Modeling the alkylation of amines with alkyl bromides: explaining the low selectivity due to multiple alkylation.

CONTEXT: Nucleophilic substitution reactions of aliphatic amines with alkyl halides represent a simple and direct mechanism for obtaining higher-order aliphatic amines. However, it is well known that these reactions suffer from low selectivity due to multiple alkylations, which is attributed to the higher reactivity of the newly formed amine. In order to provide a detailed explanation for this kind of system, we have investigated the reactivity of primary and secondary amines with 1-bromopropane and 2-bromopropane. The free energy profile in acetonitrile solution was obtained and a detailed microkinetic analysis was needed to analyze this complex reaction system. We have found that the product of the first alkylation is an ion pair corresponding to the protonated secondary amine and the bromide ion, which can transfer the proton to the reactant primary amine. Then, the newly formed secondary amine can also react, leading to a second alkylation to produce a tertiary protonated amine. Our modeling points out that both the proton transfer equilibria and the similar reactivity of the primary and secondary amines produce reduced selectivity. The proton transfer equilibria also contribute to slowing down the kinetics of the first alkylation. METHODS: The exploration of the mechanism was done by geometry optimization using the CPCM/X3LYP/ma-def2-SVP method, followed by harmonic frequency calculation at this same level of theory. A composite approach was used to obtain the free energy profile, using the more accurate ωB97X-D3/ma-def2-TZVPP level of theory for electronic energy and the SMD model for the solvation free energy. These calculations were performed with the ORCA 4 program. The detailed microkinetic analysis was done using the Kintecus program.

Mechanical Properties of Experimental Composites with Different Photoinitiator.

OBJECTIVE: The effect of different photoinitiators on mechanical properties of experimental composites was evaluated. MATERIALS AND METHODS: Resin composites were formulated by using a blend of bisphenol A-glycidyl and triethylene glycol (50/50 wt%) dimethacrylate monomers, and 65 wt% of barium aluminium silicate and silica filler particles. Photoinitiators used were 0.2% camphorquinone (CQ) and 0.8% co-initiator (DMAEMA); 0.2% phenyl-propanedione and 0.8% DMAEMA; 0.1% CQ + 0.1% phenyl propanedione and 0.8% DMAEMA; 0.42% mono(acyl)phosphine oxide (MAPO); and 0.5% bis(acyl)phosphine oxide (BAPO). Specimens (n = 10) were light cured by using a multiple-emission peak light-emitting diode for 20 seconds at 1,200 mW/cm2 of irradiance and Knoop hardness and plasticization, depth of cure, flexural strength, and elastic modulus were evaluated. Data were statiscally analyzed at significance level of α = 5%. RESULTS: Experimental composites containing MAPO and BAPO photoinitiators showed the highest values of flexural strength, elastic modulus, top surface hardness, and lower hardness reduction caused by alcohol compared with CQ. Composites containing CQ and PPD showed similar results, except for depth of cure and hardness of bottom surface. CONCLUSION: BAPO and MAPO showed higher flexural strength, elastic modulus, hardness on top surface, and lower polymer plasticization to CQ.

Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut.

Aneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the spindle assembly checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.

Proposal of a theoretical model to identify organizational decline.

This study aimed to propose a conceptual model of Identification of Organizational Decline, based on two indicators: Organizational Satisfaction Indicator and Financial Indicator. For the study, we used two bibliometric reviews, which, ultimately, associated the variables of the foundations of excellence in quality with organizational decline. As a result, we observed that the topic of organizational decline in companies has factors of managerial, physical, financial, and behavioral nature, and that their performances worsen by their lack of initiative in using the three planning processes (strategic planning, budget, and control) in a structured way. Regarding companies that seek excellence in quality, these concerns become increasing demands for their managers, who must develop responsible practices and tools to achieve a good performance, bearing in mind the constant search for satisfaction and retention of customers not only for the final product, but throughout the chain process. Thus, the literature on this topic is vast, and this study is justified because it notes a strong relationship between the lack of factors of excellence in management and organizational decline.

Chemical composition and roughness of enamel and composite after bleaching, acidic beverages and toothbrushing.

BACKGROUND: In this study was assessed the surface roughness and chemical composition of tooth enamel and composite resin after bleaching treatment, immersion in acidic beverages, and simulated toothbrushing. MATERIAL AND METHODS: One hundred and twenty dental blocks (10 x 10 x 3 mm) were randomly assigned (n = 10) according to surface treatment [none (N), bleaching (B), toothbrushing (T), and B+T] and storage medium [saliva (S), whiskey (W), and orange juice (O)]: experimental groups - N+S, N+W, N+O, B+S, B+W, B+O, S+T, W+T, O+T, B+S+T, B+W+T, and B+O+T. Two bleaching sessions were conducted using 38% hydrogen peroxide (3 applications). Surface roughness was measured using a roughness tester and composition was determined by micro energy-dispersive X-ray fluorescence spectrometry (µ-EDXRF) before and after treatments. Calcium/phosphorus (Ca/P) ratio in enamel and silica (Si) content in composite were evaluated. Data were statistically analyzed by ANOVA and Tukey's test (α = 0.05). RESULTS: Overall, increased values of surface roughness for enamel and composite were observed mainly after immersion in orange juice and bleaching/toothbrushing association. Moreover, this association and immersion in whiskey resulted in lower Ca/P ratio and after aging methods, bleached and bleached/toothbrushed groups showed decreased in Ca/P ratio compared to initial values. All groups showed Si content decrease at the end, except the group without surface treatment and immersed in saliva, and bleaching followed by immersion in orange juice and toothbrushing caused the highest Si reduction. CONCLUSIONS: Bleaching and toothbrushing combination strengthened the effects caused by acidic drinks on roughness and chemical composition of enamel and composite. Key words:Tooth bleaching, toothbrushing, physical properties, chemical properties.

Tissue stem cells: the new actors in the aneuploidy field.

The development of multicellular organisms and the maintenance of its tissues relies on mitosis. However, this process represents a major challenge for genomic stability as each time a cell division occurs there are multiple steps where errors can lead to an abnormal chromosomal content in daughter cells - aneuploidy. Aneuploidy was first postulated to act as a tumour promoting agent over one century ago. Since then, we have learned to appreciate the complexity involving the cellular responses to aneuploidy and to value the importance of models where aneuploidy is induced in vivo and in a cell-type specific manner. Recent data suggests that stem cells evolved a distinct response to aneuploidy, being able to survive and proliferate as aneuploid. Since stem cells are the main cells responsible for tissue renewal, it is of the utmost importance to place the spotlight on stem cells within the aneuploidy field. Here, we briefly review some of the biological mechanisms implicated in aneuploidy, the relationship between aneuploidy and tissue pathologies, and summarize the most recent findings in Drosophila on how tissue stem cells respond to aneuploidy. Once we understand how stem cell behavior is impacted by aneuploidy, we might be able to better describe the complicated link between aneuploidy and tumourigenesis.

Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila.

Aneuploidy is associated with different human diseases including cancer. However, different cell types appear to respond differently to aneuploidy, either by promoting tumorigenesis or causing cell death. We set out to study the behavior of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of chromosome missegregation either by abrogation of the spindle assembly checkpoint or through kinetochore disruption or centrosome amplification. These conditions induce moderate levels of aneuploidy in ISCs, and we find no evidence of apoptosis. Instead, we observe a significant accumulation of ISCs associated with increased stem cell proliferation and an excess of enteroendocrine cells. Moreover, aneuploidy causes up-regulation of the JNK pathway throughout the posterior midgut, and specific inhibition of JNK signaling in ISCs is sufficient to prevent dysplasia. Our findings highlight the importance of understanding the behavior of different stem cell populations to aneuploidy and how these can act as reservoirs for genomic alterations that can lead to tissue pathologies.

Effect of beverages with different alcoholic concentration on composite resins / Efeito de bebidas com diferentes concentrações alcoólicas em resinas compostas

Objective: To evaluate if alcoholic beverages can cause color change in composite resins, if the alcoholic concentration influences this variation besides analyzing within the composite resins tested, which would present greater color stability when subjected to the experiment. Material and Methods: 90 specimens of three different composite resins (IPS Empress Direct, Grandio®So and Filtek Z350 XT) were immersed in distilled water (control group), red wine and vodka. The samples were 2 mm thick and 8 mm in diameter, photopolymerized for 20 s on each side, polished with sandpaper, silicon carbide tip and felt disc with prophylactic paste and immersed in distilled water at 37 °C for 24 h prior to subgrouping. For the evaluation of the color variation, the formula prioritized by the CIEL *a *b* system was used. Data were analyzed by ANOVA and Tukey's test at 95% significance. Results: The lowest variations occurred with the Grandio®So resin when exposed to wine, and Filtek Z350 XT when exposed to vodka. There was a statistically significant difference between the groups in water (p < 0.01) and in red wine (p < 0.01), but not in vodka (p > 0.05). The soaking medium that most caused staining was red wine. Conclusion: Red wine was the drink that generated the highest staining in all the resins tested, vodka did not change color stability significantly, the alcoholic concentrations tested did not directly influence the color change and the composite resin Grandio®So presented greater color stability when exposed to red wine. (AU)

Objetivo: Avaliar se bebidas alcóolicas podem provocar alteração de cor em resinas compostas, se a concentração alcóolica tem influência nesta variação além de analisar dentre as resinas compostas testadas, qual apresentaria maior estabilidade de cor quando submetidas ao experimento. Material e métodos: Foram confeccionados 90 espécimes de 3 diferentes resinas compostas (IPS Empress Direct, Grandio®So e Filtek Z350 XT) e imersos em água destilada (grupo controle), vinho tinto e vodca. As amostras mediam 2 mm de espessura e 8 mm de diâmetro, foram fotopolimerizados por 20 s cada lado, polidos com disco de lixa, ponta de carbeto de silício e disco de feltro com pasta profilática e imersos em água destilada a 37 ºC por 24 h antes da divisão em subgrupos. Para a avaliação da variação de cor foi utilizada a fórmula priorizada pelo sistema CIEL*a*b*. Os dados foram analisados por ANOVA e teste de Tukey a 95% de significância. Resultados: As menores variações ocorreram com a resina Grandio®So quando exposta ao vinho, e a Filtek Z350 XT quando exposta à vodca. Houve diferença estatisticamente significante entre os grupos na água (p < 0.01) e no vinho tinto (p < 0.01), mas não na vodca (p > 0,05). O meio de imersão que mais causou manchamento foi o vinho tinto. Conclusão: O vinho tinto foi a bebida que gerou o maior manchamento em todas as resinas testadas, a vodca não alterou a estabilidade de cor de maneira significativa, as concentrações alcóolicas testadas não influenciaram diretamente na alteração de cor e a resina composta Grandio®So apresentou maior estabilidade de cor frente ao vinho tinto. (AU)

Pilot testing model to uncover industrial symbiosis in Brazilian industrial clusters.

The main objective of this study was to create a pilot model to uncover industrial symbiosis practices in Brazilian industrial clusters. For this purpose, a systematic revision was conducted in journals selected from two categories of the ISI Web of Knowledge: Engineering, Environmental and Engineering, Industrial. After an in-depth revision of literature, results allowed the creation of an analysis structure. A methodology based on fuzzy logic was applied and used to attribute the weights of industrial symbiosis variables. It was thus possible to extract the intensity indicators of the interrelations required to analyse the development level of each correlation between the variables. Determination of variables and their weights initially resulted in a framework for the theory of industrial symbiosis assessments. Research results allowed the creation of a pilot model that could precisely identify the loopholes or development levels in each sphere. Ontology charts for data analysis were also generated. This study contributes to science by presenting the foundations for building an instrument that enables application and compilation of the pilot model, in order to identify opportunity to symbiotic development, which derives from "uncovering" existing symbioses.

Intestinal stem cell ablation reveals differential requirements for survival in response to chemical challenge.

The Drosophila intestine is maintained by multipotent intestinal stem cells (ISCs). Although increased intestinal stem cell (ISC) proliferation has been correlated with a decrease in longevity, there is some discrepancy regarding whether a decrease or block in proliferation also has negative consequences. Here we identify headcase (hdc) as a novel marker of ISCs and enteroblasts (EBs) and demonstrate that Hdc function is required to prevent ISC/EB loss through apoptosis. Hdc depletion was used as a strategy to ablate ISCs and EBs in order to test the ability of flies to survive without ISC function. While flies lacking ISCs showed no major decrease in survival under unchallenged conditions, flies depleted of ISCs and EBs exhibited decreased survival rates in response to damage to mature enterocytes (EC) that line the intestinal lumen. Our findings indicate that constant renewal of the intestinal epithelium is not absolutely necessary under normal laboratory conditions, but it is important in the context of widespread chemical-induced damage when significant repair is necessary.

Blood pressure and phosphate level in diabetic and non-diabetic kidney disease: Results of the cross-sectional "Low Clearance Consultation" study.

HIGHLIGHTS: A statistically significant and moderate positive correlation was verified between systolic blood pressure and plasma phosphate concentration in the whole sample (diabetic and non-diabetic), due to the diabetic chronic kidney disease group.A statistically significant and moderate positive correlation was verified between the diastolic blood pressure and plasma phosphate concentration in the whole sample (diabetic and non-diabetic), due to the diabetic chronic kidney disease group.A statistically significant and strong negative correlation was found between diastolic blood pressure and estimated glomerular filtration rate in the diabetic chronic kidney disease group, but there was no statistically significant correlation in the whole sample (diabetic and non-diabetic). ABSTRACT: Diabetic kidney disease features certain clinical and laboratorial characteristics that differ from chronic kidney disease of other etiologies. We performed a transversal study comparing some of these characteristics and assessed potential associations among blood pressure, plasma phosphate concentration and estimated glomerular filtration rate between patients with diabetic and non-diabetic chronic kidney disease.We found a positive correlation between both systolic and diastolic blood pressure and the plasma phosphate concentration in the diabetic kidney disease group, but not in the non-diabetic group. Also, diastolic blood pressure was negatively correlated with the estimated glomerular filtration rate in the diabetic group, yet not in the non-diabetic group.In conclusion, these data support the hypothesis of a close link between systolic and diastolic blood pressure and hyperphosphatemia, as well as between diastolic blood pressure and estimated glomerular filtration rate, in patients with diabetic kidney disease. Therapeutic approaches directed at these factors might prove to be important to delay the decline of renal function in the subgroup of patients with diabetic kidney disease.

A cross-sectional electromyography assessment in linear scleroderma patients.

BACKGROUND: Muscle atrophy and asymmetric extremity growth is a common feature of linear scleroderma (LS). Extra-cutaneous features are also common and primary neurologic involvement, with sympathetic dysfunction, may have a pathogenic role in subcutaneous and muscle atrophy. The aim was investigate nerve conduction and muscle involvement by electromyography in pediatric patients with LS. METHODS: We conducted a retrospective review of LS pediatric patients who had regular follow up at a single pediatric center from 1997-2013. We selected participants if they had consistently good follow up and enrolled consecutive patients in the study. We examined LS photos as well as clinical, serological and imaging findings. Electromyograms (EMG) were performed with bilateral symmetric technique, using surface and needle electrodes, comparing the affected side with the contralateral side. Abnormal muscle activity was categorized as a myopathic or neurogenic pattern. RESULTS: Nine LS subjects were selected for EMG, 2 with Parry-Romberg/Hemifacial Atrophy Syndrome, 7 linear scleroderma of an extremity and 2 with mixed forms (linear and morphea). Electromyogram analysis indicated that all but one had asymmetric myopathic pattern in muscles underlying the linear streaks. Motor and sensory nerve conduction was also evaluated in upper and lower limbs and one presented a neurogenic pattern. Masticatory muscle testing showed a myopathic pattern in the atrophic face of 2 cases with head and face involvement. CONCLUSION: In our small series of LS patients, we found a surprising amount of muscle dysfunction by EMG. The muscle involvement may be possibly related to a secondary peripheral nerve involvement due to LS inflammation and fibrosis. Further collaborative studies to confirm these findings are needed.

Escargot restricts niche cell to stem cell conversion in the Drosophila testis.

Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs) and germline stem cells (GSCs) and are a primary component of the testis stem cell niche. The shutoff (shof) mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg). Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP), which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.

A radiologic morphometric study of sellar, infrassellar and parasellar regions by magnetic resonance in adults.

OBJECTIVE: To evaluate variations of some anatomic structures of sellar and parasellar regions and their possible differences between genders and age groups. PATIENTS AND METHODS: Magnetic resonance images (MRI) of 380 patients were performed to analyze the dimensions of the sphenoid sinus, pituitary gland, optic chiasm, intra-cavernous carotid distances, distance between columella nasal - sphenoid sinus; and columella nasal-pituitary gland. The patients age ranged between 20 and 80 years (mean age 48 years). The study included 235 females (mean age 53 years) and 145 males (mean age 40 years). RESULTS: The transverse length of the pituitary, the inter-carotid distance and the height of the pituitary were similar between genders and age groups. The width and height of the optic chiasm showed differences only between females of different ages. Males presented greater distances between nasal columella and sphenoid sinus. The most common type of pneumatization of the sphenoid sinus was the sellar, and depending on the age group, sphenoid sinus was larger in males than females. CONCLUSION: The anatomy of the Sellar and parasellar regions is complex and varies widely within the normal range. They are a small area, rich in anatomical details affecting multiple physiological systems in the body and, therefore, have great importance in several medical fields. A better understanding of these complex structures is essential in clinical diagnosis and treatment of disease.

Headcase promotes cell survival and niche maintenance in the Drosophila testis.

At the apical tip of the Drosophila testis, germline and somatic stem cells surround a cluster of somatic cells called the hub. Hub cells produce a self-renewal factor, Unpaired (Upd), that activates the JAK-STAT pathway in adjacent stem cells to regulate stem cell behavior. Therefore, apical hub cells are a critical component of the stem cell niche in the testis. In the course of a screen to identify factors involved in regulating hub maintenance, we identified headcase (hdc). Hub cells depleted for hdc undergo programmed cell death, suggesting that anti-apoptotic pathways play an important role in maintenance of the niche. Using hdc as paradigm, we describe here the first comprehensive analysis on the effects of a progressive niche reduction on the testis stem cell pool. Surprisingly, single hub cells remain capable of supporting numerous stem cells, indicating that although the size and number of niche support cells influence stem cell maintenance, the testis stem cell niche appears to be remarkably robust in the its ability to support stem cells after severe damage.

Local signaling within stem cell niches: insights from Drosophila.

Tissue stem cells are found in specialized microenvironments (niches) where they are exposed to diverse systemic and local signals that are integrated with cell intrinsic factors to regulate stem cell behavior. In general, systemic signals are utilized to coordinate the response of tissues to acute or long-term changes that affect the whole organism, such as variations in nutrient availability or aging. In contrast, local signaling regulates tissue maintenance by balancing stem cell self-renewal with differentiation under homeostatic conditions and in response to local damage. In this review, we highlight the role of the JAK-STAT pathway in two Drosophila stem cell systems, the testis and intestine, and compare and contrast how activation of this pathway leads to tissue maintenance under both homeostatic conditions and in response to stress or injury.