Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 608
Filtrar
1.
Int J Pharm ; : 118806, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678519

RESUMO

Breast cancer is one of the most frequent malignancies in the female population. Recently, the development of medical products has been advanced for this disease; however, patients still suffer from the failure of current treatments and new therapeutic strategies are urgently required. In this study, due to the overexpression of the estrogen receptor (ER) in breast cancer and the ability of ER to specifically bind to its ligand estrone (ES), an ES-targeted PEGylated epirubicin (EPI) and paclitaxel (PTX) co-loaded liposomal nanoparticle (NP) (termed as ES-SSL-EPI/PTX) was developed. Physicochemical studies demonstrated that the ES-SSL-EPI/PTX had a nanoscaled particle size (∼ 120 nm) and a neutral zeta potential (∼ -5 mV) and presented favorable stability in physiological media. In vitro, the ES-SSL-EPI/PTX showed a significantly higher cellular uptake in human breast cancer MCF-7 cells mainly via the receptor-ligand mediated pathway resulting in effective cytotoxic activity. In vivo targeting study, the accumulation of targeted liposomes in tumor was significantly improved. The systemic circulation time and biodistribution in main organs of EPI and PTX delivered by ES-SSL-Liposomes were increased. Consequently, the ES-SSL-EPI/PTX significantly suppressed tumor growth in the MCF-7-derived tumor-bearing mouse model without inducing toxicity. These results suggested that the ES-SSL-EPI/PTX was a promising formulation for co-delivery of chemotherapeutics in the treatment of breast cancer.

2.
Biosci Rep ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31693733

RESUMO

The aim of this study was to explore the role of long non-coding RNA (lncRNA) non-coding repressor of NFAT (NRON) in the atrial fibrosis and to explore whether its underlying mechanism was associated with macrophage polarization. ELISA analysis of pro-inflammatory cytokines revealed that NRON overexpression suppressed, whereas NRON silencing facilitated the angiotensin II (Ang II) -induced inflammatory response in primary cultured atrial myocytes. The ChIP results showed that NFATc3 was recruited to the promoter region of IL-12 in atrial myocytes. Further data showed that NRON overexpression suppressed, whereas NRON silencing further promoted the Ang-II-induced NFATc3 nuclear transport and IL-12 expression in atrial myocytes. Moreover, RAW264.7 macrophages were incubated with the conditioned medium from the Ang II-treated atrial myocytes transfected with NRON and IL-12 overexpression vectors. IL-12 overexpression abrogated the NRON overexpression-mediated inhibition of RAW264.7 macrophage polarization to the M1-like phenotype. Additionally, mouse atrial fibroblasts were incubated with the culture medium from RAW264.7 macrophages treated as described above. IL-12 overexpression rescued the NRON overexpression-inhibited protein levels of fibrosis markers Collagen I/III in mouse atrial fibroblasts. Collectively, our data indicate that lncRNA NRON alleviates atrial fibrosis through suppression of M1 macrophages activated by atrial myocytes.

3.
Plant Cell ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628168

RESUMO

Actins are among the most abundant and conserved proteins in plant, mammalian and other eukaryotic cells, where they form filamentous structures to perform vital roles in key cellular processes. Although large amounts of data on the biochemical activities, dynamic behaviors and important cellular functions of plant actin filaments have been accumulated, their structural basis is still elusive. Here, we report a 3.9 Å structure of the plant actin filament (ZMPA) from Zea mays pollen using cryo-electron microscopy. The structure shows a right-handed, parallel and staggered architecture that is stabilized by intra- and interstrand interactions. While the overall structure resembles that of other actin filaments, its DNase I-binding loop (D-loop) bends further outward, adopting an open conformation similar to that of the jasplakinolide- or BeFx-stabil1ized rabbit skeleton muscle actin (RSMA) filament. Single-molecule magnetic tweezers analysis revealed that the ZMPA filament can resist greater stretching force than the RSMA filament. Overall, these data provide evidence that plant actin filaments have greater stability than animal actin filaments, which is important for their roles as tracks for long-distance vesicle and organelle transportation.

4.
Mol Genet Genomic Med ; : e974, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31637879

RESUMO

BACKGROUND: The study sought to determine the effects of earthquake on the working memory of adults who experienced earthquake either as infants or fetuses and also investigates whether earthquake exposure and corticotropin-releasing factor receptor 1 (CRHR1) variants rs242924 and rs7209436 interacted with each other in modulating working memory. METHODS: We enrolled subjects who experienced the Tangshan Earthquake as fetuses (group I) or infants (group II), as well as those who did not experience the earthquake (group III). Their working memory was measured using Brief Visuospatial Memory Test-Revised (BVMT-R) and Hopkins Verbal Learning Test-Revised (HVLT-R). Two single-nucleotide polymorphisms (SNPs) of CRHR1 rs242924 and rs7209436 were analyzed by fluorescence quantitative polymerase chain reaction (PCR). RESULTS: The study enrolled 535 subjects, including 172 subjects in group I, 176 subjects group II, and 187 subjects in group III. Both group I and II had significantly lower BVMT-R scores than group III (p < .05). Moreover, no difference was observed in HVLT-R scores among the three groups (p > .05). The allele frequency was 84.7% for AA, 82.8% for TT, 13.6% for AC, and 15.9% for TC. C gene carriers in group II (t = -4.231, p < .01) and group I (t = -3.201, p < .05) had significantly lower visual spatial memory scores than group III. Furthermore, AT gene carriers had significantly lower visual spatial memory scores than C gene carriers in group III (t = 2.215, p < .05). Moreover, there was significant interaction between earthquake exposure and CRHR1 genotype in their effects on visual spatial memory (F = 4.028, p < .05). CONCLUSIONS: Our cross-sectional study has demonstrated that infant or fetus exposure to earthquake impairs visual spatial memory during adulthood and CRHR1 polymorphisms and earthquake exposure may interact with each other to accentuate this impairment.

5.
BMC Cardiovasc Disord ; 19(1): 216, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601179

RESUMO

BACKGROUND: Infantile hepatic hemangioma (IHH) is a rare endothelial cell neoplasm, which may be concurrent with severe complications and result in poor outcomes. Moreover, the coexistence of IHH and congenial heart disease is even rarer. CASE PRESENTATION: We present a 10-day-old male born with IHH associated with patent ductus arteriosus (PDA), atrial septal defect (ASD) and pulmonary hypertension. Moreover, we reviewed a series of studies of IHH-associated high-output cardiac failure between 1974 and 2018, and summarized the treatment outcomes. CONCLUSIONS: Infantile hepatic hemangioma (IHH) has been known to induce high-output heart failure. There is no literature to summarize the severity of its impact on heart, which can lead to a high mortality rate. When IHH is detected by ultrasound, the heart should be evaluated to facilitate treatment. The outcomes of IHH associated with heart failure are good.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31596601

RESUMO

S-Nitrosothiols (SNOs) are endogenous signaling compounds with a diverse spectrum of beneficial airway effects that are both cGMP-dependent and -independent. SNOs are present in healthy human airways, but levels are low in the airways of cystic fibrosis (CF) patients. Here, we evaluated the interactions of SNOs with molecular co-chaperone C-terminus Hsc70 interacting protein (CHIP)- an E3 ubiquitin ligase that targets improperly folded CFTR for degradation. CHIP was expressed in primary human bronchial epithelial and CFBE41o - cells expressing either wild type or F508del CFTR. Confocal microscopy and immunoprecipitation studies showed the cellular co-localization of CFTR and CHIP and showed that GSNO inhibits the CHIP-CFTR interaction. SNOs significantly reduced both the expression and activity of CHIP, leading to higher levels of both the immature and mature forms of F508del CFTR; in fact, inhibition of the expression and function of CHIP by SNOs not only improved CFTR maturation, but also increased CFTR stability at the cell membrane. GSNO treated cells also had more S-nitrosylated CHIP and less ubiquitinated CFTR than untreated cells, suggesting that S-nitrosylation of CHIP prevents CFTR ubiquitination by inhibiting CHIP's E3 ubiquitin ligase function. Further, the exogenous SNOs S-nitrosoglutathione diethyl ester (GNODE) and S-nitro-N-acetylcysteine (SNOAC) increased CFTR expression at the cell surface. Following CHIP knockdown with siRNA duplexes specific for CHIP, F508del CFTR expression increased at the cell surface. We conclude that SNOs effectively reduce CHIP-mediated degradation of CFTR, resulting in increased F508del CFTR expression on the surface of airway epithelial cells.

7.
Sci China Life Sci ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31625022

RESUMO

Three-dimensional electron microscopy (3D-EM) has attracted considerable attention because of its ability to provide detailed information with respect to developmental analysis. However, large-scale high-resolution 3D reconstruction of biological samples remains challenging. Herein, we present a 3D view of a Picea wilsonii Mast. pollen grain with 100 nm axial and 38.57 nm lateral resolution using AutoCUTS-SEM (automatic collector of ultrathin sections-scanning electron microscopy). We established a library of 3,127 100 nm thick serial sections of pollen grains for preservation and observation, demonstrating that the protocol can be used to analyze large-volume samples. After obtaining the SEM images, we reconstructed an entire pollen grain comprising 734 serial sections. The images produced by 3D reconstruction clearly revealed the main components of the P. wilsonii pollen grain, i.e., two sacci and pollen corpus, tube cell, generative cell, and two degenerated prothallial cells, and their internal organization. In addition, we performed a quantitative analysis of the different pollen grain cells, including sacci, and found that there were 202 connections within a saccus SEM image. Thus, for the first time, this study provided a global 3D view of the entire pollen grain, which will be useful for analyzing pollen development and growth.

8.
FASEB J ; 33(11): 12602-12615, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31450978

RESUMO

Protein interactions that stabilize the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) at the apical membranes of epithelial cells have not yet been fully elucidated. We identified keratin 19 (CK19 or K19) as a novel CFTR-interacting protein. CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl- secretion across human bronchial epithelial (HBE) cells. CK19 prevention of Rab7A-mediated lysosomal degradation was a key mechanism in apical CFTR stabilization. Unexpectedly, CK19 expression was decreased by ∼40% in primary HBE cells from homogenous F508del patients with CF relative to non-CF controls. CK19 also positively regulated multidrug resistance-associated protein 4 expression at the PM, suggesting that this keratin may regulate the apical expression of other ATP-binding cassette proteins as well as CFTR.-Hou, X., Wu, Q., Rajagopalan, C., Zhang, C., Bouhamdan, M., Wei, H., Chen, X., Zaman, K., Li, C., Sun, X., Chen, S., Frizzell, R. A., Sun, F. CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathway degradation.

9.
Reprod Biol Endocrinol ; 17(1): 66, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416446

RESUMO

BACKGROUND: Sperm morphology mainly refers to the shape of the head, the length of the flagellar segments, including the midpiece, principal piece and end piece, and the size of the accessory structures, including axonemes, outer dense fibers (ODFs), mitochondrial sheath (MS) and fibrous sheath (FS). Across species, there is considerable diversity in morphology. An established theory posits that the length of the sperm flagellum, especially the length of the midpiece, is a critical factor influencing sperm metabolism and velocity. However, our understanding of the relationships between sperm ultrastructures and the sperm flagellar length is incomplete. METHODS: The morphologies of sperm from 10 mammalian species, human, mouse, rat, dog, rabbit, goat, pig, bull, guinea pig and golden hamster, were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). According to the SEM and TME images, the length of sperm heads and flagellar segments, the cross-sectional areas of the accessory structures and flagella and the width of sperm heads were measured using Image J software. The variation tendencies (referred to as slope) of the accessory structures along flagella were calculated by the linear regression method. Mitochondrial functions were measured using commercial kits. The velocities of sperm were measured using CASA software. RESULTS: The three-dimensional morphologies of sperm from 10 species and the slopes of internal accessory structures along flagella were obtained. The width of the axoneme tapered slightly from the base to the tip of the sperm flagellum, and slopes of the axonemes correlated negatively with the variability in flagellar length across species. Additionally, the cross-sectional areas of the ODFs and/or the MS were positively correlated with the lengths of the midpiece, principal piece, and total flagellum, as well as with sperm velocities. Mitochondrial volumes were positively correlated with ATP content and sperm swimming velocities. CONCLUSIONS: Our results not only show the relationship between sperm internal structures, flagellar length and sperm physiology but also provide sizes of mitochondria and ODFs as new targets with which to study the regulation of sperm length and velocity.

10.
J Am Geriatr Soc ; 67(S3): S584-S589, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31403189

RESUMO

BACKGROUND/OBJECTIVES: Somatization of depressive symptoms among Chinese American older adults remains understudied. This study aimed to identify whether the relationship between depressive symptoms and use of health services (ie, doctor visits, hospital, and emergency department) could be due to pain and whether acculturation played a role in the relations among depressive symptoms, pain, and health service use. DESIGN AND PARTICIPANTS: Secondary data came from the Population Study of Chinese Elderly in Chicago that surveyed 3159 Chinese community-dwelling older adults in the greater Chicago area. The average age was 76.3 years (standard deviation = 8.4); 57.95% were female). Negative binominal models were used to identify the effects of depression and pain on each type of health service use, controlling for sociodemographics and health-related factors (eg, chronic illness). MEASUREMENTS: Depressive symptoms were assessed using the Patient Health Questionnaire-9; pain was assessed by self-reported pain severity. Participants were classified into low, moderate, and high acculturation groups based on acculturation scores. RESULTS: Depressive symptoms and pain were positively related to health service use on the bivariate level. For groups with both low and high acculturation levels, depression and pain each independently predicted more health service use, whereas for the group with a moderate acculturation level, the effect of somatization was substantialized. CONCLUSION: Depression largely influenced health service use independently and partially through pain for older Chinese Americans. The somatization tended to be only salient for the moderate acculturation group, calling for more research attention to the complicated effect of acculturation. J Am Geriatr Soc 67:S584-S589, 2019.

11.
Mol Immunol ; 114: 314-322, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442915

RESUMO

Hematopoietic development occurs in the bone marrow, and this process begins with hematopoietic stem cells (HSCs). Ubc9 is a unique E2-conjugating enzyme required for SUMOylation, an evolutionarily conserved post-translational modification system. We herein show that a conditional Ubc9 deletion in the hematopoietic system caused decreased thymus weight and reduced lymphocyte to myeloid cell ratio. Importantly, Ubc9 deletion in the hematopoietic system only selectively impaired the development of common lymphoid progenitors (CLPs) in the bone marrow and perturbed their potential to differentiate into lymphocytes, thereby decreasing the number of T/B cells in the periphery. Ubc9 was found to be required for CLP viability, and therefore, Ubc9 deficiency rendered CLPs to undergo apoptosis and attenuated their proliferation. Thus, Ubc9 plays a critical role in the regulation of CLP function during hematopoietic development in the bone marrow.

12.
J Mol Neurosci ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31399937

RESUMO

The etiology of Alzheimer's disease (AD) has been intensively studied. However, little is known about the molecular alterations in early-stage and late-stage AD. Hence, we performed RNA sequencing and assessed differentially expressed genes (DEGs) in the hippocampus of 18-month and 7-month-old APP/PS1 mice. Moreover, the DEGs induced by treatment with nicotine, the nicotinic acetylcholine receptor agonist that is known to improve cognition in AD, were also analyzed in old and young APP/PS1 mice. When comparing old APP/PS1 mice with their younger littermates, we found an upregulation in genes associated with calcium overload, immune response, cancer, and synaptic function; the transcripts of 14 calcium ion channel subtypes were significantly increased in aged mice. In contrast, the downregulated genes in aged mice were associated with ribosomal components, mitochondrial respiratory chain complex, and metabolism. Through comparison with DEGs in normal aging from previous reports, we found that changes in calcium channel genes remained one of the prominent features in aged APP/PS1 mice. Nicotine treatment also induced changes in gene expression. Indeed, nicotine augmented glycerolipid metabolism, but inhibited PI3K and MAPK signaling in young mice. In contrast, nicotine affected genes associated with cell senescence and death in old mice. Our study suggests a potential network connection between calcium overload and cellular signaling, in which additional nicotinic activation might not be beneficial in late-stage AD.

13.
Nat Commun ; 10(1): 3409, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363100

RESUMO

Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Phosphatidic acid (PA) and diacylglycerol (DAG) have been found previously to be required for the fission stage of COPI vesicle formation. Here, we find that PA with varying lipid geometry can all promote early fission, but only PA with shortened acyl chains promotes late fission. Moreover, diacylglycerol (DAG) acts after PA in late fission, with this role of DAG also requiring shorter acyl chains. Further highlighting the importance of the short-chain lipid geometry for late fission, we find that shorter forms of PA and DAG promote the vesiculation ability of COPI fission factors. These findings advance a general understanding of how lipid geometry contributes to membrane deformation for vesicle fission, and also how proteins and lipids coordinate their actions in driving this process.

14.
Am J Alzheimers Dis Other Demen ; 34(7-8): 523-529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266345

RESUMO

OBJECTIVES: This study examined the efficacy of the General Practitioner Assessment of Cognition-Chinese version (GPCOG-C) in screening dementia and mild cognitive impairment (MCI) among older Chinese. METHODS: Survey questionnaires were administered to 293 participants aged 80 or above from a university hospital in mainland China. Alzheimer disease and MCI were diagnosed in light of the National Institute on Aging and the Alzheimer's Association (NIA/AA) criteria. The sensitivity and specificity of GPCOG-C and Mini-Mental State Examination (MMSE) in screening dementia and MCI were compared to the NIA/AA criteria. RESULTS: The GPCOG-C had the sensitivity of 62.3% and specificity of 84.6% in screening MCI, which had comparable efficacy as the NIA/AA criteria. In screening dementia, GPCOG-C had a lower sensitivity (63.7%) than the MMSE and a higher specificity (82.6%) higher than the MMSE. CONCLUSIONS: The GPCOG-C is a useful and efficient tool to identify dementia and MCI in older Chinese in outpatient clinical settings.

15.
ACS Nano ; 13(9): 9895-9906, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31356751

RESUMO

Multienzyme complexes, or metabolons, are assemblies or clusters of sequential enzymes that naturally exist in metabolic pathways. These nanomachineries catalyze the conversion of metabolites more effectively than the freely floating enzymes by minimizing the diffusion of intermediates in vivo. Bioengineers have devised synthetic versions of multienzyme complexes in cells to synergize heterologous biosynthesis, to improve intracellular metabolic flux, and to achieve higher titer of valuable chemical products. Here, we utilized orthogonal protein reactions (SpyCatcher/SpyTag and SnoopCatcher/SnoopTag pairs) to covalently assemble three key enzymes in the mevalonate biosynthesis pathway and showed 5-fold increase of lycopene and 2-fold increase of astaxanthin production in Escherichia coli. The multienzyme complexes are ellipsoidal nanostructures with hollow interior space and uniform thickness and shapes. Intracellular covalent enzyme assembly has yielded catalytic nanomachineries that drastically enlarged the flux of carotenoid biosynthesis in vivo. These studies also deepened our understanding on the complexity of hierarchical enzyme assembly in vivo.

16.
Mar Biotechnol (NY) ; 21(5): 643-654, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273567

RESUMO

Asian seabass is an important food fish species. While improving growth, increasing the nutritional value is important, omega-3 fatty acids are indispensable to human health. Identifying and validating DNA markers associated with traits is the first step towards marker-assisted selection (MAS). We quantified 13 different fatty acids and three growth traits in 213 F2 Asian seabass from a family at the age 270 days post hatch, and screened QTL for these traits. The content of total fatty acids in 100 g flesh was 2.57 ± 0.80 g, while the proportions of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were 16.96 ± 2.20% and 5.42 ± 0.90%, respectively. A linkage map with 2424 SNPs was constructed and used for QTL mapping. For fatty acid compositions, 14 significant QTL were identified on three linkage groups (LG5, LG11 and LG14), with phenotypic variance explained (PVE) from 12.8 to 24.6%. Thirty-nine suggestive QTL were detected on 16 LGs. Two significant QTL for EPA were identified on LG5 and LG14, with PVE of 15.2% and 15.1%, respectively. No significant QTL was identified for DHA. For growth traits, six significant and 13 suggestive QTL were identified on two and seven LGs, respectively. Only a few significant QTL for fatty acids overlapped with previously mapped QTL for these traits, suggesting that most QTL detected in a family are family-specific and could only be used in MAS in the family per se. To facilitate population-wide molecular breeding, more powerful methods (e.g. GWAS) should be used to identify SNPs for genomic selection.

17.
J Exp Clin Cancer Res ; 38(1): 289, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277685

RESUMO

BACKGROUND: Glioblastoma (GBM) cells with stem cell-like properties are called glioma stem cells (GSCs). GSCs display highly treatment resistance and are responsible for tumor recurrence. Napabucasin (BBI608), a novel small molecule inhibitor of STAT3, has been identified to eliminate stemness-like tumor cells in some cancers. However, the influence of Napabucasin on GBM cells, especially on GSCs, is currently unclear. In this study, we explored the influence and underlying mechanisms of Napabucasin on GBM cells. METHODS: STAT3 expression and its correlation with the glioma grade and patient survival were analyzed using CGGA and TCGA glioma databases. The influence of Napabucasin on proliferation, stemness, the cell cycle, apoptosis, and invasion of human GBM cell lines U87MG and LN229 was tested by CCK8, EdU incorporation, colony formation, Transwell invasion, and three-dimensional spheroid assays as well as flow cytometry, qPCR, and western blot analysis. The ability of Napabucasin to inhibit cell proliferation of U87MG tumor xenografts in mice was assessed using a live animal bioluminescence imaging system and immunohistochemistry. RESULTS: Napabucasin suppressed the proliferation, colony formation, and invasion of U87MG and LN229 cells. Furthermore, Napabucasin induced cell cycle arrest and apoptosis. More importantly, Napabucasin treatment obviously inhibited expression of stemness-associated genes including STAT3 and suppressed the spheroid formation of glioma cells in vitro. Napabucasin also disrupted the NF-κB signaling pathway via downregulation of RelA (p65). Finally, glioma growth was effectively impaired by Napabucasin in nude mice bearing intracranial glioma xenografts. CONCLUSIONS: Napabucasin treatment may be a novel approach for the treatment of GBM, particularly GSCs.

18.
PLoS Comput Biol ; 15(7): e1007081, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31291238

RESUMO

Studies on the Bin-Amphiphysin-Rvs (BAR) domain have advanced a fundamental understanding of how proteins deform membrane. We previously showed that a BAR domain in tandem with a Pleckstrin Homology (PH domain) underlies the assembly of ACAP1 (Arfgap with Coil-coil, Ankryin repeat, and PH domain I) into an unusual lattice structure that also uncovers a new paradigm for how a BAR protein deforms membrane. Here, we initially pursued computation-based refinement of the ACAP1 lattice to identify its critical protein contacts. Simulation studies then revealed how ACAP1, which dimerizes into a symmetrical structure in solution, is recruited asymmetrically to the membrane through dynamic behavior. We also pursued electron microscopy (EM)-based structural studies, which shed further insight into the dynamic nature of the ACAP1 lattice assembly. As ACAP1 is an unconventional BAR protein, our findings broaden the understanding of the mechanistic spectrum by which proteins assemble into higher-ordered structures to achieve membrane deformation.

19.
Org Lett ; 21(15): 5967-5970, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31298860

RESUMO

An efficient Pd-catalyzed hydrocarboxylation of alkenes with HCOOH is described. A wide variety of linear carboxylic acids bearing various functional groups can be obtained with excellent chemo- and regioselectivities under mild reaction conditions. The reaction process is operationally simple and requires no handling of toxic CO.

20.
Mol Reprod Dev ; 86(9): 1199-1209, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318116

RESUMO

G kinase-anchoring protein 1 (GKAP1) is a G kinase-associated protein that is conserved in many eutherians and is mainly expressed in the testis, especially in spermatocytes and round spermatids. The function of GKAP1 in the testis is largely unknown. Here, we revealed that deletion of GKAP1 led to an increase in sperm production with swollen epididymis, and germ cell apoptosis was found to decrease in GKAP1 knock-out mice. Further investigations showed that a deficiency of GKAP1 could partly change the cellular location of cGK-Iα and increase the amount of active cAMP response element-binding protein (CREB) in the nucleus. Therefore, the expression of a particular inhibitor of apoptosis proteins (IAPs) was upregulated because of the activation of CREB, and this increase in IAPs was associated with a decrease in the level of activated caspase-3. These results suggest that a deficiency of GKAP1 in mouse testis could increase sperm production through a reduction of the spontaneous apoptosis of germ cells in the testis, possibly because of a change in the activity of the cGK-Iα pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA