Evolution at the Origins of Life?

The role of evolutionary theory at the origin of life is an extensively debated topic. The origin and early development of life is usually separated into a prebiotic phase and a protocellular phase, ultimately leading to the Last Universal Common Ancestor. Most likely, the Last Universal Common Ancestor was subject to Darwinian evolution, but the question remains to what extent Darwinian evolution applies to the prebiotic and protocellular phases. In this review, we reflect on the current status of evolutionary theory in origins of life research by bringing together philosophy of science, evolutionary biology, and empirical research in the origins field. We explore the various ways in which evolutionary theory has been extended beyond biology; we look at how these extensions apply to the prebiotic development of (proto)metabolism; and we investigate how the terminology from evolutionary theory is currently being employed in state-of-the-art origins of life research. In doing so, we identify some of the current obstacles to an evolutionary account of the origins of life, as well as open up new avenues of research

Endocytosis of coacervates into liposomes

[Image: see text] Recent studies have shown that the interactions between condensates and biological membranes are of functional importance. Here, we study how the interaction between complex coacervates and liposomes as model systems can lead to wetting, membrane deformation, and endocytosis. Depending on the interaction strength between coacervates and liposomes, the wetting behavior ranged from nonwetting to engulfment (endocytosis) and complete wetting. Endocytosis of coacervates was found to be a general phenomenon: coacervates made from a wide range of components could be taken up by liposomes. A simple theory taking into account surface energies and coacervate sizes can explain the observed morphologies. Our findings can help to better understand condensate–membrane interactions in cellular systems and provide new avenues for intracellular delivery using coacervates

HIMMO - A lightweight collusion-resistant key predistribution scheme

In this paper we introduce HIMMO as a truly practical and lightweight collusion-resistant key predistribution scheme. The scheme is reminiscent ofBlundo et al\u27s elegant key predistribution scheme, in which the master key is a symmetric bivariate polynomial over a finite field, and a unique common key is defined for every pair of nodes as the evaluation of the polynomial at the finite field elements associated with the nodes. Unlike Blundo et al\u27s scheme, however, which completely breaks down once the number of colluding nodes exceeds the degree of the polynomial, the new scheme is designed to tolerateany number of colluding nodes. Key establishment in HIMMO amounts to the evaluation of a single low-degree univariate polynomial involving reasonably sized numbers, thus exhibiting excellent performance even for constrained devices such as 8-bit CPUs, as we demonstrate. On top of this, the scheme is very versatile, as it not only supports implicit authentication of the nodes like any key predistribution scheme, but also supports identity-based key predistribution in a natural and efficient way. The latter property derives from the fact that HIMMO supports long node identifiers at a reasonable cost, allowing outputs of a collision-resistant hash function to be used as node identifiers. Moreover, HIMMO allows for a transparent way to split the master key between multiple parties. The new scheme is superior to any of the existing alternatives due to the intricate way it combines the use of multiple symmetric bivariate polynomials evaluated over ``different\u27\u27 finite rings. We have extensively analyzed the security of HIMMO against two attacks. For these attacks, we have identified the Hiding Information (HI) problem and the Mixing Modular Operations (MMO) problem as the underlying problems. These problems are closely related to some well-defined lattice problems, and therefore the best attacks on HIMMO are dependent on lattice-basis reduction. Based on these connections, we propose concrete values for all relevant parameters, for which we conjecture that the scheme is secure

Attacks and parameter choices in HIMMO

The HIMMO scheme has been introduced as a lightweight collusion-resistant key pre-distribution scheme, with excellent efficiency in terms of bandwidth, energy consumption and computation time. As its cryptanalysis relies on lattice techniques, HIMMO is also an interesting quantum-safe candidate. Unlike the schemes by Blom, by Matsumoto and Imai, and by Blundo {\em et al}, which break down once the number of colluding nodes exceeds a given threshold, it aims at tolerating any number of colluding nodes. In 2015, a contest for the verification of the scheme was held. During the contest, a method was developed to guess a key by finding an approximate solution of one of the problems underlying the scheme. This attack involves finding a short vector in a lattice of dimension linear in a system parameter $\alpha$ and allowed key recovery for several challenges. Thwarting this attack by increasing $\alpha$ would lead to a significant performance degradation, as CPU and memory requirements for the implementation of the scheme scale quadratically in $\alpha$. This paper describes a generalization of HIMMO parameters that allows configuring the scheme such that both its performance and the dimension of the lattice involved in the attack grow linearly in $\alpha$. Two attacks inspired by the one developed in the contest are described, and the impact of those attacks for different parameter choices is discussed. Parameters choices are described that thwart existing attacks while enabling high performance implementations of the scheme

Endocytosis of coacervates into liposomes

Recent studies have shown that the interactions between condensates and biological membranes is of functional importance. Here, we study how the interaction between complex coacervates and liposomes as model systems can lead to membrane deformation and endocytosis. Depending on the interaction strength between coacervates and liposomes, the wetting behavior ranged from non-wetting, to partial wetting (adhesion), engulfment (endocytosis), and finally complete wetting. Endocytosis of coacervates was found to be a general phenomenon: coacervates made from a wide range of components could be taken up by liposomes. A simple theory that takes into account surface energies and coacervate sizes can explain the observed coacervate-liposome interactions. Our findings can help to better understand condensate-membrane interactions in cellular systems and provide new avenues for intracellular delivery using coacervates

Assessment of fatigability in patients with spinal muscular atrophy : development and content validity of a set of endurance tests

Background: Fatigability has emerged as an important dimension of physical impairment in patients with Spinal Muscular Atrophy (SMA). At present reliable and valid outcome measures for both mildly and severely affected patients are lacking. Therefore the primary aim of this study is the development of clinical outcome measures for fatigability in patients with SMA across the range of severity. Methods: We developed a set of endurance tests using five methodological steps as recommended by the 'COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). In this iterative process, data from multiple sources were triangulated including a scoping review of scientific literature, input from a scientific and clinical multidisciplinary expert panel and three pilot studies including healthy persons (N = 9), paediatric patients with chronic disorders (N = 10) and patients with SMA (N = 15). Results: Fatigability in SMA was operationalised as the decline in physical performance. The following test criteria were established; one method of testing for patients with SMA type 2-4, a set of outcome measures that mimic daily life activities, a submaximal test protocol of repetitive activities over a longer period; external regulation of pace. The scoping review did not generate suitable outcome measures. We therefore adapted the Endurance Shuttle Walk Test for ambulatory patients and developed the Endurance Shuttle Box and Block Test and the - Nine Hole Peg Test for fatigability testing of proximal and distal arm function. Content validity was established through input from experts and patients. Pilot testing showed that the set of endurance tests are comprehensible, feasible and meet all predefined test criteria. Conclusions: The development of this comprehensive set of endurance tests is a pivotal step to address fatigability in patients with SMA

Feeding and Swallowing Problems in Infants with Spinal Muscular Atrophy Type 1: an Observational Study

Background: Infantile hereditary proximal spinal muscular atrophy (SMA) type 1 is characterized by onset in the first 6 months of life and severe and progressive muscle weakness. Dysphagia is a common complication but has not been studied in detail. Objective: To study feeding and swallowing problems in infants with SMA type 1, and to explore the relation between these problems and functional motor scores. Methods: We prospectively included 16 infants with SMA type 1 between September 2016 and October 2018. Eleven infants received palliative care and five infants best supportive care in combination with nusinersen. We compiled and used an observation list with feeding related issues and observed feeding sessions during inpatient and outpatient visits. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) was used as a measure of motor function. Results: All infants in the palliative care group (median onset of disease 14 days (range 1–56); median inclusion in the study 52 days (range 16–252) demonstrated symptoms of fatigue during feeding and unsafe swallowing. Symptoms were short nursing sessions (10–15 minutes), and not being able to finish the recommended feeding volumes (72%); increased frequency of feeding sessions (55%); coughing when drinking or eating (91%), and wet breathing during and after feeding (64%).Two out of five infants in the nusinersen group (median onset of disease 38 days (range 21–90); inclusion in the study at 63 days (range 3–218) were clinically pre-symptomatic at the start of treatment. The other three infants showed symptoms of fatigue and unsafe swallowing at inclusion in the study. These symptoms initially decreased after the start of the treatment, but (re)appeared in all five infants between the ages of 8 to 12 months, requiring the start tube of feeding. In the same period motor function scores significantly improved (median increase CHOP INTEND 16 points). Conclusion: Impaired feeding and swallowing remain important complications in infants with SMA type 1 after the start of nusinersen. Improvement of motor function does not imply similar gains in bulbar function

Assessment of fatigability in patients with spinal muscular atrophy: development and content validity of a set of endurance tests

Abstract Background Fatigability has emerged as an important dimension of physical impairment in patients with Spinal Muscular Atrophy (SMA). At present reliable and valid outcome measures for both mildly and severely affected patients are lacking. Therefore the primary aim of this study is the development of clinical outcome measures for fatigability in patients with SMA across the range of severity. Methods We developed a set of endurance tests using five methodological steps as recommended by the ‘COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). In this iterative process, data from multiple sources were triangulated including a scoping review of scientific literature, input from a scientific and clinical multidisciplinary expert panel and three pilot studies including healthy persons (N = 9), paediatric patients with chronic disorders (N = 10) and patients with SMA (N = 15). Results Fatigability in SMA was operationalised as the decline in physical performance. The following test criteria were established; one method of testing for patients with SMA type 2–4, a set of outcome measures that mimic daily life activities, a submaximal test protocol of repetitive activities over a longer period; external regulation of pace. The scoping review did not generate suitable outcome measures. We therefore adapted the Endurance Shuttle Walk Test for ambulatory patients and developed the Endurance Shuttle Box and Block Test and the - Nine Hole Peg Test for fatigability testing of proximal and distal arm function. Content validity was established through input from experts and patients. Pilot testing showed that the set of endurance tests are comprehensible, feasible and meet all predefined test criteria. Conclusions The development of this comprehensive set of endurance tests is a pivotal step to address fatigability in patients with SMA