NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control th...NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.展开更多
Planarian is among the simplest animals that possess a centralized nervous system (CNS), and its neural regenera- tion involves the replacement of cells lost to normal 'wear and tear' (cell turnover), and/or inj...Planarian is among the simplest animals that possess a centralized nervous system (CNS), and its neural regenera- tion involves the replacement of cells lost to normal 'wear and tear' (cell turnover), and/or injury. In this review, we state and discuss the recent studies on molecular control of neural regeneration in planarians. The spatial and temporal expression patterns of genes in intact and regenerating planarian CNS have already been described relatively clearly. The bone morphogenetic protein (BMP) and Wnt signaling pathways are identified to regulate neural regeneration. During neural regeneration, conserved axon guidance mechanisms are necessary for proper wiring of the nervous system. In addition, apoptosis may play an important role in controlling cell numbers, eliminating unnecessary tissues or cells and remodeling the old tissues for regenerating CNS. The bilateral symmetry is established by determination of anterior-posterior (A-P) and dorsal-ventral (D-V) patterns. Moreover, neurons positive to dopamine, serotonin (5-HT), and gamma-aminobutyric acid (GABA) have been detected in planarians. Therefore, planarians present us with new, experimentally accessible contexts to study the molecular actions guiding neural regeneration.展开更多
Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believ...Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believed that this sensitization is due to the transcriptional blockade of genes regulated by NF-κB. Nevertheless, such evidence has remained elusive in the nervous system. Here, we show that TNF-α cannot normally induce apoptosis in PC12 cells or cortical neurons. However, cells treated with Actinomycin D (ActD) become susceptible to TNF-α-induced cell death through the activation of caspase-8, generation of tBid and activation of caspase-9 and -3. Analysis of several proteins involved in TNF-α receptor signaling showed no significant downregulation of NF-κB target genes, such as IAPs or FLIP, under such conditions. However, Bcl-XL protein levels, but not those of Bcl-2, Bax and Bak, are reduced by ActD or TNF-α/ ActD treatments. Moreover, Bcl-xL overexpression fully protects cells against TNF-α/ActD-induced cell death. When endogenous levels of Bcl-XL are specifically downregulated by lentiviral-based RNAi, cells no longer require ActD to be sensitive to TNF-α-triggered apoptosis. Furthermore, Bcl-xL downregulation does not affect TNF-α-mediated NF-κB activation. Altogether, our results demonstrate that Bcl-XL, and not Bci-2, FLIP or IAPs, acts as the endogenous regulator of neuronal resistance/sensitivity to TNF-α-induced apoptosis in an NF-κB-independent manner.展开更多
The authors have invented the superior wind power unit, which is composed of the tandem wind rotors and the double rotational armature type generator without the traditional stator. The large-sized front wind rotor an...The authors have invented the superior wind power unit, which is composed of the tandem wind rotors and the double rotational armature type generator without the traditional stator. The large-sized front wind rotor and the small-sized rear wind rotor drive, as for the upwind type, the inner and the outer rotational armatures, respectively, in keeping the rotational torque counter-balanced between both wind rotors/armatures. The unique rotational behaviors of the tandem wind rotors and the fundamental performances of the unit have been discussed at the previous paper. Continuously, this paper investigates experimentally and numerically the flow condition around the wind rotors to know the flow interactions between the front and the rear wind rotors, and optimizes the blade profile in the front wind rotor. The front blade should work fruitfully at the larger radius and had better not work at the smaller radius for giving plenty of wind energy to the rear wind rotor, taking account of the flow interaction between both wind rotors.展开更多
Treatment with bevacizumab,an antiangiogenic agent,in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan.Bevacizumab improves the survival of patients with metastati...Treatment with bevacizumab,an antiangiogenic agent,in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan.Bevacizumab improves the survival of patients with metastatic colorectal cancer;however,it may lead to complications such as bleeding,which are sometimes fatal.Bevacizumab should be administered only after careful consideration because the potential risks of therapy outweigh its benefits.Therefore,pharma-ceutical companies do not recommend bevacizumab therapy for patients with brain metastases.While some reports support the cautious use of bevacizumab,others report that it is not always necessary to prohibit its use in patients with metastases to the central nervous system(CNS),including the brain.Thus,bevacizumab therapy in colorectal cancer patients with brain metastases is controversial,and it is unclear whether brainmetastases are a risk factor for intracranial hemor-rhage during anti-vascular endothelial growth factor(VEGF)therapy.We report a 64-year-old man and a 65-year-old man with recurrent colorectal cancer with-out brain metastases;these patients developed multifocal and solitary intracranial hemorrhage,respectively,after the administration of bevacizumab.Our findings suggest that intracranial hemorrhage can occur even if the patient does not have brain metastases prior to bevacizumab treatment and also suggest that brain metastases are not a risk factor for intracranial hemor-rhage with bevacizumab treatment.These findings also question the necessity of excluding patients with brain metastases from clinical trials on anti-VEGF therapy.展开更多
Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcrip...Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.展开更多
A new system is developed to recognize promoter sequences from non promoter sequences based on position weight matrix and backpropagation neural network in this paper. The system performs significantly better on the t...A new system is developed to recognize promoter sequences from non promoter sequences based on position weight matrix and backpropagation neural network in this paper. The system performs significantly better on the training set and the test set, the mean recognition rate is as high as 99% on the training set and 97% on the testing set. Experimental results demonstrate the effectiveness of the system to recognize the promoter sequences that have been trained and the promoter sequences that have not been seen previously.展开更多
Fractional-slot concentrated-coil electric machines are often used in those applications where a number of rotor poles close to the number of stator slots is required. A major criticality of such machines is the occur...Fractional-slot concentrated-coil electric machines are often used in those applications where a number of rotor poles close to the number of stator slots is required. A major criticality of such machines is the occurrence of large air-gap field harmonics due to winding distribution and to slotting effects. Predicting such harmonics analytically with adequate accuracy is a good way to significantly speed-up subsequent investigations, concerning the rotor effects of the field harmonics in terms of rotor losses. This paper proposes different analytical formulations for this purpose, covering the case of a generic number of stator phases and differing by how slotting effects are taken into account. The various approaches proposed are evaluated by comparing analytical results with finite-element analysis computations on a sample machine geometries.展开更多
The Sox proteins play critical roles during the development of animals, including sex determination and central nervous system development. In this study, the SoxB2 gene was cloned from a mollusk, the Zhikong scallop ...The Sox proteins play critical roles during the development of animals, including sex determination and central nervous system development. In this study, the SoxB2 gene was cloned from a mollusk, the Zhikong scallop (Chlamysfarreri), and characterized with respect to phylogeny and tissue distribution. The full-length cDNA and genomic DNA sequences of C. farreri SoxB2 (CflSoxB2) were obtained by rapid amplification of cDNA ends and genome walking, respectively, using a partial cDNA fragment from the highly conserved DNA-binding domain, i.e., the High Mobility Group (HMG) box. The full-length cDNA sequence of CJSoxB2 was 2 048 bp and encoded 268 amino acids protein. The genomic sequence was 5 551 bp in length with only one exon. Several conserved elements, such as the TATA-box, GC-box, CAAT-box, GATA-box, and Sox/sry-sex/testis-determining and related HMG box factors, were found in the promoter region. Furthermore, real-time quantitative reverse transcription PCR assays were carried out to assess the mRNA expression of CJSoxB2 in different tissues. SoxB2 was highly expressed in the mantle, moderately in the digestive gland and gill, and weakly expressed in the gonad, kidney and adductor muscle. In male and female gonads at different developmental stages of reproduction, the expression levels of CfS;oxB2 were similar. Considering the specific expression and roles of SoxB2 in other animals, in particular vertebrates, and the fact that there are many pallial nerves in the mantle, cerebral ganglia in the digestive gland and gill nerves in gill, we propose a possible essential role in nervous tissue function for SoxB2 in C.farreri.展开更多
Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Fo...Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Foxn4,a member of the forkhead box/winged-helix transcription factor superfamily,is expressed in mitotic progenitors and/or postmitotic precursors in both neural(e.g.,retina and spinal cord)and non-neural tissues(e.g.,atrioventricular canal and proximal airway).During development of the central nervous system,Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling.Moreover,it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis.In development of non-neural tissues,Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development.In this review,we highlight current understanding of the structure,expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.展开更多
基金National Natural Science Foundation of China (No. 30571909) the Youth Teacher's Research Foundation of Jiangsu Province, China (No. BU 134701 ) the Medical Development Foundation of Soochow University (No. EE134615).
文摘NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.
基金the Southeast University Foundation for Excellent Young Scholars (No. 4023001013)the Program for New Century Excellent Talents in University.
文摘Planarian is among the simplest animals that possess a centralized nervous system (CNS), and its neural regenera- tion involves the replacement of cells lost to normal 'wear and tear' (cell turnover), and/or injury. In this review, we state and discuss the recent studies on molecular control of neural regeneration in planarians. The spatial and temporal expression patterns of genes in intact and regenerating planarian CNS have already been described relatively clearly. The bone morphogenetic protein (BMP) and Wnt signaling pathways are identified to regulate neural regeneration. During neural regeneration, conserved axon guidance mechanisms are necessary for proper wiring of the nervous system. In addition, apoptosis may play an important role in controlling cell numbers, eliminating unnecessary tissues or cells and remodeling the old tissues for regenerating CNS. The bilateral symmetry is established by determination of anterior-posterior (A-P) and dorsal-ventral (D-V) patterns. Moreover, neurons positive to dopamine, serotonin (5-HT), and gamma-aminobutyric acid (GABA) have been detected in planarians. Therefore, planarians present us with new, experimentally accessible contexts to study the molecular actions guiding neural regeneration.
文摘Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believed that this sensitization is due to the transcriptional blockade of genes regulated by NF-κB. Nevertheless, such evidence has remained elusive in the nervous system. Here, we show that TNF-α cannot normally induce apoptosis in PC12 cells or cortical neurons. However, cells treated with Actinomycin D (ActD) become susceptible to TNF-α-induced cell death through the activation of caspase-8, generation of tBid and activation of caspase-9 and -3. Analysis of several proteins involved in TNF-α receptor signaling showed no significant downregulation of NF-κB target genes, such as IAPs or FLIP, under such conditions. However, Bcl-XL protein levels, but not those of Bcl-2, Bax and Bak, are reduced by ActD or TNF-α/ ActD treatments. Moreover, Bcl-xL overexpression fully protects cells against TNF-α/ActD-induced cell death. When endogenous levels of Bcl-XL are specifically downregulated by lentiviral-based RNAi, cells no longer require ActD to be sensitive to TNF-α-triggered apoptosis. Furthermore, Bcl-xL downregulation does not affect TNF-α-mediated NF-κB activation. Altogether, our results demonstrate that Bcl-XL, and not Bci-2, FLIP or IAPs, acts as the endogenous regulator of neuronal resistance/sensitivity to TNF-α-induced apoptosis in an NF-κB-independent manner.
文摘The authors have invented the superior wind power unit, which is composed of the tandem wind rotors and the double rotational armature type generator without the traditional stator. The large-sized front wind rotor and the small-sized rear wind rotor drive, as for the upwind type, the inner and the outer rotational armatures, respectively, in keeping the rotational torque counter-balanced between both wind rotors/armatures. The unique rotational behaviors of the tandem wind rotors and the fundamental performances of the unit have been discussed at the previous paper. Continuously, this paper investigates experimentally and numerically the flow condition around the wind rotors to know the flow interactions between the front and the rear wind rotors, and optimizes the blade profile in the front wind rotor. The front blade should work fruitfully at the larger radius and had better not work at the smaller radius for giving plenty of wind energy to the rear wind rotor, taking account of the flow interaction between both wind rotors.
文摘Treatment with bevacizumab,an antiangiogenic agent,in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan.Bevacizumab improves the survival of patients with metastatic colorectal cancer;however,it may lead to complications such as bleeding,which are sometimes fatal.Bevacizumab should be administered only after careful consideration because the potential risks of therapy outweigh its benefits.Therefore,pharma-ceutical companies do not recommend bevacizumab therapy for patients with brain metastases.While some reports support the cautious use of bevacizumab,others report that it is not always necessary to prohibit its use in patients with metastases to the central nervous system(CNS),including the brain.Thus,bevacizumab therapy in colorectal cancer patients with brain metastases is controversial,and it is unclear whether brainmetastases are a risk factor for intracranial hemor-rhage during anti-vascular endothelial growth factor(VEGF)therapy.We report a 64-year-old man and a 65-year-old man with recurrent colorectal cancer with-out brain metastases;these patients developed multifocal and solitary intracranial hemorrhage,respectively,after the administration of bevacizumab.Our findings suggest that intracranial hemorrhage can occur even if the patient does not have brain metastases prior to bevacizumab treatment and also suggest that brain metastases are not a risk factor for intracranial hemor-rhage with bevacizumab treatment.These findings also question the necessity of excluding patients with brain metastases from clinical trials on anti-VEGF therapy.
文摘Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.
文摘A new system is developed to recognize promoter sequences from non promoter sequences based on position weight matrix and backpropagation neural network in this paper. The system performs significantly better on the training set and the test set, the mean recognition rate is as high as 99% on the training set and 97% on the testing set. Experimental results demonstrate the effectiveness of the system to recognize the promoter sequences that have been trained and the promoter sequences that have not been seen previously.
文摘Fractional-slot concentrated-coil electric machines are often used in those applications where a number of rotor poles close to the number of stator slots is required. A major criticality of such machines is the occurrence of large air-gap field harmonics due to winding distribution and to slotting effects. Predicting such harmonics analytically with adequate accuracy is a good way to significantly speed-up subsequent investigations, concerning the rotor effects of the field harmonics in terms of rotor losses. This paper proposes different analytical formulations for this purpose, covering the case of a generic number of stator phases and differing by how slotting effects are taken into account. The various approaches proposed are evaluated by comparing analytical results with finite-element analysis computations on a sample machine geometries.
基金Supported by the National Natural Science Foundation of China(Nos.31072190,30972239)the National Basic Research Program of China(973 Program)(No.2010CB126406)+2 种基金the Taishan Scholar Program of Shandong Provincethe Doctoral Fund of Ministry of Education of China(No.20100132110014)the Natural Science Foundation of Shandong Province(No.ZR2009DM019)
文摘The Sox proteins play critical roles during the development of animals, including sex determination and central nervous system development. In this study, the SoxB2 gene was cloned from a mollusk, the Zhikong scallop (Chlamysfarreri), and characterized with respect to phylogeny and tissue distribution. The full-length cDNA and genomic DNA sequences of C. farreri SoxB2 (CflSoxB2) were obtained by rapid amplification of cDNA ends and genome walking, respectively, using a partial cDNA fragment from the highly conserved DNA-binding domain, i.e., the High Mobility Group (HMG) box. The full-length cDNA sequence of CJSoxB2 was 2 048 bp and encoded 268 amino acids protein. The genomic sequence was 5 551 bp in length with only one exon. Several conserved elements, such as the TATA-box, GC-box, CAAT-box, GATA-box, and Sox/sry-sex/testis-determining and related HMG box factors, were found in the promoter region. Furthermore, real-time quantitative reverse transcription PCR assays were carried out to assess the mRNA expression of CJSoxB2 in different tissues. SoxB2 was highly expressed in the mantle, moderately in the digestive gland and gill, and weakly expressed in the gonad, kidney and adductor muscle. In male and female gonads at different developmental stages of reproduction, the expression levels of CfS;oxB2 were similar. Considering the specific expression and roles of SoxB2 in other animals, in particular vertebrates, and the fact that there are many pallial nerves in the mantle, cerebral ganglia in the digestive gland and gill nerves in gill, we propose a possible essential role in nervous tissue function for SoxB2 in C.farreri.
基金supported in part by Sun Yat-sen University,Zhongshan Ophthalmic Center,and the National Institutes of Health(EY020849 and EY012020 to XiangMengQing)
文摘Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Foxn4,a member of the forkhead box/winged-helix transcription factor superfamily,is expressed in mitotic progenitors and/or postmitotic precursors in both neural(e.g.,retina and spinal cord)and non-neural tissues(e.g.,atrioventricular canal and proximal airway).During development of the central nervous system,Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling.Moreover,it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis.In development of non-neural tissues,Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development.In this review,we highlight current understanding of the structure,expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.