Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma.

We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.

The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse.

CCCTC-binding factor (CTCF) and cohesin are key players in three-dimensional chromatin organization. The topologically associating domains (TADs) demarcated by CTCF are remarkably well conserved between species, although genome-wide CTCF binding has diverged substantially following transposon-mediated motif expansions. Therefore, the CTCF consensus motif poorly predicts TADs, and additional factors must modulate CTCF binding and subsequent TAD formation. Here, we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs. In Adnp knockout cells, novel insulated regions are formed at sites normally bound by ChAHP, whereas proximal canonical boundaries are weakened. These data reveal that CTCF-mediated loop formation is modulated by a distinct zinc-finger protein complex. Strikingly, ChAHP-bound loci are mainly situated within less diverged SINE B2 transposable elements. This implicates ChAHP in maintenance of evolutionarily conserved spatial chromatin organization by buffering novel CTCF binding sites that emerged through SINE expansions.

MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.

Bone metastasis is a frequent and incurable consequence of advanced prostate cancer (PC). An interplay between disseminated tumor cells and heterogeneous bone resident cells in the metastatic niche initiates this process. Melanoma differentiation associated gene-9 (mda-9/Syntenin/syndecan binding protein) is a prometastatic gene expressed in multiple organs, including bone marrow-derived mesenchymal stromal cells (BM-MSCs), under both physiological and pathological conditions. We demonstrate that PDGF-AA secreted by tumor cells induces CXCL5 expression in BM-MSCs by suppressing MDA-9-dependent YAP/MST signaling. CXCL5-derived tumor cell proliferation and immune suppression are consequences of the MDA-9/CXCL5 signaling axis, promoting PC disease progression. mda-9 knockout tumor cells express less PDGF-AA and do not develop bone metastases. Our data document a previously undefined role of MDA-9/Syntenin in the tumor and microenvironment in regulating PC bone metastasis. This study provides a framework for translational strategies to ameliorate health complications and morbidity associated with advanced PC.

Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX.

The Lysinibacillus sphaericus proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito Culex quinquefasciatus and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the design of improved biopesticides. Tpp49Aa1 is naturally expressed as a crystalline inclusion within the host bacterium, and MHz serial femtosecond crystallography using the novel nanofocus option at an X-ray free electron laser allowed rapid and high-quality data collection to determine the structure of Tpp49Aa1 at 1.62 Å resolution. This revealed the packing of Tpp49Aa1 within these natural nanocrystals as a homodimer with a large intermolecular interface. Complementary experiments conducted at varied pH also enabled investigation of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals-a crucial step in its mechanism of action. To better understand the cooperation between the two proteins, assays were performed on a range of different mosquito cell lines using both individual proteins and mixtures of the two. Finally, bioassays demonstrated Tpp49Aa1/Cry48Aa1 susceptibility of Anopheles stephensi, Aedes albopictus, and Culex tarsalis larvae-substantially increasing the potential use of this binary toxin in mosquito control.

CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation.

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.

Generation of anti-idiotypic antibodies mimicking Cry2Aa toxin from an immunized mouse phage display library as potential insecticidal agents against Plutella xylostella.

This study tried to generate anti-idiotypic antibodies (Ab2s) which mimic Cry2Aa toxin using a phage-display antibody library (2.8 × 107 CFU/mL). The latter was constructed from a mouse immunized with F (ab')2 fragments digested from anti-Cry2Aa polyclonal antibodies. The F (ab')2 fragments and Plutella xylostella (P. xylostella) brush border membrane vesicles (BBMV) were utilized as targets for selection. Eight mouse phage-display single-chain variable fragments (scFvs) were isolated and identified by enzyme-linked immunoassay (ELISA), PCR and DNA sequencing after four rounds of biopanning. Among them, M3 exhibited the highest binding affinity with F (ab')2, while M4 bound the best with the toxin binding region of cadherin of P. xylostella (PxCad-TBR). Both of these two fragments were chosen for prokaryotic expression. The expressed M3 and M4 proteins with molecular weights of 30 kDa were purified. The M4 showed a binding affinity of 29.9 ± 2.4 nM with the PxCad-TBR and resulted in 27.8 ± 4.3 % larvae mortality against P. xylostella. Computer-assisted molecular modeling and docking analysis showed that mouse scFv M4 mimicked some Cry2Aa toxin binding sites when interacting with PxCad-TBR. Therefore, anti-idiotypic antibodies generated by BBMV-based screening could be useful for the development of new bio-insecticides as an alternative to Cry2Aa toxin for pest control.

Genetic and epigenetic orchestration of Gfi1aa-Lsd1-cebpa in zebrafish neutrophil development.

Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling neutrophil differentiation remains incompletely understood. GFI1 is associated with several myeloid disorders, but its role and the role of its co-regulators in granulopoiesis and pathogenesis are far from clear. Here, we demonstrate that zebrafish gfi1aa deficiency induces excessive neutrophil progenitor proliferation, accumulation of immature neutrophils from the embryonic stage, and some phenotypes similar to myelodysplasia syndrome in adulthood. Both genetic and epigenetic analyses demonstrate that immature neutrophil accumulation in gfi1aa-deficient mutants is due to upregulation of cebpa transcription. Increased transcription was associated with Lsd1-altered H3K4 methylation of the cebpa regulatory region. Taken together, our results demonstrate that Gfi1aa, Lsd1 and cebpa form a regulatory network that controls neutrophil development, providing a disease progression-traceable model for myelodysplasia syndrome. Use of this model could provide new insights into the molecular mechanisms underlying GFI1-related myeloid disorders as well as a means by which to develop targeted therapeutic approaches for treatment.

Predicting genetic risk factors for AA amyloidosis in Algerian patients with familial Mediterranean fever.

Renal amyloid-associated (AA) amyloidosis is a harmful complication of familial Mediterranean fever (FMF). Its occurrence involves polymorphisms and mutations in the Serum Amyloid A1 (SAA1) and Mediterranean Fever (MEFV) genes, respectively. In Algeria, the association between SAA1 variants and FMF-related amyloidosis was not investigated, hence the aim of this case-control study. It included 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis, and 21 without amyloidosis). All were genotyped for the SAA1 alleles (SAA1.1, SAA1.5, and SAA1.3), and a subset of them for the - 13 C/T polymorphism by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were performed using Chi-square and Fisher tests. The SAA1.1/1.1 genotype was predominant in amyloid FMF patients, compared to non-amyloid FMF patients (p = 0.001) and controls (p < 0.0001). SAA1.1/1.5 was higher in non-amyloid patients (p = 0.0069) and in controls (p = 0.0082) than in patients with amyloidosis. Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1.1/1.3 [OR 5.700; 95% CI: 1.435-22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119). The SAA1.1/1.5 genotype [OR 0.152; 95% CI: 0.040-0.587] (p = 0.0062) was protective against amyloidosis. In all groups, the - 13 C/C genotype predominated, and was not related to renal complication [OR 0.88; 95% CI: 0.07-10.43] (p = 0.915). In conclusion, in contrast to the - 13 C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population.

A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc.

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.

Kidney Transplantation in Patients With AA Amyloidosis: Outcomes in a French Multicenter Cohort.

RATIONALE & OBJECTIVE: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018. EXPOSURES: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels. OUTCOMES: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events. ANALYTICAL APPROACH: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively. RESULTS: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospitalization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplantation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P=0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P=0.02). LIMITATIONS: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored. CONCLUSIONS: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease. PLAIN-LANGUAGE SUMMARY: AA amyloidosis is a severe and rare disease. Kidney involvement is frequent and leads to end-stage kidney disease. Because of the involvement of other organs, these patients are often frail, which has raised concerns about their suitability for kidney transplantation. We reviewed all patients with AA amyloidosis nephropathy who underwent kidney transplantation in France in the recent era (2008-2018) and found that the outcomes after kidney transplantation were favorable, with 85.5% of patients still alive 5 years after transplantation, a survival rate that is comparable to the outcomes of patients receiving a transplant for other forms of kidney diseases. Recurrence of amyloidosis in the transplanted kidney was infrequent (5.8%). These data support the practice of kidney transplantation for patients with AA amyloidosis who experience kidney failure.

Characteristics and course of patients with AA amyloidosis: single centre experience with 174 patients from Turkey.

OBJECTIVES: This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis. METHODS: Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed. RESULTS: Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year. CONCLUSION: FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease.

Could tocilizumab be used in familial Mediterranean Fever? A systematic review.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1ß (IL-1ß), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1ß inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented. OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF. METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF. RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF. CONCLUSION: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1ß inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Extended phenotypic characterization of a novel Helsmoortel-van der Aa syndrome case series.

The neurodevelopmental disorder known as Helsmoortel-van der Aa syndrome (HVDAS, MIM#616580) or ADNP syndrome (Orphanet, ORPHA:404448) is a multiple congenital anomaly (MCA) condition, reported as a syndrome in 2014, associated with deleterious variants in the ADNP gene (activity-dependent neuroprotective protein; MIM*611386) in several children. First reported in the turn of the century, ADNP is a protein with crucial functions for the normal development of the central nervous system and with pleiotropic effects, explaining the multisystemic character of the syndrome. Affected individuals present with striking facial dysmorphic features and variable congenital defects. Herein, we describe a novel case series of HVDAS Italian patients, illustrating their clinical findings and the related genotype-phenotype correlations. Interestingly, the cutaneous manifestations are also extensively expanded, giving an important contribution to the clinical characterization of the condition, and highlighting the relation between skin abnormalities and ADNP defects.

Blockade of endothelial adenosine receptor 2 A suppresses atherosclerosis in vivo through inhibiting CREB-ALK5-mediated endothelial to mesenchymal transition.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and morbidity and mortality rates continue to rise. Atherosclerosis constitutes the principal etiology of CVDs. Endothelial injury, inflammation, and dysfunction are the initiating factors of atherosclerosis. Recently, we reported that endothelial adenosine receptor 2 A (ADORA2A), a G protein-coupled receptor (GPCR), plays critical roles in neovascularization disease and cerebrovascular disease. However, the precise role of endothelial ADORA2A in atherosclerosis is still not fully understood. Here, we showed that ADORA2A expression was markedly increased in the aortic endothelium of humans with atherosclerosis or Apoe-/- mice fed a high-cholesterol diet. In vivo studies unraveled that endothelial-specific Adora2a deficiency alleviated endothelial-to-mesenchymal transition (EndMT) and prevented the formation and instability of atherosclerotic plaque in Apoe-/- mice. Moreover, pharmacologic inhibition of ADORA2A with KW6002 recapitulated the anti-atherogenic phenotypes observed in genetically Adora2a-deficient mice. In cultured human aortic endothelial cells (HAECs), siRNA knockdown of ADORA2A or KW6002 inhibition of ADORA2A decreased EndMT, whereas adenoviral overexpression of ADORA2A induced EndMT. Mechanistically, ADORA2A upregulated ALK5 expression via a cAMP/PKA/CREB axis, leading to TGFß-Smad2/3 signaling activation, thereby promoting EndMT. In conclusion, these findings, for the first time, demonstrate that blockade of ADORA2A attenuated atherosclerosis via inhibition of EndMT induced by the CREB1-ALK5 axis. This study discloses a new link between endothelial ADORA2A and EndMT and indicates that inhibiting endothelial ADORA2A could be an effective novel strategy for the prevention and treatment of atherosclerotic CVDs.

Protein quality of commercially important edible bivalves.

Bivalves are a high-quality source of animal protein for human consumption. In recent years, the demand for bivalve proteins has increased dramatically, leading to a sharp increase in global production of marine bivalves. To date, although the amino acid profiles of many bivalves have been reported, such information has not been well organized. Therefore, there is an urgent need for a comprehensive scientific review of the protein quality of bivalves, especially commercially important edible bivalves. In this context, this study was conducted to evaluate the protein quality of commercially important edible bivalves. In general, most bivalves are rich in protein (> 50% of their dry weight) and amino acids (> 30 g/100g protein). Although most species of bivalves are rich in essential amino acids (EAA) (up to 50 g/100g protein), some species of edible bivalves have very low levels of EAA (< 5 g/100g protein). Based on the AA score, almost all bivalves have at least two limiting AAs. Most bivalve proteins provides delicious flavors with unami, sweetness and a hint of bitterness. The findings of this study not only serve as a a guide for selecting appropriate bivalves based on consumer preferences for specific AAs or AA scores, but also provide information on potential bivalve species for aquaculture to produce higher protein quality to meet the growing demand for high quality animal protein.

Ecologically mediated differences in electric organ discharge drive evolution in a sodium channel gene in South American electric fishes.

Active electroreception-the ability to detect objects and communicate with conspecifics via the detection and generation of electric organ discharges (EODs)-has evolved convergently in several fish lineages. South American electric fishes (Gymnotiformes) are a highly species-rich group, possibly in part due to evolution of an electric organ (EO) that can produce diverse EODs. Neofunctionalization of a voltage-gated sodium channel gene accompanied the evolution of electrogenic tissue from muscle and resulted in a novel gene (scn4aa) uniquely expressed in the EO. Here, we investigate the link between variation in scn4aa and differences in EOD waveform. We combine gymnotiform scn4aa sequences encoding the C-terminus of the Nav1.4a protein, with biogeographic data and EOD recordings to test whether physiological transitions among EOD types accompany differential selection pressures on scn4aa. We found positive selection on scn4aa coincided with shifts in EOD types. Species that evolved in the absence of predators, which likely selected for reduced EOD complexity, exhibited increased scn4aa evolutionary rates. We model mutations in the protein that may underlie changes in protein function and discuss our findings in the context of gymnotiform signalling ecology. Together, this work sheds light on the selective forces underpinning major evolutionary transitions in electric signal production.

Patterns of recovery in extant and extirpated seabirds after the world's largest multipredator eradication.

Eradicating invasive predators from islands can result in substantial recovery of seabirds, but the mechanisms that drive population changes remain poorly understood. Meta-analyses have recently revealed that immigration is surprisingly important to the recovery of philopatric seabirds, but it is not known whether dispersal and philopatry interact predictably to determine rates of population growth and changes of distribution. We used whole-island surveys and long-term monitoring plots to study the abundance, distribution, and trends of 4 burrowing seabird species on Macquarie Island, Australia, to examine the legacy impacts of invasive species and ongoing responses to the world's largest eradication of multiple species of vertebrates. Wekas (Gallirallus australis) were eradicated in 1988; cats (Felis catus) in 2001; and rabbits (Oryctolagus cuniculus), black rats (Rattus rattus), and mice (Mus mus) in 2011-2014. We compared surveys from 1976-1979 and 2017-2018 and monitoring from the 1990s and 2000s onward. Antarctic prions (Pachyptila desolata) and white-headed petrels (Pterodroma lessonii) increased ∼1% per year. Blue petrels (Halobaena caerulea) and gray petrels (Procellaria cinerea) recolonized following extirpation from the main island in the 1900s but remained spatially and numerically rare in 2018. However, they increased rapidly at 14% and 10% per year, respectively, since cat eradication in 2001. Blue and gray petrel recolonization occurred on steep, dry, west-facing slopes close to ridgelines at low elevation (i.e., high-quality petrel habitat). They overlapped <5% with the distribution of Antarctic prion and white-headed petrels which occurred in suboptimal shallow, wet, east-facing slopes at high elevation. We inferred that the speed of population growth of recolonizing species was related to their numerically smaller starting size compared with the established species and was driven by immigration and selection of ideal habitat.

Patrones de recuperación en aves marinas existentes y extirpadas después de la mayor erradicación mundial de multidepredadores Resumen La erradicación de depredadores invasores en las islas puede derivar en la recuperación sustancial de aves marinas, aunque entendemos muy poco los mecanismos que causan los cambios poblacionales. Los metaanálisis recientes han revelado que la inmigración es de gran importancia para la recuperación de aves marinas filopátricas, aunque no sabemos si la dispersión y la filopatría interactúan de forma predecible para poder determinar las tasas de crecimiento poblacional y los cambios en la distribución. Aplicamos censos de isla completa y parcelas de monitoreo a largo plazo para estudiar la abundancia, distribución y tendencias de cuatro especies de aves marinas cavadoras en la Isla Macquarie, Australia, para analizar los impactos heredados de las especies invasoras y la respuesta continua a la mayor erradicación mundial de varias especies de vertebrados. El rascón weka (Gallirallus australis) se erradicó en 1988; los gatos (Felis catus) en 2001; y los conejos (Oryctolagus cuniculus), ratas (Rattus rattus) y ratones (Mus mus) entre 2011 y 2014. Comparamos los censos de 1976­1979 y 2017­2018 y el monitoreo realizado en los 90s y del año 2000 en adelante. El pato petrel antártico (Pachyptila desolata) y el petrel cabeciblanco (Pterodroma lessonii) incrementaron ∼1% por año. El petrel azulado (Halobaena caerulea) y la pardela gris (Procellaria cinerea) recolonizaron la isla después de su extirpación en la década de 1900, pero todavía eran especies raras espacial y numéricamente en 2018. Sin embargo, esta especie incrementó rápidamente en un 14% y 10% por año respectivamente desde que se erradicaron los gatos en 2001. La recolonización ocurrió desde las laderas empinadas, secas y con orientación al oeste en los sistemas montañosos de baja elevación (es decir, hábitats de gran calidad para los petreles). La distribución del petrel azulado y la pardela gris ocurrió en laderas someras subóptimas y húmedas con orientación al este a altas elevaciones. Esta distribución se traslapó menos del 5% con la del pato petrel antártico y la del petrel cabeciblanco. Inferimos que la velocidad del crecimiento poblacional de las especies que recolonizaron estuvo relacionada con el menor tamaño inicial en comparación con las especies establecidas y fue causada por la inmigración y la selección del hábitat ideal.

Assessing the conservation value of cemeteries to urban biota worldwide.

Cemeteries are key urban green spaces with multifaceted societal and ecological importance. Their biodiversity is shaped by unique environmental and cultural factors. They can potentially protect rare and endangered species, yet their conservation value compared with other urban green spaces remains largely unexplored. We sought to fill this gap by systematically reviewing literature to investigate the conservation value of cemeteries relative to other urban green spaces (botanical gardens, institutional premises, natural remnants, and parks) by comparing species richness and proportions of native and unique species. We analyzed data from 70 papers covering 50 cities in 27 countries with linear and binomial mixed-effects models at both site and city level. Cemetery conservation value was similar to urban parks, except for the proportion of unique species, for which parks had significantly higher proportions (21.9% vs. 14.2%, p < 0.001). Cemeteries hosted slightly higher proportions of native species at the city level than botanical gardens (99.7% vs. 99.6%, p < 0.001) and institutional green spaces (96.3% vs. 94.1%, p = 0.034) and proportions comparable to parks and natural remnants (p > 0.05). They also had similar or higher values than institutional premises in species richness and unique species proportions (p > 0.05) and a higher site-level proportion of native species (p < 0.001). In contrast, species richness (slopes = -0.11 and -0.25, respectively) and unique species proportions (4.4% and 6.9%, respectively, p < 0.001 for both) were lower in cemeteries than in remnants of natural areas and in botanical gardens. The conservation value of cemeteries and parks was similar for animals, but parks had a higher value for plants. Overall, cemeteries were generally at least as valuable as some other green spaces for urban biodiversity and mostly native biota. Their religious and cultural significance suggests they will remain intact in the long term; thus, it is essential to prioritize and further promote their biodiversity in conservation and sustainable urban design plans.

Análisis del valor de conservación que tienen los cementerios para la biota urbana a nivel mundial Resumen Los cementerios son espacios urbanos verdes con una importancia social y ecológica multifacética. Su biodiversidad está moldeada por factores ambientales y culturales únicos. Los cementerios tienen el potencial para proteger especies raras y en peligro, pero su valor de conservación sigue sin ser explorado cuando se compara con otros espacios urbanos verdes. Buscamos llenar este vacío con una revisión sistemática de la bibliografía para investigar el valor de conservación de los cementerios en relación a otros espacios urbanos verdes (jardines botánicos, sedes institucionales, remanentes naturales y parques) al comparar la riqueza de especies y la proporción de especies nativas y únicas. Analizamos con modelos lineales y binomiales de efectos mixtos a nivel de sitio y de ciudad los datos de 70 artículos enfocados en 50 ciudades de 27 países. El valor de conservación de los cementerios fue similar al de los parques urbanos, excepto para la proporción de especies únicas, para la cual los parques tuvieron una proporción significativamente más alta (21.9% vs. 14.2%, p<0.001). A nivel de ciudad, los cementerios albergaron una proporción ligeramente mayor de especies nativas en comparación con los jardines botánicos (99.7% vs. 99.6%, p<0.001) y las sedes institucionales (96.3% vs. 94.1%, p = 0.034) y tuvieron una proporción comparable a los parques y los remanentes naturales (p>0.05). Los cementerios también tuvieron un valor similar o mayor a los espacios verdes institucionales en cuanto a riqueza de especies y proporción de especies únicas (p>0.05) y una proporción mayor a nivel de sitio de especies nativas (p<0.001). Al contrario, la riqueza de especies (pendientes = ­0.11 y ­0.25, respectivamente) y la proporción de especies únicas (4.4% y 6.9%, respectivamente, p<0.001 para ambas) fueron menores en los cementerios que en los remanentes de las áreas naturales y en los jardines botánicos. El valor de conservación de los cementerios y los parques fue similar para los animales, pero los parques tuvieron un valor mayor para las plantas. En general, los cementerios fueron al menos tan valiosos como otros espacios verdes para la biodiversidad urbana y casi toda la biota nativa. El significado religioso y cultural que tienen los cementerios sugiere que seguirán intactos a largo plazo; por ello, es esencial priorizar y promover aún más su biodiversidad en la conservación y en los planes de diseño urbano sustentable.

Using historical habitat loss to predict contemporary mammal extirpations in Neotropical forests.

Understanding which species will be extirpated in the aftermath of large-scale human disturbance is critical to mitigating biodiversity loss, particularly in hyperdiverse tropical biomes. Deforestation is the strongest driver of contemporary local extinctions in tropical forests but may occur at different tempos. The 2 most extensive tropical forest biomes in South America-the Atlantic Forest and the Amazon-have experienced historically divergent pathways of habitat loss and biodiversity decay, providing a unique case study to investigate rates of local species persistence on a single continent. We quantified medium- to large-bodied mammal species persistence across these biomes to elucidate how landscape configuration affects their persistence and associated ecological functions. We collected occurrence data for 617 assemblages of medium- to large-bodied mammal species (>1 kg) in the Atlantic Forest and the Amazon. Analyzing natural habitat cover based on satellite data (1985-2022), we employed descriptive statistics and generalized linear models (GLMs) to investigate ecospecies occurrence patterns in relation to habitat cover across the landscapes. The subregional erosion of Amazonian mammal assemblage diversity since the 1970s mirrors that observed since the colonial conquest of the Atlantic Forest, given that 52.8% of all Amazonian mammals are now on a similar trajectory. Four out of 5 large mammals in the Atlantic Forest were prone to extirpation, whereas 53% of Amazonian mammals were vulnerable to extirpation. Greater natural habitat cover increased the persistence likelihood of ecospecies in both biomes. These trends reflected a median local species loss 63.9% higher in the Atlantic Forest than in the Amazon, which appears to be moving toward a turning point of forest habitat loss and degradation. The contrasting trajectories of species persistence in the Amazon and Atlantic Forest domains underscore the importance of considering historical habitat loss pathways and regional biodiversity erosion in conservation strategies. By focusing on landscape configuration and identifying essential ecological functions associated with large vertebrate species, conservation planning and management practices can be better informed.

Uso de la pérdida histórica de hábitat para predecir la desaparición de mamíferos contemporáneos en los bosques neotropicales Resumen Tener conocimiento de cuáles especies desaparecerán después de una perturbación humana es de suma importancia para mitigar la pérdida de la biodiversidad, particularmente en los biomas híper diversos. La deforestación es la principal causante de las extinciones locales contemporáneas en los bosques tropicales, aunque puede ocurrir en diferentes tiempos. Los dos bosques tropicales más extensos de América del Sur ­ el Bosque Atlántico y la Amazonia ­ han experimentado formas históricamente divergentes de pérdida de hábitat y decadencia de biodiversidad, lo que proporciona un caso único de estudio para investigar las tasas de persistencia de las especies locales en un solo continente. Cuantificamos la persistencia de las especies de mamíferos de talla mediana a grande en estos dos bosques para aclarar cómo la configuración del paisaje afecta su persistencia y las funciones ecológicas asociadas. Recolectamos datos de presencia de 617 ensambles de especies de mamíferos de talla mediana a grande (>1 kg) en el Bosque Atlántico y en la Amazonia. Analizamos la cobertura natural del hábitat con base en datos satelitales (1985­2022) y empleamos estadística descriptiva y modelos lineales generalizados (MLG) para investigar los patrones de presencia de las eco especies en relación con la cobertura del hábitat en los distintos paisajes. La erosión subregional de la diversidad de ensambles de mamíferos en la Amazonia desde los 70s es igual a la observada en el Bosque Atlántico desde la conquista colonial, dado que 52.8% de todos los mamíferos amazónicos se encuentran en una trayectoria similar. Cuatro de los cinco grandes mamíferos en el Bosque Atlántico estaban propensos a desaparecer, mientras que el 53% de los mamíferos amazónicos estaban vulnerables a desaparecer. Una mayor cobertura natural del hábitat incrementó la probabilidad de persistencia de las eco especies en ambos bosques. Estas tendencias reflejaron una pérdida mediana de especies locales 63.9% mayor en el Bosque Atlántico que en la Amazonia, lo cual parece dirigirse hacia un momento decisivo para la degradación y pérdida del hábitat del bosque. Las trayectorias contrastantes de la persistencia de especies en el Bosque Atlántico y la Amazonia destacan la importancia de considerar dentro de las estrategias de conservación las maneras en las que se ha perdido históricamente el hábitat y la erosión de la biodiversidad regional. Si nos enfocamos en la configuración del paisaje y en la identificación de las funciones ecológicas esenciales asociadas con las especies grandes de vertebrados, podemos informar de mejor manera a la planeación de la conservación y las prácticas de manejo.