resilience by developing both a longer-term perspective and policy learning framework.
Mobility-Guided Estimation of COVID-19 Transmission Rates
Authors: Parker Dylan , Pianykh Oleg
Published: January 2021

It is of critical importance to estimate changing disease-transmission rates and their dependence on population mobility. A common approach to this problem involves fitting daily transmission rates using a susceptible-exposed-infected-recovered-(SEIR) model (regularizing to avoid overfitting) and then computing the relationship between the estimated transmission rate and mobility. Unfortunately, there are often several very different transmission-rate trajectories that can fit the reported cases well, meaning that the choice of regularization determines the final solution (and thus the mobility–transmission rate relationship) selected by the SEIR model. Moreover, the classical approaches to regularization—penalizing the derivative of the transmission rate trajectory—do not correspond to realistic properties of pandemic spread. Consequently, models fitted using derivative-based regularization are often biased toward underestimating the current transmission rate and future deaths. In this work, we propose mobility-driven regularization of the SEIR transmission rate trajectory. This method rectifies the artificial regularization problem, produces more accurate and unbiased forecasts of future deaths, and estimates a highly interpretable relationship between mobility and the transmission rate. For this analysis, mobility data related to the coronavirus disease 2019 pandemic was collected by Safegraph (San Francisco, California) from major US cities between March and August 2020.
Genetic insight into sick sinus syndrome
Authors: Thorolfsdottir Rosa B , Sveinbjornsson Gardar , Aegisdottir Hildur M , Benonisdottir Stefania , Stefansdottir Lilja , Ivarsdottir Erna V , Halldorsson Gisli H , Sigurdsson Jon K , Torp-Pedersen Christian , Weeke Peter E , Brunak Søren , Westergaard David , Pedersen Ole B , Sorensen Erik , Nielsen Kaspar R , Burgdorf Kristoffer S , Banasik Karina , Brumpton Ben , Zhou Wei , Oddsson Asmundur , Tragante Vinicius , Hjorleifsson Kristjan E , Davidsson Olafur B , Rajamani Sridharan , Jonsson Stefan , Torfason Bjarni , Valgardsson Atli S , Thorgeirsson Gudmundur , Frigge Michael L , Thorleifsson Gudmar , Norddahl Gudmundur L , Helgadottir Anna , Gretarsdottir Solveig , Sulem Patrick , Jonsdottir Ingileif , Willer Cristen J , Hveem Kristian , Bundgaard Henning , Ullum Henrik , Arnar David O , Thorsteinsdottir Unnur , Gudbjartsson Daniel F , Holm Hilma , Stefansson Kari ,   DBDS Genomic Consortium, Andersen Steffen , Erikstrup Christian , Hansen Thomas F , Hjalgrim Henrik , Jemec Gregor , Jennum Poul , Nyegaard Mette , Bruun Mie T , Petersen Mikkel , Werge Thomas , Johansson Per I
Published: January 2021

Aims

The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.

Methods and results

We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).

Conclusion

We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Temporal changes in total and hippocampal brain volume and cognitive function in patients with chronic heart failure—the COGNITION.MATTERS-HF cohort study
Authors: Frey Anna , Homola György A , Henneges Carsten , Mühlbauer Larissa , Sell Roxane , Kraft Peter , Franke Maximilian , Morbach Caroline , Vogt Marius , Müllges Wolfgang , Ertl Georg , Solymosi László , Pirpamer Lukas , Schmidt Reinhold , Pham Mirko , Störk Stefan , Stoll Guido
Published: January 2021

Aims

We quantified the concurring dynamics affecting total and hippocampal brain volume and cognitive function in patients with chronic heart failure (HF) over a period of three years.

Methods and results

A total of 148 patients with mild stable HF entered this monocentric prospective cohort study: mean age 64.5 (10.8) years; 16.2% female; 77% in New York Heart Association functional classes I–II; 128 and 105 patients attended follow-up visits after 1 and 3 years, respectively. The assessment included cardiological, neurological, psychological work-up, and brain magnetic resonance imaging. Total and regional brain volumes were quantified using an operator-independent fully automated approach and reported normalized to the mean estimated intracranial volume. At baseline, the mean hippocampal volume was ∼13% lower than expected. However, the 3-year progressive hippocampal volume loss was small: −62 mm3 [95% confidence interval (CI) −81 to −42, P < 0.0001). This corresponded to a relative change of −1.8% (95% CI −2.3 to −1.2), which was similar in magnitude as observed with physiological aging. Moreover, the load of white matter hypointensities increased within the limits of normal aging. Cognitive function during the 3-year observation period remained stable, with ‘intensity of attention’ as the only domain declining (LSmean −1.82 points, 95% CI −3.05 to −0.58, P = 0.004). After 3 years, performance in all domains of cognition remained associated with hippocampal volume (r ≥ 0.29).

Conclusion

In patients with predominantly mild HF, the markedly reduced hippocampal volume observed at baseline was associated with impaired cognitive function, but no accelerated deterioration in cognition and brain atrophy became evident over a mid-term period of three years.
Capturing the diversity of the human milk microbiota through culture-enriched molecular profiling: a feasibility study
Authors: Moossavi Shirin , Fontes Michelle E , Rossi Laura , Fusch Gerhard , Surette Michael G , Azad Meghan B
Published: January 2021

Previous human milk studies have confirmed the existence of a highly diverse bacterial community using culture-independent and targeted culture-dependent techniques. However, culture-enriched molecular profiling of milk microbiota has not been done. Additionally, the impact of storage conditions and milk fractionation on microbiota composition is not understood. In this feasibility study, we optimized and applied culture-enriched molecular profiling to study culturable milk microbiota in eight milk samples collected from mothers of infants admitted to a neonatal intensive care unit. Fresh samples were immediately plated or stored at −80°C for 2 weeks (short-term frozen). Long-term samples were stored at −20°C for >6 months. Samples were cultured using 10 different culture media and incubated both aerobically and anaerobically. We successfully isolated major milk bacteria, including Streptococcus, Staphylococcus and Bifidobacterium, from fresh milk samples, but were unable to culture any bacteria from the long-term frozen samples. Short-term freezing shifted the composition of viable milk bacteria from the original composition in fresh samples. Nevertheless, the inter-individual variability of milk microbiota composition was observed even after short-term storage. There was no major difference in the overall milk microbiota composition between milk fractions in this feasibility study. This is among the first studies on culture-enriched molecular profiling of the milk microbiota demonstrating the effect of storage and fractionation on milk microbiota composition.
THE GENETIC STRUCTURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. XV. NATURE OF DEVELOPMENTAL HOMEOSTASIS FOR VIABILITY
Authors: Mukai Terumi , Chigusa Sadao I , Kusakabe Shin-Ichi
Published: January 2021

Developmental homeostasis of relative viability was examined for homozygotes and heterozygotes using second chromosomes from two populations of Drosophila melanogaster. One was a chromosome population in which spontaneous mutations were allowed to accumulate since it was begun with a single near-normal second chromosome. The second was a natural population approximately at equilibrium. For the estimation of relative viability, the Cy method was employed (Wallace 1956), and environmental variance between simultaneously replicated cultures was used as the index of developmental homeostasis. A new method was used in the estimation of sampling variance for relative viability that was employed for the calculation of environmental variance (error variance between simultaneously replicated cultures — sampling variance). The following findings were obtained.: (1) The difference in environmental variance between homozygotes and heterozygotes could not be seen when a chromosome population with variation due to new mutations was tested. (2) When a chromosome group isolated from an approximate equilibrium population was examined, heterozygotes manifested a smaller environmental variance than the homozygotes if their relative viabilities were approximately the same. (3) There was a slight negative correlation between viability and environmental variance, although opposite results were found when the viabilities of individuals were high, especially when overdominance (coupling overdominance, Mukai 1969 a, b) was manifest. On the basis of these findings, it was concluded that developmental homeostasis was a product of natural selection, and its mechanism was discussed.
GENETIC VARIABILITY FOR DENSITY SENSITIVITY OF THREE COMPONENTS OF FITNESS IN DROSOPHILA MELANOGASTER
Authors: Marks R William
Published: January 2021

This study examines natural genetic variation in density sensitivity of three components of fitness in Drosophila melanogaster using the method of chromosome extraction. Different lines are differentially sensitive to density. The distribution of measures of density sensitivity of chromosomal homozygotes is different from that of random chromosomal heterozygotes for both location and dispersion. Density sensitivity of the components is about as variable as any of the fitness components themselves at fixed densities. The consequences of the exact nature of this density dependence are discussed with respect to the stage of the life cycle at which density dependence occurs, and the mathematical form that it takes. There is no evidence of trade-offs among the components or their density sensitivity.
A STUDY OF rDNA MAGNIFICATION PHENOMENON IN A REPAIR-RECOMBINATION DEFICIENT MUTANT OF DROSOPHILA MELANOGASTER
Authors: Polito Lino C , Cavaliere Daniela , Zazo Anna , Furia Maria
Published: January 2021

The rDNA magnification process consists of a rapid and inheritable rDNA increase occurring in bobbed males: in a few generations the bb loci acquire the wild-type rDNA value and reach a bb+ phenotype.—We have analyzed the rDNA magnification process in the repair-recombination-deficient mutant mei9a, both at the phenotypical and rDNA content levels. In mei9a bb double mutants the recovery of bb+ phenotype is strongly disturbed and the rDNA redundancy value fails to reach the wild-type level. The strong effect of this meiotic mutation on rDNA magnification suggests a close relationship between this phenomenon and the repair-recombination processes.
FILICIDAL RING-Y CHROMOSOMES IN D. MELANOGASTER
Authors: Stone James C
Published: January 2021

Ring-Y chromosomes are recovered infrequently from crosses of ring-Y-bearing males to females of certain strains (Oster 1964). Experiments described here have unveiled a diverse class of genes that exert a maternal effect on the behavior during cleavage of these "filicidal" ring chromosomes. Cytological observations of inviable embryos have revealed that the ring-Y chromosome causes gross disorganization of the cleavage nuclei. This inviability may be equivalent to the "dominant lethality" attributed to unstable ring-X chromosomes (Hinton 1955; Pasztor 1971). Mapping studies indicate that no single region of the normal Y is solely responsible for the unusual behavior of ring-Y chromosomes.
CHI-STIMULATED RECOMBINATION BETWEEN PHAGE Λ AND THE PLASMID Λdv
Authors: Stahl Franklin W , Stahl Mary M , Young Lisa , Kobayashi Ichizo
Published: January 2021

Chi promotes Rec-mediated recombination between phage λ DNA and the homologous plasmid λdv. In the absence of Chi, some of the interactions splice λdv into λ, whereas others patch information from λdv into λ. When Chi is in the phage DNA, splices and patches are increased in frequency by the same factor. This result strengthens the analogy between Chi and recombination-promoting elements in fungi. It also rules out one model for the previously reported orientation dependence of Chi phenotype.
CIS-TRANS EFFECTS INDUCED BY LINKAGE DISEQUILIBRIUM
Authors: Turelli Michael
Published: January 2021

This note concerns theoretical and experimental studies of multifactorial traits, especially fitness and its components, in which (1) the loci studied are only a subset of those relevant to the character of interest and (2) the genotypes at the loci studied are in nonrandom association (linkage disequilibrium) with genotypes at the loci ignored. In these cases, phenotypic differences between cis and trans double heterozygotes can occur even though no linkage phase effects are inherent in the genetic determination of the trait. Examples are drawn from both theoretical and experimental work, and implications in both areas are discussed.
FREQUENCY OF γ-RAY INDUCED SPECIFIC LOCUS AND RECESSIVE LETHAL MUTATIONS IN MATURE GERM CELLS OF THE ZEBRAFISH, BRACHYDANIO RERIO
Authors: Chakrabarti Sankar , Streisinger George , Singer Fred , Walker Charline
Published: January 2021

Specific locus and recessive lethal mutations are induced by γ-rays with approximately first order kinetics in the zebrafish (Brachydanio rerio) with frequencies of 4 × 10-5 r-1 and 4 × 10-3 r-1, respectively. The surprisingly low ratio (100:1) of recessive lethals to specific locus mutations may be due to the induction of large deficiencies by γ-rays.
ANALYSIS OF Y-LINKED MUTATIONS TO MALE STERILITY IN DROSOPHILA MELANOGASTER
Authors: Kennison James A
Published: January 2021

The frequencies of newly induced male-sterilizing lesions on both the X and Y chromosomes of Drosophila melanogaster were determined after either 4000 r of γ-irradiation or adult feeding of ethyl methanesulfonate. The Y chromosome is approximately twice as sensitive as the X chromosome to newly induced male-sterilizing lesions after γ-irradiation, but slightly less sensitive after ethyl methanesulfonate treatment. A large proportion of the radiation-induced lesions are associated with Y-autosome or X-autosome translocations, with the Y chromosome recovered in translocations far in excess of the frequency expected from metaphase lengths. Although translocations between the X and Y chromosomes or between autosomes do not appear to sterilize heterozygous males, interchanges between sex chromosomes and autosomes often sterilize males carrying them in a dominant manner, suggesting that the organization of the genome is critical for normal spermatogenesis. Complementation tests between recessive Y-linked male-sterilizing mutants do not reveal the existence of any additional fertility loci beyond the six previously defined.
MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY
Authors: Konno Ryuichi , Yasumura Yosihiro
Published: January 2021

d-Amino acid oxidase activity in the kidney homogenates of mice of seven strains was measured to search for a mutant for this enzyme. There was a consistent sex difference in the enzyme activity in these strains: male mice showed higher levels of the enzyme activity than females. In contrast to other strains, some mice of the ddY strain did not possess enzyme activity. This trait was inheritable, and a mouse stock without enzyme activity (DAO-) was established. The allele (Dao-1c) carried by the DAO- mice was recessive and behaved as a single autosomal gene in inheritance. Heterozygous mice for this gene (Dao-1  +/Dao-1c) showed nearly half the enzyme activity of the wild-type homozygotes (Dao-1  +/Dao-1  +), suggesting that Dao-1c is a null allele and that there is a gene dosage effect on the enzyme activity.
HUMAN MITOCHONDRIAL DNA VARIATION AND EVOLUTION: ANALYSIS OF NUCLEOTIDE SEQUENCES FROM SEVEN INDIVIDUALS
Authors: Aquadro Charles F , Greenberg Barry D
Published: January 2021

We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the importance of recognizing the large standard errors associated with estimates of sequence variability, particularly when constructing phylogenies among closely related sequences. Analysis of the observed number and direction of substitutions revealed several significant biases, most notably a strand dependence of substitution type and a 32-fold bias favoring transitions over transversions. The results also revealed a significantly nonrandom distribution of nucleotide substitutions and sequence length variation. Significantly more multiple substitutions were observed than expected for these closely related sequences under the assumption of uniform rates of substitution. The bias for transitions has resulted in predominantly convergent or parallel changes among the observed multiple substitutions. There is no convincing evidence that recombination has contributed to the mtDNA sequence diversity we have observed.
THE EFFECT OF DDT ON THE POLYMORPHISM AT THE G6pd AND Pgd LOCI IN DROSOPHILA MELANOGASTER
Authors: Bijlsma R , Kerver J W M
Published: January 2021

For the degradation of DDT and other chlorohydrocarbon insecticides energy in the form of NADPH is needed which for the greater part is supplied by the pentose phosphate shunt. Therefore the influence of DDT on the polymorphism at the G6pd and Pgd loci in Drosophila melanogaster was investigated by studying its effect on egg to adult survival and adult survival. The results show the existence of significant differences in fitness between the different genotypes of the two loci for both components. It is found that the effect of DDT supplementation differs significantly from the effect of sodium octanoate addition. DDT treatment also increases the activity of the pentose phosphate shunt as measured by the activity of G6PD and 6PGD. In larvae a 50% increase in activity is found and in adults a 100% increase. As there is little doubt that the activities of G6PD and 6PGD are somehow correlated with the fitness of flies, the data are discussed in relation to the in vitro and in vivo differences in activity between the different allozymes of both G6PD and 6PGD.
AN APPROACH TO POPULATION AND EVOLUTIONARY GENETIC THEORY FOR GENES IN MITOCHONDRIA AND CHLOROPLASTS, AND SOME RESULTS
Authors: Birky C William , Maruyama Takeo , Fuerst Paul
Published: January 2021

We developed population genetic theory for organelle genes, using an infinite alleles model appropriate for molecular genetic data, and considering the effects of mutation and random drift on the frequencies of selectively neutral alleles. The effects of maternal inheritance and vegetative segregation of organelle genes are dealt with by defining new effective gene numbers, and substituting these for 2Ne in classical theory of nuclear genes for diploid organisms. We define three different effective gene numbers. The most general is N  λ, defined as a function of population size, number of organelle genomes per cell, and proportions of genes contributed by male and female gametes to the zygote. In many organisms, vegetative segregation of organelle genomes and intracellular random drift of organelle gene frequencies combine to produce a predominance of homoplasmic cells within individuals in the population. Then, the effective number of organelle genes is Neo, a simple function of the numbers of males and females and of the maternal and paternal contributions to the zygote. Finally, when the paternal contribution is very small, Neo is closely approximated by the number of females, Nf. Then if the sex ratio is 1, the mean time to fixation or loss of new mutations is approximately two times longer for nuclear genes than for organelle genes, and gene diversity is approximately four times greater. The difference between nuclear and organelle genes disappears or is reversed in animals in which males have large harems. The differences between nuclear and organelle gene behavior caused by maternal inheritance and vegetative segregation are generally small and may be overshadowed by differences in mutation rates to neutral alleles. For monoecious organisms, the effective number of organelle genes is approximately equal to the total population size N. We also show that a population can be effectively subdivided for organelle genes at migration rates which result in panmixis for nuclear genes, especially if males migrate more than females.
EXPECTED LINKAGE DISEQUILIBRIUM FOR A NEUTRAL LOCUS LINKED TO A CHROMOSOMAL ARRANGEMENT
Authors: Strobeck Curtis
Published: January 2021

The expected value of the squared linkage disequilibrium is derived for a neutral locus associated with a chromosomal arrangement that is maintained in the population by strong balancing selection. For a given value of recombination, the expected squared linkage disequilibrium is shown to decrease as the intensity of selection maintaining the arrangement increases. The transient behavior of the expected square linkage disequilibrium is also derived. This theory applies to loci that are closely linked to inversions in Drosophila species and to loci closely linked to the differential segments of the translocation complexes in ring-forming species of Oenothera. In both cases the strong linkage disequilibria that have been observed in natural populations can be explained by random drift.
MULTIPLE-LOCUS DEPARTURES FROM PANMICTIC EQUILIBRIUM WITHIN AND BETWEEN VILLAGE GENE POOLS OF AMERINDIAN TRIBES AT DIFFERENT STAGES OF AGGLOMERATION
Authors: Smouse Peter E , Neel James V , Liu Wanda
Published: January 2021

A comparative analysis of departures from multiple-locus Hardy-Weinberg equilibrium is presented for a set of four tribal Indian groups (the Yanomama, Makiritare, Wapishana and Ticuna) from the lowlands of South America. These tribes span a range of agglomeration and acculturation from the most traditional, swidden horticulturalists to frontier townspeople. The small-group social organization typical of traditional horticulturalists leads to substantial departures from tribal panmixia, as manifested by the distribution of multiple-locus genotypes both within and between villages. Within villages, the departures from single-locus Hardy-Weinberg equilibrium are small and nonsignificant, but the departures from gametic equilibrium (independence of loci) are substantial, even for the unlinked loci we have used to characterize these populations. The departures from single-locus homogeneity across villages are also substantial. One of the normal concomitants of increasing acculturation in this setting is an increase in agglomeration. As agglomeration increases, the departures from multiple-locus panmixia decrease, a process that can be very rapid. We discuss both the shifting balance theory of evolution and punctuated evolutionary rates in light of the small group social organization that must have obtained throughout most of human evolution.
A NEW METHOD FOR ESTIMATING THE EFFECTIVE POPULATION SIZE FROM ALLELE FREQUENCY CHANGES
Authors: Pollak Edward
Published: January 2021

A new procedure is proposed for estimating the effective population size, given that information is available on changes in frequencies of the alleles at one or more independently segregating loci and the population is observed at two or more separate times. Approximate expressions are obtained for the variances of the new statistic, as well as others, also based on allele frequency changes, that have been discussed in the literature. This analysis indicates that the new statistic will generally have a smaller variance than the others. Estimates of effective population sizes and of the standard errors of the estimates are computed for data on two fly populations that have been discussed in earlier papers. In both cases, there is evidence that the effective population size is very much smaller than the minimum census size of the population.
EGG-LAYING DEFECTIVE MUTANTS OF THE NEMATODE CAENORHABDITIS ELEGANS
Authors: Trent Carol , Tsung Nancy , Horvitz H Robert
Published: January 2021

We have isolated 145 fertile mutants of C. elegans that are defective in egg laying and have characterized 59 of them genetically, behaviorally and pharmacologically. These 59 mutants define 40 new genes called egl, for egg-lay ing abnormal. Most of the other mutants are defective in previously identified genes. The egl mutants differ with respect to the severity of their egg-laying defects and the presence of behavioral or morphological pleiotropies. We have defined four distinct categories of mutants based on their responses to the pharmacological agents serotonin and imipramine, which stimulate egg laying by wild-type hermaphrodites. These drugs test the functioning of the vulva, the vulval and uterine muscles and the hermaphrodite-specific neurons (HSNs), which innervate the vulval muscles. Mutants representing 14 egl genes fail to respond to serotonin and to imipramine and are likely to be defective in the functioning of the vulva or the vulval and uterine muscles. Four mutants (representing four different genes) lay eggs in response to serotonin but not to imipramine and appear to be egg-laying defective because of defects in the HSNs; three of these four were selected specifically for these drug responses. Mutants representing seven egl genes lay eggs in response to serotonin and to imipramine. One egl mutant responds to imipramine but not to serotonin. The remaining egl mutants show variable or intermediate responses to the drugs. Two of the HSN-defective mutants, egl-1 and her-1(n695), lack HSN cell bodies and are likely to be expressing the normally male-specific program of HSN cell death. Whereas egl-1 animals appear to be defective specifically in HSN development, her-1(n695) animals exhibit multiple morphological pleiotropies, displaying partial transformation of the sexual phenotype of many cells and tissues. At least two of the egl mutants appear to be defective in the processing of environmental signals that modulate egg laying and may define new components of the neural circuitry that control egg laying.