Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

GOLPH3 promotes tumor malignancy via inhibition of ferroptosis by upregulating SLC7A11 in cholangiocarcinoma.

Golgi phosphoprotein 3 (GOLPH3) has been reported as an oncogene in various tumors; however, the role and function of GOLPH3 and its relevant molecular mechanism in cholangiocarcinoma (CCA) are unclear. Herein, GOLPH3 expression in CCA tissues was observed to be significantly higher than that in paired adjacent noncancerous tissues. Clinicopathological analysis showed that GOLPH3 expression correlated positively with the tumor-node-metastasis stage. In addition, GOLPH3 expression correlated inversely with the overall survival of patients with CCA. Multivariate analysis showed that GOLPH3 was an independent prognostic factor for patients with CCA. Transcriptome analysis (RNA sequencing) of GOLPH3 knockdown cells showed that the expression levels of nine ferroptosis-related genes were significantly changed, indicating the important biological function of GOLPH3 in ferroptosis in CCA cells. Furthermore, GOLPH3 knockdown could significantly promote Erastin-induced ferroptosis in vitro and suppress tumor growth in vivo. Overexpression of GOLPH3 had the opposite effect on this phenotype. Further studies revealed that GOLPH3 knockdown was significantly associated with a decrease in cysteine content, an accumulation of the lipid peroxidation product malondialdehyde, an increase in reactive oxygen species, and sensitized CCA cells to Erastin-induced ferroptosis. Moreover, changes in GOLPH3 expression were found to be consistent with the expression of light chain subunit solute carrier family 7 member 11 (SLC7A11). Thus, our study suggested that GOLPH3 functions as an oncoprotein in CCA and may suppress ferroptosis by facilitating SLC7A11 expression, suggesting that GOLPH3 could serve as a therapeutic target for CCA treatment.

In situ decrease in rhodolith growth associated with Arctic climate change.

Rhodoliths built by crustose coralline algae (CCA) are ecosystem engineers of global importance. In the Arctic photic zone, their three-dimensional growth emulates the habitat complexity of coral reefs but with a far slower growth rate, growing at micrometers per year rather than millimeters. While climate change is known to exert various impacts on the CCA's calcite skeleton, including geochemical and structural alterations, field observations of net growth over decade-long timescales are lacking. Here, we use a temporally explicit model to show that rising ocean temperatures over nearly 100 years were associated with reduced rhodolith growth at different depths in the Arctic. Over the past 90 years, the median growth rate was 85 µm year-1 but each °C increase in summer seawater temperature decreased growth by a mean of 8.9 µm (95% confidence intervals = 1.32-16.60 µm °C-1, p < .05). The decrease was expressed for rhodolith occurrences in 11 and 27 m water depth but not at 46 m, also having the shortest time series (1991-2015). Although increasing temperatures can spur plant growth, we suggest anthropogenic climate change has either exceeded the population thermal optimum for these CCA, or synergistic effects of warming, ocean acidification, and/or increasing turbidity impair rhodolith growth. Rhodoliths built by calcitic CCA are important habitat providers worldwide, so decreased growth would lead to yet another facet of anthropogenic habitat loss.

Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma.

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) - a multicenter, randomized, controlled, open-label investigator-initiated trial.

BACKGROUND: Despite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy. METHODS/DESIGN: ACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material. DISCUSSION: ACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.

Glycerophospholipid-driven lipid metabolic reprogramming as a common key mechanism in the progression of human primary hepatocellular carcinoma and cholangiocarcinoma.

Metabolic reprogramming, a key mechanism regulating the growth and recurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), still lacks effective clinical strategies for its integration into the precise screening of primary liver cancer. This study utilized ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry to conduct a comprehensive, non-targeted metabolomics analysis, revealing significant upregulation of lipid metabolites such as phosphatidylcholine and lysophosphatidylcholine in patients with HCC and CCA, particularly within the glycerophospholipid metabolic pathway. Hematoxylin and eosin and immunohistochemical staining demonstrated marked upregulation of phospholipase A2 in tumor tissues, further emphasizing the potential of lipid metabolism as a therapeutic target and its important part in the course of cancer. This work provides a new viewpoint for addressing the clinical challenges associated with HCC and CCA, laying the groundwork for the broad application of early diagnosis and personalized treatment strategies, and ultimately aiming to provide tailored and precise therapeutic options for patients.

An Audiovisual Correlation Matching Method Based on Fine-Grained Emotion and Feature Fusion.

Most existing intelligent editing tools for music and video rely on the cross-modal matching technology of the affective consistency or the similarity of feature representations. However, these methods are not fully applicable to complex audiovisual matching scenarios, resulting in low matching accuracy and suboptimal audience perceptual effects due to ambiguous matching rules and associated factors. To address these limitations, this paper focuses on both the similarity and integration of affective distribution for the artistic audiovisual works of movie and television video and music. Based on the rich emotional perception elements, we propose a hybrid matching model based on feature canonical correlation analysis (CCA) and fine-grained affective similarity. The model refines KCCA fusion features by analyzing both matched and unmatched music-video pairs. Subsequently, the model employs XGBoost to predict relevance and to compute similarity by considering fine-grained affective semantic distance as well as affective factor distance. Ultimately, the matching prediction values are obtained through weight allocation. Experimental results on a self-built dataset demonstrate that the proposed affective matching model balances feature parameters and affective semantic cognitions, yielding relatively high prediction accuracy and better subjective experience of audiovisual association. This paper is crucial for exploring the affective association mechanisms of audiovisual objects from a sensory perspective and improving related intelligent tools, thereby offering a novel technical approach to retrieval and matching in music-video editing.

Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells.

We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3ß/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.

Reception of experimental pedagogy and psychology in Chile. Analysis of the intellectual influences of Wilhelm Mann, 1904-1915.

This article provides a detailed analysis of the intellectual research project of Wilhelm Mann, one of the pioneers of experimental and educational psychology in Chile. Mann's work has been the object of so little analysis that his intellectual influences and networks are not clearly known. We analyzed 338 intratext citations from 22 works by Wilhelm Mann published during the period 1904-1915. As a result, we obtained a mapping of his cooperation networks and used a quantitative approach to study the authors who most influenced his career, among whom were William Stern, Herbert Spencer, Wilhelm Wundt, Alfred Binet, and Ernst Meumann. Mann was closely connected to the international and contemporary advances and discussions of his time, despite the lack of infrastructure and difficulties in communication. Mann was the first psychologist to develop a long-term project in Chile that aimed to measure the individualities of Chilean students and their intellectual development.

Mutations that alter Arabidopsis flavonoid metabolism affect the circadian clock.

Flavonoids are a well-known class of specialized metabolites that play key roles in plant development, reproduction, and survival. Flavonoids are also of considerable interest from the perspective of human health, as both phytonutrients and pharmaceuticals. RNA sequencing analysis of an Arabidopsis null allele for chalcone synthase (CHS), which catalyzes the first step in flavonoid metabolism, has uncovered evidence that these compounds influence the expression of genes associated with the plant circadian clock. Analysis of promoter-luciferase constructs further showed that the transcriptional activity of CCA1 and TOC1, two key clock genes, is altered in CHS-deficient seedlings across the day/night cycle. Similar findings for a mutant line lacking flavonoid 3'-hydroxylase (F3'H) activity, and thus able to synthesize mono- but not dihydroxylated B-ring flavonoids, suggests that the latter are at least partially responsible; this was further supported by the ability of quercetin to enhance CCA1 promoter activity in wild-type and CHS-deficient seedlings. The effects of flavonoids on circadian function were also reflected in photosynthetic activity, with chlorophyll cycling abolished in CHS- and F3'H-deficient plants. Remarkably, the same phenotype was exhibited by plants with artificially high flavonoid levels, indicating that neither the antioxidant potential nor the light-screening properties of flavonoids contribute to optimal clock function, as has recently also been demonstrated in animal systems. Collectively, the current experiments point to a previously unknown connection between flavonoids and circadian cycling in plants and open the way to better understanding of the molecular basis of flavonoid action.

Inter-individual single-trial classification of MEG data using M-CCA.

Neuroscientific studies often involve some form of group analysis over multiple participants. This requires alignment of recordings across participants. A naive solution is to assume that participants' recordings can be aligned anatomically in sensor space. However, this assumption is likely violated due to anatomical and functional differences between individual brains. In magnetoencephalography (MEG) recordings the problem of inter-subject alignment is exacerbated by the susceptibility of MEG to individual cortical folding patterns as well as the inter-subject variability of sensor locations over the brain due to the use of a fixed helmet. Hence, an approach to combine MEG data over individual brains should relax the assumptions that a) brain anatomy and function are tightly linked and b) that the same sensors capture functionally comparable brain activation across individuals. Here we use multiset canonical correlation analysis (M-CCA) to find a common representation of MEG activations recorded from 15 participants performing a grasping task. The M-CCA algorithm was applied to transform the data of a set of multiple participants into a common space with maximum correlation between participants. Importantly, we derive a method to transform data from a new, previously unseen participant into this common representation. This makes it useful for applications that require transfer of models derived from a group of individuals to new individuals. We demonstrate the usefulness and superiority of the approach with respect to previously used approaches. Finally, we show that our approach requires only a small number of labeled data from the new participant. The proposed method demonstrates that functionally motivated common spaces have potential applications in reducing training time of online brain-computer interfaces, where models can be pre-trained on previous participants/sessions. Moreover, inter-subject alignment via M-CCA has the potential for combining data of different participants and could become helpful in future endeavors on large open datasets.

Substrate Affinity Versus Catalytic Efficiency: Ancestral Sequence Reconstruction of tRNA Nucleotidyltransferases Solves an Enzyme Puzzle.

In tRNA maturation, CCA-addition by tRNA nucleotidyltransferase is a unique and highly accurate reaction. While the mechanism of nucleotide selection and polymerization is well understood, it remains a mystery why bacterial and eukaryotic enzymes exhibit an unexpected and surprisingly low tRNA substrate affinity while they efficiently catalyze the CCA-addition. To get insights into the evolution of this high-fidelity RNA synthesis, the reconstruction and characterization of ancestral enzymes is a versatile tool. Here, we investigate a reconstructed candidate of a 2 billion years old CCA-adding enzyme from Gammaproteobacteria and compare it to the corresponding modern enzyme of Escherichia coli. We show that the ancestral candidate catalyzes an error-free CCA-addition, but has a much higher tRNA affinity compared with the extant enzyme. The consequence of this increased substrate binding is an enhanced reverse reaction, where the enzyme removes the CCA end from the mature tRNA. As a result, the ancestral candidate exhibits a lower catalytic efficiency in vitro as well as in vivo. Furthermore, the efficient tRNA interaction leads to a processive polymerization, while the extant enzyme catalyzes nucleotide addition in a distributive way. Thus, the modern enzymes increased their polymerization efficiency by lowering the binding affinity to tRNA, so that CCA synthesis is efficiently promoted due to a reduced reverse reaction. Hence, the puzzling and at a first glance contradicting and detrimental weak substrate interaction represents a distinct activity enhancement in the evolution of CCA-adding enzymes.

IgG4-related cholangitis - a mimicker of fibrosing and malignant cholangiopathies.

IgG4-related cholangitis (IRC) is the major hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder. The pathogenesis of IgG4-RD and IRC is currently viewed as multifactorial, as there is evidence of a genetic predisposition while environmental factors, such as blue-collar work, are major risk factors. Various autoantigens have been described in IgG4-RD, including annexin A11 and laminin 511-E8, proteins which may exert a partially protective function in cholangiocytes by enhancing secretion and barrier function, respectively. For the other recently described autoantigens, galectin-3 and prohibitin 1, a distinct role in cholangiocytes appears less apparent. In relation to these autoantigens, oligoclonal expansions of IgG4+ plasmablasts are present in patients with IRC and disappear upon successful treatment. More recently, specific T-cell subtypes including regulatory T cells, follicular T helper 2 cells, peripheral T helper cells and cytotoxic CD8+ and CD4+ SLAMF7+ T cells have been implicated in the pathogenesis of IgG4-RD. The clinical presentation of IRC often mimics other biliary diseases such as primary sclerosing cholangitis or cholangiocarcinoma, which may lead to inappropriate medical and potentially invalidating surgical interventions. As specific biomarkers are lacking, diagnosis is made according to the HISORt criteria comprising histopathology, imaging, serology, other organ manifestations and response to therapy. Treatment of IRC aims to prevent or alleviate organ damage and to improve symptoms and consists of (i) remission induction, (ii) remission maintenance and (iii) long-term management. Glucocorticosteroids are highly effective for remission induction, after which immunomodulators can be introduced for maintenance of remission as glucocorticosteroid-sparing alternatives. Increased insight into the pathogenesis of IRC will lead to improved diagnosis and novel therapeutic strategies in the future.

Knockdown of UBE2I inhibits tumorigenesis and enhances chemosensitivity of cholangiocarcinoma via modulating p27kip1 nuclear export.

The asymptomatic nature of cholangiocarcinoma (CCA), particularly during its early stages, in combination with its high aggressiveness and chemoresistance, significantly compromises the efficacy of current therapeutic options, contributing to a dismal prognosis. As a tumor suppressor that inhibits the cell cycle, abnormal cytoplasmic p27kip1 localization is related to chemotherapy resistance and often occurs in various cancers, including CCA. Nevertheless, the underlying mechanism is unclear. SUMOylation, which is involved in regulating subcellular localization and the cell cycle, is a posttranslational modification that regulates p27kip1 activity. Here, we confirmed that UBE2I, as the only key enzyme for SUMOylation, was highly expressed and p27kip1 was downregulated in CCA tissues, which were associated with poor outcomes in CCA. Moreover, UBE2I silencing inhibited CCA cell proliferation, delayed xenograft tumor growth in vivo, and sensitized CCA cells to the chemotherapeutics, which may be due to cell cycle arrest induced by p27kip1 nuclear accumulation. According to the immunoprecipitation result, we found that UBE2I could bind p27kip1, and the binding amount of p27kip1 and SUMO-1 decreased after UBE2I silencing. Moreover, nuclear retention of p27kip1 was induced by UBE2I knockdown and SUMOylation or CRM1 inhibition, further suggesting that UBE2I could cooperate with CRM1 in the nuclear export of p27kip1. These data indicate that UBE2I-mediated SUMOylation is a novel regulatory mechanism that underlies p27kip1 export and controls CCA tumorigenesis, providing a therapeutic option for CCA treatment.

Predicting how defaunation-induced changes in seed predation and dispersal will affect tropical tree populations.

The loss of large animals due to overhunting and habitat loss potentially affects tropical tree populations and carbon cycling. Trees reliant on large-bodied seed dispersers are thought to be particularly negatively affected by defaunation. But besides seed dispersal, defaunation can also increase or decrease seed predation. It remains unclear how these different defaunation effects on early life stages ultimately affect tree population dynamics. We reviewed the literature on how tropical animal loss affects different plant life stages, and we conducted a meta-analysis of how defaunation affects seed predation. We used this information to parameterize models that altered matrix projection models from a suite of tree species to simulate defaunation-caused changes in seed dispersal and predation. We assessed how applying these defaunation effects affected population growth rates. On average, population-level effects of defaunation were negligible, suggesting that defaunation may not cause the massive reductions in forest carbon storage that have been predicted. In contrast to previous hypotheses, we did not detect an effect of seed size on changes in seed predation rates. The change in seed predation did not differ significantly between exclosure experiments and observational studies, although the results of observational studies were far more variable. Although defaunation surely affects certain tree taxa, species that benefit or are harmed by it and net changes in forest carbon storage cannot currently be predicted based on available data. Further research on how factors such as seed predation vary across tree species and defaunation scenarios is necessary for understanding cascading changes in species composition and diversity.

Predicciones de cómo los cambios inducidos en la dispersión y depredación de semillas por la pérdida de fauna afectará a las poblaciones de árboles tropicales Resumen La pérdida de animales grandes debido a la caza excesiva y la pérdida del hábitat afecta potencialmente a las poblaciones de árboles tropicales y al ciclo del carbono. Se considera que los árboles que dependen de dispersores de semillas de talla grande son los más afectados negativamente por la pérdida de fauna. La defaunación también puede incrementar o disminuir la depredación de semillas, además de su dispersión. Todavía no está claro cómo afectan al final a las dinámicas poblaciones de los árboles los diferentes efectos de la pérdida de fauna en las etapas temprana de vida. Revisamos la literatura sobre cómo la pérdida de animales tropicales afecta las diferentes etapas de vida de las plantas y realizamos un metaanálisis sobre cómo la pérdida de fauna afecta a la depredación de semillas. Usamos esta información para definir los parámetros de los modelos que alteraron los modelos de proyección de matriz a partir de un conjunto de especies de árboles y así simular los cambios causados por la pérdida de fauna en la dispersión y depredación de semillas. Analizamos cómo la aplicación de estos efectos de pérdida de fauna afectó las tasas de crecimiento poblacional. En promedio, los efectos de la pérdida de fauna a nivel poblacional fueron no significativas, lo que sugiere que la pérdida de fauna puede no ser la causa de las reducciones masivas que se han pronosticado en el almacenamiento de carbono forestal. Contrario a las hipótesis previas, no detectamos ningún efecto del tamaño de las semillas sobre los cambios en las tasas de depredación. El cambio en la depredación de semillas no difirió significativamente entre los experimentos de encierro y los estudios de observación, aunque los resultados de los últimos fueron mucho más variables. Mientras que la pérdida de fauna seguramente afecta a ciertos taxones de árboles, actualmente no se pueden pronosticar, con base en los datos disponibles, las especies que se benefician o perjudican por esta pérdida y los cambios netos en el almacenamiento de carbono forestal. Se necesita una investigación más avanzada sobre cómo varían los factores, como la depredación de semillas, entre especies de árboles y escenarios de pérdida de fauna para entender los cambios en cascada en la composición y diversidad de las especies.

Creating conservation strategies with value-focused thinking.

Biodiversity and human well-being strategies are only as good as the set of ideas people think about. We evaluated value-focused thinking (VFT), a framework that emphasizes creating objectives and strategies that are responsive to the objectives. We performed a proof-of-concept study of VFT with 6 conservation planning teams at a global conservation organization. We developed a package of materials related to VFT, including meeting-session agendas, a virtual facilitation template, facilitator's guide, and evaluation questionnaires. We used these materials to test whether VFT applied in a group setting resulted in high-quality conservation strategies and participant satisfaction and whether our materials were scalable, meaning that someone newly trained in VFT could facilitate planning meetings that resulted in high-quality strategies and participant satisfaction, as compared with an experienced VFT facilitator. Net response indicated positive compelling, feasible, creative, and representative ratings for the conservation strategies per team. Participants indicated satisfaction overall, although satisfaction was greater for objectives than for strategies. Among the participants with previous conservation planning experience, all were at least as satisfied with their VFT strategies compared with previously developed strategies, and none were less satisfied (p = 0.001). Changes in participant satisfaction were not related to facilitator type (experienced or inexperienced with VFT) (p > 0.10). Some participants had a preconceived sense of shared understanding of important values and interests before participating in the study, which VFT strengthened. Our results highlight the advantages of structuring the development and evaluation of conservation planning frameworks around VFT.

Creación de estrategias de conservación con el pensamiento orientado a valores Resumen Las estrategias para la biodiversidad y el bienestar humano son tan buenas como el conjunto de ideas en el que piensan las personas. Evaluamos el pensamiento orientado a valores (POV), un marco que promueve la creación de objetivos y estrategias responsivas a los objetivos. Realizamos un estudio de prueba de concepto del POV con seis equipos de planeación de la conservación en una organización mundial de conservación. Desarrollamos un paquete de materiales relacionado con el POV que incluyó orden del día de las reuniones, una plantilla de asesoramiento virtual, una guía para el facilitador y cuestionarios de evaluación. Usamos estos materiales para probar si el POV aplicado en un entorno de grupo da como resultado estrategias de conservación de gran calidad y la satisfacción de los participantes. También probamos si nuestros materiales podían ampliarse, es decir, si alguien con entrenamiento reciente de POV podría facilitar la planeación de reuniones para que resultaran en estrategias de gran calidad y la satisfacción de los participantes en comparación con un facilitador experimentado. Por equipo, la respuesta neta indicó calificaciones positivas, convincentes, factibles, creativas y representativas para las estrategias de conservación. Los participantes indicaron una satisfacción generalizada, aunque ésta fue mayor para los objetivos que para las estrategias. Entre los participantes con experiencia previa en la planeación de la conservación, todos estuvieron satisfechos al menos con sus estrategias de POV en comparación con las estrategias previas y ninguno estuvo menos satisfecho (p= 0.001). Los cambios en la satisfacción de los participantes no estuvieron relacionados con el tipo de facilitador (con o sin experiencia en POV) (p> 0.10). Antes de participar en el estudio, algunos participantes ya tenían un sentido preconcebido del entendimiento compartido de los valores e intereses importantes, lo que el POV fortaleció. Nuestros resultados resaltan las ventajas de la estructuración del desarrollo y la evaluación en torno al POV de los marcos de planeación de la conservación.

Achieving a real-time online monitoring system for conservation culturomics.

Environmental monitoring is increasingly shifting toward a set of systems that describe changes in real time. In ecology specifically, a series of challenges have prevented the rollout of real-time monitoring for features such as biodiversity change or ecosystem service provision. Conservation culturomics, a field concerned with interactions between people and nature, is well placed to demonstrate how monitoring might move toward a network of real-time platforms, given its existence exclusively in the digital realm. We examined a set of considerations associated with the development of real-time monitoring platforms for conservation culturomics and introduce a near real-time platform for the Species Awareness Index, a global index of changing biodiversity awareness derived from the rate of change in page views for species on Wikipedia. This platform will update automatically each month, operating in near real time (https://joemillard.shinyapps.io/Real_time_SAI/). There are plans to make the underlying data queryable via an application programing interface independent of the platform. The real-time Species Awareness Index will represent the first real-time and entirely automated conservation culturomic platform and one of the first real-time platforms in the discipline of ecology. Real-time monitoring for culturomics can provide insight into human-nature interactions as they play out in the physical realm and provide a framework for the development of real-time monitoring in ecology. Real-time monitoring metrics can be processed on private virtual machines and hosted on publicly available cloud services. Conservation now needs an online, real-time observatory that can evolve with the structure of the web.

Obtención de un sistema virtual de monitoreo en tiempo real para la culturomía de la conservación Resumen El monitoreo ambiental se enfoca cada vez más en un conjunto de sistemas que describen los cambios en tiempo real. En cuanto a la ecología, una serie de obstáculos ha impedido el despliegue del monitoreo en tiempo real para funciones como el cambio en la biodiversidad o el suministro de servicios ambientales. La culturomía de la conservación, un campo enfocado en las interacciones entre las personas y la naturaleza, es una buena opción para demostrar cómo el monitoreo podría transformarse en una red de plataformas en tiempo real, dado que sólo existe en el ámbito digital. Analizamos una serie de consideraciones asociadas con el desarrollo de plataformas de monitoreo en tiempo real para la culturomía de la conservación e introdujimos una plataforma casi en tiempo real para el Índice de Conciencia de Especies, un índice mundial del cambio en la conciencia sobre la biodiversidad derivado de la tasa de cambio en las visitas a las páginas de Wikipedia de diferentes especies. Esta plataforma se actualizará automáticamente cada mes, por lo que opera casi en tiempo real (https://joemillard.shinyapps.io/Real_time_SAI/). Existen planes para hacer que los datos subyacentes sean consultables por medio de una interfaz de programación de aplicaciones independiente de la plataforma. El Índice de Conciencia de Especies en tiempo real será la primera plataforma de culturomía de la conservación automatizada por completo y en tiempo real, así como una de las primeras plataformas de este tipo para la disciplina de la ecología. El monitoreo en tiempo real de la culturomía puede proporcionar información sobre las interacciones humano-naturaleza conforme se desarrollan en el ámbito físico y también un marco de trabajo para el desarrollo del monitoreo en tiempo real para la ecología. Las medidas del monitoreo en tiempo real pueden procesarse en máquinas virtuales privadas y albergarse en servicios públicos de nubes de almacenamiento. Hoy en día, la conservación necesita un observatorio en línea y en tiempo real que pueda evolucionar con la estructura de la web.

RNF4 promotes tumorigenesis, therapy resistance of cholangiocarcinoma and affects cell cycle by regulating the ubiquitination degradation of p27kip1 in the nucleus.

Among the hallmarks of cholangiocarcinoma (CCA) progression and unresponsiveness to therapy is impaired ubiquitin-dependent degradation of nuclear tumor suppressor protein. In the previous stage, our research group found that as a key tumor suppressor, nuclear dysfunction of p27kip1 is closely related to chemotherapy resistance of CCA, but the specific mechanism is unclear. It was recently shown that p27kip1-driven tumors were strongly dependent on the SUMO pathway. RNF4, as the SUMO-targeted ubiquitin ligase (STUbL), identifies SUMOylated proteins as a substrate through sumo-interacting motifs (SIM) and causes its degradation via the ubiquitin proteasome pathway. Here we described that the expression of RNF4 was upregulated in CCA tissues and related to malignant features. Silencing RNF4 arrested human CCA cells at the G1 phase, which was associated with the upregulation of p27kip1 and the downregulation of its downstream cycle-related proteins. Silencing RNF4 inhibited cell proliferation and migration, increased cell apoptosis, and sensitized CCA cells to treatment of chemotherapeutic drugs in vitro. Immunofluorescence showed that p27kip1 and RNF4 were mainly co-located in the nucleus. Immunoprecipitation and Western blot showed that p27kip1 was a target protein for SUMOylation and high expression of RNF4 decreased the levels of nuclear p27kip1, enhanced the levels of ubiquitinated and SUMOylated p27kip1, indicating that RNF4 could regulate cell cycle progression via recognizing SUMOylated p27kip1 and facilitating its ubiquitination degradation. These data indicate that RNF4-mediated ubiquitination degradation of SUMOylated proteins is a novel regulatory mechanism of p27kip1 dysfunction and CCA tumorigenesis, which provides a potential option for therapeutic intervention of CCA.

Putative Local Adaptive SNPs in the Genus Avicennia.

The genus Avicennia with eight species grow in intertidal zones of tropical and temperate regions, ranging in distribution from West Asia, to Australia, and Latin America. These mangroves have several medicinal applications for mankind. Many genetic and phylogenetic studies have been carried out on mangroves, but none is concerned with geographical adaptation of SNPs. We therefore, used ITS sequences of about 120 Avicennia taxa growing in different parts of the world and undertook computational analyses to identify discriminating SNPs among these species and to study their association with geographical variables. A combination of multivariate and Bayesian approaches such as CCA, RDA, and LFMM were conducted to identify the SNPs with potential adaptation to geographical and ecological variables. Manhattan plot revealed that many of these SNPs are significantly associated with these variables. The genetic changes accompanied by local and geographical adaptation were illustrated by skyline plot. These genetic changes occurred not under a molecular clock model of evolution and probably under a positive selection pressure imposed in different geographical regions in which these plants grow.

Studies on phytoremediation of chromated copper arsenate (CCA) using Acacia plant species (Fabaceae).

Soils contaminated with elevated levels of toxic heavy metals affect the soil quality. Phytoremediation is one of the constructive methods used in the mitigation of toxic metals from the soil. A pot experiment was performed by application of eight different concentrations of CCA viz 250, 500, 750, 1,000, 1,250, 1,500, 2,000, and 2,500 mg kg-1 soil to evaluate the efficiency of Acacia mangium and Acacia auriculiformis in phytoremediation of CCA compounds. Results showed that the shoot and root length, height, collar diameter, and biomass of the seedlings were significantly reduced with increase in CCA concentrations. The roots of the seedlings accumulated 1.5- to 2.0-fold higher amounts of CCA than in stem and leaves. The amount of Cr, Cu, and As found in the roots of A. mangium and A. auriculiformis at 2,500 mg CCA were 10.01 and 10.13, 8.51 and 8.84 mg, and 0.18 and 0.33 mg g-1, respectively. Similarly, the amount of Cr, Cu, and As found in stem and leaves were 4.33 and 7.84, 3.51 and 6.62, and 0.10 and 0.11 mg g-1, respectively. The quantity of Cr, Cu, and As found in stem and leaves were 5.95 and 9.00, 4.86 and 7.18, and 0.09 and 0.14 mg g-1, respectively. Overall, the present study advocates potential use of A. mangium and A. auriculiformis in phytoremediation of Cr, Cu, and As contaminated soils.

Phytoremediation of soils contaminated with heavy metals is well documented. Interestingly, information on the influence of Acacia tree species in remediation of chromated copper arsenate (CCA) is scanty. We found that the higher concentrations of CCA (1,000­5,000 mg) significantly reduced the seed germination, growth, and biomass of seedlings. Further, the results revealed that accumulation of Cr, Cu, and As were 1.5- to 2-fold higher in roots than in shoots. Present study adds knowledge on efficacy of Acacia mangium and Acacia auriculiformis in phytoremediation of CCA contaminated soils.