Characterization of sugar diversity in floral and extra-floral nectar from the Coastal Coral Tree(Erythrina caffra Thunb.)in Southern California

The Coastal Coral Tree (Erythrina caffra Thunb.) produces floral nectar (FN) that serves to attract pollinating insects, but also secretes nectar from extra-floral (EFN) glands that serves to attract predatory insects, such as ants. While studies on myrmecophytes (i.e. specialized plants that attract and interact with ants) have primarily focused on interspecific evaluations of EFN chemistry, the Coastal Coral tree offers an opportunity to contrast intraspecific nectar chemistry with differing evolutionary and ecological functions. We hypothesized that the richness of (molecular) sugar species, relative concentrations, and diversity of sugars in FN and foliar EFN would diverge due to differences in the ecological role of the two types of nectar. High performance liquid chromatography with refractive index detection was used to identify the richness of sugar species (based on retention time), measure the relative concentrations, and evaluate the diversity of sugars in FN and foliar EFN secretions. We detected sugar species unique to each gland type and reported significant differences in the relative concentration of one sugar species common to both gland types. While the mean diversity index of sugars was similar for both gland types, the diversity of foliar EFN sugars was significantly more variable than that of FN sugars. The composition of FN showed little variation, and was reflective of its fundamental role in plant reproduction. Foliar EFN, however, demonstrated the variability expected of a context-dependent myrmecophyte that interacts with a facultative ant species assemblage across a mosaic of abiotic and biotic conditions.

Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL;p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL;p-value 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

Separation of NMR Spin-Spin Multi-relaxation Process and Imaging-Phantom Investigation

A physical-mathematical model was proposed for the NMR relaxation processes,which can automatically identify the multi-relaxation process;the automatic separation of the spin-spin relaxation processes of water sample in a home made phantom was carried out;two kinds of proton pure spin-spin relaxation time images and two kinds of proton computed pure density images have been obtained on a 1.0T supercondlrtive magnet MR-Scanner.

Dexmedetomidine Causes Increased Hypotension in Older Adults When Used for Cataract Surgery Compared to Propofol

Purpose: This study evaluated the hemodynamic effects, suitability and safety of dexmedetomidine (DEX) compared with propofol (PRO) in older adults having outpatient cataract surgery under monitored anesthesia care. The patients, surgeon and the anesthesia staff evaluated satisfaction for both drugs.Method: This prospective, single blind, randomized study was conducted using forty-seven patients ≥55 years old undergoing cataract surgery. The two patient groups received either i.v. dexmedetomidine 1 μg/kg over 10 min;followed by maintenance i.v. infusion at 0.2 -0.7 μg/kg/hr (DEX group, N = 24), or propofol infused between 25 -120 μg/kg/min (PRO group, N = 23). Both agents were titrated to patient comfort. Results: Patients’ mean arterial pressures (SEM) at baseline were 104.7 (2.6) and 107.5 (2.7) mmHg for the DEX and PRO groups, respectively (p = 0.45). At discharge the pressures were 78.1 (2.5) and 98.1 (2.6) mmHg in DEX and PRO groups, respectively (p 0.05). Patients’ heart rates (SEM) at baseline were 74.8 (3.0) for the DEX group and 73.2 (2.8) bpm for the PRO groups (p = 0.71). At the time of discharge following surgery, the mean heart rate for the DEX group was 61.5 (2.2) bpm vs. 69.1 (2.3) bpm (p 0.05) for the PRO group. Three patients in the DEX group developed complications precluding discharge or requiring readmission while none of the patience in the PRO group had complications (p = 0.08). Patient and surgeon satisfaction scores were similar between the groups. Conclusion: Dexmedetomidine is a less suitable sedative compared with propofol use in older patients undergoing cataract surgery due to the decrease in hemodynamic parameters and noted increases in complication rates.

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

AIM:To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy(EGD) over the past decade.METHODS:EGDs with the indication of dysphagia at an urban,university medical center in 1999,2004 and 2009 were retrospectively identified from the electronic medical record.The entire patient chart,including EGD,pathology,manometry,radiographic and clinician reports,was reviewed for demographic and clinical data and to determine the etiology of dysphagia.The number of EGDs in which an esophageal biopsy was performed was also noted.Gastroesophageal reflux disease(GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition(PPI).Cases of eosinophilic esophagitis(EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field.PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008.Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999,2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS:A total of 1371 cases(mean age 54 years,43% male) met pre-specified inclusion criteria with 191,504 and 675 cases in 1999,2004 and 2009,respectively.Patients were older in 2004 compared to 2009(mean ± SD,54.0 ± 15.7 years vs 52.3 ± 16.8 years,P = 0.02) and there were more males in 1999 compared to 2004(57.5% vs 40.8%,P = 0.005).Overall,GERD(27.6%) and EoE(7.7%) were the most common identifiable causes of dysphagia.An unspecified diagnosis accounted for 21% of overall cases.There were no significant differences in the relative prevalence of achalasia or other motility disorders,peptic stricture,Schatzki's ring,esophageal cancer or unspecified diagnoses over the 10-year time period.There was,however,a decrease in the relative prevalence of GERD(39.3% vs 24.1%,P < 0.001) and increases in the relative prevalence of EoE(1.6% vs 11.2%,P < 0.001) and oropharyngeal disorders(1.6% vs 4.2%,P = 0.02) from 1999 to 2009.Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009(5.4% vs 11.6%,P < 0.001),but not between 1999 and 2004(1.6% P 5.4%,P = 0.21).On the other hand,the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004(39.3% vs 27.7%,P = 0.006),but not between 2004 and 2009(27.7% vs 24.1%,P = 0.36).There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009(36.7% vs 68.7%,P < 0.001) as well as between 2004 and 2009(37.5% vs 68.7%,P < 0.001).While total EGD volume did increase over the 10-year time period,the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION:EoE has emerged as a dominant cause of dysphagia in adults.Whether this was due to a rise in disease incidence or increased recognition is unclear.

A lead role for a“secondary”axonal injury response

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

New evidence-based adaptive clinical trial methods for optimally integrating predictive biomarkers into oncology clinical development programs

Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict.

Repeated operations for infiltrative low - grade gliomas without intervening therapy.

OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.

Laser capture microdissection enables cellular and molecular studies of tooth root development

Epithelial-mesenchymal interactions（EMIs） are critical for tooth development.Molecular mechanisms mediating these interactions in root formation is not well understood.Laser capture microdissection（LCM） and subsequent microarray analyses enable large scale in situ molecular and cellular studies of root formation but to date have been hindered by technical challenges of gaining intact histological sections of non-decalcified mineralized teeth or jaws with well-preserved RNA.Here,we describe a new method to overcome this obstacle that permits LCM of dental epithelia,adjacent mesenchyme,odontoblasts and cementoblasts from mouse incisors and molars during root development.Using this method,we obtained RNA samples of high quality and successfully performed microarray analyses.Robust differences in gene expression,as well as genes not previously associated with root formation,were identified.Comparison of gene expression data from microarray with real-time reverse transcriptase polymerase chain reaction（RT-PCR） supported our findings.These genes include known markers of dental epithelia,mesenchyme,cementoblasts and odontoblasts,as well as novel genes such as those in the fibulin family.In conclusion,our new approach in tissue preparation enables LCM collection of intact cells with well-preserved RNA allowing subsequent gene expression analyses using microarray and RT-PCR to define key regulators of tooth root development.

Aberrant oligodendroglial-vascular interactions disrupt the blood brain barrier triggering CNS inflammation

Disruption of the blood brain barrier(BBB)is critical to initiation and perpetuation of disease in multiple sclerosis(MS).We report here an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent demyelinating injury.We find perivascular clustering of oligodendrocyte precursor cells(OPCs)in certain active MS lesions,representing an inability to properly detach from vessels following perivascular migration.Perivascular OPCs can themselves disrupt the BBB,interfering with astrocyte end feet and endothelial tight junction integrity,resulting in altered vascular permeability and an associated CNS inflammation.

超耐热酸性α-淀粉酶基因的克隆及其在酵母细胞中的表达

用PCR方法扩增来源于极端嗜热厌氧古菌Pyrococcus furiosus中的超耐热酸性α-淀粉酶的结构基因，将该结构基因引入载体pPIC9K中，将重组质粒pPIC9K—Amy转化大肠杆菌DH5α细胞，测序结果表明，克隆到的α-淀粉酶结构基因为1305bp，其编码的成熟肽为435个氨基酸。将正确构建的重组质粒转化毕赤酵母GS115细胞，得到酵母工程菌株。在酵母α-Factor及AOX1基因启动子和终止信号的调控下，超耐热酸性α-淀粉酶在甲醇酵母中大量表达并分泌到胞外，该酶的表达受甲醇的严格调控和诱导，随着诱导培养时间的增加，在培养基上清液中的单位体积酶活力相应上升，在诱导培养7d后酶活力达到最大值。该酶最适反应温度为90-100℃，最适反应pH值为4．5—5．5。该酶具有非常好的温度稳定性，在100℃条件下热处理5h。仍具有60％以上的酶活力。该酶的这些优点使其非常适于在工业生产上应用。

应用虚拟筛选方法寻找链阳霉素A乙酰转移酶抑制剂(英文)

维吉尼亚霉素乙酰转移酶D(VatD)通过灭活链阳霉素A而在链阳霉素耐药性的产生中起重要作用。本研究采用虚拟筛选技术寻找VatD的抑制剂,此VatD抑制剂可以和链阳霉素联合使用,从而提供新的治疗耐药菌感染的方法。作者首次应用基于结构的虚拟筛选方法(分子对接)从含300000化合物的商业化数据库中筛选对抗VatD底物结合位点的化合物,从200个评分最高的化合物中选取26个测定对VatD酶活性的抑制作用。将构建的质粒pRSETB/vatD转染宿主细胞E.coli(TrxB)用于过表达,纯化的VatD对维吉尼亚霉素M1表现乙酰转移酶活性。26个化合物中有3个对VatD表现抑制作用,IC50分别为168.6,91.0和55.2μmol.L-1。其他化合物在反应体系中不溶解和/或对酶活性的抑制作用很小(IC50>200μmol.L-1)。本文首次设计VatD的小分子化合物抑制剂,发现了3个有活性的化合物,希望其可作为先导化合物进一步发展为新的对抗链阳霉素耐药性的药物。

重组超耐热酸性α-淀粉酶的分离纯化及其性质研究

基因工程菌所产生的重组超耐热酸性α-淀粉酶,通过超滤浓缩、脱盐和聚丙烯酰胺垂直板凝胶电泳进行纯化,得到电泳纯的超耐热酸性α-淀粉酶,纯化倍数为11.7,活力回收率为29.8%。用SDSPAGE测得该酶的分子量为55kD,酶的等电点pI(室温)为5.0,以可溶性淀粉为底物的Km值为1.12gL,用硫酸酚法测得其含糖量为15.4%。该酶的最适反应温度为95℃,最适反应pH值为4.5。在pH4.0～7.0室温放置48h酶活没有变化,110℃保温1h残留60%活力。Cr3+、Fe2+、Cu2+抑制酶的活性,Ca2+对酶活无影响。EDTA和DTT对酶的活性无影响。

Cementomimetics——constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides

Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides （HABPs） previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 （ADP5） was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.

Regulation of drug metabolism and toxicity by multiple factors of genetics,epigenetics,lncRNAs,gut microbiota,and diseases:a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations(MDO)

Variations in drug metabolism may alter drug efficacy and cause toxicity;better understanding of the mechanisms and risks shall help to practice precision medicine.At the 21 st International Symposium on Microsomes and Drug Oxidations held in Davis,California,USA,in October 2-6,2016,a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity,and discussed potential implications to personalized medications.A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption,distribution,metabolism,and excretion(ADME) and drug response.Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented.In addition,the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed.These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

颅骨发育生物学

对于艺术家,面貌是灵魂的镜子;对于生物学家,面貌反映了显著的结构多样性——试想一下斗牛犬或猎犬与加拉帕戈斯云雀间的区别。面部骨骼形态的巨大差异是如何产生的?它的发育机制与身体其他部位的骨骼发育机制相同吗?答案就在于产生神经嵴细胞、控制其迁移并指导其向软骨和骨分化的分子机制。“面貌究竟是什么?是相片?是妆容?抑或是这个或那个画家绘制的肖像?…难道每个人不是以自己特别的方式看自己的吗?其实,畸形是不存在的。”PabloPicasso[1]语。

Incidence of Acute Disseminated Encephalomyelitis in China: First National Survey

In this issue,the publication of Xiu et al.[1]provides novel and important information on the incidence and outcomes of acute disseminated encephalomyelitis(ADEM)nationwide in China.The study analyzed information from 2,976 cases of ADEM that occurred over a 3-year period,and confirms ADEM is much less common than diseases such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorders.

同时性传入刺激引起大鼠体感皮层的功能重组

将大鼠的一对面部须毛粘合以便提供对须毛的同时刺激,4～8d后利用微电极在初级体感皮层测定各须毛的代表区,发现粘合须毛与正常对照大鼠须毛及自身的未粘合须毛相比,其皮层代表区有了显著的改变,主要是该对须毛代表区会聚面积的扩大。这一发现支持过去的假设;皮层代表区及感受野的形成是由输入的相对强度及输入的时间结构决定的。

Molecular determinants for the layering and coarsening of biological condensates

Many membraneless organelles,or biological condensates,form through phase separation,and play key roles in signal sensing and transcriptional regulation.While the functional importance of these condensates has inspired many studies to characterize their stability and spatial organization,the underlying principles that dictate these emergent properties are still being uncovered.In this review,we examine recent work on biological condensates,especially multicomponent systems.We focus on connecting molecular factors such as binding energy,valency,and stoichiometry with the interfacial tension,explaining the nontrivial interior organization in many condensates.We further discuss mechanisms that arrest condensate coalescence by lowering the surface tension or introducing kinetic barriers to stabilize the multidroplet state.

尿道下裂修补术后产生幻觉

The authors report a case of a 4-year-old child who developed hallucinations after hypospadias repair.He was brought to the emergency department the mornin g after outpatient surgery where the diagnosis of central anticholinergic syndro me was made.We review oxybutynin overdose and the importance of providing clear instruction to parents and caregivers about the administration of medications.