Sgs1 and Exo1 Redundantly Inhibit Break-Induced Replication and De Novo Telomere Addition at Broken Chromosome Ends

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5′ to 3′ resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Δ exo1Δ strains, where there is little 5′ to 3′ resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Δ, or exo1Δ cells. In sgs1Δ exo1Δ, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 5′ to 3′ resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5′ to 3′ resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition

Web-based Cognitive-behavioral Intervention for Pain in Pediatric Acute Recurrent and Chronic Pancreatitis: Protocol of a Multicenter Randomized Controlled Trial from the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC)

Introduction Abdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response. Methods This single-blinded randomized placebo-controlled multicenter trial aims to enroll 260 youth (ages 10–18) with ARP/CP and their parents from twenty-one INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) centers. Participants will be randomly assigned to either a web-based cognitive behavioral pain management intervention (Web-based Management of Adolescent Pain Chronic Pancreatitis; WebMAP; N = 130) or to a web-based pain education program (WebED; N = 130). Assessments will be completed at baseline (T1), immediately after completion of the intervention (T2) and at 6 months post-intervention (T3). The primary study outcome is abdominal pain severity. Secondary outcomes include pain-related disability, pain interference, health-related quality of life, emotional distress, impact of pain, opioid use, and healthcare utilization. Conclusions This is the first clinical trial to evaluate the efficacy of a psychological pain intervention for children with CP for reduction of abdominal pain and improvement of health-related quality of life. Findings will inform delivery of web-based pain management and potentially identify patient-specific biological and psychosocial factors associated with favorable response to therapy

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Tunable nano-interfaces between MnOx and layered double hydroxides boost oxygen evolving electrocatalysis

The development of low overpotential, non-precious metal oxide electrocatalysts is important for sustainable water oxidation using renewable energy. Here we report the fabrication of nano-interfaces between MnOx nanoscale islands and NiFe layered double hydroxide (LDH) nanosheets, which were chosen as baseline electrocatalysts for OER activity tuning. The MnOx nano-islands were grown on the surfaces of NiFe-LDH nanosheets by atomic layer deposition (ALD). Morphological and structural characterization indicated that the MnOx formed flat nanoscale islands which uniformly covered the surfaces of NiFe-LDH nanosheets, giving rise to a large density of threedimensional nano-interfaces at the NiFe-LDH/MnOx/electrolyte multi-phase boundaries. We showed by X-ray spectroscopic characterization that these nano-interfaces induced electronic interactions between NiFe-LDH nanosheets and MnOx nano-islands. Through such modifications, the Fermi level of the original NiFe-LDHwas lowered by donating electrons to the MnOx nano-islands, dramatically boosting the OER performance of these electron-deficient NiFe-LDH catalysts. Using only 10 cycles of ALD MnOx, the MnOx/NiFe-LDH nanocomposites exhibited remarkable and enhanced electrocatalytic activity with an overpotential of 174 mV at 10 mA cm(-2). This work demonstrates a promising pathway for tuning transition metal electrocatalysts via a generic ALD surface modification technique

Low-Temperature Carbon Capture Using Aqueous Ammonia and Organic Solvents

Current postcombustion CO₂ capture technologies are energy intensive, require high-temperature heat sources, and dramatically increase the cost of power generation. In this work, we introduce a new carbon capture process requiring significantly lower temperatures and less energy, creating further impetus to reduce CO₂ emissions from power generation. In this process, high-purity CO₂ is generated through the addition of an organic solvent (acetone, dimethoxymethane, or acetaldehyde) to a CO₂ rich, aqueous ammonia/carbon dioxide solution under room-temperature and -pressure conditions. The organic solvent and CO₂-absorbing solution are then regenerated using low-temperature heat. When acetone, dimethoxymethane, or acetaldehyde was added at a concentration of 16.7% (v/v) to 2 M aqueous ammonium bicarbonate, 39.8, 48.6, or 86.5%, respectively, of the aqueous CO₂ species transformed into high-purity CO₂ gas over 3 h. Thermal energy and temperature requirements for recovering acetaldehyde, the best-performing organic solvent investigated, and the CO₂-absorbing solution were 1.39 MJ/kg of CO₂ generated and 68 °C, respectively, 75% less energy than the amount used in a pilot chilled ammonia process and a temperature 53 °C lower. Our findings exhibit the promise of economically viable carbon capture powered entirely by abundant low-temperature waste heat

Selective adsorption of arsenic over phosphate by transition metal cross-linked chitosan

The ability of transition metal chitosan complexes (TMCs) of varying valence and charge to selectively adsorb As(III) and As(V) over their strongest adsorptive competitor, phosphate is examined. Fe(III)-chitosan, Cu(II)-chitosan, Al(III)-chitosan, Ni(II)-chitosan, and Zn(II)-chitosan are synthesized, characterized via Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray Diffractometry (XRD), and their selective sorption capabilities towards arsenite and arsenate over phosphate are evaluated. It was found that the stability of the metal-chitosan complexes varied, with Al(III)- and Zn(II)-chitosan forming unstable complexes resulting in precipitation of gibbsite, and Wulfingite and zincite, respectively. Cu(II)-, Ni(II)-, and Fe(III)- chitosan formed a mixture of monodentate and bidentate complexes. The TMCs which formed the bidentate complex (Cu(II)-, Ni(II)-, and Fe(III)-) showed greater adsorption capability for arsenate in competitive systems with phosphate. Using the binary separation factor ∝t/c, it can be shown that only Fe(III)-chitosan is selective for As(V) and As(III) over phosphate. Density Functional Theory (DFT) modeling and extended X-ray absorption fine structure (EXAFS) determined that Fe(III)-chitosan and Ni(II)-chitosan adsorbed As(V) and As(III) via inner-sphere complexation, while Cu(II)-chitosan formed mainly outer-sphere complexes with As(V) and As(III). These differences in complexation likely result in the observed differences in selective adsorption capability towards As(V) and As(III) over phosphate

Hydrogen evolution activity tuning via twodimensional electron accumulation at buried interfaces

Developing efficient earth-abundant transition metal-based electrocatalysts for the hydrogen evolution reaction (HER) is crucial for hydrogen production at scale. This paper reports that the buried electrocatalytic interfaces between Ni-Fe sulfide (NiFeS) nanosheets and TiO2 conformal coatings (about 5 nm) achieved remarkable HER activity improvement, lowering the HER overpotential from 170 mV to 107 mV at 50 mA cm 2 in a base. Non-HER active, permeable TiO2 coatings grown by atomic layer deposition (ALD) achieved continuous fine-tuning of the electronic properties at the buried TiO2/ NiFeS interfaces, as a novel strategy and the main factor for electron accumulation at the interface. Core-level and valence band X-ray photoelectron spectroscopy (XPS) was used to investigate the TiO2 electronicstructure tuning effect on the charge-transfer energetics during the HER. Their alkaline HER mechanism was elucidated by supplementing characterizations of membrane permeation, Tafel slope, and synchrotron X-ray absorption spectroscopy, which verified that the buried TiO2/ NiFeS interfaces are electrocatalytically active. This study offers a general strategy for improving the charge-transfer kinetics of an electrocatalytic system by confining catalysis at a permeable solid-solid interface. The broad applicability of permeable and tunable coatings potentially accelerates the optimization of earthabundant catalysts to achieve high performance under operationally relevant conditions

Scalable production of single 2D van der Waals layers through atomic layer deposition: bilayer silica on metal foils and films

Hutchings GS, Shen X, Zhou C, et al. Scalable production of single 2D van der Waals layers through atomic layer deposition: bilayer silica on metal foils and films. 2D Materials. 2022;9(2): 021003.The self-limiting nature of atomic layer deposition (ALD) makes it an appealing option for growing single layers of two-dimensional van der Waals (2D-VDW) materials. In this paper it is demonstrated that a single layer of a 2D-VDW form of SiO2 can be grown by ALD on Au and Pd polycrystalline foils and epitaxial films. The silica was deposited by two cycles of bis(diethylamino) silane and oxygen plasma exposure at 525 K. Initial deposition produced a three-dimensionally disordered silica layer; however, subsequent annealing above 950 K drove a structural rearrangement resulting in 2D-VDW. The annealing could be performed at ambient pressure. Surface spectra recorded after annealing indicated that the two ALD cycles yielded close to the silica coverage obtained for 2D-VDW silica prepared by precision SiO deposition in ultra-high vacuum (UHV). Analysis of ALD-grown 2D-VDW silica on a Pd(111) film revealed the co-existence of amorphous and incommensurate crystalline 2D phases. In contrast, ALD growth on Au(111) films produced predominantly the amorphous phase while SiO deposition in UHV led to only the crystalline phase, suggesting that the choice of Si source can enable phase control

Hydrophobic CuO Nanosheets Functionalized with Organic Adsorbates

A new class of hydrophobic CuO nanosheets is introduced by functionalization of the cupric oxide surface with <i>p</i>-xylene, toluene, hexane, methylcyclohexane, and chlorobenzene. The resulting nanosheets exhibit a wide range of contact angles from 146° (<i>p</i>-xylene) to 27° (chlorobenzene) due to significant changes in surface composition induced by functionalization, as revealed by XPS and ATR-FTIR spectroscopies and computational modeling. Aromatic adsorbates are stable even up to 250–350 °C since they covalently bind to the surface as alkoxides, upon reaction with the surface as shown by DFT calculations and FTIR and ¹H NMR spectroscopy. The resulting hydrophobicity correlates with H₂ temperature-programmed reduction (H₂-TPR) stability, which therefore provides a practical gauge of hydrophobicity

Fundamental Role of Oxygen Stoichiometry in Controlling the Band Gap and Reactivity of Cupric Oxide Nanosheets

CuO is a nonhazardous, earth-abundant material that has exciting potential for use in solar cells, photocatalysis, and other optoelectronic applications. While progress has been made on the characterization of properties and reactivity of CuO, there remains significant controversy on how to control the precise band gap by tuning conditions of synthetic methods. Here, we combine experimental and theoretical methods to address the origin of the wide distribution of reported band gaps for CuO nanosheets. We establish reaction conditions to control the band gap and reactivity via a high-temperature treatment in an oxygen-rich environment. SEM, TEM, XRD, and BET physisorption reveals little to no change in nanostructure, crystal structure, or surface area. In contrast, UV–vis spectroscopy shows a modulation in the material band gap over a range of 330 meV. A similar trend is found in H₂ temperature-programmed reduction where peak H₂ consumption temperature decreases with treatment. Calculations of the density of states show that increasing the oxygen to copper coverage ratio of the surface accounts for most of the observed changes in the band gap. An oxygen exchange mechanism, supported by ¹⁸O₂ temperature-programmed oxidation, is proposed to be responsible for changes in the CuO nanosheet oxygen to copper stoichiometry. The changes induced by oxygen depletion/deposition serve to explain discrepancies in the band gap of CuO, as reported in the literature, as well as dramatic differences in catalytic performance