Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.
Ovarian cancer; cisplatin resistance; miRNA; TP73
Understanding the neural correlates of behavior in the mammalian cortex requires measurements of activity in awake, behaving animals. Rodents have emerged as a powerful model for dissecting the cortical circuits underlying behavior attributable to the convergence of several methods. Genetically encoded calcium indicators combined with viral-mediated or transgenic tools enable chronic monitoring of calcium signals in neuronal populations and subcellular structures of identified cell types. Stable one- and two-photon imaging of neuronal activity in awake, behaving animals is now possible using new behavioral paradigms in head-fixed animals, or using novel miniature head-mounted microscopes in freely moving animals. This mini-symposium will highlight recent applications of these methods for studying sensorimotor integration, decision making, learning, and memory in cortical and subcortical brain areas. We will outline future prospects and challenges for identifying the neural underpinnings of task-dependent behavior using cellular imaging in rodents.
AIM: To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma.
METHODS: From January 2007 to December 2010, 257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study. Forty patients who underwent living-donor liver transplantation (LDLT) constituted the LDLT group, and deceased-donor liver transplantation (DDLT) was performed in 217 patients. Patients in the LDLT group were randomly matched (1:2) to patients who underwent DDLT using a multivariate case-matched method, so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study. We compared the two groups in terms of clinicopathological characteristics, postoperative complications, long-term cumulative survival and relapse-free survival outcomes. The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications. Furthermore, we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups.
RESULTS: The clinicopathological characteristics of the enrolled patients were comparable between the two groups. The duration of operation was significantly longer (553 min vs 445 min, P < 0.001) in the LDLT group than in the DDLT group. Estimated blood loss (1188 mL vs 1035 mL, P = 0.055) and the proportion of patients with intraoperative transfusion (60.0% vs 43.8%, P = 0.093) were slightly but not significantly greater in the LDLT group. In contrast to DDLT, LDLT was associated with a lower rate of perioperative grade II complications (45.0% vs 65.0%, P = 0.036) but a higher risk of overall biliary complications (27.5% vs 7.5%, P = 0.003). Nonetheless, 21 patients (52.5%) in the LDLT group and 46 patients (57.5%) in the DDLT group experienced perioperative complications, and overall perioperative complication rates were similar between the two groups (P = 0.603). No significant difference was observed in 5-year overall survival (74.1% vs 66.6%, P = 0.372) or relapse-free survival (72.9% vs 70.9%, P = 0.749) between the LDLT and DDLT groups.
CONCLUSION: Although biliary complications were more common in the LDLT group, this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.
Liver cancer; Hepatocellular carcinoma; Liver transplantation; Living donor; Survival; Recurrence; Complication
We compared growth kinetics of Prorocentrum donghaiense cultures on different nitrogen (N) compounds including nitrate (NO3−), ammonium (NH4+), urea, glutamic acid (glu), dialanine (diala) and cyanate. P. donghaiense exhibited standard Monod-type growth kinetics over a range of N concentraions (0.5–500 μmol N L−1 for NO3− and NH4+, 0.5–50 μmol N L−1 for urea, 0.5–100 μmol N L−1 for glu and cyanate, and 0.5–200 μmol N L−1 for diala) for all of the N compounds tested. Cultures grown on glu and urea had the highest maximum growth rates (μm, 1.51±0.06 d−1 and 1.50±0.05 d−1, respectively). However, cultures grown on cyanate, NO3−, and NH4+ had lower half saturation constants (Kμ, 0.28–0.51 μmol N L−1). N uptake kinetics were measured in NO3−-deplete and -replete batch cultures of P. donghaiense. In NO3−-deplete batch cultures, P. donghaiense exhibited Michaelis-Menten type uptake kinetics for NO3−, NH4+, urea and algal amino acids; uptake was saturated at or below 50 μmol N L−1. In NO3−-replete batch cultures, NH4+, urea, and algal amino acid uptake kinetics were similar to those measured in NO3−-deplete batch cultures. Together, our results demonstrate that P. donghaiense can grow well on a variety of N sources, and exhibits similar uptake kinetics under both nutrient replete and deplete conditions. This may be an important factor facilitating their growth during bloom initiation and development in N-enriched estuaries where many algae compete for bioavailable N and the nutrient environment changes as a result of algal growth.
There have only been a few reports of thyroid-like follicular carcinoma of the kidney (TLFCK) to date. In the present study, two patients with TLFCK are reported. Patient 1 was a 65-year-old male exhibiting repeated hematuria and right back pain. No tumors were located in the patient’s thyroid or lungs. The physical examination revealed percussion tenderness over the right kidney region was noticed. Enhanced computed tomography (CT) indicated a right renal pelvic carcinoma, for which the patient underwent a radical right nephrectomy. Patient 2 was a 59-year-old male with a mass in the right kidney, located during a health examination and who exhibited no obvious clinical symptoms. The patient was clinically diagnosed with right renal carcinoma, confirmed by an enhanced CT. The patient underwent a radical right nephrectomy. The clinical features, imaging results, pathology, immune phenotypes, treatment and prognosis were analyzed. The associated literature was also reviewed. The cut surface of each tumor showed gray-white material with a central solid area, including scattered gray-brown necrotic and gray hemorrhagic areas and small cystic cavities. Microscopically, the arrangement of the tumor cells mimicked thyroid follicles with red-stained colloid-like material in the lumen. No renal hilar lymph node involvement was noted. The tumor tissue of patient 1 was immunohistochemically positive for vimentin, epithelial membrane antigen (EMA), cytokeratin (CK), CK7, and neuron specific enolase; and negative for CK34BE12, synapsin (Syn), CK20, cluster of differentiation 56 (CD56), CD10, Wilm’s tumor-1 (WT-1), CD34, CD57, P53, CD99, thyroid transcription factor-1 (TTF-1), CD15 and thyroglobulin (TG); with a Ki-67 labeling index (LI) of 30%. The tumor tissue of patient 2 was immunohistochemically positive for vimentin, EMA, CK7 and CK20; and negative for CD56, CD10, WT-1, CD34, CD57, P53, CD117, TTF-1, CD15, CD99, TG, chromogranin A and Syn; with a Ki-67 LI of 20%. TLFCK is a rare renal tumor with low malignancy but medium invasiveness. It morphologically resembles thyroid follicular carcinoma but does not express TTF-1 or TG. Radical nephrectomy can achieve good patient outcomes.
thyroid-like follicular carcinoma of the kidney; features; treatment; prognosis
Patients with neuroblastoma due to N-Myc oncogene amplification have a high frequency of tumor metastasis. However, it is not clear how N-Myc induces cell migration, invasion and metastasis. The histone demethylase JMJD1A activates gene transcription by demethylating the lysine 9 residue of histone H3 (H3K9) at target gene promoters. The long noncoding RNA MALAT1 induces lung cancer cell migration and plays a pivotal role in lung cancer metastasis. Here we demonstrated that N-Myc up-regulated the expression of JMJD1A in N-Myc oncogene-amplified human neuroblastoma cells by directly binding to the JMJD1A gene promoter. Affymetrix microarray studies revealed that the gene second most significantly up-regulated by JMJD1A was MALAT1. Consistent with this finding, RT-PCR and chromatin immunoprecipitation assays showed that JMJD1A bound to the MALAT1 gene promoter and demethylated histone H3K9 at the MALAT1 gene promoter. Moreover, JMJD1A and MALAT1 induced, while the small molecule JMJD1A inhibitor DMOG suppressed, neuroblastoma cell migration and invasion. Taken together, our data identify a novel pathway through which N-Myc causes neuroblastoma cell migration and invasion, and provide important evidence for further development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis.
neuroblastoma; N-Myc; JMJD1A; histone demethylation; MALAT1
Light-absorbing and electrically conductive binary CNx nanocone (CNNC) arrays have been fabricated using a glow discharge plasma-assisted reaction deposition method. The intact CNNCs with amorphous structure and central nickel-filled pipelines could be vertically and neatly grown on nickel-covered substrates according to the catalyst-leading mode. The morphologies and composition of the as-grown CNNC arrays can be well controlled by regulating the methane/nitrogen mixture inlet ratio, and their optical absorption and resistivity strongly depend on their morphologies and composition. Beside large specific surface area, the as-grown CNNC arrays demonstrate high wideband absorption, good conduction, and nice wettability to polymer absorbers.
CNx nanocone arrays; Wideband absorption; Electrical conduction; Wettability to polymer absorbers; 81.07.Bc; 61.46.Np; 52.77.Dq
Online friend recommendation is a fast developing topic in web mining. In this paper, we used SVD matrix factorization to model user and item feature vector and used stochastic gradient descent to amend parameter and improve accuracy. To tackle cold start problem and data sparsity, we used KNN model to influence user feature vector. At the same time, we used graph theory to partition communities with fairly low time and space complexity. What is more, matrix factorization can combine online and offline recommendation. Experiments showed that the hybrid recommendation algorithm is able to recommend online friends with good accuracy.
Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 1 diabetes mellitus (T1DM). However, the results to date have been inconclusive. We performed a meta-analysis to examine the association between 2 polymorphisms (FokI and BsmI) of the VDR gene and T1DM in the Asian population.
Literature was retrieved from PubMed, Web of Science, CBM, Embase and Chinese databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model.
In total, 20 papers (BsmI: 13 studies; FokI: 13 studies) were included. In contrast to the FokI polymorphism, the BsmI polymorphism was associated with an increased risk of T1DM in the Asian population (OR = 1.47, 95% CI = 1.13–1.91, P = 0.004 for B vs. b). Upon stratification by regional geography, an increased risk of T1DM in association with the BsmI polymorphism was observed in the East Asian population (OR = 1.97, 95% CI = 1.38–2.83, P<0.001 for B vs. b), whereas the FokI polymorphism was associated with an increased risk of T1DM in the West Asian population (OR = 1.45, 95% CI = 1.12–1.88, P = 0.004 for F vs. f).
Our meta-analysis suggests that the BsmI polymorphism may be a risk factor for susceptibility to T1DM in the East Asian population, and the FokI polymorphism is associated with an increased risk of T1DM in the West Asian population. However, because the study size was limited, further studies are essential to confirm our results.
CdS nanoneedles with different morphologies, structures, and growth modes have been grown on Ni-coated Si(100) surface under different experimental conditions by pulsed laser deposition method. The effects of catalyst layer, substrate temperature, and laser pulse energy on the growth of the CdS nanoneedles were studied in detail. It was confirmed that the formation of the molten catalyst spheres is the key to the nucleation of the CdS nanoneedles by observing the morphologies of the Ni catalyst thin films annealed at different substrate temperatures. Both the substrate temperature and laser pulse energy strongly affected the growth modes of the CdS nanoneedles. The secondary growth of the smaller nanoneedles on the top of the main nanoneedles was found at appropriate conditions. A group of more completed pictures of the growth modes of the CdS nanoneedles were presented.
CdS nanoneedles; Substrate temperature; Laser pulse energy; Growth mode; 61.46.-w; 61.46.Km; 68.37.Lp
The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings.
Active dendritic synaptic integration enhances the computational power of neurons. Such nonlinear processing generates an object-localization signal in the apical dendritic tuft of layer 5B cortical pyramidal neurons during sensory-motor behaviour. Here we employ electrophysiological and optical approaches in brain-slices and behaving animals to investigate how excitatory synaptic input to this distal dendritic compartment influences neuronal output. We find that active dendritic integration throughout the apical dendritic tuft is highly compartmentalized by voltage-gated potassium (KV) channels. A high-density of both transient and sustained KV channels was observed in all apical dendritic compartments. These channels potently regulated the interaction between apical dendritic tuft, trunk, and axo-somatic integration zones to control neuronal output in vitro as well as the engagement of dendritic nonlinear processing in vivo during sensory-motor behaviour. Thus, KV channels dynamically tune the interaction between active dendritic integration compartments in layer 5B pyramidal neurons to shape behaviourally relevant neuronal computations.
Aligned ZnO/ZnSe core/shell nanorods (NRs) with type-II energy band alignment were fabricated by pulsed laser deposition of ZnSe on the surfaces of hydrothermally grown ZnO NRs. The obtained ZnO/ZnSe core/shell NRs are composed of wurtzite ZnO cores and zinc blende ZnSe shells. The bare ZnO NRs are capable of emitting strong ultraviolet (UV) near band edge (NBE) emission at 325-nm light excitation, while the ZnSe shells greatly suppress the emission from the ZnO cores. High-temperature processing results in an improvement in the structures of the ZnO cores and the ZnSe shells and significant changes in the optical properties of ZnO/ZnSe core/shell NRs. The fabricated ZnO/ZnSe core/shell NRs show optical properties corresponding to the two excitonic band gaps of wurtzite ZnO and zinc blende ZnSe and the effective band gap between the conduction band minimum of ZnO and the valence band maximum ZnSe. An extended photoresponse much wider than those of the constituting ZnO and ZnSe and a multi-band photoluminescence including the UV NBE emission of ZnO and the blue NBE emission of ZnSe are observed.
ZnO/ZnSe core/shell nanorods; Type-II heterojunction; Photoresponse; Near band edge emission; Suppression of luminescence
To determine if mutations in NELF, a gene isolated from migratory GnRH neurons, cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS)
Molecular analysis correlated with phenotype
Academic medical center
168 IHH/KS patients along with unrelated controls were studied for NELF mutations.
NELF coding regions/splice junctions were subjected to PCR-based DNA sequencing, Eleven additional IHH/KS genes were sequenced in three patients with NELF mutations.
Main Outcome Measure
Mutations were confirmed by SIFT, RT-PCR, and western blot analysis.
Three novel NELF mutations absent in 372-ethnically matched controls were identified in 3/168(1.8%) IHH/KS patients. One IHH patient had compound heterozygous NELF mutations (c.629-21C>G and c.629-23G>C); and he did not have mutations in 11 other known IHH/KS genes. Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; p.Cys163del of KAL1) and NELF/TACR3 (c. 1160-13C>T of NELF and c.824G>A; p.Trp275X of TACR3). In vitro evidence of these NELF mutations included reduced protein expression and splicing defects.
Our findings suggest that NELF is associated with normosmic IHH and KS, either singly or in combination with a mutation in another gene.
Nasal embryonic LHRH factor; hypogonadotropic hypogonadism; Kallmann syndrome; gonadotropin-releasing hormone (GnRH); GnRH neuron migration
The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.
apolipoprotein M; promoter; polymorphism; expression; coronary artery diseases
The tissue inhibitor of metalloproteinase-1 (TIMP-1) is an endogenous inhibitor of matrix metalloproteinases and potential biomarker of various types of human cancers. However, the association between TIMP-1 expression and the clinical features of laryngeal squamous cell carcinoma (LSCC) is barely investigated. In this study, one-step quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining with tissue microarrays were employed to evaluate the relationship between TIMP-1 expression and the clinicopathological characteristics of LSCC. Results showed that the TIMP-1 mRNA and protein expression levels were significantly higher in LSCC than in the corresponding non-cancerous tissues (p<0.05). TIMP-1 protein expression in LSCC was associated with tumor differentiation (p=0.012) and overall survival (p=0.043). Kaplan-Meier method and Cox multi-factor analysis suggested that high TIMP-1 expression (p=0.008) and positive lymph node metastasis (p=0.029) were significantly associated with the poor survival of patients with LSCC. These data indicated that TIMP-1 may be identified as a prognostic marker of LSCC.
TIMP-1; LSCC; qPCR; immunohistochemistry; prognosis
In the title compound, C11H8N2O2S, the oxadiazinone ring is nearly planar [maximum deviation = 0.016 (4) Å], and is approximately coplanar with the benzothiophene ring system [dihedral angle = 3.1 (5)°]. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming chains running along the b-axis direction.
MicroRNAs (miRNAs) play important roles in the pathogenesis of cardiovascular diseases. Circulating miRNAs were recently identified as biomarkers for various physiological and pathological conditions. In this study, we aimed to identify the circulating miRNA fingerprint of vulnerable coronary artery disease (CAD) and explore its potential as a novel biomarker for this disease.
Methods and Results
The Taqman low-density miRNA array and coexpression network analyses were used to identify distinct miRNA expression profiles in the plasma of patients with typical unstable angina (UA) and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). Significantly elevated expression levels of miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126*, and miR-451 were observed in UA patients compared to controls. These findings were validated by real-time PCR in another 45 UA patients, 31 stable angina patients, and 37 controls. In addition, miR-106b, miR-25, miR-92a, miR-21, miR-590-5p, miR-126* and miR-451 were upregulated in microparticles (MPs) isolated from the plasma of UA patients (n = 5) compared to controls (n = 5). Using flow cytometry and immunolabeling, we further found that Annexin V+ MPs were increased in the plasma samples of UA patients compared to controls, and the majority of the increased MPs in plasma were shown to be Annexin V+ CD31+ MPs. The findings suggest that Annexin V+ CD31+ MPs may contribute to the elevated expression of the selected miRNAs in the circulation of patients with vulnerable CAD.
The circulating miRNA signature, consisting of the miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126* and miR-451, may be used as a novel biomarker for vulnerable CAD.
Chinese Clinical Trial Register, ChiCTR-OCH-12002349.
In the title compound, C27H22N2O4, the two indole ring systems are approximately perpendicular to each other, with a dihedral angle of 84.5 (5)° between their planes; the benzene ring is twisted with respect to the two indole ring systems at angles of 78.5 (5) and 86.5 (3)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, weak C—H⋯O and C—H⋯N hydrogen bonds, and C—H⋯π interactions into a three-dimensional supramolecular architecture.
Spermatocytic seminoma (SS) is a rare testicular neoplasm characterized by a palpable, painless, slowly enlarging mass in the testis. Even more rare is a synchronous bilateral presentation. Only eight cases of bilateral SS have been reported in the literature, of which three cases were present with synchronous testis enlargement, and five were sequential. Here, we report an additional case of synchronous bilateral SS and present a comprehensive relevant literature review concerning clinical features, histopathology, and treatment.
Spermatocytic seminoma; Fine-needle aspiration cytology; Bilateral spermatocytic seminoma; Testicular cancer
Directed carotid cavernous fistula means high blood flow shunts between the internal carotid artery and the cavernous sinus. Obstructing the abnormal shunt between the internal carotid artery and the cavernous sinus while preserving the internal carotid artery is the key role in fistula treatment. Transarterial balloon embolization is currently the gold standard treatment for most of the carotid cavernous fistulas. But there are still some technical difficulties in the use of detachable balloon to treat carotid cavernous fistulas. Here, we describe undetachable balloon-assisted technique in the embolization of three patients who got complete immediate occlusion of the shunt and preserved the internal carotid artery at the same time.
Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation.
Cortical feed-back projections to primary sensory areas terminate most heavily in layer (L) 11,2, where they make synapses with tuft dendrites of pyramidal neurons. L1 input is thought to provide ‘contextual’ information3, but the signals transmitted by L1 feedback remain uncharacterized. In the rodent somatosensory system, the spatially diffuse4 vibrissal motor cortex (vM1)→ vibrissal somatosensory cortex (barrel cortex, vS1) feedback projection may allow whisker touch to be interpreted in the context of whisker position to compute object location5,6. When mice palpate objects with their whiskers to localize object features7,8, whisker touch excites vibrissal somatosensory cortex (barrel cortex, vS1)9 and later vibrissal motor cortex (vM1) in a somatotopic manner10,11,12,13. Here we used axonal calcium imaging to track activity in vM1→ vS1 afferents in L1 of barrel cortex, while mice performed whisker-dependent object localization. Spatially intermingled individual axons represented whisker movements, touch, and other behavioral features. In a subpopulation of axons, activity depended on object location and persisted for seconds after touch. Neurons in the barrel cortex thus have information to integrate movements and touches of multiple whiskers over time, key components of object identification and navigation by active touch.
N-myc downstream-regulated gene 2 (NDRG2) has been documented to be a pro-differentiative and anti-proliferative gene in cancer research. Our previous study found a significant NDRG2 up-regulation in reactive astrocytes of penumbra after transient focal cerebral ischemia, which was parallel to the enhancement of TUNEL-positive signals. However, it is still uncertain whether NDRG2 participates in cellular apoptosis induced by ischemia-reperfusion injury in brain. In this study, we investigated the role of NDRG2 in cellular apoptosis induced by oxygen-glucose deprivation (OGD) in IL-6-differentiated C6 glioma cells. The results showed that NDRG2 was up-regulated and translocated from the cytoplasm to the nucleus after OGD exposure. NDRG2 over-expression exhibited an anti-proliferative effect and increased the Bax/Bcl-2 ratio after OGD exposure, while NDRG2 silencing promoted the cellular proliferation and attenuated the up-regulation of Bax/Bcl-2 ratio. The pro-apoptotic effect of p53 was verified by the results in which p53 silencing greatly reduced the percentage of OGD-induced apoptotic cells. p53 silencing also reduced the OGD-induced NDRG2 up-regulation. However, over-expression of p53 did not further improve the NDRG2 up-regulation. In conclusion, NDRG2 is a p53-associated regulator of apoptosis in C6-originated astrocytes after OGD exposure. These findings bring insight to the roles of NDRG2 in ischemic-hypoxic injury and provide potential targets for future clinical therapies on stroke.
By using silver cations (Ag+) as the ionic reagent in reactive extractive electrospray ionization mass spectrometry (EESI-MS), the concentrations of acetonitrile in exhaled breath samples from the volunteers including active smokers, passive smokers, and non-smokers were quantitatively measured in vivo, without any sample pretreatment. A limit of detection (LOD) and relative standard deviation (RSD) were 0.16 ng/L and 3.5% (n = 8), respectively, for the acetonitrile signals in MS/MS experiments. Interestingly, the concentrations of acetonitrile in human breath continuously increased for 1–4 hours after the smoker finished smoking and then slowly decreased to the background level in 7 days. The experimental data of a large number of (> 165) samples indicated that the inhaled acetonitrile is excreted most likely by facilitated diffusion, instead of simple diffusion reported previously for other volatile compounds.