Deprotection Research Articles

Open areas associated with traditional agriculture promote functional connectivity among amphibian demes in Mediterranean agrosystems

ContextFunctional connectivity across fragmented habitat patches is essential for the conservation of animal populations in humanized landscapes. Given their low dispersal capacity, amphibians in the Mediterranean region are threatened by habitat fragmentation and loss due to changes in land use, including agricultural intensification.ObjectivesWe assessed patterns of functional connectivity of a Near Threatened Mediterranean amphibian, the sharp ribbed newt (Pleurodeles waltl), in an agricultural landscape matrix in NW Spain subject to different intensification regimes.MethodsWe sampled newts in 17 ponds embedded in a terrestrial habitat matrix dominated by agricultural land uses. Genome-wide molecular markers (1390 SNPs) were used to assess patterns of genetic diversity and gene flow among ponds. We tested the role of landscape features on functional connectivity using isolation by resistance models incorporating information on Normalized Difference Vegetation Index (NDVI) data.ResultsWe found low levels of genetic diversity in all sampled populations. Global FST estimates and cluster analyses revealed shallow but significant genetic structure in the study area, with NDVI-based resistance models showing that open areas (rainfed crops and grasslands) offer lower resistance to gene flow and thus promote functional connectivity among demes.ConclusionsOur study highlights the important role of landscape features, such as open areas resulting from traditional rainfed agriculture, in promoting functional connectivity between amphibian populations in Mediterranean agrosystems. Conservation policies must adopt a functional network strategy and protect groups of inter-connected temporary ponds across the traditional agricultural matrix to efficiently preserve their associated biotic communities.

Controllable Photocleavage of Blebbistatin Derivatives as Photoremovable Protecting Groups.

Blebbistatin was demonstrated as a promising two-photon near-infrared activated photoremovable protecting group of hydroxyl radicals with various potential applications. However, the photocleavage mechanism of the blebbistatin derivatives remains ambiguous. Herein, blebbistatin derivatives with various electronic characteristic leaving groups were synthesized and studied, and the photocleavage mechanism(s) and the tunable effect of the leaving groups were unveiled by combining photoproduct analysis, reactive oxygen radical species detection, femtosecond transient absorption spectroscopy, and density functional theory calculation. More substantial electron-withdrawing leaving groups facilitate heterolysis of the C-O bond, which results in a cationic intermediate and a corresponding remnant. Weaker electron-withdrawing groups lead to a higher proportion of homolysis of the C-O bond, accompanied by the generation of the reactive oxygen radical species. With this structure-property relationship, the protected groups of the molecules of interest can be rationally chosen to satisfy the different requirements needed for specific applications.

Wolf contact in horses at permanent pasture in Germany.

Wolves returned to Germany in 2000, leading to fear in German horse owners that their horses could be in danger of wolf attacks or panic-like escapes from pastures when sighting wolves. However, reports from southern European countries indicate that wolf predation on horses diminishes with increasing presence of wildlife. Therefore, we conducted a long-term, filed observation between January 2015 and July 2022 on 13 non breeding riding horses, mares and geldings, kept permanently on two pastures within the range of wildlife and a stable wolf pack with annual offspring. Wildlife cameras at the fences of the pastures made 984 times recordings of wolves and 3151 times recordings of wildlife in and around the pastures. Between 1 January 2022 and 23 March 2022 we observed two stable horse groups. Pasture 1 was grazed by five horses of mixed breed, four mares and one gelding, with the median age of 8 years (min. = 6y, max. = 29y). Pasture 2 was grazed by eight heavy warmbloods and draught horses, three mares and five geldings, with the median age of 16 years (min. = 13y, max. = 22y). During this period no wolf was recorded at pasture 2, but wild boar several times, whereas at pasture 1, wolves were recorded 89 times, and for the wildlife mostly hare. Wolves may have avoided pasture 2 because of the presence of wild boar or because the large group of older, heavy breed horses may have formed a stable, protective group. The latter needs to be confirmed in a follow-up field observation, which records anti-predator behavior and welfare indicators in horses. In conclusion, wolves did not attack the mature horses on pastures with plenty of wildlife and the horses did not respond to the presence of wolves with visible signs of reduced welfare or panic. This indicates that wolves may prefer to prey on easily accessible wildlife around and at horse pastures and that Central European horses become accustom to the presence of non-hunting wolves.

Synthesis of (±)-zeapyranolactone, a noncanonical strigolactone isolated from maize, and determination of its overall relative configuration

Strigolactones are a class of apocarotenoids known as rhizosphere semiochemicals and plant hormones. They are classified as either canonical, with a tricyclic lactone (ABC ring) and a butenolide (D ring) comprising their basic skeleton, or noncanonical, deviating from the basic skeleton. Here, zeapyranolactone, a noncanonical strigolactone isolated from maize, was synthesized for the first time as a racemic and diastereomeric mixture, and its relative stereochemistry was determined by three-dimensional electron diffraction crystallography as 4S*,4aS*,2′R*. The synthetic route developed is straightforward and does not rely on the use of typical protective groups.

Multi-Body Hydrodynamic Interactions in Fish-Like Swimming

Abstract Many animals in nature travel in groups either for protection, survival, or endurance. Among these, certain species do so under the burden of aero/hydrodynamic loads, which incites questions as to the significance of the multibody fluid-mediated interactions that are inherent to collective flying/swimming. Prime examples of such creatures are fish, which are commonly seen traveling in highly organized groups of large numbers. Indeed, over the years, there have been numerous attempts to examine hydrodynamic interactions among self-propelled fish-like swimmers. Though many have studied this phenomenon, their motivations have varied from understanding animal behavior to extracting universal fluid dynamical principles and transplanting them into engineering applications. The approaches utilized to carry out these investigations include theoretical and computational analyses, field observations, and experiments using various abstractions of biological fish. Here, we compile representative investigations focused on the collective hydrodynamics of fish-like swimmers. The selected body of works are reviewed in the context of their methodologies and findings, so as to draw parallels, contrast differences, and highlight open questions. Overall, the results of the surveyed studies provide foundational insights into the conditions (such as the relative positioning and synchronization between the members, as well as their swimming kinematics and speed) under which hydrodynamic interactions can lead to efficiency gains and/or group cohesion in two- and three-dimensional scenarios. They also shed some light on the mechanisms responsible for such energetic and stability enhancements in the context of wake-body, wake-wake, and body-body interactions.

Incorporation of Protecting Groups in Organic Chemistry: A Mini-Review.

The approach of utilizing protecting groups (PGs) in organic chemistry has led to the successful syntheses of an array of useful organic compounds. This strategy has also addressed some of the complexities associated with many organic reactions. These PGs find useful applications in simple and complex reactions that involve the synthesis of large organic compounds such as peptides, and oligosaccharides. The fundamental role of PGs is to prevent undesired reactions that could hinder the progress or completion of such reactions. Ideal PGs must be utilized in this regard to achieve the desired objectives. This review describes the diverse protecting groups found in the literatures, the functional moieties for the protection, deprotection strategies, and their relevant applications in organic synthesis.

Contribution of contrast-enhanced ultrasound in the diagnosis of adnexal torsion (AGATA): protocol for a prospective comparative study

IntroductionAdnexal torsion is a surgical emergency and its prognosis depends on the time elapsed prior to treatment. The diagnosis relies on pelvic ultrasound in which sensitivity remains low and may...

Multimodal and dynamic cross-linking of modular thiolated alginate-based bioinks

Engineered extracellular matrix-mimicking hydrogels can facilitate 3D cell culture and fabrication of tissue-like constructs and biologically relevant disease models. Processing of cell-laden hydrogels using additive manufacturing techniques further allows for the development of tissue-mimetic structures with higher spatial complexity. Whereas a wide range of printable hydrogels is available, they tend to lack biological functionality and cell compatibility. Here we show an enzymatically mediated thiol-based cross-linking strategy for the design of modular and cytocompatible hydrogel-based bioinks for 3D bioprinting of dynamic multi-material architectures. Alginate is functionalized with cysteines modified with an enzyme-labile thiol protection group. Deprotection using penicillin G acylase (PGA) generates free thiols on-demand, enabling hydrogel cross-linking using thiol-reactive cross-linkers and intermolecular disulfides while avoiding undesired and uncontrolled thiol oxidation. Remaining free thiols can be used for post-printing hydrogel functionalization and lamination of multilayer structures. Moreover, the addition of PGA to a thermo-reversible hydrogel support bath enables the bioprinting of cell-laden 3D structures with high cell viability and excellent shape fidelity. The possibilities to enzymatically generate free thiols during bioprinting facilitate cross-linking and tuning of bioink properties using cytocompatible chemistries and allow for the printing of complex and dynamic cell-laden structures.

Synthesis of 1,2,3-triazoles using Grignard reactions through the protection of azides.

An efficient method to prepare organomagnesium intermediates having a protected azido group is reported. Protection of azido groups with di-(tert-butyl)(4-(dimethylamino)phenylphosphine (amphos) and following iodine-magnesium exchange realized the preparation of organomagnesium intermediates, which served in the synthesis of diverse azides by transformation with various electrophiles followed by deprotection with elemental sulfur. Furthermore, click reactions of azides with alkynes enabled synthesizing a wide variety of 1,2,3-triazoles.

Synthesis of Enantiomerically Pure Bambus[6]urils Utilizing Orthogonal Protection of Glycolurils.

A general strategy for the synthesis of 2N,4N'-disubstituted glycoluril enantiomers on a multigram scale using orthogonal protection is reported. The use of these glycolurils is demonstrated in the synthesis of enantiomerically pure bambus[6]uril macrocycles. Moreover, the deprotection of (S)-1-phenylethyl substituents on the macrocycle was achieved, opening access to various chiral bambus[6]urils via post-macrocyclization modification strategy.

Protective impacts of Withania somnifera leaf extract from Taif area against diclofenac induced hepato-renal toxicity: role of antioxidants, inflammation, apoptosis, and anti-oxidative stress biomarkers.

Current study examined the boosting impacts of Withania somnifera leaf extract from Taif area (high-altitude area) against hepatic and renal toxicity induced by diclofenac in experimental rats. Withania is highly grown on Taif area as environmental herb with multiple functions. Diclofenac is non-steroidal medication used for treatment of pain but over dose has severe side effects. Thirty-two adult Wistar rats of male type were subdivided into 4 groups. The control rats (group 1) received saline. Second group received diclofenac (50mg/kg BW intraperitoneally) at days 4 and 5. Third group received W. somnifera leaf extract (250mg /kg body weight) for 6days. The fourth protective group, received W. somnifera leaf extract plus diclofenac for 6days as shown in groups 2 and 3. Diclofenac significantly increased serum AST, ALT, and decreased albumin and total proteins levels. It also increased serum concentrations of uric acid and creatinine. In addition, it increased lipid peroxidation, and decreased reduced glutathione and superoxide dismutase levels. Diclofenac increased inflammatory cytokines secretion and up-regulated hepatic oxidative stress genes (HO-1; hemoxygenase-1 and Nrf2nuclear factor erythroid 2-related factor 2 (Nrf2) and renal inflammatory transcriptional markers (TGF-β1; transforming growth factor-beta1 and COX-2; cycloxygenas-2). In parallel, hepatic caspase-3 expression was up-regulated as an apoptotic marker, while Bcl2; (B-cell lymphoma 2) mRNA expression was down regulated as anti-apoptotic marker. W. somnifera pre-administration in the protective group ameliorated the altered parameters induced by diclofenac. In conclusion, W. somnifera leaf extract has the potential to antagonize side effects of diclofenac by regulating the pathways of oxidative stress, inflammation, and apoptosis/antiapoptosis.

Screening Serum Biomarkers for Rats Preconditioned with Hyperbaric Oxygen: Potential of Predicting Prognosis for Stroke.

Stroke is a major health concern and a leading cause of mortality and morbidity. We and other groups have documented that hyperbaric oxygen preconditioning could significantly alleviate neuronal damage in ischemia‒reperfusion models through various mechanisms. However, we found that some of the subjects did not benefit from preconditioning with hyperbaric oxygen. The preconditioning phenomenon is similar to vaccination, in which the endogenous survival system is activated to fight against further injuries. However, with vaccine inoculations, we could test for specific antibodies against the pathogens to determine if the vaccination was successful. Likewise, this experiment was carried out to explore a biomarker that can reveal the effectiveness of the preconditioning before neuronal injury occurs. Middle cerebral artery occlusion (MCAO) was used to induce focal cerebral ischemia-reperfusion injury. 2D-DIGE-MALDI-TOF-MS/MS proteomic technique was employed to screen the differentially expressed proteins in the serum of rats among the control (Con) group (MCAO model without hyperbaric oxygen (HBO) preconditioning), hyperbaric oxygen protective (HBOP) group (in which the infarct volume decreased after HBO preconditioning vs. Con), and hyperbaric oxygen nonprotective (HBOU) group (in which the infarct volume remained the same or even larger after HBO preconditioning vs. Con). Candidate biomarkers were confirmed by western blot and enzyme linked immunosorbent assay (ELISA), and the relationship between the biomarkers and the prognosis of cerebral injury was further validated. Among the 15 differentially expressed protein spots detected in the HBOP group by Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), 3 spots corresponding to 3 different proteins (haptoglobin, serum albumin, and haemopexin) products were identified by MALDI-TOF-MS/MS. Serum albumin and haemopexin were upregulated, and haptoglobin was downregulated in the HBOP group (p < 0.05 vs. Con and HBOU groups). After the western blot study, only the changes in haemopexin were validated and exhibited similar changes in subjects from the HBOP group in accordance with MALDI-TOF-MS/MS proteomic analysis and enzyme linked immunosorbent assay (ELISA) analysis. The serum level of the hemopexin (HPX) at 2 h after HBO preconditioning was correlated with the infarct volume ratio after MCAO. Haemopexin may be developed as a predictive biomarker that indicated the effectiveness of a preconditioning strategy against cerebral ischaemic injury.

Biocompatible Lysine Protecting Groups for the Chemoenzymatic Synthesis of K48/K63 Heterotypic and Branched Ubiquitin Chains.

The elucidation of emerging biological functions of heterotypic and branched ubiquitin (Ub) chains requires new strategies for their preparation with defined lengths and connectivity. While in vitro enzymatic assembly using expressed E1-activating and E2-conjugating enzymes can deliver homotypic chains, the synthesis of branched chains typically requires extensive mutations of lysines or other sequence modifications. The combination of K48- and K63-biased E2-conjugating enzymes and two new carbamate protecting groups-pyridoxal 5'-phosphate (PLP)-cleavable aminobutanamide carbamate (Abac group) and periodate-cleavable aminobutanol carbamate (Aboc group)-provides a strategy for the synthesis of heterotypic and branched Ub trimers, tetramers, and pentamers. The Abac- and Aboc-protected lysines are readily prepared and incorporated into synthetic ubiquitin monomers. As these masking groups contain a basic amine, they preserve the overall charge and properties of the Ub structure, facilitating folding and enzymatic conjugations. These protecting groups can be chemoselectively removed from folded Ub chains and monomers by buffered solutions of PLP or NaIO4. Through the incorporation of a cleavable C-terminal His-tag on the Ub acceptor, the entire process of chain building, iterative Abac deprotections, and global Aboc cleavage can be conducted on a resin support, obviating the need for handling and purification of the intermediate oligomers. Simple modulation of the Ub monomers affords various K48/K63 branched chains, including tetramers and pentamers not previously accessible by synthetic or biochemical methods.

The legal concept of discrimination by association: where does it fit into the digital era?

Personal autonomy, a core human rights principle, refers to the ability to both design and conduct the course of one’s life through making choices from a range of valuable options. This plays a pivotal role in the realm of equality and non discrimination, which are relevant in the context of the European Union (EU). Through case law, the concept of discrimination by association has emerged as a crucial step in strengthening anti-discrimination, recognising that individuals who are not part of a protected group but who have a relationship with someone who is, or are in some way associated with them, may be treated unfavourably, thus requiring appropriate remedies. Currently, the field of non-discrimination increasingly warrants attention, due to the rapid advancement of technology, which harbours unique discriminatory potential. For instance, through data mining and the use of artificial intelligence tools for profiling and clustering, people may be grouped based on collective characteristics that may not accurately represent their individual features, resulting in differential treatment regardless of whether legally recognised vulnerable groups are involved. It therefore becomes crucial to question to what extent discrimination by association can effectively address this discriminatory power or whether new measures need to be developed to safeguard personal autonomy and prevent the proliferation of such phenomena in the current digital landscape.

Anti-inflammatory and Protective Effects of Melatonin on Rats Exposed to Anticancer Drugs

ABSTRACT This study was aimed to investigate the effects of Melatonin at )10mg/kg) on liver function enzymes AST,ALT,ALP activity and determination the inflammatory marker CRP activity and total counting of WBC on rats exposed to anticancer drugs Gemcitabine, and protective effects of melatonin in the liver tissue.Materials and Methods: sixty four adult male albino rats were used in this study, weighing (250-350) gm at temperature 22±20C , The animals were feeding and drinking water as needed . the animals were divided into 5 main groups as follow : Group A( Control group n=8 ) given a daily D.W. Group B:(melatonin group n=8)given a daily melatonin 10mg/kg/orally. Group C (Gemcitabine n=16) this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg). Group D (protective group n=16): this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg ) together with given a daily melatonin in dose (10mg /kg) orally.Group E (protective and treatment group n=16) : this group was divided into two group according to Gemcitabine dose (25 and 50 mg/kg ). This group was given a daily melatonin in dose (10mg /kg) orally as a treatment. The results showed that melatonin reduced the activity of AST, ALT enzymes compare with gemcitabine treated groups, While increased the activity of ALP in A, B groups compare with gemcitabine treated groups , that induced by chemotherapy drug ,While decreased the activity of CRP inflammatory marker in A, B groups compare with another groups that treated with anticancer drug. Melatonin given protective effect on liver enzymes and tissues from damaged that happened by Gemcitabine in two different dose (25,50 mg/kg ) .

Influence of amino acid and N-terminal protection residue structures on peptide p-nitroanilide adsorption on polystyrene-based support.

Polystyrene-based support Bio-Beads® SM-2 was employed for desalting peptide-p-nitroanilides from Oxone®. Neither tosyl, 9-fluorenyl(methoxycarbonyl), p-nitroanilide groups nor indolyl or p-hydroxyphenyl side-chains of Trp and Tyr ensured an efficient adsorption of peptide-p-nitroanilides onto Bio-Beads® SM-2. Only unsubstituted phenyl-containing protection groups (carbobenzoxy or benzoyl) and Phe residues provided the adsorption of peptides on Bio-Beads® SM-2 and their efficient desalting. This support is well suitable for multiple parallel phenyl group-containing peptide derivative separations and high-throughput screenings.

Practical Synthesis of N-Formylmethionylated Peptidyl-tRNA Mimics.

Hydrolysis-resistant RNA-peptide conjugates that mimic peptidyl-tRNAs are frequently needed for structural and functional studies of protein synthesis in the ribosome. Such conjugates are accessible by chemical solid-phase synthesis, allowing for the utmost flexibility of both the peptide and the RNA sequence. Commonly used protection group strategies, however, have severe limitations with respect to generating the characteristic Nα-formylmethionyl terminus because the formyl group of the conjugate synthesized at the solid support is easily cleaved during the final basic deprotection/release step. In this study, we demonstrate a simple solution to the problem by coupling appropriately activated Nα-formyl methionine to the fully deprotected conjugate. The structural integrity of the obtained Nα-formylmethionyl conjugate─and hence the chemoselectivity of the reaction─were verified by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry sequence analysis. Additionally, we confirmed the applicability of our procedure for structural studies by obtaining two structures of the ribosome in complex with either fMAI-nh-ACCA or fMFI-nh-ACCA in the P site and ACC-PMN in the A site of the bacterial ribosome at 2.65 and 2.60 Å resolution, respectively. In summary, our approach for hydrolysis-resistant Nα-formylated RNA-peptide conjugates is synthetically straightforward and opens up new avenues to explore ribosomal translation with high-precision substrate mimics.

From Pyridine to (−)‐Agelastatin A

Abstract(−)‐Agelastatin A was synthetized employing a flow photorearrangement of a pyridinium salt, constructing in one step the cyclopentene core possessing the desired functionalities and relative configurations. A flow enzymatic kinetic resolution of the resulting bicyclic vinyl aziridine delivered the enantiopure precursor to the natural product. This total synthesis required the use of a single protective group. Two novel agelastatin N3‐derivatives were synthesized and their cytotoxicity evaluated against a series of cancer cell lines, which corroborated the importance of unsubstituted N3 in the biological activity of (−)‐agelastatin A.

PupillOmetry for preDIction of DeliriUM in ICU (PODIUM): protocol for a prospective multicentre cohort study

IntroductionDelirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate...

Which spontaneous breathing trial to predict effort to breathe after extubation according to five critical illnesses: the cross-over GLOBAL WEAN study protocol

IntroductionReadiness to be freed from ventilatory support can be evaluated by spontaneous breathing trial (SBT) assessing the patient’s ability to sustain respiratory effort after extubation. Current SBT practices are heterogenous...