Lethal Damage Research Articles

Signaling through TLR5 mitigates lethal radiation damage by neutrophil-dependent release of MMP-9

Acute radiation syndrome (ARS) is a major cause of lethality following radiation disasters. A TLR5 agonist, entolimod, is among the most powerful experimental radiation countermeasures and shows efficacy in rodents and non-human primates as a prophylactic (radioprotection) and treatment (radiomitigation) modality. While the prophylactic activity of entolimod has been connected to the suppression of radiation-induced apoptosis, the mechanism by which entolimod functions as a radiomitigator remains poorly understood. Uncovering this mechanism has significant and broad-reaching implications for the clinical development and improvement of TLR5 agonists for use as an effective radiation countermeasure in scenarios of mass casualty resulting from accidental exposure to ionizing radiation. Here, we demonstrate that in contrast to radioprotection, neutrophils are essential for the radiomitigative activity of entolimod in a mouse model of lethal ARS. Neutrophils express functional TLR5 and rapidly exit the bone marrow (BM), accumulate in solid tissues, and release MMP-9 following TLR5 stimulation which is accompanied by an increase in the number of active hematopoietic pluripotent precursors (HPPs) in the BM. Importantly, recombinant MMP-9 by itself has radiomitigative activity and, in the absence of neutrophils, accelerates the recovery of the hematopoietic system. Unveiling this novel TLR5-neutrophil-MMP-9 axis of radiomitigation opens new opportunities for the development of efficacious radiation countermeasures to treat ARS following accidental radiation disasters.

Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a cancer phototherapy that uses antibody-IR700 conjugate (Ab-IR700) and NIR light. Ab-IR700 forms aggregates on the plasma membranes of targeted cancer cells after light exposure, inducing lethal physical damage within the membrane. Low-molecular-weight (LMW) ligands are candidate targeting moieties instead of antibodies, but whether LMW-IR700 conjugates induce cell death by aggregation, the same mechanism as Ab-IR700, is unknown. Thus, we investigated differences in cytotoxicity and mechanisms between LMW-IR700 and Ab-IR700 targeting prostate-specific membrane antigen (PSMA). Both conjugates decreased cell viability to the same degree after light irradiation, but different morphological changes were observed in PSMA-positive LNCaP cells by microscopy. Cell swelling and bleb formation were induced by Ab-IR700, but only swelling was observed in cells treated with LMW-IR700, suggesting the cells were damaged via different cytotoxic mechanisms. However, LMW-IR700 induced bleb formation, a hallmark of NIR-PIT with Ab-IR700, when singlet oxygen was quenched or LMW-IR700 was localized only on the plasma membrane. Moreover, the water-soluble axial ligands of LMW-IR700 were cleaved, consistent with previous reports on Ab-IR700. Thus, the main cytotoxic mechanisms of Ab-IR700 and LMW-IR700 differ, although LMW-IR700 on the plasma membrane can cause aggregation-mediated cytotoxicity as well as Ab-IR700.

Spartina alterniflora raised soil sulfide content by regulating sulfur cycle-associated bacteria in the Jiuduansha Wetland of China

PurposeThe Spartina alterniflora invasion across the southeast coast in China significantly reduced vegetation diversity and generated associated ecological problems. Sulfur (S) is a vital nutrient, while sulfide is phytotoxic and the impact of S. alterniflora invasion on soil S cycle remains unclear. Therefore, this study aims to investigate the impacts of S. alterniflora invasion on the S cycle and associated soil microbial communities.MethodsBoth field investigation and lab-scale experiments were conducted, analyzing soil sulfide and sulfate contents, soil properties over four seasons in the Jiuduansha Wetland of Shanghai, China, the high-throughput sequencing of soil microbial communities, S cycle-related functional genes and seed germination experiments.ResultsThe contents of sulfide, soil organic carbon (SOC), and total nitrogen (TN) in the bulk soil of S. alterniflora invaded area were higher than those in the native species S. mariqueter habitat and bare mudflat soils. Spartina alterniflora invasion increased the abundance of the Nitrospiraceae and Desulfarculaceae families and reduced that of Hydrogenophilaceae. The relative abundance of the SO42− reduction functional genes (dsrA + dsrB) in the soil was increased after S. alterniflora invasion, while that of the S oxidation functional genes (yedZ + soxY) in the soil was reduced. Seed germination experiments with different sodium sulfide concentrations (Na2S) revealed that the phytotoxicity of sulfide caused more lethal damage to S. mariqueter than to S. alterniflora.ConclusionThe S. alterniflora invasion significantly increased SOC and TN contents and reduced the abundance of sulfur-oxidizing functional genes, which led to the accumulation of soil sulfide.

IFN-γ Drives TNF-α Hyperproduction and Lethal Lung Inflammation during Antibiotic Treatment of Postinfluenza Staphylococcus aureus Pneumonia.

Inflammatory cytokine storm is a known cause for acute respiratory distress syndrome. In this study, we have investigated the role of IFN-γ in lethal lung inflammation using a mouse model of postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. To mimic the clinical scenario, animals were treated with antibiotics for effective bacterial control following MRSA superinfection. However, antibiotic therapy alone is not sufficient to improve survival of wild-type animals in this lethal acute respiratory distress syndrome model. In contrast, antibiotics induce effective protection in mice deficient in IFN-γ response. Mechanistically, we show that rather than inhibiting bacterial clearance, IFN-γ promotes proinflammatory cytokine response to cause lethal lung damage. Neutralization of IFN-γ after influenza prevents hyperproduction of TNF-α, and thereby protects against inflammatory lung damage and animal mortality. Taken together, the current study demonstrates that influenza-induced IFN-γ drives a stepwise propagation of inflammatory cytokine response, which ultimately results in fatal lung damage during secondary MRSA pneumonia, despite of antibiotic therapy.

Comparison of 186Re to 662 keV photon radiation concerning biological radiation effect on the human B-cell line BV-173

Zellen der humanen Leukämie-Zelllinie BV-173 wurden mit 662keV-Photonenstrahlung respektive 186Re bestrahlt. In einem Inkubationszeitraum von 7 Tagen wurden Zahl und Vitalität der Zellen täglich bestimmt und als Dosiseffektkurven basierend auf der Vitalität dargestellt. Hierfür wurde der Zeitpunkt mit minimalem Überleben verwendet (72h 186Re und 24h Photonenstrahlung). Beide Strahlenarten zeigen am Auswertezeitpunkt (72h nach Versuchsbeginn für 186Re und 24h nach Versuchsbeginn für Photonenstrahlung) eine Überlebenskurve mit biexponentiellem Verlauf. Für Photonenstrahlung ist dies erklärbar durch eine Hypersensitivität im niedrigen Dosisbereich bis 1Gy, für die sich eine D0 von 3,3Gy ergibt, für Dosen über 1,0Gy liegt die D0 bei 10Gy. Für die 186Re-Inkubation ergibt sich eine D0 von 11,1Gy bei niedrigen Dosen verursacht durch die Reparatur subletaler Schäden, durch welche die biologische Wirkung abgeschwächt wird. Ab einer akkumulierten Dosis von etwa 1,6Gy zeichnet sich für 186Re ein wesentlich steilerer Kurvenverlauf mit einer D0 von 4,0Gy ab, der eine in diesem Bereich 2,5-fach stärkere biologische Wirkung als akute Photonenstrahlung wiedergibt (D0 4Gy für 186Re bzw. 10Gy für Photonen). Strahlung niedriger Dosisleistung zeigt eine geringere biologische Wirkung als eine akute Bestrahlung. Es existiert aber ein Grenzwert der akkumulierten Dosis, ab dem die biologische Wirkung von β-Strahlung die der Photonenstrahlung sogar übertrifft.

Histone lysine modifying enzymes and their critical roles in DNA double-strand break repair

Cells protect the integrity of the genome against DNA double-strand breaks through several well-characterized mechanisms including nonhomologous end-joining repair, homologous recombination repair, microhomology-mediated end-joining and single-strand annealing. However, aberrant DNA damage responses (DDRs) lead to genome instability and tumorigenesis. Clarification of the mechanisms underlying the DDR following lethal damage will facilitate the identification of therapeutic targets for cancer. Histones are small proteins that play a major role in condensing DNA into chromatin and regulating gene function. Histone modifications commonly occur in several residues including lysine, arginine, serine, threonine and tyrosine, which can be acetylated, methylated, ubiquitinated and phosphorylated. Of these, lysine modifications have been extensively explored during DDRs. Here, we focus on discussing the roles of lysine modifying enzymes involved in acetylation, methylation, and ubiquitination during the DDR. We provide a comprehensive understanding of the basis of potential epigenetic therapies driven by histone lysine modifications.

Exercise/Resistance Training and Muscle Stem Cells.

Skeletal muscle has attracted attention as endocrine organ, because exercise-dependent cytokines called myokines/exerkines are released from skeletal muscle and are involved in systemic functions. While, local mechanical loading to skeletal muscle by exercise or resistance training alters myofiber type and size and myonuclear number. Skeletal muscle-resident stem cells, known as muscle satellite cells (MuSCs), are responsible for the increased number of myonuclei. Under steady conditions, MuSCs are maintained in a mitotically quiescent state but exit from that state and start to proliferate in response to high physical activity. Alterations in MuSC behavior occur when myofibers are damaged, but the lethal damage to myofibers does not seem to evoke mechanical loading-dependent MuSC activation and proliferation. Given that MuSCs proliferate without damage, it is unclear how the different behaviors of MuSCs are controlled by different physical activities. Recent studies demonstrated that myonuclear number reflects the size of myofibers; hence, it is crucial to know the properties of MuSCs and the mechanism of myonuclear accretion by MuSCs. In addition, the elucidation of mechanical load-dependent changes in muscle resident cells, including MuSCs, will be necessary for the discovery of new myokines/exerkines and understating skeletal muscle diseases.

Abstract 2060: Therapeutic approaches for CCNE1-amplified HR-proficient ovarian cancer

Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors have shown great success in ovarian cancer patients that are homologous recombination deficient (HRD). However, approximately 50% of high grade serous ovarian cancer (HGSOC) are HR-proficient. HR-proficient Cancer cells evade lethal DNA damage by triggering HR pathways at the cost of genome stability and evolving of more aggressive cancer cells. Cyclin E1 (CCNE1) amplification is a major subset of known HR-proficient HGSOC. This subset of cancer responds poorly to essentially all available ovarian cancer therapies including PARP inhibitors. Our study showed that the mTOR, HR, and checkpoint pathways were enriched in CCNE1-amplifed ovarian cancer patients. Interactome mapping demonstrated that many of the interactive proteins in the mTOR pathway were also components of HR and DNA checkpoint pathways. mTOR inhibition resulted in downregulation of HR and DNA checkpoint proteins. Downregulation of ATR partly mirrored mTOR inhibition. mTOR inhibitors and ATR inhibitors synergized with PARP inhibitors in vitro and in vivo in CCNE1-amplified HGSOC tumors. This was associated with decrease in cancer stem-like cancer cells and loss of polyploid tumor cells, which are vital for evolving of more aggressive, therapy-resistant cancer cells. These studies will have potential impact on further preclinical validation and clinical applications to cure CCNE1-amplifed HRP ovarian cancer. Citation Format: Shoumei Bai, Ronald J. Buckanovich. Therapeutic approaches for CCNE1-amplified HR-proficient ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2060.

Abstract 1269: Pharmacological targeting of transcription-replication conflict leads to anti-cancer efficacy with minimal side effects in preclinical models

Abstract Unchecked growth of cancer cells places simultaneous demands on DNA replication and transcription. Targeting the transcription-replication conflict (TRC), a major source of genome instability, could have important therapeutic implications. However, testing this hypothesis is difficult without agents directly targeting TRC. Here, we report a small molecule ligand (AOH1996) of the replisome component PCNA, which stabilizes interaction between PCNA and the large subunit (rpb1) of RNA polymerase II through the APIM motif, resulting in proteasome-dependent degradation of rpb1 and lethal DNA damages. Orally administrable, AOH1996 suppresses tumor growth without discernable toxicity at more than 10 time the compound's effective dose. In addition, AOH1996 works synergistically with known DNA damage agents to kill cancer cells. These results reveal TRC as cancer-selective vulnerability and demonstrated the therapeutic potential of AOH1996. Citation Format: Long Gu, Caroline Li, Robert Lingeman, Robert J. Hickey, Linda H. Malkas. Pharmacological targeting of transcription-replication conflict leads to anti-cancer efficacy with minimal side effects in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1269.

Abstract LB130: Combination of IGF-1R targeted alpha therapy with Olaparib results in synergistic efficacy against colorectal and lung cancer xenografts

Abstract Objectives: FPI-1434 is a targeted alpha-particle therapeutic consisting of an IGF-1R targeting antibody radiolabeled with Actinium-225. The primary mechanism of action for FPI-1434 is induction of double strand DNA breaks (DSB) in targeted tumors resulting in cell death. Poly (ADP-ribose) polymerase (PARP) is part of the cellular mechanism that repairs DSB. In cancer patients with genetic defects in DSB repair (eg. BRCA1/2), the PARP pathway becomes a primary repair system and its inhibition results in cell death. This mechanism has been leveraged as a therapy against DNA-repair deficient tumors leading to FDA-approval of PARP inhibitors (PARPi) including Olaparib. Treatment with PARPi to block repair of DNA damage driven by FPI-1434 may act synergistically to increase the lethal DNA damage load. To that end, Fusion has performed studies to combine FPI-1434 and Olaparib against tumor models with no pre-disposing defects in DNA repair. Methods: Colorectal (Colo-205) or lung (A549) cancer xenografts were established in Balb/c nude mice. For efficacy studies, a dose combination matrix for FPI-1434 and Olaparib was tested. FPI-1434 was dosed (i.v.) once at 20-200 nCi followed with Olaparib (i.p.) at doses of 0-50 mg/kg. Olaparib was dosed 24h after FPI-1434 using a 5 day on/2 day off schedule (5 mice/group). DSB formation (γH2AX) and apoptosis (cleaved caspase 3) were evaluated in treated tumors by IHC staining. Results: DSB formation and induction of apoptosis were detected in FPI-1434-treated tumors in a time and dose dependent manner. DSB formation was observed in all areas of tumor containing intact or apoptotic cancer cells confirming FPI-1434 mechanism. In tumor efficacy studies, Olaparib had no single-agent efficacy in the Colo-205 or A549 models. Single doses of FPI-1434 at 20 nCi had no effect on Colo-205 tumors, suppressed growth at 50 nCi and caused regression at 100 nCi. Combination efficacy was seen in the 20 and 50 nCi dose groups, including Olaparib. Doses of 20 nCi FPI-1434 and 25 mg/kg Olaparib had the strongest combined effect in this model. In the A549 model, single doses of FPI-1434 had no effect at 20 or 50 nCi, caused growth suppression at 100 nCi and regression at 200 nCi. Combination efficacy was seen in the 20, 50 and 100 nCi dose groups, including Olaparib. Doses of 50 nCi FPI-1434 and 25 mg/kg Olaparib had the strongest combined effect in this model. In general, the strongest efficacy was observed by combining ineffective single-agent doses of the two compounds. Strong efficacy of high dose FPI-1434 masked observable combination effects suggesting that FPI-1434 was the therapeutic driver. Conclusions: Olaparib co-dosing enhanced FPI-1434 efficacy which supports consideration of this combination for clinical use. Ineffective single-agent doses, when combined, resulted in synergistic efficacy in both Colo-205 and A549 models suggesting that the mechanism can be applied to multiple cancer types where predisposing mutations in DNA repair are lacking. The strongest combination effect appeared to occur at the low single-agent doses suggesting that PARP inhibition may potentiate efficacy at lower clinical doses of FPI-1434. Citation Format: Meiduo Hu, John Forbes, Ryan Simms, Yaryna Storozhuk, Eric Burak, John Valliant. Combination of IGF-1R targeted alpha therapy with Olaparib results in synergistic efficacy against colorectal and lung cancer xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB130.

The Ratio between Lethal and Mutagenic Damages in the DNA of Plasmids and Bacteriophages Induced by 8-Methoxypsoralen Plus UV (λ ≥ 320 nm) Treatment

The Ratio between Lethal and Mutagenic Damages in the DNA of Plasmids and Bacteriophages Induced by 8-Methoxypsoralen Plus UV (λ ≥ 320 nm) Treatment

Micafungin-Induced Cell Wall Damage Stimulates Morphological Changes Consistent with Microcycle Conidiation in Aspergillus nidulans.

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of β-glucans. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae in responds to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits morphological changes consistent with microcycle conidiation and that this effect is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.

Improved Asymptotic Expansions in High- and Low-Dose Ranges for Generalized Multi-Hit Model of Radiation-Induced Cell Survival.

By considering an upper bound on the number of radiation-induced potential lethal damages that can be repaired in a cell, we have proposed the generalized multi-hit (GMH) model with a closed-form solution, which can better fit various radiation-induced cell survival curves. Recent analysis shows that the asymptotic expansions that we gave before can be used to approximate the generalized single-hit single-target (GSHST) model rather than the GMH model. To illustrate the asymptotic trends of radiation-induced cell survival curves, in this study, we improve the asymptotic expansions of the GMH model in low- and high-dose ranges based on the limit formula of the incomplete gamma function in the corresponding dose ranges. When the upper limit of the number of radiation-induced potential lethal damages is one, the improved expansions of the GMH model can be reduced to the previous expansions of the GSHST model, and the improved asymptotic expansions of the GMH model also indicate that the GMH model has the generalized linear-quadratic-linear (LQL) feature. The numerical simulations indicate that the improved asymptotic expansions in high- and low-dose ranges agree well with the non-linear fitting of the GMH model in six kinds of cell lines under the corresponding dose ranges. In addition, we analyze the relative errors of the improved expansions of the GMH model in high- and low-dose ranges to demonstrate the accuracy and effectiveness of the improved expansions. Based on the error analysis, we further give the reasonable ranges of radiation dose applicable to the improved asymptotic expansions of the GMH model.

Prevalence of Motorcycle Accidents and Its Associated Factors Among Road Traffic Accident Patients in Hawassa University Comprehensive Specialized Hospital, 2019.

BackgroundRoad traffic damages were amongst the central causes of passing away, hospitalization, disability, and low socioeconomic status. About 1.3 million lethal road traffic damages and 20–50 million nonfatal damages happened consequently of road traffic accidents every year globally. Motorcycles are a small subsection of all motor vehicles significantly over-represented in total motor vehicle accidents and lead to a great rate of deaths and disabilities.ObjectiveThe study aimed to assess the prevalence of motorcycle accident and associated factors among road traffic accident patients in Hawassa University Comprehensive Specialized Hospital, Hawassa city, Ethiopia in 2019.Methods and MaterialsThe health institution/hospital-based retrospective cross-sectional study design was applied and a systematic random sampling technique was implemented to select the sample size of 274 patient’s cards from January 2018 to January 2019. The data were entered and analyzed on SPSS 20.ResultsFrom 274 patients’ medical records reviewed in the study period, 151 (55.1%) injuries were due to motorcycle accident. In a multiple logistic regression analysis, age, sex, high speed, and types of roads showed significant association with motorcycle accidents.ConclusionThe prevalence of motorcycle accidents was the main cause of injuries among others, which was 55.1%. Motorcycle accidents occurred mainly in males and in people with the age category of 20–29 years. Age, sex, high speed, and type of road were significantly associated with a motorcycle accident.

Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma.

Glioblastoma (GBM) is highly resistant to chemotherapies, immune-based therapies, and targeted inhibitors. To identify novel drug targets, we screened orthotopically implanted, patient-derived glioblastoma sphere-forming cells using an RNAi library to probe essential tumor cell metabolic programs. This identified high dependence on mitochondrial fatty acid metabolism. We focused on medium-chain acyl-CoA dehydrogenase (MCAD), which oxidizes medium-chain fatty acids (MCFA), due to its consistently high score and high expression among models and upregulation in GBM compared with normal brain. Beyond the expected energetics impairment, MCAD depletion in primary GBM models induced an irreversible cascade of detrimental metabolic effects characterized by accumulation of unmetabolized MCFAs, which induced lipid peroxidation and oxidative stress, irreversible mitochondrial damage, and apoptosis. Our data uncover a novel protective role for MCAD to clear lipid molecules that may cause lethal cell damage, suggesting that therapeutic targeting of MCFA catabolism may exploit a key metabolic feature of GBM. SIGNIFICANCE: MCAD exerts a protective role to prevent accumulation of toxic metabolic by-products in glioma cells, actively catabolizing lipid species that would otherwise affect mitochondrial integrity and induce cell death. This work represents a first demonstration of a nonenergetic role for dependence on fatty acid metabolism in cancer.This article is highlighted in the In This Issue feature, p. 2659.

Thiophene-2-carboxamide derivatives of anthraquinone: A new potent antitumor chemotype.

The anthraquinone scaffold has long been known as a source of efficacious antitumor drugs. In particular, the various chemical modifications of the side chains in this scaffold have yielded the compounds potent for the wild type tumor cells, their counterparts with molecular determinants of altered drug response, as well as invivo settings. Further exploring the chemotype of anticancer heteroarene-fused anthraquinones, we herein demonstrate that derivative of anthra[2,3-b]thiophene-2-carboxamide, (compound 8) is highly potent against a panel of human tumor cell lines and their drug resistant variants. Treatment with submicromolar or low micromolar concentrations of 8 for only 30min was sufficient to trigger lethal damage of K562 chronic myelogenous leukemia cells. Compound 8 (2.5μM, 3-6h) induced an apoptotic cell death as determined by concomitant activation of caspases 3 and 9, cleavage of poly(ADP-ribose) polymerase, increase of Annexin V/propidium iodide double stained cells, DNA fragmentation (subG1 fraction) and a decrease of mitochondrial membrane potential. Neither a significant interaction with double stranded DNA nor strong inhibition of the DNA dependent enzyme topoisomerase 1 by 8 were detectable in cell free systems. Laser scanning confocal microscopy revealed that some amount of 8 was detectable in mitochondria as early as 5min after the addition to the cells; exposure for 1h caused significant morphological changes and clustering of mitochondria. The bioisosteric analog 2 in which the thiophene ring was replaced with furan was less active although the patterns of cytotoxicity of both derivatives were similar. These results point at the specific role of the sulfur atom in the antitumor properties of carboxamide derivatives of heteroarene-fused anthraquinone.

High light-induced photoinhibition is not limiting seedling establishment at abrupt treeline ecotones in New Zealand.

Seedlings of New Zealand's treeline-forming Fuscospora cliffortioides (Hook.f.) perform poorly beyond the established canopy, limiting treeline advance. To test the long-standing assumption that photoinhibition impairs regeneration in the subalpine belt of New Zealand's Southern Alps, we assessed photosystem II (PSII) performance of seedling-sized individuals and microclimate variation. We performed diurnal, non-invasive chlorophyll-a-fluorescence measurements on exposed and canopy-sheltered individuals at two sites in New Zealand's Southern Alps during summer and winter. Diurnal recordings of the effective (ΦPSII) and optimal (Fv/Fm) photosynthetic quantum yield were supplemented with light response curves and micro-temperature recordings. ΦPSII returned to near-optimal values around 0.8 after 30min of shading, which rules out accumulative or long-term photoinhibition effects. The maximum electron transport rate derived from rapid light curves was significantly higher (+12%) in exposed compared with canopy-shaded individuals. Summer temperature fluctuated widely on the scree (-0.5 to 60.5°C) and near seedlings (-2 to 26.5°C). Our results revealed a remarkable level of light adaptation and contradict previous studies hinting at high light-induced photoinhibition as a treeline-limiting factor in the Southern Alps. By linking low ΦPSII on winter mornings, and large, sudden temperature drops in summer, we suspect that cold-induced photoinhibition might occur but the rapid recovery of ΦPSII seen across a wide temperature range makes lethal photo-oxidative damage rather unlikely. Given the demonstrably low summer frost tolerance of F. cliffortioides, cold-related damage resulting from frost events during the growing season or embolism induced by frost drought may offer more plausible explanations for the poor seedling establishment. Duration and frequency of these events could diminish with global warming, which may promote treeline advance.

Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity.

Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity.

Impact of mechanized clam dredging on the discarded megabenthic fauna on the Catalan coast (NW Mediterranean)

AbstractThere is an important small-scale fishery using mechanized dredges and targeting clams (mainly wedge clam Donax trunculus and striped venus clam Chamelea gallina) along the Catalan coast (NW Mediterranean Sea). This study evaluated for the first time the discards and impact of mechanized clam dredging on the Catalan coast. To this end, three surveys were performed on board standard clam vessels (September and November 2016 and January 2017). Surveys were conducted in the three main clam fishing areas (Rosas Bay, South Barcelona and Ebro Delta). The composition of discards and the impact caused to discarded species was assessed using a three-level scale (undamaged; minor or partial damage; and lethal damage). Our study revealed that a large proportion of the catch (between 67–82% weight) is discarded. Even though about 63% of the discarded species were undamaged, 11% showed minor or partial damage and 26% lethal damage. Infaunal and epifaunal species with soft-body or fragile shells were the most impacted by the fishing activity (e.g. the sea urchin Echinocardium mediterraneum (~89%) and the bivalve Ensis minor (~74%)). Our results showed different levels of impact by target species and fishing area.

β-amyrin-induced apoptosis in Candida albicans triggered by calcium

The emergence of drug-resistant pathogens has urged researchers to discover alternatives for traditional antibiotics. β-amyrin, which is included in the category of triterpenoids extracted from plants, is known for its antimicrobial activity, although the underlying mechanism has not yet been revealed. This study was conducted to elucidate the antifungal mode of action of β-amyrin against Candida albicans. Based on the relevance between triterpenoids and oxidative molecules, reactive oxygen species (ROS) concentrations were detected, which showed a noticeable increment. Disruption of Ca2+ homeostasis in the cytosol was additionally analyzed, which was supported by interactions between two. Subsequently, decrease in mitochondrial membrane potential, increment of mitochondrial Ca2+, and ROS concentration were monitored, which suggested mitochondrial dysfunction modulated by Ca2+. Further investigation confirmed oxidative damage through glutathione reduction and DNA fragmentation. Accumulation of lethal damages resulted in the activation of caspases and externalization of phosphatidylserine, indicating the induction of yeast apoptosis by β-amyrin in C. albicans.