Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental models reveal the role of phenotypic plasticity in explaining genetic evolvability

Biological evolution exhibits an extraordinary capability to adapt organisms to their environments. The explanation for this often takes for granted that random genetic variation produces at least some beneficial phenotypic variation for natural selection to act on. Such genetic evolvability could itself be a product of evolution, but it is widely acknowledged that the immediate selective gains of evolvability are small on short timescales. So how do biological systems come to exhibit such extraordinary capacity to evolve? One suggestion is that adaptive phenotypic plasticity makes genetic evolution find adaptations faster. However, the need to explain the origin of adaptive plasticity puts genetic evolution back in the driving seat, and genetic evolvability remains unexplained. To better understand the interaction between plasticity and genetic evolvability, we simulate the evolution of phenotypes produced by gene-regulation network-based models of development. First, we show that the phenotypic variation resulting from genetic and environmental change are highly concordant. This is because phenotypic variation, regardless of its cause, occurs within the relatively specific space of possibilities allowed by development. Second, we show that selection for genetic evolvability results in the evolution of adaptive plasticity and vice versa. This linkage is essentially symmetric but, unlike genetic evolvability, the selective gains of plasticity are often substantial on short, including within-lifetime, timescales. Accordingly, we show that selection for phenotypic plasticity is, in general, the most efficient and results in the rapid evolution of high genetic evolvability. Thus, without overlooking the fact that adaptive plasticity is itself a product of genetic evolution, this shows how plasticity can influence adaptive evolution and helps explain the genetic evolvability observed in biological systems.
Development of RNA-Based Assay for Rapid Detection of SARS-CoV-2 in Clinical Samples

The ongoing spread of pandemic coronavirus disease (COVID-19) is caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). In the lack of specific drugs or vaccines for SARS-CoV-2, demands rapid diagnosis and management are crucial for controlling the outbreak in the community. Here we report the development of the first rapid-colorimetric assay capable of detecting SARS-CoV-2 in the human nasopharyngeal RNA sample in less than 30 minutes. We utilized a nanomaterial-based optical sensing platform to detect RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2, where the formation of oligo probe-target hybrid led to salt-induced aggregation and changes in gold-colloid color from pink to blue in visible range. Accordingly, we found a change in colloid color from pink to blue in assay containing nasopharyngeal RNA sample from the subject with clinically diagnosed COVID-19. The colloid retained pink color when the test includes samples from COVID-19 negative subjects or human papillomavirus (HPV) infected women. The results were validated using nasopharangeal RNA samples from suspected COVID-19 subjects (n=136). Using RT-PCR as gold standard, the assay was found to have 85.29% sensitivity and 94.12% specificity. The optimized method has detection limit as little as 0.5 ng of SARS-CoV-2 RNA. Overall, the developed assay rapidly detects SARS-CoV-2 RNA in clinical samples in a cost-effective manner and would be useful in pandemic management by facilitating mass screening.
A universal RT-qPCR assay for “One Health” detection of influenza A viruses

The mutual dependence of human and animal health is central to the One Health initiative as an integrated strategy for infectious disease control and management. A crucial element of the One Health includes preparation and response to influenza A virus (IAV) threats at the human-animal interface. The IAVs are characterized by extensive genetic variability, they circulate among different hosts and establish host-specific lineages. The four main host reservoirs are: avian, swine, human and equine, with occasional transmission to other mammalian species. The host diversity is mirrored in the range of the RT-qPCR assays for IAV detection. Different assays are recommended by the responsible health authorities for generic IAV detection in birds, swine or humans. In order to unify IAV monitoring in different hosts and apply the One Health approach, we developed a single RT-qPCR assay for universal detection of all IAVs of all subtypes, species origin and global distribution. The assay design was centred on a highly conserved region of the IAV MP-segment identified by a comprehensive analysis of 99,353 sequences. The reaction parameters were effectively optimised with efficiency of 93-97% and LOD95% of approximately ten IAV templates per reaction. The assay showed high repeatability, reproducibility and robustness. The extensive in silico evaluation demonstrated high inclusivity, i.e. perfect sequence match in the primers and probe binding regions, established as 94.6% for swine, 98.2% for avian and 100% for human H3N2, pandemic H1N1, as well as other IAV strains, resulting in an overall predicted detection rate of 99% on the analysed dataset. The theoretical predictions were confirmed and extensively validated by collaboration between six veterinary or human diagnostic laboratories on a total of 1970 specimens, of which 1455 were clinical and included a diverse panel of IAV strains.
Application of cAMP-dependent catalytic subunit β (PRKACB) Low Expression in Predicting Worse Overall Survival: A Potential Therapeutic Target for Colorectal Carcinoma

Low expressions of PRKACB are related to the occurrence of various human malignancies. However, the prognostic value of PRKACB expression in colorectal cancer (CRC) patients remains controversial. In this analysis, PRKACB expression in CRC tumors was evaluated across the GEO, TCGA, and Oncomine databases, and a PRKACB survival analysis was performed based on the TCGA profile. We detected PRKACB in 7 GEO series (GSE110225, GSE32323, GSE44076, GSE9348, GSE41328, GSE21510, GSE68468) and TCGA spectra (all P <0.05). A meta-analysis performed in the Oncomine database revealed that PRKACB was significantly up-regulated in neoplastic tissues compared to normal tissues (all P <0.05). A Kaplan-Meier analysis demonstrated that lower PRKACB expression in tumors was significantly associated with poorer overall survival (OS) in patients with CRC (P <0.05). A subgroup analysis showed that low expression of PRKACB correlated with poor 1-, 3-, and 5-year OS (all P <0.05). Furthermore, in males (P = 0.0083), whites (P = 0.0463), and non-mucinous adenocarcinoma patients (P = 0.0108), the down-regulation of PRKACB expression was more significant for the OS prognostic value. Conclusion: PRKACB is down-regulated in tumors and associated with worsening OS in CRC patients.
Does it matter if herbivory is selective? Responses of an endangered herbaceous legume to experimental grazing

Background: Herbivory and inter-specific competition are major determinants of the relative abundance of plant species in grasslands. Herbivores modify competitive hierarchies among plants through selective foraging and as a result of variation in the relative tolerance of plants to herbivory. Aims: We examined the direct effects of herbivory and the role of herbivore preference on the growth, flowering and abundance of an endangered perennial legume, Cullen parvum (F. Muell.) J.W. Grimes, in a temperate Australian grassland grazed by sheep. Methods: Hand clipping was used to simulate herbivory. In each of two populations, three replicates of the factorial combination of C. parvum defoliation (C. parvum grazed or ungrazed), neighbour defoliation (neighbouring vegetation grazed or ungrazed) and three defoliation frequency treatments were randomly applied to 0.25-m2 quadrats containing C. parvum ramets. Results: The abundance, growth and flowering of C. parvum were similarly reduced by both selective and non-selective herbivory. When neighbouring vegetation but not C. parvum was defoliated, growth and abundance were similar and in some cases less than when both neighbours and C. parvum were ungrazed, suggesting little above-ground competitive effect of the grassland sward. Conclusions: The interactions between herbivory and shoot competition by dominant perennial grassy swards had little influence on the growth and abundance of C. parvum. Rather, direct effects of defoliation dominated and we predict that the species persistence in grazed grasslands will be influenced more by poor tolerance of herbivory than by how herbivores modify the competitive effect of neighbouring vegetation.
A healthy lifestyle pattern and the risk of symptomatic gallstone disease: results from 2 prospective cohort studies.

BACKGROUND Symptomatic gallstones cause high financial and disease burden for public health systems. The combined role of diet and other lifestyle factors has not been studied so far. OBJECTIVES We aimed to investigate the association between an a priori defined healthy lifestyle score (HLS, including healthy diet, moderate alcohol and regular coffee intakes, never smoking, physical activity, and normal weight) and the risk of symptomatic gallstone disease, and to estimate the proportion of cases potentially preventable by lifestyle modification. METHODS We followed 60,768 women from the Nurses' Health Study (NHS) and 40,744 men from the Health Professionals Follow-up Study (HPFS), both ongoing prospective cohort studies, from baseline (1986) until 2012. Symptomatic gallstone disease was self-reported and validated by review of medical records. The association between the HLS and the risk of symptomatic gallstone disease was investigated using Cox proportional hazards regression. RESULTS During 1,156,079 and 769,287 person-years of follow-up, respectively, 6946 women and 2513 men reported symptomatic gallstone disease. Comparing 6 with 0 points of the HLS, the multivariable HR of symptomatic gallstone disease was 0.26 (95% CI: 0.15, 0.45) for women, and 0.17 (95% CI: 0.07, 0.43) for men. For individual lifestyle factors, multivariable and mutually adjusted partial population attributable risks (women and men) were 33% and 23% for BMI <25 kg/m2, 10% and 18% for ≥2 cups of coffee per day, 13% and 7% for moderate alcohol intake, 8% and 11% for a high Alternate Healthy Eating Index 2010, 9% and 5% for being physically active, and 1% and 5% for never smoking. The full population attributable risk percentage for all factors combined was 62% and 74%, respectively. CONCLUSIONS Findings from these large prospective studies indicate that adopting a healthy lifestyle, especially maintaining a healthy weight, can help to prevent a considerable proportion of symptomatic gallstone diseases.
Oscillatoria simplicissima : an autecological study

Oscillatoria simplicissima is a blue-green alga that was first observed in the Vaal River during 1984. It replaced Microcystis aeruginosa as the dominant blue-green algal species and became dominant after an increase in the organic phosphorus supply in the Loch Vaal catchment area to form algal blooms of great intensity. Although this blue-green alga is presumably non-toxic, a study over a seven-year period shows that it is one of the most important bloom-forming blue-green algal species in the Vaal River, interfering with recreational activities as well as water purification. During this study, environmental variables influencing the development of blue-green algae in a natural environment were studied in order to provide background information for growth studies of this group under controlled conditions. This paper gives an overview of an autecological study done on O. simplicissima in the Vaal River at Balkfontein, as well as the isolation and growth requirements of this blue-green alga under controlled conditions.
Evoked chirping in the weakly electric fish Apteronotus leptorhynchus: a quantitative biophysical analysis

Apteronotus leptorhynchus, a gymnotiform fish, produces highly regular electric organ discharges of 600–1000 Hz. Short-term modulations of the electric organ discharge ("chirps") were elicited by imitating the discharges of neighboring fish. Chirps displayed an increase in frequency of approximately 100 Hz, a duration of about 15 ms, and an absolute amplitude of 0.5–2 mV. Since, similar to natural conditions, chirps summated with the beat caused by interference of the fish's own electric organ discharge and the imitating discharge, the size and shape of the chirp's amplitude envelope varied greatly according to its phase relative to the beat cycle; however, the frequency of the chirp amplitude modulation was always 50–100 Hz. All 21 males examined chirped, but their rate of chirping varied considerably (range 2–59 chirps/30 s; mean 22 chirps/30 s). In contrast, only one out of nine females chirped (mean 0.25 chirps/30 s). The latency between stimulus onset and first chirp was variable and often long (rang.
Interactions between decision-making and emotion in behavioral-variant frontotemporal dementia and Alzheimer’s disease

Abstract Negative and positive emotions are known to shape decision-making toward more or less impulsive responses, respectively. Decision-making and emotion processing are underpinned by shared brain regions including the ventromedial prefrontal cortex (vmPFC) and the amygdala. How these processes interact at the behavioral and brain levels is still unclear. We used a lesion model to address this question. Study participants included individuals diagnosed with behavioral-variant frontotemporal dementia (bvFTD, n = 18), who typically present deficits in decision-making/emotion processing and atrophy of the vmPFC, individuals with Alzheimer’s disease (AD, n = 12) who present with atrophy in limbic structures and age-matched healthy controls (CTRL, n = 15). Prior to each choice on the delay discounting task participants were cued with a positive, negative or neutral picture and asked to vividly imagine witnessing the event. As hypothesized, our findings showed that bvFTD patients were more impulsive than AD patients and CTRL and did not show any emotion-related modulation of delay discounting rate. In contrast, AD patients showed increased impulsivity when primed by negative emotion. This increased impulsivity was associated with reduced integrity of bilateral amygdala in AD but not in bvFTD. Altogether, our results indicate that decision-making and emotion interact at the level of the amygdala supporting findings from animal studies.
Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 104 PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs.
Local Economic Multipliers from Commercial Fisheries

Understanding the multiplier effect of natural resource exploitation is important for regional economic development policy. The empirical literature to date has focused on spillover effects from nonrenewable resources, such as oil and natural gas, with little attention paid to renewable resources, such as fish stocks. We address this gap by estimating local economic multipliers from commercial fishing activity in Alaska. Using exogenous variation in fish stocks and prices, we find that a 10% increase in a community’s annual fishery earnings leads to a corresponding 0.7% increase in resident income. This translates to 1.54 dollars of total income for each dollar of fisheries earnings. Our findings demonstrate the potential for local capture of commercial fishery revenues through direct effects and spillovers into other sectors; however, we argue that larger local capture may be achieved through higher levels of resident permit ownership and additional forward-and-backward linkages across sectors. JEL Classification: R12, R23, O11, Q22
Chromosome and DNA variation in Amorphophallus (Araceae)

As part of an extensive survey at Kew of the chromosomes of the Araceae, Marchant (1971) studied eleven species of Amorphophallus Bl. ex Decne. He found two basic numbers, x = 13 and 14, with the former being the more frequent. Most species were diploid but one, A. bulbifer, was triploid with 2n = 39. Some differences in chromosome size were reported. Since his investigation many new living accessions of Amorphophallus have been received by the Royal Botanic Gardens, Kew, all of which are supported by dried or spirit vouchers, and it was considered that they would be suitable for a detailed investigation into the nature of chromosome variation in the genus in order to elucidate the interrelationships of the species. In the majority of the plants chromosome size differences were also checked by a study of DNA amount. Amorphophallus comprises about 100 species with a wide tropical distribution (Willis 1966), ranging from much of Equatorial Africa in the West to India, Malaysia, the Philippines and Australia in the East. Although most species are of no known economic value at least two, A. paeoniifolius (Dennstedt) Nicolson and A. bulbifer (Roxb.) Blume, contain large amounts of edible carbohydrate in their tubers and are grown as food in Southern India, and a few species, for example A. konjac C. Koch, are grown as ornamentals. In this article the chromosome number and morphology of these species and 14 others are presented, together with DNA values in 13 of them.
Spatial and space-time clustering and demographic characteristics of human nontyphoidal Salmonella infections with major serotypes in Toronto, Canada

Nontyphoidal Salmonella enterica (NTS) causes a substantial health burden to human populations in Canada and worldwide. Exposure sources and demographic factors vary by location and can therefore have a major impact on salmonellosis clustering. We evaluated major NTS serotypes: S. Enteritidis (n = 620), S. Typhimurium (n = 150), S. Thompson (n = 138), and S. Heidelberg (n = 136) reported in the city of Toronto, Canada, between January 1, 2015, and December 31, 2017. Cases were analyzed at the forward sortation area (FSA)—level (an area indicated by the first three characters of the postal code). Serotype-specific global and local clustering of infections were evaluated using the Moran's I method. Spatial and space-time clusters were investigated using Poisson and multinomial scan statistic models. Case-case analyses using a multinomial logistic regression model was conducted to compare seasonal and demographic factors among the different serotypes. High infection rate FSAs clustered in the central region of Toronto for S. Enteritidis, in the south-central region for S. Typhimurium, in north-west region for S. Thompson, and in the south-east region for S. Heidelberg. The relative risk ratio of S. Enteritidis infections was significantly higher in cases who reported travel outside of Ontario. The relative risk ratio of infections was significantly higher in summer for S. Typhimurium, and in fall for S. Thompson. The relative risk ratio of infection was highest for the 0–9 age group for S. Typhimurium, and the 20–39 age group for S. Heidelberg. Our study will aid public health stakeholders in designing serotype-specific geographically targeted disease prevention programs.
Isolation and Functional Properties of Murine Hematopoietic Stem Cells that are Replicating In Vivo By Margaret A. Goodell, Katja Brose, Glenn Paradis,*

Summary Hematopoietic stem cells (HSC) are multipotent cells that reside in the bone marrow and replenish all adult hematopoietic hneages throughout the lifetime of the animal. While experimenting with staining of murine bone marrow cells with the vital dye, Hoechst 33342, we discovered that display of Hoechst fluorescence simultaneously at two emission wavelengths revealed a small and distinct subset of whole bone marrow ceils that had phenotypic markers of multipotential HSC. These cells were shown in competitive repopulation experiments to conrain the vast majority of HSC activity from murine bone marrow and to be enriched at least 1,000-fold for in vivo reconstitution activity. Further, these Hoechst-stained side population (SP) cells were shown to protect recipients from lethal irradiation at low cell doses, and to contribute to both lymphoid and myeloid lineages. The formation of the Hoechst SP profile was blocked when staining was performed in the presence of verapamil, indicating that the distinctly low staining pattern of the SP cells is due to a multidrug resistance protein (mdr) or mdr-like mediated efflux of the dye from HSC. The ability to block the Hoechst efl]ux activity also allowed us to use Hoechst to determine the DNA content of the SP cells. Between 1 and 3% of the HSC were shown to be in S-G2M. This also enabled the purification of the G0-G~ and S-G2M subsets of fresh purified HSC. Transplantation of these subsets of HSC revealed that S-G2M HSC had a reconstitution capacity equivalent to quiescent stem cells. These findings have implications for models of hematopoietic cell development and for the development of genetic therapies for diseases involving hematopoietic cells.