Degradation Events Research Articles

Hysteresis in soil hydraulic conductivity as driven by salinity and sodicity – a modeling framework

Abstract. Declining soil-saturated hydraulic conductivity (Ks) as a result of saline and sodic irrigation water is a major cause of soil degradation. While it is understood that the mechanisms that lead to degradation can cause irreversible changes in Ks, existing models do not account for hysteresis between the degradation and rehabilitation processes. We develop the first model for the effect of saline and sodic water on Ks that explicitly includes hysteresis. As such, the idea that a soil's history of degradation and rehabilitation determines its future Ks lies at the center of this model. By means of a “weight” function, the model accounts for soil-specific differences, such as clay content. The weight function also determines the form of the hysteresis curves, which are not restricted to a single shape, as in some existing models for irreversible soil processes. The concept of the weight function is used to develop a reversibility index, which allows for the quantitative comparison of different soils and their susceptibility to irreversible degradation. We discuss the experimental setup required to find a soil's weight function and show how the weight function determines the degree to which Ks is reversible for a given soil. We demonstrate the feasibility of this procedure by presenting experimental results showcasing the presence of hysteresis in soil Ks and using these results to calculate a weight function. Past experiments and models on the decline of Ks due to salinity and sodicity focus on degradation alone, ignoring any characterization of the degree to which declines in Ks are reversible. Our model and experimental results emphasize the need to measure “reversal curves”, which are obtained from rehabilitation measurements following mild declines in Ks. The developed model has the potential to significantly improve our ability to assess the risk of soil degradation by allowing for the consideration of how the accumulation of small degradation events can cause significant land degradation.

Human–Machine Adaptive Shared Control for Safe Driving Under Automation Degradation

In this article, a human–machine adaptive shared control method is proposed for automated vehicles (AVs) under automation performance degradation. First, a novel risk assessment module is proposed to monitor driving behavior and evaluate automation performance degradation for AVs. Then, an adaptive control authority allocation module is developed. In the event of any performance degradation, the control authority allocated to the automation system is decreased based on the assessed risk. Consequently, the control authority allocated to a human driver is adaptively increased and thus requires more driver engagement in the control loop to compensate for the automation degradation and ensure the vehicle’s safety. Experimental validation is conducted under different driving scenarios. The test results show that the approach can effectively compensate for vehicle automation performance degradation through human–machine adaptive shared control, ensuring the safety of automated driving.

Synthesis, thermal behavior and kinetic study of N-morpholinium dicationic ionic liquids by thermogravimetry

Six N-morpholinium dicationic ionic liquids (DILs) with the following general formula [C4H8NO]2(CH2)n[X]2, being n = 4, 6 and 8 and X = Br, NTf2 (where NTf2 = bis(trifluoromethane)sulfonimide) have been synthesized. Their thermal behavior was studied by thermogravimetry (TG) using five different heating rates (2, 4, 8, 10 and 12 K min−1) aiming at assessing their relative thermal stability. All the DILs investigated undergo a single step of mass loss in the temperature range between 200 and 520 °C, except in the case of both the C4 DILs (with bromide and NTf2 imide anion), where two partially overlapping steps occur. NTf2 DILs are more stable than bromide ones according to the thermal stability scale based on the onset decomposition temperature. Taking into account the kinetic analysis of the thermal decomposition, the estimated decomposition time at given degree of conversion for the same temperature (250 °C) was evaluated as an alternative stability parameter. A substantial agreement between the stability trends assessed with the two different approaches was found, and the effect of the length of the linker between the two morpholinium rings of the dicationic structures was also considered. The reaction mechanism beneath the decomposition of the shortest member (C4) of the bromide series was investigated by DFT. A double retro-SN2 pathway was found to be the reasonable two-step mechanism for the first thermal degradation event. This hypothesis was further corroborated by analyzing the samples obtained from TG after heating the bromide and NTf2 C4 DILs up to the first degradation temperatures as well as the thermal behavior of the assumed spiro intermediate ILs.

Comparative study of the reaction kinetics of three residual biomasses

Kinetic analysis for the combustion of three agro-industrial biomass residues (coconut husk, corn husk, and rice husk) was carried out in order to provide information for the generation of energy from them. The analysis was performed using the results of the data obtained by thermogravimetric analysis (TGA) at three heating rates (10, 20, and 30 K/min). The biomass residues were characterized in terms of proximate analysis, elemental analysis, calorific value, lignin content, α-cellulose content, hemicellulose content, and holocellulose content. The biomass fuels were thermally degraded in an oxidative atmosphere. The results showed that the biomass thermal degradation process is comprised of the combustion of hemicellulose, cellulose, and lignin. The kinetic parameters of the distributed activation energy model indicated that the activation energy distribution for the pseudocomponents follows lignin, cellulose, and hemicellulose in descending order. The activation energy values for each set of reactions are similar between the heating rates, which suggests that it is independent of the heating rate between 10 K/min and 30 K/min. For all the biomass samples, the increased heating rate resulted in the overlap of the hemicellulose and cellulose degradation events.

Combining 137Cs, 210Pb and dendrochronology for improved reconstruction of erosion–sedimentation events in a loess gully system (southern Poland)

AbstractDetailed knowledge on the past events of erosion and redeposition is necessary to assess the frequency and magnitude of soil degradation and to provide more complete data, among all, to calculate rainfall thresholds and to develop strategies for controlling erosion. Therefore, in this study, we aimed to obtain a more comprehensive and accurate reconstruction of erosion–sedimentation events in a gully system by combining analyses of 137Cs and 210Pb with dendrochronological dating in the same sediment profiles. We aimed to precisely determine the number and the age of erosion–sedimentation events, which led to the development of study deposits and to determine the type of erosion providing material for deposition in particular events. To this purpose, 136 soil samples and 62 roots and tree stems samples were collected in eight research profiles at the gully bottom. We compared the results obtained with the two methods. Isotope analysis allowed us to estimate more general age of sediments and the type of erosion that provided material for individual layers. Dendrochronology provided a more precise reconstruction of the age of soil degradation events. By combining both techniques, we determined rainfall events responsible for erosion and sedimentation in the studied gully since 1980s and a rainfall threshold of 60 mm day−1 for soil erosion and redeposition in the study area.

Improved Proteomics-Based Drug Mechanism-of-Action Studies Using 16-Plex Isobaric Mass Tags.

Multiplexed quantitative proteomics enabled complex workflows to study the mechanisms by which small molecule drugs interact with the proteome such as thermal proteome profiling (TPP) or multiplexed proteome dynamics profiling (mPDP). TPP measures changes in protein thermal stability in response to drug treatment and thus informs on direct targets and downstream regulation events, while the mPDP approach enables the discovery of regulated protein synthesis and degradation events caused by small molecules and other perturbations. The isobaric mass tags available for multiplexed proteomics have thus far limited the efficiency and sensitivity by which such experiments could be performed. Here we evaluate a recent generation of 16-plex isobaric mass tags and demonstrate the sensitive and time efficient identification of Staurosporine targets in HepG2 cell extracts by recording full thermal denaturation/aggregation profiles of vehicle and compound treated samples in a single mass spectrometry experiment. In 2D-TPP experiments, isothermal titration over seven concentrations per temperature enabled comprehensive selectivity profiling of Staurosporine with EC50 values for kinase targets tightly matching to the kinobeads gold standard assay. Finally, we demonstrate time and condition-based multiplexing of dynamic SILAC labeling experiments to delineate proteome-wide effects of the molecular glue Indisulam on synthesis and degradation rates.

The Vital Role of Proteomics in Characterizing Novel Protein Degraders.

Mass spectrometry-based proteomics profiling is a discovery tool that enables researchers to understand the mechanisms of action of drug candidates. When applied to proteolysis targeting chimeras (PROTACs) such approaches provide unbiased perspectives of the binding, degradation selectivity, and mechanism related to efficacy and safety. Specifically, global profiling experiments can identify direct degradation events and assess downstream pathway modulation that may result from degradation or off-target inhibition. Targeted proteomics approaches can be used to quantify the levels of relevant E3 ligases and the protein of interest in cell lines and tissues of interest, which can inform the line of sight and provide insights on possible safety liabilities early in the project. Furthermore, proteomics approaches can be applied to understand protein turnover and resynthesis rates and inform on target tractability, as well as pharmacokinetics/pharmacodynamics understanding. In this perspective, we survey the literature around the impact of mass spectrometry-based proteomics in the development of PROTACs and present our envisioned proteomics cascade for supporting targeted protein degradation projects.

Rapid Survey of Anuran Species in Baguio-Benguet Area and Isolation of their Fungal Symbionts

Baguio City is one of the fastest-growing centers of urbanization in the Philippines. As part of the Cordillera Mountain Range, it is a biodiversity hotspot that is largely unexplored. This study is a preliminary investigation using visual encounter surveys of anuran species in various localities of the Baguio-Benguet area (BBA). These include Loakan Airport (LA), Camp John Hay (CJH), and Soroptimist Compound (SC) at the Military Cut Off, all in Baguio; Nangalisan, Tuba (NT), Benguet; and Master’s Garden (MG) at Puguis, La Trinidad, Benguet. We documented three Luzon-endemic species of frogs – namely, Kaloula rigida (Family Microhylidae), Sanguirana luzonensis (Family Ranidae), and Limnonectes macrocephalus (Family Dicroglossidae); one Philippine-endemic species, Kaloula picta (Family Microhylidae); and an invasive species, Rhinella marina (Family Bufonidae). The pathogenic fungi Batrachochytrium dendrobatidis was not detected in this study, but several cosmopolitan fungal species were isolated from the anuran integument – including Penicillium spp., Cladosporium sp., Talaromyces sp., Mucor sp., and Rhodotorula sp. The results of the study highlight the importance of regional surveys of urbanized areas in the country in aiding the conservation and preservation efforts for the remaining wildlife. Anthropogenic factors like logging and conversion of forested areas to commercial spaces, which lead to habitat degradation and catastrophic events, are still the leading threats to this understudied but presumed species-rich area. To date, this is the first update on anuran biodiversity in BBA after Inger’s study in 1954, and the first survey of fungi association with the amphibian integument in the Cordillera Administrative Region. Hence, further taxonomic and conservation research is recommended.

Helicobacter pylori-induced gastric cancer is orchestrated by MRCK\u03b2-mediated Siah2 phosphorylation

BackgroundHelicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression.MethodsH. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay.ResultsSiah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine6 (Ser6) and threonine279 (Thr279). Phosphorylation of Siah2 was mediated by MRCKβ, a Ser/Thr protein kinase. MRCKβ was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKβ could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKβ and use of proteasomal inhibitor MG132 could rescue MRCKβ from Siah2-mediated degradation. Ser6 and Thr279 phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells.ConclusionsIncreased level of Ser6 and Thr279-phosphorylated-Siah2 and downregulated MRCKβ were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKβ-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.

A Systematic Survey of the Light/Dark-dependent Protein Degradation Events in a Model Cyanobacterium

Light is essential for photosynthetic organisms and is involved in the regulation of protein synthesis and degradation. The significance of light-regulated protein degradation is exemplified by the well-established light-induced degradation and repair of the photosystem II reaction center D1 protein in higher plants and cyanobacteria. However, systematic studies of light-regulated protein degradation events in photosynthetic organisms are lacking. Thus, we conducted a large-scale survey of protein degradation under light or dark conditions in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter referred to as Synechocystis) using the isobaric labeling-based quantitative proteomics technique. The results revealed that 79 proteins showed light-regulated degradation, including proteins involved in photosystem II structure or function, quinone binding, and NADH dehydrogenase. Among these, 25 proteins were strongly dependent on light for degradation. Moreover, the light-dependent degradation of several proteins was sensitive to photosynthetic electron transport inhibitors (DCMU and DBMIB), suggesting that they are influenced by the redox state of the plastoquinone (PQ) pool. Together, our study comprehensively cataloged light-regulated protein degradation events, and the results serve as an important resource for future studies aimed at understanding light-regulated processes and protein quality control mechanisms in cyanobacteria.

PPAT'S Legal Responsibility For The Creation Of Empty Deed

Article 53 of the Regulation of the Head of the National Land Agency Number 1 Year 1960, which states that the PPAT deed is made by filling in the complete available deed blanks in accordance with the instructions for filling it. In practice carried out by a small number of PPAT there is a deed that has been prepared in advance, and has had some contents emptied containing agreements or general and standard agreements, which the purpose of which is to facilitate the work of PPAT in terms of administration and in terms of providing services by PPAT to interested parties or faces. The results showed that, Responsibility for authentic deed which is partially subtansinya empty, because PPAT is a public official who is given the authority to make authentic deed and PPAT has rules that must be obeyed by all PPAT in Indonesia regulated in Government Regulation No. 24, 2016 and the IPPAT Code of Ethics, and the position of PPAT deed which is partially subtansinya vacant in the event of degradation of PPAT deed even though the PPAT deed is a perfect evidence tool, but in the ppat certificate can experience degradation of the deed that can not be enforced as an authentic deed, but is considered a deed / handwriting under the hands caused by violation of the provisions of Article 1869 KUHPerdata.

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa.

The effects of ambient storage conditions on the structural and electrochemical properties of NMC-811 cathodes for Li-ion batteries

High-Ni cathode materials are prone to reactivity and instability upon exposure to ambient levels of humidity. This has implications for the storage and processing of cathodes for Li-ion batteries (LIBs), in order to avoid any premature degradation of the material prior to operation. NMC-811 materials were subjected to differing degrees of exposure to ambient humidity, in order to establish the impact this would have on electrochemical performance. This study used a combination of physical, chemical and electrochemical methods to investigate the operational effects that moisture can have on the battery accordingly. Longer-term cycling, d-SIMS and microscopy were used to characterise the degradation phenomena and relating to capacity fade. Post-mortem analysis revealed that the structural breakdown of the secondary particles is a dominant factor that influences charge transfer resistance increases. The study highlights the criticality of how high Ni materials are handled during storage and processing, in order to mitigate premature degradation events during operation.

Environmental change and human land‐use over the past 200 years in the Great Hinggan Mountains, Northeastern China

AbstractMountain ecosystems are sensitive to environmental changes and are affected by direct and indirect anthropogenic activities. This study sought to understand the impacts of human occupation, environmental and climate change on the Great Hinggan Mountains (GHM) in Northeastern China. The last 200 years of environmental changes are reconstructed by analyzing sediment cores from five small mountain lakes. Cores were dated using 210Pb and 137Cs radioisotopes, microscopic charcoal identified regional fire activity and fossil pollen analysis reconstructed temporal and spatial changes in vegetation. Peaks in 137Cs, 226Ra and microscopic charcoal flux were found to follow similar trends between sites. The radioisotope records reflect redistribution processes, such as erosion and fire events, which overwhelm the atmospheric fallout signal in the GHM. Microscopic charcoal increased from 1950 CE and peaked at all sites after 2000 CE suggesting that current fire management, coupled with a warmer climate due to global warming, may be leading to more wildfire events in the region. Pinus, Quercus and Betula declined at all sites as human occupation occurred in the early 1900s. Initially, open forest and grassland expanded in response to overexploitation of forests, followed by arboreal pollen reaching maximum values after 2000 CE. This study concludes that the present‐day mixed coniferous broad‐leaved forest dominating the southern region of the GHM is a product of changing fire activity, excessive logging and, more recently, forestry management and vegetation regeneration. Results suggest further management strategies are needed to address land degradation and wildfire events in mountain regions of Northeastern China.

CO2 emissions from forest degradation in Brazilian Amazon

Forest degradation is widespread around the world, due to multiple factors such as unsustainable logging, agriculture, invasive species, fire, fuelwood gathering, and livestock grazing. In the Brazilian Amazon forest degradation from August 2006 to July 2016 reached 1,1 869 800 ha. The processes of forest degradation are still poorly understood, being a missing component in anthropogenic CO2 emission estimates in tropical forests. In this work, we analyzed temporal trajectories of forest degradation from August 2006 to July 2016 in the Brazilian Amazon and assessed their impact on the regional carbon balance. We combined the degradation process with deforestation-related processes (clear-cut deforestation and secondary vegetation dynamics), using the spatially-explicit INPE-EM carbon emission model. The trajectory analysis showed that 13% of the degraded area ended up being cleared and converted in the period and 61% of the total degraded area experienced only one event of degradation throughout the whole period. Net emissions added up to 5.4 GtCO2, considering the emissions from forest degradation and deforestation, absorption from degraded forest recovery, and secondary vegetation dynamics. The results show an increase in the contribution of forest degradation to net emissions towards the end of the period, related to the decrease in clear-cut deforestation rates, decoupled from the forest degradation rates. The analysis also indicates that the regeneration of degraded forests absorbed 1.8 GtCO2 from August 2006 and July 2016—a component typically overlooked in the regional carbon balance.

Design, synthesis, structural analysis and biochemical studies of stapled AIF(370-394) analogues as ligand of CypA

BackgroundThe neuronal apoptotic process requires the nuclear translocation of Apoptosis Inducing Factor (AIF) in complex with Cyclophilin A (CypA) with consequent chromatin condensation and DNA degradation events. Targeting CypA by delivering an AIF-blocking peptide (AIF(370–394)) provides a significant neuroprotection, demonstrating the biological relevance of the AIF/CypA complex. To date pharmaceutical compounds targeting this complex are missing. MethodsWe designed and synthesized a set of mono and bicyclic AIF(370–394) analogs containing both disulfide and 1,2,3-triazole bridges, in the attempt to both stabilize the peptide conformation and improve its binding affinity to CypA. Peptide structures in solution and in complex with CypA have been studied by circular dichroism (CD), Nuclear Magnetic Resonance (NMR) and molecular modeling. The ability of stapled peptides to interact with CypA was evaluated by using Epic Corning label free technique and Isothermal Titration Calorimetry experiments. ResultsWe identified a stapled peptide analogue of AIF(370–394) with a ten-fold improved affinity for CypA. Molecular modeling studies reveal that the new peptide acquires β-turn/β-fold structures and shares with the parent molecule the same binding region on CypA. ConclusionsData obtained provide invaluable assistance in designing new ligand of CypA for therapeutic approaches in neurodegenerative diseases. General significanceDue to the crucial role of AIF/CypA complex formation in neurodegeneration, identification of selective inhibitors is of high importance for targeted therapies. We describe new bicyclic peptide inhibitors with improved affinity for CypA, investigating the kinetic, thermodynamic and structural effects of conformational constraints on the protein−ligand interaction, and their utility for drug design.

In-situ nanoscopic observations of dealloying-driven local corrosion from surface initiation to in-depth propagation

Dealloying is involved in materials science responsible for fabrication of nanoscale structures beneficially but for corrosion degradations detrimentally. Detailed understanding related to the latter is critical for designing corrosion-resistance alloys and dedicated inhibition systems. Thus, direct nanoscopic observations of nano-structural and compositional evolutions during the process are essential. Here using liquid phase-transmission electron microscopy (LP-TEM), for the first time, we show dynamic evolution of intricate site-specific local corrosion linked to intermetallic particles (IMPs) in aerospace aluminium alloys. To thoroughly probe degradation events, oxidation direction is controlled by purposefully masking thin specimens, allowing for observing top-view surface initiation to cross-sectional depth propagation of local degradations. Real-time capturing validated and supported by post-mortem examinations shows a dealloying-driven process that initiates at IMPs and penetrates into the depth of the alloy, establishing macroscopic corrosion pits. Besides, controversial mechanisms of noble-metal redistribution are finally elucidated.

Remaining useful life estimation with multiple local similarities

In prognostics and health management (PHM), remaining useful life (RUL) estimation has become a major focus for guaranteeing the safety and reliability of systems. Similarity-based RUL estimation methods, which predict a system’s RUL based on the RULs of other systems with similar degradation behaviors, have been proven effective when no or limited mechanism knowledge is available. Global similarity-based approaches apply the whole-life history to find similar degradation patterns and may lead to few or even no candidates. In contrast, local similarity-based methods only utilize the data close to the prediction time, and then, false positives are inevitable. A given system may have experienced several events before being tested for RUL, and each event may impact its RUL. Systems that have undergone similar events will probably degrade similarly in the future. Hence, the past events must be effectively identified and fully utilized. This paper proposes estimating a system’s RUL by using multiple impacts from its past. The system’s history is transformed into a set of local segments by which the degradation events are represented. Then, a coarse-to-fine strategy is introduced to efficiently locate the events similar to the test. The most similar segments are regarded as references, and their corresponding RULs are a natural data basis for RUL estimation. Since segments may correspond to different features, we adopt two adjustment strategies to make reference RULs more applicable. A self-adaptive weight allocation method is also proposed to further improve the prediction performance. The experimental results show the effectiveness and advantages of our proposed method.

Abstract 4322: EXOSC4, a novel gene at chromosome 8q24 loci is linked with breast cancer progression and is a prognostic marker for breast cancer survival

Abstract The chromosome 8q24 gene contains functional risk loci for multiple cancers, including prostate, colon, and breast. Breast cancer (BrCa) is one of the deadliest diseases among women. Our previous studies using TCGA clinical survival data (Cell. 2018; 173(2):400-416.e11) indicated that several genes are contributed significantly towards the survival of patients with BrCa. Over 75 such most significant genes were screened for further studies in terms of their contribution towards BrCa patient's survival. We found two genes (EXOSC4 and VPS28) with over 10% genetic copy number alterations located at chromosome 8q24 gene loci. Exosome Component 4 (EXOSC4) is located at 8q24.3 and associated with a non-catalytic component of the RNA exosome complex, which has 3' to 5' exoribonuclease activity. It also participates in cellular RNA processing and degradation events. However, the functional role of EXOSC4 towards BrCa progression or survival remains unknown. To understand the molecular basis of an elevated level of EXOSC4 in BrCa propagation, we screened the expression of this protein in different BrCa cell-lines. We also compared the expression of VPS28 within same cell lines. Data indicated that EXOSC4 was co-expressed with VPS28 and Myc, and was also secreted into extracellular space. Therefore, we next evaluated the level of EXOSC4 in patient's serum samples by reverse phase protein array (RPPA). We have well defined and categorized BrCa patients serum samples (n=240) from the Clinical Breast Care Project. The data indicated that the elevated level of EXOSC4 is associated with worse overall survival. In addition, results also showed that the high level of EXOSC4 is linked with breast cancer recurrence.In summary, through multiple modality studies we have confirmed the copy number alteration of EXOSC4 is associated with BrCa patient survival. Once validated, serum level of EXOSC4 could be a predictive biomarker for BrCa progression and survival. Additional experiments are ongoing to evaluate the regulatory role of the EXOSC4 gene which has the potential to develop into a novel therapeutic intervention of BrCa. Funding Sources: This work was supported by the grant to Dr. Meera Srivastava (DoD, DAMD17-03-1-0107). The work was also supported by the Collaborative Health Initiative Research Program (CHIRP) funding (CHIRP ID# IAA-A-HL-14-007). Disclaimers: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of The Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation (HJF), the Department of Defense (DoD), the Departments of the Army, Navy, or Air Force. Correspondence: Email: meera.srivastava@usuhs.edu Citation Format: Alakesh Bera, John Karaian, Madhan Subramanian, Michael Eklund, Eric Russ, Harvey B. Pollard, Hai Hu, Craig D. Shriver, Meera Srivastava. EXOSC4, a novel gene at chromosome 8q24 loci is linked with breast cancer progression and is a prognostic marker for breast cancer survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4322.

Vulnerability of Fishery-Based Livelihoods to Extreme Events: Local Perceptions of Damages from Hurricane Irma and Tropical Storm Alberto in Yaguajay, Central Cuba

Hurricanes can cause extensive long-term damage to small-scale fisheries. Yet, information is scarce on how communities are locally impacted by extreme events in the Caribbean and in other parts of the world. Focusing on an artisanal fishery in Yaguajay, Sancti Spiritus, Cuba, this article explores how artisanal fishers have perceived and responded to the different damages brought about by Hurricane Irma in September 2017 and the inundations associated with Storm Alberto in May 2018. Combining discussions and short interviews carried out pre and post-storms Irma and Alberto, this study identifies major environmental impacts and matching responses. In addition, the article sheds light on the evolution of small-scale fishing communities in Cuba and their current organization. Results show local perceptions of extensive biodiversity loss in terms of mangrove coverage, changes in salinity, and the quality of coastal environments that have affected the composition of captures and fish sizes. As a consequence of these changes, fishers are adjusting their effort and fishing intensity to match perturbations. Findings underscore the need to identify the synergistic relations that may exist between prior environmental degradation and different extreme events such as droughts, hurricanes, and excessive precipitation. The interrelation of these factors may result in compounded aggravated impacts that may unfold over longer temporal scales and not just as a one-time event. Authors conclude by stressing the importance of including the systematic study of extreme events along with local perceptions of ecological change in fishery management plans. Because fishers´ responses to hazards are based on their experiences and knowledge of the state of coastal and marine habitats, and especially on expectations about what constitutes normal ranges of change, threats, and levels of risks, this information is key to guide behavioral interventions and decision frameworks that can foster the development of hurricane resistant communities.