bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mexican Revolution
Authors: Johnson Benjamin H.
Published: January 2019

When rebels captured the border city of Juárez, Mexico, in May 1911 and forced the abdication of President Porfirio Díaz shortly thereafter, they not only overthrew the western hemisphere’s oldest regime but also inaugurated the first social revolution of the 20th century. Driven by disenchantment with an authoritarian regime that catered to foreign investment, labor exploitation, and landlessness, revolutionaries dislodged Díaz’s regime, crushed an effort to resurrect it, and then spent the rest of the decade fighting one another for control of the nation. This struggle, recognized ever since as foundational for Mexican politics and identity, also had enormous consequences for the ethnic makeup, border policing, and foreign policy of the United States. Over a million Mexicans fled north during the 1910s, perhaps tripling the country’s Mexican-descent population, most visibly in places such as Los Angeles that had become overwhelmingly Anglo-American. US forces occupied Mexican territory twice, nearly bringing the two nations to outright warfare for the first time since the US–Mexican War of 1846–1848. Moreover, revolutionary violence and radicalism transformed the ways that much of the American population and its government perceived their border with Mexico, providing a rationale for a much more highly policed border and for the increasingly brutal treatment of Mexican-descent people in the United States. The Mexican Revolution was a turning point for Mexico, the United States, and their shared border, and for all who crossed it.
Ellis Island Immigration Station
Authors: Cannato Vincent J.
Published: January 2019

The Ellis Island Immigration Station, located in New York Harbor, opened in 1892 and closed in 1954. During peak years from the 1890s until the 1920s, the station processed an estimated twelve million immigrants. Roughly 75 percent of all immigrants arriving in America during this period passed through Ellis Island. The station was run by the federal Immigration Service and represented a new era of federal control over immigration. Officials at Ellis Island were tasked with regulating the flow of immigration by enforcing a growing body of federal laws that barred various categories of “undesirable” immigrants. As the number of immigrants coming to America increased, so did the size of the inspection facility. In 1907, Ellis Island processed more than one million immigrants. The quota laws of the 1920s slowed immigration considerably and the rise of the visa system meant that Ellis Island no longer served as the primary immigrant inspection facility. For the next three decades, Ellis Island mostly served as a detention center for those ordered deported from the country.

After Ellis Island closed in 1954, the facility fell into disrepair. During a period of low immigration and a national emphasis on assimilation, the immigrant inspection station was forgotten by most Americans. With a revival of interest in ethnicity in the 1970s, Ellis Island attracted more attention, especially from the descendants of immigrants who entered the country through its doors. In the 1980s, large-scale fundraising for the restoration of the neighboring Statue of Liberty led to a similar effort to restore part of Ellis Island. In 1990, the Main Building was reopened to the public as an immigration museum under the National Park Service. Ellis Island has evolved into an iconic national monument with deep meaning for the descendants of the immigrants who arrived there, as well as a contested symbol to other Americans grappling with the realities of contemporary immigration.
Poverty in the Modern American City
Authors: Howard Ella
Published: January 2019

American cities expanded during the late 19th century, as industrial growth was fueled by the arrival of millions of immigrants and migrants. Poverty rates escalated, overwhelming existing networks of private charities. Progressive reformers created relief organizations and raised public awareness of urban poverty. The devastating effects of the Great Depression inspired greater focus on poverty from state and federal agencies. The Social Security Act, the greatest legacy of the New Deal, would provide a safety net for millions of Americans. During the postwar era of general prosperity, federal housing policies often reinforced and deepened racial and socioeconomic inequality and segregation. The 1960s War on Poverty created vital aid programs that expanded access to food, housing, and health care. These programs also prompted a rising tide of conservative backlash against perceived excesses. Fueled by such critical sentiments, the Reagan administration implemented dramatic cuts to assistance programs. Later, the Clinton administration further reformed welfare by tying aid to labor requirements. Throughout the 20th century, the urban homeless struggled to survive in hostile environments. Skid row areas housed the homeless for decades, providing shelter, food, and social interaction within districts that were rarely visited by the middle and upper classes. The loss of such spaces to urban renewal and gentrification in many cities left many of the homeless unsheltered and dislocated.
The Central Business District in American Cities
Authors: Remus Emily
Published: January 2019

The central business district, often referred to as the “downtown,” was the economic nucleus of the American city in the 19th and 20th centuries. It stood at the core of urban commercial life, if not always the geographic center of the metropolis. Here was where the greatest number of offices, banks, stores, and service institutions were concentrated—and where land values and building heights reached their peaks. The central business district was also the most easily accessible point in a city, the place where public transit lines intersected and brought together masses of commuters from outlying as well as nearby neighborhoods. In the downtown, laborers, capitalists, shoppers, and tourists mingled together on bustling streets and sidewalks. Not all occupants enjoyed equal influence in the central business district. Still, as historian Jon C. Teaford explained in his classic study of American cities, the downtown was “the one bit of turf common to all,” the space where “the diverse ethnic, economic, and social strains of urban life were bound together, working, spending, speculating, and investing.”

The central business district was not a static place. Boundaries shifted, expanding and contracting as the city grew and the economy evolved. So too did the primary land uses. Initially a multifunctional space where retail, wholesale, manufacturing, and financial institutions crowded together, the central business district became increasingly segmented along commercial lines in the 19th century. By the early 20th century, rising real estate prices and traffic congestion drove most manufacturing and processing operations to the periphery. Remaining behind in the city center were the bulk of the nation’s offices, stores, and service institutions. As suburban growth accelerated in the mid-20th century, many of these businesses also vacated the downtown, following the flow of middle-class, white families. Competition with the suburbs drained the central business district of much of its commercial vitality in the second half of the 20th century. It also inspired a variety of downtown revitalization schemes that tended to reinforce inequalities of race and class.
Deep root growth, ABA adjustments and root water uptake response to soil water deficit in giant reed
Authors: Zegada-Lizarazu Walter , Monti Andrea
Published: January 2019

Background and Aims

Giant reed (Arundo donax L.) is a deep-rooted crop that can survive prolonged dry periods probably as a result of its capacity to uptake water from below ground, but specific information on the functioning of deep/shallow roots is missing. The objective of this study was to understand the dynamic interrelationships of root water acquisition, canopy water conservation and abscisic acid (ABA) signals from both shallow and deep roots.

Methods

In transparent split top–bottom rhizotron systems (1-m-high columns), where hydraulically isolated and independently watered layers were created with the aid of calibrated soil moisture sensors, water uptake trends were monitored. Rooting patterns were traced on the walls of the rhizotrons. Leaf gas exchange was determined using a portable infrared gas analyser. Leaf and root ABA concentrations were monitored.

Key Results

Under well-watered conditions, water uptake from both upper and deeper soil layers was similar. Water uptake from deeper soil layers increased gradually by up to 2.2-fold when drought stress was imposed to upper layers compared to the control conditions. Despite the significant increase in water uptake from deeper layers, surface root length density of drought-treated plants remained unchanged, suggesting increased root water uptake efficiency by these roots. However, these adjustments were not sufficient to sustain photosynthesis and therefore biomass accumulation, which was reduced by 42 %. The ABA content in shallower drought-treated roots increased 2.6-fold. This increase closely and positively correlated with foliar ABA concentration, increased intrinsic water use efficiency and leaf water potential (LWP).

Conclusions

Giant reed is able to change its water sources depending on water availability and to maximize water uptake efficiency to satisfy canopy evapotranspirative demands. The regulation of deep root functioning and distribution, adjustment of canopy size, and root/foliar synthesized ABA play a central role in controlling LWP and leaf transpiration efficiency.
R
h = ct and the eternal coasting cosmological model
Authors: John Moncy V
Published: January 2019

We point out that the non-empty Rh = ct cosmological model has some known antecedents in the literature. Some of those eternal coasting models are published even before the discovery of the accelerated expansion of the Universe and were shown to have none of the commonly discussed cosmological problems and also that H0t0 = 1. The Rh = ct model is only the special (flat) case of the eternal coasting model. An additional feature in the coasting model is that Ωm/Ωdark energy  = some constant of the order of unity, so that also the cosmic coincidence problem is avoided.
Weaning From Long-term Opioid Therapy
Authors: MOSS CHAILEE , BOSSANO CARLA , PATEL SILKA , POWELL ANNA , CHAN SEAY RACHEL , BORAHAY MOSTAFA A.
Published: January 2019

Opioid use for chronic noncancer pain poses a challenge to the gynecologist, and weaning opioids is often a goal for clinicians and patients. In some cases, opioid cessation can be achieved by weaning a patient’s prescribed opioid or with symptomatic management with long-acting opioids or alpha2-adrenergic medications. This review imparts a basic understanding of the physiology of opioid withdrawal, strategies for achieving opioid abstinence, medications for treating the symptoms of withdrawal, and alternatives to opioid taper.
Differential regulation of native and learned behavior by creb-1/crh-1 in Caenorhabditis elegans
Authors: Dahiya Yogesh , Rose Saloni , Thapliyal Shruti , Bhardwaj Shivam , Prasad Maruthi , Babu Kavita
Published: January 2019

1.

Memory formation is crucial for the survival of animals. Here, we study the effect of differentcrh-1(C. eleganshomolog of mammalian CREB1) mutations on the ability ofC. elegansto form long-term memory (LTM). Null mutants increb1/crh-1are defective in LTM formation across phyla. We show that specific isoforms of CREB1/CRH-1, CRH-1c and CRH-1e, are primarily responsible for memory related functions of the transcription factor inC. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolishes the long-term memory of the animal. Further, CRH-1e expression in RIM or AVE neurons is sufficient to rescue long-term memory defects ofcreb1/crh-1null mutants. We show that apart from being LTM defective,creb1/crh-1null mutant animals show defects in native chemotaxis behavior. We characterize the amino acids K247 and K266 as responsible for the LTM related functions of CRH-1 while being dispensable for it’s native chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor and can be further exploited to find CREB1 targets involved in the process of memory formation.
Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A
Authors: Göbl Christoph , Morris Vanessa K , van Dam Loes , Visscher Marieke , Polderman Paulien E. , Hartlmüller Christoph , de Ruiter Hesther , Hora Manuel , Liesinger Laura , Birner-Gruenberger Ruth , Vos Harmjan R. , Reif Bernd , Madl Tobias , Dansen Tobias B.
Published: January 2019

Accumulation of the CDK4/6 inhibitor p16INK4Ain response to oncogenic transformation leads to cell cycle arrest and senescence and is therefore frequently lost in cancer. p16INK4Ais also known to accumulate under conditions of oxidative stress and thus could potentially be regulated by the reversible oxidation of cysteines (redox signaling). Indeed, oxidation of the single cysteine in p16INK4Ain human cells occurs under relatively mild oxidizing conditions and leads to disulfide-dependent dimerization. p16INK4Ais an all alpha-helical protein, but here we report that upon cysteine-dependent dimerization, p16INK4Aundergoes a dramatic structural rearrangement and forms aggregates that have the typical features of amyloid fibrils, including binding of diagnostic dyes, presence of cross-β sheet structure, and typical dimensions found in electron microscopy. p16INK4Aamyloid formation abolishes its function as a CDK4/6 inhibitor. Collectively, these observations mechanistically link the cellular redox state to the inactivation of p16INK4Athrough the formation of amyloid fibrils.
Mammalian Amoeboid Swimming is propelled by molecular and not protrusion-based paddling in Lymphocytes
Authors: Aoun Laurene , Nègre Paulin , Farutin Alexander , Garcia-Seyda Nicolas , Rizvi Mohd Suhail , Galland Rémi , Michelot Alphée , Luo Xuan , Biarnes-Pelicot Martine , Hivroz C. , Rafai Salima , Sibarita Jean-Baptiste , Valignat Marie-Pierre , Misbah Chaouqi , Theodoly Olivier
Published: January 2019

Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like fibroblasts crawling, relies on maturation of adhesion complexes and actin fiber traction, while the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on 2D and in 3D solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming. We show here experimentally and computationally that leukocytes do swim, and that propulsion is not fueled by waves of cell deformation but by a rearward and inhomogeneous treadmilling of the cell envelope. We model the propulsion as a molecular paddling by transmembrane proteins linked to and advected by the actin cortex, whereas freely diffusing transmembrane proteins hinder swimming. This mechanism explains that swimming is five times slower than the cortex retrograde flow. Resultantly the ubiquitous ability of mammalian amoeboid cells to migrate in various environments can be explained for lymphocytes by a single machinery of envelope treadmilling.
Different integrins mediate haptotaxis of T lymphocytes towards either lower or higher adhesion zones
Authors: Luo X , Aoun L , Biarnes-Pelicot M. , Strale Pierre-Olivier , Studer V , Valignat M.-P. , Theodoly O.
Published: January 2019

Guidance of cells by molecules anchored on a substrate, known as haptotaxis, is arguably crucial in development, immunology and cancer, however the exact cues and mechanisms driving cell orientation in vivo are hardly identified. Adhesive haptotaxis has been described in the case of mesenchymatous cells that develop strong pulling forces with their substrates and orient via a tug of war mechanism – a competition between cells’ pulling edges. In the case of amoeboid cells that migrate with minimal interaction with their substrate, existence of adhesive haptotaxis remains unclear. Here, we studied the crawling of human T lymphocytes on substrates with spatially modulated adhesivity, and observed haptotaxis with surface concentrations of integrin ligands found on high endothelial veinules. Overexpression of ICAM-1 and VCAM-1 molecules observed in vivo at transmigration portals can therefore promote leukocyte recruitment. Mechanistically, we show that integrin-mediated haptotaxis of lymphocytes differ both from active chemotaxis, because no mechanotransduction was detected, and from the passive tug of war mechanism of mesenchymatous cells, because different integrins support opposite phenotypes. Cells favored more adherent zones with VLA-4 and, counterintuitively, less adherent zones with LFA-1. These results reveal that integrins control differential adhesive haptotaxis behaviors without mechanotransduction, and this smart capability may support unsuspected ways for cells path selection.
Microextrusion Printing Cell-Laden Networks of Type I Collagen with Patterned Anisotropy and Geometry
Authors: Nerger Bryan A. , Brun P.-T. , Nelson Celeste M.
Published: January 2019

Type I collagen self-assembles into three-dimensional (3D) fibrous networks. These dynamic viscoelastic materials can be remodeled in response to mechanical and chemical cues to form anisotropic networks, the structure of which influences tissue development, homeostasis, and disease progression. Conventional approaches for fabricating anisotropic networks of type I collagen are often limited to unidirectional alignment over small areas. Here, we describe a new approach for engineering cell-laden anisotropic networks of type I collagen fibers using 3D microextrusion printing of a collagen-Matrigel ink. By adding molecular crowders, we demonstrate hierarchical control of 3D-printed collagen with the ability to spatially pattern collagen fiber anisotropy and geometry. Our data suggest that collagen anisotropy results from a combination of molecular crowding in the ink and shear and extensional flows present during 3D-printing. We demonstrate that human breast cancer cells cultured on 3D-printed collagen orient along the direction of collagen fiber alignment. We also demonstrate the ability to simultaneously bioprint epithelial cell clusters and control the alignment and geometry of collagen fibers surrounding cells in the bioink. The resulting cell-laden constructs consist of epithelial cell clusters fully embedded in aligned networks of collagen fibers. We foresee that cell-laden collagen-Matrigel constructs with spatially-patterned anisotropy and geometry will be broadly useful for the fields of developmental biology, tissue engineering, and regenerative medicine.
The virome in adult monozygotic twins with concordant or discordant gut microbiomes
Authors: Moreno-Gallego J. Leonardo , Chou Shao-Pei , Di Rienzi Sara C. , Goodrich Julia K. , Spector Timothy , Bell Jordana T. , Youngblut  , Hewson Ian , Reyes Alejandro , Ley Ruth E.
Published: January 2019

The virome is one of the most variable components of the human gut microbiome. Within twin-pairs, viromes have been shown to be similar for infants but not for adults, indicating that as twins age and their environments and microbiomes diverge, so do their viromes. The degree to which the microbiome drives the virome’s vast diversity is unclear. Here, we examined the relationship between microbiome diversity and virome diversity in 21 adult monozygotic twin pairs selected for high or low microbiome concordance. Viromes derived from virus-like particles were unique to each subject, dominated by Caudovirales and Microviridae, and exhibited a small core that included crAssphage. Microbiome-discordant twins had more dissimilar viromes compared to microbiome-concordant twins, and the richer the microbiomes, the richer the viromes. These patterns were driven by the bacteriophages, not eukaryotic viruses. These observations support a strong role of the microbiome in patterning the virome.
Locally Fixed Alleles: A method to localize gene drive to island populations
Authors: Sudweeks Jaye , Hollingsworth Brandon , Blondel Dimitri V. , Campbell Karl J. , Dhole Sumit , Eisemann John D. , Edwards Owain , Godwin John , Howald Gregg R. , Oh Kevin , Piaggio Antoinette J. , Prowse Thomas A. A. , Ross Joshua V. , Saah J. Royden , Shiels Aaron B. , Thomas Paul , Threadgill David W. , Vella Michael R. , Gould Fred , Lloyd Alun L.
Published: January 2019

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to multiple genomic alleles becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.
A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases
Authors: Liang Haoyu , Jiang Lin , Jiang Qiyun , Shi Jie , Xiang Jingxi , Yan Xiaohui , Zhu Xiangcheng , Zhao Lixing , Shen Ben , Duan Yanwen , Huang Yong
Published: January 2019

Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for β-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs throughin silicogenome mining, sequence and genome neighborhood network analysis. Using HCS-based probes, the survey of 1207 inhouse strains and 18 soil samples from different geological locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs.
Sensory feedback independent pre-song vocalizations correlate with current state of motor preparation
Authors: Rao Divya , Kojima Satoshi , Rajan Raghav
Published: January 2019

Many self-initiated, learned, motor sequences begin by repeating a simple movement, like ball-bouncing before a tennis serve, and this repetition is thought to represent motor preparation. Do these simple movements provide real-time sensory feedback used by the brain for getting ready or do they simply reflect internal neural preparatory processes? Here, we addressed this question by examining the introductory notes (INs) that zebra finches repeat before starting their learned song sequence. INs progress from a variable initial state to a stereotyped final state before each song and are thought to represent motor preparation before song. Here, we found that the mean number of INs before song and the progression of INs to song were not affected by removal of two sensory feedback pathways (auditory and proprioceptive). In both feedback-intact and feedback-deprived birds, the presence of calls (other non-song vocalizations), just before the first IN, was correlated with fewer INs before song and an initial state closer to song. Finally, the initial IN state correlated with the time to song initiation. Overall, these results show that INs do not provide real-time sensory feedback for preparing the motor system. Rather, repetition of INs, and possibly, other such simple movements, may reflect the “current” state of internal neural preparatory processes involved in getting the brain ready to initiate a learned movement sequence.

SUMMARY STATEMENT

The number and progression of introductory notes to song in the zebra finch are not affected by removal of sensory feedback.
Neural differentiation is increased by GSK-3β inhibition and decreased by tankyrase inhibition in human neural precursor cells
Authors: Telias Michael , Ben-Yosef Dalit
Published: January 2019

Glycogen synthase kinase-3β (GSK-3β) and tankyrase-1/2 (TANK) are two enzymes known to play multiple roles in cell biology, including regulation of proliferation, differentiation and metabolism. Both of them act on the canonical Wnt/β-Catenin pathway, but are also involved in many other independent intracellular mechanisms. More importantly, GSK-3β and TANK have been shown to play crucial roles in different diseases, including cancer and neurological disorders. The GSK-3β-inhibitor ‘CHIR’ and the TANK-inhibitor ‘XAV’ are two pyrimidine molecules, holding high potential as possible therapeutic drugs. However, their effect on neural tissue is poorly understood. In this study, we tested the effects of CHIR and XAV on human neural precursor cells (hNPCs) derived from human embryonic stem cells. We found that CHIR-mediated inhibition of GSK-3β promotes neural differentiation. In contrast, XAV-mediated inhibition of TANK leads to de-differentiation. These results highlight the relative importance of these two enzymes in determining the neurodevelopmental status of hNPCs. Furthermore, they shed light on the roles of Wnt signaling during early human neurogenesis.
History-dependent perturbation response in limb muscle
Authors: Libby Thomas , Chukwueke Chidinma , Sponberg Simon
Published: January 2019

1

Muscle mediates movement but movement is typically unsteady and perturbed. Muscle is known to behave non-linearly and with history dependent properties during steady locomotion, but the importance of history dependence in mediating muscles function during perturbations remains less clear. To explore muscle’s capacity to mitigate perturbations, we constructed a series of perturbations that varied only in kinematic history, keeping instantaneous position, velocity and time from stimulation constant. We discovered that muscle’s perturbation response is profoundly history dependent, varying by four fold as baseline frequency changes, and dissipating energy equivalent to ~ 6 times the kinetic energy of all the limbs (nearly 2400 WKg−1). Muscle’s energy dissipation during a perturbation is predicted primarily by the force at the onset of the perturbation. This relationship holds across different frequencies and timings of stimulation. This history dependence behaves like a viscoelastic memory producing perturbation responses that vary with the frequency of the underlying movement.

Summary Statement

The response of muscles to rapid, identical strain perturbations is history dependent, but is captured by a viscoelastic model with memory. Muscle function during perturbations therefore depends on locomotor frequency.
Genetic interactions of histone acetyl-transferase enzymes encoding genesGcn5andMofwithhsrωlncRNA gene
Authors: Chaturvedi Deo Prakash
Published: January 2019

The hsrω lncRNAs are known to interact with the Iswi chromatin remodeler while Iswi is known to interact with Gcn5, a general histone acetyl transferase, and Mof, a male-specific HAT essential for H4K16 acetylation and consequent hyperactivity of the single X-chromosome in maleDrosophila. We show here thathsrωgenetically interacts with Gcn5 as well as Mof, but unlike the suppression of phenotypes due to down-regulation or absence of Iswi, those following down-regulation of Gcn5 or Mof are suppressed by over-expression ofhsrω. General lethality caused byAct-GAL4driven global expression ofGcn5-RNAiand the male-specific lethality followingMof-RNAitransgene expression were partially suppressed by over-expression ofhsrω, but not by down regulation throughhsrω-RNAi. Likewise, eye phenotypes followingey-GAL4driven down-regulation of Gcn5 or Mof were also partially suppressed by over-expression ofhsrω. Act-GAL4driven global over-expression ofhsrωalong withGcn5-RNAitransgene substantially restored levels of Gcn5 RNA as well as protein that were reduced by Gcn5-RNAi.Mof-RNAitransgene expression reduced Megator and Msl-2 levels and their nuclear distribution patterns; over-expression ofhsrωalong withMof-RNAisubstantially restored Megator levels and its distribution at the nuclear rim and in nucleoplasmic speckles and at the same time restored the male X-chromosome specific localization of Msl-2. Earlier reported antagonistic interactions of Mof with Iswi and interaction of hsrω transcripts with Megator appear to underlie the suppression of Gcn5 and Mof phenotypes by over-expression of the lncRNAs. Present results add the dosage compensation pathway to the list of diverse pathways in which the multiple lncRNAs produced by thehsrωare known to have important roles.
BjuWRR1, a CC-NB-LRR gene identified in Brassica juncea, confers resistance to white rust caused by Albugo Candida
Authors: Arora Heena , Padmaja K. Lakshmi , Paritosh Kumar , Mukhi Nitika , Tewari A. K. , Mukhopadhyay Arundhati , Gupta Vibha , Pradhan Akshay K , Pental Deepak
Published: January 2019

White rust caused by oomycete pathogen Albugo candida is a significant disease of crucifer crops including Brassica juncea (mustard), a major oilseed crop of the Indian subcontinent. Earlier a resistance-conferring locus named AcB1-A5.1 was mapped in an east European gene pool line of B. juncea – Donskaja-IV. This line was tested along with some other lines of B. juncea (AABB), B. rapa (AA) and B. nigra (BB) for resistance to six isolates of A. candida collected from different mustard growing regions of India. Donskaja-IV was found to be completely resistant to all the tested isolates. Sequencing of a BAC spanning the locus AcB1-A5.1 showed the presence of a single CC-NB-LRR protein encoding R gene. The genomic sequence of the putative R gene with its native promoter and terminator was used for the genetic transformation of a susceptible Indian gene pool line Varuna and was found to confer complete resistance to all the isolates. This is the first white rust resistance-conferring gene described from Brassica species and has been named BjuWRR1. Allelic variants of the gene in B. juncea germplasm and orthologues in the Brassicaceae genomes were studied to understand the evolutionary dynamics of the BjuWRR1 gene.

Highlight

BjuWRR1, a CNL type R gene, was identified from an east European gene pool line of Brassica juncea and validated for conferring resistance to white rust by genetic transformation.
Disparate evolution of virus populations in upper and lower airways of mechanically ventilated patients
Authors: Koel Björn F. , van Someren Gréve Frank , Vigeveno René M. , Pater Maarten , Russell Colin A. , de Jong Menno D.
Published: January 2019

In routine surveillance and diagnostic testing, influenza virus samples are typically collected only from the upper respiratory tract (URT) due to the invasiveness of sample collection from the lower airways. Very little is known about virus variation in the lower respiratory tract (LRT) and it remains unclear if the virus populations at different sites of the human airways may develop to have divergent genetic signatures. We used deep sequencing of serially obtained matched nasopharyngeal swabs and endotracheal aspirates from four mechanically ventilated patients with influenza A/H3N2 infections. A physical barrier separating both compartments of the respiratory tract introduced as part of the medical procedures enabled us to track and compare the genetic composition of the virus populations during isolated evolution in the same host. Amino acid variants reaching majority proportions emerged during the course of infection in both nasopharyngeal swabs and endotracheal aspirates, and amino acid variation was observed in all influenza virus proteins. Genetic variation of the virus populations differed between the URT and LRT and variants were frequently uniquely present in either URT or LRT virus populations of a patient. These observations indicate that virus populations in spatially distinct parts of the human airways may follow different evolutionary trajectories. Selectively sampling from the URT may therefore fail to detect potentially important emerging variants.

Importance

Influenza viruses are rapidly mutating pathogens that easily adapt to changing environments. Although advances in sequencing technology make it possible to identify virus variants at very low proportions of the within-host virus population, several aspects of intrahost viral evolution have not been studied because sequentially collected samples and samples from the lower respiratory tract are not routinely obtained for influenza surveillance or clinical diagnostic purposes. Importantly, how virus populations evolve in different parts of the human respiratory tract remains unknown. Here we used serial clinical specimens collected from mechanically ventilated influenza patients to compare how virus populations develop in the upper and lower respiratory tract. We show that virus populations in the upper and lower respiratory tract may evolve along distinct evolutionary pathways, and that current sampling and surveillance regimens likely capture only part of the complete intrahost virus variation.
The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease
Authors: van Rijn Anneloes L. , van Boheemen Sander , Carbo Ellen C. , Pappas Nikos , Sidorov Igor , Mei Hailiang , Aanerud Marianne , Bakke Per , Claas Eric C.J. , Eagan Tomas M. , Hiemstra Pieter S. , Kroes Aloys C.M. , de Vries Jutte J.C.
Published: January 2019

Introduction

Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger for the occurrence of such exacerbations. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations.

Objectives

To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS.

Study design

88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006-2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an lllumina library preparation protocol with in-house adaptations.

Results

By mNGS, 23/88 samples tested positive. Sensitivity and specificity were both 96% for diagnostic targets (23/24 and 1067/1120, respectively). Viral pathogens only detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral species reads (p=0.008). Patients with viral pathogens had lower percentages of bacteriophages (p<0.000). No correlation was found between viral reads (species and genus level) and clinical markers.

Conclusions

The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome, and speculatively the bacterial population, during infection.
MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains
Authors: Wiel Laurens , Baakman Coos , Gilissen Daan , Veltman Joris A. , Vriend Gerrit , Gilissen Christian
Published: January 2019

The growing availability of human genetic variation has given rise to novel methods of measuring genetic tolerance that better interpret variants of unknown significance. We recently developed a novel concept based on protein domain homology in the human genome to improve variant interpretation. For this purpose we mapped population variation from the Exome Aggregation Consortium (ExAC) and pathogenic mutations from the Human Gene Mutation Database (HGMD) onto Pfam protein domains. The aggregation of these variation data across homologous domains into meta-domains allowed us to generate base-pair resolution of genetic intolerance profiles for human protein domains.

Here we developed MetaDome, a fast and easy-to-use web service that visualizes meta-domain information and gene-wide profiles of genetic tolerance. We updated the underlying data of MetaDome to contain information from 56,319 human transcripts, 71,419 protein domains, 12,164,292 genetic variants from gnomAD, and 34,076 pathogenic mutations from ClinVar. MetaDome allows researchers to easily investigate their variants of interest for the presence or absence of variation at corresponding positions within homologous domains. We illustrate the added value of MetaDome by an example that highlights how it may help in the interpretation of variants of unknown significance. The MetaDome web server is freely accessible at https://stuart.radboudumc.nl/metadome.
STAM Interaction with Hrs Controls JAK/STAT Activation by Interferon-α at the Early Endosome
Authors: Zanin Natacha , Blouin Cédric M. , de Lesegno Christine Viaris , Chmiest Daniela , Johannes Ludger , Lamaze Christophe
Published: January 2019

Activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway by type I interferons (IFN) requires clathrin-dependent endocytosis of the IFN-α/β receptor (IFNAR). The molecular machinery that brings about the selective activation of IFN-α/β-induced JAK/STAT signaling on endosomes remains unknown. Here we show that the constitutive association of STAM with IFNAR1 and the TYK2 Janus kinase at the plasma membrane prevents the activation of TYK2 by type I IFNs. IFN-α stimulated endocytosis leads to the interaction of IFNAR1 with Hrs on early endosomes, which then relieves TYK2 inhibition by STAM and thereby allows for TYK2 and IFNAR signaling. In contrast, IFN-β stimulation results in sorting of IFNAR to a distinct endosomal subdomain where the receptor is activated independently from Hrs. Our results identify the molecular machinery that controls the spatiotemporal activation of TYK2 and establish the central role of endosomal sorting in the differential regulation of JAK/STAT signaling by IFN-α and IFN-β.

The spatiotemporal activation of JAK/STAT signaling by IFN-α is controlled by STAM association with Hrs at the early endosome.
Self-determination motivation theory in R: The software package S D T
Authors: Ünlü Ali
Published: January 2019

This paper presents the technical details of the software package SDT in the R computing and graphics environment, implementing a convex quadratic program that was recently proposed in the literature on self-determination theory of human motivation. Three main features are addressed, with their accompanying code for computation in R: first, the application of the quadratic program and corresponding code for the analysis of the extent of motivation internalization or externalization; second, for exploring the simplex structure assumption of motivation; and third, for adjusting the confounded scoring protocol, called the self-determination or relative autonomy index, to account for the mixture of internal motivation and external motivation. We describe the functions of the R package SDT. The computations are demonstrated with example data accompanying the package, so researchers can run the methodology on their own datasets.
The influence of kinesthetic motor imagery and effector specificity on the long-latency stretch response
Authors: Forgaard Christopher J. , Franks Ian M. , Maslovat Dana , Chua Romeo
Published: January 2019

The long-latency “reflexive” response (LLR) following an upper-limb mechanical disturbance is generated by neural circuitry shared with voluntary control. This feedback response supports many task-dependent behaviours and permits the expression of goal-directed corrections at latencies shorter than voluntary reaction time. An extensive body of literature has demonstrated that the LLR shows flexibility akin to voluntary control, but it has never been tested whether instruction-dependent LLR changes can also occur in the absence of an overt voluntary response. The present study used kinesthetic motor imagery (Experiment 1) and instructed participants to execute a voluntary response in a non-stretched contralateral muscle (Experiment 2) to explore the relationship between the overt production of a voluntary response and LLR facilitation. Activity in stretched right wrist flexors were compared to standard “not-intervene” and “compensate” conditions. Our findings revealed that on ~40% of imagery and ~50% of contralateral trials, a partial voluntary response “leaked-out” into the stretched right wrist flexor muscle. On these “leaked” trials, the early portion of the LLR (R2) was facilitated and displayed a similar increase to compensate trials. The latter half of the LLR (R3) showed further modulation, mirroring the patterns of voluntary response activity. By contrast, the LLR on “non-leaked” imagery and contralateral trials did not modulate. We suggest that even though a hastened voluntary response cannot account for all instruction-dependent LLR modulation, the overt execution of a voluntary response in the same muscle(s) as the LLR is a pre-requisite for facilitation of this rapid feedback response.

New and Noteworthy

We examined volitional modulation of the long-latency stretch response (LLR) using two novel approaches: motor imagery and the execution of contralateral movements. The LLR was only facilitated on imagery or contralateral trials when a voluntary response “leaked-out” into stretched muscle suggesting that a voluntary response in the same muscle as the LLR is a prerequisite for facilitation. Our findings also demonstrate an important distinction between the early (R2) and late (R3) portions of the LLR.
Isolation of High-Molecular-Weight DNA from Mouse Yolk Sacs and the Like
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: January 2019

Often, genotyping of mouse embryos is required, and a small part, such as the yolk sac, can be used for this purpose. Here, DNA samples are prepared from extra-embryonic tissues by digestion with Proteinase K and subsequent extraction. The yolk sac of mid-gestation or later-stage embryos provides a sufficient amount of DNA for Southern analysis. Small tissues of a few hundred cells are used for genotyping early postimplantation- and preimplantation-stage embryos by polymerase chain reaction (PCR).
Preparing and Using Adjuvants
Authors: Greenfield Edward A.
Published: January 2019

Nonspecific stimulators of the immune response are known as adjuvants. The judicious use of adjuvants is essential to induce a strong antibody response to soluble antigens. The most commonly used adjuvant for research work is Freund's adjuvant. Described here is the preparation and use of Freund's adjuvant as well as four alternative adjuvants: Ribi, Hunter's TiterMax, Magic Mouse, and aluminum hydroxide.
Optimizing time, cost and quality in multi-mode resource-constrained project scheduling
Authors: Kannimuthu Marimuthu , Raphael Benny , Palaneeswaran Ekambaram , Kuppuswamy Ananthanarayanan
Published: January 2019

Purpose

The purpose of this paper is to develop a framework to optimize time, cost and quality in a multi-mode resource-constrained project scheduling environment.

Design/methodology/approach

A case study approach identified the activity execution modes in building construction projects in India to support multi-mode resource-constrained project scheduling. The data required to compute time, cost and quality of each activity are compiled from real construction projects. A binary integer-programming model has been developed to perform multi-objective optimization and identify Pareto optimal solutions. The RR-PARETO3 algorithm was used to identify the best compromise trade-off solutions. The effectiveness of the proposed framework is demonstrated through sample case study projects.

Findings

Results show that good compromise solutions are obtained through multi-objective optimization of time, cost and quality.

Research limitations/implications

Case study data sets were collected only from eight building construction projects in India.

Practical implications

It is feasible to adopt multi-objective optimization in practical construction projects using time, cost and quality as the objectives; Pareto surfaces help to quantify relationships among time, cost and quality. It is shown that cost can be reduced by increasing the duration, and quality can be improved only by increasing the cost.

Originality/value

The use of different activity execution modes compiled from multiple projects in optimization is illustrated, and good compromise solutions for the multi-mode resource-constrained project scheduling problems using multi-objective optimization are identified.