Heated fiber optic distributed temperature sensing for measuring soil volumetric heat capacity and water content: A dual probe heat-pulse approach

The first feasibility study of using dual-probe heated fiber optics with distributed temperature sensing to measure soil volumetric heat capacity and soil water content is presented. Although results using different combinations of cables demonstrate feasibility, further work is needed to gain accuracy, including a model to account for the finite dimension and the thermal influence of the probes. Implementation of the dual-probe heat-pulse (DPHP) approach for measurement of volumetric heat capacity (C) and water content (θ) with distributed temperature sensing heated fiber optic (FO) systems presents an unprecedented opportunity for environmental monitoring (e.g., simultaneous measurement at thousands of points). We applied uniform heat pulses along a FO cable and monitored the thermal response at adjacent cables. We tested the DPHP method in the laboratory using multiple FO cables at a range of spacings. The amplitude and phase shift in the heat signal with distance was found to be a function of the soil volumetric heat capacity. Estimations of C at a range of moisture contents (θ = 0.09– 0.34 m3 m−3) suggest the feasibility of measurement via responsiveness to the changes in θ, although we observed error with decreasing soil water contents (up to 26% at θ = 0.09 m3 m−3). Optimization will require further models to account for the finite radius and thermal influence of the FO cables. Although the results indicate that the method shows great promise, further study is needed to quantify the effects of soil type, cable spacing, and jacket configurations on accuracy

Potential of the active heat pulse method with fiber optic temperature sensing for estimation of water content and infiltration in agricultural soils

The principle of temperature measurement along a fiber optic cable is based on the thermal sensitivity of the relative intensities of backscattered Raman Stokes and anti Stokes photons that arise from collisions with electrons in the core of the glass fiber. A laser pulse, generated by the Distributed Temperature Sensing unit DTS, traversing a fiber optic cable will result in Raman backscatter at two frequencies, referred to as Stokes and anti-Stokes

Mapping variability of soil water content and flux across 1¿1000 m scales using the actively heated fiber optic method

The Actively Heated Fiber Optic (AHFO) method is shown to be capable of measuring soil water content several times per hour at 0.25 m spacing along cables of multiple kilometers in length. AHFO is based on distributed temperature sensing (DTS) observation of the heating and cooling of a buried fiber-optic cable resulting from an electrical impulse of energy delivered from the steel cable jacket. The results presented were collected from 750 m of cable buried in three 240 m colocated transects at 30, 60, and 90 cm depths in an agricultural field under center pivot irrigation. The calibration curve relating soil water content to the thermal response of the soil to a heat pulse of 10 W m−1 for 1 min duration was developed in the lab. This calibration was found applicable to the 30 and 60 cm depth cables, while the 90 cm depth cable illustrated the challenges presented by soil heterogeneity for this technique. This method was used to map with high resolution the variability of soil water content and fluxes induced by the nonuniformity of water application at the surface

Targeting BER enzymes in cancer therapy

Base excision repair (BER) repairs mutagenic or genotoxic DNA base lesions, thought to be important for both the etiology and treatment of cancer. Cancer phenotypic stress induces oxidative lesions, and deamination products are responsible for one of the most prevalent mutational signatures in cancer. Chemotherapeutic agents induce genotoxic DNA base damage that are substrates for BER, while synthetic lethal approaches targeting BER-related factors are making their way into the clinic. Thus, there are three strategies by which BER is envisioned to be relevant in cancer chemotherapy: (i) to maintain cellular growth in the presence of endogenous DNA damage in stressed cancer cells, (ii) to maintain viability after exogenous DNA damage is introduced by therapeutic intervention, or (iii) to confer synthetic lethality in cancer cells that have lost one or more additional DNA repair pathways. Here, we discuss the potential treatment strategies, and briefly summarize the progress that has been made in developing inhibitors to core BER-proteins and related factors

NEIL3 prevents senescence in hepatocellular carcinoma by repairing oxidative lesions at telomeres during mitosis

Hepatocellular carcinoma (HCC) patients suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for non-transformed cells. NEIL3-depleted HCC cell lines accumulated oxidative DNA lesions specifically at telomeres, resulting in telomere dysfunctional foci and 53BP1 foci formation. Following oxidative DNA damage during mitosis, NEIL3 relocated to telomeres and recruited apurinic endonuclease 1 (APE1), indicating activation of base excision repair. META-FISH revealed that NEIL3, but not NEIL1 or NEIL2, is required to initiate APE1 and Polβ-dependent base excision repair at oxidized telomeres. Repeated exposure of NEIL3-depleted cells to oxidizing damage induced chromatin bridges and damaged telomeres. These results demonstrate a novel function for NEIL3 in repair of oxidative DNA damage at telomeres in mitosis, which is important to prevent senescence of HCC cells. Furthermore, these data suggest that NEIL3 could be a target for therapeutic intervention for HCC

Small-molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation

The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo

Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function

Oxidative DNA damage is recognised by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1), initiating repair. Here, we describe a small molecule (TH10785) that interacts with the Phe319 and Gly42 amino acids of OGG1, increases the enzyme activity 10-fold and generates a novel β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and ageing.European Research Council TAROX-695376Swedish Research Council 2015-00162 and 2018-03406Ministry of Science and Innovation, Spain/State Research Agency, Spain/10.13039/501.100011033European Regional Development Fund (ERDF) BFU2017-83900-PCrafoord Foundation 20190532Alfred Osterlund FoundationSwedish Pain Relief FoundationSwedish Cancer Society CAN 2018/0658 and CAN 2017/716Torsten and Ragnar Soderberg foundationDr. Ake-Olsson Foundation for Hematological Research 2020-00306Thomas Helleday Foundation for medical research postdoctoral stipendsNTNU Enabling Technology Programme on BiotechnologyEMBO Short-Term Fellowship 9005FEBS Short-Term FellowshipScandinavian ExchangeGerman Research Foundation (DFG) 239748522Sonderforschungsbereich (SFB) 1127Leibniz AwardNorwegian Research Council 303369Karolinska Institutet Research Foundation 2020-02186Lars Hiertas Minne StiftelseAsociacion Espanola Contra Cancer grant Postdoctoral AECC 2020 POSTD20042BENIInstituto de Salud Carlos III CP19/00063, PI20/00329 and PI19/00640European Social Fund (ESF)Innovative Medicines Initiative 2 Joint Undertaking (JU) 875510European Union's Horizon 2020 research and innovation program, Marie Sklodowska-Curie 722729Accepte