Alternative Template Research Articles

Optimizing lactic acid production for agricultural wastes revalorization via sugars hydrothermal conversion with zirconia-based catalysts: response surface methodology

The hydrothermal conversion of a complex sugars solution comprising glucose, arabinose, and xylose with zirconia-based catalysts to produce lactic acid (LA) was studied. Catalysts were synthesized by a simple template-assisted sol–gel method. Alternative template removal procedures, such as refluxing ethanol extraction, were compared to the conventional direct calcination. The catalyst obtained after ethanol extraction (Z-Ex) reported the highest specific surface area (323 m2 g−1), total pore volume (0.21 cm3 g−1) and density of acid sites (1.111 µmol m−2), with a significant contribution of strong acid sites. On the other hand, template removal by thermal treatment transformed the hydrous zirconia into crystalline tetragonal phase, reducing the specific surface area and removing most of the acid sites. Catalytic tests were carried out in a stirred batch reactor, resulting Z-Ex the most selective towards LA production. A four-factor experimental design was performed for Z-Ex catalyst by varying temperature, reaction time, initial pressure, and catalyst/reactants ratio. Results were analyzed using the response surface methodology (RSM) to maximize the LA production. A molar yield of 61.2% towards LA and complete sugars conversion were reached at optimized operating conditions: 189 °C, 208 min, 0.5 g catalyst g−1 reactants, and 10 bar N2. Additionally, fitting models for main by-products molar yields (furans, glyceraldehyde, glycolic, formic, acetic, and levulinic acids) were obtained with good accuracy prediction. All responses were jointly studied to understand the reaction mechanisms involved in generation of intermediaries and undesired degradation products.Graphical Abstract

Establishment of decellularized extracellular matrix scaffold derived from caprine pancreas as a novel alternative template over porcine pancreatic scaffold for prospective biomedical application.

In this study, the caprine pancreas has been presented as an alternative to the porcine organ for pancreatic xenotransplantation with lesser risk factors. The obtained caprine pancreas underwent a systematic cycle of detergent perfusion for decellularization. It was perfused using anionic (0.5% w/v sodium dodecyl sulfate) as well as non-ionic (0.1% v/v triton X-100, t-octyl phenoxy polyethoxy ethanol) detergents and washed intermittently with 1XPBS supplemented with 0.1% v/v antibiotic and nucleases in a gravitation-driven set-up. After 48h, a white decellularized pancreas was obtained, and its extracellular matrix (ECM) content was examined for scaffold-like properties. The ECM content was assessed for removal of cellular content, and nuclear material was evaluated with temporal H&E staining. Quantified DNA was found to be present in a negligible amount in the resultant decellularized pancreas tissue (DPT), thus prohibiting it from triggering any immunogenicity. Collagen and fibronectin were confirmed to be preserved upon trichrome and immunohistochemical staining, respectively. SEM and AFM images reveal interconnected collagen fibril networks in the DPT, confirming that collagen was unaffected. sGAG was visualized using Prussian blue staining and quantified with DMMB assay, where DPT has effectively retained this ECM component. Uniaxial tensile analysis revealed that DPT possesses better elasticity than NPT (native pancreatic tissue). Physical parameters like tensile strength, stiffness, biodegradation, and swelling index were retained in the DPT with negligible loss. The cytocompatibility analysis of DPT has shown no cytotoxic effect for up to 72h on normal insulin-producing cells (MIN-6) and cancerous glioblastoma (LN229) cells in vitro. The scaffold was recellularized using isolated mouse islets, which have established in vitro cell proliferation for up to 9 days. The scaffold received at the end of the decellularization cycle was found to be non-toxic to the cells, retained biological and physical properties of the native ECM, suitable for recellularization, and can be used as a safer and better alternative as a transplantable organ from a xenogeneic source.

Abstract 5688: RNA-mediated DNA repair: A novel repair pathway in homologous recombination-deficient cancers

Abstract Genome instability has long been considered the primary driver of most cancer types. A double strand break (DSB) in DNA can have deleterious consequences for a cell, which if not repaired faithfully, can lead to mutations and chromosomal rearrangements, or even cell death. DSBs can be processed by several DNA repair pathways, of which homologous recombination (HR) is the preferred method due to its error-free nature. HR uses an intact homologous DNA sequence as a template for recovering the information lost at the break site. A significant proportion of all cancers, especially triple-negative breast, ovarian pancreatic and prostate cancers, have loss of function alterations affecting genes involved in HR-mediated DNA repair. Alternate repair pathways operate when HR is defective in tumors, but the pathways operative in this context remain a matter of contention. Previous work in vivo in yeast and in vitro systems has established a new role of RNA in DNA repair. Owing to its abundance in the cell and its sequence similarity to parental DNA, we sought to define whether RNA can act as a template for the repair of DSBs in human cells. We developed a novel high throughput assay to test if DNA breaks can be repaired using RNA as an alternative template in mammalian cells. Human cells were transfected with a guide RNA cloned in a Cas9 expression vector to generate a site-specific DSB at the AAVS1 locus, a safe harbour, in the human genome. Furthermore, a donor template in the form of DNA or RNA (homologous to the DSB locus) containing a unique mutational signature was provided at the time of transfection. The unique mutational signature enables us to determine if the donor has been utilized as a template for DNA repair. Using this assay, we demonstrate that cells can use a spliced RNA transcript as a functional template to repair a DSB. We have identified that Rev3L, a key component of the translesion synthesis polymerase Pol Zeta (ζ), has a novel reverse-transcriptase activity in human cells and can help repair the DSB using RNA as a template. Further characterization of this repair pathway and its associated mutational scar will provide new insights into the mutational signatures seen in HR-defective cancers, enabling a better understanding of the DNA repair pathways upregulated in these tumours. The proposed studies could help prioritize novel therapeutic approaches by exploiting synthetic lethality in HR-deficient cancers as well as HR-proficient cancers when used in combinatorial cancer therapy. Citation Format: Manisha Jalan, Juber Patel, Kyrie S Olsen, Sana Ahmed-Seghir, Daniel S Higginson, Jorge S Reis-Filho, Nadeem Riaz, Simon N Powell. RNA-mediated DNA repair: A novel repair pathway in homologous recombination-deficient cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5688.

Building micro-capsules using water-in-water emulsion droplets as templates

The use of templates in materials chemistry is a well-established approach for producing membrane-bounded hollow spheres used for microencapsulation applications, but also in synthetic biology to assemble artificial cell-like compartments. Sacrificial solid or gel micro-particles, but also liquid-like oil-in-water or water-in-oil emulsion droplets are routinely used as templates to produce capsules. Yet, disruption of the core sacrificial material often requires harsh experimental conditions, such as organic solvents, which limits the use of such approach to encapsulate fragile solutes, including biomolecules. Recently, water-in-water emulsion droplets have emerged as promising alternative templates to produce capsules in solvent-free conditions. These water-in-water droplets result from liquid-liquid phase separation in dilute aqueous polymer or surfactants solutions. Their ease of preparation, the large palette of components they can be assembled from and the lack of harsh solvent or oil used for their production make water-in-water emulsions of practical importance in materials chemistry. Water-in-water droplets can also spontaneously sequester solutes by equilibrium partitioning, which provides a simple strategy to locally accumulate molecules of interest and encapsulate them in capsules after interfacial shell formation. Here, we review recent works that employ water-in-water emulsion droplets to prepare capsules and suggest possible additional applications in materials chemistry.

Functional Subdivisions of the Cerebellum in Naturalistic Paradigm Functional Magnetic Resonance Imaging.

Compelling evidence has suggested that the human cerebellum is engaged in a wide range of cognitive tasks besides traditional opinions of motor control, and it is organized into a set of distinct functional subregions. The existing model-driven cerebellum parcellations through resting-state functional MRI (rsfMRI) and task-fMRI are relatively coarse, introducing challenges in resolving the functions of the cerebellum especially when the brain is exposed to naturalistic environments. The current study took the advantages of the naturalistic paradigm (i.e., movie viewing) fMRI (nfMRI) to derive fine parcellations via a data-driven dual-regression-like sparse representation framework. The parcellations were quantitatively evaluated by functional homogeneity, and global and local boundary confidence. In addition, the differences of cerebellum–cerebrum functional connectivities between rsfMRI and nfMRI for some exemplar parcellations were compared to provide qualitatively functional validations. Our experimental results demonstrated that the proposed study successfully identified distinct subregions of the cerebellum. This fine parcellation may serve as a complementary solution to existing cerebellum parcellations, providing an alternative template for exploring neural activities of the cerebellum in naturalistic environments.

Understanding Imagination in Entrepreneurship

Abstract Using interviews to explore the role imagination plays in the South American Nikkei phenomenon (a fusion of Japanese haute cuisine with Peruvian ingredients) and employing the alternate templates research strategy to analytically compare three entrepreneurial behaviors (adaptive bricolage, strategic planning, and transformative effectuation), this case study found that the current theoretical boundary conditions are insufficient to separate the three archetypes. Therefore, based on data, new concepts are proposed to explain entrepreneurial behaviors where they overlap (e.g., creative imagination as a bridging construct of the entrepreneurial process). A novel entrepreneurial trilemma and a behavioral model focused on the conceptual overlaps are introduced to frame the new concepts and to visually depict the relationships between them.

Systematic biopsy should not be omitted in the era of combined magnetic resonance imaging/ultrasound fusion-guided biopsies of the prostate

To evaluate prostate cancer detection rates with classical trans-rectal ultrasound-guided systematic 10-core biopsies (SB), targeted biopsies (TB) guided by magnetic resonance (MR)/US fusion imaging and their combination in biopsy-naïve and patients with previously negative prostate biopsies. We compared pathology results after radical prostatectomy with biopsy findings. Consecutive patients with prostate imaging-reporting and data system lesions grade ≥ 3 submitted to MRI/US-guided TB and subsequent standard 10-core SB between December 2015 and June 2019 were analyzed. Detection rate (TB- or SB-positive) in 563 included patients (192 naïve, 371 with previous biopsies) was 56.7% (67.7% for the first, 50.9% for repeated biopsies). With TB (disregarding SB), the rates were 41.4%, 52.1% and 35.8%, respectively. With SB (disregarding TB), the rates were 49.1%, 63.0% and 41.8%, respectively. Eventually, 118 patients underwent surgery and clinically significant cancer was found in 111 (94.1%) specimens. Of those, 23 (20.7%) would have been missed had we relied upon a negative TB and 14 (12.6%) would have been missed had we relied upon a negative SB, disregarding a positive finding on the alternative biopsy template. SB should not be omitted since TB and SB combination have higher detection rate of clinically relevant prostate cancer than either procedure alone.

An Alternative Dermal Template for Reconstruction of Complex Upper Extremity Wounds.

Summary:The management of upper extremity soft-tissue defects with full-thickness skin loss and denuded tendon and/or bone traditionally requires vascularized tissue reconstruction. Herein, we present patient outcomes utilizing Novosorb Bio-degradable Temporizing Matrix (PolyNovo, Wilmington, Del.), a novel bilaminar dermal regenerative template, followed by skin grafting, for reconstruction of complex upper extremity injuries with exposed tendon and/or bone. We retrospectively reviewed all patients treated at our Level I trauma center with upper extremity trauma and exposed tendon and/or bone who had application of Novosorb Bio-degradable Temporizing Matrix over a 1-year period. At the time of surgery, all nonviable tissue was debrided, and the product was applied according to the manufacturer’s instructions. If required, split thickness skin grafting was performed once neodermis appeared perfused, or after the sealing layer delaminated spontaneously. Six patients (four men, two women) with an average age of 49.8 (35–60) years were included in the study. Average defect size measured 97 cm2 (10–440). Average time to complete healing was 45 days (27–57). Three patients reepithelialized spontaneously and did not require grafting; average defect size in these patients was 26 cm2 (10–42). There were no infections and no loss of the dermal matrix or skin graft, when performed. All patients healed without complication after grafting and did not require further surgical treatment. Therefore, we contend that Novosorb BTM is a dermal regenerative template that shows potential as an alternative option to flap reconstruction in select patients after upper extremity trauma and soft-tissue defects with exposed tendon and/or bone. Further studies will be required to refine indications and evaluate outcomes.

MRI brain templates of the male Yucatan minipig

The pig is growing in popularity as an experimental animal because its gyrencephalic brain is similar to humans. Currently, however, there is a lack of appropriate brain templates to support functional and structural neuroimaging pipelines. The primary contribution of this work is an average volume from an iterative, non-linear registration of 70 five- to seven-month-old male Yucatan minipigs. In addition, several aspects of this study are unique, including the comparison of linear and non-linear template generation, the characterization of a large and homogeneous cohort, an analysis of effective resolution after averaging, and the evaluation of potential in-template bias as well as a comparison with a template from another minipig species using a “left-out” validation set. We found that within our highly homogeneous cohort, non-linear registration produced better templates, but only marginally so. Although our T1-weighted data were resolution limited, we preserved effective resolution across the multi-subject average, produced templates that have high gray-white matter contrast and demonstrate superior registration accuracy compared to an alternative minipig template.

Meiotic DNA break repair can utilize homolog-independent chromatid templates in C. elegans

During meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes.1 In meiotic prophase I, double-strand DNA breaks (DSBs) are induced and a subset of these DSBs are repaired as interhomolog crossovers to ensure proper chromosome segregation. DSBs not resolved as crossovers with the homolog must be repaired by other pathways to ensure genome integrity.2 To determine if alternative repair templates can be engaged for meiotic DSB repair during oogenesis, we developed an assay to detect sister and/or intra-chromatid repair events at a defined DSB site during Caenorhabditis elegans meiosis. Using this assay, we directly demonstrate that the sister chromatid or the same DNA molecule can be engaged as a meiotic repair template for both crossover and noncrossover recombination, with noncrossover events being the predominant recombination outcome. We additionally find that the sister or intra-chromatid substrate is available as a recombination partner for DSBs induced throughout meiotic prophase I, including late prophase when the homolog is unavailable. Analysis of noncrossover conversion tract sequences reveals that DSBs are processed similarly throughout prophase I. We further present data indicating that the XPF-1 nuclease functions in late prophase to promote sister or intra-chromatid repair at steps of recombination following joint molecule processing. Despite its function in sister or intra-chromatid repair, we find that xpf-1 mutants do not exhibit severe defects in progeny viability following exposure to ionizing radiation. Overall, we propose that C.elegans XPF-1 may assist as an intersister or intrachromatid resolvase only in late prophase I.

Short-range template switching in great ape genomes explored using pair hidden Markov models.

Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes' genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons.

Near-Infrared Chiral Plasmonic Microwires through Precision Assembly of Gold Nanorods on Soft Biotemplates

Directing the assembly of plasmonic nanoparticles into chiral superstructures has diverse applications including, chiroptical sensing, nonlinear optics, and biomedicine. Though soft template-mediated assemblies of both spherical and nonspherical gold nanoparticles have made significant progress, most approaches require sophisticated chemical synthesis or advanced methodologies. Besides, reports of structurally precise chiral plasmonic assemblies beyond nanoscale are limited. Here, we propose an efficient yet simple strategy to grow such precision assemblies up to mesoscale, which is beneficial for a broader community. Briefly, cationic gold nanorods (AuNRs) are allowed to systematically assemble along atomically precise, chiral, rodlike tobacco mosaic virus (TMV) particles via electrostatic attraction under ambient condition. This leads to spontaneous formation of helical hybrid microwires with high structural precision, as evidenced by cryogenic transmission electron microscopy and tomography. Resulting composite superstructures show a strong circular dichroism response at the plasmon wavelength of the AuNRs, which is supported by simulations using discrete dipole approximation. Further, chirality of the system is investigated at a single-microwire level using polarized dark-field scattering microscopy. An alternative chiral template, negatively charged colloidal cellulose nanocrystals, also arrange AuNRs into similar chiral microstructures. Thus, our report proposes a generic methodology to obtain chiral plasmonic response at the NIR region using inexpensive templates that will encourage the exploration of a wider range of nanoscale templates for creating hybrid mesostructures with emerging optoelectronic properties.

Multiple and Sustained Climaxes in Icelandic Post-Rock: For an Expansion of the Notion of Musical Climax

Effects produced by music and sex are similar insofar as they make us feel the present moment intensely (Frith 1996): this is probably the reason why our discourses frequently borrow vocabulary from the sexual lexical field when we want to name instants where our musical perception is most stimulated. The word “climax” is a transparent example, since it can literally refer to an orgasm, but is also used to talk about the intensity peak of a piece of music. This metaphor comes with unfortunate restrictions, in this case, the viewing of a climax as the equivalent of one standardized representation of male pleasure – the single orgasm. Yet, to see a musical climax as an intensity peak preceded by a crescendo and followed by an immediate fallout has its limits. It is generally relevant in tonal, classical music, but this outline loses its accuracy when it comes to other genre families, like rock music, which progresses step by step, and does not necessarily include one precise identifiable peak.This article focuses on a post-rock corpus and shows the importance of a more flexible use of the notion of climax in musicology. The studied climaxes, shaped as long sections instead of one-time peaks, illustrate how musical analysis can benefit from alternative templates, namely those of multiple and sustained orgasms. Using these two models as formal references, and relying on Brad Osborn’s work (2013), which evidenced the role of terminal climactic sections in recent rock music, this paper stresses the internal crescendos of the climactic sections often – but not exclusively – heard in post-rock. Their form, instrumentation, harmonic strategies, use of technology and performance highlight the main characteristics of these expanded climaxes: an extended temporality, replicability and reduced teleology.

Template Enhancement and Mask Generation for Siamese Tracking

Siamese tracking methods have become the focus of visual tracking in recent years. Advanced Siamese trackers perform well on certain benchmarks, but there are still some limitations. First, most Siamese trackers adopt the initial frame as a single template, which leads to underfitting and reduces the ability to predict instances. Second, mainstream trackers report a rectangular bounding box as a prediction, resulting in poor accuracy of non-rigid objects. Therefore, we propose the template enhancement and mask generation for Siamese tracking. Given that the essence of Siamese trackers is instance learning, we propose constructing an alternative template explicitly to address the underfitting of the instance space. Moreover, in order to improve the tracking accuracy, we obtain the descriptor aggregation to transform the semantic segmentation outputs for mask prediction. Finally, we propose the SiamEM through the fusion of the above approaches. Comprehensive experiments show that template enhancement and mask generation significantly improve Siamese trackers on benchmarks.

A semi-covalent molecularly imprinted fluorescent sensor for highly specific recognition and optosensing of bisphenol A.

A novel mesoporous fluorescent molecularly imprinted sensor for selective detection of bisphenol A (BPA) in food materials was fabricated via a semi-covalent imprinting method. The imprinting precursor that served as an alternative template molecule for BPA was prepared via thermally reversible isocyanate bonding, which effectively improved the imprinting efficiency for the molecularly imprinted sensor. Carbon dots (CDs) were embedded in mesoporous silica as signal recognition elements that exhibited quenching upon BPA binding. Subsequently, through the sol-gel process, the molecularly imprinted layer was coated on the CDs silica layer and provided specific recognition sites for BPA. The composite of CDs embedded in the mesoporous molecularly imprinted polymer (CDs@MIP) was characterized with scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurements and thermogravimetric analysis. The mechanism of carbon dots quenching and the high selectivity of CDs@MIP towards BPA were explored. The linear response range of the sensor was from 0.025 mg L-1 to 2 mg L-1 with a limit of detection of 0.016 mg L-1. The method was successfully applied for the determination of food samples and recoveries ranged from 92.5% to 101.1%. The BPA contents in actual samples were determined using high performance liquid chromatography and the proposed sensor, showing no significant difference between the two methods.

Registration quality filtering improves robustness of voxel-wise analyses to the choice of brain template

MotivationMany clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results. ResultsWe present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a “distance” between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice.

The dynamics of SME growth processes and the role of enabling constraints: an evidence-based theoretical framework

PurposeThis paper aims to explain the dynamics of entrepreneurial decisions and actions (D&As) in the small and medium-sized enterprise (SME) growth process. The study focuses on the changing portfolio and relationship governance and captures these dynamics by using the concept of “enabling constraints” (ECs).Design/methodology/approachIn-depth, long-term and multiple-case study method was adopted based on six high-growth SMEs. Pattern-matching and alternative template approach formed a basis for developing a research framework, further corroborated and advanced in the empirical study.FindingsThe research provides empirical evidence of ECs as entrepreneurial perceptions that both limit (constrain) the range of accessible options and facilitate (enable) new opportunities. This study’s results point to how owner-managers' judgments about growth motives and rationales constrain their choices and how they enable new directions, acknowledging the changing context.Originality/valueThis work contributes to the research on SME growth processes by specifying their dynamics in terms of a creative mutual causality. Here, D&As stem from entrepreneurs' perceptions that are affected by the context, with the latter also shaped by prior decisions and actions. This theoretical contribution has been synthesized in the form of a framework of ECs in the SME growth process with related propositions.

Chromosome-wide characterization of meiotic noncrossovers (gene conversions) in mouse hybrids.

During meiosis, the recombination-initiating DNA double-strand breaks (DSBs) are repaired by crossovers or noncrossovers (gene conversions). While crossovers are easily detectable, noncrossover identification is hampered by the small size of their converted tracts and the necessity of sequence polymorphism. We report identification and characterization of a mouse chromosome-wide set of noncrossovers by next-generation sequencing of 10 mouse intersubspecific chromosome substitution strains. Based on 94 identified noncrossovers, we determined the mean length of a conversion tract to be 32 bp. The spatial chromosome-wide distribution of noncrossovers and crossovers significantly differed, although both sets overlapped the known hotspots of PRDM9-directed histone methylation and DNA DSBs, thus supporting their origin in the standard DSB repair pathway. A significant deficit of noncrossovers descending from asymmetric DSBs proved their proposed adverse effect on meiotic recombination and pointed to sister chromatids as an alternative template for their repair. The finding has implications for the molecular mechanism of hybrid sterility in mice from crosses between closely related Mus musculus musculus and Mus musculus domesticus subspecies.

Design, synthesis, and biological activity of novel 1,2,4-oxadiazole derivatives

BackgroundPlant diseases seriously threaten food security, it is urgent to discover efficient and low-risk chemical pesticides. 1,2,4-Oxadiazole derivatives exhibit broad spectrum of agricultural biological activities. For discovering novel molecules with excellent agricultural activities, novel 1,2,4-oxadiazole derivatives were synthesized and evaluated for their agricultural activities.ResultBioassays results showed that the title compounds exhibited moderate nematocidal activity against Meloidogyne incognita and anti-fungal activity to Rhizoctonia solani. It’s worth noting that compounds 5m, 5r, 5u, 5v, 5x and 5y showed strong antibacterial effects on Xanthomonas oryzae pv. oryzae (Xoo), with EC50 values of 36.25, 24.14, 28.82, 19.44, 25.37 and 28.52 μg/mL, respectively, superior to bismerthiazol (BMT, EC50 = 77.46 μg/mL) and thiodiazole copper (TDC, EC50 = 99.31 μg/mL). Compounds 5p, 5u and 5v exhibited excellent antibacterial ability against Xanthomonas oryzae pv. oryzicola (Xoc), with EC50 values of 31.40, 19.04 and 21.78 μg/mL, respectively, better than that of BMT (EC50 = 68.50 μg/mL) and TDC (EC50 = 91.05 μg/mL). In addition, compound 5v exerted moderate antibacterial effects on rice bacterial leaf blight.ConclusionsTwenty-six novel 1,2,4-oxadiazole derivatives were obtained and their biological activities were evaluated. Compound 5u and 5v exhibited excellent antibacterial activity Xoo and Xoc. These results indicated that 1,2,4-oxadiazole derivatives containing a trifluoromethyl pyridine moiety could be as potential alternative templates for discovering novel antibacterial agents.

Selective Affimers Recognise the BCL-2 Family Proteins BCL-xL and MCL-1 through Noncanonical Structural Motifs*.

: The BCL‐2 family is a challenging group of proteins to target selectively due to sequence and structural homologies across the family. Selective ligands for the BCL‐2 family regulators of apoptosis are useful as probes to understand cell biology and apoptotic signalling pathways, and as starting points for inhibitor design. We have used phage display to isolate Affimer reagents (non‐antibody‐binding proteins based on a conserved scaffold) to identify ligands for MCL‐1, BCL‐xL, BCL‐2, BAK and BAX, then used multiple biophysical characterisation methods to probe the interactions. We established that purified Affimers elicit selective recognition of their target BCL‐2 protein. For anti‐apoptotic targets BCL‐xL and MCL‐1, competitive inhibition of their canonical protein‐protein interactions is demonstrated. Co‐crystal structures reveal an unprecedented mode of molecular recognition; where a BH3 helix is normally bound, flexible loops from the Affimer dock into the BH3 binding cleft. Moreover, the Affimers induce a change in the target proteins towards a desirable drug‐bound‐like conformation. These proof‐of‐concept studies indicate that Affimers could be used as alternative templates to inspire the design of selective BCL‐2 family modulators and more generally other protein‐protein interaction inhibitors.