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Purpose: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. Methods: This retrospective study enrolled 133 patients (median age, 63 [range, 24–85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. Results: Among patients with pT1–pT4 disease, MRI with OAI (accuracy: 88.7–94.7%, sensitivity: 66.7–93.0%, specificity: 91.5–100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2–88.7%, sensitivity: 46.2–83.1%, specificity: 85.5–99.1%) and CT (accuracy: 88.0–92.5%, sensitivity: 53.3–90.1%, specificity: 88.7–98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p <.001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p =.35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). Conclusion: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the identification of tumor deposits (TDs) and the prognostic significance of an MRI tumor regression grade for TDs in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). Methods: Ninety-one patients with cT3 or cT4 rectal cancer who underwent surgery following nCRT between August 2014 and June 2020 were retrospectively analyzed. Changes in pre-nCRT MRI-detected TDs (mrTDs) were described as mrTD regression grade. The diagnostic performance of post-nCRT MRI-detected TDs (ymrTDs) was compared with histopathological reference standard. The correlation between ymrTDs, mrTD regression grade, and disease-free survival (DFS) was assessed. Results: The sensitivity and specificity of ymrTDs were 88.00% and 89.39%, respectively. The area under the receiver operating characteristic curve was 0.887 (95% confidence interval [CI]: 0.803–0.944). The 3-year DFS of patients with positive ymrTDs was significantly lower than of the negative group (44.83% vs 82.73%, p < 0.001). The 3-year DFS was 33.33% for patients with poor regression of mrTDs following nCRT and 55.56% for those with moderate regression, compared to 69.23% in good responders and 83.97% in patients without mrTDs (p < 0.001). On multivariable Cox regression, mrTD regression grade was the only independent MRI factor associated with DFS (p = 0.042). Conclusions: Diagnostic performance of ymrTDs was moderate. The mrTD regression grade was independently correlated with DFS, which may have a prognostic implication for treatment and follow-up. Clinical relevance statement: Patients with poor regression of MRI-detected tumor deposits may benefit from more aggressive treatments, such as chemoradiation therapy plus induction or consolidation chemotherapy. Key Points: • MRI provides a preoperative and noninvasive way to visualize tumor deposits (TDs) after neoadjuvant chemoradiotherapy (nCRT). • Post-nCRT MRI-detected TDs are a poor prognostic marker in cT3 and cT4 rectal cancer patients. • The regression of MRI-detected TDs after nCRT is associated with an improved disease-free survival. [ABSTRACT FROM AUTHOR]

Background The growing demands in integrating digital pedagogies in learning (e.g., social media) contribute to disrupting many fields, including the medical humanities education. However, the strengths and barriers behind social media and medical humanities context are blurred and contradictive. We examined the perceptions of integrating social media-Facebook-into a narrative medicine (NM) programme for 5th -year clerkship in Taiwan. Methods We used purposive sampling to recruit participants. Sixteen medical students (Female/Male: 7/9) participated in four group interviews. Semi-structured focus group interviews were conducted to explore students’ perceptions and experiences of the social media integrated into the NM programme. We analysed the data using a descriptive thematic analysis with a team-based approach. Data were managed and coded using ATLAS.ti version 9.0. Results We identified six main themes: (1) Positive experiences of social media integration; (2) Negative experiences of social media integration; (3) Barriers on writing and sharing NM stories in social media; (4) Barriers on reading NM stories in social media; (5) Barriers on reacting contents in social media; (6) Suggestions for future improvement. Conclusions The study revealed the strengths and barriers from medical students’ perceptions, when integrating social media into a NM programme. It is important to match students’ experiences, barriers, and perceptions towards learning. Understanding participants’ suggestions for future improvement are also crucial. With this knowledge, we might better develop the social media integration systems that achieve our desired outcomes based on the medical humanities education curricula. [ABSTRACT FROM AUTHOR]

Objectives: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. Methods: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. Results: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min−1 vs 0.054 min−1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min−1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. Conclusion: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. Clinical relevance statement: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. Key Points: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer. [ABSTRACT FROM AUTHOR]

The eukaryotic chaperonin TRiC/CCT assists the folding of about 10% of cytosolic proteins through an ATP-driven conformational cycle, and the essential cytoskeleton protein tubulin is the obligate substrate of TRiC. Here, we present an ensemble of cryo-EM structures of endogenous human TRiC throughout its ATPase cycle, with three of them revealing endogenously engaged tubulin in different folding stages. The open-state TRiC-tubulin-S1 and -S2 maps show extra density corresponding to tubulin in the cis-ring chamber of TRiC. Our structural and XL-MS analyses suggest a gradual upward translocation and stabilization of tubulin within the TRiC chamber accompanying TRiC ring closure. In the closed TRiC-tubulin-S3 map, we capture a near-natively folded tubulin—with the tubulin engaging through its N and C domains mainly with the A and I domains of the CCT3/6/8 subunits through electrostatic and hydrophilic interactions. Moreover, we also show the potential role of TRiC C-terminal tails in substrate stabilization and folding. Our study delineates the pathway and molecular mechanism of TRiC-mediated folding of tubulin along the ATPase cycle of TRiC, and may also inform the design of therapeutic agents targeting TRiC-tubulin interactions. Cryo-EM and XL-MS analyses reveal the conformational landscape of TRiCmediated tubulin folding along TRiC's ATPase cycle and the interaction sites between tubulin and the closed TRiC chamber. [ABSTRACT FROM AUTHOR]

Somatosensory neurons are highly heterogeneous with distinct types of neural cells responding to specific stimuli. However, the distribution and roles of cell‐type‐specific long intergenic noncoding RNAs (lincRNAs) in somatosensory neurons remain largely unexplored. Here, by utilizing droplet‐based single‐cell RNA‐seq (scRNA‐seq) and full‐length Smart‐seq2, we show that lincRNAs, but not coding mRNAs, are enriched in specific types of mouse somatosensory neurons. Profiling of lincRNAs from single neurons located in dorsal root ganglia (DRG) identifies 200 lincRNAs localized in specific types or subtypes of somatosensory neurons. Among them, the conserved cell‐type‐specific lincRNA CLAP associates with pruritus and is abundantly expressed in somatostatin (SST)‐positive neurons. CLAP knockdown reduces histamine‐induced Ca2+ influx in cultured SST‐positive neurons and in vivo reduces histamine‐induced scratching in mice. In vivo knockdown of CLAP also decreases the expression of neuron‐type‐specific and itch‐related genes in somatosensory neurons, and this partially depends on the RNA binding protein MSI2. Our data reveal a cell‐type‐specific landscape of lincRNAs and a function for CLAP in somatosensory neurons in sensory transmission. Synopsis: A single‐cell lincRNA landscape of DRG cells is constructed and hundreds of highly expressed lincRNAs are characterized in distinct types and subtypes of mouse DRG neurons. A highly conserved lincRNA CLAP specifically expressed in somatostatin‐positive neurons regulates histamine‐mediated neuronal activation, acute itch, and type‐specific gene expression. scRNA‐seq reveals that hundreds of lincRNAs are preferentially enriched in the specific type and subtype of somatosensory neurons.Knockdown of CLAP, a conserved and abundant lincRNA in somatostatin‐positive neurons, reduces histamine‐induced neuronal activation and itch sensation.In vivo repression of CLAP reduces neuron type‐specific and itch‐related gene expression, and this partially depends on the RNA binding protein MSI2. [ABSTRACT FROM AUTHOR]

Background: The mesorectum surrounding the rectum provides an ideal substrate for tumour spread. However, preoperative risk assessment is still an issue. This study aimed to investigate the microstructural features of mesorectum with different prognostic statuses by intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI).Methods: Patients with pathologically proven rectal adenocarcinoma underwent routine high-resolution rectal magnetic resonance imaging (MRI) and IVIM DWI sequences were acquired. The MRI-detected circumferential resection margin (mrCRM) and extramural vascular invasion (mrEMVI) were evaluated. IVIM parameters of the mesorectum adjacent to (MAT) and distant from (MDT) the tumour were measured and compared between and within the prognostic factor groups.Results: The positive mrCRM (pMAT < 0.001; pMDT = 0.013) and mrEMVI (pMAT = 0.001; pMDT < 0.001) groups demonstrated higher D values in the MAT and MDT than the corresponding negative groups. Conversely, the positive mrCRM (p = 0.001) and mrEMVI (p < 0.001) groups both demonstrated lower f values in the MAT. Similarly, in the self-comparison between the MAT and MDT in the above subgroups, D showed a significant difference in all subgroups (p < 0.001 for all), and f showed a significant difference in the positive mrCRM (p = 0.001) and mrEMVI (p = 0.002) groups. Moreover, the MAT displayed a higher D* in the positive mrCRM (p = 0.014), negative mrCRM (p = 0.009) and negative mrEMVI groups (p < 0.001).Conclusion: The microstructure of the mesorectum in patients with rectal cancer with poor prognostic status shows changes based on IVIM parameters. IVIM parameters might be promising imaging biomarkers for risk assessment of tumour spread in mesorectum preoperatively. [ABSTRACT FROM AUTHOR]

Highland barley (Hordeum vulgare L.), as the dominant crop on the Qinghai-Tibetan Plateau, is a typical representative of plants adapted to extreme environmental conditions. However, the harsh environment, severe salinisation and frequent freezing and thawing in the Qinghai-Tibetan Plateau are main limiting factor for crop growth in this region. The physiological response of highland barley to salinisation and freeze–thaw stresses was studied in this paper. Under the combined stresses of 60 mmol/L NaCl·60 mmol/L NaHCO3 and freeze–thaw cycles (10, −5, and 10°C), the changes in the relative moisture content, relative electrical conductivity, soluble protein, malondialdehyde (MDA) and photosynthetic indices Pn and E in seedling leaves of eight groups of treatments (CK, S, A, S-A, CK (FT), S (FT), A (FT), and S-A (FT)) were analysed. Results showed that a single stress did not cause a change in the MDA content. All of the combined stresses in S-A, CK (FT), S (FT), A (FT), and S-A (FT) treatments increased the MDA content of barley seedlings, and the MDA content of S-A (FT) reached 28.438 at T2 (−5°C) μmol/g. During the freeze–thaw cycle, the cell membrane of seedlings was damaged more seriously by alkali stress, which showed a significant increase in relative conductivity. The relative moisture content value of seedlings was more than 100% because the seedlings could absorb more moisture due to mechanical injury. The protein content of osmoregulatory substances in highland barley seedlings increased with increasing stress, indicating resistance to stress. Moreover, the effect of freeze–thaw stress on photosynthesis was more significant. The changes in indices proved that an appropriate amount of salt stress could improve the resistance of the plant cell membrane. Alkali stress had a significant effect on the growth of highland barley seedlings. Freezing and thawing can aggravate the damage of saline–alkali stress to highland barley seedlings, resulting in changes in the biological membrane permeability and photosynthesis of seedlings. The fluctuation of osmoregulation substance content confirmed that highland barley seedlings had a certain degree of stress resistance. Freeze–thaw cycles will aggravate the damage of land salinisation to highland barley seedlings. To better reduce the impact and loss of land salinisation and freeze–thaw disasters on agriculture in the Qinghai-Tibetan Plateau, priority should be given to solving freeze–thaw stress in the process of grain production. Highland barley (Hordeum vulgare L.) is one of the important food crops for Tibetans. However, the environment in the Qinghai-Tibet Plateau is challenging for plant growth with combined stresses of saline–alkali and freeze–thaw affecting grain yield and quality. Research shows that the freeze–thaw cycle aggravate the damage of saline–alkali stress to highland barley seedlings, affecting biofilm permeability, osmotic adjustment and seedling photosynthesis. The results of this study will provide guidance and suggestions for improving crop production. [ABSTRACT FROM AUTHOR]

In Qinghai-Tibet Plateau, crops are commonly subjected to freeze–thaw and salt stress factors simultaneously, and allelopathy is common, which affects the growth of highland barley (Hordeum vulgare L.), the largest food crop in Tibet. In order to explore the effects of artemisinin, salt and freeze–thaw (FAS) stress on physiological characteristics of highland barley seedlings, hydroponic experiment was carried out with the addition of 20 mg/L artemisinin and 150 mM NaCl as well as the simulation of freeze–thaw environment. The results suggested that under combined stress, the soluble protein content in combined stresses of artemisinin, FAS increased by 97.8%, the variation of relative conductivity in FAS group was lower than that in combined salt and freeze–thaw stress (FS), the relative water content decreased significantly (P < 0.05), the malondialdehyde (MDA), H2O2 and soluble sugar content in FAS group accumulated but less than those in FS group, and the superoxide dismutase (SOD) activity in combined artemisinin and freeze–thaw stress (FA) and FAS groups decreased. In addition, after freeze–thaw treatment, photosynthesis was weakened, and internal CO2 conentration (C i) in FAS group significantly decreased (P < 0.05). This study proved that appropriate amount of artemisinin can alleviate the damage of salt and freeze–thaw stress on barley seedlings. Freeze–thaw and NaCl stress limit plant growth. We focus on the effect of combined stress on seedlings of highland barley (Hordeum vulgare L.). Appropriate concentration of artemisinin can enhance the resistance to adverse environment. [ABSTRACT FROM AUTHOR]

Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3′ untranslated regions (3′ UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders. [Display omitted] • Depletion of PQBP1 reduces NSPC proliferation and promotes neuronal differentiation • PQBP1 selectively regulates APA profiles in NSPCs • PQBP1 competes with CFIm for binding to UGUA motif and suppresses mRNA 3′ end processing • PQBP1 C-terminal truncation disrupts the RNA-binding ability and impairs neurogenesis Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Liu et al. discover PQBP1 as a novel APA regulator that actively maintains cell-specific APA profiles in neural stem/progenitor cells (NSPCs) and delicately manages the balance between NSPC proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Microtubules consisting of α/β-tubulin dimers play critical roles in cells. More than seven genes encode α-tubulin in vertebrates. However, the property of microtubules composed of different α-tubulin isotypes is largely unknown. Here, we purified recombinant tubulin heterodimers of mouse α-tubulin isotypes including α1A and α1C with β-tubulin isotype β2A. In vitro microtubule reconstitution assay detected that α1C/β2A microtubules grew faster and underwent catastrophe less frequently than α1A/β2A microtubules. Generation of chimeric tail-swapped and point-mutation tubulins revealed that the carboxyl-terminal (C-terminal) tails of α-tubulin isotypes largely accounted for the differences in polymerization dynamics of α1A/β2A and α1C/β2A microtubules. Kinetics analysis showed that in comparison to α1A/β2A microtubules, α1C/β2A microtubules displayed higher on-rate, lower off-rate, and similar GTP hydrolysis rate at the plus-end, suggesting a contribution of higher plus-end affinity to faster growth and less frequent catastrophe of α1C/β2A microtubules. Furthermore, EB1 had a higher binding ability to α1C/β2A microtubules than to α1A/β2A ones, which could also be attributed to the difference in the C-terminal tails of these two α-tubulin isotypes. Thus, α-tubulin isotypes diversify microtubule properties, which, to a great extent, could be accounted by their C-terminal tails. [ABSTRACT FROM AUTHOR]

Tri-methylation on lysine 40 of α-tubulin (α-TubK40me3) is a recently identified post-translational modification involved in mitosis and cytokinesis. However, knowledge about α-TubK40me3 in microtubule function and post-mitotic cells remains largely incomplete. Here, we report that α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. α-TubK40me3 is enriched in mouse cerebral cortex during embryonic day (E)14 to E16. Knockdown of α-tubulin methyltransferase SETD2 at E14 leads to the defects in neuronal migration, which could be restored by overexpressing either a cytoplasm-localized SETD2 truncation or α-TubK40me3-mimicking mutant. Furthermore, α-TubK40me3 is preferably distributed on polymerized microtubules and potently promotes tubulin nucleation. Downregulation of α-TubK40me3 results in reduced microtubule abundance in neurites and disrupts neuronal polarization, which could be rescued by Taxol. Additionally, α-TubK40me3 is increased after losing α-tubulin K40 acetylation (α-TubK40ac) and largely rescues α-TubK40ac function. This study reveals a critical role of α-TubK40me3 in microtubule formation and neuronal development. Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the role of hepatic mosaic enhancement pattern (HMEP) on computed tomography images in the disease activity and therapeutic outcome of Crohn's Disease (CD). Methods: Twenty-five CD patients with HMEP comprised the HMEP group, and 25 CD patients without HMEP, who had a similar onset age, sex, and disease course with those in the HMEP group, comprised the non-HMEP group. No underlying liver/biliary disease was observed in any of the patients. Clinical characteristics, laboratory test results, Lémann index, and CD endoscopic index of severity (CDEIS) were compared between the groups using the Student t-, Mann–Whitney U, Chi square, or Fisher's exact tests. Patients received top-down, step-up, or traditional treatment during the follow-up period. After the 1-year follow-up, therapeutic outcomes (active inflammation [CDEIS > 3.5 if the endoscopic data were available, or C-reactive protein level > 5 mg/L if the endoscopic data were unavailable] or remission) were evaluated. Results: The occurrence rate of fistulas/abscesses was higher in the HMEP group (84%, 21/25) than in the non-HMEP group (48%, 12/25) with no statistical significance (P = 0.056). The HMEP group showed a higher C-reactive protein level (P = 0.001), erythrocyte sedimentation rate (P = 0.013), and blood platelet count (P = 0.005). There was no significant difference in therapeutic strategies between the groups (P = 0.509). The HMEP group showed a significantly lower remission ratio after anti-inflammatory treatment than the non-HMEP group (P = 0.045). Conclusions: HMEP was correlated with increased inflammatory activity and adverse therapeutic outcomes in CD. This finding provided insights regarding novel markers of CD diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To determine the utility of diffusion kurtosis imaging (DKI) for assessing bowel fibrosis and to establish a new magnetic resonance imaging (MRI)-based classification based on DKI and conventional MRI parameters for characterizing intestinal strictures in Crohn's disease (CD) using the histological evaluation of resected intestine samples as the reference standard. Methods: Thirty-one patients with CD undergoing preoperative conventional MRI and diffusion-weighted imaging (DWI) (b values = 0–2000 s/mm2) were consecutively enrolled. We classified the mural T2-weighted signal intensity and arterial-phase enhancement patterns on conventional MRI. We also measured DWI-derived apparent diffusion coefficients (ADCs) and DKI-derived apparent diffusion for non-Gaussian distribution (Dapp) and apparent diffusional kurtosis (Kapp). A new MRI-based classification was established to characterize intestinal strictures in CD. Its performance was validated in nine additional patients with CD. Results: Histological inflammation grades were significantly correlated to T2-weighted signal intensity (r = 0.477; P < 0.001) and ADC (r = − 0.226; P = 0.044). Histological fibrosis grades were moderately correlated to Kapp (r = 0.604, P < 0.001); they were also correlated to Dapp (r = − 0.491; P < 0.001) and ADC (r = − 0.270; P = 0.015). T2-weighted signal intensity could differentiate between no-to-mild and moderate-to-severe bowel inflammation (sensitivity, 0.970; specificity, 0.479). Kapp could differentiate between no-to-mild and moderate-to-severe bowel fibrosis (sensitivity, 0.959; specificity, 0.781). The agreement between the new MRI-based classification and the histological classification was moderate in the test (κ = 0.507; P < 0.001) and validation (κ = 0.530; P < 0.001) sets. Conclusions: DKI can be used to assess bowel fibrosis. The new MRI-based classification can help to distinguish between fibrotic and inflammatory intestinal strictures in patients with CD. [ABSTRACT FROM AUTHOR]

FXYD6, an unnecessary auxiliary subunit of Na+,K+-ATPase, is expressed in the nervous system. However, its functions remain largely unclear. In the present study, we find that FXYD6 is involved in the thermal nociception. FXYD6 was mainly expressed in small-diameter DRG neurons expressing transient receptor potential channel V1 (TRPV1). In the SNS-Cre / Fxyd6F/F mice, loss of FXYD6 in these sensory neurons impaired the behavioral responses to noxious heat stimulus and intraplantar injection of capsaicin. The capsaicin-induced and TRPV1-mediated currents were decreased in the FXYD6–deficient DRG neurons. Heterologous expression of FXYD6 could increase the TRPV1 capsaicin-sensitive currents in HEK293 cells. Furthermore, we found that the negatively charged PGDEE motif in C-terminal of FXYD6 is required for the FXYD6/TRPV1 interaction and FXYD6-mediated enhancement of TRPV1. Disrupting the FXYD6/TRPV1 interaction with the TAT-PGDEE peptide could elevate the threshold of thermal nociception. Therefore, FXYD6 maintains the thermal nociception via interacting with TRPV1 channel in nociceptors. [ABSTRACT FROM AUTHOR]

Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β -tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α -tubulin in vivo and in vitro. The SUMOylation on α -tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble α -tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on α -tubulin reduced catastrophe frequency and increased the proportion of polymerized α -tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced α -tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient α -tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on α -tubulin represents a new player in the regulation of MT properties. [ABSTRACT FROM AUTHOR]

FXYD6, an unnecessary auxiliary subunit of Na+,K+-ATPase, is expressed in the nervous system. However, its functions remain largely unclear. In the present study, we find that FXYD6 is involved in the thermal nociception. FXYD6 was mainly expressed in small-diameter DRG neurons expressing transient receptor potential channel V1 (TRPV1). In the SNS-Cre / Fxyd6F/F mice, loss of FXYD6 in these sensory neurons impaired the behavioral responses to noxious heat stimulus and intraplantar injection of capsaicin. The capsaicin-induced and TRPV1-mediated currents were decreased in the FXYD6–deficient DRG neurons. Heterologous expression of FXYD6 could increase the TRPV1 capsaicin-sensitive currents in HEK293 cells. Furthermore, we found that the negatively charged PGDEE motif in C-terminal of FXYD6 is required for the FXYD6/TRPV1 interaction and FXYD6-mediated enhancement of TRPV1. Disrupting the FXYD6/TRPV1 interaction with the TAT-PGDEE peptide could elevate the threshold of thermal nociception. Therefore, FXYD6 maintains the thermal nociception via interacting with TRPV1 channel in nociceptors. [ABSTRACT FROM AUTHOR]

More than 30% of patients with Crohn's disease (CD) develop fibrotic strictures in the bowel as the disease progresses. Excessive deposition of extracellular matrix components in the submucosa and smooth muscle hypertrophy or hyperplasia are the main features of fibrosis in CD. Cross‐sectional imaging technology provides a wealth of information on the anatomy, histological composition, and physiological function of the bowel, allowing for a non‐invasive and complete evaluation of associated abnormalities. This review summarizes recent advances in and the potential technologies of cross‐sectional imaging for assessing intestinal fibrosis in CD, including ultrasound imaging, computed tomography, and magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Background: A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn's disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis.Methods: We analyzed the histopathological data of 31 patients with Crohn's disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis.Results: Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn's disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001).Conclusions: Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis. [ABSTRACT FROM AUTHOR]

Objectives: Although diffusion-weighted imaging (DWI) is reported to be accurate in detecting bowel inflammation in Crohn's disease (CD), its ability to assess bowel fibrosis remains unclear. This study assessed the role of DWI in the characterization of bowel fibrosis using surgical histopathology as the reference standard.Methods: Abdominal DWI was performed before elective surgery in 30 consecutive patients with CD. The apparent diffusion coefficients (ADCs) in pathologic bowel walls were calculated. Region-by-region correlations between DWI and the surgical specimens were performed to determine the histologic degrees of bowel fibrosis and inflammation.Results: ADCs correlated negatively with bowel inflammation (r = - 0.499, p < 0.001) and fibrosis (r = - 0.464, p < 0.001) in 90 specimens; the ADCs in regions of nonfibrosis and mild fibrosis were significantly higher than those in regions of moderate-severe fibrosis (p = 0.008). However, there was a significant correlation between the ADCs and bowel fibrosis (r = - 0.641, p = 0.001) in mildly inflamed segments but not in moderately (r = - 0.274, p = 0.255) or severely (r = - 0.225, p = 0.120) inflamed segments. In the mildly inflamed segments, the ADCs had good accuracy with an area under the receiver-operating characteristic curve of 0.867 (p = 0.004) for distinguishing nonfibrosis and mild fibrosis from moderate-severe fibrosis.Conclusions: ADC can be used to assess bowel inflammation in patients with CD. However, it only enables the accurate detection of the degree of bowel fibrosis in mildly inflamed bowel walls. Therefore, caution is advised when using ADC to predict the degree of intestinal fibrosis.Key Points: • Diffusion-weighted imaging was used to assess bowel inflammation in patients with Crohn's disease. • The ability of diffusion-weighted imaging to evaluate bowel fibrosis decreased with increasing bowel inflammation. • Diffusion-weighted imaging enabled accurate detection of the degree of fibrosis only in mildly inflamed bowel walls. [ABSTRACT FROM AUTHOR]

Abstract: An unprecedented substrate‐dependent [5+1] annulation of 2‐isocyanochalcones with nitroalkanes was developed for the efficient synthesis of functionalized quinolines and 3‐nitrodihydroquinolines. This transformation delivers both the aromatic and dihydroquinolines by selectively elimination or retention of the nitro group. Moreover, 3‐nitroquinolines and tricyclic pyrrolo[2,3‐c]quinolines were conveniently constructed from the resulting 3‐nitrodihydroquinolines through a single operation, respectively. [ABSTRACT FROM AUTHOR]

With the increasing occurrence of haze during the summer, the physicochemical characteristics and toxicity differences in PM2.5 in different seasons are of great concern. Hangzhou is located in an area that has a subtropical monsoon climate where the humidity is very high during both the summer and winter. However, there are limited studies on the seasonal differences in PM2.5 in these weather conditions. In this test, PM2.5 samples were collected in the winter and summer, the morphology and chemical composition of PM2.5 were analyzed, the toxicity of PM2.5 to human bronchial cells BEAS-2B was compared, and the correlation between PM2.5 toxicity and the chemical composition was discussed. The results showed that during both the winter and summer, the main compounds in the PM2.5 samples were water-soluble ions, particularly SO42−, NO3−, and NH4+, followed by organic components, while heavy metals were present at lower levels. The higher the mass concentration of PM2.5, the greater its impact on cell viability and ROS levels. However, when the mass concentration of PM2.5 was similar, the water extraction from the summer samples showed a greater impact on BEAS-2B than that from the winter samples. The cytotoxicity of PM2.5 was closely associated with heavy metals and organic pollutants but less related to water-soluble ions. [ABSTRACT FROM AUTHOR]

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In the current study, we investigated nitrite-dependent anaerobic methane oxidation (N-DAMO) as a potential methane sink in the Hangzhou Bay and the adjacent Zhoushan sea area. The potential activity of the N-DAMO process was primarily observed in Hangzhou Bay by means of C-labeling experiments, whereas very low or no potential N-DAMO activity could be detected in the Zhoushan sea area. The measured potential N-DAMO rates ranged from 0.2 to 1.3 nmol CO g (dry sediment) day, and the N-DAMO potentially contributed 2.0-9.4 % to the total microbial methane oxidation in the examined sediments. This indicated that the N-DAMO process may be an alternative pathway in the coastal methane cycle. Phylogenetic analyses confirmed the presence of Candidatus Methylomirabilis oxyfera-like bacteria in all the examined sediments, while the group A members (the dominant bacteria responsible for N-DAMO) were found mainly in Hangzhou Bay. Quantitative PCR showed that the 16S rRNA gene abundance of Candidatus M. oxyfera-like bacteria varied from 5.4 × 10 to 5.0 × 10 copies g (dry sediment), with a higher abundance observed in Hangzhou Bay. In addition, the overlying water NO concentration and salinity were identified as the most important factors influencing the abundance and potential activity of Candidatus M. oxyfera-like bacteria in the examined sediments. This study showed the evidence of N-DAMO in coastal environments and indicated the importance of N-DAMO as a potential methane sink in coastal environments. [ABSTRACT FROM AUTHOR]

Medicago truncatulais a model legume species with a diverse genetic diversity. To explore whether different ecotypes ofMedicago truncatuladiffer in their response to sulfur deficiency, the effects of sulfur (S) deficiency on the two ecotypes (A17 and R108) were investigated. Sulfur deficiency stimulated lateral root initiation in the root apical region of both ecotypes, but did not affect their overall biomass. The S deficiency-induced changes in root morphology were more distinct in R108 plants than in A17 plants. Exposure to S deficiency led to a greater reduction in leaves and roots of R108 than those of A17 plants. The concentrations of majority of other mineral nutrients were increased in A17 plants, while they were mainly reduced in R108 plants under S-deficient conditions. A greater reduction in R108 plants than in A17 plants was found under S-deficient conditions. An accumulation of anthocyanin in R108 was observed under S-deficient conditions. These results indicate that the ecotype R108 appears more sensitive to S deficiency than the ecotype A17. [ABSTRACT FROM AUTHOR]

The establishment of a functional vasculature requires endothelial cells to enter quiescence during the completion of development, otherwise pathological overgrowth occurs. How such a transition is regulated remains unclear. Here, we uncover a role of Zeb1 in defining vascular quiescence entry. During quiescence acquisition, Zeb1 increases along with the progressive decline of endothelial progenitors' activities, with Zeb1 loss resulting in endothelial overgrowth and vascular deformities. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) analyses reveal that Zeb1 represses Wif1, thereby activating Wnt/β-catenin signaling. Knockdown of Wif1 rescues the overgrowth induced by Zeb1 deletion. Importantly, local administration of surrogate Wnt molecules in the retina ameliorates the overgrowth defects of Zeb1 mutants. These findings show a mechanism by which Zeb1 induces quiescence of endothelial progenitors during the establishing of vascular homeostasis, providing molecular insight into the inherited neovascular pathologies associated with human ZEB1 mutations, suggesting pharmacological activation of Wnt/β-catenin signaling as a potential therapeutical approach. [Display omitted] • Zeb1-Wif1-Wnt/β-catenin signaling governs endothelial progenitors' quiescence entry • Zeb1 deficiency results in vascular deformities resembling patients with PPCD • Wnt/β-catenin local activation ameliorates vascular pathologies in Zeb1 ECKO The establishment of a functional vasculature requires the quiescence entry of endothelial cells (ECs) when development is completed, otherwise, pathological overgrowth occurs. In this study, Yu et al. identify Zeb1, which acts upstream of Wnt/β-catenin signaling, to govern the quiescence of EC progenitors and the transition into homeostasis. [ABSTRACT FROM AUTHOR]

Long intergenic noncoding RNAs (lincRNAs) are crucial regulators in numerous biological processes. However, the functions and mechanisms of m6A-modified lincRNAs in neuronal development remain unclear. Here, we report an m6A-modified lincRNA, Dppa2 upstream binding RNA (Dubr), abundantly expressed at the early developmental stage of dorsal root ganglion (DRG) and cerebral cortex. Silencing Dubr impairs axon elongation of DRG neurons and axon projection and migration of cortical neurons, whereas lacking m6A modification of Dubr fully loses its functions. Mechanically, Dubr interacts with m6A-binding proteins, the YTHDF1/3 complex, through its m6A motifs to protect YTHDF1/3 from degradation via the proteasome pathway. Furthermore, Tau and Calmodulin are regulated by YTHDF1/3 and m6A-modified Dubr. Overexpression of YTHDF1/3 not only rescues the reduced Tau and Calmodulin but also restores axon elongation of DRG neurons by Dubr knockdown. This study uncovers a critical role of m6A-modified lincRNA in neuronal development by regulating the degradation of RNA-binding protein. [Display omitted] • m6A-modified lincRNA Dubr is required for neuronal development • Dubr binds and stabilizes YTHDF1/3 via its m6A modification sites • m6A-modified Dubr stabilizes the YTHDF1/3 complex and facilitates mRNA translation Huang et al. find that the m6A-modified lincRNA Dubr binds and stabilizes the YTHDF1/3 complex through its m6A modification, thereby facilitating the translation of Tau and Calmodulin, as well as maintaining subsequent axon elongation and neuronal migration. The findings provide insight into how m6A-modified lincRNA orchestrates neuronal development. [ABSTRACT FROM AUTHOR]

Summary Subcellular targeting and local translation of mRNAs are critical for axon development. However, the precise local control of mRNA translation requires investigation. We report that the Fmr1 -encoded protein, FMRP-mediated axonal delivery of miR-181d negatively regulates axon elongation by locally targeting the transcripts of MAP1B ( Map1b ) and calmodulin ( Calm1 ) in primary sensory neurons. miR-181d affected the local synthesis of MAP1B and calmodulin in axons. FMRP was associated with miR-181d, Map1b , and Calm1 . Both FMRP deficiency in Fmr1 I304N mice and Fmr1 knockdown impeded the axonal delivery of miR-181d, Map1b , and Calm1 and reduced the protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) induced Map1b and Calm1 release from FMRP and miR-181d-repressing granules, thereby promoting axon elongation. Both miR-181d overexpression and FMRP knockdown impaired NGF-induced axon elongation. Our study reveals a mechanism for the local regulation of translation by miR-181d and FMRP during axon development. [ABSTRACT FROM AUTHOR]

Background The important role of angiogenesis displaying in tumor development and metastasis has been generally realized. Vascular endothelial growth factor ( VEGF), basic fibroblast growth factor ( bFGF) and endostatin ( ES) are critical members of angiogenesis modulating the balance between pro-angiogenenic and anti-angiogenenic factors. The aim of this study was to evaluate the circulating level of these factors in serum and explore their prognostic significance in 96 operable non-small cell lung cancer ( NSCLC) patients. Methods Pre-operational serum VEGF, bFGF, and ES were determined by commercially available enzyme-link immunosorbent assay for 96 NSCLC patients and compared to a cohort of healthy controls (n = 51). Values were correlated with clinicopathological features and overall survival ( OS). Results The pretreatment serum levels of VEGF, b FGF and ES in NSCLC were significantly higher than in the healthy control ( P < 0.001, P = 0.009 and P = 0.016, respectively). Univariate survival analysis showed that a high bFGF level correlated with shorter OS and remained an independent factor in multivariate analysis (hazard ratio [ HR] = 1.918, 95% confidence interval [ CI], 1.061-3.464). In the squamous subtype, a high bFGF indicated a particularly poor prognosis ( HR = 2.609, 95% CI, 1.188-5.729). Conclusions bFGF is an independent predictor of poor survival in patients with NSCLC. For patients with high serum bFGF, aggressive antitumor treatments should be given after surgery. Approaches targeting the bFGF signaling pathway should be considered as potentially promising therapeutic strategies in NSCLC, especially for the squamous subtype. [ABSTRACT FROM AUTHOR]

Na+,K+-ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma of the lung (ACCL) is a rare salivary gland-type malignant neoplasm that occurs infrequently as a primary tumor of the airway. Owing to its low incidence, the clinicopathological features, immunohistochemical expression spectrum, treatment and long-term survival have not been fully elucidated. The present study retrospectively assessed the clinical features, immunohistochemical characters, treatment strategy and long-term survival of 34 patients diagnosed with ACCL at the Beijing Chest Hospital, Capital Medical University (Beijing, China) between January 1993 and June 2014. ACCL tended to occur in younger patients, with an approximate male/female ratio of 1:1. The majority of ACCL arose from the central airway. Positive immunochemical staining was found in wide-spectrum keratin (n=17), cytokeratin (CK)7 (n=11), p63 (11/12), S-100 (7/8), vimentin (10/12) and smooth muscle actin (6/9). No staining of thyroid transcription factor-1 (0/14), synaptophysin (0/7), cluster of differentiation 56 (0/7), CK20 (0/4) or chromogranin A (0/4) was observed. In the operable group (n=26), the addition of adjuvant radiotherapy to a positive margin resection (R1 resection) obtained long-term survival times equivalent to that found in patients with a negative margin resection (R0 resection). No significant survival benefit from post-operative radiotherapy was observed in the R0 resection group. For advanced cases, palliative radiotherapy and chemotherapy did not work efficiently. In addition, epidermal growth factor receptor mutation was a rare event in the ACCL patients. The results indicated that surgical resection is the optimal management for ACCL whenever feasible. Adjuvant radiotherapy with R1 resection is able to obtain long-term survival times comparable with those found using an R0 resection. The recommendation of post-operative radiotherapy for all patients with ACCL undergoing resection appears controversial. Owing to a poor response to radiotherapy and chemotherapy, more focus should be placed on the study of advanced ACCL in order to improve overall survival. [ABSTRACT FROM AUTHOR]

Nitrite-dependent anaerobic methane oxidation (n-damo) is a recently discovered process that is catalysed by ' Candidatus Methylomirabilis oxyfera'. In the present study, the vertical distribution (0-10, 20-30, 50-60 and 90-100 cm) of M. oxyfera-like bacteria was investigated in Xiazhuhu wetland, the largest natural wetland on the southern Yangtze River (China). Phylogenetic analyses showed that group A of M. oxyfera-like bacteria and pmoA genes occurred primarily at depths of 50-60 and 90-100 cm. Quantitative PCR further confirmed the presence of M. oxyfera-like bacteria in soil cores from different depths, with the highest abundance of 5.1 × 10 copies g dry soil at depth of 50-60 cm. Stable isotope experiments demonstrated that the n-damo process occurred primarily at depths of 50-60 and 90-100 cm, with the potential rates ranging from 0.2 to 14.5 nmol CO g dry soil d. It was estimated that the methane flux may increase by approximately 2.7-4.3 % in the examined wetland in the absence of n-damo. This study shows that the deep wetland soils (50-60 and 90-100 cm) are the preferred habitats for M. oxyfera-like bacteria. The study also highlights the potential importance of these bacteria in the methane and nitrogen cycles in deep wetland soils. [ABSTRACT FROM AUTHOR]

Endostatin, as the most potential antiangiogenic factor, is a naturally occurring fragment of collagen XVIII in bloodstream capable of inhibiting tumor growth and metastasis. This study was conducted to explore the clinical value of endostatin in serum and tumor tissue in patients with operable non-small cell lung cancer (NSCLC). ELISA and immunohistochemistry were applied to detect the expression of endostatin in serum and tumor tissue in 105 patient-matched operable NSCLC patients. The serum level of endostatin was significantly higher in NSCLC patients than healthy individuals (P=0.0018). Cases with poorer differentiation showed a higher endostatin serum level (P=0.008). There was no significant correlation between tumor tissue expression and clinical parameters, such as TNM stage, differentiation degree, histological type and lymph node invasion status. A stronger expression of endostain in tumor tissue was associated with a higher serum level (r=0.223). The univariate and multivariate analyses with Cox proportional hazards model for overall survival showed that tumor stage and node status were independent prognostic factors, whereas neither endostatin levels in serum nor in tumor tissue showed potential in predicting the long-term survival of operable NSCLC patients. In conclusion, the results observed in the present study did not support the prediction of overall survival in operable NSCLC based on the expression levels of endostatin in serum and tumor tissue. [ABSTRACT FROM AUTHOR]

Nitrite-dependent anaerobic methane oxidation (N-DAMO) is a recently discovered process linking the global carbon and nitrogen cycles. This process was reported to be mediated by ' Candidatus Methylomirabilis oxyfera'. To date, M. oxyfera-like bacteria have been detected in a limited number of freshwater habitats, but whether these bacteria occur in estuarine habitats is currently unknown. In this study, the distribution, diversity and abundance of M. oxyfera-like bacteria were studied in the sediment of the Jiaojiang Estuary of the East Sea (China). Both the 16S ribosomal RNA (rRNA) and pmoA genes confirmed the occurrence of M. oxyfera-like bacteria in the examined estuary. The recovered 16S rRNA gene sequences showed 91.5-97.2 % identity to the 16S rRNA gene of M. oxyfera, and the recovered pmoA gene sequences showed 85.1-95.4 % identity to the pmoA gene of M. oxyfera. Quantitative PCR further confirmed the occurrence of M. oxyfera-like bacteria in this estuary, with the abundance varying from 5.80 ± 0.28 × 10 to 8.35 ± 0.52 × 10 copies g (dry weight). Correlation analysis indicated that the sediment organic content was the most important factor affecting the distribution of M. oxyfera-like bacterial communities in the examined sediments among the environmental factors investigated. This study demonstrated for the first time the existence of M. oxyfera-like bacteria in an estuarine environment and showed the correlations between the distribution of these bacteria and the estuarine environmental conditions. [ABSTRACT FROM AUTHOR]

Background Resequencing can be used to identify genome variations underpinning many morphological and physiological phenotypes. Legume model plant Medicago truncatula ecotypes Jemalong A17 (J. A17) and R108 differ in their responses to mineral toxicity of aluminum and sodium, and mineral deficiency of iron in growth medium. The difference may result from their genome variations, but no experimental evidence supports this hypothesis. Results A total of 12,750 structure variations, 135,045 short insertions/deletions and 764,154 single nucleotide polymorphisms were identified by resequencing the genome of R108. The suppressed expression of MtAACT that encodes a putative aluminum-induced citrate efflux transporter by deletion of partial sequence of the second intron may account for the less aluminum-induced citrate exudation and greater accumulation of aluminum in roots of R108 than in roots of J. A17, thus rendering R108 more sensitive to aluminum toxicity. The higher expression-level of MtZpt2-1 encoding a TFIIIA-related transcription factor in J. A17 than R108 under conditions of salt stress can be explained by the greater number of stressresponsive elements in its promoter sequence, thus conferring J. A17 more tolerant to salt stress than R108 plants by activating the expression of downstream stress-responsive genes. YSLs (Yellow Stripe-Likes) are involved in long-distance transport of iron in plants. We found that an YSL gene was deleted in the genome of R108 plants, thus rendering R108 less tolerance to iron deficiency than J. A17 plants. Conclusions The deletion or change in several genes may account for the different responses of M. truncatula ecotypes J. A17 and R108 to mineral toxicity of aluminum and sodium as well as iron deficiency. Uncovering genome variations by resequencing is an effective method to identify different traits between species/ecotypes that are genetically related. These findings demonstrate that analyses of genome variations by resequencing can shed important light on differences in responses of M. truncatula ecotypes to abiotic stress in general and mineral stress in particular. [ABSTRACT FROM AUTHOR]

The P2X3 receptor plays a vital role in sensory processing and transmission. The assembly and trafficking of the P2X3 receptor are important for its function in primary sensory neurons. As an important inflammation mediator, ATP is released from different cell types around primary sensory neurons, especially under pathological pain conditions. Here, we show that α, β-MeATP dramatically promoted membrane delivery of the P2X3 receptor both in HEK293T cells expressing recombinant P2X3 receptor and in rat primary sensory neurons. α, β-MeATP induced P2X3 receptor-mediated Ca2+ influx, which further activated Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα). The N terminus of the P2X3 receptor was responsible for CaMKIIα binding, whereas Thr388 in the C terminus was phosphorylated by CaMKIIα. Thr388 phosphorylation increased P2X3 receptor binding to caveolin-1. Caveolin-1 knockdown abrogated the α, β-MeATP-induced membrane insertion of the P2X3 receptor. Moreover, α, β-MeATP drove the CaMKIIα-mediated membrane coinsertion of the P2X2 receptor with the P2X3 receptor. The increased P2X3 receptors on the cell membrane that are due to Thr388 phosphorylation facilitated P2X3 receptor-mediated signal transduction. Together, our data indicate that CaMKIIα and caveolin-1 cooperate to drive ligand-induced membrane delivery of the P2X3 receptor and may provide a mechanism of P2X3 receptor sensitization in pain development. [ABSTRACT FROM PUBLISHER]

The receptor for advanced glycation end products (RAGE) has previously been suggested to stimulate the growth, survival, and metastatic spread of colorectal cancers (CRC). The genetic variant Gly82Ser of RAGE influences its function and is associated with an increased risk of gastric cancer and multiple sclerosis. To investigate the association between the Gly82Ser polymorphisms of RAGE and the risk of CRC, 90 CRC patients and 78 control subjects with benign polyps were genotyped and the results were analyzed using the SPSS statistical software. In comparing with the control group, the CRC group has a higher ratio in the Gly82Ser polymorphism. The odds ratio (OR) for heterozygous GS is 2.037 (95 % CI 1.207-3.438); the OR for carriers with the S allele (SS) is 3.32 (95 % CI 0.94-11.65). Further stratification analysis of the correlation of the Gly82Ser polymorphism with tumor stages and differentiation indicated that CRC patients with TNM (III + IV) and/or patients with poorly differentiated colorectal cancer have an elevated Gly82Ser polymorphism. The OR for TNM (III + IV) is 3.575, 95 % CI 1.495-8.550, and the OR for poorly differentiated is 3.580, 95 % CI 1.390-9.217. In conclusion, the RAGE gene Gly82Ser polymorphism may confer not only an increased risk of CRC but also an increased invasion of CRC in the Chinese population. [ABSTRACT FROM AUTHOR]

The process of nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and shown to be mediated by "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Here, evidence for n-damo in three different freshwater wetlands located in southeastern China was obtained using stable isotope measurements, quantitative PCR assays, and 16S rRNA and particulate methane monooxygenase gene clone library analyses. Stable isotope experiments confirmed the occurrence of n-damo in the examined wetlands, and the potential n-damo rates ranged from 0.31 to 5.43 nmol CO2 per gram of dry soil per day at different depths of soil cores. A combined analysis of 16S rRNA and particulate methane monooxygenase genes demonstrated that M. oxyfera- like bacteria were mainly present in the deep soil with a maximum abundance of 3.2 × 107 gene copies per gram of dry soil. It is estimated that ∼0.51 g of CH4 m-2 per year could be linked to the n-damo process in the examined wetlands based on the measured potential n-damo rates. This study presents previously unidentified confirmation that the n-damo process is a previously overlooked microbial methane sink in wetlands, and n-damo has the potential to be a globally important methane sink due to increasing nitrogen pollution. [ABSTRACT FROM AUTHOR]