The evolutionary impacts of synonymous mutations

During the 50 years since the genetic code was cracked, our understanding of the evolutionary consequences of synonymous mutations has undergone a dramatic shift. Synonymous codon changes were initially considered selectively neutral, and as such, exemplars of evolution via genetic drift. However, the pervasive and non-negligible fitness impacts of synonymous mutations are now clear across organisms. Despite the accumulated evidence, it remains challenging to incorporate the effects of synonymous changes in studies of selection, because the existing analytical framework was built with a focus on the fitness effects of nonsynonymous mutations. In this chapter, I trace the development of this topic and discuss the evidence that gradually transformed our thinking about the role of synonymous mutations in evolution. I suggest that our evolutionary framework should encompass the impacts of all mutations on various forms of information transmission. Folding synonymous mutations into a common distribution – rather than setting them apart as a distinct category – will allow a more complete and cohesive picture of the evolutionary consequences of new mutations.

Genetic features and clinical outcomes of patients with isolated and comutated DDX41-mutated myeloid neoplasms

DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.

5-azacytidine for the treatment of massive hepatosplenomegaly in a case of myelodysplastic/myeloproliferative neoplasm-unclassifiable

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) represent a distinct category of myeloid diseases in the World Health Organization classification, defined at diagnosis by clinical, morphologic and laboratory features which overlap both those of MDS and MPN. Within the “Overlap” MDS/MPN syndromes, MDS/MPN-Unclassifiable (MDS/MPN-U) is the least well characterized. MDS/MPN-U is a rare diagnosis, making up less than 5% of all myeloid disorders with no standard prognostic or treatment algorithms. 5-azacytidine is a standard treatment for MDS, but controversial results are available about its role for MDS/MPN-U and its effectiveness on extramedullary disease and hepatosplenomegaly. We reported the clinical management of a MDS/MPN-U patient characterized by massive hepatosplenomegaly with optimal response to 5-azacytidine.

The Emergence of an Auction Category: Iranian Art at Christie’s Dubai, 2006–2016

The expansion of the British auction houses Christie’s, Sotheby’s and Bonhams to markets in the Middle East has played a crucial role in building an international market for art from the region. They have also been essential in providing an international platform for the sale of art from Iran, a country whose economy is otherwise isolated from global markets. In this paper, I address the growth of the market for Iranian art specifically via Christie’s auctions in Dubai. Through close analysis of auction catalogs, ethnographic data drawn from live auctions and interviews with key staff members, I document the emergence of Iranian art into the international arena and the solidification of both Iranian and Middle Eastern art as a distinct category of sales. In particular, I explore the notion of “seeing with the other eye”, a way that auction specialists nudge local collectors into the arena of “international” taste. Through analysis of the particular tropes used to narrate artist biographies in auction catalogs, I demonstrate how artists are painted as interpreters and translators of “local” and “global” aesthetic registers.

AUTORI ROMÂNI DE EXPRESIE GERMANĂ

This chapter presents six contemporary authors of Romanian origin and German expression. Classified as so-called “immigrant literature” - a distinct category outlined in German literary studies in the last four decades - the six authors were selected according to the following criteria: Romanian mother tongue, the experience of immigration in the German-speaking area, and the abandonment of the mother tongue in favor of German. In addition to bio-bibliographic data, the paper provides a representative text analysis for each author

Auto-compasiunea și auto-eficacitateaca – resurse personale în cazul terapeuților

One of the special human qualities is the compassion shown towards our fellow, in special situations, people who live certain states determined by the moments of life they go through. Self-compassion refers to the ability to show compassion, understanding and protection to oneself. It is operationalized by researcher Kristin Neff. Self-efficacy, proposed by Albert Bandura, refers to the perception of self and is related to the belief in one's own abilities, in one's own ability to solve situations. The interest of the study aims the relationship between self-compassion and self-efficacy in the case of a distinct category, that of therapists, professionally faced with situations that require personal resources. Methods: The level of self-compassion was assessed with the Self-Compassion Scale, 26 items, proposed by Kristin Neff. The level of self-efficacy was assessed using the New General Self-Efficacy Scale, the 8-item scale proposed by Gilad Chen & co (2001). Both questionnaires were distributed electronically. The data obtained were statistically analyzed and interpreted. Results: In the professional categories investigated, there are underline links and relations between the two constructs, with professional implications. The results show (1) Therapists have high values in assessing selfefficacy; (2) Therapists have high values of self-compassion; (3) Therapists have a high level of self-compassion and a low level of self-criticism as indicated by the self-compassion sub-scales; (4) There is a direct relationship between self-efficacy and self-compassion; (5) Therapists with high level of self-compassion also have a high level of self-efficacy (6) The level of self-efficacy is influenced by age and professional experience. (7) The level of self-compassion is influenced by age and professional experience Conclusion: The two concepts discussed are important in relation to certain professional categories and under the auspices of situations considered stressful and with emotional burden.

Fingernails Torn from Flesh: Intiz̤ār Ḥusain, Rām Laʿl, and Travel Writing across the India-Pakistan Border

Studies on the Partition of India have historically examined the years immediately before and after 1947, drawing heavily on Urdu fiction. Recent historiographic advances, however, emphasize “partitioning” to convey partition’s prolonged, indeterminate, and ongoing nature. This article suggests that the Urdu travel account is a primary literary space to negotiate the long-term signification of Partition and, as such, exemplifies processes of partitioning. It argues for the existence of a distinct category, the “cross-border travel account,” offering a critical and comparative reading of works by Intiz̤ār Ḥusain and Rām Laʿl to explore how the genre negotiates the legacy and future of Partition.

Involuntary autobiographical memories and their relation to other forms of spontaneous thoughts

Involuntary autobiographical memories are memories of personal events that come to mind spontaneously—that is, with no conscious initiation of the retrieval process. Such spontaneously arising memories were long ignored in cognitive psychology, which generally has focused on controlled and strategic forms of remembering, studied in laboratory settings. Recent evidence shows that involuntary memories of past events are highly frequent in daily life, and that they represent a context-sensitive, and associative way of recollecting past events that involves little executive control. They operate by constraints that favour recent events and events with a distinct feature overlap to the current situation, which optimizes the probability of functional relevance to the ongoing situation. In addition to adults, they are documented in young children and great apes and may be an ontogenetic and evolutionary forerunner of strategic retrieval of past events. Findings suggest that intrusive involuntary memories observed clinically after traumatic events should be viewed as a dysfunctional subclass of otherwise functional involuntary autobiographical memories. Because of their highly constrained, situation-dependent and automatic nature, involuntary autobiographical memories form a distinct category of spontaneous thought that cannot be equated with mind wandering. This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.

What Makes Musical Prodigies?

Musical prodigies reach exceptionally high levels of achievement before adolescence. Despite longstanding interest and fascination in musical prodigies, little is known about their psychological profile. Here we assess to what extent practice, intelligence, and personality make musical prodigies a distinct category of musician. Nineteen former or current musical prodigies (aged 12–34) were compared to 35 musicians (aged 14–37) with either an early (mean age 6) or late (mean age 10) start but similar amount of musical training, and 16 non-musicians (aged 14–34). All completed a Wechsler IQ test, the Big Five Inventory, the Autism Spectrum Quotient, the Barcelona Music Reward Questionnaire, the Dispositional Flow Scale, and a detailed history of their lifetime music practice. None of the psychological traits distinguished musical prodigies from control musicians or non-musicians except their propensity to report flow during practice. The other aspects that differentiated musical prodigies from their peers were the intensity of their practice before adolescence, and the source of their motivation when they began to play. Thus practice, by itself, does not make a prodigy. The results are compatible with multifactorial models of expertise, with prodigies lying at the high end of the continuum. In summary, prodigies are expected to present brain predispositions facilitating their success in learning an instrument, which could be amplified by their early and intense practice happening at a moment when brain plasticity is heightened.

Member States’ Due Diligence Obligations to Supervise International Organisations

There are two reasons to consider member states’ obligations to supervise international organisations as a distinct category of due diligence obligations. First, due diligence obligations typically require states to regulate third parties in some way. But it is harder for states to regulate international organisations than other private actors because international law protects the autonomy of international organisations. Second, such due diligence obligations merit attention because they may compensate for the dearth of mechanisms to hold international organisations accountable when they cause harm. This chapter canvasses member states’ existing obligations vis-à-vis international organisations, and argues in particular that the International Law Commission (ILC) missed an opportunity to frame broader obligations when drafting the Articles on the Responsibility of International Organizations (the ARIO). The chapter closes by making the normative case for establishing a due diligence obligation on member states to ensure that international organisations do not abuse their immunities.