Distinguishing personal belief from scientific knowledge for the betterment of killer whale welfare – a commentary

We contest publication of Marino et al. regarding captive killer whale (Orcinus orca) welfare because of misrepresentations of available data and the use of citations that do not support assertions. Marino et al. misrepresent stress response concepts and erroneously cite studies, which appear to support Marino et al.’s philosophical beliefs regarding the cetacean hypothalamic–pituitary–adrenal axis. To be clear, these misrepresentations are not differences of scientific opinion, as the authors’ conclusions lack any scientific basis. More extensive review of Marino et al.’s citations reveal a dearth of empirical evidence to support their assertions. Further, Marino et al.’s approach to animal welfare is not consistent with conventional veterinary approaches to animal welfare, including their apparent opposition to use of preventative and therapeutic veterinary interventions. While Marino et al. argue that killer whales’ cognitive and spatial needs preclude management of this species under human care, misrepresentation of the citations used to support this opinion invalidates their arguments. Misleading interpretations of data relative to killer whales’ cognitive and emotional needs and specious and unsubstantiated comparisons with states experienced by humans with posttraumatic stress disorder and other conditions, represent a number of strategies used to misrepresent knowledge regarding killer whale welfare. These misrepresentations and fallacies are inconsistent with scientific ethical standards for credible, peer-reviewed journals (ICMJE, 2018), and are barriers to rigorous discourse and identification of strategies for optimizing killer whale welfare. Assertions in the paper amount to nothing more than a compilation of conclusory, philosophical statements. We would also like to mention that manuscripts such as Marino et al.’s do great damage to the fields of comparative psychology and to behavioral science as a whole

A Human Cytomegalovirus-Encoded microRNA Regulates Expression of Multiple Viral Genes Involved in Replication

Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA targets of the virus-encoded miRNA miR-UL112-1. Bioinformatics analysis of the known HCMV mRNA 3′ untranslated regions (UTRs) revealed 14 potential viral transcripts that were predicted to contain functional target sites for miR-UL112-1. The potential target sites were screened using luciferase reporters that contain the HCMV 3′UTRs in co-transfection assays with miR-UL112-1. Three of the 14 HCMV miRNA targets were validated, including the major immediate early gene encoding IE72 (UL123, IE1), UL112/113, and UL120/121. Further analysis of IE72 regulation by miR-UL112-1 with clones encoding the complete major immediate early region revealed that the IE72 3′UTR target site is necessary and sufficient to direct miR-UL112-1-specific inhibition of expression in transfected cells. In addition, miR-UL112-1 regulation is mediated through translational inhibition rather than RNA degradation. Premature expression of miR-UL112-1 during HCMV infection resulted in a significant decrease in genomic viral DNA levels, suggesting a functional role for miR-UL112-1 in regulating the expression of genes involved in viral replication. This study demonstrates the ability of a viral miRNA to regulate multiple viral genes

A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5 ' UTRs

Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3′ untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5′UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5′UTRs

Proteasome-associated HECT-type ubiquitin ligase activity is required for plant immunity

<div><p>Regulated degradation of proteins by the 26S proteasome plays important roles in maintenance and signalling in eukaryotic cells. Proteins are marked for degradation by the action of E3 ligases that site-specifically modify their substrates by adding chains of ubiquitin. Innate immune signalling in plants is deeply reliant on the ubiquitin-26S proteasome system. While progress has been made in understanding substrate ubiquitination during plant immunity, how these substrates are processed upon arrival at the proteasome remains unclear. Here we show that specific members of the HECT domain-containing family of ubiquitin protein ligases (UPL) play important roles in proteasomal substrate processing during plant immunity. Mutations in <i>UPL1</i>, <i>UPL3</i> and <i>UPL5</i> significantly diminished immune responses activated by the immune hormone salicylic acid (SA). In depth analyses of <i>upl3</i> mutants indicated that these plants were impaired in reprogramming of nearly the entire SA-induced transcriptome and failed to establish immunity against a hemi-biotrophic pathogen. UPL3 was found to physically interact with the regulatory particle of the proteasome and with other ubiquitin-26S proteasome pathway components. In agreement, we demonstrate that UPL3 enabled proteasomes to form polyubiquitin chains, thereby regulating total cellular polyubiquitination levels. Taken together, our findings suggest that proteasome-associated ubiquitin ligase activity of UPL3 promotes proteasomal processivity and is indispensable for development of plant immunity.</p></div

Nuclear Factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3′ untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs

Proteasome-associated ubiquitin ligase relays target plant hormone-specific transcriptional activators

The ubiquitin-proteasome system is vital to hormone-mediated developmental and stress responses in plants. Ubiquitin ligases target hormone-specific transcriptional activators (TAs) for degradation, but how TAs are processed by proteasomes remains unknown. We report that in Arabidopsis, the salicylic acid– and ethylene-responsive TAs, NPR1 and EIN3, are relayed from pathway-specific ubiquitin ligases to proteasome-associated HECT-type UPL3/4 ligases. Activity and stability of NPR1 were regulated by sequential action of three ubiquitin ligases, including UPL3/4, while proteasome processing of EIN3 required physical handover between ethylene-responsive SCF(EBF2) and UPL3/4 ligases. Consequently, UPL3/4 controlled extensive hormone-induced developmental and stress-responsive transcriptional programs. Thus, our findings identify unknown ubiquitin ligase relays that terminate with proteasome-associated HECT-type ligases, which may be a universal mechanism for processive degradation of proteasome-targeted TAs and other substrates

Distinguishing personal belief from scientific knowledge for the betterment of killer whale welfare \u2013 a commentary

We contest publication of Marino et al. regarding captive killer whale (Orcinus orca) welfare because of misrepresentations of available data and the use of citations that do not support assertions. Marino et al. misrepresent stress response concepts and erroneously cite studies, which appear to support Marino et al.\u2019s philosophical beliefs regarding the cetacean hypothalamic\u2013pituitary\u2013adrenal axis. To be clear, these misrepresentations are not differences of scientific opinion, as the authors\u2019 conclusions lack any scientific basis. More extensive review of Marino et al.\u2019s citations reveal a dearth of empirical evidence to support their assertions. Further, Marino et al.\u2019s approach to animal welfare is not consistent with conventional veterinary approaches to animal welfare, including their apparent opposition to use of preventative and therapeutic veterinary interventions. While Marino et al. argue that killer whales\u2019 cognitive and spatial needs preclude management of this species under human care, misrepresentation of the citations used to support this opinion invalidates their arguments. Misleading interpretations of data relative to killer whales\u2019 cognitive and emotional needs and specious and unsubstantiated comparisons with states experienced by humans with posttraumatic stress disorder and other conditions, represent a number of strategies used to misrepresent knowledge regarding killer whale welfare. These misrepresentations and fallacies are inconsistent with scientific ethical standards for credible, peer-reviewed journals (ICMJE, 2018), and are barriers to rigorous discourse and identification of strategies for optimizing killer whale welfare. Assertions in the paper amount to nothing more than a compilation of conclusory, philosophical statements. We would also like to mention that manuscripts such as Marino et al.\u2019s do great damage to the fields of comparative psychology and to behavioral science as a whole

Amplifying Voices: Information and Expression

In a variety of ways, information and expression remain constrained despite the expansion of the information highway. In some cases, there is heavy-handed silencing by governments through repressive laws and actions; in others, the media self-censors itself on certain sensitive or volatile issues. Persons with sensory disabilities have to function in a world with a dearth of sign language, Braille, and interpretation services to accommodate them to function fully in society.  This issue of Amplifying Voices, a publication of the Open Society Initiative for Eastern Africa, discusses the provision of information through accessible formats so that people can engage and make informed judgments on issues that have a bearing on their lives.