as a model to study polymicrobial synergy and dysbiosis.

The fruit fly has emerged as a valuable model for investigating human biology, including the role of the microbiome in health and disease. Historically, studies involving the infection of with single microbial species have yielded critical insights into bacterial colonization and host innate immunity. However, recent evidence has underscored that multiple microbial species can interact in complex ways through physical connections, metabolic cross-feeding, or signaling exchanges, with significant implications for healthy homeostasis and the initiation, progression, and outcomes of disease.

A Model Framework for the Estimation of Animal 'Suffering': Its Use in Predicting and Retrospectively Assessing the Impact of Experiments on Animals.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and reproducibly, as well as helping to implement any national legal severity limits in subacute and chronic animal experiments, e.g., as specified by the competent authority.

The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila.

The generation of a diversity of photoreceptor (PR) subtypes with different spectral sensitivities is essential for color vision in animals. In the Drosophila eye, the Hippo pathway has been implicated in blue- and green-sensitive PR subtype fate specification. Specifically, Hippo pathway activation promotes green-sensitive PR fate at the expense of blue-sensitive PRs.

Opposing transcriptional and post-transcriptional roles for Scalloped in binary Hippo-dependent neural fate decisions.

The Hippo tumor suppressor pathway plays many fundamental cell biological roles during animal development. Two central players in controlling Hippo-dependent gene expression are the TEAD transcription factor Scalloped (Sd) and its transcriptional co-activator Yorkie (Yki). Hippo signaling phosphorylates Yki, thereby blocking Yki-dependent transcriptional control.

Deletion of a specific exon in the voltage-gated calcium channel gene disrupts locomotion in larvae.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein that regulates transcription, translation and alternative splicing of mRNA. We have shown previously that null mutations of the ortholog, (), causes severe locomotion defects in larvae that are mediated by a reduction in the expression of a type II voltage-gated calcium channel, (). We also showed that TDP-43 regulates the inclusion of alternatively spliced exons of ; mutants showed significantly increased expression of isoforms lacking exon 7, a particularly notable finding as only one out of the 15 predicted isoforms lacks exon 7.

Exploring the Interaction of TDP-43 and the Type II Voltage-Gated Calcium Channel, , in Regulating Motor Function and Behavior.

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neurodegenerative disease. The cause of the disease remains obscure, and as such there is no effective treatment or cure. Amyotrophic lateral sclerosis and other neurodegenerative diseases are frequently characterized by dysfunction of the RNA-binding protein, TDP-43.

Challenges facing the veterinary profession in Ireland: 2. On-farm use of veterinary antimicrobials.

Background: Antimicrobial resistance has emerged in recent years as a significant public health threat, which requires both an ethical and a scientific approach. In a recent Policy Delphi study, on-farm use of antimicrobials was a key concern identified by veterinary professionals in Ireland. In this case study (the second in a series of three resulting from a research workshop exploring the challenges facing the veterinary profession in Ireland; the other two case studies investigate clinical veterinary services and emergency/casualty slaughter certification) we aim to provide a value-based reflection on the constraints and possible opportunities for responsible use of veterinary antimicrobials in Ireland.

Restoration of Motor Defects Caused by Loss of TDP-43 by Expression of the Voltage-Gated Calcium Channel, , in Central Neurons.

Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae.

Challenges facing the veterinary profession in Ireland: 3. emergency and casualty slaughter certification.

Background: Veterinarians are faced with significant conflicts of interest when issuing certificates for the transport and slaughter of acutely injured and casualty livestock. In a recent Policy Delphi study, emergency and casualty slaughter certification was a key concern identified by veterinary professionals in Ireland. In this case study (the third in a series of three resulting from a research workshop exploring challenges facing the veterinary profession in Ireland; the other two case studies investigate clinical veterinary services and the on-farm use of veterinary antimicrobials), we aim to provide a value-based reflection on the constraints and opportunities for best practice in emergency and casualty slaughter certification in Ireland.

Drosophila lines with mutant and wild type human TDP-43 replacing the endogenous gene reveals phosphorylation and ubiquitination in mutant lines in the absence of viability or lifespan defects.

Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines.

Challenges facing the veterinary profession in Ireland: 1. clinical veterinary services.

Background: The provision of veterinary clinical services is known to elicit a range of challenges which require an ethical appraisal. In a recent Policy Delphi study, referrals/second opinions and 24 h emergency care were identified as matters of key concern by veterinary professionals in Ireland. In this case study (the first in a series of three resulting from a research workshop exploring challenges facing the veterinary profession in Ireland; the other two case studies investigate the on-farm use of veterinary antimicrobials and emergency/casualty slaughter certification) we aim to provide a value-based reflection on the constraints and possible opportunities for two prominent veterinary clinical services in Ireland: referrals/second opinions and 24 h emergency care.

Multifaceted biological insights from a draft genome sequence of the tobacco hornworm moth, Manduca sexta.

Manduca sexta, known as the tobacco hornworm or Carolina sphinx moth, is a lepidopteran insect that is used extensively as a model system for research in insect biochemistry, physiology, neurobiology, development, and immunity. One important benefit of this species as an experimental model is its extremely large size, reaching more than 10 g in the larval stage. M.

The upper limits of pain and suffering in animal research.

The control of risk and harm in human research often calls for the establishment of upper limits of risk of pain, suffering, and distress that investigators must not exceed. Such upper limits are uncommon in animal research, in which limits of acceptability are usually left to the discretion of individual investigators, institutions, national inspectors, or ethics review committees. We here assess the merits of the European Directive 2010/63/EU on the Protection of Animals Used for Scientific Purposes and its accompanying instruments, such as guides and examples.

Role for Rab10 in Methamphetamine-Induced Behavior.

Lipid rafts are specialized, cholesterol-rich membrane compartments that help to organize transmembrane signaling by restricting or promoting interactions with subsets of the cellular proteome. The hypothesis driving this study was that identifying proteins whose relative abundance in rafts is altered by the abused psychostimulant methamphetamine would contribute to fully describing the pathways involved in acute and chronic effects of the drug. Using a detergent-free method for preparing rafts from rat brain striatal membranes, we identified density gradient fractions enriched in the raft protein flotillin but deficient in calnexin and the transferrin receptor, markers of non-raft membranes.

Motor neuron expression of the voltage-gated calcium channel cacophony restores locomotion defects in a Drosophila, TDP-43 loss of function model of ALS.

Dysfunction of the RNA-binding protein, TDP-43, is strongly implicated as a causative event in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). TDP-43 is normally found in the nucleus and pathological hallmarks of ALS include the presence of cytoplasmic protein aggregates containing TDP-43 and an associated loss of TDP-43 from the nucleus. Loss of nuclear TDP-43 likely contributes to neurodegeneration.

Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila.

The human Tar-DNA binding protein, TDP-43, is associated with amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. TDP-43 contains two conserved RNA-binding motifs and has documented roles in RNA metabolism, including pre-mRNA splicing and repression of transcription. Here, using Drosophila melanogaster as a model, we generated loss-of-function and overexpression genotypes of Tar-DNA binding protein homolog (TBPH) to study their effect on the transcriptome of the central nervous system (CNS).

Drosophila gustatory preference behaviors require the atypical soluble guanylyl cyclases.

The intracellular messenger cGMP has been suggested to play a role in taste signal transduction in both vertebrates and invertebrates. In the present study, we have examined the role of the Drosophila atypical soluble guanylyl cyclases (sGCs), Gyc-89Da and Gyc-89Db, in larval and adult gustatory preference behaviors. We showed that in larvae, sucrose attraction requires Gyc-89Db and caffeine avoidance requires Gyc-89Da.

Behavioral responses to hypoxia and hyperoxia in Drosophila larvae: molecular and neuronal sensors.

The ability to detect changes in oxygen concentration in the environment is critical to the survival of all animals. This requires cells to express a molecular oxygen sensor that can detect shifts in oxygen levels and transmit a signal that leads to the appropriate cellular response. Recent biochemical, genetic and behavioral studies have shown that the atypical soluble guanylyl cyclases function as oxygen detectors in Drosophila larvae triggering a behavioral escape response when exposed to hypoxia.