Media composition influences yeast one- and two-hybrid results

Although yeast two-hybrid experiments are commonly used to identify protein interactions, the frequent occurrence of false negatives and false positives hampers data interpretation. Using both yeast one-hybrid and two-hybrid experiments, we have identified potential sources of these problems: the media preparation protocol and the source of the yeast nitrogen base may not only impact signal range but also effect whether a result appears positive or negative. While altering media preparation may optimize signal differences for individual experiments, media preparation must be reported in detail to replicate studies and accurately compare results from different experiments

Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans (PLoS Negl Trop Dis)

Publisher Copyright: © 2021 Moyes et al.After the publication of this article [1] the authors noticed citation errors in Table 2. The citations for item 5 listed under pyrethroids and items 2, 3, and 4 listed under temephos refer to the wrong references and these citations have been corrected in the updated Table 2 below. The citations for items 1, 3 and 4 listed under pyrethroids and item 1 listed under temephos are also incorrect and should cite references that have been omitted from the reference list. These citations have been corrected in the updated Table 2 below and the following corre-sponding references 79–82 should be added to the reference list: 79. Bariami V, Jones CM, Poupardin R, Vontas J, Ranson H. Gene amplification, ABC trans-porters and cytochrome P450s: unraveling the molecular basis of pyrethroid resistance in the dengue vector, Aedes aegypti. PLoS Negl Trop Dis. 2012;6: e1692. pmid:22720108 80. Saavedra-Rodriguez K, Suarez AF, Salas IF, Strode C, Ranson H, Hemingway J, et al. Transcription of detoxification genes after permethrin selection in the mosquito Aedes aegypti. Insect Mol Biol. 2012;21: 61–77. pmid:22032702 81. David J-P, Faucon F, Chandor-Proust A, Poupardin R, Riaz MA, Bonin A, et al. Comparative analysis of response to selection with three insecticides in the dengue mosquito Aedes aegypti using mRNA sequencing. BMC Genomics. 2014;15: 174. pmid:24593293 82. Strode C, de Melo-Santos M, Magalhaes T, Araujo A, Ayres C. Expression profile of genes during resistance reversal in a temephos selected strain of the dengue vector, Aedes aegypti. PloS One. 2012;7: e39439. pmid: 22870187.publishersversionpublishe

Cross-Frequency Integration for Consonant and Vowel Identification in Bimodal Hearing

Purpose: Improved speech recognition in binaurally combined acoustic–electric stimulation (otherwise known as bimodal hearing) could arise when listeners integrate speech cues from the acoustic and electric hearing. The aims of this study were (a) to identify speech cues extracted in electric hearing and residual acoustic hearing in the low-frequency region and (b) to investigate cochlear implant (CI) users' ability to integrate speech cues across frequencies. Method: Normal-hearing (NH) and CI subjects participated in consonant and vowel identification tasks. Each subject was tested in 3 listening conditions: CI alone (vocoder speech for NH), hearing aid (HA) alone (low-pass filtered speech for NH), and both. Integration ability for each subject was evaluated using a model of optimal integration—the PreLabeling integration model (Braida, 1991). Results: Only a few CI listeners demonstrated bimodal benefit for phoneme identification in quiet. Speech cues extracted from the CI and the HA were highly redundant for consonants but were complementary for vowels. CI listeners also exhibited reduced integration ability for both consonant and vowel identification compared with their NH counterparts. Conclusion: These findings suggest that reduced bimodal benefits in CI listeners are due to insufficient complementary speech cues across ears, a decrease in integration ability, or both.National Organization for Hearing ResearchNational Institute on Deafness and Other Communication Disorders (U.S.) (Grant R03 DC009684-01)National Institute on Deafness and Other Communication Disorders (U.S.) (Grant R01 DC007152-02

Efficacy and Safety of Autologous Tumor-Infiltrating Lymphocytes in Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, and Pancreatic Ductal Adenocarcinoma

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture. METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was evaluation of objective response rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 with secondary endpoints including disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 17 patients underwent TIL harvest and 16 were treated on protocol (NCT03610490), including 8 CRC, 5 PDAC, and 3 OVCA patients. Median age was 57.5 (range 33-70) and 50% were females. Median number of lines of prior therapy was 2 (range 1-8). No responses were observed at 12 weeks. Ten subjects achieved at least one stable disease (SD) assessment for a DCR of 62.5% (95% CI 35.4% to 84.8%). Best response included prolonged SD in a patient with PDAC lasting 17 months. Median PFS and OS across cohorts were 2.53 months (95% CI 1.54 to 4.11) and 18.86 months (95% CI 4.86 to NR), respectively. Grade 3 or higher toxicities attributable to therapy were seen in 14 subjects (87.5%; 95% CI 61.7% to 98.4%). Infusion product analysis showed the presence of effector memory cells with high expression of CD39 irrespective of tumor type and low expression of checkpoint markers. CONCLUSIONS: TIL manufactured with assistance of 4-1BB and CD3 agonism is feasible and treatment is associated with no new safety signals. While no responses were observed, a significant portion of patients achieved SD suggesting early/partial immunological effect. Further research is required to identify factors associated with resistance and functionally enhance T cells for a more effective therapy

Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility

10.1371/journal.pone.0072037PLoS ONE88-POLN

Caregiver awareness of reproductive health issues for women with intellectual disabilities

<p>Abstract</p> <p>Background</p> <p>Limited attention has been paid to the issue of reproductive health as it affects women with intellectual disabilities, despite reproductive health being a vital issue in public health policy for women in the general population. This paper describes caregiver awareness of reproductive health issues relative to women with intellectual disabilities who are being cared for in welfare institutions in Taiwan.</p> <p>Methods</p> <p>The study employed a cross-sectional, questionnaire-based study which recruited 1,152 caregivers (response rate = 71.87%) from 32 registered disability welfare institutions in Taiwan. We classified their understanding/awareness of reproductive health issues into four domains: menstrual (1) and menopause (2) issues, sex education (3), and reproductive health services (4). Each domain had five associated yes/no questions and the total score for the four domains was out of a maximum of 20. Data were analyzed using SPSS 15.0 software.</p> <p>Results</p> <p>We found that most of the caregivers were familiar with matters concerning sex education, menopause, and reproductive health services, but they lacked adequate understanding of issues associated with menstruation in women with ID. Many aspects of reproductive health such as "menstrual pain", "age at menarche", "masturbation", "diet during perimenopause", and "publicly available reproductive health services" were issues in which caregivers lacked adequate knowledge and required further instruction. Logistic regression analysis revealed that female caregivers with a university degree, and those who had experience assisting with reproductive health care were more inclined to have higher reproductive health awareness scores than their counterparts.</p> <p>Conclusions</p> <p>This study highlights that service providers should offer appropriate reproductive health education to institutional caregivers, and that more attention be focused on the personal experiences and concerns of intellectually disabled women in future research.</p

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81