148 research outputs found
Cladribine and Fludarabine Nucleoside Change the Levels of CD Antigens on B-Lymphoproliferative Disorders
The purine analogs, fludarabine nucleoside (FdA), and cladribine (CdA) (1 μM, 24 hours), significantly changed the levels of some surface antigens on the human B-cell lines MEC2 and Raji. Changes in the surface proteins were identified using a Cluster of Differentiation (CD) antibody microarray that captures live cells and confirmed by flow cytometry. For Raji cells, CdA up-regulated CD10, CD54, CD80, and CD86, with repression of CD22, while FdA up-regulated CD20, CD54, CD80, CD86 and CD95. For MEC2 cells, CdA up-regulated CD11a, CD20, CD43, CD45, CD52, CD54, CD62L, CD80, CD86, and CD95, but FdA had no effect. Up-regulation of particular CD antigens induced on a B-cell lymphoproliferative disorder by a purine analog could provide targets for therapeutic antibodies with synergistic cell killing
Effect of Influenza Vaccination on Viral Replication and Immune Response in Persons Infected with Human Immunodeficiency Virus Receiving Potent Antiretroviral Therapy
Nineteen patients infected with human immunodeficiency virus (HIV) with varying levels of viral suppression achieved with antiretroviral therapy were evaluated to determine whether trivalent influenza vaccine activated HIV replication. Humoral immune responses and CD4+ lymphocyte subsets were compared in 5 HIV-uninfected vaccinated subjects. Transient elevations of plasma HIV RNA levels (76-89 copies/mL) appeared within 2 weeks in 3 of 11 patients with 50 copies/mL. HIV DNA decreased in patients with <400 RNA copies/mL at baseline and showed an HIV RNA increase after vaccination (n = 8) when compared with 8 patients with <50 copies/mL at baseline who lacked viral response to vaccination. Concurrent decreases in proviral DNA and memory phenotype CD4+ cells in association with increased plasma HIV RNA after vaccination in patients with <400 RNA copies/mL at baseline suggest that in vivo mobilization of the latently infected cell reservoir may occur during potent antiretroviral therap
Perturbing PSD-95 Interactions With NR2B-subtype Receptors Attenuates Spinal Nociceptive Plasticity and Neuropathic Pain
Peripheral inflammation or nerve injury induces a primary afferent barrage into the spinal cord, which can cause N-methyl -aspartate (NMDA) receptor-dependent alterations in the responses of dorsal horn sensory neurons to subsequent afferent inputs. This plasticity, such as “wind-up” and central sensitization, contributes to the hyperexcitability of dorsal horn neurons and increased pain-related behavior in animal models, as well as clinical signs of chronic pain in humans, hyperalgesia and allodynia. Binding of NMDA receptor subunits by the scaffolding protein postsynaptic density protein-95 (PSD-95) can facilitate downstream intracellular signaling and modulate receptor stability, contributing to synaptic plasticity. Here, we show that spinal delivery of the mimetic peptide Tat-NR2B9c disrupts the interaction between PSD-95 and NR2B subunits in the dorsal horn and selectively reduces NMDA receptor-dependent events including wind-up of spinal sensory neurons, and both persistent formalin-induced neuronal activity and pain-related behaviors, attributed to central sensitization. Furthermore, a single intrathecal injection of Tat-NR2B9c in rats with established nerve injury-induced pain attenuates behavioral signs of mechanical and cold hypersensitivity, with no effect on locomotor performance. Thus, uncoupling of PSD-95 from spinal NR2B-containing NMDA receptors may prevent the neuronal plasticity involved in chronic pain and may be a successful analgesic therapy, reducing side effects associated with receptor blockade
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To which world regions does the valence–dominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of
how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social
judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether
these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across
11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy,
the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated
dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance
model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed
when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007);
L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from
CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social
Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing
Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were
supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E.
Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council
of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad
de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant
from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick
and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak
Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported
by a French National Research Agency ‘Investissements d’Avenir’ programme grant
(ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research
Training Program Scholarship. The Raipur Group is thankful to: (1) the University
Grants Commission, New Delhi, India for the research grants received through its
SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science;
and (2) the Center for Translational Chronobiology at the School of Studies in Life
Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by
a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was
supported by grants from the Beijing Natural Science Foundation (5184035) and CAS
Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported
by the National Science Foundation Graduate Research Fellowship (R010138018). We
acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States
International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E.
Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova);
S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of
Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R.
C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New
Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T.
Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera);
J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B.
Todorova (University of Vienna, Austria). The funders had no role in study design, data
collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog
To which world regions does the valence–dominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution
A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.
The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world
Melanoma and the Unfolded Protein Response
The UPR (unfolded protein response) has been identified as a key factor in the progression and metastasis of cancers, notably melanoma. Several mediators of the UPR are upregulated in cancers, e.g., high levels of GRP78 (glucose-regulator protein 78 kDa) correlate with progression and poor outcome in melanoma patients. The proliferative burden of cancer induces stress and activates several cellular stress responses. The UPR is a tightly orchestrated stress response that is activated upon the accumulation of unfolded proteins within the ER (endoplasmic reticulum). The UPR is designed to mediate two conflicting outcomtes, recovery and apoptosis. As a result, the UPR initiates a widespread signaling cascade to return the cell to homeostasis and failing to achieve cellular recovery, initiates UPR-induced apoptosis. There is evidence that ER stress and subsequently the UPR promote tumourigenesis and metastasis. The complete role of the UPR has yet to be defined. Understanding how the UPR allows for adaption to stress and thereby assists in cancer progression is important in defining an archetype of melanoma pathology. In addition, elucidation of the mechanisms of the UPR may lead to development of effective treatments of metastatic melanoma
Cell surface markers in colorectal cancer prognosis
The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC
Colorectal cancer therapeutic antibodies
Colorectal cancer (CRC) may occur in the colon, rectum or appendix. It is the third most common form of cancer and the third leading cause of cancer-related death in the Western world. CRC is the fourth most common cancer in men and the third in women, though significant international variations in the distribution of CRC have been observed. World-wide, nearly 1.2 million new cases of CRC were diagnosed in 2007, resulting in about 630,000 deaths (8 percent of all cancer deaths). Many CRC are thought to arise from adenomatous polyps in the colon, which are usually benign, but may develop into cancer over time. Localized CRC is generally detected by colonoscopy. Therapy is usually through surgery, often followed by chemotherapy. Recently, antibody-based therapies have also been used
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