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Caddisflies (Trichoptera) are among the most diverse groups of freshwater animals with more than 16 000 described species. They play a fundamental role in freshwater ecology and environmental engineering in streams, rivers and lakes. Because of this, they are frequently used as indicator organisms in biomonitoring programmes. Despite their importance, key questions concerning the evolutionary history of caddisflies, such as the timing and origin of larval case making, remain unanswered owing to the lack of a well-resolved phylogeny. Here, we estimated a phylogenetic tree using a combination of transcriptomes and targeted enrichment data for 207 species, representing 48 of 52 extant families and 174 genera. We calibrated and dated the tree with 33 carefully selected fossils. The first caddisflies originated approximately 295 million years ago in the Permian, and major suborders began to diversify in the Triassic. Furthermore, we show that portable case making evolved in three separate lineages, and shifts in diversification occurred in concert with key evolutionary innovations beyond case making.
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Evolução Biológica , Fósseis , Insetos , Filogenia , Animais , Insetos/genética , TranscriptomaRESUMO
The viviparous eelpout Zoarces viviparus is a common fish across the North-East Atlantic and has successfully colonized habitats across environmental gradients. Due to its wide distribution and predictable phenotypic responses to pollution, Z. viviparus is used as bioindicator organism and has been routinely sampled over decades by several countries to monitor marine environmental health. Additionally, this species is a promising model to study adaptive processes related to environmental change, specifically global warming. Here, we report the chromosome-level genome assembly of Z. viviparus, which has a size of 663 mega base pairs (mbp) and consists of 607 scaffolds (N50 = 26 mbp). The 24 largest represent the 24 chromosomes of the haploid Z. viviparus genome, which harbors 98% of the complete BUSCOs defined for ray-finned fish, indicating that the assembly is highly contiguous and complete. Comparative analyses between the Z. viviparus assembly and chromosome-level genomes of two other eelpout species revealed a high synteny, but also an accumulation of repetitive elements in the Z. viviparus genome. Our reference genome will be an important resource enabling future in-depth genomic analyses of the effects of environmental change in this important bioindicator species.
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OBJECTIVE: In many medical disciplines, facial attractiveness is part of the diagnosis, yet its scoring might be confounded by facial expressions. The intent was to apply deep convolutional neural networks (CNN) to identify how facial expressions affect facial attractiveness and to explore whether a dedicated training of the CNN is able to reduce the bias of facial expressions. MATERIALS AND METHODS: Frontal facial images (n = 840) of 40 female participants (mean age 24.5 years) were taken adapting a neutral facial expression and the six universal facial expressions. Facial attractiveness was computed by means of a face detector, deep convolutional neural networks, standard support vector regression for facial beauty, visual regularized collaborative filtering and a regression technique for handling visual queries without rating history. CNN was first trained on random facial photographs from a dating website and then further trained on the Chicago Face Database (CFD) to increase its suitability to medical conditions. Both algorithms scored every image for attractiveness. RESULTS: Facial expressions affect facial attractiveness scores significantly. Scores from CNN additionally trained on CFD had less variability between the expressions (range 54.3-60.9 compared to range: 32.6-49.5) and less variance within the scores (P ≤ .05), but also caused a shift in the ranking of the expressions' facial attractiveness. CONCLUSION: Facial expressions confound attractiveness scores. Training on norming images generated scores less susceptible to distortion, but more difficult to interpret. Scoring facial attractiveness based on CNN seems promising, but AI solutions must be developed on CNN trained to recognize facial expressions as distractors.
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The species- and clone-specific susceptibility of Staphylococcus cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycosylation-dependent phage-WTA interactions in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new S. epidermidis WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses. S. epidermidis glycerolphosphate WTA was found to be modified with glucose in a tagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs, suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits interspecies horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcus interaction and horizontal gene transfer, and it will help in the design of anti-staphylococcal phage therapies.IMPORTANCEPhages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genus Staphylococcus bind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) species has remained unknown. We describe that S. epidermidis glycosylates its WTA backbone with glucose, and we identify a cluster of three genes responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72, suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.
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Infecções Estafilocócicas , Staphylococcus epidermidis , Humanos , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/metabolismo , Staphylococcus aureus/genética , Coagulase/metabolismo , Glucose/metabolismo , Ácidos Teicoicos/metabolismo , Staphylococcus/metabolismo , Fagos de Staphylococcus/genética , DNA/metabolismo , Parede Celular/metabolismo , Infecções Estafilocócicas/metabolismoRESUMO
The antibiotic fosfomycin (FOS) is widely recognized for the treatment of lower urinary tract infections with Escherichia coli and has lately gained importance as a therapeutic option to combat multidrug-resistant bacteria. However, resistance to FOS frequently develops through mutations reducing its uptake. Although the inner-membrane transport of FOS has been extensively studied in E. coli, its outer-membrane (OM) transport remains insufficiently understood. While evaluating minimal inhibitory concentrations in OM porin-deficient mutants, we observed that the E. coli ΔompFΔompC strain is four times more resistant to FOS than the wild type and the respective single mutants. Continuous monitoring of FOS-induced lysis of porin-deficient strains additionally highlighted the importance of LamB. The relevance of OmpF, OmpC, and LamB to FOS uptake was confirmed by electrophysiological and transcriptional analysis. Our study gives for the first time in-depth insight into the transport of FOS through the OM in E. coli.
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Proteínas de Escherichia coli , Fosfomicina , Escherichia coli/genética , Escherichia coli/metabolismo , Fosfomicina/farmacologia , Transporte Biológico , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Porinas/genética , Porinas/metabolismoRESUMO
Metazoa-level universal single-copy orthologs (mzl-USCOs) are universally applicable markers for DNA taxonomy in animals that can replace or supplement single-gene barcodes. Previously, mzl-USCOs from target enrichment data were shown to reliably distinguish species. Here, we tested whether USCOs are an evenly distributed, representative sample of a given metazoan genome and therefore able to cope with past hybridization events and incomplete lineage sorting. This is relevant for coalescent-based species delimitation approaches, which critically depend on the assumption that the investigated loci do not exhibit autocorrelation due to physical linkage. Based on 239 chromosome-level assembled genomes, we confirmed that mzl-USCOs are genetically unlinked for practical purposes and a representative sample of a genome in terms of reciprocal distances between USCOs on a chromosome and of distribution across chromosomes. We tested the suitability of mzl-USCOs extracted from genomes for species delimitation and phylogeny in four case studies: Anopheles mosquitos, Drosophila fruit flies, Heliconius butterflies and Darwin's finches. In almost all instances, USCOs allowed delineating species and yielded phylogenies that corresponded to those generated from whole genome data. Our phylogenetic analyses demonstrate that USCOs may complement single-gene DNA barcodes and provide more accurate taxonomic inferences. Combining USCOs from sources that used different versions of ortholog reference libraries to infer marker orthology may be challenging and, at times, impact taxonomic conclusions. However, we expect this problem to become less severe as the rapidly growing number of reference genomes provides a better representation of the number and diversity of organismal lineages.
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Borboletas , Animais , Filogenia , Borboletas/genética , DNA , Genoma , Hibridização GenéticaRESUMO
The excess Gibbs-energy of a two-component liquid molecular mixture is modeled based on discrete clusters of molecules. These clusters preserve the three-dimensional geometric information about local molecule neighborhoods that inform the interaction energies of the clusters. In terms of a discrete Markov-chain, the clusters are used to hypothetically construct the mixture using sequential insertion steps. Each insertion step and, therefore, cluster is assigned a probability of occurring in an equilibrium system that is determined via the constrained minimization of the Helmholtz free energy. For this, informational Shannon entropy based on these probabilities is used synonymously with thermodynamic entropy. A first approach for coupling the model to real molecules is introduced in the form of a molecular sampling algorithm, which utilizes a force-field approach to determine the energetic interactions within a cluster. An exemplary application to four mixtures shows promising results regarding the description of a variety of excess Gibbs-energy curves, including the ability to distinguish between structural isomers.
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Staphylococcus epidermidis expresses glycerol phosphate wall teichoic acid (WTA), but some health care-associated methicillin-resistant S. epidermidis (HA-MRSE) clones produce a second, ribitol phosphate (RboP) WTA, resembling that of the aggressive pathogen Staphylococcus aureus. RboP-WTA promotes HA-MRSE persistence and virulence in bloodstream infections. We report here that the TarM enzyme of HA-MRSE [TarM(Se)] glycosylates RboP-WTA with glucose, instead of N-acetylglucosamine (GlcNAc) by TarM(Sa) in S. aureus. Replacement of GlcNAc with glucose in RboP-WTA impairs HA-MRSE detection by human immunoglobulin G, which may contribute to the immune-evasion capacities of many invasive S. epidermidis. Crystal structures of complexes with uridine diphosphate glucose (UDP-glucose), and with UDP and glycosylated poly(RboP), reveal the binding mode and glycosylation mechanism of this enzyme and explain why TarM(Se) and TarM(Sa) link different sugars to poly(RboP). These structural data provide evidence that TarM(Se) is a processive WTA glycosyltransferase. Our study will support the targeted inhibition of TarM enzymes, and the development of RboP-WTA targeting vaccines and phage therapies.
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Glicosiltransferases , Staphylococcus aureus , Humanos , Glicosiltransferases/química , Staphylococcus epidermidis , Ácidos Teicoicos/química , Ácidos Teicoicos/metabolismo , Difosfato de Uridina/metabolismo , Glucose/metabolismo , Fosfatos/metabolismoRESUMO
Pesticides are major agricultural stressors for freshwater species. Exposure to pesticides can disrupt the biotic integrity of freshwater ecosystems and impair associated ecosystem functions. Unfortunately, physiological mechanisms through which pesticides affect aquatic organisms are largely unknown. For example, the widely-used insecticide chlorantraniliprole is supposed to be highly selective for target pest species, i.e. Lepidoptera (butterflies), but its effect in aquatic non-target taxa is poorly studied. Using RNA-sequencing data, we quantified the insecticide effect on three aquatic invertebrate species: the caddisfly Lepidostoma basale, the mayfly Ephemera danica and the amphipod Gammarus pulex. Further, we tested how the insecticide-induced transcriptional response is modulated by biotic interaction between the two leaf-shredding species L. basale and G. pulex. While G. pulex was only weakly affected by chlorantraniliprole exposure, we detected strong transcriptional responses in L. basale and E. danica, implying that the stressor receptors are conserved between the target taxon Lepidoptera and other insect groups. We found in both insect species evidence for alterations of the developmental program. If transcriptional changes in the developmental program induce alterations in emergence phenology, pronounced effects on food web dynamics in a cross-ecosystem context are expected.
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Anfípodes , Borboletas , Ephemeroptera , Inseticidas , Praguicidas , Animais , Inseticidas/toxicidade , Ecossistema , Insetos , Transcriptoma , Invertebrados , Praguicidas/análise , Anfípodes/fisiologiaRESUMO
The bacterial cell wall consists of a three-dimensional peptidoglycan layer, composed of peptides linked to the sugars N-acetylmuramic acid (MurNAc) and GlcNAc. Unlike other bacteria, the pathogenic Tannerella forsythia, a member of the red complex group of bacteria associated with the late stages of periodontitis, lacks biosynthetic pathways for MurNAc production and therefore obtains MurNAc from the environment. Sugar kinases play a crucial role in the MurNAc recycling process, activating the sugar molecules by phosphorylation. In this study, we present the first crystal structures of a MurNAc kinase, called murein sugar kinase (MurK), in its unbound state as well as in complexes with the ATP analog ß-γ-methylene adenosine triphosphate (AMP-PCP) and with MurNAc. We also determined the crystal structures of K1058, a paralogous MurNAc kinase of T. forsythia, in its unbound state and in complex with MurNAc. We identified the active site and residues crucial for MurNAc specificity as the less bulky side chains of S133, P134, and L135, which enlarge the binding cavity for the lactyl ether group, unlike the glutamate or histidine residues present in structural homologs. In establishing the apparent kinetic parameters for both enzymes, we showed a comparable affinity for MurNAc (Km 180 µM and 30 µM for MurK and K1058, respectively), with MurK being over two hundred times faster than K1058 (Vmax 80 and 0.34 µmol min-1 mg-1, respectively). These data might support a structure-guided approach to development of inhibitory MurNAc analogs for pathogen MurK enzymes.
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Modelos Moleculares , Ácidos Murâmicos , Fosfotransferases , Tannerella forsythia , Ácidos Murâmicos/metabolismo , Peptidoglicano/metabolismo , Tannerella forsythia/enzimologia , Fosfotransferases/química , Fosfotransferases/metabolismo , Estrutura Terciária de Proteína , Cristalografia por Raios X , Domínio Catalítico , Ativação EnzimáticaRESUMO
BACKGROUND: The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity. METHODS: REDUCE-GAD was a prospective, multicentric, biobanking study to determine whether established serum markers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], tau protein, ubiquitin-carboxyl-terminal-hydrolase (UCH-L1), S100B and matrix-metalloproteinase 9 [MMP9]) are predictive of CE-positive MRI lesions. Blood samples were obtained from patients undergoing MRI 5 days before or after collection. RESULTS: Patients (N = 102) from four different centers with confirmed MS or related disorders were included; n = 57 (55.9%) showed CE on MRI versus n = 45 (44.1%) without CE. Only higher NfL values indicated CE (odds ratio [OR] 1.05; 95% CI 1.0-1.09) and were correlated with number (ρ = 0.47; p < 0.001) and diameter of CE lesions (ρ = 0.58; p < 0.001). Nfl Z-scores improved diagnostic accuracy (OR 1.52; 95% CI 1.06-2.18). Receiver operator characteristic analysis revealed a reasonable cut-off value for NfL at 14.1 pg/mL (sensitivity 49.1%; specificity 82.2%; positive predictive value 77.8%; negative predictive value 56.0%). NfL ≥59.2 pg/mL was exclusively observed in patients with CE. CONCLUSIONS: Evaluation of several possible serum biomarkers for CE in MS patients provided the most robust results for NfL, particularly as Z-scores. Following further evaluation, biomarkers may help stratify the application of contrast agents for brain imaging in MS patients.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Gadolínio , Estudos Prospectivos , Bancos de Espécimes Biológicos , Meios de Contraste , Biomarcadores , Proteína Glial Fibrilar Ácida , Proteínas de NeurofilamentosRESUMO
YgfB-mediated ß-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa. We show that YgfB upregulates expression of the ß-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antiterminator AlpA induces expression of the alpBCDE autolysis genes and of the peptidoglycan amidase AmpDh3. YgfB interacts with AlpA and represses the ampDh3 expression. Thus, YgfB indirectly prevents AmpDh3 from reducing the levels of cell wall-derived 1,6-anhydro-N-acetylmuramyl-peptides, required to induce the transcriptional activator AmpR in promoting the ampC expression and ß-lactam resistance. Ciprofloxacin-mediated DNA damage induces AlpA-dependent production of AmpDh3 as previously shown, which should reduce ß-lactam resistance. YgfB, however, counteracts the ß-lactam enhancing activity of ciprofloxacin by repressing ampDh3 expression and lowering the benefits of this drug combination. Altogether, YgfB represents an additional player in the complex regulatory network of AmpC regulation.
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Pseudomonas aeruginosa , Resistência beta-Lactâmica , Pseudomonas aeruginosa/genética , Resistência beta-Lactâmica/genética , Ciprofloxacina/farmacologia , beta-Lactamas/farmacologiaRESUMO
Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses.
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Pirimidinas , Ciclo Celular , Diferenciação CelularRESUMO
The obligate intracellular Chlamydiaceae do not need to resist osmotic challenges and thus lost their cell wall in the course of evolution. Nevertheless, these pathogens maintain a rudimentary peptidoglycan machinery for cell division. They build a transient peptidoglycan ring, which is remodeled during the process of cell division and degraded afterwards. Uncontrolled degradation of peptidoglycan poses risks to the chlamydial cell, as essential building blocks might get lost or trigger host immune response upon release into the host cell. Here, we provide evidence that a primordial enzyme class prevents energy intensive de novo synthesis and uncontrolled release of immunogenic peptidoglycan subunits in Chlamydia trachomatis. Our data indicate that the homolog of a Bacillus NlpC/P60 protein is widely conserved among Chlamydiales. We show that the enzyme is tailored to hydrolyze peptidoglycan-derived peptides, does not interfere with peptidoglycan precursor biosynthesis, and is targeted by cysteine protease inhibitors in vitro and in cell culture. The peptidase plays a key role in the underexplored process of chlamydial peptidoglycan recycling. Our study suggests that chlamydiae orchestrate a closed-loop system of peptidoglycan ring biosynthesis, remodeling, and recycling to support cell division and maintain long-term residence inside the host. Operating at the intersection of energy recovery, cell division and immune evasion, the peptidoglycan recycling NlpC/P60 peptidase could be a promising target for the development of drugs that combine features of classical antibiotics and anti-virulence drugs.
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Chlamydia trachomatis , Peptidoglicano , Chlamydia trachomatis/metabolismo , Peptidoglicano/metabolismo , Evasão da Resposta Imune , Proteínas de Bactérias/metabolismo , Divisão Celular , Parede Celular/metabolismo , Peptídeo Hidrolases/metabolismoRESUMO
BACKGROUND: Freshwaters are exposed to multiple anthropogenic stressors, leading to habitat degradation and biodiversity decline. In particular, agricultural stressors are known to result in decreased abundances and community shifts towards more tolerant taxa. However, the combined effects of stressors are difficult to predict as they can interact in complex ways, leading to enhanced (synergistic) or decreased (antagonistic) response patterns. Furthermore, stress responses may remain undetected if only the abundance changes in ecological experiments are considered, as organisms may have physiological protective pathways to counteract stressor effects. Therefore, we here used transcriptome-wide sequencing data to quantify single and combined effects of elevated fine sediment deposition, increased salinity and reduced flow velocity on the gene expression of the amphipod Gammarus fossarum in a mesocosm field experiment. RESULTS: Stressor exposure resulted in a strong transcriptional suppression of genes involved in metabolic and energy consuming cellular processes, indicating that G. fossarum responds to stressor exposure by directing energy to vitally essential processes. Treatments involving increased salinity induced by far the strongest transcriptional response, contrasting the observed abundance patterns where no effect was detected. Specifically, increased salinity induced the expression of detoxification enzymes and ion transporter genes, which control the membrane permeability of sodium, potassium or chloride. Stressor interactions at the physiological level were mainly antagonistic, such as the combined effect of increased fine sediment and reduced flow velocity. The compensation of the fine sediment induced effect by reduced flow velocity is in line with observations based on specimen abundance data. CONCLUSIONS: Our findings show that gene expression data provide new mechanistic insights in responses of freshwater organisms to multiple anthropogenic stressors. The assessment of stressor effects at the transcriptomic level and its integration with stressor effects at the level of specimen abundances significantly contribute to our understanding of multiple stressor effects in freshwater ecosystems.
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EcossistemaRESUMO
Several metal-based carbon monoxide-releasing molecules (CORMs) are active CO donors with established antibacterial activity. Among them, CORM conjugates with azole antibiotics of type [Mn(CO)3(2,2'-bipyridyl)(azole)]+ display important synergies against several microbes. We carried out a structure-activity relationship study based upon the lead structure of [Mn(CO)3(Bpy)(Ctz)]+ by producing clotrimazole (Ctz) conjugates with varying metal and ligands. We concluded that the nature of the bidentate ligand strongly influences the bactericidal activity, with the substitution of bipyridyl by small bicyclic ligands leading to highly active clotrimazole conjugates. On the contrary, the metal did not influence the activity. We found that conjugate [Re(CO)3(Bpy)(Ctz)]+ is more than the sum of its parts: while precursor [Re(CO)3(Bpy)Br] has no antibacterial activity and clotrimazole shows only moderate minimal inhibitory concentrations, the potency of [Re(CO)3(Bpy)(Ctz)]+ is one order of magnitude higher than that of clotrimazole, and the spectrum of bacterial target species includes Gram-positive and Gram-negative bacteria. The addition of [Re(CO)3(Bpy)(Ctz)]+ to Staphylococcus aureus causes a general impact on the membrane topology, has inhibitory effects on peptidoglycan biosynthesis, and affects energy functions. The mechanism of action of this kind of CORM conjugates involves a sequence of events initiated by membrane insertion, followed by membrane disorganization, inhibition of peptidoglycan synthesis, CO release, and break down of the membrane potential. These results suggest that conjugation of CORMs to known antibiotics may produce useful structures with synergistic effects that increase the conjugate's activity relative to that of the antibiotic alone.
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Climate extremes, such as heat waves, droughts, extreme rainfall can lead to harvest failures, flooding and consequently threaten the food security worldwide. Improving our understanding about climate extremes can mitigate the worst impacts of climate change and extremes. The objective here is to investigate the changes in climate and climate extremes by considering two time slices (i.e., 1962-1990 and 1991-2019) in all climate zones of Pakistan by utilizing observed data from 54 meteorological stations. Different statistical methods and techniques were applied on observed station data to assess changes in temperature, precipitation and spatio-temporal trends of climatic extremes over Pakistan from 1962 to 2019. The Mann-Kendal test demonstrated increasing precipitation (DJF) and decreasing maximum and minimum temperatures (JJA) at the meteorological stations located in the Karakoram region during 1962-1990. The decadal analysis, on the other hand, showed a decrease in precipitation during 1991-2019 and an increase in temperature (maximum and minimum) during 2010-2019, which is consistent with the recently observed slight mass loss of glaciers related to the Karakoram Anomaly. These changes are highly significant at 5% level of significance at most of the stations. In case of temperature extremes, summer days (SU25) increased except in zone 4, TX10p (cold days) decreased across the country during 1962-1990, except for zones 1 and 2. TX90p (warm days) increased between 1991-2019, with the exception of zone 5, and decreased during 1962-1990, with the exception of zones 2 and 5. The spatio-temporal trend of consecutive dry days (CDD) indicated a rising tendency from 1991 to 2019, with the exception of zone 4, which showed a decreasing trend. PRCPTOT (annual total wet-day precipitation), R10 (number of heavy precipitation days), R20 (number of very heavy precipitation days), and R25mm (very heavy precipitation days) increased (decreased) considerably in the North Pakistan during 1962-1990 (1991-2019). The findings of this study can help to address some of the sustainable development goals related climate action, hunger and environment. In addition, the findings can help in developing sustainable adaptation and mitigation strategies against climate change and extremes. As the climate and extremes conditions are not the uniform in all climate zone, therefore, it is suggested to the formers and agriculture department to harvest crops resilient to the climatic condition of each zone. Temperature has increasing trend in the northern Pakistan, therefore, the concerned stakeholders need to make rational plans for higher river flow/flood situation due to snow and glacier melt.
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Mudança Climática , Rios , Camada de Gelo , Paquistão , TemperaturaRESUMO
BACKGROUND: Facial aesthetics is a major motivating factor for undergoing orthodontic treatment. OBJECTIVES: To ascertain-by means of artificial intelligence (AI)-the influence of dental alignment on facial attractiveness and perceived age, compared to other modifications such as wearing glasses, earrings, or lipstick. MATERIAL AND METHODS: Forty volunteering females (mean age: 24.5) with near perfectly aligned upper front teeth [Aesthetic Component scale of the Index of Orthodontic Treatment Need (AC-IOTN) = 1 and Peer Assessment Rating Index (PAR Index) = 0 or 1] were photographed with a standardized pose while smiling, in the following settings (number of photographs = 960): without modifications, wearing eyeglasses, earrings, or lipstick. These pictures were taken with natural aligned dentition and with an individually manufactured crooked teeth mock-up (AC-IOTN = 8) to create the illusion of misaligned teeth. Images were assessed for attractiveness and perceived age, using AI, consisting of a face detector and deep convolutional neural networks trained on dedicated datasets for attractiveness and age prediction. Each image received an attractiveness score from 0 to 100 and one value for an age prediction. The scores were descriptively reviewed for each setting, and the facial modifications were tested statistically whether they affected the attractiveness score. The relationship between predicted age and attractiveness scores was examined with linear regression models. RESULTS: All modifications showed a significant effect (for all: P < 0.001) on facial attractiveness. In faces with misaligned teeth, wearing eyeglasses (-17.8%) and earrings (-3.2%) had an adverse effect on facial aesthetics. Tooth alignment (+6.9%) and wearing lipstick (+7.9%) increased attractiveness. There was no relevant effect of any assessed modifications or tooth alignment on perceived age (all: <1.5 years). Mean attractiveness score declined with predicted age, except when wearing glasses, in which case attractiveness was rated higher with increasing predicted age. CONCLUSIONS: Alignment of teeth improves facial attractiveness to a similar extent than wearing lipstick, but has no discernable effect on perceived age. Wearing glasses reduces attractiveness considerably, but this effect vanishes with age.
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Inteligência Artificial , Má Oclusão , Adulto , Estética Dentária , Face , Feminino , Humanos , Índice de Necessidade de Tratamento Ortodôntico , Lactente , Má Oclusão/terapia , Sorriso , Adulto JovemRESUMO
The visualization of metabolic flux in real time requires sensor molecules that transduce variations of metabolite concentrations into an appropriate output signal. In this regard, fluorogenic RNA-based biosensors are promising molecular tools as they fluoresce only upon binding to another molecule. However, to date no such sensor is available that enables the direct observation of key metabolites in mammalian cells. Toward this direction, we selected and characterized an RNA light-up sensor designed to respond to fructose 1,6-bisphosphate and applied it to probe glycolytic flux variation in mammal cells.
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Técnicas Biossensoriais , RNA , Animais , Glicólise , Mamíferos/metabolismo , RNA/metabolismoRESUMO
The evolution of complex phenotypes like reproductive strategies is challenging to understand, as they often depend on multiple adaptations that only jointly result in a specific functionality. Sulawesi ricefishes (Adrianichthyidae) evolved a reproductive strategy termed as pelvic brooding. In contrast to the more common transfer brooding, female pelvic brooders carry an egg bundle connected to their body for weeks until the fry hatches. To examine the genetic architecture of pelvic brooding, we crossed the pelvic brooding Oryzias eversi and the transfer brooding Oryzias nigrimas (species divergence time: â¼3.6 my). We hypothesize, that a low number of loci and modularity have facilitated the rapid evolution of pelvic brooding. Traits associated to pelvic brooding, like rib length, pelvic fin length, and morphology of the genital papilla, were correlated in the parental species but correlations were reduced or lost in their F1 and F2 hybrids. Using the Castle-Wright estimator, we found that generally few loci underlie the studied traits. Further, both parental species showed modularity in their body plans. In conclusion, morphological traits related to pelvic brooding were based on a few loci and the mid-body region likely could evolve independently from the remaining body parts. Both factors presumably facilitated the evolution of pelvic brooding.