Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra.

Transposable elements are one of the major contributors to genome-size differences in metazoans. Despite this, relatively little is known about the evolutionary patterns of element expansions and the element families involved. Here we report a broad genomic sampling within the genus Hydra, a freshwater cnidarian at the focal point of diverse research in regeneration, symbiosis, biogeography, and aging. We find that the genome of Hydra is the result of an expansion event involving long interspersed nuclear elements and in particular a single family of the chicken repeat 1 (CR1) class. This expansion is unique to a subgroup of the genus Hydra, the brown hydras, and is absent in the green hydra, which has a repeat landscape similar to that of other cnidarians. These features of the genome make Hydra attractive for studies of transposon-driven genome expansions and speciation.

Nodal signalling determines biradial asymmetry in Hydra.

In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis. Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cnidarian polyp Hydra, and we report evidence of Nodal in a pre-bilaterian clade. We identified a Nodal-related gene (Ndr) in Hydra magnipapillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates, Nodal acts downstream of ß-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of ß-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians.

Gastric Emphysema: A Cannot-Miss Emergency Medicine Diagnosis.

The radiographic finding of gastric emphysema with portal venous gas is classically an ominous finding, associated with a high rate of mortality. Although classically the case, this imaging finding must be quickly correlated with the overall clinical picture, allowing for the essential differentiation between the highly lethal emphysematous gastritis and the much more benign gastric emphysema, each of which has drastically different management strategies. We report a case of gastric emphysema with portal venous gas likely attributable to a gastric outlet obstruction and gastric mucosal defect in a 17-year-old girl with a chief complaint of syncope that was diagnosed in the emergency department and treated conservatively.

Stable isotopes of algae and macroinvertebrates in streams respond to watershed urbanization, inform management goals, and indicate food web relationships.

Watershed development and anthropogenic sources of nitrogen are among leading causes of negative impacts to aquatic ecosystems around the world. The δ15N of aquatic biota can be used as indicators of anthropogenic sources of nitrogen enriched in 15N, but this mostly has been done at small spatial extents or to document effects of point sources. In this study, we sampled 77 sites along a forest to urban land cover gradient to examine food webs and the use of δ15N of periphyton and macroinvertebrate functional feeding groups (FFGs) as indicators of watershed development and nitrogen effects on streams. Functional feeding groups had low δ15N variability among taxa within sites. Mean absolute differences between individual taxa and their respective site FFG means were < 0.55‰, whereas site means of δ15N of FFGs had ranges of approximately 7-12‰ among sites. The δ15N of periphyton and macroinvertebrate FFGs distinguished least disturbed streams from those with greater watershed urbanization, and they were strongly correlated with increasing nitrogen concentrations and watershed impervious cover. Nonmetric multidimensional scaling, using δ15N of taxa, showed that changes in macroinvertebrate assemblages as a whole were associated with forest-to-urban and increasing nitrogen gradients. Assuming an average +3.4‰ per trophic level increase, δ15N of biota indicated that detrital pathways likely were important to food web structure, even in streams with highly developed watersheds. We used periphyton and macroinvertebrate FFG δ15N to identify possible management goals that can inform decisions affecting nutrients and watershed land use. Overall, the δ15N of periphyton and macroinvertebrates were strong indicators of watershed urban development effects on stream ecosystems, and thus, also could make them useful for quantifying the effectiveness of nitrogen, stream, and watershed management efforts.

An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning.

Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.

FTO gene variant modulates the neural correlates of visual food perception.

Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive. Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity.

A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration.

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration.

Quantifying Urban Watershed Stressor Gradients and Evaluating How Different Land Cover Datasets Affect Stream Management.

Watershed management and policies affecting downstream ecosystems benefit from identifying relationships between land cover and water quality. However, different data sources can create dissimilarities in land cover estimates and models that characterize ecosystem responses. We used a spatially balanced stream study (1) to effectively sample development and urban stressor gradients while representing the extent of a large coastal watershed (>4400 km(2)), (2) to document differences between estimates of watershed land cover using 30-m resolution national land cover database (NLCD) and <1-m resolution land cover data, and (3) to determine if predictive models and relationships between water quality and land cover differed when using these two land cover datasets. Increased concentrations of nutrients, anions, and cations had similarly significant correlations with increased watershed percent impervious cover (IC), regardless of data resolution. The NLCD underestimated percent forest for 71/76 sites by a mean of 11 % and overestimated percent wetlands for 71/76 sites by a mean of 8 %. The NLCD almost always underestimated IC at low development intensities and overestimated IC at high development intensities. As a result of underestimated IC, regression models using NLCD data predicted mean background concentrations of NO3 (-) and Cl(-) that were 475 and 177 %, respectively, of those predicted when using finer resolution land cover data. Our sampling design could help states and other agencies seeking to create monitoring programs and indicators responsive to anthropogenic impacts. Differences between land cover datasets could affect resource protection due to misguided management targets, watershed development and conservation practices, or water quality criteria.

The comprehensive analysis of DEG/ENaC subunits in Hydra reveals a large variety of peptide-gated channels, potentially involved in neuromuscular transmission.

BACKGROUND: It is generally the case that fast transmission at neural synapses is mediated by small molecule neurotransmitters. The simple nervous system of the cnidarian Hydra, however, contains a large repertoire of neuropeptides and it has been suggested that neuropeptides are the principal transmitters of Hydra. An ion channel directly gated by Hydra-RFamide neuropeptides has indeed been identified in Hydra - the Hydra Na+ channel (HyNaC) 2/3/5, which is expressed at the oral side of the tentacle base. Hydra-RFamides are more widely expressed, however, being found in neurons of the head and peduncle region. Here, we explore whether further peptide-gated HyNaCs exist, where in the animal they are expressed, and whether they are all gated by Hydra-RFamides. RESULTS: We report molecular cloning of seven new HyNaC subunits - HyNaC6 to HyNaC12, all of which are members of the DEG/ENaC gene family. In Xenopus oocytes, these subunits assemble together with the four already known subunits into thirteen different ion channels that are directly gated by Hydra-RFamide neuropeptides with high affinity (up to 40 nM). In situ hybridization suggests that HyNaCs are expressed in epitheliomuscular cells at the oral and the aboral side of the tentacle base and at the peduncle. Moreover, diminazene, an inhibitor of HyNaCs, delayed tentacle movement in live Hydra. CONCLUSIONS: Our results show that Hydra has a large variety of peptide-gated ion channels that are activated by a restricted number of related neuropeptides. The existence and expression pattern of these channels, and behavioral effects induced by channel blockers, suggests that Hydra co-opted neuropeptides for fast neuromuscular transmission.

Contact Tracing Different Age Groups During the COVID-19 Pandemic: Retrospective Study From South-West Germany.

BACKGROUND: Contact tracing was implemented in many countries during the COVID-19 pandemic to prevent disease spread, reduce mortality, and avoid overburdening health care systems. In several countries, including Germany, new systems were needed to trace potentially infected individuals. OBJECTIVE: Using data collected in the Rhine-Neckar and Heidelberg (RNK/HD) districts in southwest Germany (population: 706,974), this study examines the overall effectiveness and efficiency of contact tracing in different age groups and stages of the pandemic. METHODS: From January 27, 2020, to April 30, 2022, the RNK/HD Health Authority collected data on COVID-19 infections, quarantines, and deaths. Data on infection, quarantine, and death was grouped by age (young: 0-19 years; adult: 20-65 years; and senior citizens: >65 years) and pandemic phase (infectious wave plus subsequent lull periods) and analyzed for proportion, risk, and relative risk (RR). The overall effectiveness and efficiency of contact tracing were determined by calculating quarantine sensitivity (proportion of the infected population captured in quarantine), positive predictive value (PPV; proportion of the quarantined population that was infected), and the weighted Fß-score (combined predictive performance). RESULTS: Of 706,974 persons living in RNK/HD during the study period, 192,175 (27.2%) tested positive for SARS-CoV-2, 74,810 (10.4%) were quarantined, and 932 (0.132%) died following infection. Compared with adults, the RR of infection was lower among senior citizens (0.401, 95% CI 0.395-0.407) and while initially lower for young people, was ultimately higher for young people across all 5 phases (first-phase RR 0.502, 95% CI 0.438-0.575; all phases RR 1.35, 95% CI 1.34-1.36). Of 932 COVID-19-associated deaths during the study period, 852 were senior citizens (91.4%), with no deaths reported among young people. Relative to adults, senior citizens had the lowest risk of quarantine (RR 0.436, 95% CI 0.424-0.448), while young people had the highest RR (2.94, 95% CI 2.90-2.98). The predictive performance of contact tracing was highest during the second and third phases of the pandemic (Fß-score=0.272 and 0.338, respectively). In the second phase of the pandemic, 5810 of 16,814 COVID-19 infections were captured within a total quarantine population of 39,687 (sensitivity 34.6%; PPV 14.6%). In the third phase of the pandemic, 3492 of 8803 infections were captured within a total quarantine population of 16,462 (sensitivity 39.7%; PPV 21.2%). CONCLUSIONS: The use of quarantine aligned with increasing risks of COVID-19 infection and death. High levels of quarantine sensitivity before the introduction of the vaccine show how contact tracing systems became increasingly effective at capturing and quarantining the infected population. High levels of PPV and Fß-scores indicate, moreover, that contact tracing became more efficient at identifying infected individuals. Additional analysis of transmission pathways is needed to evaluate the application of quarantine in relation to infection and death risks within specific age groups.

Temporally remote destabilization of prediction after rare breaches of expectancy.

While neural signatures of breaches of expectancy and their immediate effects have been investigated, thus far, temporally more remote effects have been neglected. The present fMRI study explored neural correlates of temporally remote destabilization of prediction following rare breaches of expectancy with a mean delay of 14 s. We hypothesized temporally remote destabilization to be reflected either in an attenuation of areas related to long-term memory or in an increase of lateral fronto-parietal loops related to the encoding of new stimuli. Monitoring a deterministic 24-digit sequence, subjects were asked to indicate occasional sequential omissions by key press. Temporally remote destabilization of prediction was expected to be revealed by contrasting sequential events whose equivalent was omitted in the preceding sequential run n-1 (destabilized events) with sequential events without such history (nondestabilized events). Temporally remote destabilization of prediction was reflected in an attenuation of activity in the dorsal frontomedian cortex (Brodmann Area (BA) 9) bilaterally. Moreover, activation of the left medial BA 9 was enhanced by contrasting nondestabilized events with breaches. The decrease of dorsal frontomedian activation in the case of destabilized events might be interpreted as a top-down modulation on perception causing a less expectation-restricted encoding of the current stimulus and hence enabling the adaptation of expectation and prediction in the long run.

Apoptotic cell-derived factors induce arginase II expression in murine macrophages by activating ERK5/CREB.

Apoptotic cell (AC)-derived factors alter the physiology of macrophages (MΦs) towards a regulatory phenotype, characterized by reduced nitric oxide (NO) production. Impaired NO formation in response to AC-conditioned medium (CM) was facilitated by arginase II (ARG II) expression, which competes with inducible NO synthase for L-arginine. Here we explored signaling pathways allowing CM to upregulate ARG II in RAW264.7 MΦs. Sphingosine-1-phosphate (S1P) was required and acted synergistically with a so far unidentified factor to elicit high ARG II expression. S1P activated S1P(2), since S1P(2) knockdown prevented ARG II upregulation. Furthermore, ERK5 knockdown attenuated CM-mediated ARG II protein induction. CREB was implicated as shown by EMSA analysis and decoy-oligonucleotides scavenging CREB in RAW264.7 MΦs, which blocked ARG II expression. We conclude that AC-derived S1P binds to S1P(2) and acts synergistically with other factors to activate ERK5 and concomitantly CREB. This signaling cascade shapes an anti-inflammatory MΦ phenotype by ARG II induction.

Peroxisome proliferator-activated receptor γ-induced T cell apoptosis reduces survival during polymicrobial sepsis.

RATIONALE: Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator-activated receptor (PPAR) γ was increased in isolated T cells of patients with sepsis. OBJECTIVES: We determined the importance of targeting PPARγ for sepsis treatment and underlying molecular mechanisms for T-cell apoptosis in vivo. METHODS: To mimic human systemic inflammation and septic conditions, we used a nonlethal endotoxemia and a lethal cecum ligation and puncture polymicrobial sepsis model. MEASUREMENTS AND MAIN RESULTS: PPARγ inhibition in T cells with either the PPARγ antagonist GW9662 or a newly generated T cell-specific PPARγ knockout (Tc-PPARγ(-/-)) mice provided a survival advantage during polymicrobial sepsis in mice, which correlated with abrogated T-cell depletion in both in vivo models. Pathway analysis revealed increased antiapoptotic IL-2 and Bcl-2 expression, and activated prosurvival PI3K/Akt signaling under PPARγ-deficient conditions. In line, neutralizing IL-2 in Tc-PPARγ(-/-) mice resulted in T-cell apoptosis and increased mortality. CONCLUSIONS: Our results provide evidence for a pivotal involvement of PPARγ in T-cell depletion by activating two important apoptosis pathways, and subsequently provoking the breakdown of defense mechanisms during systemic inflammation and sepsis.

Evaluation of Nitrogen and Carbon Stable Isotopes in Filter Feeding Bivalves and Surficial Sediment for Assessing Aquatic Condition in Lakes and Estuaries.

Excessive inputs of nitrogen from anthropogenic activities in watersheds can cause detrimental effects to aquatic ecosystems, but these effects can be difficult to determine based solely on nitrogen concentrations because of their temporal variability and the need to link human activities to ecological responses. Here, we (1) tested the use of stable isotopes of nitrogen (δ15N) and carbon (δ13C) in benthic organic matter (BOM) as proxies for isotope ratios of filter feeding bivalves in lakes and estuaries, which can be used as indicators but are harder to sample and often spatially sparse, and (2) evaluated if stable isotope ratios in benthic organic matter could be used to assess impacts from anthropogenic land development of watersheds. The δ15N in BOM isolated from surficial sediment (δ15NBOM) was significantly correlated with δ15N in filter feeding unionid mussels (Elliptio complanata, δ15NUN) from lakes and with hard-shell clams (Mercenaria mercenaria, δ15NMM) from estuaries. In lakes, δ13CBOM was significantly correlated with δ13CUN, but δ13CBOM was not significantly correlated with δ13CMM in estuaries. Values of δ15NBOM and δ15NUN were significantly and positively correlated with increasing amounts of impervious surface, urban land cover, and human populations in watersheds surrounding lakes. In estuaries, δ15NBOM was only significantly and positively correlated with greater percent impervious surface in the watersheds. Correlations of δ13CBOM in lakes and estuaries, δ13CUN, and δ13CMM with land use and human population were mostly non-significant or weak. Overall, these results show that δ15NBOM can serve as a proxy for δ15N of filter feeding bivalves in lakes and estuaries and is useful for assessing anthropogenic impacts on aquatic systems and resources. Our study area was limited in size, but our results support further studies to test the application of this sediment stable isotope-based technique for assessing and ranking aquatic resources across broad geographical areas.

Three homologous subunits form a high affinity peptide-gated ion channel in Hydra.

Recently, three ion channel subunits of the degenerin (DEG)/epithelial Na(+) channel (ENaC) gene family have been cloned from the freshwater polyp Hydra magnipapillata, the Hydra Na(+) channels (HyNaCs) 2-4. Two of them, HyNaC2 and HyNaC3, co-assemble to form an ion channel that is gated by the neuropeptides Hydra-RFamides I and II. The HyNaC2/3 channel is so far the only cloned ionotropic receptor from cnidarians and, together with the related ionotropic receptor FMRFamide-activated Na(+) channel (FaNaC) from snails, the only known peptide-gated ionotropic receptor. The HyNaC2/3 channel has pore properties, like a low Na(+) selectivity and a low amiloride affinity, that are different from other channels of the DEG/ENaC gene family, suggesting that a component of the native Hydra channel might still be lacking. Here, we report the cloning of a new ion channel subunit from Hydra, HyNaC5. The new subunit is closely related to HyNaC2 and -3 and co-localizes with HyNaC2 and -3 to the base of the tentacles. Coexpression in Xenopus oocytes of HyNaC5 with HyNaC2 and -3 largely increases current amplitude after peptide stimulation and affinity of the channel to Hydra-RFamides I and II. Moreover, the HyNaC2/3/5 channel has altered pore properties and amiloride affinity, more similarly to other DEG/ENaC channels. Collectively, our results suggest that the three homologous subunits HyNaC2, -3, and -5 form a peptide-gated ion channel in Hydra that could contribute to fast synaptic transmission.

Quantitative assessment and localization of the hollowing of the temple after craniectomy and cranioplasty-The frontozygomatic shadow.

BACKGROUND: After cranioplasty, in many cases a not negligible soft tissue defect remains in the temporozygomatical area, also referred to as a hollowing defect of the temple. OBJECTIVE: To assess the precise localization and volume of the hollowing defect, to optimize future cranioplasties. METHODS: CT data of patients who received craniectomy and conventional CAD cranioplasty in our institution between 2012 and 2018 were analyzed. CT datasets prior to craniectomy and after cranioplasty were subtracted to quantify the volume and localization of the defect. RESULTS: Out of 91 patients, 21 had suitable datasets. Five cases had good cosmetic results with no defect visible, 16 patients had an apparent hollowing defect. Their average defect volume was 5.0 cm3 ± 4.5 cm3. The defect localizations were in the area behind the zygomatic process and just below the superior temporal line, covering an area of app. 3x3 cm2. Surgical attempts of temporal muscle restoration were more often found in reports of good results (p<0.01), but also in 50% of reports, whose surgeries resulted in hollowing of the temple. Mean time between the two surgeries was 112 ± 43 days. No significant differences between patients with and without hollowing defect were detected regarding time between the two surgeries, age or performing surgeon. CONCLUSION: This work supplies evidence for the indication of a surgical corrective during cranioplasty in the small but cosmetically relevant area of the "frontozygomatic shadow". Based on our 3D data analysis, future focused surgical strategies may obtain better aesthetical results here.

Public Health Leadership in a VUCA World Environment: Lessons Learned during the Regional Emergency Rollout of SARS-CoV-2 Vaccinations in Heidelberg, Germany, during the COVID-19 Pandemic.

The purpose of this work is to share methods used and lessons learned during a comprehensive inter-institutional pandemic disaster response in Heidelberg, Germany, conveying experiences of the regional SARS-CoV-2 vaccination rollout campaign for up to 1,000,000 vaccines in the year 2020. In this volatile, uncertain, complex, and ambiguous (VUCA) environment, the following five strategic elements were pertinent for institutional arrangements so that specific contributions of the various project partners would be available fast without the necessity of extensive negotiations or information exchange: (1) robust mandate, (2) use of established networks, (3) fast onboarding and securing of commitment of project partners, (4) informed planning of supply capacity, and (5) securing the availability of critical items. Planning tools included analyses through a VUCA lens, analyses of stakeholders and their management, possible failures, and management of main risks including mitigation strategies. The method of the present analysis (VUCA factors combined with analyses of possible failures, and management of stakeholders and risks) can theoretically be adjusted to any public health care emergency anywhere across the globe. Lessons learned include ten tactical leadership priorities and ten major pitfalls.

Population genetic diversity and fitness in multiple environments.

BACKGROUND: When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, Americamysis bahia with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater) and stressful conditions (diluted seawater). The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis. RESULTS: Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation between AFLP diversity and population fitness overall; however, AFLP markers performed poorly at detecting modest but consequential losses of genetic diversity. High diversity lines in the stressful environment showed some evidence of relative improvement as the experiment progressed while the low diversity lines did not. CONCLUSIONS: The combined effects of reduced average fitness and increased variability contributed to increased extinction rates for very low diversity populations. More modest losses of genetic diversity resulted in measurable decreases in population fitness; AFLP markers did not always detect these losses. However when AFLP markers indicated lost genetic diversity, these losses were associated with reduced population fitness.

Sumoylation of peroxisome proliferator-activated receptor gamma by apoptotic cells prevents lipopolysaccharide-induced NCoR removal from kappaB binding sites mediating transrepression of proinflammatory cytokines.

Efficient clearance of apoptotic cells (AC) by professional phagocytes is crucial for tissue homeostasis and resolution of inflammation. Macrophages respond to AC with an increase in antiinflammatory cytokine production but a diminished release of proinflammatory mediators. Mechanisms to explain attenuated proinflammatory cytokine formation remain elusive. We provide evidence that peroxisome proliferator-activated receptor gamma (PPARgamma) coordinates antiinflammatory responses following its activation by AC. Exposing murine RAW264.7 macrophages to AC before LPS stimulation reduced NF-kappaB transactivation and lowered target gene expression of, that is, TNF-alpha and IL-6 compared with controls. In macrophages overexpressing a dominant negative mutant of PPARgamma, NF-kappaB transactivation in response to LPS was restored, while macrophages from myeloid lineage-specific conditional PPARgamma knockout mice proved that PPARgamma transmitted an antiinflammatory response, which was delivered by AC. Expressing a PPARgamma-Delta aa32-250 deletion mutant, we observed no inhibition of NF-kappaB. Analyzing the PPARgamma domain structures within aa 32-250, we anticipated PPARgamma sumoylation in mediating the antiinflammatory effect in response to AC. Interfering with sumoylation of PPARgamma by mutating the predicted sumoylation site (K77R), or knockdown of the small ubiquitin-like modifier (SUMO) E3 ligase PIAS1 (protein inhibitor of activated STAT1), eliminated the ability of AC to suppress NF-kappaB. Chromatin immunoprecipitation analysis demonstrated that AC prevented the LPS-induced removal of nuclear receptor corepressor (NCoR) from the kappaB site within the TNF-alpha promoter. We conclude that AC induce PPARgamma sumoylation to attenuate the removal of NCoR, thereby blocking transactivation of NF-kappaB. This contributes to an antiinflammatory phenotype shift in macrophages responding to AC by lowering proinflammatory cytokine production.

Resilience of aquatic systems: Review and management implications.

Our understanding of how ecosystems function has changed from an equilibria-based view to one that recognizes the dynamic, fluctuating, nonlinear nature of aquatic systems. This current understanding requires that we manage systems for resilience. In this review, we examine how resilience has been defined, measured and applied in aquatic systems, and more broadly, in the socioecological systems in which they are embedded. Our review reveals the importance of managing stressors adversely impacting aquatic system resilience, as well as understanding the environmental and climatic cycles and changes impacting aquatic resources. Aquatic resilience may be enhanced by maintaining and enhancing habitat connectivity as well as functional redundancy and physical and biological diversity. Resilience in aquatic socioecological system may be enhanced by understanding and fostering linkages between the social and ecological subsystems, promoting equity among stakeholders, and understanding how the system is impacted by factors within and outside the area of immediate interest. Management for resilience requires implementation of adaptive and preferably collaborative management. Implementation of adaptive management for resilience will require an effective monitoring framework to detect key changes in the coupled socioecological system. Research is needed to (1) develop sensitive indicators and monitoring designs, (2) disentangle complex multi-scalar interactions and feedbacks, and (3) generalize lessons learned across aquatic ecosystems and apply them in new contexts.