Electrophoretic and heat-stability polymorphism at the phosphoglucomutase (Pgm) locus in natural populations of Drosophila melanogaster

Genetic polymorphism for electrophoretic and heat-sensitive alleles is known at the phosphoglucomutase (Pgm) locus in Drosophila melanogaster. Analysis of the distribution of electrophoretic and thermosensitive (ts) alleles was carried out in natural populations from Canada and West Africa and compared with already known data on Italian populations [Trippa, G., Loverre, A., and Catamo, A. (1976). Nature 260:42]. The data show the existence of five common alleles, Pgm ^1.00,tr, Pgm ^1,00,ts, Pgm ^0.70,ts, Pgm ^1.20,ts, and Pgm ^1.50,tr, and two rare alleles, Pgm ^0.55,ts and Pgm ^1.20,tr. The most frequent allele is always Pgm ^1.00,tr; the second most common allele is always of the ts type. The cumulated frequencies of ts alleles in the populations varies between 11 and 32%. The heat stability polymorphism is present in all populations examined and shows again the uniform geographic pattern that has been found for electrophoretic variation at this locus.This research was partially supported by an operating grant (to G.R.C.) from the Canadian National Science and Engineering Research Council (NSERC).     

Crystallization of halophilic malate dehydrogenase from Halobacterium marismortui

Malate dehydrogenase from the extreme halophile Halobacterium marismortui crystallizes in highly concentrated phosphate solution in space group 12 with cell dimensions a = 113.8 A, b = 122.8 A, c = 126.7 A, beta = 98.1 degrees. The halophilic enzyme was found to be unstable at lower concentrations of phosphate. It associates with unusually large amounts of water and salt, and the combined particle volume shows a tight fit in the unit cell.     

Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells

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Opioid and Notch signaling pathways are reciprocally regulated through miR- 29a and miR-212 expression

Background

The abuse of opioids, such as morphine and phentanyl or other drugs as heroin is a social and health problem that affects an increasing number of people each year. The activation of the mu opioid receptor triggers several molecular changes that alter the expression of diverse genes, including miRNAs. The dysregulation of these molecules could explain some of the developmental alterations that are induced after drug intake. In addition, the Notch signaling cascade has also been related to alterations on these processes.

Using abundance and habitat variables to identify high conservation value areas for threatened mammals

The present study used abundance and habitat variables to design High Conservation Value Forests for wildlife protection. We considered great apes (Gorilla gorilla gorilla and Pan troglodytes troglodytes) as model species, and we used nest surveys, dietary analysis and botanical inventories to evaluate whether the traditional methods that use abundance data alone were consistent with the survival of the species. We assumed that setting a local priority area for animal conservation can be made possible if at least one variable (abundance or habitat variables) is spatially clustered and that the final decision for a species may depend on the pattern of spatial association between abundance, nesting habitat and feeding habitat. We used Kernel Density Estimation to evaluate the spatial pattern of each biological variable. The results indicate that all three variables were spatially clustered for both gorillas and chimpanzees. The abundance variables of both animal species were spatially correlated to their preferred nesting habitat variables. But while the chimpanzee feeding habitat variable was spatially correlated to the abundance and nesting habitat variables, the same pattern was not observed for gorillas. We then proposed different methods to be considered to design local priority areas for the conservation of each great ape species. Alone, the abundance variable does not successfully represent the spatial distribution of major biological requirements for the survival of wildlife species; we, therefore, recommend the integration of the spatial distribution of their food resources to overcome the mismatch caused by the existence of a biological interaction between congeneric species.     

Lung ultrasound for the diagnosis of pneumonia in children with acute bronchiolitis

Background

Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients.

Methods

We enrolled children admitted to our hospital in 2016–2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient’s clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines.

Results

Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation >?1?cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen’s kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93).

Conclusions

This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size >?1?cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement.

Trial registration

Identifier: NCT03280732. Registered 12 September 2017 (retrospectively registered).

     

The Association of the Nm23-M1 Protein and β-Tubulin Correlates with Cell Differentiation

The Nm23 protein is a nucleoside diphosphate kinase (NDPK) and is thought to play a critical role in metastatic behavior. It has been reported that a NDPK activity is present in microtubules assembled in vitro. Since microtubule assembly is determinant in cell growth and differentiation, we investigated whether Nm23-M1 forms molecular complexes with β-tubulin in murine cells either actively proliferating or differentiating. For this purpose a polyclonal antibody against the GST-Nm23-M1 fusion protein was generated and employed to detect Nm23-M1/β-tubulin complexes in murine tumor cells derived from the Lewis lung carcinoma (3LL) and in undifferentiated and differentiated myogenic cells (C2C12). Immunoblotting and immunoprecipitation experiments performed using the anti-fusion protein antibody demonstrated that the Nm23-M1 protein is detectable in in vitro tumor cell lines and in in vivo primary tumors but not in spontaneous lung metastases. These data are in good agreement with data previously reported. Immunoprecipitation experiments demonstrated that the Nm23-M1 protein forms complexes with β-tubulin in in vitro tumor cell lines, but not in primary tumors. Furthermore, the Nm23-M1 protein forms complexes with β-tubulin in myogenic cells prior to and after differentiation. Interestingly, however, the level of the Nm23-M1/β-tubulin complexes is remarkably increased in differentiated myotubes. In conclusion, the results indicate that the Nm23-M1 protein forms molecular complexes with β-tubulin and that the number of complexes increases during the differentiation process of murine cells.     

Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia

BackgroundWe hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP.MethodsWe performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.FindingsNo significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29–6·44, p = 0·01). Patients with severe OSA (AHI≥30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11–11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006).ConclusionsOSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01071421","term_id":"NCT01071421"}}NCT01071421     

Binding of divalent copper ions to aspartic acid residue 52 in hen egg-white lysozyme

Divalent copper was found to inhibit non-competitively the lysis of Micrococcus lysodeikticus cells by hen egg-white lysozyme, with an inhibition constant K_a= 3.8 × 10²m^?1. The association constants of Cu²⁺ for lysozyme and for a derivative of lysozyme in which tryptophan residue 108 was selectively modified, were measured spectrofluorimetrieally and found to be 1.8 × 10²m^?1 and 1.0 × 10³m^?1, respectively. The electron spin resonance spectrum of Cu²⁺ was not affected by the addition of lysozyme, whereas many new lines appeared on addition of the modified protein. This was interpreted as evidence for the binding of Cu²⁺ in the neighbourhood of tryptophan 108. To unequivocally establish the site of ligation of Cu²⁺, crystals of lysozyme soaked in Cu²⁺ were examined by X-ray crystallography and the results compared to those obtained from crystals of native lysozyme. Cu²⁺ was found to be located 2 to 3 Å from the carboxyl side-chain of aspartic acid 52, 5 Å from the carboxyl of glutamic acid 35 and about 7 Å from tryptophan 108.The addition of a saccharide inhibitor to lysozyme was found to increase the association constant of Cu²⁺ for lysozyme from a value of 1.8 × 10²m^?1 to 6.0 × 10²m^?1. This finding was interpreted as indicative of a change in conformation around tryptophan 108 and glutamic acid 35 induced by the interaction of saccharides with the enzyme, which affects the metal binding properties of aspartic acid 52.