DNA Repair Mechanisms as Drug Targets in Prokaryotes

Nowadays, a great amount of pathogenic bacteria has been identified such as Mycobacterium sp. and Helicobacter pylori and have become a serious health problem around the world. These bacteria have developed several DNA repair mechanisms as a strategy to neutralize the effect of the exposure to endogenous and exogenous agents that will lead to two different kinds of DNA damage: single strand breaks (SSBs) and double strand breaks (DSBs). For SSBs repair, bacteria use the base excision repair (BER) and nucleotide excision repair (NER) mechanisms, which fix the damaged strand replacing the damaged base or nucleotide. DSBs repair in bacteria is performed by homologous recombination repair (HRR) and non-homologous end-joining (NHEJ). HRR uses the homologous sequence to fix the two damaged strand, while NHEJ repair does not require the use of its homologous sequence. The use of unspecific antibiotics to treat bacterial infections has caused a great deal of multiple resistant strains making less effective the current therapies with antibiotics. In this review, we emphasized the mechanisms mentioned above to identify molecular targets that can be used to develop novel and more efficient drugs in future.Nowadays, a great amount of pathogenic bacteria has been identified such as Mycobacterium sp. and Helicobacter pylori and have become a serious health problem around the world. These bacteria have developed several DNA repair mechanisms as a strategy to neutralize the effect of the exposure to endogenous and exogenous agents that will lead to two different kinds of DNA damage: single strand breaks (SSBs) and double strand breaks (DSBs). For SSBs repair, bacteria use the base excision repair (BER) and nucleotide excision repair (NER) mechanisms, which fix the damaged strand replacing the damaged base or nucleotide. DSBs repair in bacteria is performed by homologous recombination repair (HRR) and non-homologous end-joining (NHEJ). HRR uses the homologous sequence to fix the two damaged strand, while NHEJ repair does not require the use of its homologous sequence. The use of unspecific antibiotics to treat bacterial infections has caused a great deal of multiple resistant strains making less effective the current therapies with antibiotics. In this review, we emphasized the mechanisms mentioned above to identify molecular targets that can be used to develop novel and more efficient drugs in future

Temporal characterisation of soil-plant natural recovery related to fire severity in burned Pinus halepensis Mill. forests

Despite Mediterranean ecosystems' high resilience to fire, both climate and land use change, and alterations in fire regimes increase their vulnerability to fire by affecting the long-term natural recovery of ecosystem services. The objective of this work is to study the effects of fire severity on biochemical soil indicators, such as chemical composition or enzymatic activity, related to time after fire and natural vegetation recovery (soil-plant interphase). Soil samples from three wildfires occurring 3, 15 and 21 years ago were taken in the south-eastern Iberian Peninsula (semiarid climate). Sampling included three fire severity levels in naturally regenerated (and changing to shrublands) Pinus halepensis Mill. forests. In the short-term post-fire period, phosphorus concentration, electrical conductivity and urease activity were positively linked to fire severity, and also influenced β-glucosidade activity in a negative relationship. During the 15–21-year post-fire period, the effects related to medium-high fire severity were negligible and soil quality indicators were linked to natural regeneration success. The results showed that most soil properties recovered in the long term after fire (21 years). These outcomes will help managers and stakeholders to implement management tools to stabilise soils and to restore burned ecosystems affected by medium-high fire severity. Such knowledge can be considered in adaptive forest management to reduce the negative effects of wildfires and desertification, and to improve the resilience of vulnerable ecosystems in a global change scenario.This study was supported by a grant for research initiation provided by the Excma. Diputación Albacete (DIPU4-AB2015) and by the funds provided by University Castilla-La Mancha to the Forest Ecology Research Group.The authors with to thank the Spanish Institute for Agricultural and Food Research and Technology (INIA) for the funding awarded through National Research Projects GEPRIF (RTA2014-00011-C06)

Ground-State Spin Blockade in a Single-Molecule Junction

It is known that the quantum mechanical ground state of a nanoscale junction has a significant impact on its electrical transport properties. This becomes particularly important in transistors consisting of a single molecule. Because of strong electron-electron interactions and the possibility of accessing ground states with high spins, these systems are eligible hosts of a current-blockade phenomenon called a ground-state spin blockade. This effect arises from the inability of a charge carrier to account for the spin difference required to enter the junction, as that process would violate the spin selection rules. Here, we present a direct experimental demonstration of a ground-state spin blockade in a high-spin single-molecule transistor. The measured transport characteristics of this device exhibit a complete suppression of resonant transport due to a ground-state spin difference of 3/2 between subsequent charge states. Strikingly, the blockade can be reversibly lifted by driving the system through a magnetic ground-state transition in one charge state, using the tunability offered by both magnetic and electric fields

Perception of the primary health care response capacity by patients with and without mental health problems, and health professionals: qualitative study

BACKGROUND: The objective of this study is to deepen our understanding of perceptions towards Primary Health Care Response Capacity by specifically using patients with and without mental disorders, as well as family doctors and a manager, in order to compare and endorse perspectives. For it, a qualitative study was performed. In-depth interviews were conducted with 28 patients with and without mental health disorders and focus groups were held with 21 professionals and a manager. An inductive thematic content analysis was performed in order to explore, develop and define the emergent categories of analysis. RESULTS: The fundamental domains for patients are dignity, communication, and rapid service. People with mental health problems also highlight the domain of confidentiality as relevant, while patients who do not have a mental health problem prioritize the domain of autonomy. Patients with mental health disorders report a greater number of negative experiences in relation to the domain of dignity. Patients do not consider their negative experiences to be a structural problem of the system. These findings are also endorsed by health care professionals. CONCLUSIONS: It is necessary to take these results into account as responsive systems can improve service uptake, ensure adherence to treatment, and ultimately enhance patient welfare

On the similarity of Sturm-Liouville operators with non-Hermitian boundary conditions to self-adjoint and normal operators

We consider one-dimensional Schroedinger-type operators in a bounded interval with non-self-adjoint Robin-type boundary conditions. It is well known that such operators are generically conjugate to normal operators via a similarity transformation. Motivated by recent interests in quasi-Hermitian Hamiltonians in quantum mechanics, we study properties of the transformations in detail. We show that they can be expressed as the sum of the identity and an integral Hilbert-Schmidt operator. In the case of parity and time reversal boundary conditions, we establish closed integral-type formulae for the similarity transformations, derive the similar self-adjoint operator and also find the associated "charge conjugation" operator, which plays the role of fundamental symmetry in a Krein-space reformulation of the problem.Comment: 27 page

The caCORE Software Development Kit: Streamlining construction of interoperable biomedical information services

BACKGROUND: Robust, programmatically accessible biomedical information services that syntactically and semantically interoperate with other resources are challenging to construct. Such systems require the adoption of common information models, data representations and terminology standards as well as documented application programming interfaces (APIs). The National Cancer Institute (NCI) developed the cancer common ontologic representation environment (caCORE) to provide the infrastructure necessary to achieve interoperability across the systems it develops or sponsors. The caCORE Software Development Kit (SDK) was designed to provide developers both within and outside the NCI with the tools needed to construct such interoperable software systems. RESULTS: The caCORE SDK requires a Unified Modeling Language (UML) tool to begin the development workflow with the construction of a domain information model in the form of a UML Class Diagram. Models are annotated with concepts and definitions from a description logic terminology source using the Semantic Connector component. The annotated model is registered in the Cancer Data Standards Repository (caDSR) using the UML Loader component. System software is automatically generated using the Codegen component, which produces middleware that runs on an application server. The caCORE SDK was initially tested and validated using a seven-class UML model, and has been used to generate the caCORE production system, which includes models with dozens of classes. The deployed system supports access through object-oriented APIs with consistent syntax for retrieval of any type of data object across all classes in the original UML model. The caCORE SDK is currently being used by several development teams, including by participants in the cancer biomedical informatics grid (caBIG) program, to create compatible data services. caBIG compatibility standards are based upon caCORE resources, and thus the caCORE SDK has emerged as a key enabling technology for caBIG. CONCLUSION: The caCORE SDK substantially lowers the barrier to implementing systems that are syntactically and semantically interoperable by providing workflow and automation tools that standardize and expedite modeling, development, and deployment. It has gained acceptance among developers in the caBIG program, and is expected to provide a common mechanism for creating data service nodes on the data grid that is under development

Nanoparticle penetration and transport in living pumpkin plants: in situ subcellular identification

<p>Abstract</p> <p>Background</p> <p>In recent years, the application of nanotechnology in several fields of bioscience and biomedicine has been studied. The use of nanoparticles for the targeted delivery of substances has been given special attention and is of particular interest in the treatment of plant diseases. In this work both the penetration and the movement of iron-carbon nanoparticles in plant cells have been analyzed in living plants of <it>Cucurbita pepo</it>.</p> <p>Results</p> <p>The nanoparticles were applied <it>in planta </it>using two different application methods, injection and spraying, and magnets were used to retain the particles in movement in specific areas of the plant. The main experimental approach, using correlative light and electron microscopy provided evidence of intracellular localization of nanoparticles and their displacement from the application point. Long range movement of the particles through the plant body was also detected, particles having been found near the magnets used to immobilize and concentrate them. Furthermore, cell response to the nanoparticle presence was detected.</p> <p>Conclusion</p> <p>Nanoparticles were capable of penetrating living plant tissues and migrating to different regions of the plant, although movements over short distances seemed to be favoured. These findings show that the use of carbon coated magnetic particles for directed delivery of substances into plant cells is a feasible application.</p

Magnetic nanoparticles penetration and transport in planta

Resumen del póster presentado en la 9th International Conference on the Scientific and Clinical Applications of Magnetic Carriers, celebrada en Minneapolis (Estados Unidos) del 22 al 26 de mayo de 2012.Magnetic nanoparticles are very suitable for a broad range of applications, like those involving synthesis and use of ferrofluids for bio-applications in general. In medicine the aim is to use them in diagnosis as well as in therapy. The ongoing research and results obtained up to now in these fields open a wide range of possibilities for using magnetic nanoparticles in other disciplines, for example in general plant research and agronomy. To study the use of nanoparticles in agriculture the first stage is to work out the penetration and transport into living plants and plant cells. We present here an overview of the research carried out within the scope of an interdisciplinary collaboration, on how inorganic nanoparticles interact with plant cells and tissues.