Sequencings in Semidirect Products via the Polynomial Method

The partial sums of a sequence ${\mathbf x} = x_1, x_2, \ldots, x_k$ of distinct non-identity elements of a group $(G,\cdot)$ are $s_0 = id_G$ and $s_j = \prod_{i=1}^j x_i$ for $0 < j \leq k$. If the partial sums are all different then ${\mathbf x}$ is a linear sequencing and if the partial sums are all different when $|i-j| \leq t$ then ${\mathbf x}$ is a $t$-weak sequencing. We investigate these notions of sequenceability in semidirect products using the polynomial method. We show that every subset of order $k$ of the non-identity elements of the dihedral group of order $2m$ has a linear sequencing when $k \leq 12$ and either $m>3$ is prime or every prime factor of $m$ is larger than $k!$, unless $s_k$ is unavoidably the identity; that every subset of order $k$ of a non-abelian group of order three times a prime has a linear sequencing when $5 < k \leq 10$, unless $s_k$ is unavoidably the identity; and that if the order of a group is $pe$ then all sufficiently large subsets of the non-identity elements are $t$-weakly sequenceable when $p>3$ is prime, $e \leq 3$ and $t \leq 6$.Comment: arXiv admin note: text overlap with arXiv:2203.1665

Induction of a Protective Response in Mice by the Dengue Virus NS3 Protein Using DNA Vaccines

The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serino-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus. In the present work, we investigate the protective efficacy of DNA vaccines based on the NS3 protein from DENV2. Different recombinant plasmids were constructed, encoding either the full-length NS3 protein or only its functional domains (protease and helicase), fused or not to a signal peptide (t-PA). The recombinant proteins were successfully expressed in transfected BHK-21 cells, and only plasmids encoding the t-PA signal sequence mediated protein secretion. Balb/c mice were immunized with the different DNA vaccines and challenged with a lethal dose of DENV2. Most animals immunized with plasmids encoding the full-length NS3 or the helicase domain survived challenge, regardless of the presence of the t-PA. However, some mice presented clinical signs of infection with high morbidity (hind leg paralysis and hunched posture), mainly in animal groups immunized with the DNA vaccines based on the helicase domain. On the other hand, inoculation with plasmids encoding the protease domain did not induce any protection, since mortality and morbidity rates in these mouse groups were similar to those detected in the control animals. The cellular immune response was analyzed by ELISPOT with a specific-CD8+ T cell NS3 peptide. Results revealed that the DNA vaccines based on the full-length protein induced the production of INF-γ, thus suggesting the involvement of this branch of the immune system in the protection

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated. © 2001 Cancer Research Campaign http://www.bjcancer.co

Wood smoke exposure of Portuguese wildland firefighters: DNA and oxidative damage evaluation

Portugal is among the European Union countries most devastated by forest fires each year. In the last three decades, more than 3.8 million hectares of forest were burned. Wildland firefighters are exposed to a variety of hazards, including many toxic combustion products that may lead to deleterious health effects. Epidemiological studies showed a positive association between firefighting and several chronic diseases, including cancer. Results from biomonitoring studies in firefighters, particularly concerning genotoxicity evaluation, constitute a valuable tool for investigating important occupational hazards. Thus, the aim of this study was to assess genotoxicity in a group of wildland firefighters using the comet assay for DNA damage and oxidative stress. Both parameters were increased in firefighters compared to controls, but significance was only found for basal DNA damage. No significant influence was found regarding major confounding variables on the genotoxic endpoints studied, with the exception of age. Data obtained provide preliminary information on human health effects of wildland firefighting exposure at genetic and molecular levels. These findings may also provide new important data to serve as public awareness to the potential adverse health risks involving wildland firefighting. Implementation of security and hygiene measures in this sector as well as good practices campaigns may be crucial to decrease risk.info:eu-repo/semantics/publishedVersio

Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Background Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. Scope and approach In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. Key findings and conclusions The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCβ3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCβ3 and the TRPV1 channel; 2) serotonin, or a selective agonist, α-methyl-serotonin (α-Me-5-HT), requires the presence of PLCβ3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCβ3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD^+ neurons that represent ≈90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1+ nociceptors led to a significant behavioral deficit for pruritogens, including α-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways

Bacteriologic investigation of the effects of sodium hypochlorite and chlorhexidine during the endodontic treatment of teeth with apical periodontitis

SIQUEIRA JR. et al. Bacteriologic investigation of the effects of sodium hypochlorite and chlorhexidine during the endodontic treatment of teeth with apical periodontitis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., v. 104, n. 1, p. 122-130, 2007.Objective. This clinical study was undertaken to compare the effectiveness of 2.5% sodium hypochlorite (NaOCl) and 0.12% chlorhexidine digluconate as irrigants in reducing the cultivable bacterial populations in infected root canals of teeth with apical periodontitis. Study design. According to stringent inclusion/exclusion criteria, 32 teeth with primary intraradicular infections and chronic apical periodontitis were selected and followed in the study. Bacterial samples were taken at the baseline (S1) and after chemomechanical preparation using either NaOCl (n 16) or chlorhexidine (n 16) as irrigants (S2). Cultivable bacteria recovered from infected root canals at the 2 stages were counted. Isolates from S2 samples were identified by means of 16S rRNA gene sequencing analysis. Results. At S1, all canals were positive for bacteria, and the median number of bacteria per canal was 7.32 105 for the NaOCl group and 8.5 105 for the chlorhexidine group. At S2, the median number of bacteria in canals irrigated with NaOCl and chlorhexidine was 2.35 103 and 2 102, respectively. Six of 16 (37.5%) canals from the NaOCl group and 8 of 16 (50%) canals from the chlorhexidine group yielded negative cultures. Chemomechanical preparation using either solution substantially reduced the number of cultivable bacteria in the canals. No significant difference was observed between the NaOCl and chlorhexidine groups with regard to the number of cases yielding negative cultures (P .72) or quantitative bacterial reduction (P .609). The groups irrigated with NaOCl or chlorhexidine showed a mean number of 1.3 and 1.9 cultivable species per canal, respectively. The great majority of isolates in S2 were from gram-positive bacteria, with streptococci as the most prevalent taxa. Conclusions. The present findings revealed no significant difference when comparing the antibacterial effects of 2.5% NaOCl and 0.12% chlorhexidine used as irrigants during the treatment of infected canal

Differential Midgut Attachment of Leishmania (Viannia) braziliensis in the Sand Flies Lutzomyia (Nyssomyia) whitmani and Lutzomyia (Nyssomyia) intermedia

The interaction between Leishmania and sand flies has been demonstrated in many Old and New World species. Besides the morphological differentiation from procyclic to infective metacyclic promastigotes, the parasite undergoes biochemical transformations in its major surface lipophosphoglycan (LPG). An upregulation of β-glucose residues was previously shown in the LPG repeat units from procyclic to metacyclic phase in Leishmania (Viannia) braziliensis, which has not been reported in any Leishmania species. LPG has been implicated as an adhesion molecule that mediates the interaction with the midgut epithelium of the sand fly in the Subgenus Leishmania. These adaptations were explored for the first time in a species from the Subgenus Viannia, L. (V.) braziliensis with its natural vectors Lutzomyia (Nyssomyia) intermedia and Lutzomyia (Nyssomyia) whitmani. Using two in vitro binding techniques, phosphoglycans (PGs) derived from procyclic and metacyclic parasites were able to bind to the insect midgut and inhibit L. braziliensis attachment. Interestingly, L. braziliensis procyclic parasite attachment was ∼11-fold greater in the midgut of L. whitmani than in L. intermedia. The epidemiological relevance of L. whitmani as a vector of American Cutaneous Leishmaniasis (ACL) in Brazil is discussed