Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption

Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∼2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia) in the framework of the projects: PTDC/CTM/101484/2008; PEst-C/SAU/LA0002/2013; Pest-C/QUI/UI0081/2013. Fabiola Costa acknowledges FCT for the PhD grant SFRH/BD/72471/2010

Low‐cost tools mitigate climate change during reproduction in an endangered marine ectotherm

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordData Availability Statement: Data available via the Dryad Digital Repository https://doi.org/10.5061/dryad.3r2280gfq. (Clarke et al., 2021)The impacts of anthropogenic climate change will be most dramatic for species that live in narrow thermal niches, such as reptiles. Given the imminent threat to biodiversity, and that actions to reduce carbon emissions are not yet sufficient, it is important that a sound evidence base of potential mitigation options is available for conservation managers. Successful incubation and production of male sea turtle hatchlings is threatened by increased global temperatures (sex is determined by the temperature at which eggs incubate). Here we test two conservation tools to reduce incubation temperatures: clutch splitting and clutch shading, on a nesting loggerhead turtle (Caretta caretta) population in the Eastern Atlantic Ocean. During the thermosensitive period of incubation, split and shaded clutches were both 1.00 ˚C cooler than control nests. Clutch splitting (mean: 45 eggs) reduced nest temperatures by reducing metabolic heating during incubation compared to controls (mean: 92 eggs). Modelled primary sex ratios differed between nest treatments, with 1.50 % (± 6 % S.E.) females produced in shaded nests, 45.00 % (± 7 % S.E.) females in split nests and 69.00 % (± 6% S.E.) females in controls. Neither treatment affected hatchling size, success, mass or vigour. When clutch splitting was repeated two years later, hatch success was higher in split clutches compared to controls. Synthesis and Applications: Clutch splitting and clutch shading successfully altered the thermal profile of incubating turtle nests. When there is sufficient knowledge to better understand the effects of intervention on fundamental population demographics, they will be useful for reducing incubation temperatures in sea turtle nests, potentially increasing nest survival and male hatchling production. The effect of clutch splitting in reducing nest temperature was lower relative to clutch shading, but requires significantly less funding, materials and specialist skill, key factors for management of turtle rookeries that are often in remote, resource‐limited areas.Worldwide Fund for NatureWAVE Foundation of Newport Aquariu

Investigation of the long-term sustainability of changes in appetite after weight loss

Background/Objective Diet-induced weight loss (WL) leads to a compensatory increase in appetite and changes in the plasma concentration of appetite-regulating hormones are likely to play a role. Whether these changes are transient or sustained remains unclear. This study aimed to assess if changes in subjective and objective appetite markers observed with WL are sustained after 1 year (1Y).Subjects/Methods In total 100 (45 males) individuals with obesity (BMI: 37 +/- 4 kg/m(2), age: 43 +/- 10 years) underwent 8 weeks (wks) of a very-low energy diet (VLED), followed by 4 wks refeeding, and a 1Y maintenance program. Fasting/postprandial subjective ratings of hunger, fullness, desire to eat, and prospective food consumption (PFC) were assessed, and plasma concentration of active ghrelin (AG), total peptide YY (PYY), active glucagon-like peptide 1, cholecystokinin (CCK), and insulin measured, at baseline, week 13 (Wk13) and 1Y.Results At Wk13, 16% WL (-18 +/- 1 kg, P < 0.001) was associated with a significant increase in fasting and postprandial hunger ratings (P < 0.01 and P < 0.05, respectively), and postprandial fullness (P < 0.01) combined with a reduction in PFC (P < 0.001). These were accompanied by a significant rise in basal and postprandial AG concentrations (P < 0.001, for both), a reduction in postprandial CCK (P < 0.01) and in basal and postprandial insulin (P < 0.001). At 1Y follow-up, with sustained WL (15%; -16 +/- 1 kg, P < 0.001), fasting hunger and postprandial fullness ratings remained increased (P < 0.05 for both), and postprandial PFC reduced (P < 0.001). Basal and postprandial AG remained elevated and insulin reduced (P < 0.001, for all), while postprandial CCK was increased (P < 0.01) and PYY decreased (P < 0.001).Conclusion With a 15% sustained WL at 1Y, the drive to eat in the fasting state is increased, but this may be balanced out by raised postprandial feelings of fullness. To assist with WL maintenance, new strategies are required to manage increased hunger and drive to eat

On Tackling the Limits of Resolution in SAT Solving

The practical success of Boolean Satisfiability (SAT) solvers stems from the CDCL (Conflict-Driven Clause Learning) approach to SAT solving. However, from a propositional proof complexity perspective, CDCL is no more powerful than the resolution proof system, for which many hard examples exist. This paper proposes a new problem transformation, which enables reducing the decision problem for formulas in conjunctive normal form (CNF) to the problem of solving maximum satisfiability over Horn formulas. Given the new transformation, the paper proves a polynomial bound on the number of MaxSAT resolution steps for pigeonhole formulas. This result is in clear contrast with earlier results on the length of proofs of MaxSAT resolution for pigeonhole formulas. The paper also establishes the same polynomial bound in the case of modern core-guided MaxSAT solvers. Experimental results, obtained on CNF formulas known to be hard for CDCL SAT solvers, show that these can be efficiently solved with modern MaxSAT solvers

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Quercetin Impact in Pancreatic Cancer: An Overview on Its Therapeutic Effects

Pancreatic cancer (PC) is a lethal malignancy cancer, and its mortality rates have been increasing worldwide. Diagnosis of this cancer is complicated, as it does not often present symptoms, and most patients present an irremediable tumor having a 5-year survival rate after diagnosis. Regarding treatment, many concerns have also been raised, as most tumors are found at advanced stages. At present, anticancer compounds-rich foods have been utilized to control PC. Among such bioactive molecules, flavonoid compounds have shown excellent anticancer abilities, such as quercetin, which has been used as an adjunctive or alternative drug to PC treatment by inhibitory or stimulatory biological mechanisms including autophagy, apoptosis, cell growth reduction or inhibition, EMT, oxidative stress, and enhancing sensitivity to chemotherapy agents. The recognition that this natural product has beneficial effects on cancer treatment has boosted the researchers’ interest towards more extensive studies to use herbal medicine for anticancer purposes. In addition, due to the expensive cost and high rate of side effects of anticancer drugs, attempts have been made to use quercetin but also other flavonoids for preventing and treating PC. Based on related studies, it has been found that the quercetin compound has significant effect on cancerous cell lines as well as animal models. Therefore, it can be used as a supplementary drug to treat a variety of cancers, particularly pancreatic cancer. This review is aimed at discussing the therapeutic effects of quercetin by targeting the molecular signaling pathway and identifying antigrowth, cell proliferation, antioxidative stress, EMT, induction of apoptotic, and autophagic features.The authors acknowledge the Molecular Medicine Research Center, Bio-Medicine Institute, Tabriz University of Medical Sciences, and the Clinical Research Development Unit of Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran. This work was supported and funded by Tabriz University of Medical Sciences, Tabriz, Iran (grant number: 68344)

Low‐cost tools mitigate climate change during reproduction in an endangered marine ectotherm

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordData Availability Statement: Data available via the Dryad Digital Repository https://doi.org/10.5061/dryad.3r2280gfq. (Clarke et al., 2021)The impacts of anthropogenic climate change will be most dramatic for species that live in narrow thermal niches, such as reptiles. Given the imminent threat to biodiversity, and that actions to reduce carbon emissions are not yet sufficient, it is important that a sound evidence base of potential mitigation options is available for conservation managers. Successful incubation and production of male sea turtle hatchlings is threatened by increased global temperatures (sex is determined by the temperature at which eggs incubate). Here we test two conservation tools to reduce incubation temperatures: clutch splitting and clutch shading, on a nesting loggerhead turtle (Caretta caretta) population in the Eastern Atlantic Ocean. During the thermosensitive period of incubation, split and shaded clutches were both 1.00 ˚C cooler than control nests. Clutch splitting (mean: 45 eggs) reduced nest temperatures by reducing metabolic heating during incubation compared to controls (mean: 92 eggs). Modelled primary sex ratios differed between nest treatments, with 1.50 % (± 6 % S.E.) females produced in shaded nests, 45.00 % (± 7 % S.E.) females in split nests and 69.00 % (± 6% S.E.) females in controls. Neither treatment affected hatchling size, success, mass or vigour. When clutch splitting was repeated two years later, hatch success was higher in split clutches compared to controls. Synthesis and Applications: Clutch splitting and clutch shading successfully altered the thermal profile of incubating turtle nests. When there is sufficient knowledge to better understand the effects of intervention on fundamental population demographics, they will be useful for reducing incubation temperatures in sea turtle nests, potentially increasing nest survival and male hatchling production. The effect of clutch splitting in reducing nest temperature was lower relative to clutch shading, but requires significantly less funding, materials and specialist skill, key factors for management of turtle rookeries that are often in remote, resource‐limited areas.Worldwide Fund for NatureWAVE Foundation of Newport Aquariu