Insect antimicrobial peptides: potential weapons to counteract the antibiotic resistance

Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization

High performance wearable ultrasound as a human-machine interface for wrist and hand kinematic tracking

Objective: Non-invasive human machine interfaces (HMIs) have high potential in medical, entertainment, and industrial applications. Traditionally, surface electromyography (sEMG) has been used to track muscular activity and infer motor intention. Ultrasound (US) has received increasing attention as an alternative to sEMG-based HMIs. Here, we developed a portable US armband system with 24 channels and a multiple receiver approach, and compared it with existing sEMG- and US-based HMIs on movement intention decoding. Methods: US and motion capture data was recorded while participants performed wrist and hand movements of four degrees of freedom (DoFs) and their combinations. A linear regression model was used to offline predict hand kinematics from the US (or sEMG, for comparison) features. The method was further validated in real-time for a 3-DoF target reaching task. Results: In the offline analysis, the wearable US system achieved an average R2 of 0.94 in the prediction of four DoFs of the wrist and hand while sEMG reached a performance of R2=0.06 . In online control, the participants achieved an average 93% completion rate of the targets. Conclusion: When tailored for HMIs, the proposed US A-mode system and processing pipeline can successfully regress hand kinematics both in offline and online settings with performances comparable or superior to previously published interfaces. Significance: Wearable US technology may provide a new generation of HMIs that use muscular deformation to estimate limb movements. The wearable US system allowed for robust proportional and simultaneous control over multiple DoFs in both offline and online settings

Insect antimicrobial peptides: potential weapons to counteract the antibiotic resistance

Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization

Dopamine and Glutamate Induce Distinct Striatal Splice Forms of Ania-6, an RNA Polymerase II-Associated Cyclin

AbstractControl of neuronal gene expression by drugs or neurotransmitters is a critical step in long-term neural plasticity. Here, we show that a gene induced in the striatum by cocaine or direct dopamine stimulation, ania-6, is a member of a novel family of cyclins with homology to cyclins K/T/H/C. Further, different types of neurotransmitter stimulation cause selective induction of distinct ania-6 isoforms, through alternative splicing. The longer Ania-6 protein colocalizes with nuclear speckles and is associated with key elements of the RNA elongation/processing complex, including the hyperphosphorylated form of RNA polymerase II, the splicing factor SC-35, and the p110 PITSLRE cyclin-dependent kinase. Distinct types of neuronal stimulation may therefore differentially modulate nuclear RNA processing, through altered transcription and splicing of ania-6

Advances in Azorella glabra Wedd. Extract research: In vitro antioxidant activity, antiproliferative effects on acute myeloid leukemia cells and bioactive compound characterization

Azorella glabra Wedd. (AG) is traditionally used to treat gonorrhea or kidney's problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of AG chloroform fraction (AG CHCl3) and of its ten sub-fractions (I-X) and to identify their possible bioactive compounds. We determined their in vitro antioxidant activity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) and superoxide anion (SO) assays, and their phytochemical profile by spectrophotometric and LC-MS/MS techniques. I-X action on two acute myeloid leukemia (AML) cell lines viability, apoptosis and cell cycle were evaluated by MTS, western blotting and cytofluorimetric assays. Different polyphenol, flavonoid and terpenoid amount, and antioxidant activity were found among all samples. Most of I-X induced a dose/time dependent reduction of cell viability higher than parent extract. IV and VI sub-fractions showed highest cytotoxic activity and, of note, a negligible reduction of healthy cell viability. They activated intrinsic apoptotic pathway, induced a G0/G1 block in leukemic cells and, interestingly, led to apoptosis in patient AML cells. These activities could be due to mulinic acid or azorellane terpenoids and their derivatives, tentatively identified in both IV and VI. In conclusion, our data suggest AG plant as a source of potential anti-AML agents

Distributed normal faulting in the tip zone of the South Alkyonides Fault System, Gulf of Corinth, constrained using 36Cl exposure dating of late-Quaternary wave-cut platforms

The geometry, rates and kinematics of active faulting in the region close to the tip of a major crustal-scale normal fault in the Gulf of Corinth, Greece, are investigated using detailed fault mapping and new absolute dating. Fault offsets have been dated using a combination of 234U/230Th coral dates and in situ 36Cl cosmogenic exposure ages for sediments and wave-cut platforms deformed by the faults. Our results show that deformation in the tip zone is distributed across as many as eight faults arranged within ~700 m across strike, each of which deforms deposits and landforms associated with the 125 ka marine terrace of Marine Isotope Stage 5e. Summed throw-rates across strike achieve values as high as 0.3–1.6 mm/yr, values that are comparable to those at the centre of the crustal-scale fault (2–3 mm/yr from Holocene palaeoseismology and 3–4 mm/yr from GPS geodesy). The relatively high deformation rate and distributed deformation in the tip zone are discussed in terms of stress enhancement from rupture of neighbouring crustal-scale faults and in terms of how this should be considered during fault-based seismic hazard assessment

CIRCULATING PLACENTAL VESCICLES CARRY HLA-DR IN PRE - ECLAMPSIA : A NEW POTENTIAL MARKER OF THE SYNDROME

Pre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Out of phase Quaternary uplift-rate changes reveal normal fault interaction, implied by deformed marine palaeoshorelines

We have mapped and constrained the timing of tectonically deformed uplifted Late Quaternary palaeoshorelines in the Messina Strait, southern Italy, an area above a subduction zone containing active normal faults. The palaeoshorelines are preserved from up to thirteen Late Quaternary sea-level highstands, providing a record of the deformation over this timescale (~500 ka) for the Messina-Taormina Fault, the Reggio Calabria Fault and the Armo Fault. The palaeoshorelines reveal spatial patterns of uplift through time along the strike of these normal faults, and, given the across strike arrangement of the faults, also reveal how the contribution of each fault to the regional strain-rate progressed through time. The results reveal that the uplift rates mapped within the fault hangingwalls and footwalls were not constant through time, with a marked change in the location of strain accumulation at ~50 ka. The uplift rates, once converted into throw-rates, imply that the three faults comprised similar throw-rates prior to ~50 ka (in the range 0.77–0.96 mm/yr), with the Armo and Reggio Calabria faults then switching to lower rates (0.32 mm/yr and 0.33 mm/yr respectively), whilst the Messina-Taormina Fault accelerated to 2.34 mm/yr. The regional extension rate, gained by summing the implied heave rates across the three faults, was maintained through time despite this re-organisation of local strain accumulation at ~50 ka. We explain these out-of-phase fault throw-rate changes during the constant-rate regional extension conditions as due to interactions between these upper plate normal faults. We finally discuss how fault throw-rates changing through time may affect a long-term seismic hazard assessment within active normal fault systems