Longitudinal patterns in an Arkansas River Valley stream: an Application of the River Continuum Concept

The River Continuum Concept (RCC) provides the framework for studying how lotic ecosystems vary from headwater streams to large rivers. The RCC was developed in streams in eastern deciduous forests of North America, but watershed characteristics and land uses differ across ecoregions, presenting unique opportunities to study how predictions of the RCC may differ across regions. Additionally, RCC predictions may vary due to the influence of fishes, but few studies have used fish taxa as a metric for evaluating predictions of the RCC. Our goal was to determine if RCC predictions for stream orders 1 through 5 were supported by primary producer, macroinvertebrate, and fish communities in Cadron Creek of the Arkansas River Valley. We sampled chlorophyll a, macroinvertebrates, and fishes at five stream reaches across a gradient of watershed size. Contrary to RCC predictions, chlorophyll a did not increase in concentration with catchment size. As the RCC predicts, fish and macroinvertebrate diversity increased with catchment size. Shredding and collecting macroinvertebrate taxa supported RCC predictions, respectively decreasing and increasing in composition as catchment area increased. Herbivorous and predaceous fish did not follow RCC predictions; however, surface-water column feeding fish were abundant at all sites as predicted. We hypothesize some predictions of the RCC were not supported in headwater reaches of this system due to regional differences in watershed characteristics and altered resource availability due to land use surrounding sampling sites

Glutathione Metabolism in Renal Cell Carcinoma Progression and Implications for Therapies

A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The proposed mechanism for increased GSH levels is to counteract damaging ROS to sustain the viability and growth of the malignancy. Here, we review the current knowledge about the three main RCC subtypes, namely clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism. A further discussion addresses the question of how the manipulation of GSH levels can be exploited as a potential treatment strategy for RCC

CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma.

BackgroundCytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.MethodsExpression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses.ResultsFirst, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples.ConclusionsCYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC

Renal Cell Carcinoma Presenting as Metastasis to Scrotum and Spermatic Cord

Unusual site metastasis as presenting complaint of renal cell carcinoma (RCC) has been reported previously in literature. RCC is a notorious tumor with unpredictable behavior. We present a case of RCC who presented with scrotal mass and on subsequent investigation was found to have metastasis to scrotum and spermatic cord. Both testes were normal with no evidence of metastasis

Analytical Model of TCP Relentless Congestion Control

We introduce a model of the Relentless Congestion Control proposed by Matt Mathis. Relentless Congestion Control (RCC) is a modification of the AIMD (Additive Increase Multiplicative Decrease) congestion control which consists in decreasing the TCP congestion window by the number of lost segments instead of halving it. Despite some on-going discussions at the ICCRG IRTF-group, this congestion control has, to the best of our knowledge, never been modeled. In this paper, we provide an analytical model of this novel congestion control and propose an implementation of RCC for the commonly-used network simulator ns-2. We also improve RCC with the addition of a loss retransmission detection scheme (based on SACK+) to prevent RTO caused by a loss of a retransmission and called this new version RCC+. The proposed models describe both the original RCC algorithm and RCC+ improvement and would allow to better assess the impact of this new congestion control scheme over the network traffic.Comment: Extended version of the one presented at 6th International Workshop on Verification and Evaluation of Computer and Communication Systems (Vecos 2012

UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gen