Corrigendum: Evaluations of the disease surveillance centre network in Scotland: what parts has it reached?

[This corrects the article DOI: 10.3389/fvets.2023.1099057.].

Evaluations of the Disease Surveillance Centre network in Scotland: What parts has it reached?

Regular evaluation is a prerequisite for systems that provide surveillance of animal populations. Scotland's Rural College Veterinary Services' Disease Surveillance Centre (DSC) network plays an integral part in surveillance to detect new and re-emerging threats within animal populations, predominantly livestock. In response to surveillance reviews and proposed changes to the network, an initial evaluation of diagnostic submissions data in 2010 to mid-2012 established a baseline "footprint," while highlighting challenges with the data. In this recent evaluation for the period 2013­2018, we developed a new denominator using a combination of agricultural census and movement data, to identify relevant holdings more accurately. Iterative discussions between those processing submissions data and those involved in collection at source took place to understand the intricacies of the data, establish the most appropriate dataset, and develop the processes required to optimise the data extraction and cleansing. The subsequent descriptive analysis identifies the number of diagnostic submissions, the number of unique holdings making submissions to the network and shows that both the surrounding geographic region of, and maximum distance to the closest DSC vary greatly between centres. Analysis of those submissions classed as farm animal post-mortems also highlights the effect of distance to the closest DSC. Whether specific differences between the time periods are due to changes in the behavior of the submitting holdings or the data extraction and cleaning processes was difficult to disentangle. However, with the improved techniques producing better data to work with, a new baseline footprint for the network has been created. This provides information that can help policy makers and surveillance providers make decisions about service provision and evaluate the impact of future changes. Additionally, the outputs of these analyses can provide feedback to those employed in the service, providing evidence of what they are achieving and why changes to data collection processes and ways of working are being made. In a different setting, other data will be available and different challenges may arise. However, the fundamental principles highlighted in these evaluations and the solutions developed should be of interest to any surveillance providers generating similar diagnostic data.

The Use of Sheep Movement Data to Inform Design and Interpretation of Slaughterhouse-Based Surveillance Activities.

The design of surveillance strategies is often a compromise between science, feasibility, and available resources, especially when sampling is based at fixed locations, such as slaughter-houses. Advances in animal identification, movement recording and traceability should provide data that can facilitate the development, design and interpretation of surveillance activities. Here, for the first time since the introduction of electronic identification of sheep, the utility of a statutory sheep movement database to inform the design and interpretation of slaughter-house based surveillance activities has been investigated. Scottish sheep movement records for 2015-2018 were analyzed in combination with several other data sources. Patterns of off-farm movements of Scottish sheep to slaughter were described and the spatial distribution of several distinct slaughter populations, throughputs and catchment areas for Scottish slaughterhouses were determined. These were used to evaluate the coverage of a convenience-sample slaughter-house based survey for antimicrobial resistance (AMR). In addition, non-slaughter sheep movements within and between Scottish regions were described and inter-and intra-regional movement matrices were produced. There is potential at a number of levels for bias in spatially-associated factors for ovine surveillance activities based at Scottish slaughterhouses. The first is intrinsic because the slaughtered in Scotland population differs from the overall Scottish sheep slaughter population. Other levels will be survey-dependent and occur when the catchment area differs from the slaughtered in Scotland population and when the sampled sheep differ from the catchment area. These are both observed in the AMR survey. Furthermore, the Scottish non-slaughter sheep population is dynamic. Inter-regional movements vary seasonally, driven by the sheep calendar year, structure of the Scottish sheep industry and management practices. These sheep movement data provide a valuable resource for surveillance purposes, despite a number of challenges and limitations that were encountered. They can be used to identify and characterize the spatial origin of relevant populations and so inform the interpretation of existing slaughterhouse-based surveillance activities. They can be used to improve future design by exploring the feasibility and cost:benefit of alternative sampling strategies. Further development could also contribute to other surveillance activities, such as situational awareness and resource allocation, for the benefit of stakeholders.

CREB4, a transmembrane bZip transcription factor and potential new substrate for regulation and cleavage by S1P.

Regulated intramembrane proteolysis of the factors SREBP and ATF6 represents a central control mechanism in sterol homeostasis and stress response within the endoplasmic reticulum. Here, we compare localization of ATF6-related bZip factors CREB4, CREB-H, Luman, and OASIS. These factors contain the defining features of a bZip domain, a predicted transmembrane domain and an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites. Each factor localizes to the endoplasmic reticulum (ER), but a population of CREB4 was also observed in the Golgi. Deletion of the transmembrane domain in CREB4 resulted in efficient nuclear accumulation. An N-terminal variant of CREB4 containing the BZIp domain potently activated expression from a target gene containing ATF6 binding sites and from the promoter for the ER chaperone GRP78/BIP. CREB4 was cleaved in a site-specific manner in response to brefeldin A disruption of the Golgi or by coexpression with S1P but only after deletion or substitution of its C-terminal lumenal domain. Thus, S1P cleavage of CREB4 may be suppressed by a determinant in the C-terminal region. Dithiothreitol induced more complete transport of CREB4 to the Golgi, but not cleavage. Together, the data identify at least one additional bZip factor whose localization responds to ER stress, and we propose a model based on these results that indicates additional levels of control of this novel class of transcription factors.

Luman, the cellular counterpart of herpes simplex virus VP16, is processed by regulated intramembrane proteolysis.

Luman is a human basic leucine zipper transcription factor that, like the herpes simplex virus transcription factor VP16, requires the host cell factor, HCF, for activity. Although both HCF and Luman have been implicated in cell growth, their biological roles have not been clearly defined. Luman conforms to a type II membrane-associated glycoprotein with its carboxyl terminus embedded in cellular membranes and its amino terminus, which contains all its identified functional domains, in the cytoplasm. Here we show that Luman is processed by regulated intramembrane proteolysis (RIP). The site 1 protease (S1P), a Golgi apparatus-resident enzyme responsible for catalyzing the first step in the RIP pathway of the sterol regulatory element binding proteins (SREBPs) and ATF6, may also be involved in the processing of Luman. Thus, processing of Luman was highly stimulated by brefeldin A, a compound that causes the reflux of Golgi apparatus enzymes to the endoplasmic reticulum (ER). In addition, coexpression of Luman with S1P containing a KDEL ER retrieval signal resulted in virtually quantitative cleavage of Luman in the absence of any treatment. Finally, Luman contains a sequence, RQLR, immediately downstream from the transmembrane domain which bears similarity to the consensus S1P cleavage site identified by others. Substitution of arginine residues within this motif abolished S1P cleavage, providing robust evidence that S1P is involved in Luman processing. We observed that following S1P cleavage, the majority of the cleaved Luman was retained in cytoplasmic membranes, indicating that an additional step or enzymes yet to be identified are involved in complete cleavage and release to yield the product which ultimately enters the nuclei of cells.

Complete sequence characterization of the genome of the St Croix River virus, a new orbivirus isolated from cells of Ixodes scapularis.

An orbivirus identified as St Croix River virus (SCRV) was isolated from cells of Ixodes scapularis ticks. Electron microscopy showed particles with typical orbivirus morphology. The SCRV genome was sequenced completely and compared to previously characterized orbivirus genomes. Significant identity scores (21-38%) were detected between proteins encoded by segments S1, S2, S4, S5, S6, S8, S9 and S10 of SCRV and those encoded by segments S1, S3, S4, S5, S6, S7, S9 and S10, respectively, of Bluetongue virus (BTV), the prototype orbivirus species. The protein encoded by SCRV genome segment 3 (VP3) is thought to be the equivalent of VP2 of BTV. Segment 7 encodes a protein homologous to non-structural protein NS2(ViP) of BTV. Analysis of VP1(Pol) (segment 1) shows that SCRV is an orbivirus, distantly related to the other sequenced species. Blot hybridizations and sequence comparisons of the conserved protein encoded by genome segment 2 (the T2 subcore shell protein) with previously identified orbiviruses confirm that SCRV is a distinct orbivirus species, unrelated to another tick-borne species, Great Island virus. The presence of SCRV in cells prepared from tick eggs suggests that transovarial transmission of SCRV may occur in ticks.