We consider measurements of exclusive rare semi-tauonic
b
-hadron decays, mediated by the
b
→
s
τ
+
τ
-
transition, at a future high-energy circular electron–positron collider (FCC-
ee
). We argue ...that the high boosts of
b
-hadrons originating from on-shell
Z
boson decays allow for a full reconstruction of the decay kinematics in hadronic
τ
decay modes (up to discrete ambiguities). This, together with the potentially large statistics of
Z
→
b
b
¯
, opens the door for the experimental determination of
τ
polarizations in these rare
b
-hadron decays. In the light of the current experimental situation on lepton flavor universality in rare semileptonic
B
decays, we discuss the complementary short-distance physics information carried by the
τ
polarizations and suggest suitable theoretically clean observables in the form of single- and double-
τ
polarization asymmetries.
Snake venoms are natural sources of biologically active molecules that are able to act selectively and specifically on different cellular targets, modulating physiological functions. Thus, these ...mixtures, composed mainly of proteins and peptides, provide ample and challenging opportunities and a diversified molecular architecture to design and develop tools and agents of scientific and therapeutic interest. Among these components, peptides and small proteins play diverse roles in numerous physiological processes, exerting a wide range of pharmacological activities, such as antimicrobial, antihypertensive, analgesic, antitumor, analgesic, among others. The pharmaceutical and cosmetic industries have recognized the huge potential of these privileged frameworks and believe them to be a promising alternative to contemporary drugs. A number of natural or synthetic peptides from snake venoms have already found preclinical or clinical applications for the treatment of pain, hypertension, cardiovascular diseases and aging skin. A well-known example is captopril, whose natural peptide precursor was isolated from Bothrops jararaca snake venom, which is a peptide-based drug that inhibits the angiotensin-converting enzyme, producing an anti-hypertensive effect. The present review looks at the main peptides (natriuretic peptides, bradykinin-potentiating peptides and sarafotoxins) and low mass proteins (crotamine, disintegrins and three-Finger toxins) from snake venoms, as well as synthetic peptides inspired by them, describing their biochemical, structural and physiological features, as well as their applications as research tools and therapeutic agents.
This study evaluates the antifungal activity and mechanism of action of a new chemotype of
Lavandula multifida
from Portugal. The essential oil was analyzed by gas chromatography (GC) and gas ...chromatography/mass spectrometry (GC/MS), and the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) of the oil and its major compounds were determined against several pathogenic fungi responsible for candidosis, meningitis, dermatophytosis, and aspergillosis. The influence of the oil on the dimorphic transition in
Candida albicans
was also studied, as well as propidium iodide (PI) and FUN-1 staining of
C. albicans
cells by flow cytometry. The essential oil was characterized by high contents of monoterpenes, with carvacrol and
cis
-
β
-ocimene being the main constituents. The oil was more effective against dermatophytes and
Cryptococcus neoformans
, with MIC and MLC values of 0.16 μL/mL and 0.32 μL/mL, respectively. The oil was further shown to completely inhibit filamentation in
C. albicans
at concentrations below the respective MIC (0.08 μL/mL), with
cis
-
β
-ocimene being the main compound responsible for this inhibition (0.02 μL/mL). The flow cytometry results suggest a mechanism of action ultimately leading to cytoplasmic membrane disruption and cell death.
L. multifida
essential oil may be useful in complementary therapy to treat disseminated candidosis, since the inhibition of filamentation alone appears to be sufficient to treat this type of infection.
Tetrahydropyran (THP) rings are common in several natural products, therefore, various strategies are being developed to synthesize these rings. The present work described the study of a one-pot ...synthesis of 2,4,6-trisubstituted tetrahydropyran compounds promoted by the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate BMIMPF
through a Barbier-Prins reaction between allyl bromide and aldehydes. The use of BMIMPF
gave Prins products from several aldehydes in good yields and reaction times. We also found that the anion, PF
-, accelerates the Barbier reaction when used alone, and the excess SnBr
from the reaction conditions of the Barbier reaction leads to the formation of the THP rings, thus acting as a catalyst for Prins cyclization. Additionally, we demonstrate that ionic liquid can be recovered and reused five times in the preparation of 4-bromo-tetrahydro-2,6-diphenyl-2H-pyran without significant yield loss.
The membrane-active nature of phospholipase A2-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake ...venom Lys49-PLA2 toxins (p-AppK and p-Acl), differing by a leucine/phenylalanine substitution, were synthesized and their bioactivity was evaluated. Their capacity to interfere with the survival of Gram-positive and Gram-negative bacteria as well as with solid and liquid tumors was assessed in vitro. Toxicity to red blood cells was investigated via in silico and in vitro techniques. The mode of action was mainly studied by molecular dynamics simulations and membrane permeabilization assays. Briefly, both peptides have dual activity, i.e., they act against both bacteria, including multidrug-resistant strains and tumor cells. All tested bacteria were susceptible to both peptides, Pseudomonas aeruginosa being the most affected. RAMOS, K562, NB4, and CEM cells were the main leukemic targets of the peptides. In general, p-Acl showed more significant activity, suggesting that phenylalanine confers advantages to the antibacterial and antitumor mechanism, particularly for osteosarcoma lines (HOS and MG63). Peptide-based treatment increased the uptake of a DNA-intercalating dye by bacteria, suggesting membrane damage. Indeed, p-AppK and p-Acl did not disrupt erythrocyte membranes, in agreement with in silico predictions. The latter revealed that the peptides deform the membrane and increase its permeability by facilitating solvent penetration. This phenomenon is expected to catalyze the permeation of solutes that otherwise could not cross the hydrophobic membrane core. In conclusion, the present study highlights the role of a single amino acid substitution present in natural sequences towards the development of dual-action agents. In other words, dissecting and fine-tuning biomembrane remodeling proteins, such as snake venom phospholipase A2 isoforms, is again demonstrated as a valuable source of therapeutic peptides.
Reference broth microdilution protocols for the antifungal susceptibility testing (AST) of yeasts are available, but routine AST relies more on simpler alternatives. In this work, the Etest and a ...novel flow cytometry (FC) method were compared to the Clinical Laboratory Standards Institute (CLSI) protocol M27-A3. Caspofungin and anidulafungin were tested against 60 clinical isolates of
Candida glabrata
,
C. krusei
, and
C. parapsilosis
. There were two intermediate susceptibility results and 19 out of 20 tested
C. krusei
strains were categorized as resistant to caspofungin (minimum inhibitory concentration MIC of 1.0 mg/L). There was a generally excellent essential agreement with the reference method, only interrupted by Etest results for the anidulafungin susceptibility of
C. glabrata
(80%) and the FC method’s results for caspofungin with
C. krusei
(40%). Categorical agreements were excellent, with the notable exception of the caspofungin-resistant
C. krusei
, with 19 very major errors for the FC method and 19 minor errors plus one very major error for the Etest (5% and 0% categorical agreements, respectively). Two additional minor errors were registered for the FC method when testing
C. parapsilosis
with anidulafungin and caspofungin. Overall, these data come to question the suitability of recently approved clinical breakpoints in the case of
C. krusei
. Further studies including
fks
mutants are now required.
Although reference broth microdilution protocol is currently available for filamentous fungi antifungal susceptibility testing (AFST), simpler alternatives as Etest
®
tend to be favoured in clinical ...routine, making their validation of utmost importance. In this study, Etest
®
method using 2 % glucose supplemented Muller–Hinton agar was compared to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 protocol for filamentous fungi AFST. The echinocandins, caspofungin and anidulafungin, the azoles voriconazole and posaconazole, and the polyene amphotericin B were tested against 48
Aspergillus
spp., seven
Fusarium
spp., one
Beauveria bassiana
and three
Paecilomyces lilacinus
isolates. The majority of the isolates were susceptible to the antifungals tested, and the overall level of agreement between the CLSI and Etest methods was 71.9 % for one dilution and 99.7 % when using two dilutions. Since interpretative breakpoints for filamentous fungi employing the CLSI or Etest methods are not available yet, the established epidemiological cut-off values for
Aspergillus
spp. were used to distinguish wild-type isolates from those with acquired resistance mechanisms. Forty-five
Aspergillus
strains did not evidence resistance mutations.
This study investigated the effect of silicon (Si) on resistance of bean plants (cv. ‘Peróla’) to anthracnose, caused by Colletotrichum lindemuthianum, grown in a nutrient solution containing 0 (−Si) ...or 2 mmol Si L−1 (+Si). The concentration of Si in leaf tissue and the incubation period increased by 55.2% and 14.3%, respectively, in +Si plants in relation to −Si plants. The area under anthracnose progress curve and the severity estimated by the software QUANT significantly decreased by 32.9% and 27%, respectively, for +Si plants. Si did not affect the concentration of total soluble phenolics. Chitinases activity was higher in the advanced stages of infection by C. lindemuthianum for leaves of −Si plants. β‐1,3‐Glucanase activity increased after C. lindemuthianum infection, but it was not enhanced by Si. Peroxidase and polyphenoloxidase activities had no apparent effect on the resistance of bean plants to anthracnose, regardless of the presence of Si. The increase in lignin concentration as well as on the phenylalanine ammonia‐lyase and lipoxygenase activities were important for the resistance of +Si plants against anthracnose. The results of this study suggest that Si may increase resistance to anthracnose in bean plants by enhancing certain biochemical mechanisms of defence as opposed to just acting as a physical barrier to penetration by C. lindemuthianum.
Mucositis induced by antineoplastic drugs is an important, dose-limiting, and costly side effect of cancer therapy.
To investigate the role of nitric oxide (NO) on the pathogenesis of 5-fluorouracil ...(5-FU)-induced oral mucositis.
Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) in male hamsters. Animals were treated subcutaneously with saline (0.4 ml), 1,400 W (1 mg/kg), aminoguanidine (5 or 10 mg/kg) or Nphi-Nitro-L-Arginine Methyl Ester (L-NAME) (5, 10, or 20 mg/kg) 1 h before the injections of 5-FU and daily until sacrifice, on the tenth day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase (MPO) activity, nitrite level, and immunohistochemistry for induced nitric oxide synthase (iNOS).
Treatment with 1,400 W or aminoguanidine reduced macroscopic and histological parameters of oral mucositis, and reduced the inflammatory cell infiltration as detected by histopathology and by MPO activity. In contrast, the administration of L-NAME did not significantly reverse the inflammatory alterations induced by experimental mucositis. Increased NOS activity, nitrite level and immunostaining for iNOS were detected on the check pouch tissue of animals submitted to 5-FU-induced oral mucositis on the tenth day.
These results suggest an important role of NO produced by iNOS in the pathogenesis of oral mucositis induced by 5-FU.
ABSTRACT
Deserts and arid regions are generally perceived as bare and rather homogeneous areas of low diversity. The Sahara is the largest warm desert in the world and together with the arid Sahel ...displays high topographical and climatic heterogeneity, and has experienced recent and strong climatic oscillations that have greatly shifted biodiversity distribution and community composition. The large size, remoteness and long‐term political instability of the Sahara‐Sahel, have limited knowledge on its biodiversity. However, over the last decade, there have been an increasing number of published scientific studies based on modern geomatic and molecular tools, and broad sampling of taxa of these regions. This review tracks trends in knowledge about biodiversity patterns, processes and threats across the Sahara‐Sahel, and anticipates needs for biodiversity research and conservation. Recent studies are changing completely the perception of regional biodiversity patterns. Instead of relatively low species diversity with distribution covering most of the region, studies now suggest a high rate of endemism and larger number of species, with much narrower and fragmented ranges, frequently limited to micro‐hotspots of biodiversity. Molecular‐based studies are also unravelling cryptic diversity associated with mountains, which together with recent distribution atlases, allows identifying integrative biogeographic patterns in biodiversity distribution. Mapping of multivariate environmental variation (at 1 km × 1 km resolution) of the region illustrates main biogeographical features of the Sahara‐Sahel and supports recently hypothesised dispersal corridors and refugia. Micro‐scale water‐features present mostly in mountains have been associated with local biodiversity hotspots. However, the distribution of available data on vertebrates highlights current knowledge gaps that still apply to a large proportion of the Sahara‐Sahel. Current research is providing insights into key evolutionary and ecological processes, including causes and timing of radiation and divergence for multiple taxa, and associating the onset of the Sahara with diversification processes for low‐mobility vertebrates. Examples of phylogeographic patterns are showing the importance of allopatric speciation in the Sahara‐Sahel, and this review presents a synthetic overview of the most commonly hypothesised diversification mechanisms. Studies are also stressing that biodiversity is threatened by increasing human activities in the region, including overhunting and natural resources prospection, and in the future by predicted global warming. A representation of areas of conflict, landmines, and natural resources extraction illustrates how human activities and regional insecurity are hampering biodiversity research and conservation. Although there are still numerous knowledge gaps for the optimised conservation of biodiversity in the region, a set of research priorities is provided to identify the framework data needed to support regional conservation planning.
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