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Mitophagy, as one of the most important cellular processes to ensure quality control of mitochondria, aims at transporting damaged, aging, dysfunctional or excess mitochondria to vacuoles (plants and fungi) or lysosomes (mammals) for degradation and recycling. The normal functioning of mitophagy is critical for cellular homeostasis from yeasts to humans. Although the role of mitophagy has been well studied in mammalian cells and in certain model organisms, especially the budding yeast

This study aims to explore the effects of aquatic strength training on the postural balance and walking function of stroke patients.A total of 56 chronic stroke patients more than 6 months post-stroke with walking and balance impairments were included in this study. After baseline evaluations, patients were randomly assigned to either the experiment group (n = 29) or control group (n = 27). Patients in the control group underwent conventional hydrotherapy, whereas patients in the experiment group received conventional hydrotherapy combined with aquatic lower extremity strength training. After six weeks of rehabilitation, all patients were evaluated by a blinded assessor, and the functional assessments including: Berg Balance Scale (BBS); Timed Up and Go Test (TUG and mTUG); 2 Minute Walk Test (2MWMT); and Gait analysis.There were no significant differences (P .05) between the two groups in all evaluation indexes before rehabilitation. Six weeks after treatments, the results from both groups showed significant improvements compared with those in the baseline evaluations (P .05). Notably, compared with the control group, BBS, TUG and mTUG, 2MWMT, and Gait analysis including stride length in the non-hemiplegic side, stride length, as well as walking speed and stride frequency in the hemiplegic side in experiment group were markedly improved (P .05).Aquatic strength training can improve postural balance and lower extremity motor functions in chronic stroke patients.

Cong Zhou,1 Qiang Wu,1 Leqi He,1 Hui Zhang,1 Maosuo Xu,1 Baoyu Yuan,2 Zhi Jin,3 Fang Shen1 1Department of Clinical Laboratory Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Fang ShenDepartment of Clinical Laboratory Medicine, Shanghai Fifth People’s Hospital, Fudan University, No. 128, Ruili Road, Minhang District, Shanghai, 200240, People’s Republic of ChinaTel +86 18021073261Email shenfang5th@aliyun.comBackground: The convergence of carbapenem-resistance and hypervirulence in Klebsiella pneumoniae has led to a significant public health challenge. In recent years, there have been more and more reports on carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates.Materials and Methods: Clinical data of patients infected with CR-hvKP from January 2019 to December 2020 in a tertiary hospital were retrospectively evaluated. The number of isolates of Klebsiella pneumoniae, hypermucoviscous Klebsiella pneumoniae (hmKP), carbapenem-resistant hypermucoviscous Klebsiella pneumoniae (CR-hmKP) and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) collected during the period of 2 years was calculated. The antimicrobial resistance gene, virulence-associated gene, capsular serotype gene and multilocus sequence typing (MLST) of CR-hvKP isolates were detected by PCR.Results: During the study period, a total of 1081 isolates of non-repeat Klebsiella pneumoniae were isolated, including 392 isolates of hypermucoviscous Klebsiella pneumoniae (36.3%), 39 isolates of CR-hmKP (3.6%), and 16 isolates of CR-hvKP (1.5%). About 31.2% (5/16) of CR-hvKP were isolated from 2019, and 68.8% (11/16) of CR-hvKP were isolated from 2020. Among the 16 isolates of CR-hvKP, 13 isolates were ST11 and serotype K64, 1 isolate was ST11 and serotype K47, 1 isolate was ST23 and serotype K1, and 1 isolate was ST86 and serotype K2. The virulence-associated genes entB, fimH, rmpA2, iutA, iucA were present in all of 16 CR-hvKP isolates, followed by mrkD (n=14), rmpA (n=13), aerobactin (n=2), allS (n=1). Sixteen CR-hvKP isolates all carry carbapenemase gene blaKPC-2 and extended-spectrum β-lactamase gene blaSHV. ERIC-PCR DNA fingerprinting results showed that 16 CR-hvKP isolates were highly polymorphic, and there were significant differences in bands among the isolates, presenting a sporadic state.Conclusion: Although CR-hvKP was sporadically distributed, it showed an increasing trend year by year. Therefore, clinical attention should be paid, and necessary measures should be taken to avoid the cloning and transmission of superbacterium CR-hvKP.Keywords: Klebsiella pneumoniae, carbapenem-resistant, hypervirulent, hypermucoviscous, epidemiology

The amphiphilic humic acid ester ether (HAEE), as a kind of solid-phase extractant with characteristics of easy separation and hydrophilic-hydrophobic amphiphilic property, was prepared and used to extract micro or trace nitrofen, 2,4-dichlorophenol and p-nitrotrophenol (NIPs) from water and soil. Degradation of NIPs and extractant regeneration were carried out by simple photocatalysis. The adsorption equilibrium of the mono- or three mixed NIPs by HAEE in aqueous could be quickly reached within 20 min. The adsorption process was fit to quasi-second-order kinetics model and Friendlich thermodynamics model. The possible adsorption interaction was discussed. Results suggested that the adsorption of NIPs onto HAEE predominated by hydrogen bonding, hydrophobic interaction and π-π interaction. The extraction capacity of mixed NIPs (80 μg/L each component) by HAEE was up to 0.38 mg/g and tended to be multi-layer adsorption, in which p-nitrotrophenol had higher adsorption competitiveness because of lower resistance to HAEE. When HAEE-NIPs were degraded by photo-catalyst Fe

Background Glucose transporter (GLUT)-mediated glucose uptake is an important process in the development of laryngeal carcinoma, one of the most common malignancies of the head and neck. GLUT-1, together with HIF-1α, is also an indicator of hypoxia. Both proteins play a critical role in glucose uptake and glycolysis in laryngeal carcinoma cells under hypoxic stress. A double gene knockout model in which HIF-1α and GLUT-1 are no longer expressed can provide important information about carcinogenesis in laryngeal carcinoma. Purpose In this study we used the CRISPR/Cas 9 system to induce HIF-1α and GLUT-1 double gene knockout in HEp-2 cells and then used the knocked-out cells to study the role of these markers in laryngeal carcinoma, including in chemoradioresistance. Methods High-grade small-guide RNAs (sgRNAs) of HIF-1α and GLUT-1 were designed using an online tool and inserted into the pUC57-T7-gRNA vector. The recombinant plasmids were transfected into HEp-2 cells and positive cells were screened using the dilution method. Gene mutation and expression were determined by sequence analysis and immunoblotting. Results In HIF-1α and GLUT-1 double gene knockout HEp-2 cells, a 171-bp deletion in the HIF-1α genomic sequence was detected, whereas multiple base insertions resulted in frameshift mutations in the GLUT-1 gene. Neither HIF-1α nor GLUT-1 protein was expressed in positive cells. The proliferation, migration, and invasion of HEp-2 cells were significantly decreased afterward. The possible mechanism may be that the inhibition PI3K/AKT/mTOR pathway by HIF-1α and GLUT-1 double gene knockout using CRISPR/Cas9 technique lead to reduction of glucose uptake and lactic acid generation. Conclusion Our HIF-1α and GLUT-1 double gene knockout HEp-2 cell model, obtained using a CRISPR/Cas9-based system, may facilitate studies of the pathogenesis of laryngeal carcinoma.

Objective Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method of screening malignant thyroid nodules such as papillary thyroid carcinoma. However, not much data are available regarding the diagnostic efficacy of US-FNAB for papillary thyroid microcarcinoma (≤10 mm in diameter). We aim to compare the diagnostic efficacy of US-FNAB on thyroid nodules between two groups divided by a diameter of 10 mm by correlating the cytological results of US-FNAB with the histopathologic diagnoses in selected patients. Patients and methods Eight hundred twenty-two thyroid nodules (Group A: diameter ≤10 mm, n=620; Group B: diameter >10 mm, n=202) from 797 patients treated between March 2014 and June 2017 were retrospectively evaluated. Only nodules with Thyroid Imaging Reporting and Data System (TIRADS) categories 4-6 were enrolled and sampled by US-FNAB, followed by surgical resection. Results According to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories, 94 thyroid nodules were classified as I, III and IV, and were excluded from the analysis. The resultant 728 thyroid nodules from 721 patients were analyzed. The malignant tendency (TBSRTC V and VI) rates on US-FNAB were 88.2% and 84.6% (P=0.202) in Group A and Group B, respectively, and the malignant rates were 89.5% and 86.9% (P=0.330), respectively, on histopathology. There was a high concordance between cytology and histopathology diagnoses (kappa value =0.797), and no statistical difference in terms of US-FNAB accuracy was found between the two groups (P=0.533). Conclusion For thyroid nodules of TIRADS category 4-6, the diagnostic efficacy of US-FNAB is similar for thyroid nodules either smaller or greater than 10 mm in their maximum diameter.

Tumor necrosis factor (TNF) and interleukin (IL)-17A are pleiotropic cytokines implicated in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). JNJ-61178104 is a novel human anti-TNF and anti-IL-17A monovalent, bispecific antibody that binds to both human TNF and human IL-17A with high affinities and blocks the binding of TNF and IL-17A to their receptors in vitro. JNJ-61178104 also potently neutralizes TNF and IL-17A-mediated downstream effects in multiple cell-based assays. In vivo, treatment with JNJ-61178104 resulted in dose-dependent inhibition of cellular influx in a human IL-17A/TNF-induced murine lung neutrophilia model and the inhibitory effects of JNJ-61178104 were more potent than the treatment with bivalent parental anti-TNF or anti-IL-17A antibodies. JNJ-61178104 was shown to engage its targets, TNF and IL-17A, in systemic circulation measured as drug/target complex formation in normal cynomolgus monkeys (cyno). Surprisingly, quantitative target engagement assessment suggested lower apparent in vivo target-binding affinities for JNJ-61178104 compared to its bivalent parental antibodies, despite their similar in vitro target-binding affinities. The target engagement profiles of JNJ-61178104 in humans were in general agreement with the predicted profiles based on cyno data, suggesting similar differences in the apparent in vivo target-binding affinities. These findings show that in vivo target engagement of monovalent bispecific antibody does not necessarily recapitulate that of the molar-equivalent dose of its bivalent parental antibody. Our results also offer valuable insights into the understanding of the pharmacokinetics/pharmacodynamics and target engagement of other bispecific biologics against dimeric and/or trimeric soluble targets in vivo.

An actinomycete strain 200-09, isolated from a soil sample collected from the coast of Hawaii, USA, was identified as Streptomyces antibioticus on the basis of its morphological, physiological and biochemical characteristics as well as 16S rDNA analysis. A new antimycin-type antibiotic, kitamycin C (1), together with kitamycin A (2), kitamycin B (3), urauchmycin B (4), deisovaleryblastomycin (5) was isolated from a cultured broth of strain 200-09. The structure of the new compound was determined by spectroscopic data, including HR-ESI-MS and NMR. All the compounds exhibited antifungal activities against Candida albicans with MIC of about 25.0 μg mL−1.

A new secondary metabolite, (2S,3R)-l-threonine, N-[3-(formylamino)-2-hydroxybenzoyl]-ethyl ester (streptomyceamide C, 1), together with four known compounds 1, 4-dimethyl-3-isopropyl-2,5-piperidinedione (2), cyclo-((S)-Pro-8- hydroxy-(R)-Ile (3), cyclo-((S)-Pro-(R)-Leu (4), and seco-((S)-Pro-(R)-Val) (5), were isolated from the EtOH extract of the fermented mycelium of the marine-derived streptomycete strain H74-21, which was isolated from sea sediment in a mangrove site. The structure of the new compound was established on the basis of its spectroscopic data, including 1D and 2D NMR, HR-TOF-MS. Their antifungal activities against Candida albicans and cytotoxicities against human breast adenocarcinoma cell line MCF-7, human glioblastoma cell line SF-268 and human lung cancer cell line NCI-H460 were tested. Compounds 1 only displayed cytotoxicity against human breast adenocarcinoma cell line MCF-7 with the IC50 value of 27.0 μg/mL. However, compounds 1–5 do not show antifungal activities at the test concentration of 1 mg/mL, and 2–5 have no cytotoxicities at the test concentration of 50 μg/mL.

Three new compounds (1–3), together with six known compounds (4–9), were isolated from the fruits of Xanthium sibiricum. The structures and the absolute configurations of sibiricumthionol (1), (+)-(5Z)-6-methyl-2-ethenyl-5-hepten-1,2,7-triol [(+)-2], ( − )-(5Z)-6-methyl-2-ethenyl-5-hepten-1,2,7-triol [( − )-2], (2E,4E,1′S, 2′R, 4′S, 6′R)-dihydrophaseic acid (3), (+)-xanthienopyran [(+)-4] and ( − )-xanthienopyran [( − )-4] were established by extensive spectroscopic analyses, X-ray crystallographic analysis, ECCD analysis and ECD calculations. Caffeic acid (7) and caffeic acid ethyl ester (8) weekly inhibited α-glucosidase enzymatic activity by 44.5% and 40.2%, respectively, at 40 μM. Protocatechuic acid (9) selectively exhibited cytotoxicity against HepG2 cell lines, with an IC50 value of 2.92 μM.

Grafting of methyl methacrylate (MMA) and styrene (St) onto polychloroprene latex (CRL) was carried out successfully using emulsion polymerization. The chemical structure of the grafted copolymer was characterized using Fourier transform infrared spectroscopy. The compatibilizing effects of the grafted polymer CRL-g-(MMA-co-St) on the CRL/styrene-acrylate emulsion (SAE) blend were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and mechanical testing. The results showed that the mechanical properties of the contained CRL-g-(MMA-co-St) blend improved significantly in comparison to those of the simple CRL/SAE blend. For the contained CRL-g-(MMA-co-St) blend, the maximum tensile strength (6.72 MPa) and the maximum elongation at break (1142.6%) were obtained when the content of SAE was 60% (occupied by the total dry weight). At the same content of SAE, the T-peel and lap shear strengths of the contact adhesive derived from the c...

Reductions in pore space caused by soil compaction considerably impact soil permeability to air and water by crop roots. The inoculation of arbuscular mycorrhizal (AM) fungi to alleviate this probl...

Optical closure exercises are pivotal for evaluating the accuracy of water quality remote-sensing techniques. The agreement between radiometrically derived and inherent optical property (IOP)-derived above-water spectral remote-sensing reflectance Rrs(λ) is necessary for resolving IOPs, the diffuse attenuation coefficient, and biogeochemical parameters from space. We combined spectral radiometric and IOP measurements to perform an optical closure exercise for two optically contrasting Chinese waters – the Changjiang (Yangtze) River Estuary and its adjacent coastal area in the East China Sea. The final aim of our investigation was to compare two derivations of Rrs(λ): Rrs(λ), derived from radiometric measurements; and Rrs(λ), derived from simultaneous IOP measurements. Five subsequent steps have been taken to achieve this goal, including (1) estimation of the Rrs(λ) from radiometric measurements; (2) scattering correction for the non-water spectral absorption coefficient apd(λ); (3) estimation of the below...

A number of p-haloacetophenones were asymmetrically bioreduced to their corresponding (S)-alcohols by Mucor sp. CG10 with good conversion and excellent enantioselectivity. The results showed that the electronic effects of the halogen substituent (X-group) affected the conversion of the substrates and the enantioselectivity of the reaction. The trend observed was as the X-group at the para-position became more electron donating from F, to Cl, Br and I, the conversion of substrates decreased, while the enantioselectivity increased.

Grafting of methyl methacrylate (MMA) onto polychloroprene rubber latex (CRL) was carried out by emulsion polymerization using a redox initiator. The effects of the principal factors such as emulsifier, initiator and their concentrations and monomer/polymer ratio on monomer conversion, and grafting efficiency were studied. Infrared (FTIR) spectra, proton nuclear magnetic resonance (HNMR), and differential scanning calorimetry (DSC) analysis of the graft copolymer showed the occurrence of grafting. The surface-diffusion controlled process model was proposed to describe the grafting mechanism. The graft copolymer was blended with tackifier and filler for waterborne contact adhesive applications. The 180 degree peel strength of the above adhesive for canvas to other decoration materials was investigated.

This study aims at developing and testing a pragmatic expert system for HIV voluntary counseling (VCT-ES) that leverages best practices. The VCT-ES was developed via evolutionary prototyping and piloted in 10 voluntary HIV counseling and testing (VCT) clinics from Anhui and Beijing representative of prefecture and county level VCT clinics in China. All counselors with the clinics and the clients to the clinics within selected two weeks at baseline and the end of study were invited to participate. Assessment measures included essential counseling procedures (ECPs); clients' satisfaction, knowledge, and behavior efficacy. VCT-ES was developed which tries to model and facilitate standard VCT operation procedures and best practices. One hundred and eighty-two (96 at baseline vs. 86 after intervention) cases recordings, 172 (96 vs. 76) client questionnaires, 10 counselor, and 2 expert rating instruments were collected; and 17 clients and 8 counselors participated in qualitative interviews. VCT-ES increased delivery of ECPs from 18.94% to 66.39% on average; increased clients' knowledge from 40.51% to 86.34% and self-efficacy by 22.42%. The VCT-ES applications listed were rated 9.1 on average (maximum = 10). The VCT-ES could be an easy and effective solution to better routine VCT and merits further research.

Satellite estimation of chlorophyll-a (Chl-a) concentration in the Changjiang Estuary is challenging for ocean-colour retrieval algorithms. The Changjiang Estuary is characterized by suspended-sediment-dominated waters in the mouth and optically complex case 2 waters offshore of the mouth. Satellite ocean-colour products show that high-sediment loads of estuarine waters can cause overestimations or invalid flags of Chl-a concentration. A synthetic chlorophyll index (SCI) was designed for extracting chlorophyll information and for minimizing the influence of sediments on the remote-sensing reflectance spectrum. An SCI algorithm, a quadratic polynomial function of the SCI versus Chl-a concentration, was applied to the estimation of Chl-a concentration from Medium Resolution Imaging Spectrometer (MERIS) images. The overestimation of Chl-a concentration was corrected. The SCI algorithm has applications for MERIS estimation of Chl-a concentration in turbid waters with a moderate to high suspended-sediment concentration.

While investigating the mechanism of action of the HOXA9 protein, we serendipitously identified Meis1 as a HOXA9 regulatory target. Since HOXA9 and MEIS1 play key developmental roles, are cooperating DNA binding proteins and leukemic oncoproteins, and are important for normal hematopoiesis, the regulation of Meis1 by its partner protein is of interest. Loss of Hoxa9 caused downregulation of the Meis1 mRNA and protein, while forced HOXA9 expression upregulated Meis1. Hoxa9 and Meis1 expression was correlated in hematopoietic progenitors and acute leukemias. Meis1+/−Hoxa9−/− deficient mice, generated to test HOXA9 regulation of endogenous Meis1, were small and had reduced bone marrow Meis1 mRNA and significant defects in fluorescence-activated cell sorting-enumerated monocytes, mature and pre/pro-B cells, and functional B-cell progenitors. These data indicate that HOXA9 modulates Meis1 during normal murine hematopoiesis. Chromatin immunoprecipitation analysis did not reveal direct binding of HOXA9 to Meis1 promoter/enhancer regions. However, Creb1 and Pknox1, whose protein products have previously been reported to induce Meis1, were shown to be direct targets of HOXA9. Loss of Hoxa9 resulted in a decrease in Creb1 and Pknox1 mRNA, and forced expression of CREB1 in Hoxa9−/− bone marrow cells increased Meis1 mRNA almost as well as HOXA9, suggesting that CREB1 may mediate HOXA9 modulation of Meis1 expression.

Environmental protection and legislative pressure to eliminate the use of solvents in the adhesive industry have inspired the search for safer alternatives. In the area of contact adhesives, the wa...

The low‐hilly regions in South China are mainly covered with Ultisols and Alfisols with a pH of 4.5–6.0. The major factor limiting crop performance is soluble aluminum (Al) in acid soils, resulting in phytotoxicity in susceptible species. An investigation in Jiangxi and Zhejiang provinces in South China showed that many plants including some native plants and cultivated crops (total of 27 species) could grow well in acid soils of these areas. The Al‐accumulating capacity in leaves varied greatly from species to species. Camellia oleifera Abel accumulated more than 13,500 mg kg−1 Al in old leaves; Camellia sinensis (L.) O. Kuntze, Fagopyrum esculentum Moench, and Dicranopteris pedata (Houtt.) Nakaike accumulated more than 1000 mg kg−1 Al in leaves; and Oryza sativa L., Eucalyptus globulus Labill., Citrus reticulata Blanco, and Brassica chinensis L. accumulated less than 200 mg kg−1 Al in leaves. This investigation provides an important basis for further exploring Al accumulation and resistant mech...

Large cranial defects combined with hydrocephalus after decompressive craniectomy are a common, harsh reality among patients with head trauma. Typically, a shunt is first used to relieve the hydrocephalus. However, subsequently the patients may develop a severe sinking scalp flap over the skull defect before cranioplasty, which would make the procedure difficult.This problem was overcome by temporarily adjusting the shunt pressure using a programmable ventriculoperitoneal shunt tube, which allowed expansion of the depressed scalp flap and facilitated the subsequent cranioplasty. This study describes two patients who were treated for this problem after severe head trauma.When performing a titanium mesh cranioplasty after a shunt, this new method facilitated the separation of the scalp from the underlying muscle or dura and obliterated the dead space between the titanium mesh and the underlying tissue. Both patients had satisfactory outcomes without complications.This method is easy and safe and it facilitates the cranioplasty, reducing the potential complications, including intracranial haematoma, effusions and infection, and thereby improving the patient outcome.

This study was performed to evaluate the effectiveness of a minimally invasive approach to manage patients with epidural haematoma (EDH). The surgical indication and key points were investigated.Descriptive, retrospective study.Twenty-one patients with traumatic EDH were treated through the following method: After anaesthesia, twist drill trepanations were performed followed by a placement of drainage tubes. Twenty ku urokinase in 3 ml saline was injected into the haematoma cyst through the tube, which was closed for 3 hours before connection to a vacuum ball with negative pressure. The injection was repeated three times a day after operation. The fibrinolytic agents were not used in the 'acute group' because of the risk of rebleeding. CT scans were performed according to the changes of clinical manifestations.The drainage tubes were left for 3-5 days before most clots were resolved. The patients discharged after 7 days' hospitalization on average. No infections or recurrence of EDHs were observed in this series.Drilling skull plus injection of urokinase through drainage tube is a safe and effective method with less injury in the treatment of a selected part of patients with EDHs.

The objective of the study was to evaluate the effectiveness of the supraorbital "keyhole" approach with endoscope assistance in surgical treatment of benign tumors around the sellar region. Thirty-five patients, including 19 pituitary tumors, 11 craniopharyngiomas and five tuberculum sellae meningiomas, were enrolled in this study. The tumors were resected through an endoscope-assisted supraorbital keyhole approach via a small skin incision within the eyebrow. Complete removal of the sellar region tumors was achieved in all 35 cases by endoscope-assisted supraorbital keyhole approach. Mean length of hospital stay after surgery was 10.2 days (range 5 - 17). There was no patient with evidence of residual or recurrent tumor during the follow-up period. There was no infection, bleeding, further vision impairment, oculomotor nerve injury or other cranial nerve injury symptom owing to surgery. Though some patients suffered from insipidus, hyperprolactinemia, subcutaneous edema or other postoperative complications, they eventually recovered with or without drug administration. The supraorbital "keyhole" approach with endoscopic assistance in the surgical treatment of benign tumors around the sellar region is an ideal pattern.

HOXA9 expression is a common feature of acute myeloid leukemia, and high-level expression is correlated with poor prognosis. Moreover, HOXA9 overexpression immortalizes murine marrow progenitors that are arrested at a promyelocytic stage of differentiation when cultured and causes leukemia in recipient mice following transplantation of HOXA9 expressing bone marrow. The molecular mechanisms underlying the physiologic functions and transforming properties of HOXA9 are poorly understood. This study demonstrates that HOXA9 is phosphorylated by protein kinase C (PKC) and casein kinase II and that PKC mediates phosphorylation of purified HOXA9 on S204 as well as on T205, within a highly conserved consensus sequence, in the N-terminal region of the homeodomain. S204 in the endogenous HOXA9 protein was phosphorylated in PLB985 myeloid cells, as well as in HOXA9-immortalized murine marrow cells. This phosphorylation was enhanced by phorbol ester, a known inducer of PKC, and was inhibited by a specific PKC inhibitor. PKC-mediated phosphorylation of S204 decreased HOXA9 DNA binding affinity in vitro and the ability of the endogenous HOXA9 to form cooperative DNA binding complexes with PBX. PKC inhibition significantly reduced the phorbol-ester induced differentiation of the PLB985 hematopoietic cell line as well as HOXA9-immortalized murine bone marrow cells. These data suggest that phorbol ester-induced myeloid differentiation is in part due to PKC-mediated phosphorylation of HOXA9, which decreases the DNA binding of the homeoprotein.

Pbx cofactors are implicated to play important roles in modulating the DNA-binding properties of heterologous homeodomain proteins, including class I Hox proteins. To assess how Pbx proteins influence Hox DNA-binding specificity, we used a binding-site selection approach to determine high-affinity target sites recognized by various Pbx-Hox homeoprotein complexes. Pbx-Hox heterodimers preferred to bind a bipartite sequence 5'-ATGATTNATNN-3' consisting of two adjacent half sites in which the Pbx component of the heterodimer contacted the 5' half (ATGAT) and the Hox component contacted the more variable 3' half (TNATNN). Binding sites matching the consensus were also obtained for Pbx1 complexed with HoxA10, which lacks a hexapeptide but requires a conserved tryptophan-containing motif for cooperativity with Pbx. Interactions with Pbx were found to play an essential role in modulating Hox homeodomain amino-terminal arm contact with DNA in the core of the Hox half site such that heterodimers of different compositions could distinguish single nucleotide alterations in the Hox half site both in vitro and in cellular assays measuring transactivation. When complexed with Pbx, Hox proteins B1 through B9 and A10 showed stepwise differences in their preferences for nucleotides in the Hox half site core (TTAT to TGAT, 5' to 3') that correlated with the locations of their respective genes in the Hox cluster. These observations demonstrate previously undetected DNA-binding specificity for the amino-terminal arm of the Hox homeodomain and suggest that different binding activities of Pbx-Hox complexes are at least part of the position-specific activities of the Hox genes.

After detailed analysis of the influence of non-ideal factors (such as device mismatches, voltage dependency of carrier mobility and temperature-varying effect) upon the performance of the double-MOSFET block including non-linearities cancelling, a circuit model for the double-MOSFET block via device physics approach is proposed. The effects of some non-ideal factors upon the performance of the block are analysed and simulated, based upon the proposed model, which is justified by SPICE-2 simulations.

Do the socialist countries want to use foreign capital? Marx answered this question a long time ago. Lenin and Stalin, when they were leading the socialist construction in the Soviet Union, regarded the utilization of foreign capital as an important policy. In the early twenties, Russia had suffered severe war losses and urgently needed a restoration of peace and development of industry; it thus met the farmer's demand for commodities. At that time, Lenin was of the view that the most appropriate of all feasible measures was to absorb and utilize foreign capital to develop industry and forge a union between the Soviet regime and the peasants. Following the direction pointed out by Lenin, the Soviet Union obtained 2 billion rubles from Sweden, England, Germany, Italy, and Japan from 1920 to 1935. Russia overcame its economic problems, accelerated industrial construction, and consolidated the Soviet regime by using these loans.