The Far-Infrared Properties of Spatially Resolved AKARI Observations

We present the spatially resolved observations of IRAS sources from the Japanese infrared astronomy satellite AKARI All-Sky Survey during the performance verification (PV) phase of the mission. We extracted reliable point sources matched with IRAS point source catalogue. By comparing IRAS and AKARI fluxes, we found that the flux measurements of some IRAS sources could have been over or underestimated and affected by the local background rather than the global background. We also found possible candidates for new AKARI sources and confirmed that AKARI observations resolved IRAS sources into multiple sources. All-Sky Survey observations are expected to verify the accuracies of IRAS flux measurements and to find new extragalactic point sources.Comment: 11 pages, 7 figures, accepted publication in PASJ AKARI special issu

Well-being as a Function of Person-Country Fit in Human Values

It is often assumed that incongruence between individuals’ values and those of their country is distressing, but the evidence has been mixed. Across 29 countries, the present research investigated whether well-being is higher if people’s values match with those of people living in the same country or region. Using representative samples, we find that person-country and person-region value congruence predict six well-being measures (e.g., emotional well-being, relationship support; N = 54,673). Crucially, however, value type moderates whether person-country fit is positively or negatively associated with well-being. People who value self-direction, stimulation, and hedonism more and live in countries and regions where people on average share these values report lower well-being. In contrast, people who value achievement, power, and security more and live in countries and regions where people on average share these values, report higher well-being. Additionally, we find that people who moderately value stimulation report the highest well-being

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease

The accuracy of MRI in the detection of Lumbar Disc Containment

<p>Abstract</p> <p>Background</p> <p>MRI has proven to be an extremely valuable tool in the assessment of normal and pathological spinal anatomy. Accordingly, it is commonly used to assess containment of discal material by the outer fibers of the anulus fibrosus and posterior longitudinal ligaments. Determination of such containment is important to determine candidacy for intradiscal techniques and has prognostic significance. The accuracy of MRI in detecting containment has been insufficiently documented.</p> <p>Methods</p> <p>The MRI's of fifty consecutive patients undergoing open lumbar microdiscectomy were prospectively evaluated for disc containment by a neuroradiologist and senior spinal surgeon using criteria available in the literature and the classification of Macnab/McCulloch. An independent surgeon then performed the surgery and documented the actual containment status using the same methods. Statistical evaluation of accuracy was undertaken.</p> <p>Results</p> <p>MRI was found to be 72% sensitive, 68% specific, and 70% accurate in detecting containment status of lumbar herniated discs.</p> <p>Conclusion</p> <p>MRI may be inaccurate in assessing containment status of lumbar disc herniations in 30% of cases. Given the importance of containment for patient selection for indirect discectomy techniques and intradiscal therapies, coupled with prognostic significance; other methods to assess containment should be employed to assess containment when such alternative interventions are being considered.</p

Transcriptional Regulation of an Evolutionary Conserved Intergenic Region of CDT2-INTS7

In the mammalian genome, a substantial number of gene pairs (approximately 10%) are arranged head-to-head on opposite strands within 1,000 base pairs, and separated by a bidirectional promoter(s) that generally drives the co-expression of both genes and results in functional coupling. The significance of unique genomic configuration remains elusive.Here we report on the identification of an intergenic region of non-homologous genes, CDT2, a regulator of DNA replication, and an integrator complex subunit 7 (INTS7), an interactor of the largest subunit of RNA polymerase II. The CDT2-INTS7 intergenic region is 246 and 245 base pairs long in human and mouse respectively and is evolutionary well-conserved among several mammalian species. By measuring the luciferase activity in A549 cells, the intergenic human sequence was shown to be able to drive the reporter gene expression in either direction and notably, among transcription factors E2F, E2F1 approximately E2F4, but not E2F5 and E2F6, this sequence clearly up-regulated the reporter gene expression exclusively in the direction of the CDT2 gene. In contrast, B-Myb, c-Myb, and p53 down-regulated the reporter gene expression in the transcriptional direction of the INTS7 gene. Overexpression of E2F1 by adenoviral-mediated gene transfer resulted in an increased CDT2, but not INTS7, mRNA level. Real-time polymerase transcription (RT-PCR) analyses of the expression pattern for CDT2 and INTS7 mRNA in human adult and fetal tissues and cell lines revealed that transcription of these two genes are asymmetrically regulated. Moreover, the abundance of mRNA between mouse and rat tissues was similar, but these patterns were quite different from the results obtained from human tissues.These findings add a unique example and help to understand the mechanistic insights into the regulation of gene expression through an evolutionary conserved intergenic region of the mammalian genome

Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components

A Protective Mechanism against Antibiotic-Induced Ototoxicity: Role of Prestin

Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic-induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early stage

Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research

The replicability of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets replicability has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that cannot be replicated. An alternative approach is to, instead, deliberately introduce heterogeneity, known as "heterogenization" of experimental design. Here, we explore a novel perspective in the heterogenization program in a meta-analysis of variability in observed phenotypic outcomes in both control and experimental animal models of ischemic stroke. First, by quantifying interindividual variability across control groups, we illustrate that the amount of heterogeneity in disease state (infarct volume) differs according to methodological approach, for example, in disease induction methods and disease models. We argue that such methods may improve replicability by creating diverse and representative distribution of baseline disease state in the reference group, against which treatment efficacy is assessed. Second, we illustrate how meta-analysis can be used to simultaneously assess efficacy and stability (i.e., mean effect and among-individual variability). We identify treatments that have efficacy and are generalizable to the population level (i.e., low interindividual variability), as well as those where there is high interindividual variability in response; for these, latter treatments translation to a clinical setting may require nuance. We argue that by embracing rather than seeking to minimize variability in phenotypic outcomes, we can motivate the shift toward heterogenization and improve both the replicability and generalizability of preclinical research

Peptide Array X-Linking (PAX): A New Peptide-Protein Identification Approach

Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Array-formatted bait peptides containing an amino acid-derived cross-linker are photo-induced to crosslink with interacting proteins from lysates of interest. Indirect associations are removed by high stringency washes under denaturing conditions. Covalently trapped proteins are subsequently identified by LC-MS/MS and screened by cluster analysis and domain scanning. We apply this methodology to peptides with different proline-containing consensus sequences and show successful identifications from brain lysates of known and novel proteins containing polyproline motif-binding domains such as EH, EVH1, SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to capture and subsequently identify proteins by mass spectrometry is relatively broad and robust. Additionally, the approach is rapid and applicable to cell or tissue fractions from any source, making the approach a flexible tool for initial protein-protein interaction discovery.National Institutes of Health (U.S.) (Grant R21-CA-140030-01