Pollinator shifts are often related to speciation in angiosperms, and the relationship between them has been discussed in several plant taxa. Although limited information on plants pollinated by ...non-flying mammals in Central and South America and Africa is available, related research has not been conducted in Asia. Herein, I summarize the available knowledge of pollination in Asian Mucuna (Fabaceae), a genus mainly distributed in the tropics, and discuss the evolution of plants pollinated by non-flying mammals in Asia. Nineteen pollinator species have been recorded and pollination systems have been categorized into four types. An examination of the relationship between Mucuna species and their pollinators from the lineage perspective revealed that all species in Mucuna, subgenus Macrocarpa, which are distributed in Asia, are pollinated exclusively by non-flying mammals. Additionally, plants pollinated by non-flying mammals were found to have diverged from bat-pollinated and non-flying mammal-pollinated plants, while plants pollinated by non-flying mammals have evolved multiple times. This is a unique example of evolutionary transition. I hypothesize that the diversification of squirrel species in tropical Asia may have led to the speciation and diversification of Mucuna in Asia. Furthermore, the behavioural and ecological characteristics of bats and birds in Asia differ from the characteristics of those in other regions, implying that Asian Mucuna species do not rely on bat or bird pollinators. The adaptation of floral characteristics to pollinators is not well understood in Asia. Mammal-pollinated plants in Asia may have evolved differently from those in other regions and have unique pollination systems.
Several lines of research suggest that Bcl‐xL‐mediated anti‐apoptotic effects may contribute to the pathogenesis of myeloproliferative neoplasms driven by JAK2V617F and serve as therapeutic target. ...Here, we used a knock‐in JAK2V617F mouse model and confirmed that Bcl‐xL was overexpressed in erythroid progenitors. The myeloproliferative neoplasm (MPN)‐induced phenotype in the peripheral blood by conditional knock‐in of JAK2V617F was abrogated by conditional knockout of Bcl2l1, which presented anemia and thrombocytopenia independently of JAK2 mutation status. Mx1‐Cre Jak2V617W/VF/Bcl2l1f/f mice presented persistent splenomegaly as a result of extramedullary hematopoiesis and pro‐apoptotic stimuli in terminally differentiated erythroid progenitors. The pan‐BH3 mimetic inhibitor obatoclax showed superior cytotoxicity in JAK2V617F cell models, and reduced clonogenic capacity in ex vivo assay using Vav‐Cre Jak2V617F bone marrow cells. Both ruxolitinib and obatoclax significantly reduced spleen weights in a murine Jak2V617F MPN model but did not show additive effect. The tumor burden reduction was observed with either ruxolitinib or obatoclax in terminal differentiation stage neoplastic cells but not in myeloid‐erythroid precursors. Therefore, disrupting the BCL2 balance is not sufficient to treat MPN at the stem cell level, but it is certainly an additional option for controlling the critical myeloid expansion of the disease.
We demonstrate that manipulating the intrinsic apoptotic pathway may be an alternative strategy to treat MPN induced by JAK2V617F. Disrupting the BCL2 balance is not sufficient to treat MPN at the stem cell level, but it is certainly an option for controlling the myeloid expansion that leads to clinical complications dependent on increased cell counts and splenomegaly.
The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified ...as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.
Summary Objective To determine the prevalence of radiographic patellofemoral osteoarthritis (OA) from population- and symptom-based cohorts and to evaluate if knee pain, physical function and quality ...of life (QOL) differ between people with isolated patellofemoral OA, isolated tibiofemoral OA and combined patellofemoral and tibiofemoral OA. Method Terms associated with “patellofemoral OA”, “prevalence” and “clinical features” were used to search Medline, EMBASE, CINAHL, SCOPUS, AMED and Web of Science databases with no language restriction' from inception to August 2014. Two independent reviewers screened papers for eligibility. Studies were included if they reported prevalence of compartmental patterns of radiographic knee OA in population- or symptom-based cohorts. Studies were excluded if they evaluated a targeted sample (e.g., occupation-specific participants) or repeated already reported data from the same cohorts. Point prevalence estimates of patellofemoral OA were extracted from eligible studies, pooled and quantitatively analysed. A critical appraisal tool was used to evaluate methodological quality. Results The search yielded 1891 records. The inclusion criteria were met by 32 studies. The crude prevalence of patellofemoral OA was 25% in the population-based cohorts (aged >20 years) and 39% in the symptom-based cohorts (aged >30 years). Eight studies reported knee pain, physical function and QOL in people with different compartmental disease; however no significant differences were found. Conclusion These findings confirm the substantial prevalence of patellofemoral OA, demonstrating the need to specifically consider the patellofemoral joint in knee OA research and clinical settings.
Aims/hypothesis Diabetic retinopathy is a progressive neurodegenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its ...influence on retinal neurodegeneration, using an antioxidant, lutein. Methods C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. Results Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. Conclusions/interpretation The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes.
Magnetic refrigeration (MR) is a key technique for hydrogen liquefaction. Although the MR has ideally higher performance than the conventional gas compression technique around the hydrogen ...liquefaction temperature, the lack of MR materials with high magnetic entropy change in a wide temperature range required for the hydrogen liquefaction is a bottle-neck for practical applications of MR cooling systems. Here, we show a series of materials with a giant magnetocaloric effect (MCE) in magnetic entropy change (-∆S
> 0.2 J cm
K
) in the Er(Ho)Co
-based compounds, suitable for operation in the full temperature range required for hydrogen liquefaction (20-77 K). We also demonstrate that the giant MCE becomes reversible, enabling sustainable use of the MR materials, by eliminating the magneto-structural phase transition that leads to deterioration of the MCE. This discovery can lead to the application of Er(Ho)Co
-based alloys for the hydrogen liquefaction using MR cooling technology for the future green fuel society.
The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression ...profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.
Context. The interstellar medium (ISM) in starburst galaxies contains many chemical elements that are synthesised by core-collapse supernova explosions. By measuring the abundances of these metals, ...we can study the chemical enrichment within the galaxies and the transportation of metals into the circumgalactic environment through powerful outflows. Aims. We performed a spectral analysis of the X-ray emissions from the core of M 82 using the Reflection Grating Spectrometer (RGS) on board XMM-Newton to accurately estimate the metal abundances in the ISM. Methods. We analysed over 300 ks of RGS data observed with 14 position angles, covering a cross-dispersion width of 80 arcsec. We employed multi-temperature thermal plasma components in collisional ionisation equilibrium (CIE) to reproduce the observed spectra, each of which exhibited a different spatial broadening. Results. The O VII band CCD image shows a broader distribution that those for the O VIII and Fe-L bands. The O VIII line profiles have a prominent double-peaked structure that corresponds to the north- and southward outflows. The O VII triplet feature exhibits marginal peaks. A single CIE component that is convolved with the O VII band image approximately reproduces the spectral shape. A CIE model combined with a charge-exchange emission model also successfully reproduces the O VII line profiles. However, the ratio of these two components varies significantly with the observed position angles, which is physically implausible. Spectral fitting of the broadband spectra suggests a multi-temperature phase in the ISM that is approximated by three components at 0.1, 0.4, and 0.7 keV. Notably, the 0.1 keV component exhibits a broader distribution than the 0.4 and 0.7 keV plasmas. The derived abundance pattern shows super-solar N/O, solar Ne/O and Mg/O, and half-solar Fe/O ratios. These results indicate the chemical enrichment by core-collapse supernovae in starburst galaxies.
Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although ...the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as “NLRC5” NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5, has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8⁺ cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.
Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring
mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected ...by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and single-cell ATAC-seq analyses to define the transcriptional and epigenetic landscape of parental cells, DTPs, and tumor cells in a fully resistant state. In addition to
,
, and
, which are all known to induce EGFR-TKI resistance,
was identified as a novel gene that plays a critical role in the drug-tolerant state.
and
experiments demonstrated that CD74 upregulation confers resistance to the EGFR-TKI osimertinib and blocks apoptosis, enabling tumor regrowth. Overall, this study provides new insight into the mechanisms underlying resistance to EGFR-TKIs. SIGNIFICANCE: Single-cell analyses identify diverse mechanisms of resistance as well as the state of tolerant cells that give rise to resistance to EGFR tyrosine kinase inhibitors.
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