326 research outputs found
An Investigation on the antimicrobial activity of some endemic plant species from Turkey
In this study performed on six endemic plant species, antimicrobial activity was observed in Campanula lyrata subsp.lyrata and Abies nordmanniana subsp. bornmuelleriana plants. The minimum inhibitoryconcentration of C. lyrata subsp. lyrata (leaf and flower) extract was found to be 29 mg/ml for Baccillus subtilis and 14.5 mg/ml for Staphylococcus aureus, and the minimum inhibitory concentration (MIC) of Abies nordmanniana subsp. bornmuelleriana (leaf) extract was found to be > 314 mg/ml for B. subtilis and when minimum bacteriocidal concentration (MBC) results were evaluated, it was observed that the plant extracts had bacteriocidal effects. No antimicrobial activity was observed inthe other plant extracts, namely, Onosma bornmuelleri (leaf- flower), Dianthus balansae (leaf- flower), Alyssum pateri subsp. pateri (seed) and Scabiosa columbaria subsp. paphlagonica (leaf) extracts thatwere tested
Unusual cause of a painful right testicle in a 16-year-old man: a case report
<p>Abstract</p> <p>Introduction</p> <p>Urgent surgical exploration of the scrotum of a child or teenager who presents with a painful and swollen testicle is paramount if testicular torsion is not to be missed. It is extremely rare for a non-scrotal pathology to present with acute scrotal signs. Here we present such a rare case and emphasize the importance of being aware of this potential clinical pitfall.</p> <p>Case presentation</p> <p>A 16-year-old Caucasian man presented as a surgical emergency with a five to six hour history of a painful, red, and swollen right hemiscrotum. He also complained of vague lower abdominal pain, vomiting, and watery diarrhea. He had a temperature of 38.5°C and a tender, red, and swollen right hemiscrotum. The right testicle appeared elevated. He was mildly tender in his central and upper abdomen and less so in the lower abdomen. No convincing localizing abdominal signs were noted. He had an increased white cell count (15 × 10<sup>9</sup>/L) and C-reactive protein (CRP; 300 mg/L). Urgent right hemiscrotal exploration revealed about 5 ml of pus in the tunica vaginalis and a normal testicle. A right iliac fossa incision identified the cause: a perforated retrocecal appendix. Appendectomy was performed, and both the abdomen and scrotum washed copiously with saline before closure. The patient made an uneventful recovery.</p> <p>Conclusion</p> <p>Acute appendicitis presenting with scrotal signs due to a patent processus vaginalis is an extremely rare clinical entity. To date, fewer than five such cases have been reported in the medical literature. It is, therefore, extremely important to be aware of this unusual clinical scenario, as only a high index of suspicion will enable prompt, successful management of both the appendicitis and the scrotal abscess.</p
Effects of treatment with chitosan on sensory and chemical quality parameters of frozen shrimp
Activity Dependent Protein Degradation Is Critical for the Formation and Stability of Fear Memory in the Amygdala
Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses
The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study
Background We recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. Methods Following the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains. Results Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types. Conclusions Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania
Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy
Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control
NMR and in silico studies of fucosylated chondroitin sulfate (fCS) and its interactions with selectins
This thesis describes structural studies on the interactions between the fucosylated
chondroitin sulfate (fCS) oligosaccharides and human proteins known as selectins. fCS is a
carbohydrate obtained from sea cucumbers, that can be classified as a branched
glycosaminoglycan (GAG). It has attracted much attention due to its anti-coagulant, anti-inflammatory,
antimetastatic and anti-HIV properties and its structure was previously
determined by NMR. Selectins constitute a family of proteins involved in cell adhesion
processes, such as inflammation, attachment of viral particles and migration of tumour cells.
fCS oligosaccharides have been shown to bind to selectins, which is likely a reason behind
their biological activity. However, the mechanism of this interaction is currently unknown.
The initial part of the thesis describes the experimental work on expression and purification
of the recombinant L- and P-selectin constructs in Pichia pastoris, Escherichia coli and HEK
293 cells. The aim of these experiments was to produce two constructs for each selectin, a
single domain construct, consisting of the C-type lectin domain only, and a double domain
construct, consisting of both the C-type lectin and the EGF-like domains. The intention was
that the recombinant proteins would be labelled with 13C and 15N to allow for the in-depth
structural NMR studies on the fCS-selectin interaction. Various experimental approaches
have been explored, including the use of different cell lines, modifications to construct design,
as well as alterations to expression and purification conditions. Although it was not possible
to produce soluble selectin constructs in either bacterial or yeast cells, protein expression
tests in HEK293 cells, performed in collaboration with the Oxford Protein Production facility
(OPPF), led to production of a soluble L-selectin construct, consisting of the L-selectin C-type
lectin domain.
The produced L-selectin construct, as well as two commercially available constructs of the Land
P-selectin extracellular domains, were used in the Saturation Transfer Difference (STD)
NMR experiments to provide new information about the nature of the fCS-selectin binding.
The STD experiments allowed to identify the regions within the fCS oligosaccharides that are
in direct contact with the protein and likely play an important role in this interaction.
Experiments on different protein constructs allowed the comparison of fCS binding to P-selectin
and to two different recombinant constructs of L-selectin. Results of these studies
suggest that the binding occurs via a similar mechanism for both L- and P-selectins and that
the fCS oligosaccharides bind to one-domain L-selectin construct with similar affinity as to a
larger construct, consisting of the entire extracellular region of the protein.
Alongside the experimental work, theoretical in silico studies on the fCS-selectin binding
were undertaken as part of this project. The existing X-ray structures of selectin complexes
were subjected to Molecular Dynamics (MD) simulations, which allowed to explore the
dynamic behaviour of E-selectin upon binding to sialyl Lewis x (sLex). It was found that sLex
forms a more favourable interaction with the extended conformation of E-selectin and that
the protein in this conformation is characterised by a high degree of interdomain flexibility,
with a new type of interdomain movement observed in the MD studies on this complex.
In further in silico studies, the fCS oligosaccharides were docked to the existing P-selectin
structures. The docking tests were performed on the computationally produced fCS
trisaccharides with fucose branches either 2,4 or 3,4-sulfated. Results were evaluated with
MD simulations and analysed in the light of current knowledge of selectin-ligand binding and
the STD NMR experimental results. The in silico studies allowed to identify a subset of P-selectin
residues that are likely involved in the interaction with fCS oligosaccharides in vivo.
The conformational behaviour of P-selectin upon binding to fCS was also explored and it was
found that the interdomain hinge is flexible during this interaction and allows transition from
bent to extended conformational state.
Finally, a new NMR method was developed to facilitate the studies of complex carbohydrates,
incorporating the concepts of G-matrix Fourier Transform (GFT) NMR into 2D HSQC and 2D
HSQC-TOCSY experiments. The method allows to separate peaks in the regions of high
spectral overlap, providing information that can simplify the assignment process. The new
experiments facilitated the structural evaluation of a sample containing a mixture of
oligosaccharides resulting from the depolymerisation of fCS polysaccharide
Forest biodiversity, carbon sequestration, and wood production: modeling synergies and trade-offs for ten forest landscapes across Europe
Original ResearchEurope’s forests provide vital habitat for biodiversity and essential ecosystem services
whose provision must be sustained or enhanced over the coming century. However,
the potential to secure or increase forest ecosystem services, while securing the
habitat requirements of taxa remains unclear, especially within the context of uncertain
climate and socio-economic developments. To tease out the associated trade-offs
and synergies, we used 10 case study landscapes within nine countries throughout
Europe. Starting with the current status of the forests in the case study landscapes,
we simulated forest development 100 years into the future. Simulations were embedded
in three combined climate and socio-economic frame scenarios based on global and
European policies which varied in their climate change mitigation efficiency. Scenarios
were translated into country specific projections of climate variables, and resultant
demands for wood products. Forest management regimes were projected to vary in
response to these scenarios at local scales. The specific combinations of alternative
forest management practices were based on parallel research and input from local forest
stakeholders. For each case study, a specific forest growth simulator was used. In
general, the climate scenarios applied did not cause fundamentally different ecosystem
service outputs at the case study level. Our results revealed almost no reduction in outcomes for biodiversity indicators with an increase in wood production, and in some
cases synergistic results occurred when diversity was actively promoted as part of the
management concept. Net carbon uptake was not strongly correlated with biodiversity,
indicating that biodiversity-friendly forest management doesn’t need to curtail carbon
sequestration. Notably, we obtained heterogeneous results for the relation between
sustainable wood production and net carbon uptake. Most scenarios resulted in a
more or less reduced net carbon uptake over the long term, often due to stand age
class distribution shifts. Levels of sustainable wood production varied widely during
the simulation period, from significant increases (Sweden, Lithuania) to minor changes
(Slovakia, Turkey) and slight decreases (Ireland, Netherlands). We place our results
within the larger context of European forest policy and the challenges of simulating and
contrasting forest biodiversity and the ecosystem services that societies depend on outcomes for biodiversity indicators with an increase in wood production, and in some
cases synergistic results occurred when diversity was actively promoted as part of the
management concept. Net carbon uptake was not strongly correlated with biodiversity,
indicating that biodiversity-friendly forest management doesn’t need to curtail carbon
sequestration. Notably, we obtained heterogeneous results for the relation between
sustainable wood production and net carbon uptake. Most scenarios resulted in a
more or less reduced net carbon uptake over the long term, often due to stand age
class distribution shifts. Levels of sustainable wood production varied widely during
the simulation period, from significant increases (Sweden, Lithuania) to minor changes
(Slovakia, Turkey) and slight decreases (Ireland, Netherlands). We place our results
within the larger context of European forest policy and the challenges of simulating and
contrasting forest biodiversity and the ecosystem services that societies depend oninfo:eu-repo/semantics/publishedVersio
Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe
Proteasomes must efficiently remove their substrates throughout the cells in a timely manner as many of these proteins can be toxic. This study shows that proteasomes can do so efficiently because they are highly mobile. Furthermore this study uncovers that proteasome mobility requires functional Arc3, a subunit of the Arp2/3 complex
Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development
Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common “gatekeepers” which may drive nutritional programming
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