邻苯二甲酸酯类化合物与睾丸源性生殖障碍综合征

流行病学研究显示妇女在怀孕期间接触邻苯二甲酸酯类化合物后,所产男婴易患隐睾、尿道下裂、成年期睾丸肿瘤及精液质量低下等症状。这类症状可统称为睾丸源性生殖障碍综合征(testicular dysgenesis syndrome,TDS)。TDS可能是由男性胎儿睾丸的发育在子宫内受到影响不能发育出具有正常功能的睾丸间质(Leydig)细胞和支持(Sertoli)细胞引起的。例如,睾丸间质细胞接触邻苯二甲酸酯类化合物后,睾丸间质细胞的两种产物———睾酮和胰岛素样生长因子3(INSL3)———受到了抑制,两者对于睾丸下降起关键作用。成年期睾丸的胎儿型间质细胞和支持细胞错位可能是精子生成减少的原因。

Overexpression of PGA37/MYB118 and MYB115 promotes vegetative-to-embryonic transition in Arabidopsis

Formation of somatic embryos from non-germline cells is unique to higher plants and can be manipulated in a variety of species. Previous studies revealed that overexpression of several Arabidopsis genes, including WUSCHEL （WUS）/PLANT GROWTH ACTIVATOR6 （PGA6）, BABY BOOM, LEAFY COTYLEDON1 （LEC1）, and LEC2, is able to cause vegetative-to-embryonic transition or the formation of somatic embryos. Here, we report that a gain-offunction mutation in the Arabidopsis PGA37 gene, encoding the MYBI18 transcription factor, induced vegetative-toembryonic transition, the formation of somatic embryos from root explants, and an elevated LEC1 expression level. Double mutant analysis showed that WUS was not required for induction of somatic embryos by PGA37/MYB118. In addition, overexpression of MYBll5, a homolog of PGA37/MYB118, caused a pga37-like phenotype. A myb118 myb115 double mutant did not show apparent developmental abnormalities. Collectively, these results suggest that PGA37/ MYB118 and MYB115 promote vegetative-to-embryonic transition, through a signaling pathway independent of WUS.

Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo

Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone （LH） or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin- releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7a-methyl-nortestosterone （MENT）, which is an androgen resistant to metabolism by 5a-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igfl, Lifr, Pdgfra, Bcl2, Ccnd3and Pcnawere upregulated by MENT, and those of Pdgfra, Ccnd3and Pcnawere upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.

Snapshot of HIV pathogenesis in China

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.

New insights into calcium,dairy and colon cancer

This paper is to review recent information about the relationship of calcium and dairy foods to colon cancer. The review focuses on primary prevention, discusses the potential components in dairy foods that might be anti-neoplastic, reviews the epidemiologic information and describes intervention studies demonstrating efficacy of calcium and vitamin D in reducing colorectal polyp recurrence. Since vitamin D is important in cancer prevention, pertinent data is discussed and potential mechanisms of actions presented. Calcium and vitamin D are important agents for the primary prevention of colorectal neoplasia.

11β-hydroxysteroid dehydrogenase types 1 and 2. in postnatal development of rat testis： gene express,on, localization and regulation by luteinizing hormone and androgens

11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.

Comparison of the Immunogenicities of HIV-1 Mutants Based on Structural Modification of env

Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γ ELISPOT. Overall, five mutants (dWt, M2, M5-2, M5-1 and dM7) induced higher neutralization activities for both pseudoviruses than plasmid Wt, while only two of the mutants (dWt and M5-2) showed significant differences (P<0.05). Two mutants (M2 and dM2) induced more Env-specific T cells than plasmid Wt. Statistically however, significance was only reached for mutant M2. Thus, properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.

银屑病患者CD68^+/CD11c^+阳性的髓衍生细胞大量产生IL-20:基因调节和细胞效应

We assessed expression of IL-20 and its receptors in psoriasis,given the recent implication of IL-20 in epidermal hyperplasia.Psoriatic lesional(LS)skin consistently expressed more IL-20 mRNA than nonlesional(NL)skin.Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+(myeloid-derived)dermal leukocytes.Because this contrasted with earlier reports of a keratinocyte source,we assessed IL-20 mRNA expression in a variety of cells in vitro,and confirmed a myeloid-derived cellular source(monocytes).Plastic adhesion,activation of β2 integrins,and incubation with tumor necrosis factor-αstimulated expression in these cells.IL-20 receptor(IL-20R)αand IL-20RβmRNA was decreased in LS versus NL skin,which also contrasted with earlier findings.To investigate the relationship between IL-20 and disease activity,we examined psoriasis patients treated with the CD2-targeted agent alefacept.In therapeutic responders,lesional IL-20 mRNA decreased to NL levels,suggesting that CD2+leukocytes may proximally regulate IL-20.Finally,to assess IL-20 function,we used microarrays to screen IL-20-treated keratinocytes,which demonstrated upregulation of disease-related and IFN-γ-induced genes.Hence,IL-20 may influence inflammation through IFN-like effects.Together,these data indicate that IL-20 may be an important effector cytokine in psoriasis,and that its inhibition may represent a potential therapeutic target.

Repressors of reprogramming

Induced pluripotent stem cells(i PSCs) have been the focal point of ever increasing interest and scrutiny as they hold the promise of personalized regenerative medicine. However, creation of i PSCs is an inefficient process that requires forced expression of potentially oncogenic proteins. In order to unlock the full potential of i PSCs, both for basic and clinical research, we must broaden our search for more reliable ways of inducing pluripotency in somatic cells. This review surveys an area of reprogramming that does not receive as much focus, barriers to reprogramming, in the hope of stimulating new ideas and approaches towardsdeveloping safer and more efficient methods of reprogramming. Better methods of i PSC creation will allow for more reliable disease modeling, better basic research into the pluripotent state and safer i PSCs that can be used in a clinical setting.

Composition of the Putative Prepore Complex of <i>Bacillus thuringiensis</i>Cry1Ab Toxin

Prepore formation is hypothesized to be an obligate step in the insertion of Cry1Ab toxin into insect brush border membrane vesicles. We examined the architecture of the putative prepore when isolated using the published protocols [1] [2]. Our results demonstrate that the putative prepore form of Cry1Ab is a combination of receptor proteins attached to the toxin, when purified. The results also suggest that this prepore form as prepared by the methods published is different from other membrane-extracted oligomeric forms of Cry toxins and prepore of other toxins in general. While most other known prepores are composed of multimers of a single protein, the Cry1Ab prepore, as generated, is a protein-receptor complex oligomer and monomers of Cry toxins.

Nanotechnological Contribution to Drug Delivery System: A Reappraisal

With the emergence of Nanotechnology, there has been remarkable improvement in the field of drug delivery system over the past decade. Nanotechnology in drug delivery system is an upcoming field and significant research has been conducted in this regard. It has been able to overcome some limitations encountered with the traditional routine drug delivery systems and hence emerged as an effective alternative. This article reviews nanotechnology based different types of drug delivery systems and their therapeutic applications.

Bacteremia Caused by <i>Acinetobacter baumannii</i>: Epidemiologic Features, Antimicrobial Susceptibility, and Outcomes

Acinetobacter baumannii bacteremia is becoming more prevalent and is associated with increasing morbidity and mortality. Escalating antibacterial resistance further contributes to therapeutic dilemmas, enhanced infection control support and poorer outcomes in patients infected with these bacteria. A retrospective analysis of patients whose blood cultures produced A. baumannii from January 2007 through January 2013 was performed. Data regarding the epidemiologic features, antimicrobial susceptibility and outcomes of patients with A. baumannii bacteremia were collected and analyzed. Sixty A. baumannii isolates each from a different patient were identified. The Charlson Comorbidity Index (≥3) was the greatest among patients with multi-drug resistance (MDR) compared to intermediate drug resistance (IDR) and pan-sensitive (PS) A. baumannii. The mean APACHE II scores for MDR, IDR and PS A. baumannii bacteremia were 21, 15 and 11, respectively (P < 0.05, MDR v. PS). Seventy-three percent of the isolates were resistant to quinolones, 44% to piperacillin/tazobactam, 45% to amikacin, 22% to imipenem, 0% to ticarcillin/clavulanate, and 0% to polymyxin. Among 28 patients with MDR A. baumannii bacteremia, 20 received inadequate empiric treatment, and 16 of these patients died (80%). Of the remaining eight patients with MDR bacteremia who received adequate empiric antibiotics, only two died (25%). The severity of underlying illness, degree of antibiotic resistance and receiving inadequate initial antibiotic therapy are associated with mortality among patients with bacteremia due to A. baumannii.

超声波传导速度与儿童、青少年和成人骨的几何特征间的关系

Objectives: To investigate the relation between volumetric bone mineral density (vBMD) and speed of sound (SOS). Study design: Total and trabecular vBMD were measured by peripheral quantitative computed tomography at the forearm in a population of 216 individuals of a pediatric outpatient clinic. Moreover, SOS was measured by a quan-titative ultrasound device (QUS) at the thumb, patella, and os calcis. Results: Linear regression analysis revealed that the prediction of SOS by vBMD is relatively weak (R2 < 0.1). Moreover, body height and measures of bone size have a stronger influence on SOS than vBMD. The influence of bone size on SOS also depends on the location of measurement (highest prediction of SOS by body height at patella with R2 = 0.56). Anthropometric characteristics have a stronger influence on SOS than measures of bone mineral density at the thumb and patella in comparison to os calcis (body height predicts SOS at os calcis, with R2 = 0.03). Conclusions: QUS is not a suitable method to assess bone density. If QUS is applied for the assessment of bone development and of bone fracture risk, the measurement should be performed with consideration of anthropometric measurements.

慢性酒精中毒患者的认知功能障碍与弥散性大脑白质萎缩的关系研究

Objective: Diffuse brain white matter atrophy is often seen in chronic alcohol ics, but its relation with cognitive impairment remains to be solved. In order t o address this issue, in alcoholics with cognitive impairment at different level s, we studied relations of the central sensory conduction time (CSCT)or brain ma gnetic resonance imaging (MRI) findings with the cognitive function. Methods: Su bjects were 35 alcoholics with mild cognitive impairment (mini-mental state exa mination score, MMSE,≥24; mean±SD, 27.7±1.9), 12 with moderate to severe cogn itive impairment (MMSE < 24; 20.3±2.7), 15 with Alzheimer’s disease (AD) (MMSE , 18.9±4.3) (disease control)and 20 healthy volunteers (MMSE, 28.5±1.6) (norma l control). Median nerve SEPs were recorded in the all subjects,and the latencie s and amplitudes of their N9, N11, P13/14, N20 and P25 components were measured. The ventri culocranial ratio (VCR) and the width of cortical sulci were measure d on MRIs. These physiological parameters and MRI findings were compared between the 4 groups of the subject, and correlations between those all features were a lso analyzed. Results: CSCT and VCR were significantly greater in alcoholics wit h moderate to severe cognitive impairment than those in the other 3 groups. Pear son’s product-moment correlation analyses of the alcoholics disclosed that bot h the CSCT and VCR had significant negative correlations with the MMSE score. Mo reover, the CSCT and VCR were positively correlated. Conclusions: Both physiolog ical and morphological estimates of the white matter function (CSCT and VCR) had a significant correlation with the cognitive dysfunction. Significance: The dif fuse white matter atrophy may be one of the factors causing cognitive impairment in chronic alcoholics.

中国部分地区HIV-1流行株基因型分布与母婴传播

目的 了解中国部分地区艾滋病病毒(HIV)-1主要流行区的病毒基因型分布特征及其对母婴传播的影响。方法 通过巢式聚合酶链反应对来自全国11个省(区)的HIV-1阳性病例(包括母婴病例)的gag基因和env基因的部分区域进行扩增并测序,采用DNA分析软件进行系统树和距离等分析。结果 共完成gag基因p17测序60例,env基因C2-V4区测序69例。新疆自治区和河南地区的流行株均很单一,前者为C亚型,河南省及周边地区为泰国B亚型(B'),云南地区主要为C和E亚型,而在北京和上海地区有A、B、C、E等多种不同亚型。新疆的病毒株与云南地区的C亚型极为相似,来源相似。在32对母婴病例中,主要为B和C亚型,E亚型1例,未定型2例。B亚型母亲的母婴传播率(50.0％)较明显地高于C亚型(26.7％),但差异无统计学意义。结论 中国部分地区HIV-1的亚型分布具有明显的地域特性,亚型对母婴传播的影响尚不清楚。

Beclin 1-Vps34 complex architecture： Understanding the nuts and bolts of therapeutic targets

Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin I-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.

In vitro flowering of Dendrobium candidum

Dendrobium candidum, a wild orchid species from China, normally requires three to four years of cultivation before it can produce flowers. The effects of plant hormones and polyamines on flower initiation of this species in tissue culture were investigated. The addition of spermidine, or BA, or the combination of NAA and BA to the culture medium can induce protocorms or shoots to flower within three to six months with a frequency of 31.6% -45.8%. The flowering frequency can be further increased to 82.8 % on the average by pre-treatment of protocorms in an ABA-containing medium followed by transfer onto MS medium with BA. The induction of precocious flowering de-pends on the developmental stage of the experimental materials (protocorms, shoots and plantlets) used , and usually occurs only when root formation is inhibited.

Blood:血管系统变化可能会导致阿兹海默症

随着人口老龄化的趋势不断上升，阿兹海默症的发病成为越来越重要的健康问题。最近，科学家们试图利用各种手段清除患者大脑中造成疾病的斑块，但是药物的结果往往不尽如人意。来自洛克菲勒大学的科学家们利用一项最新的技术对阿兹海默症发病的生物学机制进行了解。意想不到的是，他们发现了一种常见于血栓以及炎症反应中的血浆成分在一些患者体内也检查得到。这并不是第一次将阿兹海默症与心血管疾病联系在了一起。”有大量证据表明锻炼身体能够帮助维持血管的健康以及血流的稳定，同时也能够有效避免阿兹海默症的发生”，神经生物学家Sidney Strickland说道：”另外。我们知道阿兹海默症会影响血管系统，就像糖尿病那样，提高人们血管疾病的发生风险”。

Default polyfunctional T helper 1 response to ample signal 1 alone

CD4^(+)T cells integrate well-defined signals from the T-cell receptor(TCR)(signal 1)and a host of costimulatory molecules(signal 2)to initiate clonal expansion and differentiation into diverse functional T helper(Th)subsets.However,our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited.Using cell-based vaccines,we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II(pMHC II)complex in the absence of classic costimulation.Contrary to expectations,amplified signal 1 alone was strongly immunogenic and selectively expanded highaffinity TCR clonotypes,despite delivering intense TCR signals.In contrast to natural infection or standard vaccines,amplified signal 1,presented by a variety of professional and nonprofessional antigen-presenting cells(APCs),induced exclusively polyfunctional Th1 effector and memory cells,which protected against retroviral infection and tumor challenge,and expanded tumor-reactive CD4^(+)T cells otherwise rendered unresponsive in tumor-bearing hosts.Together,our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination.

The impact of social isolation on health and behavior in Drosophila melanogaster and beyond

Many organisms,including humans,have evolved dynamic social behaviors to promote survival.Public health studies show that isolation from social groups is a major risk factor for adverse health outcomes in humans,but these studies lack mechanistic understanding.Animal models can provide insight into the molecular and neural mechanisms underlying how social isolation impacts health through investigations using genetic,genomic,molecular,and neuroscience methods.In this review,we discuss Drosophila melanogaster as a robust genetic model for studying the effects of social isolation and for developing a mechanistic understanding of the perception of social isolation and how it impacts health.