Self-Organized Cultural Cycles and the Uncertainty of Archaeological Thought

Contributing to the issue of complex relationship between social and cultural evolution, this paper aims to analyze repetitive patterns, or cycles, in the development of material culture. Our analysis focuses on culture change associated with sociopolitical and economic stasis. The proposed toy model describes the cyclical character of the quantitative and qualitative composition of archaeological assemblages, which include hierarchically organized cultural traits. Cycles sequentially process the stages of unification, diversity, and return to unification. This complex dynamic behavior is caused by the ratio between cultural traits’ replication rate and the proportion of traits of the higher taxonomic order’s related unit. Our approach identifies a shift from conformist to anti-conformist transmission, corresponding with open and closed phases in cultural evolution in respect to the introduction of innovations. The model also describes the dependence of a probability for horizontal transmission upon orders of taxonomic hierarchy during open phases. The obtained results are indicative for gradual cultural evolution at the low orders of taxonomic hierarchy and punctuated evolution at its high orders. The similarity of the model outcomes to the patters of material culture change reflecting societal transformations enables discussions around the uncertainty of explanation in archaeology and anthropology.

Comparison of Plaque Size, Thermal Stability, and Replication Rate among SARS-CoV-2 Variants of Concern

SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including alpha (B.1.1.7, Clade GRY), beta (B.1.351, Clade GH), gamma (P.1, Clade GR), and delta (B.1.617.2, Clade G). VOCs are likely to have some effect on transmissibility, antibody evasion, and changes in therapeutic or vaccine effectiveness. However, the physiological and virological understanding of these variants remains poor. We demonstrated that these four VOCs exhibited differences in plaque size, thermal stability at physiological temperature, and replication rates. The mean plaque size of beta was the largest, followed by those of gamma, delta, and alpha. Thermal stability, evaluated by measuring infectivity and half-life after prolonged incubation at physiological temperature, was correlated with plaque size in all variants except alpha. However, despite its relatively high thermal stability, alpha’s small plaque size resulted in lower replication rates and fewer progeny viruses. Our findings may inform further virological studies of SARS-CoV-2 variant characteristics, VOCs, and variants of interest. These studies are important for the effective management of the COVID-19 pandemic.

Generation of a Retargeted Oncolytic Herpes Virus Encoding Adenosine Deaminase for Tumor Adenosine Clearance

Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine. Methods: Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP). Results: Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function. Conclusions: Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation.

Reduction of Rapid Proliferating Tumour Cell Lines by Inhibition of the Specific Glycine Transporter GLYT1

Studies have highlighted the relevance of extracellular glycine and serine in supporting high growth rates of rapidly proliferating tumours. The present study analysed the role of the specific glycine transporter GLYT1 in supplying glycine to cancer cells and maintaining cell proliferation. GLYT1 knockdown in the rapidly proliferating tumour cell lines A549 and HT29 reduced the number of viable cells by approximately 30% and the replication rate presented a decrease of about 50% when compared to cells transfected with control siRNA. In contrast, when compared to control, GLYT1 siRNA had only a minimal effect on cell number of the slowly proliferating tumour cell line A498, reducing the number of viable cells by 7% and no significant difference was observed when analysing the replication rate between GLYT1 knockdown and control group. When utilising a specific GLYT1 inhibitor, ALX-5407, the doubling time of rapidly proliferating cells increased by about 8 h presenting a significant reduction in the number of viable cells after 96 h treatment when compared to untreated cells. Therefore, these results suggest that GLYT1 is required to maintain high proliferation rates in rapidly proliferating cancer cells and encourage further investigation of GLYT1 as a possible target in a novel therapeutic approach.

Empirical audit and review and an assessment of evidentiary value in research on the psychological consequences of scarcity

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.

Comparison of Plaque Size, Thermal Stability, and Replication Rate among SARS-CoV-2 Variants of Concern

SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. This evolution results in the emergence of novel variants with different characteristics than their ancestral strain. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including alpha (B.1.1.7, Clade GRY), beta (B.1.351, Clade GH), gamma (P.1, Clade GR), and delta (B.1.617.2, Clade G). VOCs are likely to have some effect on transmissibility, antibody evasion, and changes in therapeutic or vaccine effectiveness. However, the physiological and virological understanding of these variants remains poor. We demonstrated that these four VOCs exhibited differences in plaque size, thermal stability at physiological temperature, and replication rates. The mean plaque size of beta was the largest, followed by those of gamma, delta, and alpha. Thermal stability, evaluated by measuring infectivity and half-life after prolonged incubation at physiological temperature, was correlated with plaque size in all variants except alpha. However, despite its relatively high thermal stability, alpha's small plaque size resulted in lower replication rates and fewer progeny viruses. Our findings may inform further virological studies of SARS-CoV-2 variant characteristics, VOCs, and variants of interest. These studies are important for the effective management of the COVID-19 pandemic.

Conceptual replication study of fifteen JDM effects: Insights from the Polish sample

We conducted pre-registered replications of 15 effects in the field of judgment and decision making (JDM). We aimed to test the generalizability of different classical and modern JDM effects, including, among others: less-is-better, anchoring, and framing to different languages, cultures, or current situations (COVID-19 pandemic). Replicated studies were selected and conducted by undergraduate psychology students enrolled in a decision-making course. Two hundred and two adult volunteers completed an online battery of replicated studies. With a classical significance criterion (p < .05), seven effects were successfully replicated (47%), five partially replicated (33%), and three did not replicate (20%). Even though research materials differed from the originals in several ways, the replication rate in our project is slightly above earlier reported findings in similar replication projects.

Nothing in evolution makes sense except in the light of parasitism: evolution of complex replication strategies

Parasitism emerges readily in models and laboratory experiments of RNA world and would lead to extinction unless prevented by compartmentalization or spatial patterning. Modelling replication as an active computational process opens up many degrees of freedom that are exploited to meet environmental challenges, and to modify the evolutionary process itself. Here, we use automata chemistry models and spatial RNA-world models to study the emergence of parasitism and the complexity that evolves in response. The system is initialized with a hand-designed replicator that copies other replicators with a small chance of point mutation. Almost immediately, short parasites arise; these are copied more quickly, and so have an evolutionary advantage. The replicators also become shorter, and so are replicated faster; they evolve a mechanism to slow down replication, which reduces the difference of replication rate of replicators and parasites. They also evolve explicit mechanisms to discriminate copies of self from parasites; these mechanisms become increasingly complex. New parasite species continually arise from mutated replicators, rather than from evolving parasite lineages. Evolution itself evolves, e.g. by effectively increasing point mutation rates, and by generating novel emergent mutational operators. Thus, parasitism drives the evolution of complex replicators and complex ecosystems.

Viral infection and Transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant

We report the first local transmission of the Delta SARS-CoV-2 variant in mainland China. All 167 infections could be traced back to the first index case. The investigation on daily sequential PCR testing of the quarantined subjects indicated the viral load of the first positive test of Delta infections was ~1000 times higher than that of the 19A/19B strains infections back in the initial epidemic wave of 2020, suggesting the potential faster viral replication rate and more infectiousness of the Delta variant at the early stage of the infection. The 126 high-quality sequencing data and reliable epidemiological data indicated some minor intra-host single nucleotide variants (iSNVs) could be transmitted between hosts and finally fixed in the virus population during the outbreak. The minor iSNVs transmission between donor-recipient contribute at least 4 of 31 substitutions identified in the outbreak suggesting some iSNVs more likely to arise and reach fixation when the virus spread rapidly. Disease control measures, including the frequency of population testing, quarantine in pre-symptomatic phase and enhancing the genetic surveillance should be adjusted to account for the increasing prevalence of the Delta variant at global level.