Miracle-dz/UniFAR-FTUs huggingface dataset:
Antimicrobial Defense and Persistent Infection in Insects

During 400 million years of existence, insects have rarely succumbed to the evolution of microbial resistance against their potent antimicrobial immune defenses. We found that microbial clearance after infection is extremely fast and that induced antimicrobial activity starts to increase only when most of the bacteria (99.5%) have been removed. Our experiments showed that those bacteria that survived exposure to the insect's constitutive immune response were subsequently more resistant to it. These results imply that induced antimicrobial compounds function primarily to protect the insect against the bacteria that persist within their body, rather than to clear microbial infections. These findings suggest that understanding of the management of antimicrobial peptides in natural systems might inform medical treatment strategies that avoid the risk of drug resistance.
Globally Distributed Uncultivated Oceanic N2-Fixing Cyanobacteria Lack Oxygenic Photosystem II

Biological nitrogen (N2) fixation is important in controlling biological productivity and carbon flux in the oceans. Unicellular N2-fixing cyanobacteria have only recently been discovered and are widely distributed in tropical and subtropical seas. Metagenomic analysis of flow cytometry–sorted cells shows that unicellular N2-fixing cyanobacteria in “group A” (UCYN-A) lack genes for the oxygen-evolving photosystem II and for carbon fixation, which has implications for oceanic carbon and nitrogen cycling and raises questions regarding the evolution of photosynthesis and N2 fixation on Earth.
Stretching the envelope of past surface environments: Neoproterozoic glacial lakes 2

13 14 One-sentence summaries: 15 Extreme multi-stable isotope compositions of sulfate and its host carbonates from 16 Svalbard reveal an extraordinary atmosphere-biosphere condition during the deposition 17 of a Neoproterozoic glacial diamictites. 18 19 Abstract 20 The oxygen isotope composition of terrestrial sulfate is affected measurably by
Metallic and Insulating Phases of Repulsively Interacting Fermions in a 3D Optical Lattice

The fermionic Hubbard model plays a fundamental role in the description of strongly correlated materials. We have realized this Hamiltonian in a repulsively interacting spin mixture of ultracold 40K atoms in a three-dimensional (3D) optical lattice. Using in situ imaging and independent control of external confinement and lattice depth, we were able to directly measure the compressibility of the quantum gas in the trap. Together with a comparison to ab initio dynamical mean field theory calculations, we show how the system evolves for increasing confinement from a compressible dilute metal over a strongly interacting Fermi liquid into a band-insulating state. For strong interactions, we find evidence for an emergent incompressible Mott insulating phase. This demonstrates the potential to model interacting condensed-matter systems using ultracold fermionic atoms.
Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveal Structure and Evolution

Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5′ untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.
International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …
Platelets Kill Intraerythrocytic Malarial Parasites and Mediate Survival to Infection

Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.
Notch Promotes Radioresistance of Glioma Stem Cells

Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with γ‐secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhance radiation‐induced cell death and impair clonogenic survival of glioma stem cells but not non‐stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protect glioma stem cells against radiation. Notch inhibition with GSIs does not alter the DNA damage response of glioma stem cells after radiation but rather reduces Akt activity and Mcl‐1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment. STEM CELLS 2010;28:17–28
The Sea-Level Fingerprint of West Antarctic Collapse

Recent projections of sea-level rise after a future collapse of theWest Antarctic Ice Sheet (for example, the Fourth Intergovernmental Panel on Climate Change Assessment Report) assume that meltwater will spread uniformly (that is, eustatically) across the oceans once marine-based sectors of the West Antarctic are filled. A largely neglected 1977 study predicted that peak values would be 20% higher than the eustatic in the North Pacific and 5 to 10% higher along the U.S. coastline. We show, with use of a state-of-the-art theory, that the sea-level rise in excess of the eustatic value will be two to three times higher than previously predicted for U.S. coastal sites.
Physical activity patterns of European 50+ populations

Introduction: Despite well-documented positive effects of physical activity on physical and mental health, the levels of activity in many countries remain very low. Activity has been shown to be related to age, education and other individual characteristics, but it is unclear if differences in distributions of these characteristics across countries are enough to explain the observed cross-country differences. Aim: The paper examines the extent to which differences in the level of physical activity among European 50+ populations can be explained by differences in observed individual characteristics, and to which the differences between countries relate to unobserved factors and could thus be referred to as resulting from “activity habits”. Material and Methods: The analysis is based on the Survey of Health Ageing and Retirement in Europe (SHARE) for 13 countries of continental Europe. The sample includes 12,652 men and 15,007 aged 50 years and older. Linear probability models are used to correct for differences in the distribution of observable characteristics. Results: From among the 13 analysed European populations aged 50+, the level of physical activity is highest in Switzerland among men and in the Netherlands among women, with the Polish population turning out to be the least active. Only 38% of Polish men and 29% of women declare ‘vigorous physical activity’ at least once a week compared to 68% of Swiss men and 67% of Dutch women. Cross-country differences become smaller once a number of individual characteristics are controlled for, but they cannot be explained without referring to country-specific “activity habits”. Conclusion: There are significant differences in the level of physical activity among European 50+ populations and their large proportion cannot be explained by differences in observed individual characteristics.
Mouse Parthenogenetic Embryonic Stem Cells with Biparental‐Like Expression of Imprinted Genes Generate Cortical‐Like Neurons That Integrate into the Injured Adult Cerebral Cortex

One strategy for stem cell‐based therapy of the cerebral cortex involves the generation and transplantation of functional, histocompatible cortical‐like neurons from embryonic stem cells (ESCs). Diploid parthenogenetic Pg‐ESCs have recently emerged as a promising source of histocompatible ESC derivatives for organ regeneration but their utility for cerebral cortex therapy is unknown. A major concern with Pg‐ESCs is genomic imprinting. In contrast with biparental Bp‐ESCs derived from fertilized oocytes, Pg‐ESCs harbor two maternal genomes but no sperm‐derived genome. Pg‐ESCs are therefore expected to have aberrant expression levels of maternally expressed (MEGs) and paternally expressed (PEGs) imprinted genes. Given the roles of imprinted genes in brain development, tissue homeostasis and cancer, their deregulation in Pg‐ESCs might be incompatible with therapy. Here, we report that, unexpectedly, only one gene out of 7 MEGs and 12 PEGs was differentially expressed between Pg‐ESCs and Bp‐ESCs while 13 were differentially expressed between androgenetic Ag‐ESCs and Bp‐ESCs, indicating that Pg‐ESCs but not Ag‐ESCs, have a Bp‐like imprinting compatible with therapy. In vitro, Pg‐ESCs generated cortical‐like progenitors and electrophysiologically active glutamatergic neurons that maintained the Bp‐like expression levels for most imprinted genes. In vivo, Pg‐ESCs participated to the cortical lineage in fetal chimeras. Finally, transplanted Pg‐ESC derivatives integrated into the injured adult cortex and sent axonal projections in the host brain. In conclusion, mouse Pg‐ESCs generate functional cortical‐like neurons with Bp‐like imprinting and their derivatives properly integrate into both the embryonic cortex and the injured adult cortex. Collectively, our data support the utility of Pg‐ESCs for cortical therapy. Stem Cells 2018;36:192–205
Technology and Informal Education: What Is Taught, What Is Learned

The informal learning environments of television, video games, and the Internet are producing learners with a new profile of cognitive skills. This profile features widespread and sophisticated development of visual-spatial skills, such as iconic representation and spatial visualization. A pressing social problem is the prevalence of violent video games, leading to desensitization, aggressive behavior, and gender inequity in opportunities to develop visual-spatial skills. Formal education must adapt to these changes, taking advantage of new strengths in visual-spatial intelligence and compensating for new weaknesses in higher-order cognitive processes: abstract vocabulary, mindfulness, reflection, inductive problem solving, critical thinking, and imagination. These develop through the use of an older technology, reading, which, along with audio media such as radio, also stimulates imagination. Informal education therefore requires a balanced media diet using each technology's specific strengths in order to develop a complete profile of cognitive skills.
My prosthesis as a part of me: a qualitative analysis of living with an osseointegrated prosthetic limb

Background: Bone-anchored prosthesis is still a rather unusual treatment for patients with limb loss. Objectives: The aim of this study was to improve our understanding about the experience of living with an osseointegrated prosthesis (OI-prosthesis) compared to one suspended with a socket, through the use of qualitative research methodology. Study design: A qualitative phenomenological research method. Methods: Thirteen Swedish patients (37–67 years) with unilateral upper or lower limb amputation (10 transfemoral, 2 transhumeral, 1 transradial), who had been using OI-prostheses for 3 to 15 years, were recruited by means of purposive sampling. An audio-taped in-depth interview was performed. The guiding question was ‘How do you experience living with your osseointegrated prosthesis compared to your earlier prostheses suspended with sockets? ’. The empirical phenomenological psychological method was used for data analysis. Results: The results showed that all participants described living with an OI-prosthesis as a revolutionary change. These experiences were described in terms of three typologies, called ‘Practical prosthesis’, ‘Pretend limb’ and ‘A part of me’. Conclusions: The most important finding was that the change went beyond the functional improvements, integrating the existential implications in the concept of quality of life. Clinical relevance This qualitative in-depth interview study on patients using bone-anchored prosthetic limbs showed that all described a revolutionary change in their lives as amputees and the meaning of that change went beyond the functional improvements, integrating existential implications in the concept of quality of life.
Green Evolution and Dynamic Adaptations Revealed by Genomes of the Marine Picoeukaryotes Micromonas

Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.
Antagonistic Actions of Msx1 and Osr2 Pattern Mammalian Teeth into a Single Row

Mammals have single-rowed dentitions, whereas many nonmammalian vertebrates have teeth in multiple rows. Neither the molecular mechanism regulating iterative tooth initiation nor that restricting mammalian tooth development in one row is known. We found that mice lacking the transcription factor odd-skipped related-2 (Osr2) develop supernumerary teeth lingual to their molars because of expansion of the odontogenic field. Osr2 was expressed in a lingual-to-buccal gradient and restricted expression of bone morphogenetic protein 4 (Bmp4), an essential odontogenic signal, in the developing tooth mesenchyme. Expansion of odontogenic field in Osr2-deficient mice required Msx1, a feedback activator of Bmp4 expression. These findings suggest that the Bmp4-Msx1 pathway propagates mesenchymal activation for sequential tooth induction and that spatial modulation of this pathway provides a mechanism for patterning vertebrate dentition.
α-Actinin Promotes Surface Localization and Current Density of the Ca2+ Channel CaV1.2 by Binding to the IQ Region of the α1 Subunit.

The voltage-gated L-type Ca2+ channel CaV1.2 is crucial for initiating heartbeat and control of a number of neuronal functions such as neuronal excitability and long-term potentiation. Mutations of CaV1.2 subunits result in serious health problems, including arrhythmia, autism spectrum disorders, immunodeficiency, and hypoglycemia. Thus, precise control of CaV1.2 surface expression and localization is essential. We previously reported that α-actinin associates and colocalizes with neuronal CaV1.2 channels and that shRNA-mediated depletion of α-actinin significantly reduces localization of endogenous CaV1.2 in dendritic spines in hippocampal neurons. Here we investigated the hypothesis that direct binding of α-actinin to CaV1.2 supports its surface expression. Using two-hybrid screens and pull-down assays, we identified three point mutations (K1647A, Y1649A, and I1654A) in the central, pore-forming α11. 2 subunit of CaV1.2 that individually impaired α-actinin binding. Surface biotinylation and flow cytometry assays revealed that CaV1.2 channels composed of the corresponding α-actinin-binding-deficient mutants result in a 35-40% reduction in surface expression compared to that of wild-type channels. Moreover, the mutant CaV1.2 channels expressed in HEK293 cells exhibit a 60-75% decrease in current density. The larger decrease in current density as compared to surface expression imparted by these α11. 2 subunit mutations hints at the possibility that α-actinin not only stabilizes surface localization of CaV1.2 but also augments its ion conducting activity.
Neural Mechanisms of a Genome-Wide Supported Psychosis Variant

A genetic polymorphism associated with schizophrenia conveys a risk for abnormal connectivity between brain regions. Schizophrenia is a devastating, highly heritable brain disorder of unknown etiology. Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706). We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage–dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. Our findings establish disturbed connectivity as a neurogenetic risk mechanism for psychosis supported by genome-wide association, show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry.
Multifamily Groups in Recovery: A Revised Multifamily Curriculum

The Center for the Study of Addiction and Recovery (CSAR; a center within the College of Human Sciences at Texas Tech University) operates a Collegiate Recovery Community. This community provides a model of support and relapse prevention for college students recovering from addictive behaviors—primarily alcohol and drug addiction. In addition, the CSAR provides the clinical management for an inpatient alcohol and drug treatment facility, The Ranch at Dove Tree (DTR). Professionals at DTR work with individuals using a number of different therapeutic techniques including individual therapy, gender-specific group therapy, multifamily therapy groups, trauma groups, and life skills groups. This article presents a revised multifamily group curriculum developed by the authors and originally tested in an outpatient treatment program. This revised multifamily curriculum was implemented as part of the multifamily programs of both the CSAR and DTR. Preliminary feedback gathered as part of the CSAR family program is presented.
Concise Review: Hitting the Right Spot with Mesenchymal Stromal Cells

Mesenchymal stromal cells or mesenchymal stem cells (MSCs) have captured considerable scientific and public interest because of their potential to limit physical and immune injury, to produce bioactive molecules and to regenerate tissues. MSCs are phenotypically heterogeneous and distinct subpopulations within MSC cultures are presumed to contribute to tissue repair and the modulation of allogeneic immune responses. As the first example of efficacy, clinical trials for prevention and treatment of graft‐versus‐host disease after hematopoietic cell transplantation show that MSCs can effectively treat human disease. The view of the mechanisms whereby MSCs function as immunomodulatory and reparative cells has evolved simultaneously. Initially, donor MSCs were thought to replace damaged cells in injured tissues of the recipient. More recently, however, it has become increasingly clear that even transient MSC engraftment may exert favorable effects through the secretion of cytokines and other paracrine factors, which engage and recruit recipient cells in productive tissue repair. Thus, an important reason to investigate MSCs in mechanistic preclinical models and in clinical trials with well‐defined end points and controls is to better understand the therapeutic potential of these multifunctional cells. Here, we review the controversies and recent insights into MSC biology, the regulation of alloresponses by MSCs in preclinical models, as well as clinical experience with MSC infusions (Table 1 ) and the challenges of manufacturing a ready supply of highly defined transplantable MSCs. STEM CELLS 2010;28:1446–1455