Microbial Mediation of Carbon, Nitrogen and Sulfur Cycles During Solid Waste Decomposition

Landfills is a unique “terrestrial ecosystem” and serves as a significant carbon sink. Microorganism convert biodegradable substances in municipal solid waste (MSW) to CH4, CO2 and microbial biomass, consisting of the carbon cycling in landfills. Meanwhile, microbial mediated N and S cycles affect carbon cycling. How microbial community structure and function respond to C, N, and S cycling during solid waste decomposition, however are not well characterized. Here we show the response of bacterial and archaeal community structure and functions to C, N, and S cycling during solid waste decomposition in a long-term (265 days) operation laboratory-scale bioreactor through 16S rRNA based pyrosequencing and metagenomics analysis. Bacterial and archaeal community composition varied during solid waste decomposition. Aerobic respiration was the main pathway for CO2 emission, while anaerobic C fixation was the main pathway in carbon fixation. Methanogenesis and denitrification increased during solid waste decomposition, suggesting increasing CH4 and N2O emission. In contract, fermentation decreased along solid waste decomposition. Interestingly, Clostridiales were abundant and showed potential for several pathways in C, N, and S cycling. Archaea were involved in many pathways of C and N cycles. There is a shift between bacteria and archaea involvement in N2 fixation along solid waste decomposition that bacteria Clostridiales and Bacteroidales were initial dominant and then Methanosarcinales increased and became dominant in methanogenic phase. These results provide extensive microbial mediation of C, N, and S cycling profiles during solid waste decomposition.

Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis

Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and β-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTHL1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a reduced activity on lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.

The Application of Nitric Oxide for Ocular Hypertension Treatment

Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using ‘nitric oxide’ and ‘glaucoma’ as key words.

DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases

Site-specific DNA methylation plays an important role in epigenetic regulation of gene expression. Chemical methylation of DNA, including the formation of various methylated nitrogenous bases, leads to the formation of genotoxic modifications that impair DNA functions. Despite the fact that different pathways give rise to methyl groups in DNA, the main pathway for their removal is oxidative demethylation, which is catalyzed by nonheme Fe(II)/α-ketoglutarate–dependent DNA dioxygenases. DNA dioxygenases share a common catalytic mechanism of the oxidation of the alkyl groups on nitrogenous bases in nucleic acids. This review presents generalized data on the catalytic mechanism of action of DNA dioxygenases and on the participation of typical representatives of this superfamily, such as prokaryotic enzyme AlkB and eukaryotic enzymes ALKBH1–8 and TET1–3, in both processes of direct repair of alkylated DNA adducts and in the removal of an epigenetic mark (5-methylcytosine).

Plasma Membrane and Organellar Targets of STIM1 for Intracellular Calcium Handling in Health and Neurodegenerative Diseases

Located at the level of the endoplasmic reticulum (ER) membrane, stromal interacting molecule 1 (STIM1) undergoes a complex conformational rearrangement after depletion of ER luminal Ca2+. Then, STIM1 translocates into discrete ER-plasma membrane (PM) junctions where it directly interacts with and activates plasma membrane Orai1 channels to refill ER with Ca2+. Furthermore, Ca2+ entry due to Orai1/STIM1 interaction may induce canonical transient receptor potential channel 1 (TRPC1) translocation to the plasma membrane, where it is activated by STIM1. All these events give rise to store-operated calcium entry (SOCE). Besides the main pathway underlying SOCE, which mainly involves Orai1 and TRPC1 activation, STIM1 modulates many other plasma membrane proteins in order to potentiate the influxof Ca2+. Furthermore, it is now clear that STIM1 may inhibit Ca2+ currents mediated by L-type Ca2+ channels. Interestingly, STIM1 also interacts with some intracellular channels and transporters, including nuclear and lysosomal ionic proteins, thus orchestrating organellar Ca2+ homeostasis. STIM1 and its partners/effectors are significantly modulated in diverse acute and chronic neurodegenerative conditions. This highlights the importance of further disclosing their cellular functions as they might represent promising molecular targets for neuroprotection.

Pharmaceutical and Antibiotic Pollutant Levels in Wastewater and the Waters of the Zarqa River, Jordan

Assamra wastewater treatment plant (WWTP) is the largest treatment facility in Jordan. Treated wastewater is discharged into the Zarqa River (ZR) and used to irrigate fodder and vegetables. ZR also includes surface runoff, stormwater, and raw wastewater illegally discharged into the river. This study examined pharmaceutically active compounds (PhAC) in water resources in the ZR basin. Samples of WWTP influent and effluent and river water from four sites along ZR were collected. Concentrations of 18 target antibiotics, one stimulant, and 15 other PhACs were determined in the samples. Five antibiotics were detected in WWTP influent (510–860 ng L−1 for ∑Antibiotics) and six in the effluent (2300–2600 ng L−1 for ∑Antibiotics). Concentrations in the effluent of all antibiotics except clarithromycin increased by 2- to 5-fold compared with those in influent, while clarithromycin concentration decreased by around 4- fold (from 308 to 82 ng L−1). WWTP influent and effluent samples contained 14 non-antibiotic PhACs, one simulant, and six antibiotics at detectable concentrations. The dominant PhACs were paracetamol (74% of ∑PhACs) in the influent and carbamazepine (78% of ∑PhACs) in the effluent. At ZR sampling sites, carbamazepine was the dominant PhAC in all cases (800–2700 ng L−1). The antibiotics detected in WWTP effluent were also detected at the ZR sites. In summary, water in ZR is contaminated with PhACs, including antibiotics, and wastewater discharge seems to be the main pathway for this contamination. The occurrence of antibiotics and other PhACs in the irrigated soil requires investigation to assess their fate.

The Vitamin D, IL-6 and the eGFR Markers a Possible Way to Elucidate the Lung–Heart–Kidney Cross-Talk in COVID-19 Disease: A Foregone Conclusion

Background: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. Methods: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. Results: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. Conclusions: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach.

NOx Storage on BaTi0.8Cu0.2O3 Perovskite Catalysts: Addressing a Feasible Mechanism

The NOx storage mechanism on BaTi0.8Cu0.2O3 catalyst were studied using different techniques. The results obtained by XRD, ATR, TGA and XPS under NOx storage–regeneration conditions revealed that BaO generated on the catalyst by decomposition of Ba2TiO4 plays a key role in the NOx storage process. In situ DRIFTS experiments under NO/O2 and NO/N2 show that nitrites and nitrates are formed on the perovskite during the NOx storage process. Thus, it seems that, as for model NSR catalysts, the NOx storage on BaTi0.8Cu0.2O3 catalyst takes place by both “nitrite” and “nitrate” routes, with the main pathway being highly dependent on the temperature and the time on stream: (i) at T < 350 °C, NO adsorption leads to nitrites formation on the catalyst and (ii) at T > 350 °C, the catalyst activity for NO oxidation promotes NO2 generation and the nitrate formation.

Caught in Motion: Human NTHL1 Undergoes Interdomain Rearrangement Necessary for Catalysis

Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and β-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTLH1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a lower binding affinity for lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.