Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in prostate cancer cells

Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in arachidonate metabolism and the conversion of arachidonic acid (AA) to prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated that the COX2 protein is up-regulated in prostate cancer cells after irradiation and that this results in elevated levels of PGE(2). In the present study, we further investigated whether radiation-induced COX2 up-regulation is dependent on the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS), and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to modulate the cellular redox status. BSO decreased the cellular GSH level and increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha-lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up-regulation is secondary to the production of ROS. The relative increases in COX2 expression and PGE(2) production induced by radiation and H(2)O(2) were even greater when PC-3 cells were pretreated with BSO. When the cells were pretreated with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2 up-regulation and PGE(2) production were markedly inhibited. These results demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is modulated by the cellular redox status. Radiation-induced increases in ROS levels contribute to the adaptive response of PC-3 cells, resulting in elevated levels of COX2.     

Quantitative imaging of mitochondrial and cytosolic free zinc levels in an in vitro model of ischemia/reperfusion

The role of zinc ion in cytotoxicity following ischemic stroke, prolonged status epilepticus, and traumatic brain injury remains controversial, but likely is the result of mitochondrial dysfunction. We describe an excitation ratiometric fluorescence biosensor based on human carbonic anhydrase II variants expressed in the mitochondrial matrix, permitting free zinc levels to be quantitatively imaged therein. We observed an average mitochondrial matrix free zinc concentration of 0.2 pM in the PC12 rat pheochromacytoma cell culture line. Cytoplasmic and mitochondrial free zinc levels were imaged in a cellular oxygen glucose deprivation (OGD) model of ischemia/reperfusion. We observed a significant increase in mitochondrial zinc 1 h following 3 h OGD, at a time point when cytosolic zinc levels were depressed. Following the increase, mitochondrial zinc levels returned to physiological levels, while cytosolic zinc increased gradually over a 24 h time period in viable cells. The increase in intramitochondrial zinc observed during reoxygenation after OGD may contribute to bioenergetic dysfunction and cell death that occurs with both in vitro and in vivo models of reperfusion.     

Reconfigurable Boolean Logic Using Magnetic Single-Electron Transistors

We propose a novel hybrid single-electron device for reprogrammable low-power logic operations, the magnetic single-electron transistor (MSET). The device consists of an aluminium single-electron transistor with a GaMnAs magnetic back-gate. Changing between different logic gate functions is realized by reorienting the magnetic moments of the magnetic layer, which induces a voltage shift on the Coulomb blockade oscillations of the MSET. We show that we can arbitrarily reprogram the function of the device from an n-type SET for in-plane magnetization of the GaMnAs layer to p-type SET for out-of-plane magnetization orientation. Moreover, we demonstrate a set of reprogrammable Boolean gates and its logical complement at the single device level. Finally, we propose two sets of reconfigurable binary gates using combinations of two MSETs in a pull-down network.     

Improving breeding efficiency in potato using molecular and quantitative genetics

Key message

Potatoes are highly heterozygous and the conventional breeding of superior germplasm is challenging, but use of a combination of MAS and EBVs can accelerate genetic gain.

Abstract

Cultivated potatoes are highly heterozygous due to their outbreeding nature, and suffer acute inbreeding depression. Modern potato cultivars also exhibit tetrasomic inheritance. Due to this genetic heterogeneity, the large number of target traits and the specific requirements of commercial cultivars, potato breeding is challenging. A conventional breeding strategy applies phenotypic recurrent selection over a number of generations, a process which can take over 10 years. Recently, major advances in genetics and molecular biology have provided breeders with molecular tools to accelerate gains for some traits. Marker-assisted selection (MAS) can be effectively used for the identification of major genes and quantitative trait loci that exhibit large effects. There are also a number of complex traits of interest, such as yield, that are influenced by a large number of genes of individual small effect where MAS will be difficult to deploy. Progeny testing and the use of pedigree in the analysis can provide effective identification of the superior genetic factors that underpin these complex traits. Recently, it has been shown that estimated breeding values (EBVs) can be developed for complex potato traits. Using a combination of MAS and EBVs for simple and complex traits can lead to a significant reduction in the length of the breeding cycle for the identification of superior germplasm.     

Impact of participant and interventionist race concordance on weight loss outcomes

Objective:

We have previously shown that racial composition of behavioral intervention groups does not affect achieved weight loss. However, it is unclear if the race of the interventionist affects intervention outcomes. The objective of this analysis is to estimate the impact of race concordance between participant and interventionist on weight change in the initial weight loss phase (phase I) of the Weight Loss Maintenance trial (WLM).

Design and Methods:

A total of 1,685 overweight or obese adults (BMI 25‐45 kg/m²) who were taking medication for hypertension and/or dyslipidemia participated in phase I of the WLM trial. All participants received a 6‐month intensive behavioral intervention in groups of 15‐20 facilitated by a trained interventionist. The main outcome is change in weight at 6 months.

Results:

Participants were on average 55 years of age, 67% female and 44% African American (AA). Three of seventeen interventionists were AA, 14 were non‐AA. Seventy‐three percent of participants shared race concordance with the interventionist. There was a small but statistically significant difference in weight change of participants who were the same race as the interventionist (?5.84 kg, s.e. 0.17) as compared with those who were not race concordant (?5.04 kg, s.e. 0.33), a difference of 0.8 kg, (P = 0.04). The impact of concordance on weight change differed by race (i.e., interaction of race and concordance was significant, P = 0.02).

Conclusions:

In a post hoc analysis of a group‐based behavioral intervention, race concordance for non‐AA participants was associated with slightly greater weight loss. Race concordance was not associated with weight loss for AA participants.

     

Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference

Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle.     

A framework to evaluate whether to pool or separate behaviors in a multilayer network

A multilayer network approach combines different network layers,which are connected by interlayer edges,to create a single mathematical object.These networks can contain a variety of information types and represent different aspects of a system.However,the process for selecting which information to include is not always straightforward.Using data on 2 agonistic behaviors in a captive population of monk parakeets(Myiopsitta monachus),we developed a framework for investigating how pooling or splitting behaviors at the scale of dyadic relationships(between 2 individuals)affects individual-and group-level social properties.We designed 2 reference models to test whether randomizing the number of interactions across behavior types results in similar structural patterns as the observed data.Although the behaviors were correlated,the first reference model suggests that the 2 behaviors convey different information about some social properties and should therefore not be pooled.However,once we controlled for data sparsity,we found that the observed measures corresponded with those from the second reference model.Hence,our initial result may have been due to the unequal frequencies of each behavior.Overall,our findings support pooling the 2 behaviors.Awareness of how selected measurements can be affected by data properties is warranted,but nonetheless our framework disentangles these efforts and as a result can be used for myriad types of behaviors and questions.This framework will help researchers make informed and data-driven decisions about which behaviors to pool or separate,prior to using the data in subsequent multilayer network analyses.     

The missing wetlands: using local ecological knowledge to find cryptic ecosystems

Small, temporally dynamic, biologically diverse isolated wetlands are among the most imperiled ecosystems, yet their conservation is hindered by lack of protective legislation and mapping. As part of an effort to better understand isolated wetland ecology in an area undergoing dramatic land use change, we mapped isolated wetlands in South Carolina’s Piedmont and Blue Ridge regions using remote sensing and local ecological knowledge (LEK). Remote detection of isolated wetlands was limited by digital resource resolution, topography, and wetland size. LEK was the most useful tool for locating small isolated wetlands. We sampled 10% of the study area using LEK and discovered 44 wetlands with “isolated” characteristics, none of which had been identified by remote sensing. Only 8 of 44 wetlands found through LEK could be identified using remote sensing after their discovery. LEK fills a gap in cryptic ecosystem detection when adequate remotely sensed data are not available. Though effective, using LEK is neither as rapid nor as repeatable as remote sensing. We suggest a two-pronged approach for finding cryptic ecosystems: remote sensing coupled with LEK where data resolution is inadequate. For remote detection of isolated wetlands, we suggest a minimum resolution of 0.33 m for Color Infrared, leaf-off, high-water photography. Despite great advances in remote sensing, data are not uniformly available worldwide and LEK may serve as an effective tool for locating cryptic resources for biodiversity conservation. Mapping cryptic resources will allow for more accurate resource and biodiversity conservation planning under current and future climate scenarios.     

Stejneger's beaked whale strandings in Alaska, 1995–2020

Presented here is the first comprehensive and updated compilation of history, distribution, and findings of Stejneger's beaked whales (Mesoplodon stejnegeri) in Alaska. Stejneger's beaked whales are a poorly understood, elusive, deep-diving cetacean species found in the North Pacific Ocean. Since Stejneger's beaked whale strandings data in Alaska through 1994 were last published, 35 additional strandings have been documented. Twenty-seven animals stranded in the Aleutian Islands, seven stranded in Southcentral Alaska, and one animal stranded on St. Lawrence Island. Twenty-two carcasses were necropsied, but only four were fresh. Seventeen of the 22 died during mass stranding events and cause of death could not be definitively determined. Barotrauma was suspected in three cases and infectious disease possibly complicated by barotrauma occurred in two cases. We documented an expansion of strandings into the northern Bering Sea, characterized a sex bias, examined stomach contents that included macroplastic, and identified parasites not previously associated with Stejneger's beaked whales. Also included are data on the largest known mass stranding of Stejneger's beaked whales, which occurred on Adak Island in 2018. The history, distribution, and findings presented here are central to further our understanding of this species.