Miracle-dz/UniFAR-FTUs huggingface dataset:
High-throughput optical quantification of mechanosensory habituation reveals neurons encoding memory in Caenorhabditis elegans

Significance A central aim of neuroscience studies is to locate physical substrates of memory, namely neurons and molecules encoding memory. Achieving this goal requires cell-specific interrogations of neural circuitry. However, it has remained difficult to rapidly and accurately quantify the memory of animals expressing a transgene in a cell-specific manner. Our study presents a powerful optical system to perform cell-specific behavioral genetic analysis in a high-throughput manner, and demonstrates its utility by identifying two interneurons as the neural substrates of mechanosensory memory in C. elegans. We propose that our identified interneurons can be novel targets for cell-specific exploration of the molecular substrates of memory. A major goal of neuroscience studies is to identify the neurons and molecules responsible for memory. Mechanosensory habituation in Caenorhabditis elegans is a simple form of learning and memory, in which a circuit of several sensory neurons and interneurons governs behavior. However, despite the usefulness of this paradigm, there are hardly any systems for rapid and accurate behavioral genetic analysis. Here, we developed a multiplexed optical system to genetically analyze C. elegans mechanosensory habituation, and identified two interneurons involved in memory formation. The system automatically trains large populations of animals and simultaneously quantifies the behaviors of various strains by optically discriminating between transgenic and nontransgenic animals. Biochemical and cell-specific behavioral analyses indicated that phosphorylation of cyclic AMP response element-binding protein (CREB), a factor known to regulate memory allocation, was facilitated during training and this phosphorylation in AVA and AVD interneurons was required for habituation. These interneurons are a potential target for cell-specific exploration of the molecular substrates of memory.
Defining Genes in the Genome of the Hyperthermophilic Archaeon Pyrococcus furiosus: Implications for All Microbial Genomes

ABSTRACT The original genome annotation of the hyperthermophilic archaeon Pyrococcus furiosus contained 2,065 open reading frames (ORFs). The genome was subsequently automatically annotated in two public databases by the Institute for Genomic Research (TIGR) and the National Center for Biotechnology Information (NCBI). Remarkably, more than 500 of the originally annotated ORFs differ in size in the two databases, many very significantly. For example, more than 170 of the predicted proteins differ at their N termini by more than 25 amino acids. Similar discrepancies were observed in the TIGR and NCBI databases with the other archaeal and bacterial genomes examined. In addition, the two databases contain 60 (NCBI) and 221 (TIGR) ORFs not present in the original annotation of P. furiosus. In the present study we have experimentally assessed the validity of 88 previously unannotated ORFs. Transcriptional analyses showed that 11 of 61 ORFs examined were expressed in P. furiosus when grown at either 95 or 72°C. In addition, 7 of 54 ORFs examined yielded heat-stable recombinant proteins when they were expressed in Escherichia coli, although only one of the seven ORFs was expressed in P. furiosus under the growth conditions tested. It is concluded that the P. furiosus genome contains at least 17 ORFs not previously recognized in the original annotation. This study serves to highlight the discrepancies in the public databases and the problems of accurately defining the number and sizes of ORFs within any microbial genome.
Use of concentrated insulin human regular (U-500) for patients with diabetes.

PURPOSE The efficacy and safety of and key clinical considerations for using U-500 insulin human regular in the treatment of high-dose insulin-treated patients in a wide variety of settings are examined. SUMMARY U-500 regular insulin has been available in the United States since 1952, but only recently has it become more commonly prescribed for patients requiring large amounts of insulin to improve their blood glucose control. This use coincides with the increasing rates of obesity and type 2 diabetes associated with significant insulin resistance, which can necessitate the need for doses of insulin exceeding 200 units/day. However, many health care professionals are relatively unfamiliar with this concentrated insulin formulation. U-500 regular insulin has a pharmacokinetic and pharmacodynamic profile that differs from U-100 human insulins and analogues. Although no randomized clinical trials using U-500 insulin have been performed, eight case series (involving 160 patients) have been published. Rare or infrequent occurrences of hypoglycemia with U-500 insulin have been reported. Of the medication errors associated with U-500 insulin, administration and dispensing errors occurred most frequently. With the increase in prescribing of U-500 insulin, pharmacists must be aware of the complex issues involved with appropriate prescribing, dispensing, and provision of patient education to maximize patient safety and avoid administration errors and dosing confusion. CONCLUSION U-500 insulin is efficacious and safe for patients with type 2 diabetes who require a high dosage of insulin to control hyperglycemia. However, health care professionals should be well educated and vigilant about patient safety issues regarding the drug's prescription, dosing, and administration.
Web-Based eHealth to Support Counseling in Routine Well-Child Care: Pilot Study of E-health4Uth Home Safety

Background Providing safety education to parents of young children is important in the prevention of unintentional injuries in or around the home. We developed a Web-based, tailored safety advice module to support face-to-face counseling in the setting of preventive youth health care (E-health4Uth home safety) in order to improve the provision of safety information for parents of young children. Objective This pilot study evaluated a Web-based, tailored safety advice module (E-health4Uth home safety) and evaluated the use of E-health4Uth home safety to support counseling in routine well-child care visits. Methods From a preventive youth health care center, 312 parents with a child aged 10-31 months were assigned to the E-health4Uth home safety condition or to the care-as-usual condition (provision of a generic safety information leaflet). All parents completed a questionnaire either via the Internet or paper-and-pencil, and parents in the E-health4Uth condition received tailored home safety advice either online or by a print that was mailed to their home. This tailored home safety advice was used to discuss the safety of their home during the next scheduled well-child visit. Parents in the care-as-usual condition received a generic safety information leaflet during the well-child visit. Results Mean age of the parents was 32.5 years (SD 5.4), 87.8% (274/312) of participants were mothers; mean age of the children was 16.9 months (SD 5.1). In the E-health4Uth condition, 38.4% (61/159) completed the online version of the questionnaire (allowing Web-based tailored safety advice), 61.6% (98/159) preferred to complete the questionnaire via paper (allowing only a hardcopy of the advice to be sent by regular mail). Parents in the E-health4Uth condition evaluated the Web-based, tailored safety advice (n=61) as easy to use (mean 4.5, SD 0.7), pleasant (mean 4.0, SD 0.9), reliable (mean 4.6, SD 0.6), understandable (mean 4.6, SD 0.5), relevant (mean 4.2, SD 0.9), and useful (mean 4.3, SD 0.8). After the well-child visit, no significant differences were found between the E-health4Uth condition and care-as-usual condition with regard to the satisfaction with the information received (n=61, P=.51). Health care professionals (n=43) rated the tailored safety advice as adequate (mean 4.0, SD 0.4) and useful (mean 3.9, SD 0.4). Conclusions Less than half of the parents accepted the invitation to complete a Web-based questionnaire to receive online tailored safety advice prior to a face-to-face consultation. Despite wide access to the Internet, most parents preferred to complete questionnaires using paper-and-pencil. In the subgroup that completed E-health4Uth home safety online, evaluations of E-health4Uth home safety were positive. However, satisfaction scores with regard to tailored safety advice were not different from those with regard to generic safety information leaflets.
Theory of Cooperation in Complex Social Networks

This paper presents a theoretical as well as empirical study on the evolution of cooperation on complex social networks, following the continuous action iterated prisoner's dilemma (CAIPD) model. In particular, convergence to network-wide agreement is proven for both evolutionary networks with fixed interaction dynamics, as well as for coevolutionary networks where these dynamics change over time. Moreover, an extension to the CAIPD model is proposed that allows to model influence on the evolution of cooperation in social networks. As such, this work contributes to a better understanding of behavioral change on social networks, and provides a first step towards their active control.
Broadening the Scope of Societal Change Research: Psychological, Cultural, and Political Impacts of Development Aid

To date, the study of societal change in social and political psychology has been dominated by an intergroup relations research agenda. But in addition to intergroup dynamics, there are other major pathways to societal change and emancipation, which are almost never systematically considered in psychological research. The distribution of technologies (e.g., “ICT for development”) or money (e.g., microcredits) are among the supposed drivers of societal change. Many development aid projects are anchored in expectations about the effect that such instruments have on anticipated primary goals and the emancipation of particular groups (such as women). In the current paper, we begin by reviewing theories in the field of social change. Social psychological theories mainly address the conditions under which social change stimulated by intergroup dynamics is likely to occur, while other mainly historical and sociological research has focused on the role of different technologies as drivers of social change in history. Next, we review recent research focusing on the anticipated primary goals and (often) unanticipated psychological and cultural changes resulting from development aid interventions, presenting two examples of such interventions in Ethiopia and Sri Lanka in more detail. We suggest that (1) development aid projects can instigate profound psychological and cultural change and (2) that the pathways to such changes are markedly different from those traditionally examined in the literature. At the political level, we reflect on the unanticipated side effects of development aid. We conclude with some recommendations for practice following from the research described.
The Ubiquitin-Specific Protease USP15 Promotes RIG-I–Mediated Antiviral Signaling by Deubiquitylating TRIM25

A deubiquitylating enzyme prolongs the innate immune response to viruses by preventing degradation of the ubiquitin E3 ligase TRIM25. Prolonging Antiviral Signaling As part of the innate immune response to infection by RNA viruses, signaling by the cytosolic RNA sensor retinoic acid–inducible gene-I (RIG-I) stimulates the production of type I interferons (IFNs). RIG-I activity depends on its Lys63-linked polyubiquitylation by the ubiquitin E3 ligase TRIM25. As part of a negative feedback mechanism, the linear ubiquitin assembly complex (LUBAC) mediates the Lys48-linked polyubiquitylation and degradation of TRIM25, leading to inhibition of RIG-I signaling. Pauli et al. found that the deubiquitylase USP15 (ubiquitin-specific protease 15) counteracted the function of LUBAC by removing polyubiquitin from TRIM25, thus promoting its stabilization and enhancing the RIG-I–dependent antiviral response. Loss of USP15 resulted in decreased type I IFN production and enhanced viral replication in infected cells. Together, these data suggest that USP15 fine-tunes the antiviral response by sustaining the production of IFNs. Ubiquitylation is an important mechanism for regulating innate immune responses to viral infections. Attachment of lysine 63 (Lys63)–linked ubiquitin chains to the RNA sensor retinoic acid–inducible gene-I (RIG-I) by the ubiquitin E3 ligase tripartite motif protein 25 (TRIM25) leads to the activation of RIG-I and stimulates production of the antiviral cytokines interferon-α (IFN-α) and IFN-β. Conversely, Lys48-linked ubiquitylation of TRIM25 by the linear ubiquitin assembly complex (LUBAC) stimulates the proteasomal degradation of TRIM25, thereby inhibiting the RIG-I signaling pathway. Here, we report that ubiquitin-specific protease 15 (USP15) deubiquitylates TRIM25, preventing the LUBAC-dependent degradation of TRIM25. Through protein purification and mass spectrometry analysis, we identified USP15 as an interaction partner of TRIM25 in human cells. Knockdown of endogenous USP15 by specific small interfering RNA markedly enhanced the ubiquitylation of TRIM25. In contrast, expression of wild-type USP15, but not its catalytically inactive mutant, reduced the Lys48-linked ubiquitylation of TRIM25, leading to its stabilization. Furthermore, ectopic expression of USP15 enhanced the TRIM25- and RIG-I–dependent production of type I IFN and suppressed RNA virus replication. In contrast, depletion of USP15 resulted in decreased IFN production and markedly enhanced viral replication. Together, these data identify USP15 as a critical regulator of the TRIM25- and RIG-I–mediated antiviral immune response, thereby highlighting the intricate regulation of innate immune signaling.
Specific immunoglobulin A antibodies in maternal milk and delayed Helicobacter pylori colonization in Gambian infants.

BACKGROUND Immunoglobulin A (IgA) in maternal milk may protect Gambian infants from early Helicobacter pylori colonization. This study sought evidence that this protection could be due to specific IgA antibodies. METHODS Sixty-five infants were screened from 12 weeks of age with [13C]-urea breath tests. Antibodies in maternal milk were measured to determine total IgA content and to detect specific IgA antibodies against crude whole-cell and recombinant H. pylori urease antigen preparations. RESULTS Ten children (15%) had no evidence of early H. pylori colonization, 10 (15%) had early H. pylori colonization, and 43 (66%) had mixed results. Levels of maternal circulating specific immunoglobulin G, total milk IgA, and IgA directed against crude whole-cell H. pylori antigen preparation were not significantly associated with the rate of infant H. pylori colonization. However, mothers of infants with no evidence of early colonization produced significantly higher levels of anti-recombinant urease IgA antibodies in milk than did control mothers, particularly at 8, 16, and 20 weeks postpartum (P<.01). CONCLUSIONS These observations support the hypothesis that antibodies in mother's milk directed against H. pylori urease can protect against colonization in human infancy.
Repository ISTITUZIONALE

—Edge computing allows computationally intensive tasks to be ofﬂoaded to nearby (more) powerful servers, passing through an edge network. The goal of such ofﬂoading is to reduce data-intensive application response time or energy consumption, crucial constraints in mobile and IoT devices. In challenged networked scenarios, such as those deployed by ﬁrst responders after a natural or man-made disaster, it is particularly difﬁcult to achieve high levels of throughput due to scarce network conditions. Inthispaper, we present an architecture for trafﬁc management that may use deep learning to support forwarding during task ofﬂoading in these challenging scenarios. In particular, our goal is to study if and when it is worth using deep learning to route trafﬁc generated by microservices and ofﬂoading requests in these situations. Our design is different than classical approaches that use learning since we do not train for centralized routing decisions, but we let each router learn how to adapt to a lossy path without coordination, by merely using signals from standard performance-unaware protocols such as OSPF. Our results, obtained with a prototype and with simulations are encouraging, and uncover a few surprising results.
In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop

The distribution, cell tropism, and cytopathology in vivo of human immunodeficiency virus (HIV) was investigated in postmortem tissue samples from a series of HIV-infected individuals who died either of complications associated with AIDS or for unrelated reasons while they were asymptomatic. Proviral sequences were detected at a high copy number in lymphoid tissue of both presymptomatic patients and patients with AIDS, whereas significant infection of nonlymphoid tissue such as that from brains, spinal cords, and lungs were confined to those with AIDS. V3 loop sequences from both groups showed highly restricted sequence variability and a low overall positive charge of the encoded amino acid sequence compared with those of standard laboratory isolates of HIV type 1 (HIV-1). The low charge and the restriction in sequence variability were comparable to those observed with isolates showing a non-syncytium-inducing (NSI) and macrophage-tropic phenotype in vitro. All patients were either exclusively infected (six of seven cases) or predominantly infected (one case) with variants with a predicted NSI/macrophage-tropic phenotype, irrespective of the degree of disease progression. p24 antigen was detected by immunocytochemical staining of paraffin-fixed sections in the germinal centers within lymphoid tissue, although little or no antigen was found in areas of lymph node or spleen containing T lymphocytes from either presymptomatic patients or patients with AIDS. The predominant p24 antigen-expressing cells in the lungs and brains of the patients with AIDS were macrophages and microglia (in brains), frequently forming multinucleated giant cells (syncytia) even though the V3 loop sequences of these variants resembled those of NSI isolates in vitro. These studies indicate that lack of syncytium-forming ability in established T-cell lines does not necessarily predict syncytium-forming ability in primary target cells in vivo. Furthermore, variants of HIV with V3 sequences characteristic of NSI/macrophage-tropic isolates form the predominant population in a range of lymphoid and nonlymphoid tissues in vivo, even in patients with AIDS.
Ethnocentrism as a research object: A bibliometric approach

Objective. To characterize the world’s scientific production on ethnocentrism and describe the evolu - tion of its research lines over the last 80 years. Design/Methodology/Approach. Web of Science was used as a data source. Articles related to the study of ethnocentrism were analyzed using bibliometric methods, such as Bradford’s Law and bibliographic coupling. A bibliographic review was also developed to describe the main research fronts identified. Results/Discussion. An exponential growth of literature was observed, as well as the absence of specialized journals on the subject, and a gradual increase of disciplines studying ethnocentrism, which shows a research activity in process of expansion and consolidation. Three main research fronts were identified and described, focused on the study of the personality of ethnocentric individuals, their group attitudes, and their behavior as consumers of products and services. Conclusions. The study provided a comprehensive overview of the current state of research on ethno-centrism, its evolution and significance in various historical and disciplinary contexts. The absence of solid library research on this topic provides opportunities for future studies on ethnocentric biases in bibliographic collections, user education, and classification systems. Originality/Value. To our knowledge, this is the first bibliometric study that analyzes the evolution of research on ethnocentrism in a global way. It also constitutes a first approach to the study of ethnocen - trism in the field of Library and Information Science.
4-Hydroxy Hexenal Derived from Docosahexaenoic Acid Protects Endothelial Cells via Nrf2 Activation

Recent studies have proposed that n-3 polyunsaturated fatty acids (n-3 PUFAs) have direct antioxidant and anti-inflammatory effects in vascular tissue, explaining their cardioprotective effects. However, the molecular mechanisms are not yet fully understood. We tested whether n-3 PUFAs showed antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes. C57BL/6 or Nrf2−/− mice were fed a fish-oil diet for 3 weeks. Fish-oil diet significantly increased the expression of heme oxygenase-1 (HO-1), and endothelium-dependent vasodilation in the aorta of C57BL/6 mice, but not in the Nrf2−/− mice. Furthermore, we observed that 4-hydroxy hexenal (4-HHE), an end-product of n-3 PUFA peroxidation, was significantly increased in the aorta of C57BL/6 mice, accompanied by intra-aortic predominant increase in docosahexaenoic acid (DHA) rather than that in eicosapentaenoic acid (EPA). Human umbilical vein endothelial cells were incubated with DHA or EPA. We found that DHA, but not EPA, markedly increased intracellular 4-HHE, and nuclear expression and DNA binding of Nrf2. Both DHA and 4-HHE also increased the expressions of Nrf2 target genes including HO-1, and the siRNA of Nrf2 abolished these effects. Furthermore, DHA prevented oxidant-induced cellular damage or reactive oxygen species production, and these effects were disappeared by an HO-1 inhibitor or the siRNA of Nrf2. Thus, we found protective effects of DHA through Nrf2 activation in vascular tissue, accompanied by intra-vascular increases in 4-HHE, which may explain the mechanism of the cardioprotective effects of DHA.
PC Cell-Derived Growth Factor Mediates Tamoxifen Resistance and Promotes Tumor Growth of Human Breast Cancer Cells

PC cell-derived growth factor, also known as progranulin, is an Mr 88,000 growth factor (referred as PCDGF/GP88) overexpressed in human breast cancer. Antisense inhibition of PCDGF/GP88 expression in MDA-MB-468 cells inhibited tumor formation in nude mice. In estrogen receptor-positive cells, PCDGF/GP88 was expressed in response to estradiol and shown to mediate its mitogenic effect. Pathologic studies indicated that PCDGF/GP88 was expressed in 80% of invasive ductal carcinomas in correlation with parameters of poor prognosis. In the present article, the relationship between PCDGF/GP88 expression and tamoxifen resistance was examined in MCF-7 cells. PCDGF/GP88 overexpression rendered MCF-7 cells able to proliferate in the absence of estrogen and in the presence of tamoxifen. The PCDGF/GP88-overexpressing cells formed tumors in ovariectomized nude mice in the absence of estradiol and in its presence, in contrast to MCF-7 cells. Tumor growth of the overexpressing cells was increased significantly when the mice were treated with tamoxifen. PCDGF/GP88 blocked tamoxifen-induced apoptosis by preventing down-regulation of bcl-2 expression and poly(ADP-ribose) polymerase cleavage. In addition, PCDGF/GP88-overexpressing cells presented higher level of the angiogenic factors vascular endothelial growth factor and angiopoietin-1 than MCF-7 control cells. Tamoxifen treatment additionally increased the level of vascular endothelial growth factor. These studies suggest that PCDGF/GP88 plays a critical role in breast cancer tumorigenesis and in the transition to estrogen independence and tamoxifen resistance, a hallmark of poor prognosis. On the basis of the in vivo studies, it is postulated that tamoxifen treatment of patients with estrogen receptor-positive breast tumors overexpressing PCDGF/GP88 could have adverse clinical consequences.