Dopamine Gates Visual Signals in Monkey Prefrontal Cortex Neurons

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Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 10⁹/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 10⁹/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.     

DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR.     

Limitations of Chromogranin A in clinical practice

Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN.     

Cytological features of chronic follicular cervicitis in liquid-based specimens: a potential diagnostic pitfall

A review of negative split-sample cervical cytology cases revealed five cases reported as chronic follicular cervicitis. These cases showed characteristic morphological features in conventional smears with lymphoid cells, plasma cells and tingible body macrophages smeared across the slides. This contrasts with the presentation of ThinPrep samples (Cytic Corporation, Boxburgh, MA, USA), where cells were observed aggregated in clumps. The different presentation noted in liquid-based samples may require careful microscopic evaluation at high-power magnification.     

Fence-Line Contact Between Wild and Farmed Cervids in Colorado: Potential for Disease Transmission

Abstract: Direct and indirect contact between wild and farmed cervids along perimeter fences may play a role in transmission of diseases like chronic wasting disease (CWD), but no studies have quantified such interactions. At 9 high-fenced commercial elk (Cervus elaphus) farms in Colorado, USA, during October 2003 to January 2005, we used animal-activated video to estimate rates of fence-line use by wild cervids, rates of direct contact between farmed and wild cervids, and probability of direct contact when wild cervids were present. We recorded 8-fold-more wild elk per unit time than mule deer (Odocoileus hemionus) at fence lines. Depending on site, we recorded 0.66 to 46.90 wild elk per 1,000 hours of camera monitoring. We documented 77 interactions between wild and farmed elk involving naso-oral contact and no contact between wild mule deer and farmed elk. Rate of direct contact ranged from 0.00 to 1.92 direct contacts per 1,000 hours of camera monitoring among sites. Given recorded presence of wild elk, estimated probability of observing direct contact during a 2-minute video recording ranged from 0.00 to 0.11 among sites. Risk of direct contact was about 3.5 times greater for single woven-wire fence compared with offset electric fence attached to a single woven-wire fence. We observed no direct contact through double woven-wire fences. Because little is currently known about infection rates associated with infection mechanisms, we cannot infer a level of CWD infection risk from our results, but some form of double fencing should reduce potential for direct and indirect transmission of disease into or out of elk farms.     

The combined effects of chlorine and ammonia on litter breakdown in outdoor experimental streams

The response of Potamogeton crispus L. breakdown to controlled doses of different levels of chlorine and chlorine + ammonia was investigated over two years in outdoor experimental streams. In 1985, downstream riffles of 2 streams were dosed (observed in-stream concentrations) at ca. 10 μg/L Total Residual Chlorine (TRC), one stream at 64 μg/L TRC and one stream at 230 μg/L TRC. Two control streams were not dosed and the upstream riffles of each stream served as within stream controls. In 1986, the downstream riffle of one stream was dosed at 70 μg/L TRC and a second stream was dosed at 200 μg/L TRC. Four streams were also dosed with 2.5 mg/L NH₃-N: one stream with no chlorine, one stream with ca. 10 μg/L TRC, one with 56 μg/L TRC, and one with 150 μg/L TRC. A seventh stream was dosed for 2 h at 2000 μg/L TRC and 2.5 mg/L ammonia and then allowed to recover (recovery stream). Each year, litter decomposition (degree day k values) was measured during two 35 day trials (Jun–Jul and Aug–Sep). In 1985, when streams were dosed with chlorine alone, decomposition was significantly reduced with the high (230 μg/L TRC) chlorine dose. Downstream decomposition was 27% (Jun–Jul) and 59% (Aug–Sep) of the upstream (control) rate. No other chlorine effects were found during this period. In Jun–Jul 1986, there was significantly lower decomposition in the downstream dosed sites of the 200 μg/L TRC alone stream, the 146 μg/L TRC + ammonia stream and the recovery stream; downstream decay rates were (respectively) 56%, 42% and 64% of the upstream control sites. No other up-down pairs were different in July 1986. In Aug–Sep, all three streams with chlorine + ammonia (6, 56 and 146 μg/L TRC + 2,5 mg/L ammonia) and the 70 μg/L TRC alone stream had significantly lower decomposition rates in the downstream dosed sites. For these streams, downstream decay rates ranged from 46% (high chlorine + ammonia) to 73% (low chlorine + ammonia) of the upstream control rates. No other up-down pairs were different during this trial. Up and downstream sites of the stream dosed with 2.5 mg/L ammonia alone were nearly identical for both trials (< 3% difference). These results indicate that TRC at less than 250 μg/L can significantly reduce litter decomposition and strongly suggest that addition of ammonia to chlorinated water can increase the toxic effect of chlorine. currently at the Department of Fisheries and Wildlife currently at the Department of Fisheries and Wildlife     

Midbrain auditory sensitivity in the spring peeper (Pseudacris crucifer): correlations with behavioral studies

1. We derived audiograms from recordings of multiunit activity in the torus semicircularis of 10 males and 6 females of the spring peeper from central Missouri, USA. We used free-field stimulation with tone bursts that had temporal properties similar to typical advertisement calls and that ranged in frequency from 500-6000 Hz. 2. Audiograms from different electrode positions in the same animal had the same general shape. There was no evidence of tonotopy. 3. Audiograms showed two regions of maximal sensitivity: a low-frequency region (500-700 Hz); and a high-frequency region (2000-4000 Hz). Absolute thresholds and frequencies of maximum sensitivity varied considerably from individual to individual. 4. Audiograms derived from all individuals of each sex indicated that in the high-frequency region, corresponding to the frequency range of advertisement calls, males were more broadly tuned than females. However, tuning in both sexes was relatively weak, and the data predict relatively little selectivity in behavioral responses over the entire range of variation in frequency of the advertisement call in local populations. 5. The results are discussed in terms of behavioral experiments with both males and females from the same populations in central Missouri. We show that merely summarizing the audiograms based on estimates of minimum thresholds of a population or species may mask significant individual differences in tuning. Moreover, most behavioral studies are conducted at playback levels considerably above threshold. For these reasons, behavioral selectivity is not always accurately predicted by inspection of "average" audiograms.     

血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动脉收缩中的作用

以黄嘌岭(X)-黄嘌呤氧化酶(XO)系统产生氧自由基,应用微量生物测定法观察慢性缺氧(5000m,10d)对大鼠氧自由基所致肺内动脉收缩的影响及内皮舒张因子(EDRF)在其中的作用。慢性缺氧大鼠有内皮的肺内动脉环对氧自由基的收缩反应较正常环境中的对照动物明显增强,加入EDRF灭活剂还原型血红蛋白(RHb)后更加显著;而加入超氧化物歧化酶(铜锌SOD)后则减弱,甚至消除。反之,不论加入RHb或SOD对氧自由基所致去内皮肺内动脉环的收缩反应均无明显影响。上述结果表明慢性缺氧引起肺内动脉收缩增强与EDRF有密切关系:慢性缺氧可能使EDRF的作用减弱,肺内动脉对氧自由基的反应性增强。表示EDRF及其与氧自由基的关系在慢性缺氧性肺动脉高压的形成中可能具有十分重要的意义。