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The degradation of shallow ecosystems has called for efforts to understand the biodiversity and functioning of Mesophotic Ecosystems. However, most empirical studies have been restricted to tropical regions and have majorly focused on taxonomic entities (i.e., species), neglecting important dimensions of biodiversity that influence community assembly and ecosystem functioning. Here, using a subtropical oceanic island in the eastern Atlantic Ocean (Lanzarote, Canary Islands), we investigated variation in (a) alpha and (b) beta functional (i.e., trait) diversity across a depth gradient (0–70 m), as a function of the presence of black coral forests (BCFs, order Antipatharian) in the mesophotic strata, a vulnerable but often overlooked ‘ecosystem engineer’ in regional biodiversity. Despite occupying a similar volume of the functional space (i.e., functional richness) than shallow (

Background Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor. Although tremendous efforts have focused on uncovering the role of APOE4 on parenchymal plaque pathogenesis in AD, mechanistic studies investigating the role of APOE4 on CAA are still lacking. Here, we addressed whether abolishing APOE4 generated by astrocytes, the major producers of APOE, is sufficient to ameliorate CAA and CAA-associated vessel damage. Methods We generated transgenic mice that deposited both CAA and plaques in which APOE4 expression can be selectively suppressed in astrocytes. At 2-months-of-age, a timepoint preceding CAA and plaque formation, APOE4 was removed from astrocytes of 5XFAD APOE4 knock-in mice. Mice were assessed at 10-months-of-age for Aβ plaque and CAA pathology, gliosis, and vascular integrity. Results Reducing the levels of APOE4 in astrocytes shifted the deposition of fibrillar Aβ from the brain parenchyma to the cerebrovasculature. However, despite increased CAA, astrocytic APOE4 removal reduced overall Aβ-mediated gliosis and also led to increased cerebrovascular integrity and function in vessels containing CAA. Conclusion In a mouse model of CAA, the reduction of APOE4 derived specifically from astrocytes, despite increased fibrillar Aβ deposition in the vasculature, is sufficient to reduce Aβ-mediated gliosis and cerebrovascular dysfunction.

Extreme climatic events can reshape the functional structure of ecological communities, potentially altering ecological interactions and ecosystem functioning. While these shifts have been widely documented, evidence of their persistence and potential flow-on effects on ecosystem structure following relaxation of extreme events remains limited. Here, we investigate changes in the functional trait structure - encompassing dimensions of resource use, thermal affinity, and body size - of herbivorous fishes in a temperate reef system that experienced an extreme marine heatwave (MHW) and subsequent return to cool conditions. We quantify how changes in the trait structure modified the nature and intensity of herbivory-related functions (macroalgae, turf, and sediment removal), and explored the potential flow-on effects on the recovery dynamics of macroalgal foundation species. The trait structure of the herbivorous fish assemblage shifted as a result of the MHW, from dominance of cool-water browsing species to increased evenness in the distribution of abundance among temperate and tropical guilds supporting novel herbivory roles (i.e. scraping, cropping, and sediment sucking). Despite the abundance of tropical herbivorous fishes and intensity of herbivory-related functions declined following a period of cooling after the MHW, the underlying trait structure displayed limited recovery. Concomitantly, algal assemblages displayed a lack of recovery of the formerly dominant foundational species, the kelp Ecklonia radiata, transitioning to an alternative state dominated by turf and Sargassum spp. Our study demonstrates a legacy effect of an extreme MHW and exemplified the value of monitoring phenotypic (trait mediated) changes in the nature of core ecosystem processes to predict and adapt to the future configurations of changing reef ecosystems.

PURPOSE: To demonstrate prognostic utility of left atrial strain(LAS) in adult patients with repaired Tetralogy of Fallot(rTOF). METHODS: Adults patients with rTOF were prospectively enrolled in this study between years 2011-2015. Left atrium(LA) phasic functions were assessed using 2D speckle tracking echocardiography(2D-STE). Association of LA strain(LAS) with primary(any cardiovascular event) and secondary(death, heart failure or arrhythmia) composite endpoints was assessed using Cox regression analysis. RESULTS: Hundred-and-twelve rTOF patients, in whom LAS was feasible and were in sinus rhythm, were included in the final analysis (age 33±10 years, 68[61%] male). Median duration of follow-up was 8.6[4.2-9.7] years in the study group. Primary composite endpoint was reached in 48 patients (mean event-free survival time: 7.2[6.6-7.9] years), and secondary composite endpoint was reached in 22 patients (mean event-free survival time: 8.7[8.1-9.2] years). LAS-r was defined as tertile groups(1st tertilend tertile=33-44%,3rd tertile>44%). Decreasing tertiles of LAS-r was associated with primary and secondary composite endpoints in Kaplan-Meier analysis(p=0.02 and 0.002, respectively). In univariable Cox-regression, both decreasing LAS-r and LAS-r tertiles were associated with primary and secondary composite endpoints. Adjusted by initial repair age and NT-proBNP quartiles, increased LAS-r was associated with significantly decreased occurrence of experiencing any events(HR=0.97,CI:0.93-0.99,p=0.037]). Decreasing LAS-r was still associated with primary endpoint when adjusted by left atrium volume index(LAVImax)(HR=0.96,CI:0.03-0.99,p=0.01),left ventricle global longitudinal strain(LV-GLS)(0.95,95%CI:0.92-0.98,p=0.002) or right ventricle free wall longitudinal strain (RV-FWLS)(0.96,95%CI:0.93-0.99,p=0.04). CONCLUSION: Assessment of LA mechanics with the use of STE has incremental utility in determination of mortality and morbidity in rTOF, and may be implemented in clinical practice.

Shark depredation, whereby hooked fish are partially or completely consumed before they can be retrieved, occurs globally in commercial and recreational fisheries. Depredation can damage fishing gear, injure sharks, cause additional mortality to targeted fish species and result in economic losses to fishers. Knowledge of the mechanisms behind depredation is limited. We used a 13 yr dataset of fishery-dependent commercial daily logbook data for the Mackerel Managed Fishery in Western Australia, which covers 15° of latitude and 10000 km of coastline, to quantify how fishing effort and environmental variables influence depredation. We found that shark depredation rates were relatively low in comparison with previous studies and varied across the 3 management zones of the fishery, with 1.7% of hooked fish being depredated in the northern Zone 1, 2.5% in the central Zone 2 and 5.7% in the southern Zone 3. Generalized additive mixed models found that measures of commercial fishing activity and a proxy for recreational fishing effort (distance from town centre) were positively correlated with shark depredation across Zones 1 and 2. Depredation rates increased during the 13 yr period in Zones 2 and 3, and were higher at dawn and dusk, suggesting crepuscular feeding in Zone 1. This study provides one of the first quantitative assessments of shark depredation in a commercial fishery in Western Australia, and for a trolling fishery globally. The results demonstrate a correlation between fishing effort and depredation, suggesting greater fishing effort in a concentrated area may change shark behaviour, leading to high rates of depredation.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are biliary tract pathologies with increased risk of HCC, although HCC is more commonly associated with viral hepatitis and steatohepatitis. HCC risk stratification in PBC/PSC populations may help select patients for surveillance. We hypothesized that metabolic syndrome associated diagnoses and co-morbid nonalcoholic fatty liver disease (NAFLD) may be risk factors for HCC in patients with PBC and PSC. We undertook a multi-institutional case control study of PSC (19 cases, 38 controls) and PBC (39 cases and controls) patients with advanced fibrosis, matched for known HCC risk factors of age and sex, who had native liver explant or resection specimens. In the PSC population, HCC risk was significantly associated with multiple metabolic syndrome associated diagnoses (OR 13, p = 0.02), hyperlipidemia (OR 29, p = 0.03), and obesity (OR 6.8, p = 0.01). In the PBC cohort, only type 2 diabetes was a risk factor for HCC (OR 4.7, p = 0.03). In the PSC cohort, thick fibrous septae were associated with HCC risk (OR 3.4, p = 0.04). No other pathologic features of the nonneoplastic liver were significantly associated with HCC, including features of NAFLD such as macrovesicular steatosis, pericellular fibrosis, and steatohepatitis. Metabolic syndrome associated diagnoses, specifically type 2 diabetes among PBC patients, is associated with HCC risk in patients with biliary type cirrhosis. However, we found no evidence that HCC risk is related to co-morbid NAFLD, indicating a likely distinct mechanism of metabolic syndrome-associated carcinogenesis in these populations.

Este artículo contiene 16 páginas, 5 figuras, 1 tabla., Aim The influence of niche and neutral mechanisms on the assembly of ecological communities have long been debated. However, we still have a limited knowledge on their relative importance to explain patterns of diversity across latitudinal gradients (LDG). Here, we investigate the extent to which these ecological mechanisms contribute to the LDG of reef fishes. Location Eastern Atlantic Ocean. Taxon Reef-associated ray-finned fishes. Methods We combined abundance data across ~60° of latitude with functional trait data and phylogenetic trees. A null model approach was used to decouple the influence of taxonomic diversity (TD) on functional (FD) and phylogenetic (PD) diversity. Standardized effect sizes (SES FD and SES PD) were used to explore patterns of overdispersion, clustering and randomness. Information theoretic approaches were used to investigate the role of large- (temperature, geographic isolation, nitrate and net primary productivity) and local-scale (human population and depth) drivers. We further assessed the role of demographic stochasticity and its interaction with species trophic identity and dispersal capacity. Results Taxonomic diversity peaked at ~15°–20°N, with a second mode of lower magnitude at ~45°N; a pattern that was predicted by temperature, geographic isolation and productivity. Tropical regions displayed a higher proportion of overdispersed assemblages, whilst clustering increased towards temperate regions. Phylogenetic and functional overdispersion were associated with warmer, productive and isolated regions. Demographic stochasticity also contributed largely to community assembly, independently of ecoregions, although variation was dependent on the trophic identity and body size of species. Main conclusions Niche-based processes linking thermal and resource constraints to local coexistence mechanisms have contributed to the LDG in reef fishes. These processes do not act in isolation, stressing the importance of understanding interactions between deterministic and stochastic factors driving community structure in the face of rapid biodiversity change., This study was partially supported by Portuguese national funds from FCT—Foundation for Science and Technology through project UIDB/04326/2020. C.R. and P.N. were financially supported by the Oceanic Observatory of Madeira Project (M1420-01-0145-FEDER-000001—Observatório Oceânico da Madeira-OOM). D.A.S. was supported by a UKRI Future Leaders Fellowship (MR/S032827/1). P.J.M. was supported by a Marie Curie Career Integration Grant (PCIG10-GA-2011-303685). T.W. received funding from the Australian Research Council (DP170100023).

Background Conventional HER2-targeting therapies improve outcomes for patients with HER2-positive breast cancer (BC), defined as tumors showing HER2 protein overexpression by immunohistochemistry and/or ERBB2 gene amplification determined by in situ hybridization (ISH). Emerging HER2-targeting compounds show benefit in some patients with neither HER2 protein overexpression nor ERBB2 gene amplification, creating a need for new assays to select HER2-low tumors for treatment with these compounds. We evaluated the analytical performance of a targeted mass spectrometry-based assay for quantifying HER2 protein in formalin-fixed paraffin-embedded (FFPE) and frozen BC biopsies. Methods We used immunoaffinity-enrichment coupled to multiple reaction monitoring-mass spectrometry (immuno-MRM-MS) to quantify HER2 protein (as peptide GLQSLPTHDPSPLQR) in 96 frozen and 119 FFPE BC biopsies. We characterized linearity, lower limit of quantification (LLOQ), and intra- and inter-day variation of the assay in frozen and FFPE tissue matrices. We determined concordance between HER2 immuno-MRM-MS and predicate immunohistochemistry and ISH assays and examined the benefit of multiplexing the assay to include proteins expressed in tumor subcompartments (e.g., stroma, adipose, lymphocytes, epithelium) to account for tissue heterogeneity. Results HER2 immuno-MRM-MS assay linearity was ≥103, assay coefficient of variation was 7.8% (FFPE) and 5.9% (frozen) for spiked-in analyte, and 7.7% (FFPE) and 7.9% (frozen) for endogenous measurements. Immuno-MRM-MS-based HER2 measurements strongly correlated with predicate assay HER2 determinations, and concordance was improved by normalizing to glyceraldehyde-3-phosphate dehydrogenase. HER2 was quantified above the LLOQ in all tumors. Conclusions Immuno-MRM-MS can be used to quantify HER2 in FFPE and frozen BC biopsies, even at low HER2 expression levels.

Mismatch repair (MMR) immunohistochemistry (IHC) is frequently used to inform prognosis, select (immuno-)therapy, and identify patients for heritable cancer syndrome testing. However, false-negative and false-positive MMR IHC interpretations have been described.Following identification of discordant MMR IHC and DNA-based microsatellite instability testing in a patient with colorectal carcinoma, we retrospectively reviewed institutional archives to identify patient samples with similar discrepancies.We report a patient with metastatic colorectal carcinoma who initially received immunotherapy on the basis of apparent isolated loss of MLH1 by IHC; notably,This study confirms that rare germline polymorphisms can result in incorrect IHC results, potentially affecting selection of optimal therapy and the decision to pursue germline testing. This case further highlights the need for expert molecular pathologic review and communication between clinical and molecular oncology teams.

PURPOSE Mismatch repair (MMR) immunohistochemistry (IHC) is frequently used to inform prognosis, select (immuno-)therapy, and identify patients for heritable cancer syndrome testing. However, false-negative and false-positive MMR IHC interpretations have been described. MATERIALS AND METHODS Following identification of discordant MMR IHC and DNA-based microsatellite instability testing in a patient with colorectal carcinoma, we retrospectively reviewed institutional archives to identify patient samples with similar discrepancies. RESULTS We report a patient with metastatic colorectal carcinoma who initially received immunotherapy on the basis of apparent isolated loss of MLH1 by IHC; notably, MLH1 promoter hypermethylation was negative. Subsequent evaluation of neoplastic tissue on a DNA-based targeted next-generation sequencing panel demonstrated microsatellite stability, low tumor mutational burden, and a benign MLH1 variant, MLH1 p.V384D, accompanied by loss of heterozygosity. The constellation of findings and repeat MLH1 IHC demonstrating retained expression using a different antibody-clone, supported reclassification of the neoplasm as MMR-proficient. Immunotherapy was discontinued, and cytotoxic chemotherapy was initiated. This index case of apparent discordance between MMR IHC and DNA-based microsatellite instability prompted a retrospective review of institutional archives to identify patient samples with similar discrepancies. Further evaluation of neoplasms harboring MLH1 p.V384D with loss of heterozygosity revealed systematic antibody-dependent interference. The review also identified a second IHC-interference candidate, MLH1 p.A441T. CONCLUSION This study confirms that rare germline polymorphisms can result in incorrect IHC results, potentially affecting selection of optimal therapy and the decision to pursue germline testing. This case further highlights the need for expert molecular pathologic review and communication between clinical and molecular oncology teams.

Study question Can we use MPA as a pituitary inhibitor instead of the GnRH antagonist in ovarian stimulation protocols in non-oncological fertility preservation and PGT-A cycles? Summary answer MPA can act as a substitute of GnRH antagonist for pituitary suppression in FP and PGT-A cycles, since the results are similar between both groups. What is known already Progestin-primed ovarian stimulation (PPOS) protocols using exogenous progesterone to replace GnRH analogs during the follicular phase of OS have emerged as an efficient alternative to prevent LH from peaking and have been used successfully in different types of patients. Fertility preservation (FP) and preimplantation genetic testing (PGT-A) have become new emerging areas of assisted reproduction. FP gives women the ability to have children using their own gametes after age-related fertility decline, while PGT-A appears to improve reproductive outcomes in advanced maternal age at increased risk of aneuploid embryos. However, few data are available for both indications regarding PPOS cycle outcomes. Study design, size, duration Multicenter, retrospective, observational, cohort study conducted in eleven IVIRMA centers attached to private universities. We included a total of 4,961 cycles of non-oncological fertility preservation that were distributed as follows: n = 494 were stimulated under a PPOS protocol while n = 4,467 received a GnRH antagonist. Regarding PGT-A cycles, we analyzed 12,461 treatments, of which n = 686 and n = 11,775 received MPA and GnRH antagonist, respectively. Cycles were performed from January 2017 to December 2021. Participants/materials, setting, methods Patients were divided according to the protocol used for preventing premature luteinization during follicular phase of OS. In the MPA group, participants received 10 mg daily administered orally, while in the control group, women received an antagonist once the main follicle reached 13 mm. In FP cycles, ovarian response specific parameters were evaluated, such as endocrine profile and mature oocytes; in PGT-A treatments, main variables were number of biopsied and aneuploid embryos and reproductive outcomes. Main results and the role of chance Regarding FP's baseline characteristics, age was statistically but not clinically significant between the two groups. Length of ovarian stimulation and total dose of hMG administered were similar in both groups, despite the significantly higher total dose of FSH administered in MPA compared to the GnRH antagonist group (p = 0.008) . Number of mature oocytes retrieved (10.2 [95% CI 9.6-10.8] vs 9 [95% CI 8.8-9.2]) was significantly higher in MPA compared to antagonist group; this trend continued regardless of age (≤ 35 or > 35 years). PGT-A cycles followed the same tendency in terms of demographic characteristics. Length of OS was comparable between groups, whilst the total dose of rFSH and hp-HMG administered in the MPA were significantly higher than that in the GnRH antagonist group. Although the number of MII was comparable and despite the lower number of embryos biopsied in the MPA group (4.5±0.2 vs 4.7±0.06, p = 0.031) the number of aneuploid embryos was similar between the two groups (2.3±0.1 vs 2.4±0.04, p = 0.474), as well as implantation (56% vs. 54% p = 0.359) and clinical pregnancy rate (64.1% vs. 62.1, p = 0.316). The miscarriage rate was significantly lower in the group treated with MPA compared to GnRH antagonists (4.7% vs. 8.2%, p = 0.001). Limitations, reasons for caution The retrospective nature of this study may be a reason for caution and only association, not causation, can be inferred from the results. Despite being the largest sample size ever reported with PPOS in no oncological FP and PGT-A, the number of patients included is still low. Wider implications of the findings The administration of PPOS yielded similar or even better results than those observed with GnRH antagonists in terms of oocytes retrieved, rate of aneuploid embryos or clinical results. Therefore, PPOS could be recommended for ovarian stimulation in non-oncological FP and PGT-A cycles as it allows for a more patient-friendly approach. Trial registration number Not applicable

Study question Is partial premature ovulation (PPO) detection during the oocyte pick-up (OPU) a sign of poor prognosis in in vitro fertilization (IVF) cycles with own oocytes? Summary answer PPO halves the number of metaphase II oocytes available for an IVF treatment without reducing their quality, demonstrated by unaltered fertilization and top-quality blastocyst rates. What is known already PPO detected during the OPU procedure has not been extensively studied in the literature. This phenomenon may result in a reduction in the number and/or competence of the oocytes retrieved, due to the potential loss of the already expelled oocytes, as well as the likely dominance exerted by the ruptured follicle/s in the rest of the cohort. Despite this, several authors have demonstrated that competent oocytes can be retrieved from these already ruptured follicles, suggesting that oocyte extrusion frequently does not occur after follicle rupture. The potential negative effect exerted in the rest of sibling oocytes remains unknown. Study design, size, duration Retrospective cohort analysis performed in IVIRMA Valencia (Spain), including 8994 cycles of controlled ovarian stimulation (COS) for an IVF treatment with fresh own oocytes, between January 2016 and May 2021. OPU procedures for oocyte cryopreservation, as well as mixed cycles with both fresh and frozen oocytes, were discarded. PPO diagnosis was based on ultrasound visualization of any already formed corpus luteum structure/s, a lower follicular count than expected, and/or free fluid. Participants/materials, setting, methods Female patients undergoing OPU after COS for a fresh IVF treatment. Cycles in which PPO has been detected will be compared with a random, and of the same size, sample without PPO. Mean number of oocytes, metaphase II, fertilized oocytes and top-quality embryos, as well as IVF success rates, will be compared between both groups. Patients’ basal characteristics and COS parameters will be analyzed in order to detect any potential early indicator of PPO. Main results and the role of chance PPO was detected in 123 of the 8994 cycles (1.37%) performed. A random control group of 123 cycles without PPO was selected. Patients’ mean age was 37.6±3.6, with a BMI of 23.3±4.1 kg/m2 and an anti-mullerian hormone of 1.62±1.3 ng/mL. Patient’s basal characteristics and COS parameters were statistically comparable among groups (p > 0.05), except for lower serum estradiol levels (2037.64 vs. 1582.24 pg/mL; p = 0.004) in the PPO group on the last ultrasound prior to OPU. Patients with PPO showed lower aspiration rates (88.95% vs. 55.78% in the PPO gr.), as well as a reduced mean number of oocytes (10.69 vs. 5.68 in the PPO gr.), metaphase II (8.41 vs. 4.33 in the PPO gr.), fertilized oocytes (6.23 vs. 3.26 in the PPO gr.) and top-quality blastocysts (2.77 vs. 1.35 in the PPO gr.) (p = 0.000). In contrast, maturation (80.72% vs. 76.57% in the PPO gr.), fertilization (73.52% vs. 75.18% in the PPO gr.) and top-quality blastocyst rates (44.03% vs. 38.68% in the PPO gr.) were statistically similar between both groups (p > 0.05). Limitations, reasons for caution The main limitations of the present study are its retrospective design and its small sample size, derived from the low frequency of the PPO phenomenon in our clinic. Larger prospective studies should be proposed in order to accurately define the negative impact of PPO in IVF success rates. Wider implications of the findings PPO clearly reduces the number of oocytes available for an IVF treatment, although it does not seem to impair the competence of the remaining cohort. Once PPO is detected, cycle cancellation may not be worth the associated loss of money, time and morale, especially given its low prevalence (around 1%). Trial registration number Not applicable

Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the management of diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury. To address this unmet need, inspired by molecular gastronomy techniques, we have developed a family of gas-entrapping materials (GEMs) for delivery of CO to the GI tract. We show highly tunable and potent delivery of CO, achieving clinically relevant CO concentrations in vivo in rodent and swine models. To support the potential range of applications of foam GEMs, we evaluated the system in three distinct disease models. We show that a GEM containing CO dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation and oxidative tissue injury, and mitigated radiation-induced gut epithelial damage in rodents. Collectively, foam GEMs have potential paradigm-shifting implications for the safe therapeutic use of CO across a range of indications.

Study question Is the individualised follitropin delta regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight effective and safe in a long GnRH agonist protocol? Summary answer Per started stimulation, the live birth rate following fresh transfer was 43% and the cumulative live birth rate following fresh and frozen transfers was 58%. What is known already Individualised follitropin delta treatment in a GnRH antagonist protocol reduces the incidence of OHSS and/or preventive interventions without compromising live birth rates. In a multinational, double-blind, randomised trial (RAINBOW, NCT03564509) exploring the efficacy and safety of choriogonadotropin beta in women undergoing ovarian stimulation in a long GnRH agonist protocol, the control group was treated with the same individualised follitropin delta regimen based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Women had one stimulation cycle and were followed up to live birth following the fresh and all frozen blastocyst transfers performed within one year after start of stimulation. Study design, size, duration Analysis of fresh and cumulative live birth rates in 104 women (30–42 years, AMH 5-35 pmol/L) down-regulated with 0.1 mg/day triptorelin and stimulated in one cycle with a fixed individualised daily dose of follitropin delta. Triggering was performed when 3 follicles ≥17 mm. Oocytes were inseminated by ICSI; blastocyst transfer was on day 5 and remaining blastocysts were cryopreserved on day 5/6 and subsequently used for frozen transfers. Participants/materials, setting, methods Data collection included live birth and neonatal health follow-up for all transfers of fresh or frozen embryos performed within one year after the start of stimulation. The data presented are based on all women who were down-regulated and started stimulation. The cumulative live birth rate was calculated as the percentage of women starting stimulation that had at least one live born neonate. Main results and the role of chance Of 104 women starting stimulation, 101 had triggering. Two subjects were cancelled due to poor response and one due to adverse event. Nine subjects had transfer cancellations; six due to no day 5 blastocyst available, and one each due to risk of OHSS, adverse event, and other reason. The average daily dose of follitropin delta was 11.0±1.6 and the duration of stimulation was 10.3±1.6 days. The mean number of oocytes was 12.5±6.4; the mean number of blastocysts was 5.1±3.4; and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate (10–11 weeks after transfer) was 43% per started stimulation. There were six cases of early OHSS (5.8%) graded as mild (3) and moderate (3) and six cases with late OHSS (5.8%) graded as moderate (3) and severe (3). In total, 92% of women had at least one fresh or frozen transfer and 150 blastocyst transfers were performed (92 fresh and 58 frozen transfers). Per started stimulation, the live-birth rate following fresh transfer was 43% and the cumulative live-birth rate following fresh and all frozen transfers was 58%. There were three neonates with congenital anomalies following fresh transfer and none following frozen transfer. Limitations, reasons for caution This is the first clinical trial investigating the individualised follitropin delta regimen in a long GnRH agonist protocol. A final evaluation of this regimen requires comparative data. Accordingly, a randomised trial comparing follitropin delta in a long GnRH agonist protocol vs. in a GnRH antagonist protocol is currently ongoing (NCT03809429). Wider implications of the findings The use of individualised follitropin delta dosing based on AMH and body weight in a long GnRH agonist protocol resulted in high fresh and cumulative live birth rates, and with an incidence of OHSS similar to previously reported for other FSH products in long GnRH agonist protocols. Trial registration number NCT03564509

Study question Is there an optimal serum progesterone (P) threshold in frozen embryo transfer (FET) modified natural cycles when luteal phase support (LPS) is given? Summary answer Serum P measured on the day of ET is not related with ongoing pregnancy outcome when doing a modified natural cycle with LPS. What is known already Recent publications showed that there is a minimum threshold of serum P that needs to be reached in artificial cycles to optimize pregnancy rates. When using micronized vaginal P (MVP), about 30% of patients show low levels of serum P ( Study design, size, duration Prospective cohort unicentric study performed in IVI RMA Valencia (Spain), including 244 cycles from February 2020 to January 2021. Participants/materials, setting, methods Infertile patients 6.5mm). MVP was used for LPS (200mg/12h). Ongoing pregnancy rate (OPR) was correlated with serum P levels on the FET day, measured within two hours before transfer. Main results and the role of chance A total of 241 patients were analyzed. Mean age was 38.1 + 3.8 years, with a mean BMI of 23.3 + 3.9. On the rec-hCG day the mean leading follicle size was 17.7±0.1 mm. The endometrium displayed a trilaminar pattern, with a mean thickness of 7.8±3.3 mm, and mean P and estradiol (E2) levels were 0.30±0.03 ng/ml and 249.39±11.03 pg/ml, respectively. A mean of 1.1 blastocysts were transferred (90.9% were single embryo transfers), 27.4% (66) from donated and 72.6 % (175) from own oocytes. On the day of FET, the mean serum P and E2 levels were 26.19 + 8.97ng/mL and 154.12 + 96.08pg/mL, respectively. The overall OPR was 51.5% (124). OPR according to quartiles of serum P (ng/mL) was 56.7% (Q1, P 20.2-24.8), 51.7% (Q3, P > 24.8-31.1), 50.0% (Q4, P > 31.1), p = 0.78). Multivariate logistic regression showed that serum P was not related with OPR after adjusting for age, BMI, E2 and origin of oocytes (aOR:0.98, 95% CI:0.93-1.04, p = 0.47). Only 2 patients had serum P levels below 10 ng/mL, with values of 8.6 and 8.8 ng/mL on the ET day and had a negative pregnancy test. Limitations, reasons for caution As part of our routine clinical practice, MVP (200mg/12h) is given for LPS in patients undergoing a FET in the context of a modified natural cycle. Thus, these results cannot be extrapolated to LPS-free or any other LPS protocol in FET modified natural cycles. Wider implications of the findings The majority of patients undergoing FET in modified natural cycles when using LPS have adequate levels of serum P and thus, do not have an impact on pregnancy outcome. According to our data, there is no need to measure serum P levels on the luteal phase of modified natural cycles. Trial registration number NCT04259996

Global warming is facilitating the range expansion of tropical herbivores, causing a tropicalization of temperate marine ecosystems, where tropical herbivores can suppress habitat‐forming macrophytes, supporting the resilience of canopy‐free ecosystem states. However, currently we lack a thorough understanding of the mechanisms that, on one hand, support the persistence of tropical herbivores and on the other support the recovery of temperate foundation species in tropicalized ecosystems, a required knowledge to predict potential regime shifts and reversals to the baseline state of the ecosystem. This study tested processes behind the persistence of the tropicalization of temperate reefs which experienced a complete loss of their kelp forests and an influx of tropical herbivores following a marine heatwave in 2011. For this, we assessed the feedback mechanisms that maintain turf‐dominated states (recruitment of tropical herbivores, browsing and grazing rates and turf cover) and those that resist it (kelp recruitment, survival and reproductiveness). We found that the reefs remained tropicalized with high abundances of turf and tropical herbivores after 9 years from the regime shift. The rabbitfish Siganus fuscescens and the chub Kyphosus bigibbus were the most important herbivores whose persistence was supported by the adjacent reef lagoon, where seagrass meadows and the backreef habitats hosted juveniles of both species, particularly rabbitfish. Tropical herbivores exerted a strong top–down control on turf seaweed and kelp during herbivory assays, rapidly consuming kelp individuals in open areas. However, in topographical refuges in the reefs, herbivory was low and kelp individuals survived, with some having reproductive tissue. Synthesis. Our findings incorporate the importance of nursery grounds for tropical herbivores and herbivory refugia for kelp individuals into the tropicalization model, where the former increases the resilience of canopy‐free states and the latter might facilitate recovering kelp populations. The restoration of abundant warm‐resistant kelp populations in shelters could provide local sources of propagules to recolonize open spaces; however, our results suggest that the reduction of herbivory and the provision of turf‐free substratum would be necessary to boost the recovery of kelp forests.

CONTEXT: Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. OBJECTIVE: To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. DESIGN: Cross-sectional case-control study. SUBJECTS AND METHODS: Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR)

Our aims were to assess performance of duodenal intraepithelial lymphocyte counting for diagnosis of Helicobacter pylori (H. pylori) gastritis, and effects of eradication therapy on intraepithelial lymphocytosis. Paired duodenal and gastric biopsies from subjects with a pathologic diagnosis of H. pylori gastritis were reviewed. Higher duodenal intraepithelial lymphocyte counts were observed in 40 subjects with H. pylori gastritis (26 ± 5 per villus) than 52 subjects negative for H. pylori (12 ± 2 per villus). After successful eradication therapy, duodenal lymphocytes were indistinguishable from H. pylori–negative subjects, whereas they remained elevated after failed eradication therapy. This study confirms previous reports of increased duodenal intraepithelial lymphocytes in patients with concurrent Helicobacter pylori gastritis. Intraepithelial lymphocyte counts of > 15 per villus or > 10 per 100 enterocytes were predictive of infection. Duodenal lymphocytosis decreases significantly after successful eradication therapy but remains elevated when treatment fails.

In the province of KwaZulu-Natal in South Africa, isiZulu is a dominant language, yet it is not used as the language of teaching and learning in schools. The linguistic rights of isiZulu-speaking l...

Introduction: Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. Methods: KP-metabolite levels were determined in plasma from PAH patients (median follow-up 42 months) and in rats with monocrotaline- and Sugen/hypoxia-induced PH. Blood sampling of PAH patients was performed at the time of diagnosis, six months and one year after PAH therapy. Results: KP activation with lower tryptophan, higher kynurenine (Kyn), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KA), and anthranilic acid was observed in treatment-naïve PAH patients compared with controls. A similar KP-metabolite profile was observed in monocrotaline, but not Sugen/hypoxia-induced PAH. Human lung primary cells (microvascular endothelial cells, pulmonary artery smooth muscle cells, and fibroblasts) were exposed to different cytokines in vitro. Following exposure to interleukin-6 (IL-6)/IL-6 receptor a (IL-6Ra) complex, all cell types exhibit a similar KP-metabolite profile as observed in PAH patients. PAH therapy partially normalized this profile in survivors after one year. Increased KP-metabolites correlated with higher pulmonary vascular resistance, shorter six-minute walking distance, and worse functional class. High levels of Kyn, 3-HK, QA, and KA measured at the latest time-point were associated with worse long-term survival. Conclusion: KP-metabolism was activated in treatment-naïve PAH patients, likely mediated through IL-6/IL-6Ra signaling. KP-metabolites predict response to PAH therapy and survival of PAH patients.

Sharks play a key role in the structure and functioning of marine ecosystems. More ecological information is essential to implement responsible management and conservation actions on this fauna, particularly at a regional level for threatened species.

Centrizonal hepatocyte dropout has been described in diverse liver pathologies, including viral hepatitis, venous outflow obstruction, and allograft cellular rejection. However, its clinical significance remains uncertain.We designed a clinicopathological study of 206 allograft liver biopsies with centrizonal hepatocyte dropout. Centrizonal hepatocyte dropout was associated most frequently with cellular rejection (n = 62), asymptomatic/protocol biopsies (n = 56), immediate post-transplantation biopsies (n = 21), biliary obstruction (n = 14), and viral hepatitis (n = 13). The differential diagnosis is informed by timing post-transplantation, biliary imaging and laboratory test results. 'Cholestatic' and 'hepatocytic' laboratory patterns were associated with biliary obstruction and cellular rejection, respectively. A mixed pattern peaking after biopsy was observed in viral hepatitis cases. In the context of cellular rejection, dropout was not associated with the time interval to normalisation of serum alanine aminotransferase (ALT), but was associated with shorter transplant-free survival (hazard ratio 4, P = 0.01) than that of histological severity-matched controls. In time zero allograft biopsies, time to ALT normalisation was prolonged (median, 15 versus 11 days, P = 0.002) in allografts with centrizonal dropout, with no effect on retransplant-free survival.Centrizonal hepatocyte dropout has low clinicopathological diagnostic specificity. However, it correlates with adverse clinical outcomes in allograft cellular rejection and time zero biopsies.

Predicates like "coloring-the-star" denote events that have a temporal duration and a culmination point (telos). When combined with perfective aspect (e.g., "Valeria has colored the star"), a culmination inference arises implying that the action has stopped, and the star is fully colored. While the perfective aspect is known to constrain the conceptualization of the event as telic, many reading studies have demonstrated that readers do not make early commitments as to whether the event is bounded or unbounded. A few visual-world studies tested the processing of telic predicates during online sentence processing, demonstrating an early integration of aspectual and temporal cues. By employing the visual-world paradigm, we tested the incremental processing of the perfective aspect in Italian in two eye-tracking studies in which listeners heard durative predicates in the perfective form in a scenario showing a completed and a non-completed event. Differently from previous studies, we compared telic durative predicates such as "coloring-the-star" to punctual predicates such as "lighting-the-candle." While for punctual predicates, the inferences of telicity (the event has a telos) and of culmination (the telos is reached) are lexically encoded in the perfective verb, for durative predicates, the degree of event completion (visually encoded) needs to be integrated with perfective aspect (linguistically encoded) for the culmination inference derivation. By modulating the interaction of visual and linguistic stimuli across the two experiments, we show that the verb's perfective aspect triggers the culmination inference incrementally during sentence processing, offering novel evidence for the continuous integration of linguistic processing with real-world visual information.

Gallbladder carcinoma is an uncommon malignancy with an overall 5-year survival of less than 5%. Gallbladder carcinoma has been strongly linked with cholelithiasis and chronic inflammation. Case reports and series have described cholecystitis with acute (neutrophilic) inflammation in association with gallbladder carcinoma, although a clear relationship to patient outcome has not been established. Our series included 8 cases of gallbladder carcinoma with high tumor-associated neutrophils (>25 per high power field) that were associated with shorter patient survival (Cox regression coefficient 6.2, p = 0.004) than age- and stage-matched controls. High tumor-associated neutrophils were not associated with gallbladder rupture/perforation or increased bacterial load measured by 16S PCR. Neutrophilic inflammation with gallbladder carcinoma correlates to shorter survival, independent of patient age and stage of carcinoma. The findings suggest that the degree of neutrophilic inflammation may have prognostic significance in specimens from patients with gallbladder carcinoma after cholecystectomy. Further studies with larger case numbers are needed to confirm and generalize these findings.

Autism Spectrum Disorder (ASD) or autism is characterized by social and non-social symptoms, including sensory hyper- and hyposensitivities. A suggestion has been put forward that some of these symptoms could be explained by differences in how sensory information is integrated with its context, including a lower tendency to leverage the past in the processing of new perceptual input. At least two history-dependent effects of opposite directions have been described in the visual perception literature: a repulsive adaptation effect, where perception of a stimulus is biased away from an adaptor stimulus, and an attractive serial choice bias, where perceptual choices are biased towards the previous choice. In this study, we investigated whether autistic participants differed in either bias from typically developing controls (TD). Sixty-four adolescent participants (31 with ASD, 33 TD) were asked to categorize oriented line stimuli in two tasks which were designed so that we would induce either adaptation or serial choice bias. Although our tasks successfully induced both biases, in comparing the two groups, we found no differences in the magnitude of adaptation nor in the modulation of perceptual choices by the previous choice. In conclusion, we find no evidence of a decreased integration of the past in visual perception of autistic individuals.

Monitoring the ecological status of marine coastal lagoons requires the integration of multiple indices. However, the efficacy of monitoring programs is complicated by the diverse array of habitats that conform coastal lagoons. In this study, we compared four sampling methods (25-m and 50-m beach seines, beam trawl and Riley push net) in the Ria Formosa coastal lagoon (South Portugal) for assessing fish assemblage and diversity. We compared species richness and assemblage structure with species accumulation curves and multivariate analysis, and assessed diversity patterns using taxonomic, phylogenetic and functional diversity indices. Variation in fish assemblage structure was mostly explained by gear type, and almost all diversity metrics varied not only according to sampling method but also depending on habitat characteristics and season. Based on operational costs and diversity patterns captured by each gear, we conclude that the combined use of 25-m beach seine and beam trawl is the preferred approach. The proposed methodology will provide the data necessary for assessment of ecological status of coastal lagoons. info:eu-repo/semantics/publishedVersion

Immunohistochemistry (IHC) is often critical for distinction between metastatic carcinomas of Mullerian organ and breast origin. Paired box family protein 8 (PAX8) has been described as a transcription factor highly specific to neoplasms derived from Mullerian organs, thyroid, and kidney. PAX8 IHC with polyclonal and monoclonal antibody reagents was performed on 27 primary and 22 metastatic breast carcinomas. Eight of 27 primary breast carcinomas (30%) were positive for PAX8 with the monoclonal antibody reagent only; 0 of 22 were polyclonal anti-PAX8 immunoreactive. Substantial numbers of metastases had positive immunoreactivity for polyclonal anti-PAX8 (23%). Each of these metastases and additional cases (45% total) also had positive immunoreactivity for monoclonal anti-PAX8, including 5 of 7 brain metastases. IHC with monoclonal anti-PAX8 was positive on 6 of 7 primary breast carcinomas corresponding to PAX8-positive metastases. Together, these results indicate a significant fraction of breast carcinoma metastases and corresponding primary neoplasms have immunoreactivity for PAX8, and positivity rates depend on the antibody used. Diagnoses of metastatic breast carcinoma were achieved with the aid of clinical history and additional IHC in cases of PAX8 immunoreactivity. Contextual interpretation is imperative for PAX8 IHC, particularly when the differential diagnosis includes metastatic breast carcinoma with limited diagnostic material available.

Female hyperandrogenism is a relatively common endocrine disorder (estimated prevalence, 7%) and has a broad range of etiologies (1). A review of 873 patients with excess androgens at a reproductive endocrinology clinic led to diagnoses of polycystic ovarian syndrome (PCOS, 82%), hyperandrogenism and hirsutism (6%), idiopathic hirsutism (4%), hyperandrogenic insulin-resistant acanthosis nigricans (4%), nonclassical and classical adrenal hyperplasia (3%), and androgen-secreting neoplasms (0.2%) (1). Although the majority of female hyperandrogenism is explained by PCOS,2 androgen-producing neoplasms are potentially surgically curable (2). Ovarian and adrenal vein sampling may have utility when a neoplasm is suspected and imaging findings are not definitive (3). We present 3 cases of intravenous sampling for hyperandrogenism. Patient 1 was a 24-year-old, never-pregnant woman referred to an endocrinologist for hyperandrogenism, characterized by 8 months of increasingly dark, coarse hair on the chin and around the nipples. Other symptoms included 4 months of increased libido, 2 months of hair loss along the partition and male-pattern recession, and worsening acne. Menstrual cycles were every 4 weeks and unremarkable. Plasma total testosterone was 130 ng/dL (4.5 nmol/L) (reference range [ref.], 0–80 ng/dL, 0–2.8 nmol/L), calculated free testosterone was 21 pg/mL (73 pmol/L) (ref., 1–18 pg/mL, 3–63 pmol/L), and dehydroepiandrosterone (DHEA) was 7250 ng/mL (25000 nmol/L) (ref., 450–3280 ng/mL, 1550–11300 nmol/L). Laboratory …

Congestive hepatopathy is a complication of right heart failure and chronically elevated right heart pressure. Histologic findings include sinusoidal dilatation, centrilobular hepatocellular plate atrophy, and fibrosis. We performed a validation study of a recently proposed scoring system (0 to 4 scale) for congestive hepatic fibrosis on 38 liver biopsies. Glutamine synthetase immunohistochemistry was also performed, and loss of centrizonal immunoreactivity correlated with increasing fibrosis score (P

The conservation of coastal seascapes requires a better understanding of how different dimensions of biodiversity are represented between juxtaposed habitats. We explored patterns of taxonomic, functional, and phylogenetic diversity of fishes between four habitats (sandy bottoms, rocky reefs of high and low relief, and mixed bottoms) within a semi-lagoon seascape (Las Canteras beach) in Gran Canaria Island. Data on fish presence in each habitat were provided by weekly snorkeling tours, at day and night, from August 2015 to August 2018. Indices that measured ‘how much’ biodiversity, i.e., ‘how many species’ (species richness), ‘how much functional dissimilarity’, and ‘how much evolutionary history’ were larger on rocky bottoms. However, indices that measured phylogenetic differentiation, i.e., ‘how different’, via the taxonomic distinctiveness and the Mean Pairwise Distance index were particularly high on sandy bottoms, because of the presence of elasmobranchs, which were absent from rocky bottoms. The ‘phylogenetic signal’, whether phylogenetically related species are functionally similar, was significant on rocky bottoms, but non-significant on sandy bottoms, reflecting phylogenetic ‘overdispersion’ on sandy bottoms and phylogenetic ‘clustering’ on hard bottoms. From a conservation perspective, sandy bottoms cannot be underrated, particularly in the context of maximizing indices that measure ‘how phylogenetically different’ biodiversity is.

Contains fulltext : 203446.pdf (Publisher’s version ) (Closed access) For decades, the extent to which visual imagery relies on the same neural mechanisms as visual perception has been a topic of debate. Here, we review recent neuroimaging studies comparing these two forms of visual experience. Their results suggest that there is a large overlap in neural processing during perception and imagery: neural representations of imagined and perceived stimuli are similar in the visual, parietal, and frontal cortex. Furthermore, perception and imagery seem to rely on similar top-down connectivity. The most prominent difference is the absence of bottom-up processing during imagery. These findings fit well with the idea that imagery and perception rely on similar emulation or prediction processes. 12 p.

Marine fisheries in coastal ecosystems in many areas of the world have historically removed large-bodied individuals, potentially impairing ecosystem functioning and the long-term sustainability of fish populations. Reporting on size-based indicators that link to food-web structure can contribute to ecosystem-based management, but the application of these indicators over large (cross-ecosystem) geographical scales has been limited to either fisheries-dependent catch data or diver-based methods restricted to shallow waters (20 m) that can misrepresent the abundance of large-bodied fished species. We obtained data on the body-size structure of 82 recreationally or commercially targeted marine demersal teleosts from 2904 deployments of baited remote underwater stereo-video (stereo-BRUV). Sampling was at up to 50 m depth and covered approximately 10,000 km of the continental shelf of Australia. Seascape relief, water depth, and human gravity (i.e., a proxy of human impacts) were the strongest predictors of the probability of occurrence of large fishes and the abundance of fishes above the minimum legal size of capture. No-take marine reserves had a positive effect on the abundance of fishes above legal size, although the effect varied across species groups. In contrast, sublegal fishes were best predicted by gradients in sea surface temperature (mean and variance). In areas of low human impact, large fishes were about three times more likely to be encountered and fishes of legal size were approximately five times more abundant. For conspicuous species groups with contrasting habitat, environmental, and biogeographic affinities, abundance of legal-size fishes typically declined as human impact increased. Our large-scale quantitative analyses highlight the combined importance of seascape complexity, regions with low human footprint, and no-take marine reserves in protecting large-bodied fishes across a broad range of species and ecosystem configurations.Las pesquerías marinas de los ecosistemas costeros en muchas áreas del mundo históricamente han removido a individuos de gran tamaño, potencialmente perjudicando el funcionamiento ambiental y la sostenibilidad a largo plazo de las poblaciones de peces. Los reportes sobre los indicadores basados en el tamaño que se vinculan con la estructura de la red alimenticia pueden contribuir al manejo basado en el ecosistema, aunque la aplicación de estos indicadores a grandes (inter-ecosistemas) escalas geográficas ha estado limitada a datos de captura dependientes de las pesquerías o métodos basados en el buceo restringidos a aguas someras (20 m), lo cual puede representar erróneamente la abundancia de peces de gran tamaño capturados para la pesca. Obtuvimos los datos de la estructura del tamaño corporal de 82 teleósteos marinos demersales focalizados por razones recreativas o comerciales tomados de 2,904 despliegues de video estéreo subacuático remoto con cebo (stereo-BRUV, en inglés). El muestreo se realizó hasta los 50 metros de profundidad y abarcó aproximadamente 10,000 km del talud continental de Australia. El relieve marino, la profundidad del agua y la gravedad humana (es decir, un indicador de los impactos humanos) fueron los pronosticadores más sólidos de la probabilidad de incidencia de los peces de gran tamaño y de la abundancia de peces por encima del tamaño legal mínimo de captura. Las reservas marinas de protección total tienen un efecto positivo sobre la abundancia de los peces que están por encima del tamaño legal, aunque el efecto varió según el grupo de especies. Como contraste, los peces de tamaño sublegal fueron pronosticados de mejor manera usando gradientes de la temperatura de la superficie marina (media y varianza). En las áreas con un impacto humano reducido, los peces de gran tamaño corporal tenían hasta tres veces mayor probabilidad de aparecer y los peces de tamaño legal eran aproximadamente cinco veces más abundantes. Para los grupos de especies conspicuas con afinidades contrastantes de hábitat, ambiente y biogeografía, la abundancia de peces de tamaño legal normalmente declinó conforme aumentó el impacto humano. Nuestros análisis cuantitativos a gran escala resaltan la importancia conjunta que tienen la complejidad marina, las regiones con una huella humana reducida y las reservas marinas de protección total para la protección de los peces de gran tamaño corporal en una extensa gama de especies y configuraciones ecosistémicas. Efectos de la Huella Humana y los Factores Biofísicos sobre la Estructura del Tamaño Corporal de Especies Marinas Capturadas para la Pesca.

Marine reserves are a key tool for the conservation of marine biodiversity, yet only ~2.5% of the world's oceans are protected. The integration of marine reserves into connected networks representing all habitats has been encouraged by international agreements, yet the benefits of this design has not been tested empirically. Australia has one of the largest systems of marine reserves, providing a rare opportunity to assess how connectivity influences conservation success. An Australia‐wide dataset was collected using baited remote underwater video systems deployed across a depth range from 0 to 100 m to assess the effectiveness of marine reserves for protecting teleosts subject to commercial and recreational fishing. A meta‐analytical comparison of 73 fished species within 91 marine reserves found that, on average, marine reserves had 28% greater abundance and 53% greater biomass of fished species compared to adjacent areas open to fishing. However, benefits of protection were not observed across all reserves (heterogeneity), so full subsets generalized additive modelling was used to consider factors that influence marine reserve effectiveness, including distance‐based and ecological metrics of connectivity among reserves. Our results suggest that increased connectivity and depth improve the aforementioned marine reserve benefits and that these factors should be considered to optimize such benefits over time. We provide important guidance on factors to consider when implementing marine reserves for the purpose of increasing the abundance and size of fished species, given the expected increase in coverage globally. We show that marine reserves that are highly protected (no‐take) and designed to optimize connectivity, size and depth range can provide an effective conservation strategy for fished species in temperate and tropical waters within an overarching marine biodiversity conservation framework., An Australia‐wide dataset was collected using baited remote underwater video systems deployed across a depth range from 0 to 100 m to assess the effectiveness of marine reserves for protecting fished species. A meta‐analytical comparison of 73 fished species within 91 marine reserves found that, on average, marine reserves had 28% greater abundance and 53% greater biomass of fished species compared to adjacent areas open to fishing. We show that marine reserves that are highly protected (no‐take) and designed to optimize connectivity, size and depth range can provide an effective conservation strategy for fished species in temperate and tropical waters.

When bacterial cells come in contact, antagonism mediated by the delivery of toxins frequently ensues. The potential for such encounters to have long-term beneficial consequences in recipient cells has not been investigated. Here, we examined the effects of intoxication by DddA, a cytosine deaminase delivered via the type VI secretion system (T6SS) of Burkholderia cenocepacia. Despite its killing potential, we observed that several bacterial species resist DddA and instead accumulate mutations. These mutations can lead to the acquisition of antibiotic resistance, indicating that even in the absence of killing, interbacterial antagonism can have profound consequences on target populations. Investigation of additional toxins from the deaminase superfamily revealed that mutagenic activity is a common feature of these proteins, including a representative we show targets single-stranded DNA and displays a markedly divergent structure. Our findings suggest that a surprising consequence of antagonistic interactions between bacteria could be the promotion of adaptation via the action of directly mutagenic toxins.