AlphaFold Models Illuminate Half of Dark Human Proteins

We investigate the use of confidence scores to predict the accuracy of a given AlphaFold model for drug discovery. Predicted accuracy is improved by eliminating confidence scores below 80, due to effects of disorder. 95% of models corresponding to a set of recent crystal structures are accurate at the fold level. Conformational discordance in the training set has a more significant effect on accuracy than sequence divergence. We propose criteria for models and residues that are possibly useful for virtual screening, by which AlphaFold provides models for half of understudied (dark) human proteins and two-thirds of residues in those models.

FoldHSphere: deep hyperspherical embeddings for protein fold recognition

Background Current state-of-the-art deep learning approaches for protein fold recognition learn protein embeddings that improve prediction performance at the fold level. However, there still exists aperformance gap at the fold level and the (relatively easier) family level, suggesting that it might be possible to learn an embedding space that better represents the protein folds. Results In this paper, we propose the FoldHSphere method to learn a better fold embedding space through a two-stage training procedure. We first obtain prototype vectors for each fold class that are maximally separated in hyperspherical space. We then train a neural network by minimizing the angular large margin cosine loss to learn protein embeddings clustered around the corresponding hyperspherical fold prototypes. Our network architectures, ResCNN-GRU and ResCNN-BGRU, process the input protein sequences by applying several residual-convolutional blocks followed by a gated recurrent unit-based recurrent layer. Evaluation results on the LINDAHL dataset indicate that the use of our hyperspherical embeddings effectively bridges the performance gap at the family and fold levels. Furthermore, our FoldHSpherePro ensemble method yields an accuracy of 81.3% at the fold level, outperforming all the state-of-the-art methods. Conclusions Our methodology is efficient in learning discriminative and fold-representative embeddings for the protein domains. The proposed hyperspherical embeddings are effective at identifying the protein fold class by pairwise comparison, even when amino acid sequence similarities are low.

COMPARISON OF THE EFFECT OF ANTIBIOTICS AND BACTERIOPHAGE PHAGE SAVB14 ON BIOFILMS FORMED BY STAPHYLOCOCCUS AUREUS VARIANT BOVIS

During the development of mastitis in cows, the formation of a biofilm pathogen is an effective way to preserve it in the microenvironment of mammary gland. Biofilm infections are difficult to treat with antimicrobials, and bacterial resistance to antibiotics increases to 1000-fold level, compared with what is observed when grown in planktonic conditions. The aim of study – to determine and compare the effect of antimicrobial drugs and bacteriophage Phage SAvB14 in the destruction of biofilms formed by S. aureus var. bovis. Isolation and species identification of staphylococci were performed according to conventional methods using BD Baird-Parker Agar medium (HiMedia, India). Determination of ability of staphylococci to form biofilms and the number of viable bacteria was determined by the Stepanovic method. The study of sensitivity of microorganisms in biofilm form was performed on daily microbial biofilms grown in plastic Petri dishes. After 24 hours of incubation of cultures, the dishes were washed three times from planktonic (unattached) microorganisms with sterile phosphate buffer and introduced the studied antibacterial agents. After exposure, the dishes were washed three times with sterile phosphate buffer, introduced 5 cm3 of sterile 0.9% sodium chloride solution and washed the biofilm, took 1.0 cm3 of suspension, prepared a series of ten-fold dilutions, inoculated 1.0 cm3 of each dilution in Petri dishes, poured MPA and incubated at temperature of 370C for 24–48 hours to determine the number of bacteria. In determining the effect of antibiotics on bacterial biofilms, it was found that of the studied antibiotics, enrofloxacin worked best probably due to its low molecular weight and ability to penetrate the pores and channels of the biofilm to microbial cells. After the action of enrofloxacin on biofilms, staphylococcal bacteria were completely inactivated. Also, the antibiotics ceftriaxone and doxycycline were effective against bacteria in biofilms. After the action of ceftriaxone, the number of surviving bacteria was lg 1.9 ± 1.1 CFU/cm2 of biofilm area, and doxycycline lg 2.5 ± 1.2 CFU/cm2. At the same time, under the action of antibiotics penicillins, aminoglycosides and macrolides, the number of surviving microbial cells was about lg 5.3 CFU/cm2 of biofilm area. In studies on the effect of bacteriophage Phage SAvB14 on biofilms formed by S. aureus var. bovis, there was their degradation. At this, viable microbial cells from the biofilm were not isolated. In this case, we can say that the phages penetrated and reached the staphylococcal cells throughout the thickness of biofilm and bacteria were susceptible to this phage. That is, there was a passive treatment of biofilm with phages, in which lysis depended on the rate of virus uptake. Therefore, the obtained results of laboratory studies indicate the prospects of effective use of our selected specific staphylococcal bacteriophage Phage SAvB14 for the destruction of biofilm formed by S. aureus var. bovis – in mastitis of cows.

Benchmarking fold detection by DaliLite v.5

Motivation Protein structure comparison plays a fundamental role in understanding the evolutionary relationships between proteins. Here, we release a new version of the DaliLite standalone software. The novelties are hierarchical search of the structure database organized into sequence based clusters, and remote access to our knowledge base of structural neighbors. The detection of fold, superfamily and family level similarities by DaliLite and state-of-the-art competitors was benchmarked against a manually curated structural classification. Results Database search strategies were evaluated using Fmax with query-specific thresholds. DaliLite and DeepAlign outperformed TM-score based methods at all levels of the benchmark, and DaliLite outperformed DeepAlign at fold level. Hierarchical and knowledge-based searches got close to the performance of systematic pairwise comparison. The knowledge-based search was four times as efficient as the hierarchical search. The knowledge-based search dynamically adjusts the depth of the search, enabling a trade-off between speed and recall. Availability and implementation http://ekhidna2.biocenter.helsinki.fi/dali/README.v5.html. Supplementary information Supplementary data are available at Bioinformatics online.

Confirmation of Glyphosate- and Acetolactate Synthase (ALS)-Inhibitor-Resistant Kochia (Kochia scoparia) in Nebraska

<p>Kochia is an early emerging weed of increasing concern across the Great Plains region of the United States due to the evolution of resistance to herbicides. Greenhouse studies were conducted to confirm and characterize the level of glyphosate and acetolactate synthase (ALS)-inhibiting herbicide resistance in kochia biotype collected from a field in Sheridan County in Nebraska. The response of kochia biotype to 9 rates (0 to 16×) of tribenuron and glyphosate was evaluated in a whole plant dose-response bioassay. On the basis of the values at the 90% effective dose (ED₉₀), the putative-resistant kochia biotype had a 6- and 15-fold level of resistance to glyphosate and tribenuron, respectively. Future research will evaluate strategies for the management of glyphosate- and ALS-resistant kochia under field conditions.</p>

The Biogeochemistry of Lantanides in Soils

The lithogenous minerals containing lantanides (Ln) are unsustainable within the zone of hypergenesis. Their dilution impoverish soils in terms of lantanides content, especially in humid regions. In conditions of neutral environmental pH in dry steppe zone, the lantanides loose their mobility, and, hence, become unavailable for plants. The lantanides are characterized by the high biochemical and biological activity. The physiologic impact of lantanides on plants is set. The separate parts of vascular plants accumulate lantanides in different degree. The difference may reach 100-fold level. For many plants the accumulation of lantanides occurs at the reverse order: roots > leaves > stalks > grain/fruits. Lantanides accumulators (such as brackens), promote their accumulation within the humus layer of soils. Fertilizers with lantanides are widely implemented in China. They powder seeds and implement top dressing in soils with lantanides deficit, i.e., with low bulk content and/or with low availability for plants. Although at moderate increasing of Ln concentration in solution, there is often observed the increasing of the crop yield in laboratory conditions. However, the implementation of lantanides in the soil does not always give the positive effect. The main share of Ln in the soils with high sorption capacity is sorbed, and the increasing of doses leads to the decrease of the yield. The light lantanides are characterized by physical and chemical properties equal to Cа2+. And the mass replacement of Cа2+ by lantanides harms the development of plants. The high doses of lantanides have a negative impact on the biochemical processes in plants. The competition with iron and phosphorus is stipulated by the close solubility of iron and lanthanum phosphates: the accumulation of La in plants tissues affects the content of P and Fe within them.

Noncompetitive Growth and Fecundity of Wisconsin Giant Ragweed Resistant to Glyphosate

Glyphosate-resistant giant ragweed has been confirmed in several Midwestern states. In some cases, weed resistance to glyphosate has been shown to carry a fitness penalty. Previous research has found that a glyphosate-resistant giant ragweed biotype from Indiana with a rapid necrosis response to glyphosate displayed early, rapid growth in the absence of glyphosate, flowered earlier, but produced 25% less seed than a sensitive biotype, suggesting that there may be a fitness penalty associated with the rapid necrosis resistance trait. In Wisconsin, we have recently identified a giant ragweed accession with a 6.5-fold level of resistance to glyphosate that does not demonstrate the rapid necrosis response. Our objective was to determine the noncompetitive growth and fecundity of the resistant accession in the absence of glyphosate, relative to a sensitive accession from a nearby field border population. In greenhouse experiments, plant height, leaf area, and dry shoot biomass were similar between the resistant and sensitive accessions during vegetative growth to the onset of flowering. The instantaneous relative growth rate, instantaneous net assimilation rate, and instantaneous leaf area ratio also did not differ between accessions. However, fecundity of resistant plants (812 seeds plant−1) was greater (P = 0.008) than sensitive plants (425 seeds plant−1). The percentage of intact viable seeds, intact nonviable seeds, and empty involucres did not differ between resistant and sensitive accessions. These results indicate that resistance of this accession of giant ragweed to glyphosate has not affected its growth and development relative to a sensitive accession. The greater fecundity and similar viability of resistant plants relative to sensitive plants suggests that in the absence of selection by glyphosate, the frequency of the resistance trait for glyphosate may increase in the giant ragweed field population over time.

Confirmation and Control of Triazine and 4-Hydroxyphenylpyruvate Dioxygenase-Inhibiting Herbicide-Resistant Palmer Amaranth (Amaranthus palmeri) in Nebraska

Palmer amaranth is a difficult-to-control broadleaf weed that infests corn and soybean fields in south-central and southwestern Nebraska and several other states in the United States. The objectives of this research were to confirm triazine and 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide-resistant Palmer amaranth in Nebraska and to determine sensitivity and efficacy of POST-applied corn herbicides for control of resistant and susceptible Palmer amaranth biotypes. Seeds from a putative HPPD-resistant Palmer amaranth biotype from Fillmore County, NE were collected from a seed corn production field in fall 2010. The response of Palmer amaranth biotypes to 12 rates (0 to 12×) of mesotrione, tembotrione, topramezone, and atrazine was evaluated in a dose–response bioassay in a greenhouse. On the basis of the values at the 90% effective dose (ED90) level, the analysis showed a 4- to 23-fold resistance depending upon the type of HPPD-inhibiting herbicide being investigated and susceptible biotype used for comparison. This biotype also had a 9- to 14-fold level of resistance to atrazine applied POST. Results of a POST-applied herbicide efficacy study suggested a synergistic interaction between atrazine and HPPD-inhibiting herbicides that resulted in > 90% control of all Palmer amaranth biotypes. The resistant biotype had a reduced sensitivity to acetolactate synthase inhibiting herbicides (halosulfuron and primisulfuron), a photosystem-II inhibitor (bromoxynil), and a protoporphyrinogen oxidase inhibitor (fluthiacet-methyl). Palmer amaranth biotypes were effectively controlled (≥ 90%) with glyphosate, glufosinate, and dicamba, whereas 2,4-D ester provided 81 to 83% control of the resistant biotype and > 90% control of both susceptible biotypes.