Ubiquitination and deubiquitination of PCNA in response to stalling of the replication fork

Following exposure of human cells to DNA damaging agents that block the progress of the replication fork, mono-ubiquitination of PCNA mediates the switch from replicative DNA polymerases to polymerases specialised for translesion synthesis. We have shown that this modification of PCNA is necessary for the survival of cells after UV-irradiation and methyl methanesulfonate, that it is independent of cell cycle checkpoint activation, and that it persists after UV damage has been removed. In this Extra-view, we compare the regulation and biological significance of PCNA ubiquitination following treatments with UV light and the replication inhibitor hydroxyurea. We show that ubiquitination persists after removal of the replication block in both cases. With UV however, the persistence of ubiquitinated PCNA correlates with disappearance of the PCNA deubiquitinating enzyme USP1, whereas this is not the case for HU. Prevention of PCNA ubiquitination sensitises the cells to killing by both UV and HU

Meetings as a positive boost? How and when meeting satisfaction impacts employee empowerment

Meetings constitute an important context for understanding organizational behavior and employee attitudes. Employees spend ever-increasing time in meetings and often complain about their meetings. In contrast, we explore the positive side of meetings and argue that satisfying meetings can empower rather than deplete individual employees. We gathered time-lagged data from an online sample of working adults in the U.S. As hypothesized, meeting satisfaction predicted employee empowerment, and information availability partially mediated this effect. Moreover, we found that these effects were stronger when employees participated in more meetings: Meeting demands moderated the link between meeting satisfaction and information availability as well as the positive, indirect effect of meeting satisfaction (through information availability) on psychological empowerment. Our findings underscore the relevance of workplace meetings for managing and promoting positive employee attitudes. We discuss implications for meeting science and the value of satisfying meetings as a managerial tool for promoting empowerment

Quantum Nature of Plasmon-Enhanced Raman Scattering

We report plasmon-enhanced Raman scattering in graphene coupled to a single plasmonic hotspot measured as a function of laser energy. The enhancement profiles of the G peak show strong enhancement (up to $10^5$) and narrow resonances (30 meV) that are induced by the localized surface plasmon of a gold nanodimer. We observe the evolution of defect-mode scattering in a defect-free graphene lattice in resonance with the plasmon. We propose a quantum theory of plasmon-enhanced Raman scattering, where the plasmon forms an integral part of the excitation process. Quantum interferences between scattering channels explain the experimentally observed resonance profiles, in particular, the marked difference in enhancement factors for incoming and outgoing resonance and the appearance of the defect-type modes.Comment: Keywords: plasmon-enhanced Raman scattering, SERS, graphene, quantum interferences, microscopic theory of Raman scattering. Content: 22 pages including 5 figures + 11 pages supporting informatio

Influence of grain direction in vibrational wood welding

Wood grain orientation differences in the two surfaces to be bonded yield bondlines of different strength in no-adhesives wood welding. Longitudinal wood grain bonding of tangential and radial wood sections yields an approximately 10% difference in strength results of the joint. Cross-grain (±90°) bonding yields instead a much lower strength result, roughly half that observed for pieces bonded with the grain parallel to each other. These differences can be explained by the very marked effect that homogeneity of fibre orientation is known to have on fibre–matrix composites. Oak yields lower results than beech and maple and is more sensitive to welding conditions. Differences in both anatomical and wood constituent composition can account for this difference in performance. Contrary to the other wood species, oak always presents joint bondlines where little or no increase in density at the interface is noticed. This explains its somewhat lower strength results. This is based on the different mode of bonding predominant in this species, while the other species present two different modes of bonding. Thus, two types of bondlines are observed by scanning electron microscopy (SEM): (i) bondlines where entangled fibre–matrix composites are formed at the interface and (ii) bondlines in which direct welding of the cell walls occurs, just by fused intercellular material or cell surface material. In this latter case the cells remain flat, without an entangled fibre–matrix composite being formed. This is the almost exclusively predominant case for oak. Both cases and even hybrid cases between the two have also been observed in beech

Activation of interferon regulatory factor 3 by replication-competent Vaccinia viruses improves antitumor efficacy mediated by T-cell responses

Recently, oncolytic vaccinia viruses (VACVs) have shown their potential to provide for clinically effective cancer treatments. The reason for this clinical usefulness is not only the direct destruction of infected cancer cells but also activation of immune responses directed against tumor antigens. For eliciting a robust antitumor immunity, a dominant T helper 1 (Th1) cell differentiation of the response is preferred, and such polarization can be achieved by activating the Toll-like receptor 3 (TLR3)-interferon regulatory factor 3 (IRF3) signaling pathway. However, current VACVs used as oncolytic viruses to date still encode several immune evasion proteins involved in the inhibition of this signaling pathway. By inactivating genes of selected regulatory virus proteins, we aimed for a candidate virus with increased potency to activate cellular antitumor immunity but at the same time with a fully maintained replicative capacity in cancer cells. The removal of up to three key genes (C10L, N2L, and C6L) from VACV did not reduce the strength of viral replication, both in vitro and in vivo, but resulted in the rescue of IRF3 phosphorylation upon infection of cancer cells. In syngeneic mouse tumor models, this activation translated to enhanced cytotoxic T lymphocyte (CTL) responses directed against tumor-associated antigens and neo-epitopes and improved antitumor activity

Nanodrawing of aligned single carbon nanotubes with a nanopen

Single-walled carbon nanotubes (SWCNTs) are considered pivotal components for molecular electronics. Techniques for SWCNT lithography today lack simplicity, flexibility, and speed of direct, oriented deposition at specific target locations. In this paper SWCNTs are directly drawn and placed with chemical identification and demonstrated orientation using fountain pen nanolithography (FPN) under ambient conditions. Placement across specific electrical contacts with such alignment is demonstrated and characterized. The fundamental basis of the drawing process with alignment has potential applications for other related systems such as inorganic nanotubes, polymers, and biological molecules

Distinct Streptococcus pneumoniae cause invasive disease in Papua New Guinea

Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. © 2022 The Authors

Trait‐based approaches reveal fungal adaptations to nutrient‐limiting conditions

The dependency of microbial activity on nutrient availability in soil is only partly understood, but highly relevant for nutrient cycling dynamics. In order to achieve more insight on microbial adaptations to nutrient limiting conditions, precise physiological knowledge is needed. Therefore, we developed an experimental system assessing traits of 16 saprobic fungal isolates in nitrogen (N) limited conditions. We tested the hypotheses that (1) fungal traits are negatively affected by N deficiency to a similar extent and (2) fungal isolates respond in a phylogenetically conserved fashion. Indeed, mycelial density, spore production and fungal activity (respiration and enzymatic activity) responded similarly to limiting conditions by an overall linear decrease. By contrast, mycelial extension and hyphal elongation peaked at lowest N supply (C:N 200), causing maximal biomass production at intermediate N contents. Optimal N supply rates differed among isolates, but only the extent of growth reduction was phylogenetically conserved. In conclusion, growth responses appeared as a switch from explorative growth in low nutrient conditions to exploitative growth in nutrient‐rich patches, as also supported by responses to phosphorus and carbon limitations. This detailed trait‐based pattern will not only improve fungal growth models, but also may facilitate interpretations of microbial responses observed in field studies