Relationship between tRNA-derived fragments and human cancers

tRNA-derived fragments, a class of small noncoding RNAs (sncRNAs), have been identified in numerous studies in recent years. tRNA-derived fragments are classified into two main groups, including tRNA halves (tiRNAs) and tRNA-derived small RNA fragments (tRFs), according to different cleavage positions of the precursor or mature tRNAs. Instead of random tRNA degradation debris, a growing body of evidence has shown that tRNA-derived fragments are precise products of specific tRNA modifications and play important roles in biological activities, such as regulating protein translation, affecting gene expression, and altering immune signaling. Recently, the relations between tRNA-derived fragments and the occurrence of human diseases, especially cancers, have generated wide interest. It has been demonstrated that tRNA-derived fragments are involved in cancer cell proliferation, metastasis, progression and survival. In this review, we will describe the biogenesis of tRNA-derived fragments, the distinct expression and function of tRNA-derived fragments in the development of cancers, and their emerging roles as diagnostic and prognostic biomarkers and precise targets of future treatments.     

Successful avoidance of superior vena cava injury during transvenous lead extraction using a tandem femoral-superior approach

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Retinal specificity in eye fragments: investigations on the retinotectal projections of different quarter-eyes in Xenopus laevis

According to Sperry's chemoaffinity hypothesis, the projection of a small eye fragment with a reduced amount of optic fibres should be restricted to that position in the optic tectum corresponding to its own specificity. However, previous investigations on different types of quarter-eyes in Xenopus laevis have revealed that their retinal projection was always restricted to the rostral part of the tectum, no matter what the origin of the remaining retinal quadrant. To get an indication of the state of specificity in such eye fragments, we investigated by electrophysiological and histological methods several features of the retinal projections of temporoventral (TV), naso-ventral (NV) and ventral (V) quarter-eyes which referred to their positional identity. Irrespective of their different origins, the projections were always located in the rostral part of the tectum, the size of the innervated tectal area depending for all fragment types on the size of the quarter-eyes, i.e. number of optic fibres. However, quantitative analyses revealed that with increasing eye size the various fragments expand their projections preferentially into those tectal areas that match their original specificity: TV projection is more concentrated in the rostral tectum, NV eyes expand their projections mainly to the caudal tectum, and V eyes enlarge their projections equally into the medial and caudal tectum. In addition, fibre-tracing experiments with cobaltic lysine showed that, according to the different origins of the quarter-eyes, retinal fibres follow the appropriate branch of the optic tract selectively: fibres of NV and V eyes pass mainly through the medial tract, and most fibres of TV eyes innervate the rostral tectum directly from a central position between the two side branches. All these findings suggest that the different types of quarter-eyes retain their original positional identity. Thus, their rostrally located retinotectal projections are not in register with their retinal specificity. We conclude that in X. laevis local positional markers in the tectum, if present at all, do not influence the development of the retinotectal projection. Instead we suggest a concept of self-sorting of the optic fibres, which can account for the partial innervation of the rostral tectum in different types of quarter-eyes.     

β淀粉样肽25-35对原代培养的海马神经元电压门控钙通道电流的影响

目的 探讨β淀粉样肽25-35(Aβ25-35)对海马神经元电压门控的钙通道电流(VGCC)的作用.方法 应用全细胞膜片钳技术记录海马神经元上的VGCC,通过设定不同的钳制电压分别记录高电压激活的钙电流(HVA-ICa)和低电压激活的钙电流(LVA-ICa),并观察Aβ25-35对其的影响.结果 分别对原代培养的海马神经元急性胞外给予2μmol/L和10 μmol/L的凝聚态Aβ25-35,在最大激活电压下加药后ICa幅度分别是加药前的99.80%±0.02%及100.00%±1.58%,差异没有统计学意义.10 μmol/L凝聚态Aβ25-35预孵育24 h可增大ICa,对照组(未给Aβ25-35)为(24.49±4.35)pA/pF,Aβ25-35组(预孵育24 h)为(46.59±7.15)pA/pF,两组差异有统计学意义(P＜0.05);但Aβ25-35组的膜电容[(14.34±1.74)pF]与对照组[(14.44±0.97)pF]相比差异没有统计学意义.结论 急性给予凝聚态Aβ25-35对VGCC没有影响,24 h预孵育凝聚态Aβ25-35增大了VGCC,而膜电容没有改变,提示凝聚态Aβ25-35可通过对细胞膜上钙通道进行分子调控以增大VGCC.     

新型重组人源抗狂犬病毒糖蛋白单链抗体的制备及活性分析

目的：利用大肠杆菌表达新型人源抗狂犬病毒糖蛋白单链抗体ScFv,并验证其活性。方法：采用基因融合获得ScFv基因,构建重组表达质粒pET-22b（＋）-ScFv,转化大肠杆菌BL21（DE3）,经IPTG诱导获得高效表达。结果：Western印迹显示目的蛋白表达正确,表达产物以包涵体形式存在,经Ni-NTA柱纯化和体外复性,获得纯度达90%的ScFv蛋白。ELISA结果显示在PBS及人血清中ScFv的结合稳定性有所提高,流式细胞术证明目的蛋白能靶向结合狂犬病毒,通过中和效价测定实验测得ScFv的中和效价为40 U/mg。结论：成功利用原核表达系统实现了对人源抗GPRV ScFv的表达,并且具有一定的中和活性。     

Calcium transport and ATPase activity in mitochondria and fragments of sarcoplasmic reticulum of the heart and muscles of rabbits with hypercholesteremia

Keeping rabbits on a high-cholesterol diet (1 g/kg) for 3–7 months led to an increase in cholesterol concentration in the mitochondrial membranes and fragments of the sarcoplasmic reticulum (SPR) of the myocardium and skeletal muscles. Saturation of the membranes with cholesterol led to a decrease in efficiency of the Ca-pump of the SPR, as reflected in lowering of the Ca/ATP ratio and an increase in the outflow of Ca⁺⁺ from the SPR. Under these conditions the rate of accumulation of Ca⁺⁺ was higher in SPR than in the mitochondria. Activity of mitochondrial Mg⁺⁺-activated 2,4-DNP-ATPase was reduced in hypercholesteremia.Laboratory of Molecular Pathology and Biochemistry, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 292–294, March, 1980.     

Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern

Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm.     

Renal metabolism of corticosteroid hormones

Summary IK and STF from male and female rats have been used to study in vitro the renal metabolism of B. in male rat tissue four lipid soluble metabolites (I–IV) have been found, I+II being more polar and III+IV being less polar than B. I and II have been identified as 11-dehydro-20-hydroxy-B and 20-hydroxy-B. The structure of III and IV remains to be determined. Renal tissue from female rats produced predominantly III indicating sexual variations of steroid metabolism in kidneys. — The literature has been reviewed which documents that the kidneys in addition to B metabolize A, cortisol, progesterone and other corticosteroids.

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Abbreviations A Aldosterone - B Corticosterone - Alb Albumin - CS Corticosteroids - MCS/GCS Mineralo-/gluco-CS - IK Isolated (perfused) kidney - STF Suspended tubular fragments Supported by Deutsche Forschungsgemeinschaft Hi 97/16     

涎腺腺样囊性癌高、低转移细胞系基因表达谱及基质金属蛋白酶表达差异

目的筛选与涎腺腺样囊性癌转移相关的候选基因，并对其中的候选基因进行初步的验证。方法用限制片段差异显示PCR技术（restriction fragments differential display PCR, RFDD-PCR）建立涎腺腺样囊性癌高、低转移细胞株（ACC-M、ACC-2）的表达谱。对两个表达谱的片段进行比较，通过生物信息学的分析，初步筛选出候选基因。用半定量逆转录PCR技术对筛选出的基因进行初步验证。结果RFDD-PCR方法共获得5420个基因片段，其中包含12个基质金属蛋白酶（matrix metalloproteinase，MMP）基因。半定量逆转录PCR方法发现MMP2、MMP7、MMP9、MMP14、MMP15、MMP24在ACC-M和ACC-2中的表达存在明显差异。结论构建了ACC-M和ACC-2细胞株的表达谱，为寻找目的基因奠定了基础。发现MMP2、MMP7、MMP9和MMP15与涎腺腺样囊性癌的发生、发展、转移有关，不同肿瘤细胞的转移能力可能与不同的MMPs家族基因相关。     

Automatic measurement of long-term heart rate variability by implanted single-chamber devices

Heart rate variability (HRV) measurement is an established technology for the assessment of cardiac autonomic status. Recently 24 h HRV has been shown to correlate with disease severity in heart failure. This potentially makes continuous 24 h HRV measurement suitable for monitoring of heart-failure patients. Day-to-day 24 h measurement of HRV is, in principle, feasible when implemented using implanted devices (pacemakers and defibrillators) used in patients who are predominantly in the sinus rhythm. However, a number of such devices used in heart-failure patients are single-chamber devices, in which the distinction between sinus rhythm beats and ectopic beats is problematic. The study investigates whether a reasonably accurate 24 h HRV measurement can be achieved by automatic algorithms, suitable for implementation using implanted devices, without the need for identification of ectopic beats. A set of 5321 nominal 24 h Holter recordings of cardiac patients are used. Each of the recordings contains at least one ectopic beat; approximately 30% of the recordings have more than 1% of ectopic beats. Conventional 24 h measures of HRV, that is the SDNN, HRV index, and SDANN indices, are obtained from each recording after elimination of the ectopic beats and are approximated by HRV measures computed by the same formulas without exclusion of the ectopic beats. The SDANN values are also approximated by the standard deviation of 5 min medians of all RR intervals (SDMRR measure). The errors introduced by including the ectopic beats in the HRV computation were evaluated using the Bland-Altman statistics and by Cohen's kappa statistics investigating the precision of identifying patients with depressed and preserved 24 h HRV. The SDNN measure is very sensitive to the quality of the RR interval sequence and cannot be reasonably used without distinction between sinus rhythm and ectopic beats. The HRV index measure is marginally more acceptable when used without ectopic elimination. The SDANN is rather insensitive, and its replacement by SDMRR values leads to relative errors in the region of 2-5% that are almost independent of the number of ectopic beats included. Even in recordings with a substantial proportion of ectopic beats, a practically acceptable (kappa > 0.9) identification of depressed and preserved SDANN values is possible without ectopic elimination. Thus, continuous monitoring of 24 h HRV is technically feasible within implanted devices, provided the SDANN measure is monitored and either computed from the sequence of all RR intervals or, potentially preferably, replaced by the SDMRR measure.