Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Synthesis of N'-Substituted-2-(5-(4-Chlorophenyl)-1,3,4- oxadiazol-2-ylthio)acetohydrazide Derivatives as Suitable Antibacterial Agents

Purpose: To evaluate antibacterial activity of a series of molecules bearing 1,3,4-oxadiazole and azomethine moieties.Methods: The 4-chlorobenzoic acid (1) was precursor to N'-substituted-2-(5-(4-chlorophenyl)-1,3,4- oxadiazol-2-ylthio)acetohydrazide, 8a-p, through a multistep synthesis of corresponding ester, 2, hydrazide, 3 and 1,3,4-oxadiazole, 4. The molecule, 4, was subjected to electrophilic substitution by ethyl-2-bromoacetate to yield 5 which was stepped to 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2- ylthio)acetohydrazide (6). The target molecules, 8a-p, were synthesized by nucleophilic addition of 6 to arylaldehydes, 7a-p. The proposed structures of all the synthesized molecules were elucidated by Infra Red (IR), Proton Nuclear Magnetic Resonance (1H-NMR) and Electron Impact Mass Spectrometry (EIMS) spectral data. Antibacterial activity was evaluated by the principle that microbial growth is in a log phase of growth and so results in increased absorbance of broth medium which is observed.Results: The molecule, 8b, was active against S. aureus and 8c against S. typhi only. The molecule, 8p, was the most active against S. typhi with minimum inhibitory concentration (MIC) value of 10.04 ± 1.25 μM while 8e was active against E. coli with MIC of 9.45 ± 1.00 μM, both relative to the reference standard, ciprofloxacin, which displayed MIC of 9.13 ± 2.00 and 8.90 ± 1.65 μM, respectively.Conclusion: Most of the synthesized molecules exhibit 50 % antibacterial activity relative to the reference. Molecules 8b and 8c are the least active compounds.Keywords: 1,3,4-Oxadiazole, 4-Chlorobenzoic acid, Antibacterial activity, Azomethin

Synthesis and antibacterial evaluation of 2-(1,3- Benzodioxol-5-ylcarbonyl)arylsulfonohydrazide derivatives

Purpose: To study the antibacterial activity of various sulfonamides derived from 1,3-benzodioxol-5- carbohydrazide.Methods: The synthesis involved the conversion of 1,3-benzodioxol-5-carboxylic acid (1) to ethyl 1,3- benzodioxol-5-carboxylate (2) and then to 1,3-benzodioxol-5-carbohydrazide (3). The target molecules, 2-(1,3-benzodioxol-5-ylcarbonyl)arylsulfonohydrazide derivatives (5a-l) were synthesized through a benignant method from aqueous medium by the reaction of 3 and arylsulfonyl chlorides (4a-l). The structural formulae of the synthesized compounds were characterized by infra red spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR) and electron impact mass spectrometry (EI-MS). The compounds were screened for in vitro antibacterial activity by determining their minimum inhibitory concentration (MIC).Results: The molecule, 5k, bearing 2-hydroxy-3,5-dichlorophenyl group exhibited the highest activity with MIC of 11.92 ± 3.40 (S. typhi), 8.37 ± 2.22 (E. coli), 9.28 ± 2.31 (P. aeroginosa), 11.76 ± 1.30 (B. subtilis) and 10.30 ± 1.63 (S. aureus) μmoles/L relative to that of ciprofloxacin with 9.42 ± 1.09, 8.02 ± 2.17, 8.11 ± 1.32, 8.88 ± 2.00 and 9.23 ± 1.87 μmoles/L respectively.Conclusion: The most potent of the synthesized compounds (5k) posesses moderate activity against all the bacterial strains, while 5g remained completely inactive.Keywords: 1,3-Benzodioxol-5-carboxylic acid, Antibacterial activity, Sulfonohydrazide, Synthesi

Cross-talk between high light stress and plant defence to the two-spotted spider mite in Arabidopsis thaliana

Little is known about how plants deal with arthropod herbivores under the fluctuating light intensity and spectra which occur in natural environments. Moreover, the role of simultaneous stress such as excess light (EL) in the regulation of plant responses to herbivores is poorly characterized. In the current study, we focused on a mite-herbivore, specifically, the two-spotted spider mite (TSSM), which is one of the major agricultural pests worldwide. Our results showed that TSSM-induced leaf damage (visualized by trypan blue staining) and oviposition rate (measured as daily female fecundity) decreased after EL pre-treatment in wild-type Arabidopsis plants, but the observed responses were not wavelength specific. Thus, we established that EL pre-treatment reduced Arabidopsis susceptibility to TSSM infestation. Due to the fact that a portion of EL energy is dissipated by plants as heat in the mechanism known as non-photochemical quenching (NPQ) of chlorophyll fluorescence, we tested an Arabidopsis npq4-1 mutant impaired in NPQ. We showed that npq4-1 plants are significantly less susceptible to TSSM feeding activity, and this result was not dependent on light pre-treatment. Therefore, our findings strongly support the role of light in plant defence against TSSM, pointing to a key role for a photo-protective mechanism such as NPQ in this regulation. We hypothesize that plants impaired in NPQ are constantly primed to mite attack, as this seems to be a universal evolutionarily conserved mechanism for herbivores

Degradation behaviors and mechanisms of MoS2 crystals relevant to bioabsorbable electronics

Monolayer molybdenum disulfide (MoS2) exhibits unique semiconducting and bioresorption properties, giving this material enormous potential for electronic/biomedical applications, such as bioabsorbable electronics. In this regard, understanding the degradation performance of monolayer MoS2 in biofluids allows modulation of the properties and lifetime of related bioabsorbable devices and systems. Herein, the degradation behaviors and mechanisms of monolayer MoS2 crystals with different misorientation angles are explored. High-angle grain boundaries (HAGBs) biodegrade faster than low-angle grain boundaries (LAGBs), exhibiting degraded edges with wedge and zigzag shapes, respectively. Triangular pits that formed in the degraded grains have orientations opposite to those of the parent crystals, and these pits grow into larger pits laterally. These behaviors indicate that the degradation is induced and propagated based on intrinsic defects, such as grain boundaries and point defects, because of their high chemical reactivity due to lattice breakage and the formation of dangling bonds. High densities of dislocations and point defects lead to high chemical reactivity and faster degradation. The structural cause of MoS2 degradation is studied, and a feasible approach to study changes in the properties and lifetime of MoS2 by controlling the defect type and density is presented. The results can thus be used to promote the widespread use of two-dimensional materials in bioabsorption applications

Hate speech and hate crimes: a data-driven study of evolving discourse around marginalized groups

This study explores the dynamic relationship between online discourse, as observed in tweets, and physical hate crimes, focusing on marginalized groups. Leveraging natural language processing techniques, including keyword extraction and topic modeling, we analyze the evolution of online discourse after events affecting these groups. Examining sentiment and polarizing tweets, we establish correlations with hate crimes in Black and LGBTQ+ communities. Using a knowledge graph, we connect tweets, users, topics, and hate crimes, enabling network analyses. Our findings reveal divergent patterns in the evolution of user communities for Black and LGBTQ+ groups, with notable differences in sentiment among influential users. This analysis sheds light on distinctive online discourse patterns and emphasizes the need to monitor hate speech to prevent hate crimes, especially following significant events impacting marginalized communities

Charge injection and trapping in TiO2 nanoparticles decorated silicon nanowires arrays

We investigate carrier transport properties of silicon nanowire (SiNW) arrays decorated with TiO2 nanoparticles (NPs). Ohmic conduction was dominant at lower voltages and space charge limited current with and without traps was observed at higher voltages. Mott’s 3D variable range hoping mechanism was found to be dominant at lower temperatures. The minimum hopping distance (Rmin) for n and p-SiNWs/TiO2 NPs devices was 1.5 nm and 0.68 nm, respectively, at 77 K. The decrease in the value of Rmin can be attributed to higher carrier mobility in p-SiNWs/TiO2 NPs than that of n-SiNWs/TiO2 NPs hybrid device

Α-Pinene-Derived organic coatings on acidic sulfate aerosol impacts secondary organic aerosol formation from isoprene in a box model

Fine particulate matter (PM2.5) is known to have an adverse impact on public health and is an important climate forcer. Secondary organic aerosol (SOA) contributes up to 80% of PM2.5 worldwide and multiphase reactions are an important pathway to form SOA. Aerosol-phase state is thought to influence the reactive uptake of gas-phase precursors to aerosol particles by altering diffusion rates within particles. Current air quality models do not include the impact of diffusion-limiting organic coatings on SOA formation. This work examines how α-pinene-derived organic coatings change the predicted formation of SOA from the acid-catalyzed multiphase reactions of isoprene epoxydiols (IEPOX). A box model, with inputs provided from field measurements taken at the Look Rock (LRK) site in Great Smokey Mountains National Park during the 2013 Southern Oxidant and Aerosol Study (SOAS), was modified to incorporate the latest laboratory-based kinetic data accounting for organic coating influences. Including an organic coating influence reduced the modeled reactive uptake when relative humidity was in the 55–80% range, with predicted IEPOX-derived SOA being reduced by up to 33%. Only sensitivity cases with a large increase in Henry's Law values of an order of magnitude or more or in particle reaction rates resulted in the large statistically significant differences form base model performance. These results suggest an organic coating layer could have an impact on IEPOX-derived SOA formation and warrant consideration in regional and global scale models

Disclosure of cancer diagnosis and quality of life in cancer patients: should it be the same everywhere?

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that truth telling and honest disclosure of cancer diagnosis could lead to improved outcomes in cancer patients. To examine such findings in Iran, this trial aimed to study the various dimensions of quality of life in patients with gastrointestinal cancer and to compare these variables among those who knew their diagnosis and those who did not.</p> <p>Methods</p> <p>A consecutive sample of patients with gastrointestinal cancer being treated in Cancer Institute in Tehran, Iran was prospectively evaluated. A psychologist interviewed patients using the Iranian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Patients were categorized into two groups: those who knew their diagnosis and those who did not. Independent sample t-test was used for group comparisons.</p> <p>Results</p> <p>In all 142 patients were interviewed. A significant proportion (52%) of patients did not know their cancer diagnosis and 48% of patients were aware that they had cancer. They were quite similar in most characteristics. The comparison of quality of life between two groups indicated that those knew their diagnosis showed a significant lower degree of physical (P = 0.001), emotional (P = 0.01) and social functioning (P < 0.001), whereas the global quality of life and other functional scales including role functioning and cognitive functioning did not show significant result. There were no statistically significant differences between symptoms scores between two groups, except for fatigue suggesting a higher score in patients who knew their diagnosis (P = 0.01). The financial difficulties were also significantly higher in patients who knew their cancer diagnosis (P = 0.005). Performing analysis of variance while controlling for age, educational status, cancer site, and knowledge of cancer diagnosis, the results showed that the knowledge of cancer diagnosis independently still contributed to the significant differences observed between two groups.</p> <p>Conclusion</p> <p>Contrary to expectation the findings indicated that patients who did not know their cancer diagnosis had a better physical, social and emotional quality of life. It seems that due to cultural differences between countries cancer disclosure guidelines perhaps should be differing.</p