Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR™ (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5–4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.
antibody discovery; humanized; optimized; SARS-CoV
Signalling through the janus kinase (JAK)/signal transducer and activator of transcription (Stat) pathway is required at different stages of mammary gland development, and this pathway is frequently hyper-activated in cancer, including tumours of the breast. Stats 3, 5 and 6 have important roles in the differentiation and survival of mammary alveolar cells, but somewhat paradoxically, both Stat3 and 5 can have oncogenic activity in the mammary gland. Constitutive activation of JAK2 could be anticipated to result in hyper-activation of Stats 1, 3, 5 and 6 with concomitant cell transformation, although the outcome is difficult to envisage, particularly since Stats 3 and 5 play opposing roles in normal mammary gland development. Here, we show that expression of a constitutively active JAK2 mutant, JAK2 V617F, leads to hyper-activation of Stat5 in mammary epithelial cells (MECs), and transgenic mice expressing JAK2 V617F specifically in the mammary gland exhibit accelerated alveologenesis during pregnancy and delayed post-lactational regression. Overexpressing JAK2 V617F in MECs in vitro results in elevated proliferation and resistance to cell death. Furthermore, constitutively active JAK2 enhances anchorage-independent cell growth in the presence of a co-operating oncogene and accelerates tumourigenesis in a xenograft model. Taken together, our results provide insights into signalling downstream of constitutively active JAK2 and could be important for understanding the molecular mechanisms of breast tumourigenesis.
JAK/Stat signalling; mammary gland development; breast cancer; JAK2 V617F; Stat5
This study aims to: (1) document the prevalence of hepatitis C virus (HCV) among methadone maintenance treatment (MMT) patients in Kunming and Shanghai; (2) examine risk factors for HCV by comparing those who tested positive with those who were negative and (3) examine if HCV serostatus is related to attitudes toward MMT.
Using data collected from 306 patients admitted to MMT in 2009–2010 in Shanghai and Kunming, we compared HCV-positive and HCV-negative patients (based on clinical records) on their HCV knowledge and risk behaviors and attitudes toward MMT.
The HCV seropositive rate was 53.3% (51.3% in Shanghai and 55.5% in Kunming) and a majority of patients did not know their serostatus. Patients scored on average fewer than 6 correct out of the 20 items in the HCV knowledge questionnaire. Recent injection use and length of opiate use were strong predictors of HCV status, while no differences were found between HCV-positive and HCV-negative individuals in sexual risks or HCV knowledge. Both groups expressed similar views toward MMT.
The high HCV prevalence and the general lack of knowledge about HCV infection, transmission and treatment suggest the need to provide HCV education and health promotion programs among patients in MMT.
communicable diseases; health services; public health
To develop a quantitative method for characterizing gestational sac shape.
Twenty first-trimester gestational sacs in normal pregnancies were studied with three-dimensional (3D) ultrasonography. The 3D coordinates of surface-point sets were obtained for each sac using 30-, 15- and six-slice sampling. Cubic spline interpolation was used with the 15- and six-slice surface-point samples to generate coordinates for those 30-slice surface points not measured. Interpolated and measured values, the latter from the 30-slice sample, were compared and the percent error calculated. Cubic spline interpolation was used to determine the coordinates of a standard surface-point sample (3660) for each sac in each slice sample. These coordinate data were used to give each sac a standard configuration by moving its center of gravity to the origin, aligning its inertial axes along the coordinate axes and converting its volume to 1.0 mL. In this form, a volume shape descriptor could be generated for each sac that was then transformed into a vector containing only shape information. The 20 shape vectors of each slice sample were subjected to principal components analysis, and principal component scores (PCSs) calculated. The first four PCSs were used to define a gestational sac shape score (GSSS-30, GSSS-15 or GSSS-6) for each sac in a given slice sample. The characteristics of each set of GSSSs were determined and those for the GSSS-15 and GSSS-6 were compared with the GSSS-30 characteristics.
Cubic spline interpolations were very accurate in most cases, with means close to 0%, and approximately 95% of the errors being less than 10%. GSSS-30 accounted for 67.6% of the shape variance, had a mean of zero and an SD of 1.1, was normally distributed and was not related to menstrual age (R = −0.16, P = 0.51). GSSS-15 and GSSS-6 had essentially the same characteristics. No significant differences between individual GSSS-30 values and those for GSSS-15 or GSSS-6 were found, indicating the absence of a slice sample effect.
Using sophisticated mathematical methods, the gestational sac shape, initially represented by the 3D coordinates of 3660 surface points, was converted to a single number, the GSSS. This score had the appropriate properties for quantitatively characterizing normal, first-trimester gestational sac shapes. As it can be obtained from as few as six slices, it should be useful in many clinical situations. This novel approach has the potential for providing quantitative shape information about a variety of biological shapes and how they change over time.
gestational sac; gestational sac shape score; quantitative shape analysis
Innate immunity factors such as conversion of the 26S proteasome to form the immunoproteasome and the Toll-like receptor signaling pathways are activated in chronic hepatitis induced by the carcinogenic drug DDC. Over time, preneoplastic hepatocyte phenotypes appear in the liver parenchyma. These changed hepatocytes expand in number because they have a growth advantage over normal hepatocytes when responding to chronic liver injury. The changed hepatocytes can be identified using immunofluorescent antibodies to preneoplastic cells e.g. FAT10/UbD, A2 macroglobulin, glutathione transpeptidase, alpha fetoprotein, glycipan 3, FAS, and gamma glutamyl transpeptidase. The formation of the preneoplastic cells occurs concomitant with activation of the Toll-like receptor signaling pathways and the transformation of the 26S proteasome to form the immunoproteasome. This transformation is in response to interferon stimulating response element on the promoter of the FAT10/UbD gene. NFκB, Erk, p38 and Jnk are also up regulated. Specific inhibitors block these responses in vitro in a mouse tumor cell line exposed to interferon gamma. Mallory-Denk bodies form in these preneoplastic cells, because of the depletion of the 26S proteasome due to formation of the immunoproteasome. Thus, MDB forming cells are also markers of the preneoplastic hepatocytes. The UbD positive preneoplastic cells regress when the liver injury induced chronic hepatitis subsides. When the drug DDC is refed to mice and chronic hepatitis is activated, the preneoplastic cell population expands and Mallory-Denk bodies rapidly reform. This response is remembered by the preneoplastic cells for at least four months indicating that an epigenetic cellular memory has formed in the preneoplastic cells. This proliferative response is prevented by feeding methyl donors such as S-adenosylmethionine or betaine. Drug feeding reduces the methylation of H3 K4, 9, and 27 and this response is prevented by feeding the methyl donors. After 8 to 15 months of drug withdrawal in mice the preneoplastic liver cells persist as single or small clusters of cells in the liver lobules. Multiple liver tumors form, some of which are hepatocellular carcinomas. The tumors immunostain positively for the same preneoplastic markers that the preneoplastic cells. Similar cells are identified in human cirrhosis and hepatocellular carcinoma indicating the relevance of the drug model described here to the preneoplastic changes associated with human chronic hepatitis and hepatocellular carcinoma.
Mallory-Denk bodies; ubiquitin D; 26S proteasome; immunoproteasome; Toll-like receptors
Man-made composite materials called “metamaterials” allow for the creation of unusual wave propagation behavior. Acoustic and elastic metamaterials in particular, can pave the way for the full control of sound in realizing cloaks of invisibility, perfect lenses and much more. In this work we design acousto-elastic surface modes that are similar to surface plasmons in metals and on highly conducting surfaces perforated by holes. We combine a structure hosting these modes together with a gap material supporting negative modulus and collectively producing negative dispersion. By analytical techniques and full-wave simulations we attribute the observed behavior to the mass density and bulk modulus being simultaneously negative.
This pilot study investigates the role of assisted-freehand ultrasound (AFUSON) elasticity imaging of the breast in assessing the contour, size and area of 23 early breast cancers by making comparison of AFUSON with the equivalent B-mode ultrasound images and gold standard histopathology slides.
The B-mode, AFUSON and digitised histopathology slides of three early breast cancers were compared for contour, size and area with histopathology scans. AFUSON features that corresponded to areas of known malignant change on the histopathology slides were regarded as diagnostic. These diagnostic criteria were then applied to the B-mode and AFUSON elasticity images of all 23 breast cancers in the pilot study without having the availability of the histopathology scans for reference. Corresponding diameters were measured and the results were compared with the equivalent measurements on the scans of the histology slides. The results were tabulated in histogram form. Diagnostic confidence levels were evaluated.
Size dimension accuracy increased from 66% using B-mode alone to 82% using combined B-mode and AFUSON elasticity images. Tumour area accuracy was also increased. A small number of cases had a striking visual similarity of shape on AFUSON elasticity scans and histopathology slides.
In spite of the shortfalls in this study, AFUSON elasticity imaging was capable of acquiring some high-quality images that showed strong correlation between AFUSON elasticity and scans of histology slides. Further studies will be carried out to refine the technique and determine if it has a role in the diagnosis and management of breast cancer.
For greenhouse gas (GHG) emissions by Beijing economy 2007, a concrete emission inventory covering carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) is presented and associated with an input-output analysis to reveal the local GHG embodiment in final demand and trade without regard to imported emissions. The total direct GHG emissions amount to 1.06E + 08 t CO2-eq, of which energy-related CO2 emissions comprise 90.49%, non-energy-related CO2 emissions 6.35%, CH4 emissions 2.33%, and N2O emissions 0.83%, respectively. In terms of energy-related CO2 emissions, the largest source is coal with a percentage of 53.08%, followed by coke with 10.75% and kerosene with 8.44%. Sector 26 (Construction Industry) holds the top local emissions embodied in final demand of 1.86E + 07 t CO2-eq due to its considerable capital, followed by energy-intensive Sectors 27 (Transport and Storage) and 14 (Smelting and Pressing of Ferrous and Nonferrous Metals). The GHG emissions embodied in Beijing's exports are 4.90E + 07 t CO2-eq, accounting for 46.01% of the total emissions embodied in final demand. The sound scientific database totally based on local emissions is an important basis to make effective environment and energy policies for local decision makers.
Blood alcohol levels (BAL) cycle up and down over a 7–8 day period when ethanol is fed continuously for one month in the intragastric tube feeding rat model (ITFRM) of alcoholic liver disease. The cycling phenomenon is due to an alternating increase and decrease in the metabolic rate. Recently, we found that S-adenosyl-methionine (SAMe) fed with alcohol prevented the BAL cycle.
Using the ITFRM we fed rats betaine (2 g/kg/day) with ethanol for 1 month and recorded the daily 24 h urine ethanol level (UAL) to measure the BAL cycle. UAL is equivalent to BAL because of the constant ethanol infusion. Liver histology, steatosis and BAL were measured terminally after 1 month of treatment. Microarray analysis was done on the mRNA extracted from the liver to determine the effects of betaine and alcohol on changes in gene expression.
Betaine fed with ethanol completely prevented the BAL cycle similar to SAMe. Betaine also significantly reduced the BAL compared to ethanol fed rats without betaine. This was also observed when SAMe was fed with ethanol. The mechanism involved in both cases is that SAMe is required for the conversion of epinephrine from norepinephrine by phenylethanolamine methyltransferase (PNMT). Epinephrine is 5 to 10 fold more potent than norepinephrine in increasing the metabolic rate. The increase in the metabolic rate generates NAD, permitting ADH to increase the oxidation of alcohol. NAD is the rate limiting factor in oxidation of alcohol by alcohol dehydrogenase (ADH). This explains how SAMe and betaine prevented the cycle. Microarray analysis showed that betaine feeding prevented the up regulation of a large number of genes including TLR2/4, Il-1b, Jax3, Sirt3, Fas, Ifngr1, Tgfgr2, Tnfrsf21, Lbp and Stat 3 which could explain how betaine prevented fatty liver.
Betaine feeding lowers the BAL and prevents the BAL cycle by increasing the metabolic rate. This increases the rate of ethanol elimination by generating NAD.
S-adenosylmethionine (SAMe); Betaine; Blood Alcohol Cycle (BAL); Microarray Analysis; NAD
Efficacy of antidepressant drugs is often limited. One of the limiting factors may be diet. This study shows that the effect of escitalopram in the forced swimming test is diminished in rats by food restriction that decreased body weight by 8%. The primary target for escitalopram is the serotonin (5-HT) transporter. Using high-speed chronoamperometry to measure 5-HT clearance in vivo in rats fed the same food restricted diet, the rate of 5-HT clearance from extracellular fluid in brain was dramatically increased. Increased 5-HT transporter function under conditions of dietary restriction might contribute to the decreased effect of escitalopram. These results suggest that diet plays an integral role in determining efficacy of antidepressant drugs, and might well generalize to other psychoactive drugs that impinge upon the 5-HT transporter.
serotonin; antidepressant; SSRI; rat; serotonin transporter
Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS−/− MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5−/−CXCR3−/− mice, the immune-promoting effect of iNOS−/− MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs.
mesenchymal stem cells; chemokine; immunomodulation; tissue repair
A sensitive and reliable method of liquid chromatography–electrospray ionization/tandem mass spectrometry (LC-ESI/MS/ MS) was developed and validated for determining 1,3-dimethylamylamine (1,3-DMAA) and 1,4-dimethylamylamine (1,4-DMAA) in geranium plants (Pelargonium graveolens). The sample was extracted with 0.5 M HCl and purified by liquid-liquid partition with hexane. The parameters for reverse-phase (C18) LC and positive ESI/MS/MS were optimized. The matrix effect, specificity, linearity, precision, accuracy and reproducibility of the method were determined and evaluated. The method was linear over a range of 0.10–10.00 ng/mL examined, with R2 of 0.99 for both 1,3-DMAA and 1,4-DMAA. The recoveries from spiked concentrations between 5.00–40.00 ng/g were 85.1%–104.9% for 1,3-DMAA, with relative standard deviation (RSD) of 2.9%–11.0%, and 82.9%–101.8% for 1,4-DMAA, with RSD of 3.2%–11.7%. The instrument detection limit was 1–2 pg for both DMAAs. The quantification limit was estimated to be 1–2 ng/g for the plant sample. This method was successfully applied to the quantitative determination of 1,3- and 1,4-DMAA in both geranium plant and geranium oil.
1,3-dimethylamylamine; 1,4-dimethylamylamine; geranium (Pelargonium graveolens); liquid chromatography-tandem mass spectrometry (LC/MS/MS)
We review the concept and the evolution of bandgap and wavefunction engineering, the seminal contributions of Dr. Chemla to the understanding of the rich phenomena displayed in epitaxially grown quantum confined systems, and demonstrate the application of these concepts to the colloidal synthesis of high quality type-II CdTe/CdSe quantum dots using successive ion layer adsorption and reaction chemistry. Transmission electron microscopy reveals that CdTe/CdSe can be synthesized layer by layer, yielding particles of narrow size distribution. Photoluminescence emission and excitation spectra reveal discrete type-II transitions, which correspond to energy lower than the type-I bandgap. The increase in the spatial separation between photoexcited electrons and holes as a function of successive addition of CdSe monolayers was monitored by photoluminescence lifetime measurements. Systematic increase in lifetimes demonstrates the high level of wavefunction engineering and control in these systems.
Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.
We aimed to determine which combination of physical examination (pe), mammography (mam), and ultrasonography (us) would optimize breast cancer detection in China.
We conducted a trial of screening with pe, mam, and us among Chinese women 25 years of age and older. All initial screenings using the three modalities were completed within 30 days of each other, and subjects were followed approximately 1 year later. The performances of the three screening methods used alone, in parallel, or in series were compared. Data were analyzed using exact confidence intervals (cis) and the McNemar test.
Between March 2009 and July 2011, 3028 eligible women completed all study examinations. At a mean follow-up of 1.3 years, 33 breast cancers were identified in the study population. Mammography detected 28 cancers; us, 24 cancers; and pe, 22 cancers. During the follow-up period, 2 false-negative cases occurred clinically. The highest sensitivity for breast cancer screening (93.9%) was achieved by paralleling mam with us, but came at the cost of a higher recall rate (12.15%). Using us alone at the first stage, followed by mam when indicated, offered high specificity (99.4%) and the lowest recall rate (1.82%), which were not reached at the expense of sensitivity (84.8%). Used in series, us and mam achieved a sensitivity similar to that for the same modalities used in parallel (McNemar p > 0.05).
Taking limited health resources into consideration, the strategy of screening with us alone at the first stage, followed by mam when indicated, may optimize breast cancer detection in most regions of China.
Breast cancer; mass screening; mammography; ultrasonography; follow-up study; Chinese women
The polarized molecules predominately distributing at hepatocyte canalicular surface play a vital role in disclosing the process of bile formation and etiopathogenisis of cholestatic live diseases. Therefore, it is important to find novel polarized molecules on hepatocyte canalicular membrane. In the present study, canalicular membrane vesicles (CMVs) isolated from rat hepatocyte by density gradient centrifugation were used as immunogens to produce hybridoma and 46 strains of monoclonal antibodies (mAb) against CMVs were obtained. With a series of morphological assay methods, including immunohistochemistry, immunofluorescence and immuno-electron microscope, the antigens recognized by canalicular mAb1 (CM1) and canalicular mAb2 (CM2) were confirmed to predominately distribute at hepatocyte canalicular membrane. Transport activity assay revealed that CM2 could inhibit ATP-dependent E217βG uptake of rat hepatocyte CMVs. Meanwhile, Western blotting analysis showed that the molecular mass of CM2 antigen was approximately 110kDa, which was much less than Mr 180kDa of multidrug resistance-associated protein 2 (MRP2) involved in glucuronide transport. These data indicated that CM2 antigen might be a potential novel molecule participating in glucuronide transport on the hepatocyte canalicular membrane.
hepatocyte canalicular membrane; glucuronide transport; canalicular mAb2 (CM2); hybridoma technique.
In this paper, a new neural-fuzzy approach is proposed for automated region segmentation in transrectal ultrasound images of the prostate. The goal of region segmentation is to identify suspicious regions in the prostate in order to provide decision support for the diagnosis of prostate cancer. The new automated region segmentation system uses expert knowledge as well as both textural and spatial features in the image to accomplish the segmentation. The textural information is extracted by two recurrent random pulsed neural networks trained by two sets of data (a suspicious tissues’ data set and a normal tissues’ data set). Spatial information is captured by the atlas-based reference approach and is represented as fuzzy membership functions. The textural and spatial features are synthesized by a fuzzy inference system, which provides a binary classification of the region to be evaluated.
TRUS; prostate cancer; RNN; fuzzy inference; tissue segmentation; textural feature; spatial feature; malignant tumor localization
Although there are a number of different allopolyploids in the plant kingdom, the exact ancestral parents of some allopolyploids have not been well characterized. We propose a strategy in which virtual allopolyploid lines derived from different types of parental species are used to investigate the progenitors of an allopolyploid. The genotypes of the parental lines and the natural allopolyploid were established using a set of DNA molecular markers. The genotypes of the virtual lines were then derived from those of the parental lines, and compared extensively with that of the natural allopolyploid. We applied this strategy to investigate the progenitors of the C subgenome of Brassica napus (rapeseed, AACC). A total of 39 accessions from 10 wild and 7 cultivated types of the B. oleracea cytodeme (CC), and 4 accessions of B. rapa (AA) were used to construct 156 virtual rapeseed lines. Genetic structure was compared among natural rapeseed, virtual rapeseed lines, and their parental lines by principal component analysis and analysis of ancestry. Our data showed that the C subgenome of natural rapeseed was related closely to the genome of cultivated B. oleracea and its related wild types, such as B. incana, B. bourgeaui, B. montana, B. oleracea ssp. oleracea and B. cretica. This finding indicated that these types or their progeny might be ancestral donors of the C subgenome of rapeseed. The successful application of the strategy of virtual allopolyploidy in rapeseed demonstrates that it can possibly be used to identify the progenitors of an allopolyploid species.
allopolyploid; Brassica napus; Brassica oleracea cytodeme; origination; virtual line
Microbial agents are regarded as a potential cause of tumors, but their direct effects on tumors, such as myeloma, are not well studied. Our studies demonstrated that expression of HLA-DR and CD40 on the myeloma cell membrane surface is upregulated by interferon-γ and/or microbial antigens (Ags). Unlike prior studies, our study showed that Th2 cells cannot promote myeloma growth directly. However, Bacillus Calmette–Guerin Vaccine (BCGV)-specific Th2 cells stimulated by BCGV-loaded dendritic cells (DCs) promoted myeloma clonogenicity directly when the myeloma cells expressed major histocompatibility complex Class-II molecules (MHC-II) and took up BCGV Ag. B-cell lymphoma 6 (Bcl-6) protein expression and the proportion of HLA-DR+ or CD40+ cells were higher in colonies of Th2 cell-stimulated myeloma cells. Furthermore, anti-HLA-DR or neutralizing CD40 antibody could prevent this increase in Bcl-6 expression and colony number. These results indicate that microbes and microbial Ag-specific Th2 cells may directly impact the biology of myeloma and contribute to tumor progression. Activation may be limited to MHC-II+ myeloma cells that retain B cell and stem cell characteristics. Taken together, our data suggest that factors involved in microbial Ag presentation, such as DCs, Th2 cells and so on, are potential targets for myeloma therapeutic intervention.
myeloma; microbial antigen; dendritic cell; Th2 cell; antigen presentation; clonogenicity
The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.
centrosome; cell cycle; ninein-like protein; Nlp; mitosis; tumourigenesis
To describe female condom (FC) use, male condom (MC) use and overall levels of protected sex before, during and after FC education and promotion (using the original prototype FC) combined with MC promotion among female sex workers in three rural or small urban settings in southern China.
The 1-year FC intervention was conducted by local health workers through outreach to establishments where sex work is conducted. Three serial cross-sectional surveys were conducted in each study town before, during and after the intervention along with process documentation throughout the intervention period.
Cross-sectional data from pre-intervention (baseline) and 6-month and 12-month post-intervention surveys from three study sites are used in a descriptive comparison of the context of the sex industry, outreach in two phases of intervention, and FC adoption after the intensive intervention phase in each site.
Approximately 75–80% of eligible women working in sex establishments, varying from 74 to 155 participants for each survey, were recruited from three study sites. After introduction and promotion of the FC along with the MC during the community public health intervention, between one-fifth and one-half of the study participants had tried the FC in the three study sites by the time of the 6-month and 12-month cross-sectional surveys. Among them, 10–30% had used the FC more than once. FC awareness increased following the intervention with much less variation across the three study sites. At baseline, 31–54% of participants across the three sites reported 100% protected sex in the last 30 days with all types of partners. At one of the sites with relatively low MC use before the intervention, the proportion of women reporting 100% protected sex in the last 30 days increased by 15%, and the proportion reporting nil protected sex in the last 30 days decreased by 13% between baseline and 12-month post-intervention surveys. More complex profiles of FC and MC use and protected sex were shown at the other two study sites, where a higher level of protection had been reached before the project started.
Different levels of FC adoption were identified after the 1-year FC promotion intervention through outreach to sex establishments. The input, output and outcomes of the intervention may be associated with women’s demographic and risk characteristics, the local capacities of intervention staff, and other contextual factors. Further analysis of these factors will help establish the role of the FC in increasing protected sex, and provide insight into how to achieve greater FC use.
Female condom; Sex workers; China; HIV/AIDS prevention; Establishment-based intervention
Optic neuritis (ON) is defined as an inflammation of the optic nerve and provides a useful model for studying the effects of inflammatory demyelination of white matter. The aim of this study was to assess the diffusion changes in both the optic nerve and optic radiation in patients with acute and chronic ON using diffusion tensor (DT) MRI.
33 patients with idiopathic demyelinating optic neuritis (IDON) and 33 gender- and age-matched healthy controls were examined with DT-MRI and with T1 and T2 weighted MRI.
Compared with controls, both first-episode and recurrent patients with IDON in the acute stage showed significantly increased radial diffusivity (λ⊥) and decreased mean fractional anisotropy (FA) in the affected nerves. Reduced FA, increased λ⊥, mean diffusivity (MD) and axial diffusivity (λ∥) were determined in patients with subacute IDON. We found no significant difference in the directional diffusivity of optic radiation in patients whose disease had lasted less than 1 year compared with healthy controls. However, significant changes in the FA and λ⊥ of the optic radiation were detected in patients with disease duration of more than 1 year.
These results show the great potential and capacity of DT-MRI measures as useful biomarkers and indicators for the evaluation of myelin injury in the visual pathway.