Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of BACON Domain Tandem Repeats in crAssphage and Novel Gut Bacteriophage Lineages

The human gut contains an expanse of largely unstudied bacteriophages. Among the most common are crAss-like phages, which were predicted to infect Bacteriodetes hosts. CrAssphage, the first crAss-like phage to be discovered, contains a protein encoding a Bacteroides-associated carbohydrate-binding often N-terminal (BACON) domain tandem repeat. Because protein domain tandem repeats are often hotspots of evolution, BACON domains may provide insight into the evolution of crAss-like phages. Here, we studied the biodiversity and evolution of BACON domains in bacteriophages by analysing over 2 million viral contigs. We found a high biodiversity of BACON in seven gut phage lineages, including five known crAss-like phage lineages and two novel gut phage lineages that are distantly related to crAss-like phages. In three BACON-containing phage lineages, we found that BACON domain tandem repeats were associated with phage tail proteins, suggestive of a possible role of these repeats in host binding. In contrast, individual BACON domains that did not occur in tandem were not found in the proximity of tail proteins. In two lineages, tail-associated BACON domain tandem repeats evolved largely through horizontal transfer of separate domains. In the third lineage that includes the prototypical crAssphage, the tandem repeats arose from several sequential domain duplications, resulting in a characteristic tandem array that is distinct from bacterial BACON domains. We conclude that phage tail-associated BACON domain tandem repeats have evolved in at least two independent cases in gut bacteriophages, including in the widespread gut phage crAssphage.
Incidence and Risk Factors for Tractional Macular Detachment after Anti-Vascular Endothelial Growth Factor Agent Pretreatment before Vitrectomy for Complicated Proliferative Diabetic Retinopathy

The study’s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65–0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11–0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02–1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.
Graded balloon atrial septostomy for palliation of congenital pulmonary hypertension in a dog: A case report

Abstract Case Description A 6‐month‐old intact female Maltese dog was presented for acute onset of syncope. Clinical Findings The dog was presented for collapse upon excitement and exercise. It collapsed at discharge and suffered cardiopulmonary arrest. Echocardiography after resuscitation indicated severe pulmonary hypertension without evidence of intracardiac or extracardiac shunting. A presumptive diagnosis of congenital pulmonary hypertension was made. Treatment and Outcome Initial treatment with sildenafil was effective at relieving syncope, but the extent of pulmonary hypertension as determined by serial echocardiography was unchanged. Graded balloon atrial septostomy was performed as a palliative procedure. Follow‐up echocardiography identified a patent interatrial communication with bidirectional shunting. The dog remained asymptomatic 18 months after treatment. Clinical Relevance To the best of our knowledge, this study is the first report in the veterinary literature of graded balloon atrial septostomy performed for therapeutic purposes. Further studies are required to determine if this palliative procedure is a beneficial treatment option for dogs with congenital or severe refractory pulmonary hypertension.
A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor

Significance Stochastic cell fate decisions are conserved and prominent processes during development, but the underlying molecular mechanisms are only partly understood. In the nematode Caenorhabditis elegans, the AWC sensory neuron pair asymmetrically differentiates into 2 distinct identities in a stochastic manner. Through identification of a unique transportin allele, we elucidate a mechanism by which a homeodomain-like factor couples voltage- and calcium-activated potassium channels to transactivation of a HMG-box transcription factor expression for the stochastic choice of AWC identities. We show that transportin drives nuclear import of the homeodomain-like factor to activate the expression of the HMG-box transcription factor for stochastic AWC identities. Our findings also provide structure-function insight into a conserved amino acid residue of transportins in cell type diversification. Stochastic neuronal cell fate choice involving notch-independent mechanisms is a poorly understood biological process. The Caenorhabditis elegans AWC olfactory neuron pair asymmetrically differentiates into the default AWCOFF and induced AWCON subtypes in a stochastic manner. Stochastic choice of the AWCON subtype is established using gap junctions and SLO BK potassium channels to repress a calcium-activated protein kinase pathway. However, it is unknown how the potassium channel-repressed calcium signaling is translated into the induction of the AWCON subtype. Here, we identify a detailed working mechanism of how the homeodomain-like transcription factor NSY-7, previously described as a repressor in the maintenance of AWC asymmetry, couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype through the identification of a unique imb-2 (transportin 1) allele. imb-2 loss-of-function mutants are not viable; however, we identify a viable imb-2 allele from an unbiased forward genetic screen that reveals a specific role of imb-2 in AWC olfactory neuron asymmetry. IMB-2 specifically drives nuclear import of NSY-7 within AWC neurons to transactivate the expression of the high mobility group (HMG)-box transcription factor SOX-2 for the specification of the AWCON subtype. This study provides mechanistic insight into how NSY-7 couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype. Our findings also provide structure-function insight into a conserved amino acid residue of transportins in brain development and suggest its dysfunction may lead to human neurological disorders.
PACAP27 mitigates an age‐dependent hippocampal vulnerability to PGJ2‐induced spatial learning deficits and neuroinflammation in mice

Inflammation in the brain is mediated by the cyclooxygenase pathway, which leads to the production of prostaglandins. Prostaglandin (PG) D2, the most abundant PG in the brain, increases under pathological conditions and is spontaneously metabolized to PGJ2. PGJ2 is highly neurotoxic, with the potential to transition neuroinflammation into a chronic state and contribute to neurodegeneration as seen in many neurological diseases. Conversely, PACAP27 is a lipophilic peptide that raises intracellular cAMP and is an anti‐inflammatory agent. The aim of our study was to investigate the therapeutic potential of PACAP27 to counter the behavioral and neurotoxic effects of PGJ2 observed in aged subjects.
Casamino acids slow motility and stimulate surface growth in an extreme oligotroph.

Environmental cues that regulate motility are poorly understood, but specific carbon and nitrogen sources, such as casamino acids (CAA), are known to stimulate motility in model organisms. However, natural environments are commonly more nutrient limited than laboratory growth media, and the effect of energy-rich CAA on the motility of oligotrophic microorganisms is unknown. In this study an extreme oligocarbotroph, Variovorax paradoxus YC1, was isolated from weathered shale rock within a disused mine level in North Yorkshire, UK. The addition of 0.1 % CAA to minimal media significantly reduced the motility of YC1 after 72 hours, and inhibited swimming motility resulting in enhanced surface growth. We propose this response to CAA is a physiological adaptation to oligotrophy, facilitating the colonization of nutrient rich environments. This article is protected by copyright. All rights reserved.
Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.
Examining the link between religiousness and fitness in a behavioural ecological framework

Abstract In recent years there have been attempts to explain religiousness from an evolutionary viewpoint. However, empirical data on this topic are still lacking. In the present study, the behavioural ecological theoretical framework was used to explore the relations between religiousness, harsh environment, fitness (reproductive success and parental investment) and fitness-related outcomes (age at first birth, desired number of children and the romantic relationship duration). The data were collected from 461 individuals from a community sample who were near the end of their reproductive phase (54% females, Mage = 51.75; SD = 6.56). Positive links between religiousness, harsh environment, fitness and fitness-related outcomes were expected, with the exception of age at first birth, for which a negative association was hypothesized. Hence, the main assumption of the study was that religiousness has some attributes of fast life-history phenotypes – that it emerges from a harsh environment and enables earlier reproduction. The study findings partially confirmed these hypotheses. Religiousness was positively related to environmental harshness but only on a zero-order level. Religious individuals had higher reproductive success (this association was especially pronounced in males) but religiousness did not show associations with parental investment. Religiousness was positively associated with desired number of children and negatively associated with age at first birth, although the latter association was only marginally significant in the multivariate analyses. Finally, path analysis showed that desired number of children and age at first birth completely mediated the relation between religiousness and reproductive success. The data confirmed the biologically adaptive function of religiousness in contemporary populations and found the mediating processes that facilitate fitness in religious individuals. Furthermore, the findings initiate a more complex view of religiousness in a life-history context which could be fruitful for future research: a proposal labelled as ‘ontogeny-dependent life-history theory of religiousness’.
Making Sense of Information Overload: Consumer Ranking of Nutritional Claims in Cereal Based Products

As a result of increased consumer awareness, demand for healthier food products is increasing day by day. Consumers seek healthier versions of food products which they relate to reduced presence of unhealthy components or increased presence of healthy ones. As a result, the food industry has not only increased the variety of products available but also uses nutritional claims to signal the presence of more substances. As an average consumer at the supermarket devotes just a few seconds to selecting each product, they are only able or willing to process that information that immediately attracts their attention or that is felt to be more important to them. This paper analyses how consumers rank different nutritional claims for two processed cereal products. Five claims were chosen to reflect the current market landscape of availability, and that relates to both “healthy” (i.e., fiber) and “unhealthy” (i.e., fat) substances. We use a direct ranking preference method with data from a survey conducted with consumers in a Spanish region in 2017. Results show that the ranking of claims differs between the two products (biscuits and pastries) and across consumers. However, consumers prefer those that show reduced presence of unhealthy substances above those that highlight the presence of healthy ones. Therefore, policy to maximize the impact of nutritional labelling should be product-specific.
Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam

A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were colloidally stable and their size and surface charge could be controlled by the polycation/polyanion ratio. The morphology of the obtained particles was visualized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The resulting structures were spherical, with hydrodynamic diameters in the range of 100–150 nm. The binding constant (Ka) of a model drug, piroxicam, to the cationic pullulan (C-PUL) was determined by spectrophotometric measurements. The value of Ka was calculated according to the Benesi—Hildebrand equation to be (3.6 ± 0.2) × 103 M−1. After binding to cationic pullulan, piroxicam was effectively entrapped inside the nanohydrogel particles and released in a controlled way. The obtained system was efficiently taken up by cells and was shown to be biocompatible.
Enhancement in Site-Specific Delivery of Carvacrol against Methicillin Resistant Staphylococcus aureus Induced Skin Infections Using Enzyme Responsive Nanoparticles: A Proof of Concept Study

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.
Machine Listening for Heart Status Monitoring: Introducing and Benchmarking HSS—The Heart Sounds Shenzhen Corpus

Auscultation of the heart is a widely studied technique, which requires precise hearing from practitioners as a means of distinguishing subtle differences in heart-beat rhythm. This technique is popular due to its non-invasive nature, and can be an early diagnosis aid for a range of cardiac conditions. Machine listening approaches can support this process, monitoring continuously and allowing for a representation of both mild and chronic heart conditions. Despite this potential, relevant databases and benchmark studies are scarce. In this paper, we introduce our publicly accessible database, the Heart Sounds Shenzhen Corpus (HSS), which was first released during the recent INTERSPEECH 2018 ComParE Heart Sound sub-challenge. Additionally, we provide a survey of machine learning work in the area of heart sound recognition, as well as a benchmark for HSS utilising standard acoustic features and machine learning models. At best our support vector machine with Log Mel features achieves 49.7% unweighted average recall on a three category task (normal, mild, moderate/severe).
HISTONE DEACETYLASE 9 stimulates auxin-dependent thermomorphogenesis in Arabidopsis thaliana by mediating H2A.Z depletion

Significance Knowledge-based development of global warming-resilient crop varieties is hindered by limited understanding of warm-temperature signaling mechanisms. Using the Arabidopsis model, we show that the chromatin-modifying enzyme HISTONE DEACETYLASE 9 (HDA9) is essential for promoting an open plant architecture that allows for efficient mitigation of the impact of warm temperature. HDA9 does not affect hypocotyl elongation in response to different light conditions, setting it apart from the shade-avoidance response that phenotypically resembles acclimation to warmth. We demonstrate that HDA9 is required for transcriptional activation of YUCCA8, the rate-limiting enzyme in the biosynthesis of the phytohormone auxin, by facilitating net eviction of the H2A.Z histone variant from YUCCA8 nucleosomes at warm temperature. Many plant species respond to unfavorable high ambient temperatures by adjusting their vegetative body plan to facilitate cooling. This process is known as thermomorphogenesis and is induced by the phytohormone auxin. Here, we demonstrate that the chromatin-modifying enzyme HISTONE DEACETYLASE 9 (HDA9) mediates thermomorphogenesis but does not interfere with hypocotyl elongation during shade avoidance. HDA9 is stabilized in response to high temperature and mediates histone deacetylation at the YUCCA8 locus, a rate-limiting enzyme in auxin biosynthesis, at warm temperatures. We show that HDA9 permits net eviction of the H2A.Z histone variant from nucleosomes associated with YUCCA8, allowing binding and transcriptional activation by PHYTOCHROME INTERACTING FACTOR 4, followed by auxin accumulation and thermomorphogenesis.
Graphene Oxide: A Smart (Starting) Material for Natural Methylxanthines Adsorption and Detection

Natural methylxanthines, caffeine, theophylline and theobromine, are widespread biologically active alkaloids in human nutrition, found mainly in beverages (coffee, tea, cocoa, energy drinks, etc.). Their detection is thus of extreme importance, and many studies are devoted to this topic. During the last decade, graphene oxide (GO) and reduced graphene oxide (RGO) gained popularity as constituents of sensors (chemical, electrochemical and biosensors) for methylxanthines. The main advantages of GO and RGO with respect to graphene are the easiness and cheapness of synthesis, the notable higher solubility in polar solvents (water, among others), and the higher reactivity towards these targets (mainly due to π–π interactions); one of the main disadvantages is the lower electrical conductivity, especially when using them in electrochemical sensors. Nonetheless, their use in sensors is becoming more and more common, with the obtainment of very good results in terms of selectivity and sensitivity (up to 5.4 × 10−10 mol L−1 and 1.8 × 10−9 mol L−1 for caffeine and theophylline, respectively). Moreover, the ability of GO to protect DNA and RNA from enzymatic digestion renders it one of the best candidates for biosensors based on these nucleic acids. This is an up-to-date review of the use of GO and RGO in sensors.