Cell cycle related proteins in hyperplasia of usual type in breast specimens of patients with and without breast cancer

Background  

Hyperplasia of usual type (HUT) is a common proliferative lesion associated with a slight elevated risk for subsequent development of breast cancer. Cell cycle-related proteins would be helpful to determine the putative role of these markers in the process of mammary carcinogenesis. The aim of this study was to analyze the expression of cell cycle related proteins in HUT of breast specimens of patients with and without breast cancer, and compare this expression with areas of invasive carcinomas.     

Effect of aging on renal blood flow velocity during static exercise

During exercise, activation of the sympathetic nervous system causes reflex renal vasoconstriction. The effects of aging on this reflex are poorly understood. This study evaluated the effects of age on renal vasoconstrictor responses to handgrip. Seven older (65 +/- 9 yr) and nine younger (25 +/- 2 yr) subjects were studied. Beat-by-beat analyses of changes in renal blood flow velocity (RBV; duplex ultrasound) were performed during two handgrip paradigms. Arterial blood pressure (BP) and heart rate were also measured, and an index of renal vascular resistance (RVR) was calculated (BP/RBV). In protocol 1, fatiguing handgrip [40% of maximal voluntary contraction (MVC)] caused a greater increase in RVR in the older subjects (old 90% +/- 15 increase, young 52% +/- 4 increase; P = 0.03). During posthandgrip circulatory arrest (isolates muscle metaboreflex), the increases in RVR were only approximately 1/2 of the increase seen at end grip. In protocol 2, 15-s bouts of handgrip at graded intensities led to increases in RVR in both subject groups. This effect was not seen until 50% MVC workload (P < 0.05). RVR responses occurred early and were greater in older than in younger subjects at 50% MVC (32 +/- 6% vs. 16 +/- 5%; P = 0.02) and 70% MVC (39 +/- 11% vs. 24 +/- 8%; P = 0.02). Static exercise-induced renal vasoconstriction is enhanced with aging. Because the characteristics of this response suggest a predominant role for mechanoreceptor engagement, we hypothesize that mechanoreceptor responses are augmented with aging.     

Renal blood flow in heart failure patients during exercise

During exercise, reflex renal vasoconstriction maintains blood pressure and helps in redistributing blood flow to the contracting muscle. Exercise intolerance in heart failure (HF) is thought to involve diminished perfusion in active muscle. We studied the temporal relationship between static handgrip (HG) and renal blood flow velocity (RBV; duplex ultrasound) in 10 HF and in 9 matched controls during 3 muscle contraction paradigms. Fatiguing HG (protocol 1) at 40% of maximum voluntary contraction led to a greater reduction in RBV in HF compared with controls (group main effect: P <0.05). The reduction in RBV early in HG tended to be more prominent during the early phases of protocol 1. Similar RBV was observed in the two groups during post-HG circulatory arrest (isolating muscle metaboreflex). Short bouts (15 s) of HG at graded intensities (protocol 2; engages muscle mechanoreflex and/or central command) led to greater reductions in RBV in HF than controls (P <0.03). Protocol 3, voluntary and involuntary biceps contraction (eliminates central command), led to similar increases in renal vasoconstriction in HF (n=4). Greater reductions in RBV were found in HF than in controls during the early phases of exercise. This effect was not likely due to a metaboreflex or central command. Thus our data suggest that muscle mechanoreflex activity is enhanced in HF and serves to vigorously vasoconstrict the kidney. We believe this compensatory mechanism helps preserve blood flow to exercising muscle in HF.     

Attenuated sympathetic nerve responses after 24 hours of bed rest

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.     

不同施肥处理对‘赤霞珠’葡萄根际土壤养分和真菌群落的影响

【背景】宁夏贺兰山东麓葡萄产区忽视有机肥的施用,果树枝条焚烧污染环境,造成土壤养分缺失,土壤质量下降。【目的】为解决长期施用化肥对土壤造成的一系列问题,通过大田试验研究施肥及喷施不同浓度菌剂对土壤理化性质、真菌群落组成及多样性的影响,为酿酒葡萄可持续健康发展提供科学依据。【方法】以‘赤霞珠’葡萄根际土壤为试验对象,采用Illumina MiSeq高通量测序技术,测定并分析根际土壤理化性质、真菌群落组成和多样性在7个处理[常规施肥(CK)、蚯蚓粪+腐熟枝条+100倍菌剂(T1)、蚯蚓粪+腐熟枝条+200倍菌剂(T2)、蚯蚓粪+腐熟枝条+300倍菌剂(T3)、蚯蚓粪+未腐熟枝条+100倍菌剂(A1)、蚯蚓粪+未腐熟枝条+200倍菌剂(A2)和蚯蚓粪+未腐熟枝条+300倍菌剂(A3)]的变化。【结果】相较于CK,葡萄根际土壤理化性质差异明显,施肥处理增加了土壤有机质含量,土壤pH含量无明显变化,改良了土壤结构,活化了土壤有效养分。相较于CK,各处理真菌分类操作单元(operational taxonomic unit, OTU)数均降低,A2处理根际土壤丰富度及多样性均显著增加。真菌群落组成...     

Microtubules and cyclic amp in human leukocytes: on the order of things

We have shown previously that the β-adrenergic agonist isoproterenol (2μM) and the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) produce a much greater increase in cyclic AMP in human leukocytes that have been pretreated with colchicine (or with other agents that affect microtubule assembly) than in control leukocytes. The effects of colchicines were both time- and dose-dependant. These and other data suggested that the generation of cyclic AMP is normally restricted by an intact system of cytoplasmic microtubules. If so, then the same time and dose dependencies might apply to other colchicines-induced changes in leukocyte function. We have now assayed the distribution of concanavalin A (Con A)-receptor complexes on the leukocyte membrane, taking into account that leukocytes competent to assemble microtubules show a uniform distribution of surface- bound Con A whereas microtubule-deficient cells accumulate Con A in surface caps. We have found that the effect of colchicine on capping is also both time- and dose dependent, and that the dose-response relationships conform to those required to increase cyclic AMP levels. These findings provide further evidence that both colchicine-induced Con-A capping and colchicine- induced cyclic AMP generation depend upon the relaxation of constraints normally imposed by cytoplasmic microtubules upon the plasma membrane, which limit, respectively, lateral mobility of the lectin-receptor complexes, and expression of hormone-sensitive adenylate cyclase. Moreover, colchicine-induced Con-A cap formation is not affected even by very large changes in leukocyte cyclic AMP levels. Thus, elevated cyclic AMP levels do not appear to promote the dissolution of microtubules; rather, the dissolution of microtubules permits the generation of increased amounts of cyclic AMP.     

A modular treatment of molecular traffic through the active site of cholinesterase

We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products.     

Magnetic stimulation of the human motor cortex evokes skin sympathetic nerve activity.

Single-pulse magnetic coil stimulation (Cadwell MES 10) over the cranium induces without pain an electric pulse in the underlying cerebral cortex. Stimulation over the motor cortex can elicit a muscle twitch. In 10 subjects, we tested whether motor cortical stimulation could also elicit skin sympathetic nerve activity (SSNA; n = 8) and muscle sympathetic nerve activity (MSNA; n = 5) in the peroneal nerve. Focal motor cortical stimulation predictably elicited bursts of SSNA but not MSNA; with successive stimuli, the SSNA responses did not readily extinguish (94% of discharges to the motor cortex evoked SSNA responses) and had predictable latencies [739 +/- 33 (SE) to 895 +/- 13 ms]. The SSNA responses were similar after stimulation of dominant and nondominant sides. Focal stimulation posterior to the motor cortex elicited extinguishable SSNA responses. In three of six subjects, anterior cortical stimulation evoked SSNA responses similar to those seen with motor cortex stimulation but without detectable movement; in the other subjects, anterior stimulation evoked less SSNA discharge than that seen with motor cortex stimulation. Contrasting with motor cortical stimulation, evoked SSNA responses were more readily extinguished with 1) peripheral stimulation that directly elicited forearm muscle activation accompanied by electromyograms similar to those with motor cortical stimulation; 2) auditory stimulation by the click of the energized coil when off the head; and 3) in preliminary experiments, finger afferent stimulation sufficient to cause tingling. Our findings are consistent with the hypothesis that motor cortex stimulation can cause activation of both alpha-motoneurons and SSNA.