Ethylene involvement in the regulation of the H\u3csup\u3e+\u3c/sup\u3e-ATPase \u3ci\u3eCsHA1\u3c/i\u3e gene and of the new isolated ferric reductase \u3ci\u3eCsFRO1\u3c/i\u3e and iron transporter \u3ci\u3eCsIRT1\u3c/i\u3e genes in cucumber plants

In previous works using ethylene inhibitors and precursors, it has been shown that ethylene participates in the regulation of several Fe-deficiency stress responses by Strategy I plants, such as enhanced ferric reductase activity, rhizosphere acidification, and subapical root hair development. Furthermore, recent evidence suggests that ethylene could regulate the expression of both the ferric reductase and the iron transporter genes of Strategy I plants by affecting the FER (or FER-like) transcription factor. Recently, two H+-ATPase genes have been isolated from cucumber roots, CsHA1 and CsHA2. CsHA1 is up-regulated under Fe deficiency while CsHA2 is constitutively expressed. In this work we have cloned and characterized the sequences of the ferric reductase (CsFRO1) and the iron transporter (CsIRT1) genes from cucumber (Cucumis sativus L. cv Ashley). Expression of CsHA1, CsFRO1, and CsIRT1 is diminished in Fe-deficient roots by treatment with ethylene inhibitors, such as Co (cobalt) or AOA (aminooxyacetic acid). Treatment with ethylene precursors, like ACC (1-aminocyclopropane-1-carboxylic acid) or Ethephon (2-chloroethylphosphonic acid), resulted in increased CsHA1, CsFRO1, and CsIRT1 transcript levels and increased ferric reductase activity during early stages of Fe deficiency. These results suggest that ethylene is involved in the regulation of CsHA1, CsFRO1, and CsIRT1 gene expression

Using GPS-enabled decoy turtle eggs to track illegal trade

The insatiable human appetite for wildlife products drives species to extinction, spreads disease and has negative consequences for the economies of source countries. As a major transnational enterprise, illegal wildlife trade is valued between eight and 26.5 billion US dollars annually. Because law enforcement is often only reactive, information on trafficking routes is key to disrupting trade and curtailing wildlife crime. In our efforts to uncover trade routes of trafficked sea turtle eggs, we developed and field-tested the InvestEGGator, a 3D-printed decoy turtle egg embedded with a GPS–GSM transmitter (Supplemental Information). Illegally collected clutches of turtle eggs containing a decoy transmitter enabled us to track the movements of traffickers, and thus gain a better understanding of illegal trade routes. The decoys, set to emit a signal once an hour, provided five tracks, the most detailed of which identified an entire trade chain, covering 137 km. Using data provided by the decoys, we identified trafficking routes and on two occasions properties of potential interest to law enforcement. Decoys also yielded anecdotal information, furthering our understanding of trafficking routes

Discovery of potent and selective inhibitors of the Escherichia coli M1-aminopeptidase via multicomponent solid-phase synthesis of tetrazole-peptidomimetics

The Escherichia coli neutral M1-aminopeptidase (ePepN) is a novel target identified for the development of antimicrobials. Here we describe a solid-phase multicomponent approach which enabled the discovery of potent ePepN inhibitors. The on-resin protocol, developed in the frame of the Distributed Drug Discovery (D3) program, comprises the implementation of parallel Ugi-azide four-component reactions with resin-bound amino acids, thus leading to the rapid preparation of a focused library of tetrazole-peptidomimetics (TPMs) suitable for biological screening. By dose-response studies, three compounds were identified as potent and selective ePepN inhibitors, as little inhibitory effect was exhibited for the porcine ortholog aminopeptidase. The study allowed for the identification of the key structural features required for a high ePepN inhibitory activity. The most potent and selective inhibitor (TPM 11) showed a non-competitive inhibition profile of ePepN. We predicted that both diastereomers of compound TPM 11 bind to a site distinct from that occupied by the substrate. Theoretical models suggested that TPM 11 has an alternative inhibition mechanism that doesn't involve Zn coordination. On the other hand, the activity landscape analysis provided a rationale for our findings. Of note, compound TMP 2 showed in vitro antibacterial activity against Escherichia coli. Furthermore, none of the three identified inhibitors is a potent haemolytic agent, and only two compounds showed moderate cytotoxic activity toward the murine myeloma P3X63Ag cells. These results point to promising compounds for the future development of rationally designed TPMs as antibacterial agents

Long-term surveillance of the feline leukemia virus in the endangered Iberian lynx (Lynx pardinus) in Andalusia, Spain (2008-2021)

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population

Common variants in alzheimer's disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Automated Cellular-Level Dual Global Fusion of Whole-Slide Imaging for Lung Adenocarcinoma Prognosis

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce a novel dual global fusion network to incorporate global and inter-patch features of cell distribution, which enables the sufficient fusion of different types and locations of cells. We further validate the proposed pipeline using The Cancer Genome Atlas lung adenocarcinoma dataset. Our model achieves a C-index of 0.675 (±0.05) in the five-fold cross-validation setting and surpasses comparable methods. Further, we extensively analyze embedded map features and survival probabilities. These experimental results manifest the potential of our proposed pipeline for applications using WSI in lung adenocarcinoma and other malignancies

Molecular characterization of the diet of the planktonic community in Málaga Bay (NW Alboran Sea)

The seasonal changes in structure and functioning of the pelagic trophic web in Málaga Bay (NW Alboran Sea) are related to the annual hydrological cycle. However, time series analyses have shown that the relationship between interannual hydrological variability and the plankton community composition is weak. This might be due to different human-induced pressures (nutrient pollution, coastal fisheries) acting on different compartments of the trophic web. The net effect of all these factors would depend on how the ecosystem channels changes in the composition and abundance of each trophic level. Interactions of phytoplankton-ciliates-zooplankton might have a central role in the regulation of the trophic web in Málaga Bay, although the trophic relations of the dominant groups remain still undefined. In order to identify the dominant trophic relationships we aimed to characterise the diet of key ichthyo- and mesozooplankton species in the field. Given that gut content preys (phyto- and microplankton) are fragile and not easy to identify visually, we developed species-specific molecular markers to detect their presence/absence within the predators gut

Immunohistochemical assessment of Pax8 expression during pancreatic islet development and in human neuroendocrine tumors

The paired box transcription factor Pax8 is critical for development of the eye, thyroid gland as well as the urinary and reproductive organs. In adult, Pax8 overexpression is associated with kidney, ovarian and thyroid tumors and has emerged as a specific marker for these cancers. Recently, Pax8 expression was also reported in human pancreatic islets and in neuroendocrine tumors, identifying Pax8 as a novel member of the Pax family expressed in the pancreas. Herein, we sought to provide a comprehensive analysis of Pax8 expression during pancreogenesis and in adult islets. Immunohistochemical analysis using the most employed Pax8 polyclonal antibody revealed strong nuclear staining in the developing mouse pancreas and in mature human and mouse islets. Astonishingly, Pax8 mRNA in mouse islets was undetectable while human islets exhibited low levels. These discrepancies raised the possibility of antibody cross-reactivity. This premise was confirmed by demonstrating that the polyclonal Pax8 antibody also recognized the islet-enriched Pax6 protein both by Western blotting and immunohistochemistry. Thus, in islets polyclonal Pax8 staining corresponds mainly to Pax6. In order to circumvent this caveat, a novel Pax8 monoclonal antibody was used to re-evaluate whether Pax8 was indeed expressed in islets. Surprisingly, Pax8 was not detected in neither the developing pancreas or in mature islets. Reappraisal of pancreatic neuroendocrine tumors using this Pax8 monoclonal antibody exhibited no immunostaining as compared to the Pax8 polyclonal antibody. In conclusion, Pax8 is not expressed in the pancreas and cast doubts on the value of Pax8 as a pancreatic neuroendocrine tumor marker