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Ballistic seed dispersal (ballochory) involves the autonomous explosive release of seeds from adult plants. The unconventional mechanics of this strategy have understandably drawn considerable scientific attention. The explosive release of seeds is achieved by a variety of physical mechanisms but broadly involves the rapid coiling or shattering of seed pods to transfer kinetic energy to seeds, facilitated largely by either the evaporation or absorption of water in seed pod tissues. There has been a bias toward researching physiological and physical aspects of ballistic plants, with the evolutionary ecology being comparatively neglected. Although ballochory is represented in 23 plant families, it has never become common. This fact should invite curiosity regarding the selective pressures that encourage its evolution. Previous research has been unable to correlate ballochory with plant traits such as morphology, generation time or habitat preferences, and so we take an alternative approach in considering the evolutionary advantages that can provide insight on the shared set of circumstances that favour the evolution of this strategy. We review the known selective advantages that ballistic dispersal can confer to plants and promote a hypothesis that ballochory may be particularly selected for in instances of concentrated predation pressure on parental canopies. For plants in static and patchy landscapes, such a strategy could balance a trade‐off between escaping concentrated natural enemies while maximising the probability of transport to suitable habitat. We account for its rarity by considering the major opportunity cost that may only be justified when other seed dispersal mechanisms are limited. Moving forward, we suggest experimental manipulations to test this hypothesis and promote a research agenda in the field of ballistic seed dispersal that illuminates its intriguing evolution. This viewpoint article describes an initial hypothesis regarding the evolutionary ecology of explosive seed dispersal. Although the physical mechanisms of this unconventional process are well understood, the evolution of this plant trait has received comparatively little attention. We suggest that predation pressure on or beneath the parent plant could help explain the repeated evolution of this trait and hope to stimulate experimental manipulations to test this.

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51 Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin <30g/l, liver disease, <18 years, of non-Black or non-White self-reported ethnicity were excluded. Agreement was assessed by bias, precision and 30%-accuracy and was stratified for ethnicity and GFR. 1888 51 Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m 2 respectively, p<0.001). Disregarding the ethnicity adjustment significantly improved GFR estimates for Black participants (bias 6.7 and 2.4ml/min/1.73m 2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p<0.001). The LM Revised equation had the smallest bias for both White and Black participants (5.8ml and -1.1ml/min/1.73m 2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m 2 compared to <60ml/min/1.73m 2 using eGFR-CKD-EPI equation for both White and Black participants (p<0.001). Multivariate regression methodology with adjustment for age, sex and log(serum creatinine) in the cohort yielded an ethnicity coefficient of 1.018 (95% CI: 1.009–1.027). Overestimation of measured GFR with eGFR equations using ethnicity adjustment factors may lead to reduced CKD diagnosis and under-recognition of severity in people of Black ethnicity. Our findings suggest that ethnicity adjustment for GFR estimation in non-African Americans may not be appropriate for use in people of Black ethnicity in the UK.

Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49-1.17) and RR0.50 (95%CI 0.42-0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed.

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection.

Background Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. Methods We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. Results Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24–4,18; p  <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27–2.53; p  <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19–2.13) for stage 1; p  < 0.005, 2.71(95%CI 1.82–4.05); p  < 0.001for stage 2 and 2.99 (95%CI 2.17–4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. Conclusions This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3–6 months.

Bacteria integrate environmental signals to regulate gene expression and protein production to adapt to their surroundings. One such behavioral adaptation is the formation of a biofilm, which can promote adherence and colonization and provide protection against antimicrobials. The marine bacterium Vibrio fischeri efficiently colonizes its symbiotic squid host, Euprymna scolopes , by producing a transient biofilm dependent on the symbiosis polysaccharide (SYP). In vitro , however, wild-type strain ES114 fails to form SYP-dependent biofilms. Instead, genetically engineered strains, such as those lacking the negative regulator BinK, have been developed to study this phenomenon. Historically, V. fischeri has been grown using LBS, a complex medium containing tryptone and yeast extract; supplementation with calcium is required to induce biofilm formation by a binK mutant. Here, through our discovery that yeast extract inhibits biofilm formation, we uncover signals and underlying mechanisms that control V. fischeri biofilm formation. In contrast to its inability to form a biofilm on unsupplemented LBS, a binK mutant formed cohesive, SYP-dependent colony biofilms on tTBS, modified LBS that lacks yeast extract. Moreover, wild-type strain ES114 became proficient to form cohesive, SYP-dependent biofilms when grown in tTBS supplemented with both calcium and the vitamin para-aminobenzoic acid (pABA); neither molecule alone was sufficient, indicating that this phenotype relies on coordinating two cues. pABA/calcium supplementation also inhibited bacterial motility. Consistent with these phenotypes, cells grown in tTBS with pABA/calcium were enriched in transcripts for biofilm-related genes and predicted diguanylate cyclases, which produce the second messenger cyclic-di-GMP (c-di-GMP). They also exhibited elevated levels of c-di-GMP, which was required for the observed phenotypes, as phosphodiesterase overproduction abrogated biofilm formation and partially rescued motility. This work thus provides insight into conditions, signals, and processes that promote biofilm formation by V. fischeri . IMPORTANCE Bacteria integrate environmental signals to regulate gene expression and protein production to adapt to their surroundings. One such behavioral adaptation is the formation of a biofilm, which can promote adherence and colonization and provide protection against antimicrobials. Identifying signals that trigger biofilm formation and the underlying mechanism(s) of action remain important and challenging areas of investigation. Here, we determined that yeast extract, commonly used for growth of bacteria in laboratory culture, inhibits biofilm formation by Vibrio fischeri , a model bacterium used for investigating host-relevant biofilm formation. Omitting yeast extract from the growth medium led to the identification of an unusual signal, the vitamin para-aminobenzoic acid (pABA), that when added together with calcium could induce biofilm formation. pABA increased the concentrations of the second messenger, c-di-GMP, which was necessary but not sufficient to induce biofilm formation. This work thus advances our understanding of signals and signal integration controlling bacterial biofilm formation.

Mitochondrial outer‐membrane permeabilization by pro‐apoptotic Bcl‐2 family members plays a crucial role in apoptosis induction. However, whether this directly causes the release of the different mitochondrial apoptogenic factors simultaneously is currently unknown. Here we report that in cells or with isolated mitochondria, pro‐apoptotic Bcl‐2 proteins cause the release of cytochrome c , Smac/Diablo and HtrA2/Omi but not endonuclease G (EndoG) and apoptosis‐inducing factor (AIF). In cells treated with Bax/Bak‐dependent pro‐apoptotic drugs, neither the caspase inhibitor zVAD‐fmk nor loss of Apaf‐1 affected the efflux of cytochrome c , Smac/Diablo and HtrA2/Omi, but both prevented the release of EndoG and AIF. Our findings identify the mitochondrial response to pro‐apoptotic stimuli as a selective process leading to a hierarchical ordering of the effectors involved in cell death induction. Moreover, as in Caenorhabditis elegans , EndoG and AIF act downstream of caspase activation. Thus EndoG and AIF seem to define a ‘caspase‐dependent’ mitochondria‐initiated apoptotic DNA degradation pathway that is conserved between mammals and nematodes.

As camera traps have become more widely used, extracting information from images at the pace they are acquired has become challenging, resulting in backlogs that delay the communication of results and the use of data for conservation and management. To ameliorate this, artificial intelligence (AI), crowdsourcing to citizen scientists and combined approaches have surfaced as solutions. Using data from the UK mammal monitoring initiative MammalWeb, we assess the accuracies of classifications from registered citizen scientists, anonymous participants and a convolutional neural network (CNN). The engagement of anonymous volunteers was facilitated by the strategic placement of MammalWeb interfaces in a natural history museum with high footfall related to the ‘Dippy on Tour’ exhibition. The accuracy of anonymous volunteer classifications gathered through public interfaces has not been reported previously, and here we consider this form of citizen science in the context of alternative forms of data acquisition. While AI models have performed well at species identification in bespoke settings, here we report model performance on a dataset for which the model in question was not explicitly trained. We also consider combining AI output with that of human volunteers to demonstrate combined workflows that produce high accuracy predictions. We find the consensus of registered users has greater overall accuracy (97%) than the consensus from anonymous contributors (71%); AI accuracy lies in between (78%). A combined approach between registered citizen scientists and AI output provides an overall accuracy of 96%. Further, when the contributions of anonymous citizen scientists are concordant with AI output, 98% accuracy can be achieved. The generality of this last finding merits further investigation, given the potential to gather classifications much more rapidly if public displays are placed in areas of high footfall. We suggest that combined approaches to image classification are optimal when the minimisation of classification errors is desired. Status of 4849 sequences considered in this analysis by each method of acquiring classifications. Correct—label matches expert label, excluded—sequences excluded because they did not meet classification criteria to be analysed (see Methods), conflicting classification—AI and human labels are incongruous, false nothing—‘nothing’ identified but expert identified animal, incorrect species—animal identified that doesn't match expert label.

Background T-type calcium channels (TTCC) are low voltage activated channels that are widely expressed in the heart, smooth muscle and neurons. They are known to impact on cell cycle progression in cancer and smooth muscle cells and more recently, have been implicated in rat and human mesangial cell proliferation. The aim of this study was to investigate the roles of the different isoforms of TTCC in mouse mesangial cells to establish which may be the best therapeutic target for treating mesangioproliferative kidney diseases.  Methods In this study, we generated single and double knockout (SKO and DKO) clones of the TTCC isoforms Ca V 3.1 and Ca V 3.2 in mouse mesangial cells using CRISPR-cas9 gene editing. The downstream signals linked to this channel activity were studied by ERK1/2 phosphorylation assays in serum, PDGF and TGF-β1 stimulated cells. We also examined their proliferative responses in the presence of the TTCC inhibitors mibefradil and TH1177. Results We demonstrate a complete loss of ERK1/2 phosphorylation in response to multiple stimuli (serum, PDGF, TGF-β1) in Ca V 3.1 SKO clone, whereas the Ca V 3.2 SKO clone retained these phospho-ERK1/2 responses. Stimulated cell proliferation was not profoundly impacted in either SKO clone and both clones remained sensitive to non-selective TTCC blockers, suggesting a role for more than one TTCC isoform in cell cycle progression. Deletion of both the isoforms resulted in cell death. Conclusion This study confirms that TTCC are expressed in mouse mesangial cells and that they play a role in cell proliferation. Whereas the Ca V 3.1 isoform is required for stimulated phosphorylation of ERK1/2, the Ca V 3.2 isoform is not. Our data also suggest that neither isoform is necessary for cell proliferation and that the anti-proliferative effects of mibefradil and TH1177 are not isoform-specific. These findings are consistent with data from in vivo rat mesangial proliferation Thy1 models and support the future use of genetic mouse models to test the therapeutic actions of TTCC inhibitors.

Osteosarcoma is an aggressive bone cancer affecting both humans and dogs, often leading to pulmonary metastasis. Despite surgery and chemotherapy being the primary treatment modalities, survival rates remain low in both species, underscoring the urgent need for more efficacious therapeutic options. Accumulating evidence indicates numerous biological and clinical similarities between human and canine osteosarcoma, making it an ideal choice for comparative oncological research that should benefit both species. The EphA2 receptor has been implicated in controlling invasive responses across different human malignancies, and its expression is associated with poor prognosis. In this study, we utilized a comparative approach to match EphA2 functions in human and canine osteosarcoma models. Our objectives were to assess EphA2 levels and its pro-malignant action in osteosarcoma cells of both species. We found that EphA2 is overexpressed in most of both canine and human osteosarcoma cell lines, while its silencing significantly reduced cell viability, migration, and invasion. Moreover, EphA2 silencing enhanced the sensitivity of osteosarcoma cells to cisplatin, a drug commonly used for treating this cancer. Furthermore, inhibition of EphA2 expression led to a significant reduction in tumor development capability of canine osteosarcoma cells. Our data suggest that these EphA2 effects are likely mediated through various signaling mechanisms, including the SRC, AKT, and ERK–MAPK pathways. Collectively, our findings indicate that EphA2 promotes malignant behaviors in both human and canine osteosarcoma and that targeting EphA2, either alone or in combination with chemotherapy, could offer potential benefits to osteosarcoma patients.