Miracle-dz/UniFAR-FTUs huggingface dataset:
Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming

Despite the availability of vaccines, human papillomavirus (HPV) infections remain a cause of significant cancer morbidity and mortality. We have previously shown that HPV16 E7 associates with and diminishes E2F6-containing polycomb repressive complexes. Here, we show that repressive trimethyl marks on lysine 27 of histone 3, which are necessary for binding of polycomb repressive complexes, are decreased in HPV16 E7-expressing cells and HPV16-positive cervical lesions. This is caused by transcriptional induction of the KDM6A and KDM6B histone 3 lysine 27-specific demethylases. HPV16 E7-mediated KDM6B induction accounts for expression of the cervical cancer biomarker, p16INK4A. Moreover, KDM6A- and KDM6B-responsive Homeobox genes are expressed at significantly higher levels, suggesting that HPV16 E7 results in reprogramming of host epithelial cells. These effects are independent of the ability of E7 to inhibit the retinoblastoma tumor suppressor protein. Most importantly, these effects are reversed when E7 expression is silenced, indicating that this pathway may have prognostic and/or therapeutic significance.
Near‐patient platelet function testing in patients undergoing coronary artery surgery: a pilot study *

Platelet dysfunction after cardiopulmonary bypass contributes to microvascular bleeding and is associated with blood transfusion and resternotomy. Platelet count can be readily performed, but currently there are no standardised, reproducible, rapidly available platelet function tests. We studied platelet function as measured by multiple electrode platelet aggregometery (multiplate) and light transmission aggregometry in 44 patients undergoing routine coronary artery surgery. Platelet aggregation as measured by multiplate was reduced during and after cardiopulmonary bypass compared with baseline with evidence of partial recovery by the time of transfer to ITU. In patients transfused blood, platelet aggregation measured by multiplate was reduced during chest closure with adenosine diphosphate (18 U vs 29 U, p = 0.01) and thrombin receptor agonist peptide‐6 agonist (65 U vs 88 U, p = 0.01) compared with patients not transfused. This suggests that multiplate, a new point of care analyser, can detect platelet dysfunction in this setting.
Spontaneous Ripple Formation in MoS2 Monolayers: Electronic Structure and Transport Effects

The spontaneous formation of ripples in molybdenum disulfide (MoS2 ) monolayers is investigated via density functional theory based tight-binding Born-Oppenheimer molecular dynamics. Monolayers with different lengths show spontaneous rippling during the simulations. The density of states reveals a decrease in the bandgap induced by the stretching of the MoS2 units due to ripple formation. Significant quenching in electron conductance was also observed. The ripples in the MoS2 monolayers have an effect on the properties of the material and could impact its application in nanoelectronics.
Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex

Uncertainty about the function of orbitofrontal cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFC's role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make it possible to measure reward-credit assignment—a crucial component of reward-value learning—independently of the decisions animals make. The mOFC lesions do not lead to impairments in reward-credit assignment that are seen after lOFC lesions. Second, we examined how the reward values of choice options were compared. We present three analyses, one of which examines reward-guided decision making independently of reward-value learning. Lesions of the mOFC, but not the lOFC, disrupted reward-guided decision making. Impairments after mOFC lesions were a function of the multiple option contexts in which decisions were made. Contrary to axiomatic assumptions of decision theory, the mOFC-lesioned animals’ value comparisons were no longer independent of irrelevant alternatives.
Revisiting human natural killer cell subset function revealed cytolytic CD56dimCD16+ NK cells as rapid producers of abundant IFN-γ on activation

The two major functions of human natural killer (NK) cells are conventionally associated with distinct cell subsets. Thus, cytolytic activity is mostly confined to the CD56dimCD16+ subset, whereas cytokine production is generally assigned to CD56brightCD16+/− cells. In this study, we reevaluated the functional capabilities of these NK subsets with regard to the production of IFN-γ at different time points after cell triggering via NKp46 and NKp30 activating receptors. Different from previous studies, cytokine production was also assessed at early intervals. We show that CD56dim NK cells produce IFN-γ already at 2 to 4 h, whereas no cytokine production is detected beyond 16 h. In contrast, CD56bright cells release IFN-γ only at late time intervals (>16 h after stimulation). The rapid IFN-γ production by CD56dim NK cells is in line with the presence of IFN-γ mRNA in freshly isolated cells. Rapid IFN-γ production was also induced by combinations of IL-2, IL-12, and IL-15. Our data indicate that not only cytolytic activity but also early IFN-γ production is a functional property of CD56dim NK cells. Thus, this subset can assure a rapid and comprehensive NK cell intervention during the early phases of innate responses.
Winter and spring warming result in delayed spring phenology on the Tibetan Plateau

Climate change has caused advances in spring phases of many plant species. Theoretically, however, strong warming in winter could slow the fulfillment of chilling requirements, which may delay spring phenology. This phenomenon should be particularly pronounced in regions that are experiencing rapid temperature increases and are characterized by highly temperature-responsive vegetation. To test this hypothesis, we used the Normalized Difference Vegetation Index ratio method to determine the beginning, end, and length of the growing season of meadow and steppe vegetation of the Tibetan Plateau in Western China between 1982 and 2006. We then correlated observed phenological dates with monthly temperatures for the entire period on record. For both vegetation types, spring phenology initially advanced, but started retreating in the mid-1990s in spite of continued warming. Together with an advancing end of the growing season for steppe vegetation, this led to a shortening of the growing period. Partial least-squares regression indicated that temperatures in both winter and spring had strong effects on spring phenology. Although warm springs led to an advance of the growing season, warm conditions in winter caused a delay of the spring phases. This delay appeared to be related to later fulfillment of chilling requirements. Because most plants from temperate and cold climates experience a period of dormancy in winter, it seems likely that similar effects occur in other environments. Continued warming may strengthen this effect and attenuate or even reverse the advancing trend in spring phenology that has dominated climate-change responses of plants thus far.
Health measurement scales. A practical guide to their development and use, 3rd ed

Edited by David L Streiner, Geoffrey R Norman. Oxford: Oxford University Press, 2003, £26.50, pp 283. ISBN 0-19852-947-7 This is the third edition of a successful book whose previous two editions were published in 1989, and 1994. It is a practical guide about health measurement scales called as well “latent outcomes”, such as cognitive abilities, attitudes, quality of life, etc, addressed to …
Transcultural Health Care: A Culturally Competent Approach

This title prepares students for the culturally rich and ethically diverse world in which they will practice. Noted researchers, educators, and clinicians, from a wealth of backgrounds, use the Purnell twelve-step model to examine more than 30 population groups from a health care perspective. Each brings a personal understanding of the traditions and customs of their societies, providing a unique perspective on the implications for patient care.Multiple vignettes in each culture-based chapter clearly illustrate situations and issues across the nursing continuum. Summaries of the chapters on 18 additional cultures online at DavisPlus appear in one-page abstracts in the Appendix. This title features: more student learning resources online at DavisPlus, including all of the Case Studies from the 2nd Edition; and, more teaching tools for instructors online at DavisPlus, including a test bank and classroom assignments for each chapter.It uses the Purnell twelve-step model to organize the discussion of each cultural group, looking at the following factors: inhabited localities, topography, and overview; communications; family roles and organization; workforce issues; biocultural ecology; high-risk behaviors; nutrition; pregnancy and childbearing practices; death rituals; spirituality; health-care practices; and, health-care practitioners.
Isometrische Maximalkraftmessungen der Quadrizepsmuskulatur

Summary The quadriceps femoris muscle (QF) plays an important role in locomotion. However, assessing the total number of attempts to evaluate the maximal isometric strength (Fmaxiso) regarding reliability and feasibility remain less characterised. Patients, methods: 28 patients with haemophilia (H) (26 severe, 2 moderate) and 27 healthy controls (C) matched for age (H: 44 ± 11, C: 42 ± 12) and anthropometric data were measured separately for the left and right leg for Fmaxiso of QF using m3 diagnos (SCHNELL®). We repeated the Fmaxiso measures after 48 h in 14 H and 13 C. Results: The system m3 diagnos showed strong reliability (ICC = 1.0; SEM = 0.0; CA = 1.0). H and C demonstrated significant differences in Fmaxiso (H r = 153 Nm, l = 164 Nm; K r= 289 Nm, l = 280 Nm; p ≤ 0.001). Additionally, H and C revealed significant differences between the 1st and 3rd to 6th attempts. No differences were observed between the 3rd, 4th, 5th and 6th attempts. Conclusion: Both groups showed high test-retest-reliability of Fmaxiso (ICC/SEM: H l = 0.98/7.1 r = 0.99/4.9; K l = 0.69/11.3 r = 0.95/5.8). Starting from the 3rd attempt, reliable measurements of the Fmaxiso in patients suffering from severe haemophilia are feasible.
Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.
25th Anniversary Article: The Evolution of Electronic Skin (E‐Skin): A Brief History, Design Considerations, and Recent Progress

Human skin is a remarkable organ. It consists of an integrated, stretchable network of sensors that relay information about tactile and thermal stimuli to the brain, allowing us to maneuver within our environment safely and effectively. Interest in large‐area networks of electronic devices inspired by human skin is motivated by the promise of creating autonomous intelligent robots and biomimetic prosthetics, among other applications. The development of electronic networks comprised of flexible, stretchable, and robust devices that are compatible with large‐area implementation and integrated with multiple functionalities is a testament to the progress in developing an electronic skin (e‐skin) akin to human skin. E‐skins are already capable of providing augmented performance over their organic counterpart, both in superior spatial resolution and thermal sensitivity. They could be further improved through the incorporation of additional functionalities (e.g., chemical and biological sensing) and desired properties (e.g., biodegradability and self‐powering). Continued rapid progress in this area is promising for the development of a fully integrated e‐skin in the near future.
Stress-inducible NHEJ in bacteria: function in DNA repair and acquisition of heterologous DNA

Abstract DNA double-strand breaks (DSB) in bacteria can be repaired by non-homologous end-joining (NHEJ), a two-component system relying on Ku and LigD. While performing a genetic characterization of NHEJ in Sinorhizobium meliloti, a representative of bacterial species encoding several Ku and LigD orthologues, we found that at least two distinct functional NHEJ repair pathways co-exist: one is dependent on Ku2 and LigD2, while the other depends on Ku3, Ku4 and LigD4. Whereas Ku2 likely acts as canonical bacterial Ku homodimers, genetic evidences suggest that Ku3-Ku4 form eukaryotic-like heterodimers. Strikingly, we found that the efficiency of both NHEJ systems increases under stress conditions, including heat and nutrient starvation. We found that this stimulation results from the transcriptional up-regulation of the ku and/or ligD genes, and that some of these genes are controlled by the general stress response regulator RpoE2. Finally, we provided evidence that NHEJ not only repairs DSBs, but can also capture heterologous DNA fragments into genomic breaks. Our data therefore suggest that NHEJ could participate to horizontal gene transfer from distantly related species, bypassing the need of homology to integrate exogenous DNA. This supports the hypothesis that NHEJ contributes to evolution and adaptation of bacteria under adverse environmental conditions.
FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation

Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms of multiple sclerosis. Its mechanism of action is thought to be immunological through an active phosphorylated metabolite, FTY720-P, that resembles S1P and alters lymphocyte trafficking through receptor subtype S1P1. However, previously reported expression and in vitro studies of S1P receptors suggested that direct CNS effects of FTY720 might theoretically occur through receptor modulation on neurons and glia. To identify CNS cells functionally contributing to FTY720 activity, genetic approaches were combined with cellular and molecular analyses. These studies relied on the functional assessment, based on clinical score, of conditional null mouse mutants lacking S1P1 in CNS cell lineages and challenged by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. All conditional null mutants displayed WT lymphocyte trafficking that responded normally to FTY720. In marked contrast, EAE was attenuated and FTY720 efficacy was lost in CNS mutants lacking S1P1 on GFAP-expressing astrocytes but not on neurons. In situ hybridization studies confirmed that astrocyte loss of S1P1 was the key alteration in functionally affected mutants. Reductions in EAE clinical scores were paralleled by reductions in demyelination, axonal loss, and astrogliosis. Receptor rescue and pharmacological experiments supported the loss of S1P1 on astrocytes through functional antagonism by FTY720-P as a primary FTY720 mechanism. These data identify nonimmunological CNS mechanisms of FTY720 efficacy and implicate S1P signaling pathways within the CNS as targets for multiple sclerosis therapies.
Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments

BDNF is produced from many transcripts that display distinct subcellular localization, suggesting that spatially restricted effects occur as a function of genetic and physiological regulation. Different BDNF 5′ splice variants give a restricted localization in the cell body or the proximal and distal compartments of dendrites; however, the functional consequences are not known. Silencing individual endogenous transcripts or overexpressing BDNF-GFP transcripts in cultured neurons demonstrated that whereas some transcripts (1 and 4) selectively affected proximal dendrites, others (2C and 6) affected distal dendrites. Moreover, segregation of BDNF transcripts resulted in a highly selective activation of the BDNF TrkB receptor. These studies indicate that spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments.
Dopamine neurons learn to encode the long-term value of multiple future rewards

Midbrain dopamine neurons signal reward value, their prediction error, and the salience of events. If they play a critical role in achieving specific distant goals, long-term future rewards should also be encoded as suggested in reinforcement learning theories. Here, we address this experimentally untested issue. We recorded 185 dopamine neurons in three monkeys that performed a multistep choice task in which they explored a reward target among alternatives and then exploited that knowledge to receive one or two additional rewards by choosing the same target in a set of subsequent trials. An analysis of anticipatory licking for reward water indicated that the monkeys did not anticipate an immediately expected reward in individual trials; rather, they anticipated the sum of immediate and multiple future rewards. In accordance with this behavioral observation, the dopamine responses to the start cues and reinforcer beeps reflected the expected values of the multiple future rewards and their errors, respectively. More specifically, when monkeys learned the multistep choice task over the course of several weeks, the responses of dopamine neurons encoded the sum of the immediate and expected multiple future rewards. The dopamine responses were quantitatively predicted by theoretical descriptions of the value function with time discounting in reinforcement learning. These findings demonstrate that dopamine neurons learn to encode the long-term value of multiple future rewards with distant rewards discounted.
αVβ3-integrin routes herpes simplex virus to an entry pathway dependent on cholesterol-rich lipid rafts and dynamin2

HSVs enter cells in a receptor-dependent [nectin1 or herpesviruses entry mediator (HVEM)] fashion by fusion of the viral envelope with plasma membrane (neutral pH compartment), by endocytosis into neutral or acidic compartments, or by macropinocytosis/phagocytosis. The cellular determinants of the route of entry are unknown. Here, we asked what cellular factors determine the pathway of HSV entry. CHO cells lack β3-integrin and the respective α-subunits’ heterodimers. We report that, in the absence of αVβ3-integrin, HSV enters CHO-nectin1 cells through a pathway independent of cholesterol-rich rafts and dynamin2. In the presence of αVβ3-integrin, HSV enters CHO-nectin1 cells through a pathway dependent on cholesterol-rich rafts and dynamin2. HSV enters J-nectin1 and 293T cells through a neutral compartment independent of cholesterol-rich rafts and dynamin2. αVβ3-integrin overexpression in these cells modifies the route of entry to an acidic compartment dependent on cholesterol-rich rafts and dynamin2, hence similar to that in αVβ3-integrin–positive CHO-nectin1 cells. In some cells, the diversion of entry from an integrin- and raft-independent pathway to an acidic compartment requiring cholesterol-rich lipids rafts and dynamin2 is irreversible. Indeed, HSV cannot infect CHO-nectin1-αVβ3 cells through any compartment when the αvβ3-integrin–dependent pathway is blocked by anti-integrin antibody, anti-dynamin2, or anti-acidification drugs. We conclude that the αvβ3-integrin is a determinant in the choice of HSV entry pathway into cells. Because the pathway dictated by αvβ3-integrin is through lipid rafts, the platforms for a number of Toll-like receptors, current findings raise the possibility that αvβ3-integrin acts as a sentinel of innate immunity.
Solution‐Grown Organic Single‐Crystalline p‐n Junctions with Ambipolar Charge Transport

Organic single-crystalline p-n junctions are grown from mixed solutions. First, C60 crystals (n-type) form and, subsequently, C8-BTBT crystals (p-type) nucleate heterogeneously on the C60 crystals. Both crystals continue to grow simultaneously into single-crystalline p-n junctions that exhibit ambipolar charge transport characteristics. This work provides a platform to study organic single-crystalline p-n junctions.
The Low Vision Rehabilitative Service Part One: Understanding Low Vision

Allied health professionals are becoming increasingly adept at identifying persons that are living with low vision. Low vision rehabilitation is among the emerging areas of practice for various allied health care providers. 1 This paper, the first of a two-part feature, provides background information that will help the allied health professional to better understand the person who will be receiving these services. The paper discusses the impact of functional vision loss, and presents a four-phase, interdisciplinary model of low vision services that can be applied to any setting, whether clinical or non-clinical. Finally, this paper describes the potential roles of the various members of the vision rehabilitation team. Part two of this series, to be presented in a subsequent publication, shall focus on methods of assessing low vision, providing clinical services, and establishing an adaptive training and instructional program.
Recent thymic emigrants are preferentially incorporated only into the depleted T-cell pool

Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, and they differ functionally and phenotypically from the rest of the naïve T-cell pool. RTEs are present in the peripheral T-cell pool throughout life but are the most common subset of T cells in neonates and adults recovering from lymphoablation. Using a murine model to study the homeostasis of RTEs, we show that under lymphoreplete conditions, RTEs are at a competitive disadvantage to already established mature naïve (MN) T cells. This disadvantage may be caused by a defect in survival, because RTEs may transduce homeostatic signals inefficiently, and their ability to survive is enhanced with increased expression of IL-7 receptor or B-cell lymphoma 2 (Bcl-2). Conversely, under lymphopenic conditions, enhanced proliferation by RTEs allows them to out-compete their MN T-cell counterparts. These results suggest that in times of need, such as in neonates or lymphopenic adults, RTEs perform well to fill the gaps in the peripheral T-cell pool, but when the periphery already is full, many RTEs are not incorporated into the pool of recirculating lymphocytes.