Miracle-dz/UniFAR-FTUs huggingface dataset:
Humanized mouse model supports development, function, and tissue residency of human natural killer cells

Significance Humanized mice represent a promising approach to study the human immune system in health and disease. However, insufficient development and function of human lymphocytes limit the applicability of humanized mice for cancer biology and therapy. We demonstrate that human SIRPA and IL15 knock-in (SRG-15) mice support efficient development of circulating and tissue-resident natural killer (NK) cells, intraepithelial lymphocytes, and innate lymphoid cell subsets. In contrast to previous humanized mouse models, human NK cells in SRG-15 mice mediate efficient antibody-dependent cellular cytotoxicity and thereby enable NK cell-targeted cancer immunotherapy of tumor xenografts. As such, SRG-15 humanized mice may facilitate translational research by enabling the development of novel NK and CD8+ T cell-based therapeutic approaches that target human infections and malignancies. Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2−/− Il2rg−/− background (SRG-15). Transplantation of human hematopoietic stem and progenitor cells into SRG-15 mice dramatically improved the development and functional maturation of circulating and tissue-resident human NK and CD8+ T cells and promoted the development of tissue-resident innate lymphoid cell (ILC) subsets. Profiling of human NK cell subsets by mass cytometry revealed a highly similar expression pattern of killer inhibitory receptors and other candidate molecules in NK cell subpopulations between SRG-15 mice and humans. In contrast to nonobese diabetic severe combined immunodeficient Il2rg−/− (NSG) mice, human NK cells in SRG-15 mice did not require preactivation but infiltrated a Burkitt’s lymphoma xenograft and efficiently inhibited tumor growth following treatment with the therapeutic antibody rituximab. Our humanized mouse model may thus be useful for preclinical testing of novel human NK cell-targeted and combinatory cancer immunotherapies and for studying how they elicit human antitumor immune responses in vivo.
Musculoskeletal pain and ergonomic aspects of dentistry

BACKGROUND AND OBJECTIVES: Dentists are considered professionals highly vulnerable to occupational problems and such injuries are sometimes caused by adopted postures and repetitive efforts during their work. This study aimed at checking the prevalence of musculoskeletal pain and to observe whether the work of dentists acting in both public and private sectors was carried out ergonomically. METHODS: This is a cross-sectional, descriptive and observational study with dentists (n=80). A self-applicable questionnaire was used to check the frequency of musculoskeletal pain and occupational injuries, as well as to record labor activities, practice of physical activity and their frequencies. Professionals were observed while carrying out dental assistance based on recommendations of the document “Adopting a healthy sitting working posture during patient treatment”, which is part of the International Standards Organization standardization 106/SC 6 N 411 from 2006. RESULTS: There has been job-related pain in at least 65.67% of dentists. The number of individuals adopting incorrect and inadequate positions during assistance was high, such as: head rotation (73.13%); spine rotation (47.76%) and legs angle less than 90o (91.04%). Medical leaves related to occupational injuries were found in a greater proportion among public service professionals (64%). CONCLUSION: There has been high prevalence of musculoskeletal pain related to inadequate postures adopted during clinical assistance and to long working hours without pause.
Greater Internet use is not associated with faster growth in political polarization among US demographic groups

Significance By many measures, Americans have become increasingly polarized in recent decades. We study the role of the Internet and social media in explaining this trend. We find that polarization has increased the most among the demographic groups least likely to use the Internet and social media, suggesting that the role of these factors is limited. We combine eight previously proposed measures to construct an index of political polarization among US adults. We find that polarization has increased the most among the demographic groups least likely to use the Internet and social media. Our overall index and all but one of the individual measures show greater increases for those older than 65 than for those aged 18–39. A linear model estimated at the age-group level implies that the Internet explains a small share of the recent growth in polarization.
Interface-induced multiferroism by design in complex oxide superlattices

Significance Developments in synthesis and characterizing artificially structured materials have greatly advanced the possibility to explore new states of matter in material science. Recent discoveries show that new quantum states can be achieved at heterointerfaces with various electric and mechanical boundary conditions. It remains an open question of how to design ultrathin layers with properties inaccessible in bulk phases that are amenable to technological applications. In this work, we grow heterostructures with extremely high-quality interfaces shown by state-of-the-art atomically resolved electron microscopy and spectroscopy. This combination allows us to identify an interface-induced structure that stabilizes ferromagnetism. Coupled with theory, we provide a conceptually useful recipe to design low-dimensional materials with unique functionalities, in line with the loop “make, measure, model. ” Interfaces between materials present unique opportunities for the discovery of intriguing quantum phenomena. Here, we explore the possibility that, in the case of superlattices, if one of the layers is made ultrathin, unexpected properties can be induced between the two bracketing interfaces. We pursue this objective by combining advanced growth and characterization techniques with theoretical calculations. Using prototype La2/3Sr1/3MnO3 (LSMO)/BaTiO3 (BTO) superlattices, we observe a structural evolution in the LSMO layers as a function of thickness. Atomic-resolution EM and spectroscopy reveal an unusual polar structure phase in ultrathin LSMO at a critical thickness caused by interfacing with the adjacent BTO layers, which is confirmed by first principles calculations. Most important is the fact that this polar phase is accompanied by reemergent ferromagnetism, making this system a potential candidate for ultrathin ferroelectrics with ferromagnetic ordering. Monte Carlo simulations illustrate the important role of spin–lattice coupling in LSMO. These results open up a conceptually intriguing recipe for developing functional ultrathin materials via interface-induced spin–lattice coupling.
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

Significance Coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) cause severe respiratory distress with high fatality rates. The spike (S) glycoprotein is a determinant of host range and is the target of neutralizing antibodies and subunit vaccine development. We describe an engineering strategy for stabilization of soluble S proteins in the prefusion conformation, which results in greatly increased expression, conformational homogeneity, and elicitation of potent antibody responses. Cryo-EM structures of the stabilized MERS-CoV S protein in complex with a stem-directed neutralizing antibody provide a molecular basis for host-cell protease requirements and identify a site of immune pressure. We also defined four conformational states of the trimer wherein each receptor-binding domain is either packed together at the membrane-distal apex or rotated into a receptor-accessible conformation. Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.
Amorphous calcium carbonate particles form coral skeletons

Significance Whether coral skeleton crystals grow by attachment of ions from solution or particles from tissue determines (i) corals’ growth rate, (ii) how they survive acidifying oceans, and (iii) the isotopes in the crystals used for reconstructing ancient temperatures. Our data show that two amorphous precursors exist, one hydrated and one dehydrated amorphous calcium carbonate; that these are formed in the tissue as ∼400-nm particles; and that they attach to the surface of coral skeletons, remain amorphous for hours, and finally crystallize into aragonite. Since these particles are formed inside tissue, coral skeleton growth may be less susceptible to ocean acidification than previously assumed. Coral bleaching and postmortem dissolution of the skeleton will occur, but a calcification crisis may not. Do corals form their skeletons by precipitation from solution or by attachment of amorphous precursor particles as observed in other minerals and biominerals? The classical model assumes precipitation in contrast with observed “vital effects,” that is, deviations from elemental and isotopic compositions at thermodynamic equilibrium. Here, we show direct spectromicroscopy evidence in Stylophora pistillata corals that two amorphous precursors exist, one hydrated and one anhydrous amorphous calcium carbonate (ACC); that these are formed in the tissue as 400-nm particles; and that they attach to the surface of coral skeletons, remain amorphous for hours, and finally, crystallize into aragonite (CaCO3). We show in both coral and synthetic aragonite spherulites that crystal growth by attachment of ACC particles is more than 100 times faster than ion-by-ion growth from solution. Fast growth provides a distinct physiological advantage to corals in the rigors of the reef, a crowded and fiercely competitive ecosystem. Corals are affected by warming-induced bleaching and postmortem dissolution, but the finding here that ACC particles are formed inside tissue may make coral skeleton formation less susceptible to ocean acidification than previously assumed. If this is how other corals form their skeletons, perhaps this is how a few corals survived past CO2 increases, such as the Paleocene–Eocene Thermal Maximum that occurred 56 Mya.
COP1 mediates dark-specific degradation of microtubule-associated protein WDL3 in regulating Arabidopsis hypocotyl elongation

Significance CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) is an E3 ubiquitin ligase acting as a central repressor of seedling photomorphogenesis in plants. Many nuclear-localized COP1 substrates have been identified in the last two decades; however, whether COP1 targets cytoplasmic factors for ubiquitination and degradation remains largely unknown. In this study, we show that COP1 interacts with a microtubule-associated protein, WAVE-DAMPENED 2-LIKE 3 (WDL3), in a dark-dependent manner at cortical microtubules. Thus, COP1 targets WDL3 for 26S proteasome-mediated degradation to control hypocotyl elongation in etiolated Arabidopsis seedlings. Collectively, our study uncovers a cytoplasmic substrate of COP1 that functions as a microtubule-associated protein in mediating hypocotyl cell elongation. CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a well-known E3 ubiquitin ligase, functions as a central regulator of plant growth and photomorphogenic development in plants, including hypocotyl elongation. It has been well-established that, in darkness, COP1 targets many photomorphogenesis-promoting factors for ubiquitination and degradation in the nucleus. However, increasing evidence has shown that a proportion of COP1 is also localized outside the nucleus in dark-grown seedlings, but the physiological function of this localization remains largely unclear. In this study, we demonstrate that COP1 directly targets and mediates the degradation of WAVE-DAMPENED 2-LIKE 3 (WDL3) protein, a member of the microtubule-associated protein (MAP) WVD2/WDL family involved in regulating hypocotyl cell elongation of Arabidopsis seedlings. We show that COP1 interacts with WDL3 in vivo in a dark-dependent manner at cortical microtubules. Moreover, our data indicate that COP1 directly ubiquitinates WDL3 in vitro and that WDL3 protein is degraded in WT seedlings but is abundant in the cop1 mutant in the dark. Consistently, introduction of the wdl3 mutation weakened, whereas overexpression of WDL3 enhanced, the short-hypocotyl phenotype of cop1 mutant in darkness. Together, this study reveals a function of COP1 in regulating the protein turnover of a cytosol-localized MAP in etiolated hypocotyls, thus providing insights into COP1-mediated degradation of downstream factors to control seedling photomorphogenesis.
Nivel de conocimiento sobre prevención de salud bucal en gestantes, hospital de la mujer, Villahermosa, Tabasco 2007

Objetivo: Determinar el nivel de conocimiento sobre prevencion de salud bucal en gestantes, Hospital de la mujer, Villahermosa, Tabasco 2007. Material y Metodos: Se realizo un estudio observacional descriptivo, de corte transversal, en 100 gestantes mayores de 18 anos, que acudieron al servicio de control prenatal en el Hospital de la Mujer (2007). Se aplico un cuestionario de 15 preguntas de opcion multiple para medir edad, escolaridad, conocimiento sobre prevencion en salud bucal, conocimiento sobre principales enfermedades bucales, gestacion y atencion odontologica. Resultados: El rango de 18 a 20 anos fue el mas frecuente (X= 24 anos, DS 5), la escolaridad mas frecuente fue la secundaria completa en un 24%; 66% de las gestantes presentaron nivel de conocimiento medio sobre prevencion bucal; en el conocimiento de las principales enfermedades bucales, 49% obtuvo nivel medio y 39% nivel bajo; finalmente, sobre gestacion y atencion odontologica predomino nivel medio con 59%. Conclusiones: Aunque el nivel de conocimiento predominante fue el medio, es insuficiente, si se consideran las consecuencias que el desconocimiento sobre enfermedades bucales puede producir a la gestante y su producto. Se necesita realizar una mayor labor educativo preventiva en pacientes gestantes de este centro hospitalario; la mayoria posee conocimientos empiricos sobre prevencion bucal.
High-intensity urban light installation dramatically alters nocturnal bird migration

Significance Artificial light at night is a novel stimulus in the evolutionary history of nocturnal animals. Light pollution can significantly alter these organisms’ behaviors, from migration to foraging to vocal communication. Nocturnally migrating birds are particularly susceptible to artificial light because of adaptations and requirements for navigating and orienting in darkness. However, light’s effects on in-flight behaviors have not been well quantified, especially in urbanized environments. Here we report that an iconic urban light installation dramatically altered multiple behaviors of nocturnally migrating birds—but these effects disappeared when lights were extinguished. We recommend selective removal of light pollution during nights with substantial bird migration to mitigate negative effects on birds, in particular collisions with lighted structures. Billions of nocturnally migrating birds move through increasingly photopolluted skies, relying on cues for navigation and orientation that artificial light at night (ALAN) can impair. However, no studies have quantified avian responses to powerful ground-based light sources in urban areas. We studied effects of ALAN on migrating birds by monitoring the beams of the National September 11 Memorial & Museum's “Tribute in Light” in New York, quantifying behavioral responses with radar and acoustic sensors and modeling disorientation and attraction with simulations. This single light source induced significant behavioral alterations in birds, even in good visibility conditions, in this heavily photopolluted environment, and to altitudes up to 4 km. We estimate that the installation influenced ≈1.1 million birds during our study period of 7 d over 7 y. When the installation was illuminated, birds aggregated in high densities, decreased flight speeds, followed circular flight paths, and vocalized frequently. Simulations revealed a high probability of disorientation and subsequent attraction for nearby birds, and bird densities near the installation exceeded magnitudes 20 times greater than surrounding baseline densities during each year’s observations. However, behavioral disruptions disappeared when lights were extinguished, suggesting that selective removal of light during nights with substantial bird migration is a viable strategy for minimizing potentially fatal interactions among ALAN, structures, and birds. Our results also highlight the value of additional studies describing behavioral patterns of nocturnally migrating birds in powerful lights in urban areas as well as conservation implications for such lighting installations.
Investment in secreted enzymes during nutrient-limited growth is utility dependent

Significance Bacteria secrete enzymes into the environment to digest macromolecules into smaller molecules that can be used as nutrients for growth. Secreted enzymes have potential benefits but also entail costs in the form of biomass and energy. How do bacteria determine how much of them to make? Using a system in which nutrient acquisition requires production of secreted enzymes, we infer that bacteria produce secreted signals in proportion to the benefit they would receive from the action of secreted enzymes. Investment in secreted enzymes is adjusted according to the magnitude of those signals. Our model provides a framework that can be applied to bacterial growth in many environments from contaminated food to microbial communities within a host. Pathogenic bacteria secrete toxins and degradative enzymes that facilitate their growth by liberating nutrients from the environment. To understand bacterial growth under nutrient-limited conditions, we studied resource allocation between cellular and secreted components by the pathogenic bacterium Pseudomonas aeruginosa during growth on a protein substrate that requires extracellular digestion by secreted proteases. We identified a quantitative relationship between the rate of increase of cellular biomass under nutrient-limiting growth conditions and the rate of increase in investment in secreted proteases. Production of secreted proteases is stimulated by secreted signals that convey information about the utility of secreted proteins during nutrient-limited growth. Growth modeling using this relationship recapitulated the observed kinetics of bacterial growth on a protein substrate. The proposed regulatory strategy suggests a rationale for quorum-sensing–dependent stimulation of the production of secreted enzymes whereby investment in secreted enzymes occurs in proportion to the utility they confer. Our model provides a framework that can be applied toward understanding bacterial growth in many environments where growth rate is limited by the availability of nutrients.
The Socio-Economic impacts of Stigmatization on young women (16-24) infected with HIV in Accra, Ghana (Ridge hospital)

This study sought to explore the socio-economic impacts of stigmatization on young women (16-24) infected with HIV in Accra, Ghana (Ridge hospital). Qualitative study was performed with five young women 16-24 infected with HIV attending HIV clinic at Ridge hospital. Interviews were conducted to explore respondents’ perception of stigmatization and discrimination based on their HIV status and gender, economic burden posed on victims as a result of the HIV infection, and investigate any changes in the victim´s social participation following realization of their HIV infection. The respondents reported that stigma and discrimination have a negative impact on their socio-economic status. There is a fear of future refusal or dismissal from work due to their HIV status, a fear of economic and social suffering due to family and spousal neglect, as well as many other challenges associated HIV and pregnancy. Some respondents were able to cope with their current situation through self-confidence, adequate pre and post HIV counseling and testing, and social and economic support from family and hiding of HIV status. Stigma and discrimination was a huge problem that all the respondents reacted to as being an obstacle to their social and economic wellbeing. A model was developed from the findings that explain the stages that potential interventions can focus on to help alleviate this burden. This model was based on the findings that respondents perceived the effects of stigma and discrimination at two levels: current and future burdens. Beneath these lies a third level that helps them to cope.
Studies on phosphoproteins from fish eggs. I. Isolation and characterization of a phosphoprotein from the eggs of pacific herring.

1. A phosphoprotein containing 10.6% of phosphorus has been isolated from the eggs of Pacific herring by means of phenol extraction and DEAE-cellulose column chromatography. 2. Only 8 kinds of amino acid including a small amount each of the 2 kinds were detectable in the acid hydrolysate of the phosphoprotein. The protein contained only serine as hydroxyl group-bearing amino acid and this amino acid occupied more than 2/3 of total amino acid residues. No amino sugar was detectable. 3. A molecular weight of 4,200±400 was calculated from the sedimentation equilibrium data for the phosphoprotein. The following formula has been given tentatively for the protein on the basis of the molecular weight: (Lys)1(Arg)i(Asp)i(Phe)i(Leu)3(Ser)23_25(Phosphate)16. 4. The results of an alkali-catalyzed ^-elimination reaction suggested that all the phosphorus in the phosphoprotein are present in the form of monoesters linked to the hydroxyl groups of serine. 5. Two moles of DNP-group were introduced per 4,200 g of the protein. The Nterminal residue of the major component of the preparation was determined to be lysine by the analysis of DNP-products.