Genomic Instability and Replicative Stress in Multiple Myeloma: The Final Curtain?

Multiple Myeloma (MM) is a genetically complex and heterogeneous hematological cancer that remains incurable despite the introduction of novel therapies in the clinic. Sadly, despite efforts spanning several decades, genomic analysis has failed to identify shared genetic aberrations that could be targeted in this disease. Seeking alternative strategies, various efforts have attempted to target and exploit non-oncogene addictions of MM cells, including, for example, proteasome inhibitors. The surprising finding that MM cells present rampant genomic instability has ignited concerted efforts to understand its origin and exploit it for therapeutic purposes. A credible hypothesis, supported by several lines of evidence, suggests that at the root of this phenotype there is intense replicative stress. Here, we review the current understanding of the role of replicative stress in eliciting genomic instability in MM and how MM cells rely on a single protein, Ataxia Telangiectasia-mutated and Rad3-related protein, ATR, to control and survive the ensuing, potentially fatal DNA damage. From this perspective, replicative stress per se represents not only an opportunity for MM cells to increase their evolutionary pool by increasing their genomic heterogeneity, but also a vulnerability that could be leveraged for therapeutic purposes to selectively target MM tumor cells.

Multiple gamma rhythms carry distinct spatial frequency information in primary visual cortex

Gamma rhythms in many brain regions, including the primary visual cortex (V1), are thought to play a role in information processing. Here, we report a surprising finding of 3 narrowband gamma rhythms in V1 that processed distinct spatial frequency (SF) signals and had different neural origins. The low gamma (LG; 25 to 40 Hz) rhythm was generated at the V1 superficial layer and preferred a higher SF compared with spike activity, whereas both the medium gamma (MG; 40 to 65 Hz), generated at the cortical level, and the high gamma HG; (65 to 85 Hz), originated precortically, preferred lower SF information. Furthermore, compared with the rates of spike activity, the powers of the 3 gammas had better performance in discriminating the edge and surface of simple objects. These findings suggest that gamma rhythms reflect the neural dynamics of neural circuitries that process different SF information in the visual system, which may be crucial for multiplexing SF information and synchronizing different features of an object.

A surprising finding of Ecclisopteryx asterix Malicky, 1979 (Insecta, Trichoptera) in Croatia with notes to DNA barcoding and new distributional data of the subfamily Drusinae

The subfamily Drusinae (Trichoptera, Limnephilidae) is represented in Croatia with eight (8) species, including Ecclisopteryx asterix Malicky, 1979 recorded for the first time in Croatian fauna. The species was collected on two occasions: March 10th 2015 and March 6th 2021 in the Šumi Spring, at the Ivanščica Mt. in Hrvatsko Zagorje (North Croatia). This new finding considerably extends the distribution of this species, previously considered a microendemic of the Alps. The distribution of the two species, Drusus schmidi Botosaneanu, 1960 and D. croaticus Marinković-Gospodnetić, 1971 has been also enlarged with new findings. Within this study, nine specimens of the aforementioned species have been DNA barcoded and sequences were entered into the BOLD database. The results of this paper contribute to the ecological and faunistic knowledge of caddisflies in Croatia, with an emphasis on the subfamily Drusinae.

On the Role of Inhibition in Suppression-Induced Forgetting

Suppressing retrieval of unwanted memories can cause forgetting, an outcome often attributed to the recruitment of inhibitory control. This suppression-induced forgetting (SIF) generalizes to different cues used to test the suppressed content (cue-independence), a property taken as consistent with inhibition. But does cue-independent forgetting necessarily imply that a memory has been inhibited? Tomlinson et al. (2009) reported a surprising finding that pressing a button also led to cue-independent forgetting, which was taken as support for an alternative interference account. Here we investigated the role of inhibition in forgetting due to retrieval suppression and pressing buttons. We modified Tomlinson et al.’s procedure to examine an unusual feature they introduced that may have caused memory inhibition effects in their experiment: the omission of explicit task-cues. When tasks were uncued, we replicated the button-press forgetting effect; but when cued, pressing buttons caused no forgetting. Moreover, button-press forgetting partially reflects output-interference effects at test and not a lasting effect of interference. In contrast, SIF occurred regardless of these procedural changes. Collectively, these findings indicate that simply pressing a button does not induce forgetting, on its own, without confounding factors that introduce inhibition into the task and that inhibition likely underlies SIF.

Revisiting the Experiential Effect: How Criminal Offending Affects Juveniles’ Perceptions of Detection Risk

Perceptual deterrence research has consistently found that criminal offending is inversely related to subsequent perceptions of the risk of being caught or arrested. This inverse relationship has been dubbed an “experiential effect,” reflecting the idea that people learn by committing (undetected) crimes that the detection or arrest risk is lower than first feared. The current study explores the validity of this experiential argument. It relies on self-report data from 3,259 adolescent participants in the panel study Crime in the modern City (Duisburg, Germany). We computed detection rates and risk perceptions, and used fixed effects models to investigate the proposed experiential learning process. Most findings support the experiential argument: (1) juvenile offenses were rarely detected by the police, (2) juveniles (especially those inexperienced with crime) tended to overestimate the detection risk, (3) juveniles reduced their risk perceptions when they committed crimes, (4) this reduction occurred primarily among those who overestimated the detection risk in periods when they were not committing crimes. However, the study also produced the surprising finding that the experiential effect seems to be short-lived: people appeared to return to initial risk perception levels when they stopped committing crimes. Overall, the results corroborate the experiential argument. However, they also indicate that the argument may need revision to account for the potential short-term nature of the experiential effect. This “ephemerality effect” is good news for policy, as lowered risk perceptions will in most cases only temporarily increase the likelihood of future delinquency.

Halide-selective, proton-coupled anion transport by phenylthiosemicarbazones

Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that the protonated PTSCs are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH.

Halide-selective, proton-coupled anion transport by phenylthiosemicarbazones

Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that the protonated PTSCs are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH.

Implementation of Circular Economy Technologies: An Empirical Study of Slovak and Slovenian Manufacturing Companies

Circular Economy (CE) practices and technologies are essential for increasing sustainability performance in manufacturing. Due to the increasing number of environmental regulations and growing public awareness of environmental issues, especially in the EU, CE is increasingly seen as a valuable factor in improving competitiveness. Therefore, there is a need for a fuller understanding of the ways in which CE technologies can be implemented into the manufacturing industries. The aim of this paper is to contribute to the identification of the characteristics of manufacturing companies and their perceptions of the barriers to the adoption of CE technologies. This survey-based study of 241 manufacturing companies (comprising a sub-sample of Slovak and Slovenian companies from the more extensive European Manufacturing Survey) uses a series of statistical tests to examine the implementation of three CE technologies. The results show that there is significant relationship between the adoption of CE technologies in manufacturing companies and their size, location, R&D activities, company age and product batch size. Finally, the research reveals the surprising finding that there is no apparent link between the perception of CE barriers and the plans of companies to implement selected CE technologies.

Acute hemodialysis catheter follows the path of least resistance

The placement of large bore double-lumen catheters for hemodialysis (HD) is one of the most frequent procedures performed in HD patients. However, these procedures are associated with complications, the most common being catheter malposition. In this context, catheter deviation to the left superior intercostal vein (LISV) is a very uncommon malposition, which must be differentiated from intrathoracic extravascular catheter lodgment. We report a case of an adult male patient on hemodialysis who presented with a thrombosed arteriovenous fistula and requiring urgent HD. His past medical history included hemophilia, allergy to contrast media, and multiple previous central vein catheterizations. A non-tunneled HD catheter was placed without any difficulty in the left internal jugular vein. However, the arterial lumen failed to pull any blood with free flow in the venous lumen. A chest X-ray revealed a surprising finding. The malpositioned catheter was removed successfully without any complications.