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Multifunctional living materials are attractive due to their powerful ability to self-repair and replicate. However, most natural materials lack electronic functionality. Here we show that an electric field, applied to electricity-producing Geobacter sulfurreducens biofilms, stimulates production of cytochrome OmcZ nanowires with 1,000-fold higher conductivity (30 S cm −1 ) and threefold higher stiffness (1.5 GPa) than the cytochrome OmcS nanowires that are important in natural environments. Using chemical imaging-based multimodal nanospectroscopy, we correlate protein structure with function and observe pH-induced conformational switching to β-sheets in individual nanowires, which increases their stiffness and conductivity by 100-fold due to enhanced π-stacking of heme groups; this was further confirmed by computational modeling and bulk spectroscopic studies. These nanowires can transduce mechanical and chemical stimuli into electrical signals to perform sensing, synthesis and energy production. These findings of biologically produced, highly conductive protein nanowires may help to guide the development of seamless, bidirectional interfaces between biological and electronic systems. Application of an electrical field to Geobacter sulfurreducens biofilms stimulates production of OmcZ nanowires, which undergo a pH-induced conformational switch that causes increased stiffness and conductivity due to enhanced heme group π-stacking.

In dentistry, over-retained deciduous teeth pose a distinct issue due to their endurance during the expected exfoliation period. This case study describes a clinical situation with a male patient who is seven years old and complaining of painful swelling over the maxillary anterior region of the jaw and clinically showing dark red-colored, firm, non-tender, purulent swelling extending from alveolar mucosa of the upper anterior to the gingival margin of the 51, 52, 53 region. The treatment plan includes the extraction of the primary teeth. This case report also highlights the importance of minimal surgical intervention for treating peri-radicular cysts to minimize healing time and damage to the underlying developing permanent tooth.

William Bishai and colleagues report that cyclic-di-adenosine monophosphate produced during infection with Mycobacterium tuberculosis induces IFN-β and contributes to the innate sensing of tuberculosis. Detection of cyclic-di-adenosine monophosphate (c-di-AMP), a bacterial second messenger, by the host cytoplasmic surveillance pathway (CSP) is known to elicit type I interferon (IFN) responses, which are crucial to antimicrobial defense 1 , 2 , 3 . However, the mechanisms and role of c-di-AMP signaling in Mycobacterium tuberculosis virulence remain unclear. Here we show that resistance to tuberculosis requires CSP-mediated detection of c-di-AMP produced by M. tuberculosis and that levels of c-di-AMP modulate the fate of infection. We found that a di-adenylate cyclase (disA or dacA) 4 -overexpressing M. tuberculosis strain that secretes excess c-di-AMP activates the interferon regulatory factor (IRF) pathway with enhanced levels of IFN-β, elicits increased macrophage autophagy, and exhibits substantial virulence attenuation in mice. We show that c-di-AMP-mediated IFN-β induction during M. tuberculosis infection requires stimulator of interferon genes (STING) 5 -signaling. We observed that c-di-AMP induction of IFN-β is independent of the cytosolic nucleic acid receptor cyclic GMP-AMP (cGAMP) synthase (cGAS) 6 , 7 , but cGAS nevertheless contributes substantially to the overall IFN-β response to M. tuberculosis infection. In sum, our results reveal c-di-AMP to be a key mycobacterial pathogen-associated molecular pattern (PAMP) driving host type I IFN responses and autophagy. These findings suggest that modulating the levels of this small molecule may lead to novel immunotherapeutic strategies against tuberculosis.

Type IVa pili (T4P) are bacterial surface structures that enable motility, adhesion, biofilm formation and virulence. T4P are assembled by nanomachines that span the bacterial cell envelope. Cycles of T4P assembly and retraction, powered by the ATPases PilB and PilT, allow bacteria to attach to and pull themselves along surfaces, so-called \"twitching motility\". These opposing ATPase activities must be coordinated and T4P assembly limited to one pole for bacteria to show directional movement. How this occurs is still incompletely understood. Herein, we show that the c-di-GMP binding protein FimX, which is required for T4P assembly in Pseudomonas aeruginosa, localizes to the leading pole of twitching bacteria. Polar FimX localization requires both the presence of T4P assembly machine proteins and the assembly ATPase PilB. PilB itself loses its polar localization pattern when FimX is absent. We use two different approaches to confirm that FimX and PilB interact in vivo and in vitro, and further show that point mutant alleles of FimX that do not bind c-di-GMP also do not interact with PilB. Lastly, we demonstrate that FimX positively regulates T4P assembly and twitching motility by promoting the activity of the PilB ATPase, and not by stabilizing assembled pili or by preventing PilT-mediated retraction. Mutated alleles of FimX that no longer bind c-di-GMP do not allow rapid T4P assembly in these assays. We propose that by virtue of its high-affinity for c-di-GMP, FimX can promote T4P assembly when intracellular levels of this cyclic nucleotide are low. As P. aeruginosa PilB is not itself a high-affinity c-di-GMP receptor, unlike many other assembly ATPases, FimX may play a key role in coupling T4P mediated motility and adhesion to levels of this second messenger.

PurposePresent research analyzes and evaluates the impact of e-resources usage factors (training modes, awareness, influencers, utilitarian benefits and ease of use) towards satisfaction and intention to use these e-resources.Design/methodology/approachThe data for present study were collected from postgraduate students of Delhi (India) and 248 valid responses were received through the survey. After reliability and validity tests, structural relationships between variables were studied.FindingsThe present study revealed that all five factors significantly affected satisfaction and intention to use e-resources. However, influencers were found to have the highest impact on satisfaction and intention to use e-resources.Originality/valueThe present study is a maiden attempt to explore the impact of e-resources usage factors on satisfaction and intention to use by postgraduate students at management schools in Delhi, India.

Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa can initially attach to surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached and express surface-associated structures, such as Type IV pili, and behaviors, including twitching motility and biofilm initiation. P. aeruginosa that lack the GTPase FlhF assemble a randomly placed flagellum that is motile; however, we observed that these mutant bacteria show defects in biofilm formation comparable to those seen for non-motile, aflagellate bacteria. This phenotype was associated with altered behavior of ΔflhF bacteria immediately following surface-attachment. Forward and reverse genetic screens led to the discovery that FlhF interacts with FimV to control flagellar rotation at a surface, and implicated cAMP signaling in this pathway. Although cAMP controls many transcriptional programs in P. aeruginosa, known targets of this second messenger were not required to modulate flagellar rotation in surface-attached bacteria. Instead, alterations in switching behavior of the motor appeared to result from direct or indirect effects of cAMP on switch complex proteins and/or the stators associated with them.

Background: Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the ‘One Health approach’ in which multiple sectors coordinate and work together to achieve better public health outcomes.Objective:We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019.Methods: Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders.Findings & Conclusion:The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach.

The remarkable capacity of bacteria to adapt in response to selective pressures drives antimicrobial resistance. Pseudomonas aeruginosa illustrates this point, establishing chronic infections during which it evolves to survive antimicrobials and evade host defenses. Many adaptive changes occur on the P. aeruginosa cell surface but methods to identify these are limited. Here we combine phage display with high-throughput DNA sequencing to create a high throughput, multiplexed technology for surveying bacterial cell surfaces, Phage-seq. By applying phage display panning to hundreds of bacterial genotypes and analyzing the dynamics of the phage display selection process, we capture important biological information about cell surfaces. This approach also yields camelid single-domain antibodies that recognize key P. aeruginosa virulence factors on live cells. These antibodies have numerous potential applications in diagnostics and therapeutics. We propose that Phage-seq establishes a powerful paradigm for studying the bacterial cell surface by identifying and profiling many surface features in parallel. Methods to identify bacterial cell surface adaptations are limited. The authors combine phage display with high-throughput DNA sequencing to create a highly-multiplexed technology for surveying bacterial cell surfaces.

A mycobacterial phosphodiesterase, CdnP, hydrolyzes bacteria-derived 3′,5′-c-di-AMP as well as host-generated 2′,3′-cGAMP, which activates the host cytosolic surveillance pathway, to dampen host responses. Mycobacterium tuberculosis infection leads to cytosolic release of the bacterial cyclic dinucleotide (CDN) c-di-AMP and a host-generated CDN, cGAMP, both of which trigger type I interferon (IFN) expression in a STING-dependent manner. Here we report that M. tuberculosis has developed a mechanism to inhibit STING activation and the type I IFN response via the bacterial phosphodiesterase (PDE) CdnP, which mediates hydrolysis of both bacterial-derived c-di-AMP and host-derived cGAMP. Mutation of cdnP attenuates M. tuberculosis virulence, as does loss of a host CDN PDE known as ENPP1. CdnP is inhibited by both US Food and Drug Administration (FDA)-approved PDE inhibitors and nonhydrolyzable dinucleotide mimetics specifically designed to target the enzyme. These findings reveal a crucial role of CDN homeostasis in governing the outcome of M. tuberculosis infection as well as a unique mechanism of subversion of the host's cytosolic surveillance pathway (CSP) by a bacterial PDE that may serve as an attractive antimicrobial target.