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The Asian longhorned tick, Haemaphysalis longicornis, an invasive species associated with human pathogens, has spread rapidly across the eastern USA. Questing H. longicornis ticks recovered from active surveillance conducted from 1 May to 6 September, 2019 throughout Pennsylvania were tested for rickettsial pathogens. Of 265 ticks tested by PCR for pathogens, 4 (1.5%) were positive for Anaplasma phagocytophilum. Sequence analysis of the 16S rRNA gene confirmed two positives as A. phagocytophilum-human agent variant. This is the first reported detection of A. phagocytophilum-human pathogenic strain DNA in exotic H. longicornis collected in the USA.

Background Hospitalization for decompensated heart failure may be prevented by early detection of fluid retention. The multisensory HeartLogic™ algorithm, incorporated in a cardiac implantable electronic device (CIED) aims to detect impending fluid retention and thereby enables timely adjustment of medical therapy. However, it is to be investigated whether HeartLogic™ provides clinical benefit compared to heart failure care with conventional telemonitoring. This analysis investigates the effects of activating HeartLogic™ on top of heart failure care with telemonitoring on the number of episodes with fluid retention and heart failure related hospitalizations. Methods Heart failure patients with a CIED were recruited from the outpatient clinics of four European cardiology departments. All patients were included from January 2017 until December 2020, and followed-up for 365 days. Patients with a CIED and an activated HeartLogic™ algorithm were compared to a 1:1 propensity score-based matched control group consisting of patients with CIED on routine telemonitoring. Data of all episodes of (impending) fluid retention with ≥2 signs and symptoms of congestion were included for analyses. Results Data of 127 patients with an activated HeartLogic™ algorithm were adequately matched with 127 heart failure patients with a CIED on routine telemonitoring. Median age was 68 [59–75], majority of patients were male (80%), 46% had an ischemic etiology of heart failure. Total follow-up consisted of 254 patient years. During follow up, 77 (61%) individual patients with HeartLogic™ experienced an episode of fluid retention, compared to 85 (67%) induvial patients on routine telemonitoring. Patients with an activated HeartLogic™ algorithm had 1.62±1.78 events of fluid retention per patient year (PPY) compared to 2.61±3.71 events PPY in patients on routine telemonitoring, p Conclusion In a real-world multicenter heart failure population, activation of the HeartLogic™ algorithm was associated with a lower number of episodes of fluid retention per patient and a shorter duration of hospitalization for congestive heart failure. Funding Acknowledgement Type of funding sources: None.

Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency., Graphical abstract, Targeting microglia in vivo using AAVs is neither robust nor reliable. Here, Maes et al. show that transduction of retinal microglia niches depends on the injection method and the degeneration environment. This informed development of a capsid-modified AAV2/6 that in combination with the Cre-loxP system improved microglia specificity.

Environmental cues influence microglial interaction with their neuronal landscape, often causing changes in microglial functional identity. This process demands rapid energy production, which is supported by an optimized mitochondrial network. Whether mitochondrial adaptations define a microglial functional state is unknown due to limitations in mitochondrial visualization and manipulation within their microenvironment.Here, we investigate the mitochondrial network of individual microglia in physiological and dysfunctional conditions during a naïve or injury-induced mouse retinal environment. After optic nerve crush (ONC) injury, we identify mitochondrial and microglial phenotypic remodeling that is distinct from the naïve environment. Remarkably, knockout of uncoupling protein 2 (UCP2) causes transient, stress-induced mitochondrial hyperfusion only in males after ONC, even though both sexes suffer from increased intrinsic stress levels. When we compare key metabolic genes between sexes in physiological conditions, only males exhibit a metabolic transition towards glycolysis in the injury-induced environment, which attenuates in UCP2 knockout resulting in acutely accelerated retinal ganglion cell death. Our data shows that the cell-extrinsic ONC environment and cell-intrinsic UCP2KO manipulation triggers several microglial states distinguishable by mitochondrial networks that are heavily influenced by sex and injury-induced stress.

Lyme disease is the most common vector-borne disease in the United States. While Lyme disease vectors are widespread, high incidence states are concentrated in the Northeast, North Central and Mid-Atlantic regions. Mapping the distribution of Lyme disease spirochetes in ticks may aid in providing data-driven explanations of epidemiological trends and recommendations for targeting prevention strategies to communities at risk. We compiled data from the literature, publicly available tickborne pathogen surveillance databases, and internal CDC pathogen testing databases to map the county-level distribution of Lyme disease spirochetes reported in host-seeking Ixodes pacificus and Ixodes scapularis across the contiguous United States. We report B. burgdorferi s.s.-infected I. scapularis from 384 counties spanning 26 eastern states located primarily in the North Central, Northeastern, and Mid-Atlantic regions, and in I. pacificus from 20 counties spanning 2 western states, with most records reported from northern and north-coastal California. Borrelia mayonii was reported in I. scapularis in 10 counties in Minnesota and Wisconsin in the North Central United States, where records of B. burgdorferi s.s. were also reported. In comparison to a broad distribution of vector ticks, the resulting map shows a more limited distribution of Lyme disease spirochetes.

Uncertainty hampers innovative mixed-fisheries management by the scales at which connectivity dynamics are relevant to management objectives. The spatial scale of sustainable stock management is species-specific and depends on ecology, life history and population connectivity. One valuable approach to understand these spatial scales is to determine to what extent population genetic structure correlates with the oceanographic environment. Here, we compare the level of genetic connectivity in three codistributed and commercially exploited demersal flatfish species living in the North East Atlantic Ocean. Population genetic structure was analysed based on 14, 14 and 10 neutral DNA microsatellite markers for turbot, brill and sole, respectively. We then used redundancy analysis (RDA) to attribute the genetic variation to spatial (geographical location), temporal (sampling year) and oceanographic (water column characteristics) components. The genetic structure of turbot was composed of three clusters and correlated with variation in the depth of the pycnocline, in addition to spatial factors. The genetic structure of brill was homogenous, but correlated with average annual stratification and spatial factors. In sole, the genetic structure was composed of three clusters, but was only linked to a temporal factor. We explored whether the management of data poor commercial fisheries, such as in brill and turbot, might benefit from population-specific information. We conclude that the management of fish stocks has to consider species-specific genetic structures and may benefit from the documentation of the genetic seascape and life-history traits. ispartof: EVOLUTIONARY APPLICATIONS vol:14 issue:2 pages:536-552 ispartof: location:England status: published

Shrimp are a valuable aquaculture species globally; however, disease remains a major hindrance to shrimp aquaculture sustainability and growth. Mechanisms mediated by endogenous viral elements have been proposed as a means by which shrimp that encounter a new virus start to accommodate rather than succumb to infection over time. However, evidence on the nature of such endogenous viral elements and how they mediate viral accommodation is limited. More extensive genomic data on Penaeid shrimp from different geographical locations should assist in exposing the diversity of endogenous viral elements. In this context, reported here is a PacBio Sequel-based draft genome assembly of an Australian black tiger shrimp (Penaeus monodon) inbred for 1 generation. The 1.89 Gbp draft genome is comprised of 31,922 scaffolds (N50: 496,398 bp) covering 85.9% of the projected genome size. The genome repeat content (61.8% with 30% representing simple sequence repeats) is almost the highest identified for any species. The functional annotation identified 35,517 gene models, of which 25,809 were protein-coding and 17,158 were annotated using interproscan. Scaffold scanning for specific endogenous viral elements identified an element comprised of a 9,045-bp stretch of repeated, inverted, and jumbled genome fragments of infectious hypodermal and hematopoietic necrosis virus bounded by a repeated 591/590 bp host sequence. As only near complete linear ∼4 kb infectious hypodermal and hematopoietic necrosis virus genomes have been found integrated in the genome of P. monodon previously, its discovery has implications regarding the validity of PCR tests designed to specifically detect such linear endogenous viral element types. The existence of joined inverted infectious hypodermal and hematopoietic necrosis virus genome fragments also provides a means by which hairpin double-stranded RNA could be expressed and processed by the shrimp RNA interference machinery.

Lyme disease is the most commonly reported vector-borne disease in the United States (US), with approximately 300,000 -to- 40,000 cases reported annually. The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease-causing spirochete, Borrelia burgdorferi sensu stricto, in high incidence regions in the upper midwestern and northeastern US. Using county-level records of the presence of I. scapularis or presence of B. burgdorferi s.s. infected host-seeking I. scapularis, we generated habitat suitability consensus maps based on an ensemble of statistical models for both acarological risk metrics. Overall accuracy of these suitability models was high (AUC = 0.76 for I. scapularis and 0.86 for B. burgdorferi s.s. infected-I. scapularis). We sought to compare which acarological risk metric best described the distribution of counties reporting high Lyme disease incidence (≥10 confirmed cases/100,000 population) by setting the models to a fixed omission rate (10%). We compared the percent of high incidence counties correctly classified by the two models. The I. scapularis consensus map correctly classified 53% of high and low incidence counties, while the B. burgdorferi s.s. infected-I. scapularis consensus map classified 83% correctly. Counties classified as suitable by the B. burgdorferi s.s. map showed a 91% overlap with high Lyme disease incidence counties with over a 38-fold difference in Lyme disease incidence between high- and low-suitability counties. A total of 288 counties were classified as highly suitable for B. burgdorferi s.s., but lacked records of infected-I. scapularis and were not classified as high incidence. These counties were considered to represent a leading edge for B. burgdorferi s.s. infection in ticks and humans. They clustered in Illinois, Indiana, Michigan, and Ohio. This information can aid in targeting tick surveillance and prevention education efforts in counties where Lyme disease risk may increase in the future.

Shrimp are a valuable aquaculture species globally; however, disease remains a major hindrance to shrimp aquaculture sustainability and growth. Mechanisms mediated by endogenous viral elements (EVEs) have been proposed as a means by which shrimp that encounter a new virus start to accommodate rather than succumb to infection over time. However, evidence on the nature of such EVEs and how they mediate viral accommodation is limited. More extensive genomic data on Penaeid shrimp from different geographical locations should assist in exposing the diversity of EVEs. In this context, reported here is a PacBio Sequel-based draft genome assembly of an Australian black tiger shrimp (Penaeus monodon) inbred for one generation. The 1.89 Gbp draft genome is comprised of 31,922 scaffolds (N50: 496,398 bp) covering 85.9% of the projected genome size. The genome repeat content (61.8% with 30% representing simple sequence repeats) is almost the highest identified for any species. The functional annotation identified 35,517 gene models, of which 25,809 were protein-coding and 17,158 were annotated using interproscan. Scaffold scanning for specific EVEs identified an element comprised of a 9,045 bp stretch of repeated, inverted and jumbled genome fragments of Infectious hypodermal and hematopoietic necrosis virus (IHHNV) bounded by a repeated 591/590 bp host sequence. As only near complete linear ~4 kb IHHNV genomes have been found integrated in the genome of P. monodon previously, its discovery has implications regarding the validity of PCR tests designed to specifically detect such linear EVE types. The existence of joined inverted IHHNV genome fragments also provides a means by which hairpin dsRNAs could be expressed and processed by the shrimp RNA interference (RNAi) machinery.

The Atlantic bluefin tuna is a highly migratory species emblematic of the challenges associated with shared fisheries management. In an effort to resolve the species' stock dynamics, a genomewide search for spatially informative single nucleotide polymorphisms (SNPs) was undertaken, by way of sequencing reduced representation libraries. An allele frequency approach to SNP discovery was used, combining the data of 555 larvae and young-of-the-year (LYOY) into pools representing major geographical areas and mapping against a newly assembled genomic reference. From a set of 184,895 candidate loci, 384 were selected for validation using 167 LYOY. A highly discriminatory genotyping panel of 95 SNPs was ultimately developed by selecting loci with the most pronounced differences between western Atlantic and Mediterranean Sea LYOY. The panel was evaluated by genotyping a different set of LYOY (n = 326), and from these, 77.8% and 82.1% were correctly assigned to western Atlantic and Mediterranean Sea origins, respectively. The panel revealed temporally persistent differentiation among LYOY from the western Atlantic and Mediterranean Sea (FST = 0.008, p = .034). The composition of six mixed feeding aggregations in the Atlantic Ocean and Mediterranean Sea was characterized using genotypes from medium (n = 184) and large (n = 48) adults, applying population assignment and mixture analyses. The results provide evidence of persistent population structuring across broad geographic areas and extensive mixing in the Atlantic Ocean, particularly in the mid-Atlantic Bight and Gulf of St. Lawrence. The genomic reference and genotyping tools presented here constitute novel resources useful for future research and conservation efforts., This work was carried out under the provision of the ICCAT Atlantic-wide Research Programme for Bluefin Tuna (GBYP), funded by the European Union, by several ICCAT CPCs, the ICCAT Secretariat and other entities (see: http://www.iccat.int/GBYP/en/Budget.htm). Additional funds were provided by the MARES Joint Doctorate Programme Selected Under Erasmus Mundus and coordinated by Ghent University (FPA 2011-0016). Larvae from the Balearic Sea were provided by the ATAME project “Bluefin tuna abundance indices: towards recruitment estimators based on larval ecology” (CTM 2011-29525-C04-02) and the BLUEFIN project “Modelling bluefin spawning areas variability and population dynamics in the Western Mediterranean” (IEO-SOCIB agreement).

BACKGROUND: Removal of the Bax gene from mice completely protects the somas of retinal ganglion cells (RGCs) from apoptosis following optic nerve injury. This makes BAX a promising therapeutic target to prevent neurodegeneration. In this study, Bax(+/−) mice were used to test the hypothesis that lowering the quantity of BAX in RGCs would delay apoptosis following optic nerve injury. METHODS: RGCs were damaged by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN and quantitative PCR were used to monitor the status of the BAX activation mechanism in the months following injury. The apoptotic susceptibility of injured cells was directly tested by virally introducing GFP-BAX into Bax(−/−) RGCs after injury. The competency of quiescent RGCs to reactivate their BAX activation mechanism was tested by intravitreal injection of the JNK pathway agonist, anisomycin. RESULTS: 24 weeks after ONC, Bax(+/−) mice had significantly less cell loss in their RGC layer than Bax(+/+) mice 3 weeks after ONC. Bax(+/−) and Bax(+/+) RGCs exhibited similar patterns of nuclear phospho-cJUN accumulation immediately after ONC, which persisted in Bax(+/−) RGCs for up to 7 weeks before abating. The transcriptional activation of BAX activating genes was similar in Bax(+/−) and Bax(+/+) RGCs following ONC. Intriguingly, cells deactivated their BAX activation mechanism between 7 and 12 weeks after crush. Introduction of GFP-BAX into Bax(−/−) cells at 4 weeks after ONC showed that these cells had a nearly normal capacity to activate this protein, but this capacity was lost 8 weeks after crush. Collectively, these data suggest that 8–12 weeks after crush, damaged cells no longer displayed increased susceptibility to BAX activation relative to their naïve counterparts. In this same timeframe, retinal glial activation and the signaling of the pro-apoptotic JNK pathway also abated. Quiescent RGCs did not show a timely reactivation of their JNK pathway following intravitreal injection with anisomycin. CONCLUSIONS: These findings demonstrate that lowering the quantity of BAX in RGCs is neuroprotective after acute injury. Damaged RGCs enter a quiescent state months after injury and are no longer responsive to an apoptotic stimulus. Quiescent RGCs will require rejuvenation to reacquire functionality.

Octopuses have evolved incredibly large and complex nervous systems that allow them to perform impressive behaviors, like plan ahead, navigate and solve puzzles. The nervous system of the common octopus (also known as Octopus vulgaris) contains over half a billion nerves cells called neurons, similar to the number found in small primates. Two thirds of these cells reside in the octopuses’ arms, while the rest make-up a central brain that sits between their eyes. Very little is known about how this central brain forms in the embryo, including where the cells originate and which molecular factors drive their maturation in to adult cells. To help answer these questions, Deryckere et al. studied the brain of Octopus vulgaris at different stages of early development using various cell staining and imaging techniques. The experiments identified an important pool of dividing cells which sit in an area outside the central brain called the ‘lateral lips’. In these cells, genes known to play a role in neural development in other animals are active, indicating that the cells had not reached their final, mature state. In contrast, the central brain did not seem to contain any of these immature cells at the point when it was growing the most. To investigate this further, Deryckere et al. used fluorescent markers to track the progeny of the dividing cells during development. This revealed that cells in the lateral lips take on a specific neuronal fate before migrating to their target region in the central brain. Newly matured neurons have also been shown to travel large distances in the embryos of vertebrates, suggesting that this mechanism may be a common strategy for building large, complex brains. Although the nervous system of the common octopus is comparable to mammals, they evolved from a very distant branch of the tree of life; indeed, their last common ancestor was a worm-like animal that lived about 600 million years ago. Studying the brain of the common octopus, as done here, could therefore provide new insights into how complex nervous systems, including our own, evolved over time.