Abstract Wildlife management requires estimates of demographic parameters that are difficult to obtain for mobile species at low densities. Biased parameter estimates often result from capture–recapture (CR) studies due to small sample sizes and unequal recapture probabilities, the latter of which can be caused by animal movements with respect to the sampling area. We developed a multistate CR model designed to minimize biases by including multiple data types (capture, harvest, natural mortality, and telemetry) and accounting for temporary emigration. We applied the model to data collected intensively from 2012 to 2014, and intermittently since the 1970s, for the Viscount Melville (VM) subpopulation of polar bears ( Ursus maritimus ) in the Canadian Arctic. The number of bears within the VM subpopulation boundary likely increased from an average of 145 (Bayesian 95% credible interval [CRI] [109, 221]) in 1989–1992 to 235 (95% CRI [148, 569]) in 2012–2014. Survival probability increased for all sex and age classes except adult females, for which estimates declined due to unknown reasons. Polar bear movements exhibited Markovian dependence with approximately 28% of the subpopulation located outside of the sampling area each spring. This contributed to inaccurate parameter estimates when using a simpler, single‐state CR model that only included capture data. Although the interpretation of demographic status was complicated by statistical uncertainty and changes in study design, our findings suggest that—as of 2014—the VM polar bear subpopulation had likely recovered from an earlier period of overharvest, was stable, and had not exhibited detectable negative effects of climate warming.
Cordycepin (3′ deoxyadenosine) has been widely researched as a potential cancer therapy, but many diverse mechanisms of action have been proposed. Here, we confirm that cordycepin triphosphate is likely to be the active metabolite of cordycepin and that it consistently represses growth factor‐induced gene expression. Bioinformatic analysis, quantitative PCR and western blotting confirmed that cordycepin blocks the PI3K/AKT/mTOR and/or MEK/ERK pathways in six cell lines and that AMPK activation is not required. The effects of cordycepin on translation through mTOR pathway repression were detectable within 30 min, indicating a rapid process. These data therefore indicate that cordycepin has a universal mechanism of action, acting as cordycepin triphosphate on an as yet unknown target molecule involved in growth factor signalling.
The phycobilisome (PBS) captures light energy and transfers it to photosystem I (PSI) and photosystem II (PSII). Which and how many copies of protein subunits in PBSs, PSI, and PSII remain unbound in thylakoids are unknown. Here, quantitative mass spectrometry (QMS) was used to quantify substantial pools of free extrinsic subunits of PSII and PSI. Interestingly, the membrane intrinsic PsaL is 3‐fold higher than PsaA/B. This scenario complements the static structures of these complexes as revealed by X‐ray crystallography and cryo‐EM. The ratios of ApcG and photoprotective OCP over PBS indicate a pool of extra ApcG. The 2.5 ratio of CpcG‐PBS over CpcL‐PBS improves our understanding of these light‐harvesting complexes involved in energy capture and photoprotection in cyanobacteria.Impact statement Our study presents the first quantitative inquiry of the free pools of proteins associated with the three major photosynthetic complexes in Synechocystis 6803. This study increases our understanding of the unbound thylakoid proteome, guiding future research into the functions of these proteins, which will facilitate efforts to enhance photosynthetic efficiency.
Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5‐year survival of < 7%, despite the addition of immunotherapy to first‐line chemotherapy. Specific tumor biomarkers, such as delta‐like ligand 3 (DLL3) and schlafen11 (SLFN11), may enable the selection of more efficacious, novel immunomodulating targeted treatments like bispecific T‐cell engaging monoclonal antibodies (tarlatamab) and chemotherapy with PARP inhibitors. However, obtaining a tissue biopsy sample can be challenging in SCLC. Circulating tumor cells (CTCs) have the potential to provide molecular insights into a patient's cancer through a “simple” blood test. CTCs have been studied for their prognostic ability in SCLC; however, their value in guiding treatment decisions is yet to be elucidated. This review explores novel and promising targeted therapies in SCLC, summarizes current knowledge of CTCs in SCLC, and discusses how CTCs can be utilized for precision medicine.
Pancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant molecular subtypes that are currently determined using tissue biopsies, which are spatially biased and highly invasive. We used whole transcriptome sequencing of 10 plasma samples with tumor‐informed subtypes, complemented by proteomic analysis for minimally invasive identification of PDAC subtype markers. Data were validated in independent large cohorts and correlated with treatment response and patient outcome. Differential transcript abundance analyses revealed 32 subtype‐specific, protein‐coding cell‐free RNA (cfRNA) transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease‐relevant cfRNA‐defined subtype markers ( DEGS1 , KDELC1 , and RPL23AP7 ) that consistently associated with basal‐like tumors across all cohorts were identified. In both tumor and liquid biopsies, the overexpression of these markers correlated with poor survival. Moreover, elevated levels of the identified markers were linked to a poor response to systemic therapy and early relapse in resected patients. Our data indicate clinical applicability of cfRNA markers in determining tumor subtypes and monitoring disease recurrence.
High‐risk neuroblastomas, often associated with MYCN protooncogene amplification, are addicted to polyamines, small polycations vital for cellular functioning. We have previously shown that neuroblastoma cells increase polyamine uptake when exposed to the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), and this mechanism is thought to limit the efficacy of the drug in clinical trials. This finding resulted in the clinical development of polyamine transport inhibitors, including AMXT 1501, which is presently under clinical investigation in combination with DFMO. However, the mechanisms and transporters involved in DFMO‐induced polyamine uptake are unknown. Here, we report that knockdown of ATPase 13A3 ( ATP13A3 ), a member of the P5B‐ATPase polyamine transporter family, limited basal and DFMO‐induced polyamine uptake, attenuated MYCN ‐amplified and non‐ MYCN ‐amplified neuroblastoma cell growth, and potentiated the inhibitory effects of DFMO. Conversely, overexpression of ATP13A3 in neuroblastoma cells increased polyamine uptake, which was inhibited by AMXT 1501, highlighting ATP13A3 as a key target of the drug. An association between high ATP13A3 expression and poor survival in neuroblastoma further supports a role of this transporter in neuroblastoma progression. Thus, this study identified ATP13A3 as a critical regulator of basal and DFMO‐induced polyamine uptake and a novel therapeutic target for neuroblastoma.