Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors

The evolution of venom resistance through coevolutionary chemical arms races has arisen multiple times throughout animalia. Prior documentation of resistance to snake venom α-neurotoxins consists of the N-glycosylation motif or the hypothesized introduction of arginine at positions 187 at the α-1 nicotinic acetylcholine receptor orthosteric site. However, no further studies have investigated the possibility of other potential forms of resistance. Using a biolayer interferometry assay, we first confirm that the previously hypothesized resistance conferred by arginine at position 187 in the honey badger does reduce binding to α-neurotoxins, which has never been functionally tested. We further discovered a novel form of α-neurotoxin resistance conferred by charge reversal mutations, whereby a negatively charged amino acid is replaced by the positively charged amino acid lysine. As venom α-neurotoxins have evolved strong positive charges on their surface to facilitate binding to the negatively charged α-1 orthosteric site, these mutations result in a positive charge/positive charge interaction electrostatically repelling the α-neurotoxins. Such a novel mechanism for resistance has gone completely undiscovered, yet this form of resistance has convergently evolved at least 10 times within snakes. These coevolutionary innovations seem to have arisen through convergent phenotypes to ultimately evolve a similar biophysical mechanism of resistance across snakes.
Whose trait is it anyways? Coevolution of joint phenotypes and genetic architecture in mutualisms

Evolutionary biologists typically envision a trait’s genetic basis and fitness effects occurring within a single species. However, traits can be determined by and have fitness consequences for interacting species, thus evolving in multiple genomes. This is especially likely in mutualisms, where species exchange fitness benefits and can associate over long periods of time. Partners may experience evolutionary conflict over the value of a multi-genomic trait, but such conflicts may be ameliorated by mutualism’s positive fitness feedbacks. Here, we develop a simulation model of a host–microbe mutualism to explore the evolution of a multi-genomic trait. Coevolutionary outcomes depend on whether hosts and microbes have similar or different optimal trait values, strengths of selection and fitness feedbacks. We show that genome-wide association studies can map joint traits to loci in multiple genomes and describe how fitness conflict and fitness feedback generate different multi-genomic architectures with distinct signals around segregating loci. Partner fitnesses can be positively correlated even when partners are in conflict over the value of a multi-genomic trait, and conflict can generate strong mutualistic dependency. While fitness alignment facilitates rapid adaptation to a new optimum, conflict maintains genetic variation and evolvability, with implications for applied microbiome science.
Learning the same motor task twice impairs its retention in a time- and dose-dependent manner

Anterograde interference emerges when two differing tasks are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when the same motor task is being learned twice, that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period—independent of fatigue—also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.
A liar and a copycat: nonverbal coordination increases with lie difficulty

Studies of the nonverbal correlates of deception tend to examine liars' behaviours as independent from the behaviour of the interviewer, ignoring joint action. To address this gap, experiment 1 examined the effect of telling a truth and easy, difficult and very difficult lies on nonverbal coordination. Nonverbal coordination was measured automatically by applying a dynamic time warping algorithm to motion-capture data. In experiment 2, interviewees also received instructions that influenced the attention they paid to either the nonverbal or verbal behaviour of the interviewer. Results from both experiments found that interviewer–interviewee nonverbal coordination increased with lie difficulty. This increase was not influenced by the degree to which interviewees paid attention to their nonverbal behaviour, nor by the degree of interviewer's suspicion. Our findings are consistent with the broader proposition that people rely on automated processes such as mimicry when under cognitive load.
Forcing the issue: testing gecko-inspired adhesives

Materials are traditionally tested either by imposing controlled displacements and measuring the corresponding forces, or by imposing controlled forces. The first of these approaches is more common because it is straightforward to control the displacements of a stiff apparatus and, if the material suddenly fails, little energy is released. However, when testing gecko-inspired adhesives, an applied force paradigm is closer to how the adhesives are loaded in practice. Moreover, we demonstrate that the controlled displacement paradigm can lead to artefacts in the assumed behaviour unless the imposed loading trajectory precisely matches the deflections that would occur in applications. We present the design of a controlled-force system and protocol for testing directional gecko-inspired adhesives and show that results obtained with it are in some cases substantially different from those with controlled-displacement testing. An advantage of the controlled-force testing approach is that it allows accurate generation of adhesive limit curves without prior knowledge of the expected behaviour of the material or the loading details associated with practical applications.
Towards personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. Objective: The aim was to investigate the test-retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Methods: Three short verum (1Hz, 10Hz, 20Hz; 200 pulses) and one sham (0.1Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG) together with behavioral tinnitus loudness ratings. Stimulation responders were identified via consistent and sham-superior behavioral or electrophysiological responses according to the prevalent neurophysiological models for tinnitus. Results: It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% responder), alpha increases (91% responder) and gamma decreases (100% responder) respectively. Contrary, test-retest correlation analyses per protocol on a group-level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were given. Conclusion: RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability on group-level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.
The Relationship between Democracy embracement and COVID-19 reported casualties worldwide

Abstract: Background: The COVID-19 toll of cases and deaths followed an uneven pattern across the world. The literature has partly explained the observed discrepancy between the different countries by country-specific and systemic patterns worldwide. In this study, we propose an additional explanation that the magnitude of COVID-19 toll reported to the WHO could be influenced by the level of free speech and Democracy in the reporting countries. Methods: We constructed a longitudinal dataset including the daily COVID-19 count of cases and deaths worldwide and each country's respective score on the Freedom in the World index. We applied two Generalized Estimating Equation models to investigate if a country's reported toll count of COVID-19 cases and deaths is related to that country's freedom level. We controlled for factors identified in the current literature to affect the pandemic's spread. Results: A country's score on the Freedom In the World Index was associated with its reported COVID-19 cases count (57028.43, 95% CI 985.3619 - 113071.5, P= 0.0461) and deaths count (3473.273, 95% CI1217.12-5729.42, P=.002). Also, despite having almost equal shares of the world's population, countries at the bottom category of the Freedom index reported 21% and 11% of the COVID-19 toll cases and death counts reported by countries of highest scores on the index, respectively. Conclusions: The known magnitude of the COVID-19 pandemic's morbidity and mortality is likely as transparent about the reality only as much as the reporting countries uphold free speech and Democracy. This could potentially misguide international aid and global vaccine distribution plans.
Seroprevalence of Chagas in urban and rural indigenous populations of the south of Gran Chaco

Background & objectives. In Latin America, Chagas disease is endemic, with high prevalence in rural indigenous communities and increasing prevalence in urban areas due to migration from rural areas with active vector transmission. The objective of the work was to assess differences in the prevalence of Chagas disease in urban and rural moqoit communities of the south of Gran Chaco, Santa Fe province, Argentina. Methods. A seroprevalence study was conducted in six moqoit populations. Belonging to an urban community was considered as an exposure variable, whereas seropositivity for Chagas disease was considered as an outcome variable Results. The results showed that 9.26% of the 702 volunteers evaluated and 3.50% of women of childbearing potential were seropositive. The prevalence of Chagas disease in urban communities was 6.41 times higher than in rural communities. Interpretation & conclusions. The seroprevalence found in the moqoit community is higher than that estimated for the general population of the same region, with greater impact in the urban area than in the rural area. The decline of vector transmission in the rural area could be related to the conservation of ancestral practices and the expansion of the agricultural model.
Evidence for Causal Effects of Smoking Initiation and Alcohol Consumption on Substance Use Outcomes

Background and Aims: The 'gateway' hypothesis proposes that initial use of drugs such as tobacco and alcohol can lead to subsequent more problematic drug use. However, it is unclear whether true casual pathways exist, or whether there is instead a shared underlying risk factor. We used bidirectional Mendelian Randomisation (MR) to test these two competing hypotheses. Methods: We conducted two-sample MR analyses, using genome-wide association data for smoking initiation, alcoholic drinks per week, cannabis use and dependence, cocaine and opioid dependence. We used several MR methods that rely on different assumptions: inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode and weighted mode. Consistent results across these methods would support stronger inference. Results: We found evidence of causal effects from smoking initiation to increased drinks per week (IVW: beta=0.06; 95% CI 0.03 to 0.09; p-value=9.44x10-06), cannabis use (IVW: OR=1.34; 95% CI 1.24 to 1.44; p-value=1.95x10-14), and cannabis dependence (IVW: OR=1.68; 95% CI 1.12 to 2.51; p-value=0.01). We also found evidence of an effect of cannabis use on increased likelihood of smoking initiation (IVW: OR=1.39; 95% CI=1.08 to 1.80; p-value=0.01). We did not find evidence of an effect of drinks per week on substance use outcomes, except for weak evidence of an effect on cannabis use. We also found evidence of an effect of opioid dependence on increased drinks per week (IVW: beta=0.002; 95% CI=0.0005 to 0.003; p-value=8.61x10-03). Conclusions: Overall, we found evidence suggesting a causal pathway from smoking initiation to alcohol consumption, and both cannabis use and dependence, which may support the gateway hypothesis. However, we also found causal effects of cannabis use on smoking initiation, and opioid dependence on alcohol consumption, which suggests the existence of a shared risk factor. Further research should explore whether this is the case, and in particular the nature of any shared risk factors.
Species identification and antimicrobial susceptibility testing of non-tuberculous mycobacteria isolated in Chongqing, Southwest China

Abstract With the rapid rise in the prevalence of non-tuberculous mycobacteria (NTM) diseases across the world, the microbiological diagnosis of NTM isolates is becoming increasingly important for the diagnosis and treatment of NTM disease. In this study, the clinical presentation, species distribution and drug susceptibility of patients with NTM disease visiting the Chongqing Public Health Medical Centre during March 2016–April 2019 were retrospectively analysed. Among the 146 patients with NTM disease, eight NTM species (complex) were identified. The predominant NTM species in these patients were identified to be Mycobacterium abscessus complex (53, 36.3%), M. intracellulare (38, 26%) and M. fortuitum (17, 11.7%). In addition, two or more species were isolated from 7.5% of the patients. Pulmonary NTM disease (142, 97.3%) showed the highest prevalence among the patients. It was observed that 40.1% of the patients with pulmonary NTM disease had chronic pulmonary obstructive disease and bronchiectasis, while 22.5% had prior tuberculosis. Male patients showed more association with the conditions of cough and haemoptysis than the female patients. In an in vitro antimicrobial susceptibility testing, most of the species showed susceptibility to linezolid, amikacin and clarithromycin, while M. fortuitum exhibited low susceptibility to tobramycin. In conclusion, the prevalence of NTM disease, especially that of the pulmonary NTM disease, is common in Southwest China. Species identification and drug susceptibility testing are thus extremely important to ensure appropriate treatment regimens for patient care and management.
Efficient CRISPR-mediated base editing in Agrobacterium spp.

Significance Agrobacteria are plant-pathogenic bacteria that can deliver DNA to plant cells as part of their infection strategy. This property has been used for decades to generate transgenic plants and, more recently, to deliver gene-editing reagents to plant cells. Notwithstanding their importance for research and industry, laboratory strains have not been improved much over the years and several aspects of Agrobacterium biology and pathogenesis remain poorly understood. Here, we developed a CRISPR-mediated base-editing approach to efficiently modify the genome of Agrobacterium. We show that single-nucleotide changes can be introduced at targeted positions in both the Agrobacterium tumefaciens and Agrobacterium rhizogenes genomes. Whole-genome analysis of edited strains revealed only a limited number of unintentional mutations. Agrobacterium spp. are important plant pathogens that are the causative agents of crown gall or hairy root disease. Their unique infection strategy depends on the delivery of part of their DNA to plant cells. Thanks to this capacity, these phytopathogens became a powerful and indispensable tool for plant genetic engineering and agricultural biotechnology. Although Agrobacterium spp. are standard tools for plant molecular biologists, current laboratory strains have remained unchanged for decades and functional gene analysis of Agrobacterium has been hampered by time-consuming mutation strategies. Here, we developed clustered regularly interspaced short palindromic repeats (CRISPR)-mediated base editing to enable the efficient introduction of targeted point mutations into the genomes of both Agrobacterium tumefaciens and Agrobacterium rhizogenes. As an example, we generated EHA105 strains with loss-of-function mutations in recA, which were fully functional for maize (Zea mays) transformation and confirmed the importance of RolB and RolC for hairy root development by A. rhizogenes K599. Our method is highly effective in 9 of 10 colonies after transformation, with edits in at least 80% of the cells. The genomes of EHA105 and K599 were resequenced, and genome-wide off-target analysis was applied to investigate the edited strains after curing of the base editor plasmid. The off-targets present were characteristic of Cas9-independent off-targeting and point to TC motifs as activity hotspots of the cytidine deaminase used. We anticipate that CRISPR-mediated base editing is the start of “engineering the engineer,” leading to improved Agrobacterium strains for more efficient plant transformation and gene editing.
Why do farmers care about rented land? Investigating the context of farmland tenure

Rental shares of agricultural land have increased in many countries, as have soil degradation and erosion. Theory suggests that these trends may be correlated, yet empirical findings are mixed. This ambiguity indicates that a “tenure effect” on conservation may be highly contextual. Our research investigates farmers’ soil conservation behavior on rented land and aims to disentangle the contextual factors involved. These factors include rental duration and security, the nature of the landlord-tenant relationship, plot-specific features of the land, formal requirements such as agri-environmental schemes (AES) or contractual obligations, as well as rental prices. We survey Austrian crop farmers and find, prima facie, no differences between rented and owned cropland in the application of 16 different soil conservation practices. We also find that, in our sample, renting appears to be secure and long term; there are few cases where landlord-tenant relationships are distant; where rented plots are far from the farmhouse; and most farmers in Austria participate in AES that are applied independent of tenure status. We therefore propose that a purported tenure effect is indeed contingent on the contextual factors listed above, which may support or counteract soil conservation on rented land. Thus, policy makers and extension services can foster soil conservation on rented land by addressing these contextual factors. Points of intervention include designing AES contracts in a way that reduces risks for tenant farmers, supporting secure and long-term renting, encouraging close landlord-tenant relationships, and promoting the inclusion of conservation requirements in rental contracts.
Reston virus causes severe respiratory disease in young domestic pigs

Significance The emergence of Reston virus (RESTV) in domestic pigs in the Philippines and, subsequently, the detection of RESTV sequences in pigs in China are serious human and animal health concerns. Food safety is an immediate fear, and pathogenicity and potential for zoonotic transmission are important concerns. To find answers for those problems, we performed a pathogenicity study in young domestic pigs. We could demonstrate that young pigs develop severe respiratory disease upon RESTV infection and shed virus from mucosal membranes of the respiratory tract. We conclude that RESTV should be considered a livestock pathogen with zoonotic transmission impacting on animal and perhaps even human health. Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.