Caulobacter crescentus CdnL is a non-essential RNA polymerase-binding protein whose depletion impairs normal growth and rRNA transcription.

CdnL is an essential RNA polymerase (RNAP)-binding activator of rRNA transcription in mycobacteria and myxobacteria but reportedly not in Bacillus. Whether its function and mode of action are conserved in other bacteria thus remains unclear. Because virtually all alphaproteobacteria have a CdnL homolog and none of these have been characterized, we studied the homolog (CdnL <sub>Cc</sub> ) of the model alphaproteobacterium Caulobacter crescentus. We show that CdnL <sub>Cc</sub> is not essential for viability but that its absence or depletion causes slow growth and cell filamentation. CdnL <sub>Cc</sub> is degraded in vivo in a manner dependent on its C-terminus, yet excess CdnL <sub>Cc</sub> resulting from its stabilization did not adversely affect growth. We find that CdnL <sub>Cc</sub> interacts with itself and with the RNAP β subunit, and localizes to at least one rRNA promoter in vivo, whose activity diminishes upon depletion of CdnL <sub>Cc</sub> . Interestingly, cells expressing CdnL <sub>Cc</sub> mutants unable to interact with the RNAP were cold-sensitive, suggesting that CdnL <sub>Cc</sub> interaction with RNAP is especially required at lower than standard growth temperatures in C. crescentus. Our study indicates that despite limited sequence similarities and regulatory differences compared to its myco/myxobacterial homologs, CdnL <sub>Cc</sub> may share similar biological functions, since it affects rRNA synthesis, probably by stabilizing open promoter-RNAP complexes

Structure-function dissection of Myxococcus xanthus CarD N-terminal domain, a defining member of the CarD-CdnL-TRCF family of RNA polymerase interacting proteins

© 2015 Bernal-Bernal et al. Two prototypes of the large CarD-CdnL-TRCF family of bacterial RNA polymerase (RNAP)-binding proteins, Myxococcus xanthus CarD and CdnL, have distinct functions whose molecular basis remain elusive. CarD, a global regulator linked to the action of several extracytoplasmic function (ECF) σ-factors, binds to the RNAP β subunit (RNAP-β) and to protein CarG via an N-terminal domain, CarDNt, and to DNA via an intrinsically unfolded C-terminal domain resembling eukaryotic high-mobility-group A (HMGA) proteins. CdnL, a CarDNt-like protein that is essential for cell viability, is implicated in σA-dependent rRNA promoter activation and interacts with RNAP-β but not with CarG. While the HMGA-like domain of CarD by itself is inactive, we find that CarDNt has low but observable ability to activate ECF σ-dependent promoters in vivo, indicating that the C-terminal DNA-binding domain is required to maximize activity. Our structure-function dissection of CarDNt reveals an N-terminal, five-stranded β-sheet Tudor-like domain, CarD1-72, whose structure and contacts with RNAP-β mimic those of CdnL. Intriguingly, and in marked contrast to CdnL, CarD mutations that disrupt its interaction with RNAP-β did not annul activity. Our data suggest that the CarDNt C-terminal segment, CarD61-179, may be structurally distinct from its CdnL counterpart, and that it houses at least two distinct and crucial function determinants: (a) CarG-binding, which is specific to CarD; and (b) a basic residue stretch, which is also conserved and functionally required in CdnL. This study highlights the evolution of shared and divergent interactions in similar protein modules that enable the distinct activities of two related members of a functionally important and widespread bacterial protein family.Peer Reviewe

Bioinspired Underwater Bonding and Debonding on Demand

Mussel glue: Bioinspired underwater chemical bonding with the possibility of phototriggered debonding is reported. A four-arm star-poly(ethyleneglycol) end-functionalized by nitrodopamine was synthesized. The nitrodopamine offered the reactivity of catechol and the chemistry of the photocleavable o-nitrophenyl ethyl group (see picture)

LOS LÍMITES DEL MODELO ESTÁNDAR ACERCA DEL COMPONENTE SEMÁNTICO EN EL ESTABLECIMIENTO DE CORRESPONDENCIAS ANALÓGICAS

We argue that the treatment given to semantics by the standard programs of analogical mapping (e.g., SME) reduces semantics to the influence of preestablished similarities between propositional elements on the mapping of these elements, and that the theoretical conception under this treatment supposes serious limits. We claim, in accordance with the High Level Perception Theory, that attempts to simulate analogical mapping should aim to equip programs with semantic abilities such as the detection of contextual similarities and the construction of analogue representations in response to mapping demands. We agree with the High Level Perception Theory in that programs like SME do not understand the analogies they produce, and in that they suppose a fallacious way of computational modeling. We argue that the responses given to the criticisms formulated by the High Level Perception Theory are not adequate, and that these criticisms deserve more attention in the field of analogical thinking.Se postula que el tratamiento dado al componente semántico en los programas dominantes del establecimiento de correspondencias analógico (e.g., SME) reduce la semántica a la influencia de similitudes preestablecidas sobre el emparejamiento de elementos proposicionales, y que la concepción teórica que subyace a este tratamiento supone importantes limitaciones. Se sostiene, junto a la teoría de percepción de alto nivel (TPAN), que los intentos de simulación computacional del establecimiento de correspondencias deberían proponerse incorporar en los programas habilidades semánticas tales como el establecimiento de similitudes contextuales y la construcción de representaciones de los análogos según las exigencias que plantea el establecimiento de correspondencias. Se apoya la idea de la TPAN de que programas como SME carecen de comprensión de las analogías que realizan y suponen un modo falaz de simulación computacional. Se postula que las respuestas dadas a las críticas formuladas por la TPAN no son adecuadas y que estas críticas deberían recibir mayor atención en el área del pensamiento por analogía

Levels and Trends of Perfluoroalkyl Substances Regulated Under the Stockholm Convention in Water from the Duero Basin in Spain

Perfluoroalkyl substances (PFAS) are a large family of synthetic chemicals with excellent thermal and chemical stability. These chemicals have been used as polymers, surfactants, stain repellents, and flame retardants in several products such as carpets, leather paper, textiles, fire-fighting foams (FFF), etc. PFAS are ubiquitous in the environment due to discharges from various sources such as manufacturing and processing industries, military areas, use of FFF, wastewater discharges and landfills. The Stockholm Convention (SC) on Persistent Organic Pollutants (POPs) included perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), their salts and related products on the restriction and elimination list in 2009, 2019 and 2022, respectively

Light-triggered carotenogenesis in myxococcus xanthus: New paradigms in photosensory signaling, transduction and gene regulation

22 pags., 6 figs. -- This article belongs to the Special Issue Myxobacteria: Physiology and RegulationMyxobacteria are Gram-negative δ-proteobacteria found predominantly in terrestrial habitats and often brightly colored due to the biosynthesis of carotenoids. Carotenoids are lipophilic isoprenoid pigments that protect cells from damage and death by quenching highly reactive and toxic oxidative species, like singlet oxygen, generated upon growth under light. The model myxobacterium Myxococcus xanthus turns from yellow in the dark to red upon exposure to light because of the photoinduction of carotenoid biosynthesis. How light is sensed and transduced to bring about regulated carotenogenesis in order to combat photooxidative stress has been extensively investigated in M. xanthus using genetic, biochemical and high-resolution structural methods. These studies have unearthed new paradigms in bacterial light sensing, signal transduction and gene regulation, and have led to the discovery of prototypical members of widely distributed protein families with novel functions. Major advances have been made over the last decade in elucidating the molecular mechanisms underlying the light-dependent signaling and regulation of the transcriptional response leading to carotenogenesis in M. xanthus. This review aims to provide an up-to-date overview of these findings and their significance.This research was funded by grants PGC2018-094635-B-C21 (to M.E.-A.) and PGC2018- 094635-B-C22 (to S.P) from the Agencia Estatal de Investigación (AEI)-Spain and European Regional Development Fund (FEDER), and by grant 20992/PI/18 (to M.E.-A.) from Fundación Séneca (Murcia)- Spain. The Ministerio de Educación y Cultura-Spain funded Ph.D. fellowships to A.J.M.-G, E.P.-M. and E.B.-M., and AEI-Spain funded that to R.P.-C

Antibacterial Strategies from the Sea: Polymer-Bound Cl-Catechols for Prevention of Biofilm Formation

Inspired by the amino acid 2-chloro-4,5-dihydroxyphenylalanine (Cl-DOPA), present in the composition of the proteinaceous glue of the sandcastle worm Phragmatopoma californica, a simple strategy is presented to confer antifouling properties to polymer surfaces using (but not releasing) a bioinspired biocide. Cl-Dopamine is used to functionalize polymer materials and hydrogel films easily, to prevent biofilm formation on themThe authors thank Uwe Rietzler from the Max-Planck-Institut für Polymerforschung for the SFM-based thickness measurements

A Dynamically Adaptable Bus Architecture for Trading-Off Among Performance, Consumption and Dependability in Cyber-Physical Systems

Cyber-Physical Systems need to handle increasingly complex tasks, which additionally, may have variable operating conditions over time. Therefore, dynamic resource management to adapt the system to different needs is required. In this paper, a new bus-based architecture, called ARTICo3, which by means of Dynamic Partial Reconfiguration, allows the replication of hardware tasks to support module redundancy, multi-thread operation or dual-rail solutions for enhanced side-channel attack protection is presented. A configuration-aware data transaction unit permits data dispatching to more than one module in parallel, or provide coalesced data dispatching among different units to maximize the advantages of burst transactions. The selection of a given configuration is application independent but context-aware, which may be achieved by the combination of a multi-thread model similar to the CUDA kernel model specification, combined with a dynamic thread/task/kernel scheduler. A multi-kernel application for face recognition is used as an application example to show one scenario of the ARTICo3 architecture

Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer’s disease.

Background: The complex pathophysiology of Alzheimer’s disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. Methods: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse− model. Results: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3–CA1 synapse, both basal synaptic transmission and longterm potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron–glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH−/− animals. Conclusion: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer’s disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the diseasepost-print4206 K