Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and analysis of a Proportional-Integral-Derivative controller with biological molecules

The ability of cells to regulate their function through feedback control is a fundamental underpinning of life. The capability to engineer de novo feedback control with biological molecules is ushering in an era of robust functionality for many applications in biotechnology and medicine. To fulfill their potential, feedback control strategies implemented with biological molecules need to be generalizable, modular and operationally predictable. Proportional-Integral-Derivative (PID) control fulfills this role for technological systems and is a commonly used strategy in engineering. Integral feedback control allows a system to return to an invariant steady-state value after step disturbances, hence enabling its robust operation. Proportional and derivative feedback control used with integral control help sculpt the dynamics of the return to steady-state following perturbation. Recently, a biomolecular implementation of integral control was proposed based on an antithetic motif in which two molecules interact stoichiometrically to annihilate each other’s function. In this work, we report how proportional and derivative implementations can be layered on top of this integral architecture to achieve a biochemical PID control design. We illustrate through computational and analytical treatments that the addition of proportional and derivative control improves performance, and discuss practical biomolecular implementations of these control strategies.
Herbivore control in connected seascapes: habitat determines when population regulation occurs in the life history of a key herbivore

Herbivore outbreaks often trigger catastrophic overgrazing events in marine macrophyte ecosystems. The sea urchin Paracentrotus lividus, the dominant herbivore of shallow Mediterranean seascapes, is capable of precipitating shifts to barrens when its populations explode. Paracentrotus lividus is found ubiquitously in rocky macroalgal communities and in sandy seagrass meadows of Posidonia oceanica, two of the most important subtidal habitats in the Mediterranean. We explored if habitat‐specific regulation across the principal stages of the urchin life cycle could help explain the persistence of these populations in connected mosaics. We measured each of three relevant ecological processes (i.e. settlement, post‐settlement survival and predation) across a wide stretch of the Mediterranean coast (ca 600 km). Our results show that habitat‐specific regulation is critical in determining urchin populations: each habitat limited urchin sub‐populations at different life stages. Settlement was never limiting; urchins settled at similar rates in both habitats across the coast. Post‐settlement survival was a clear bottleneck, particularly in seagrass meadows where no juvenile urchins were recorded. Despite this bottleneck in seagrasses, adult urchin populations were very similar in both seagrass and macroalgal habitats indicating that other processes (potentially migration) could be key in determining adult distributions across the mosaic. The fact that population regulation is clearly habitat‐specific suggests that sea urchin populations may be significantly buffered from bottlenecks in mixed seascapes where both habitats co‐occur. Sea urchin populations can therefore persist across the seascape despite strong habitat‐specific regulation either by maintaining reproductive output in one habitat or by migrating between them. By affording these regulatory escapes to habitat‐modifying species, patchy mosaics may be much more prone to herbivore outbreaks and a host of cascading effects that come in their wake.
Aspergillus niger CSR3 regulates plant endogenous hormones and secondary metabolites by producing gibberellins and indoleacetic acid

ABSTRACT In this study, an endophytic fungus, Aspergillus niger CSR3, was isolated from Cannabis sativa. The culture filtrate (CF) was initially screened for growth-promoting activities such as the presence of siderophores, phosphate solubilization, and the production of indole acetic acid (IAA) and gibberellins and was further assayed for its ability to promote the growth of mutant waito-C rice. Nearly all plant growth attributes examined (root–shoot length, biomass, and chlorophyll content) were significantly enhanced by treatment with CSR3. This growth promotion action was due to the presence of various types of gibberellins (GAs) and IAA in the endophyte CF. Moreover, the presence of GA pathway genes (P50-1, P450-3, P450-4, ggs2, and des) was confirmed by means of semi-quantitative RT-PCR. Finally, the application of CSR3 spore suspension with uniconazole and yucasin on maize seedlings revealed that, similar to exogenous IAA and GA3, CSR3 has the potential to alleviate the inhibitory effect of these inhibitors.
The effects of grafting on Tomato (Solanum lycopersicum L.) yield and quality

F1 Hybrid tomato cultivars are preferentially grown in Tanzania due to their high yield but are susceptible to some common biotic stresses. Grafting tomato onto compatible and resistant rootstocks has a greater potential to overcome soil borne diseases, abiotic stresses, improve growth, yield and fruit quality. However, in Tanzania there is limited information regarding grafting between F1 hybrid tomato cultivars and selected eggplant rootstocks. Therefore, the objectives of this study were: (1) to determine graft success between selected eggplant rootstocks and selected F1 hybrid tomato cultivars, (2) to evaluate the effect of selected eggplant rootstocks on plant growth, yield and fruit quality of F1 hybrid tomato cultivars and (3) to determine profitability of grafted F1 hybrid tomato cultivars. Experiments were laid out in a Randomized Complete Block Design with 3 replications. Tomato cv. Assila, Monica and Tengeru 97 as a control were grafted onto rootstocks EG190, EG195 and EG203 and transplanted in the field. Data for specific objectives 1 and 2 were subjected to Analysis of Variance using GenStat version 14 software (VSN International, UK). Treatment means were separated by Tukey’s Test at P≤0.05 whereas profitability data were analysed descriptively. Results revealed significantly low (p = 0.001) field grafting success after transplanting, reduced growth (p = 0.001), low yield (p = 0.001) and low profitability for grafted Assila and Monica in comparison to ungrafted Assila, Monica and grafted Tengeru 97. Conversely, grafting improved fruit taste based on enhanced total soluble solids (TSS) in rootstock/Assila and rootstock/Monica. Overall, tomato cv. Assila and Monica should not be grafted onto these eggplant rootstocks due to low graft success, low yield and low profitability. Further studies are required to identify rootstocks that are compatible with, and vigorous enough for growth, fruit quality and profit improvement.
Rod signaling in primate retina: range, routing and kinetics

Stimulus or context dependent routing of neural signals through parallel pathways can permit flexible processing of diverse inputs. For example, work in mouse shows that rod photoreceptor signals are routed through several retinal pathways, each specialized for different light levels. This light level-dependent routing of rod signals has been invoked to explain several human perceptual results, but it has not been tested in primate retina. Here we show, surprisingly, that rod signals traverse the primate retina almost exclusively through a single pathway, regardless of light level. Indeed, identical experiments in mouse and primate reveal large differences in how rod signals traverse the retina. These results require reevaluating human perceptual results in terms of flexible computation within this single pathway. This includes a prominent speeding of rod signals with light level – which we show is inherited directly from the rods photoreceptors themselves rather than from different pathways with different kinetics.
Evaluation of Rapid Detection of Nasopharyngeal Colonization with MRSA by Real-Time PCR

Objective To investigate the clinical application of Real-Time PCR for rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nasopharyngeal swab specimens. Methods We collected the nasal and throat swab specimens from patients or medical staffs in 3 intensive care units, blood laminar flow ward and respiratory ward in Beijing Hospital, Ministry of Health from December 2010 to April 2011. Each sample was tested by RT-PCR and conventional culture-based method for the presence of MRSA. Results The total number of the specimens was 206. Compared with the conventional culture-based method, we demonstrated the diagnostic values for Real-Time PCR were 96.4% sensitivity, 96.6% specificity, 81.8% positive predictive rate, and 99.4% negative predictive rate. And the limit of detection was 10 2 CFU/ml. Conclusions This Real-Time PCR is a simple, rapid, sensitive and specific method. With the high negative predictive value, it can be used for the exclusion of MRSA colonization or infection. However, the application of its low positive predictive value should be further evaluated.
Artificial MicroRNAs Promote High-Level Production of Biomolecules Through Metabolic Engineering of Phenylpropanoid Pathway

ABSTRACT Plant microRNAs (miRNAs) are tiny RNAs that are crucial for the biosynthesis of secondary metabolites such as phenylpropanoids because they regulate the activity of key transcription factors and enzymes. Here, we have discussed the significance of miRNAs that target the mRNAs encoding for enzymes and transcription factors in the phenylpropanoid pathway. Genes encoding the miRNAs involved in the synthesis of phenylpropanoids could be considered as potential candidates for metabolic engineering. We have analyzed the construction and potential value of artificial miRNAs (amiRNAs) that could be used for scrutinizing the functional importance of miRNAs in phenylpropanoid biosynthesis and manipulating the pathway for enhancing the production of secondary metabolites.
COMPARATIVE CHARACTERISTICS OF PHOTOSYNTHETIC ACTIVITY OF NECTARINE CULTIVARS AND FORMS WITH DIFFERENT COLORED LEAF PLATE

Genotypes of nectarine with red leaves were created in Nikita botanical gardens. They have commercially valuable properties and biological characteristics (resistance to powdery mildew, large-fruited, the ability of transmitting the trait of red leaves with constant result to progeny seed, etc. ). The aim of our researches was to study the main indicators of photoactivity of leaf apparatus of nectarine with green and anthocyanin leaves coloration. Investigations have been carried out in 20102015 on intact leaf plates for three cultivars and forms of nectarine with green leaves – Rubinoviy-8 (control), Chemus, Krymtsuht 53-85 and 2 forms with anthocyanin coloration of leaf plate (NektadianaKrasnolistnaya 996-88, Krasnola 495-86). Photosynthetic activity was characterized by chlorophyll fluorescence parameters (Kautsky effect). The content of chlorophyll a and b were determined by spectrophotometry. The cultivar Rubinoviy-8 and the form Krasnola 495-86 were selected according to intensity indicators of the primary reactions of photosynthesis. Anthocyanin forms concede cultivar Rubinoviy-8 in efficiency of the primary reactions of photosynthesis an average of 48-50%; but they exceed nectarines Chemus and Krymtsuht 53-85 with green color of leaves of 23-25%. The efficiency of energy supply in the "dark" reactions of photosynthesis in all varieties and forms of nectarine maintained within 41-46%. But the further ability to utilize received energy is most efficiently implemented at the nectarine cultivar Rubinoviy-8 and form Krasnola 495-86. The forms of red-leaved nectarine in comparison with traditional cultivars are distinguished by a great potential for retaining the stability and productivity of the functioning of the photosynthetic apparatus.
Phenolic characterization, antioxidant activities, and inhibitory effects of Physalis angulata and Newbouldia laevis on enzymes linked to erectile dysfunction

ABSTRACT This study reports the phenolic composition, antioxidant activity, and capacity of Physalis angulata and Newbouldia laevis leaves to inhibit enzymes (phosphodiesterase-5′ [PDE-5′], arginase, acetylcholinesterase [AChE], and angiotensin-I converting enzyme [ACE]) linked to erectile dysfunction. High-performance liquid chromatography–diode array detector analysis of the aqueous extracts revealed the presence of phenolic acids (caffeic, ellagic, chlorogenic, and gallic acids) and flavonoids (quercetin, rutin, isoquercitrin, kaempferol, and quercitrin). N. laevis exhibited significantly higher inhibitory effects on PDE-5′, arginase, and ACE activities compared to P. angulata. There was no significant (P < 0.05) difference in the AChE inhibitory activities of both extracts. Furthermore, P. angulata exhibited lower radical scavenging and chelating abilities compared to N. laevis. These findings revealed that P. angulata and N. laevis leaves are good candidates for the development of functional foods with potentials to improve erectile function.
The physical interaction of Nanog, Brachyury, Mesp1, Nkx2.5 and Desmin with their respective genes during early Cardiomyogenesis

Herz-Kreislauf Erkrankungen sind noch immer die haufigste Todesursache weltweit. Das angeborene Regenerationspotential des menschlichen Herzens ist nicht ausreichend, um Narbenbildung im Falle eines akuten kardialen Ereignisses zu verhindern. Die Entdeckung somatischer Herzstammzellen bietet zum ersten Mal die Moglichkeit Behandlungsstrategien zu entwickeln, welche die Regenerationsfahigkeit von krankem und vernarbtem Herzgewebe erhohen konnten. Um somatische Herzstammzellen erfolgreich in voll funktionsfahige Kardiomyozyten zu differenzieren, muss das transkriptionelle Netzwerk, welches die Differenzierung von Herzzellen reguliert, untersucht werden. Wir haben uns auf die Transkriptionsfaktoren Nanog, Brachyury, Mesp1, Nkx2.5 und Desmin konzentriert, um neue Erkenntnisse uber dieses transkriptionelle Netzwerk, das die fruhe Herzentwicklung reguliert, zu gewinnen. Wir untersuchten die Interaktion dieser funf Transkriptionsfaktoren mit ihren jeweiligen Genen mittels Chromatin Immunoprazipitation zu sorgfaltig ausgewahlten Zeitpunkten wahrend der Differenzierung von embryonalen Stammzellen (ESZ) und kardiovaskularen Vorlauferzellen (KVZ). Die in-vitro Modellsysteme „Embryoid Bodies“ und „Cardiac Bodies“ wurden verwendet, um Daten zu erhalten, welche die transkriptionelle Regulierung wahrend der Embryogenese beziehungsweise der Kardiomyogenese widerspiegeln. Nanog ist ein fest etablierter Marker fur Pluripotenz, aber uber seine Rolle wahrend der Differenzierung ist bisher nicht viel bekannt. Brachyury und Mesp1 sind Marker fur fruhes Mesoderm und es wurde gezeigt, dass beide das Gen des Anderen regulieren. Nkx2.5 ist ein Marker fur KVZ und wird, angefangen bei der Kardiogenese bis hin zum erwachsenen Herzen, exprimiert. Desmin ist hauptsachlich fur seine Funktion als Intermediarfilament in Muskelzellen bekannt. Es wurden jedoch auch Beweise dafur gefunden, dass Desmin zusatzlich eine wichtige Rolle in der Genregulierung wahrend der fruhen Herzentwicklung spielt. Wir konnten zeigen, dass wahrend der fruhen Stadien der Kardiomyogenese alle funf untersuchten Transkriptionsfaktoren auf eine sehr komplexe und dynamische Weise mit ihren jeweiligen Genen interagieren. Auserdem unterstreichen die durchgefuhrten Experimente die Unterschiede zwischen ESZ und KVZ und zeigen, dass einige Gene in unterschiedlicher Art und Weise in jenen zwei Zellarten reguliert werden. Weiters liefern unsere Daten Hinweise auf mogliche neue regulierende DNA Segmente in den 5 `UTRen der untersuchten Gene.
Contemporary and emerging fisheries in The Bahamas-Conservation and management challenges, achievements and future directions

Worldwide, fisheries are in decline by approximately 1.2 million tonnes per year (Pauly & Zeller, 2016) with an estimated 31% of marine fish species overfished (FAO, 2016). The Fisheries and Agriculture Organization (FAO) of the United Nations estimates that 56.6 million people are employed through the fisheries and aquaculture sector (FAO, 2016). However, anthropogenic impacts including overfishing, invasive species, climate change, coastal development and pollution are significant threats to biodiversity, ecosystem resilience and socioeconomic stability (Albins & Hixon, 2013; Cheung et al., 2012; HoeghGuldberg & Bruno, 2010). Although the status of Received: 7 December 2017 | Revised: 25 May 2018 | Accepted: 27 May 2018 DOI: 10.1111/fme.12299
Creating Standards for Evaluating Tumour Subclonal Reconstruction

Tumours evolve through time and space. To infer these evolutionary dynamics for DNA sequencing data, many subclonal reconstruction techniques have been developed and applied to large datasets. Surprisingly, though, there has been no systematic evaluation of these methods, in part due to the complexity of the mathematical and biological questions and the difficulties in creating gold-standards. To fill this gap, we systematically elucidated key algorithmic problems in subclonal reconstruction, and developed mathematically valid quantitative metrics for evaluating them. We then developed approaches to simulate realistic tumour genomes that harbour all known mutation types and processes. Finally, we benchmarked a set of 500 subclonal reconstructions, creating a key resource, and quantified the impact of sequencing read-depth and somatic variant detection strategies on the accuracy of specific subclonal reconstruction approaches. Inference of tumour phylogenies is rapidly becoming standard practice in cancer genome analysis, and this work sets standards for evaluating its accuracy.
Heterogeneity in body size and habitat complexity influence community structure

ABSTRACT Food web studies commonly ignore individual variation within a population and variation in the environment and assume these factors have insignificant effects on community dynamics relative to interspecific interactions. However, variation in body sizes within a population (size structure) and the physical structure of habitats (habitat complexity) can both affect interspecific interactions independently, with possible interactive effects. Using experimental mesocosms, we examined effects of predator size structure and habitat complexity on predation by two common predators in fishless ponds: larval aquatic beetles (Cybister fimbriolatus) and larval dragonflies (Anax junius). Cannibalism, intraguild predation, and predation on shared prey were measured at two levels of habitat complexity crossed with six size-structured pairs of predators. We found that highly complex habitats sustain a higher prey density because prey can take refuge from predators. Additionally, size structure had direct (size better predicted predation rate than did species identity) and indirect (IGP and cannibalism lowered predation rates) effects on consumptive interactions, which changed the composition and density of the predator guild. The identified size- and habitat-mediated mechanisms can change the frequencies of intraguild vs. interguild predation (a balance important in determining top–down control of predators), and therefore we argue that these sources of heterogeneity should be included in community ecology studies where possible.
A congenital pain insensitivity mutation in the nerve growth factor gene uncouples nociception from affective pain in heterozygous humans and mice

Pain is an unpleasant but necessary sensory experience, which facilitates adaptive behaviours, such as fear. Despite recent advances, the question of how the pain experience influences learning of the fear response is still debated1,2. Genetic disorders rendering patients congenitally unable to feel pain have been described, and are usually explained by defects in peripheral nociceptors3-5. It is not known how growing up without pain affects central emotional and motivational responses to aversive stimuli. The rare autosomal recessive Hereditary Sensory and Autonomic Neuropathy type V (HSAN V) is caused by a mutation in the nerve growth factor (NGF) gene (R100W). HSAN V homozygous patients display a congenital indifference to painful events, with deficits in peripheral nociceptors but without overt cognitive impairment6. In contrast, heterozygous carriers do not present with pain-related deficits and have been identified only through pedigree and genetic screening7,8. We exploited this clinically silent population to dissociate nociceptive from affective features of pain. To address this we investigated both heterozygous knock-in mice bearing the R100W mutation (NGFR100W/m mice) and a cohort of HSAN V heterozygous human carriers. Surprisingly, we found that NGFR100W/m mice, despite normal responses to a noxious conditioning stimulus, show a deficit in learned fear while their social and innate fear responses are normal. The lack of pain-related fear response was linked to a reduced activation of anterior cingulate and motor cortices and of striatum, but not in primary somatosensory cortex. Likewise, human heterozygous R100W carriers, despite perceiving noxious stimuli and reporting subjective pain thresholds, show increased reaction latencies in response to painful stimulation, alongside a decreased subjective urgency to react. Functional magnetic resonance imaging (fMRI) revealed, comparably to the mouse data, an altered processing of painful stimuli in rostral anterior cingulate, medial premotor cortical regions and striatum. These findings from both human and mouse HSAN V carriers uncover behavioural and motivational consequences of a mild genetic pain insensitivity on the establishment of pain-dependent affective responses and memories.
The contribution of melanization to Drosophila survival changes with Enterococcus faecalis V583 genomic content

Enterococcus faecalis is a human opportunist pathogen able to infect and kill Drosophila. Previous studies proved that E. faecalis carrying the Fsr quorum sensing system are extremely virulent. Fsr is the regulator of two important virulence factors, gelatinase and serine protease, which cause death of Drosophila adult flies by decreasing its tolerance to infection. The exact mechanism underlying the toxicity of these E. faecalis virulence factors is nevertheless not known, in particular the way they interfere with the host immune response. In the present study, we investigated the influence of Fsr-GelE-SprE bacterial factors on different immunity responses, namely antimicrobial peptide production, phagocytosis and melanization. Using E. faecalis V583 wild type and E. faecalis V583 ΔfsrBΔgelEΔsprE mutant we showed that both drosomycin production and phagocytosis were activated to similar levels by the two bacterial strains. However, fly pupae infected with the mutant strain showed less melanization and higher survival rates when compared to pupae infected with wild type bacteria. Using adult flies carrying the PPO1Δ PPO2Δ mutation, we found that absence of melanization had a different impact in survival of the flies when infected with the two E. faecalis strains. PPO1Δ, PPO2Δ mutant flies were more tolerant to E. faecalis deprived of its major virulence factors. By showing that the presence of the E. faecalis proteases completely alters the impact of melanization activation on Drosophila tolerance, this study provides new clues on the interactions between E. faecalis virulence factors and the fly´s immune system. Future studies on Drosophila immunity should consider the pathogen genomic content.