Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumanniicomplex

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes isolated from their functional contexts. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and micro-synteny conservation analyses. This allowed to delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with, or are found preferentially in, the pathogenic ACB clade. They unveil, at an unprecedented resolution, the genetic makeup that coincides with the manifestation of the pathogenic phenotype in the last common ancestor of the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. Specifically, we could show that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. They disclose promising routes for future therapeutic strategies.

Overview of photonic devices based on functional materials-integrated photonic crystal fibers

Photonic crystal fibers (PCFs) have brought tremendous advancements due to their predominant features of peculiar air-holes arrangement in two-dimentional direction. Functional materials like metals, magnetic fluids, nematic liquid crystals, graphene and so on, are extensively adopted to integrate with PCFs to get extraordinary transmission properties. This review takes the development stages of photonic devices based on functional materials-infiltrated PCFs into consideration, covering the overview of common materials and their photoelectric characteristics, the state-of-art infiltrating/coating techniques, as well as the corresponding applications involving polarization filtering and splittering devices in optical communication and sensing elements related to multiple parameters measurement. The cladding air hole of PCFs provides a natural optofluidic channel for materials being introduced, light-matter interaction being enhanced, and transmission properties being extended, where a lab on a fiber are able to be proceeded. It paves a space for the development of photonic devices in the aspects of compact, multi-functional integration, and electromagnetic resistance as well. According to surface plasmon resonance, the property of tunable refractive indices, and the flexible geometry structures, it comes up to some representative researches on polarization filters, multiplexer-demultiplexers, splitters, couplers and sensors, making a candidate for widespread fields of telecommunication, signal-capacity, and high-performance sensing.

A role for Lin28a in aging-associated decline of adult hippocampal neurogenesis

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein Lin28a remained existent in neural progenitor cells and granule neurons in the adult hippocampus, and decreased with aging. Loss of Lin28a inhibited the responsiveness of neural progenitor cells to niche Wnt agonist and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis as well as related cognitive functions.

Construction of a sequentially responsive nanocarrier for chemotherapy and cascade amplified NIR photodynamic therapy

A sequentially responsive nanocarrier was fabricated with three-in-one functional integration: bio-imaging, tumor microenvironment responsive chemotherapy and cascade activation of upconversion photodynamic therapy. The designed DNA outer nanoshell displayed the site-specific...

Histological examination of cranial synchondroses as functionally significant elements in the cranial osteopathic concept

Introduction. In recent decades, medical science has accumulated convincing evidence of the fact that the normal activity of a human brain depends on the functional integration of its vascular system, a circulation system of cerebrospinal fluid and biomechanical features of a skull, forming a single structural and functional system.The aim of the study is to research the histological structure of functionally significant cranial synchondroses in the middle and elderly age group, to find possible points of osteopathic influence application in their structure. Materials and methods. The study was performed on cadaver material of 27 persons (7 men — 26 %, 20 women — 74 %) who died at the age from 49 to 66 years (57,5±5,3 years) from various somatic pathologies, but had no history of craniocerebral injuries with fractures of osseous structures. Small bone fragments with sutures of interest/synchondroses (spheno-occipital synchondrosis, petro-jugular synchondrosis, sphenopetrosal synchondrosis) were subjected to standard histological processing followed by microscopy.Results. Evaluating histological specimens of spheno-occipital synchondrosis, we observed the similar pattern: highly mineralized tissues at the edges of the bodies of the sphenoid and occipital bones were connected without elements of cartilagi-nous or connective tissue. In all cases, no fibrous or nerve tissue elements were found during the in situ immunohistochemical reactions. Reactions with the CD34 antibody mark multiple vessels of the Volkmann's or Haversian canals. Evaluating histological specimens of petro-jugular and sphenopetrosal synchondroses, we found the presence of cartilage tissue in the suture in the form of small islands of various sizes (from 20 to 120 microns) with signs of degeneration and a small number of remained chondrocytes. When evaluating specimens with immunohistochemical reactions with antibodies against the S100 protein, no elements of the nervous tissue were detected.Conclusion. Spheno-occipital synchondrosis has a temporary nature. With age, its cartilaginous tissue is replaced by osseous one. According to the histological structure, sphenobasilar synchondrosis demonstrates the complete absence of a cartilaginous component in the middle and elderly age groups. Petro-jugular and sphenopetrosal synchondroses retain the cartilaginous component in their suture throughout lifetime. During histological examination of the petro-jugular and sphenopetrosal synchondroses, the cartilaginous component is represented by variety of small islands. In all synchondroses, there is an absence of vascular and nervous components. At the same time, we revealed the presence of a prominent vascular bed in the bone tissue. The fact requires emphasizing the importance of liquid potency and elastic component in cartilaginous and osseous tissues as an application point for osteopathic techniques.

Esthetic And Functional Integration Of Soft Tissue Around Dental Implants: Thickness, Width, Stability.

The long-term Functional success of the implant treatment depends on the stability of the crestal bone tissue around the implant platform. The Esthetic result is achieved by an adequate soft tissue in the peri-implant zone. Furthermore, the soft tissue creates the buffer area that ensures the mechanical and biological protection of the underlying bone. Therefore, it is necessary to maintain for a long term, not only the implant osseointegration but also the integration of the soft tissue around the Sub and Supra-structure of the restoration. In order to create the protective soft tissue area, it is necessary to ensure three criteria. This treatment approach will be defined as the TWS – Soft Tissue Management : T for Thickness , W for Width, and S for Stability . The purpose of this article is to present with clinical cases, the detailed description of each criteria. There are many ways to achieve the two first criteria and they are well described in the literature. Achieving the third criteria of the Stability become possible only in the last years since the development of the digital technology and its implementation into the dental practice. A one time abutment and the creation of peri- implant mucosal thickness with an optimal amount of the attached keratinized gingiva above and around the implant platform, for muco-gingival integration of the system, are therefore a prerequisite for functional and esthetic result. The article presents the possibility for the clinicians to use in their daily practice this new clinical approach of TWS - Soft Tissue Management.

Review on the Traditional and Integrated Passives: State-of-the-Art Design and Technologies

With the increased necessity of a high power density and efficient system in aerospace and marine industries, integrated motor drives provide an excellent solution in the modern era. Therefore, a close structural and functional integration of passive components has become a prerequisite task to make a compact overall system. This article reviews the existing motor drives system with integrated passive technologies. To start, the design aspect of the traditional and integrated filter inductors, using the area product approach, is discussed. Subsequently, layouts of traditional and integrated inductors are presented. The available capacitor technologies, suitable for integration, are also discussed with pros and cons of each capacitor type.

Prothoracicostatic Activity of the Ecdysis-Regulating Neuropeptide Crustacean Cardioactive Peptide (CCAP) in the Desert Locust

Accurate control of innate behaviors associated with developmental transitions requires functional integration of hormonal and neural signals. Insect molting is regulated by a set of neuropeptides, which trigger periodic pulses in ecdysteroid hormone titers and coordinate shedding of the old cuticle during ecdysis. In the current study, we demonstrate that crustacean cardioactive peptide (CCAP), a structurally conserved neuropeptide described to induce the ecdysis motor program, also exhibits a previously unknown prothoracicostatic activity to regulate ecdysteroid production in the desert locust, Schistocerca gregaria. We identified the locust genes encoding the CCAP precursor and three G protein-coupled receptors that are activated by CCAP with EC50 values in the (sub)nanomolar range. Spatiotemporal expression profiles of the receptors revealed expression in the prothoracic glands, the endocrine organs where ecdysteroidogenesis occurs. RNAi-mediated knockdown of CCAP precursor or receptors resulted in significantly elevated transcript levels of several Halloween genes, which encode ecdysteroid biosynthesis enzymes, and in elevated ecdysteroid levels one day prior to ecdysis. Moreover, prothoracic gland explants exhibited decreased secretion of ecdysteroids in the presence of CCAP. Our results unequivocally identify CCAP as the first prothoracicostatic peptide discovered in a hemimetabolan species and reveal the existence of an intricate interplay between CCAP signaling and ecdysteroidogenesis.

Numerical Solutions of the Mathematical Models on the Digestive System and COVID-19 Pandemic by Hermite Wavelet Technique

This article developed a functional integration matrix via the Hermite wavelets and proposed a novel technique called the Hermite wavelet collocation method (HWM). Here, we studied two models: the coupled system of an ordinary differential equation (ODE) is modeled on the digestive system by considering different parameters such as sleep factor, tension, food rate, death rate, and medicine. Here, we discussed how these parameters influence the digestive system and showed them through figures and tables. Another fractional model is used on the COVID-19 pandemic. This model is defined by a system of fractional-ODEs including five variables, called S (susceptible), E (exposed), I (infected), Q (quarantined), and R (recovered). The proposed wavelet technique investigates these two models. Here, we express the modeled equation in terms of the Hermite wavelets along with the collocation scheme. Then, using the properties of wavelets, we convert the modeled equation into a system of algebraic equations. We use the Newton–Raphson method to solve these nonlinear algebraic equations. The obtained results are compared with numerical solutions and the Runge–Kutta method (R–K method), which is expressed through tables and graphs. The HWM computational time (consumes less time) is better than that of the R–K method.

Investigation of Size Effects in Multi-Stage Cold Forming of Metallic Micro Parts from Sheet Metal

Product miniaturisation and functional integration are currently global trends to save weight, space, materials and costs. This leads to an increasing demand for metallic micro components. Thus, the development of appropriate production technologies is in the focus of current research activities. Due to its efficiency, accuracy and short cycle times, microforming at room temperature offers the potential to meet the steadily increasing demand. During microforming, size effects occur which negatively affect the part quality, process stability, tool life and handling. Within this contribution, a multi-stage bulk microforming process from sheet metal is investigated for the materials Cu-OFE and AA6014 with regard to the basic feasibility and the occurrence of size effects. The results reveal that the process chain is basically suitable to produce metallic micro parts with a high repeatability. Size effects are identified during the process. Since several studies postulate that size effects can be minimised by scaling down the metallic grain structure, the grain size of the aluminium material AA6014-W is scaled down to less than one micrometre by using an accumulative roll bonding process (ARB). Subsequently, the effects of the ultrafine grain (UFG) structure on the forming process are analysed. It could be shown that a strengthened material state increases the material utilization. Furthermore, too soft materials can cause damage on the part during ejection. The occurring size effects cannot be eliminated by reducing the grain size.