Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Escape of the dot/icm Mutants of Legionella pneumophila into the Cytosol of Mammalian and Protozoan Cells

ABSTRACT The Legionella pneumophila-containing phagosome evades endocytic fusion and intercepts endoplasmic reticulum (ER)-to-Golgi vesicle traffic, which is believed to be mediated by the Dot/Icm type IV secretion system. Although phagosomes harboring dot/icm mutants are thought to mature through the endosomal-lysosomal pathway, colocalization studies with lysosomal markers have reported contradictory results. In addition, phagosomes harboring the dot/icm mutants do not interact with endocytosed materials, which is inconsistent with maturation of the phagosomes in the endosomal-lysosomal pathway. Using multiple strategies, we show that the dot/icm mutants defective in the Dot/Icm structural apparatus are unable to maintain the integrity of their phagosomes and escape into the cytoplasm within minutes of entry into various mammalian and protozoan cells in a process independent of the type II secretion system. In contrast, mutants defective in cytoplasmic chaperones of Dot/Icm effectors and rpoS, letA/S, and letE regulatory mutants are all localized within intact phagosomes. Importantly, non-dot/icm L. pneumophila mutants whose phagosomes acquire late endosomal-lysosomal markers are all located within intact phagosomes. Using high-resolution electron microscopy, we show that phagosomes harboring the dot/icm transporter mutants do not fuse to lysosomes but are free in the cytoplasm. Inhibition of ER-to-Golgi vesicle traffic by brefeldin A does not affect the integrity of the phagosomes harboring the parental strain of L. pneumophila. We conclude that the Dot/Icm transporter is involved in maintaining the integrity of the L. pneumophila phagosome, independent of interception of ER-to-Golgi vesicle traffic, which is a novel function of type IV secretion systems.
A NEW EIMERIA SP. FROM THE PLUMBEOUS CENTRAL AMERICAN CAECILIAN, DERMOPHIS MEXICANUS (AMPHIBIA: GYMNOPHIONA) FROM VOLCÁN TAJUMULCO, DEPARTMENT OF SAN MARCOS, GUATEMALA

Fresh fecal samples from 5 caecilians (Dermophis mexicanus) were collected and examined for coccidia in the summer of 1998. The caecilians were collected in the Department of San Marcos, Guatemala. Two of the 5 (40%) specimens of caecilians contained an Eimeria species that is described here as new. This represents the first coccidia described from a gymnophionian host. Sporulated oocysts are spheroidal to subspheroidal, 19.5 × 17.7 (16–23 × 15–21) µm, micropyle and oocyst residuum are absent, and 3 (or more) polar granules are always present. Sporocysts are ovoidal, 11.0 × 7.2 (10–12 × 6–9); a Stieda body and sporocyst residuum are present.
Horse hooves and bird feathers: Two model systems for studying the structure and development of highly adapted integumentary accessory organs--the role of the dermo-epidermal interface for the micro-architecture of complex epidermal structures.

Accessory organs of the integument are locally modified parts of the potentially feather-bearing skin in birds (e.g., the rhamphotheca, claws, or scales), and of the potentially hairy skin in mammals (e.g., the rhinarium, nails, claws, or hooves). These special parts of the integument are characterised by a modified structure of their epidermal, dermal and subcutaneous layers. The developmental processes of these various integumentary structures in birds and mammals show both similarities and differences. For example, the development of the specialised epidermal structures of both feathers and the hoof capsule is influenced by the local three-dimensional configuration of the dermis. However, in feathers, in contrast to hooves, the arrangement of the corneous cells is only partially a direct result of the particular arrangement and shape of the dermal surface of the papillary body. Whereas the diameter of the feather papilla, as well as the number, length, and width of dermal ridges on the surface of the feather papilla influence the three-dimensional architecture of the feather rami, there is no apparent direct correlation between the dermo-epidermal interface and the development of the highly ordered architecture of the radii and hamuli in the feather vane. In order to elucidate this morphogenic problem and the problem of locally different processes of keratinisation and cornification, the structure and development of feathers in birds are compared to those of the hoof capsule in horses. The equine hoof is the most complex mammalian integumentary structure, which is determined directly by the dermal surface of the papillary body. Perspectives for further research on the development of modified integumentary structures, such as the role of the dermal microangioarchitecture and the selective adhesion and various differentiation pathways of epidermal cells, are discussed.
Estrogen and risk of gastric cancer: a protective effect in a nationwide cohort study of patients with prostate cancer in Sweden.

BACKGROUND The global pattern of male predominance in gastric cancer incidence remains unexplained. We tested the hypothesis that estrogen prevents gastric cancer in a cohort of men heavily exposed to estrogen. METHODS We conducted a nationwide cohort study of men with a diagnosis of prostate cancer recorded in the Swedish Cancer Register in 1961-2000. Because estrogen therapy was the treatment of choice for prostate cancer in Sweden between 1950 and 1980, cohort members diagnosed earlier than 1980 were considered exposed to estrogen. Standardized incidence ratios (SIR) estimated relative risk. Complete follow-up was achieved through cross-linkages within the cancer register and the Swedish nationwide registers of emigration and causes of death. RESULTS In 515,961 person-years of follow-up, we observed 304 gastric cancers as compared with 349 expected for the cohort members in the predefined "exposed" period 1961-1980, rendering a 13% decreased risk (SIR, 0.87; 95% confidence interval (95% CI), 0.78-0.98). Among patients with a latency of > or =15 years after a prostate cancer diagnosis in 1961-1980, SIR was 0.57 (95% CI, 0.30-0.97), suggesting a dose-response relation. Similarly, reduced risks were found for cardia cancer and noncardia gastric cancer. No decreased risk was found for the cohort members in 1981-2000, when estrogen treatment was less common (SIR, 0.99; 95% CI, 0.89-1.11). CONCLUSIONS Our study indicates a reduced risk of gastric cancer in a male cohort exposed to estrogen. These results support the hypothesis that estrogen may prevent gastric cancer, but additional studies are warranted.
Nitrogen metabolism and ornithine cycle function.

Article de synthese sur le metabolisme de l'azote et la synthese d'uree chez les mammiferes. Degradation des proteines. Transport des acides-amines entre les organes et a travers la membrane plasmique des hepatocytes. Cycle de l'ornithine et distribution des enzymes de ce cycle dans le foie. Ontogenese de la synthese d'uree. Pathophysiologie de l'hyperammonemie
Phenotypes of Two Dutch DFNA3 Families with Mutations in GJB2

Objectives: We describe the phenotype of 2 Dutch DFNA3 families with mutations in the GJB2 gene. Methods: Two patients from family 1 and one isolated patient from family 2 were studied. The audiometric examination consisted of pure tone and speech audiometry. Two patients underwent vestibular testing and high-resolution computed tomographic scanning of the temporal bone. Mutation analysis of GJB2 and GJB6 was performed. Results: All 3 patients had severe to profound sensorineural hearing impairment. Cochlear implantation was performed in 2 patients, and their phoneme recognition scores were good. Mutation analyses revealed a p. Arg184Gln mutation in GJB2 in family 1 and a p. Arg75Trp mutation in GJB2 in family 2. No mutations in GJB6 were identified. Vestibular function tests and computed tomographic scans yielded normal findings in the examined subjects. Conclusions: Severe to profound sensorineural hearing impairment was found in these DFNA3 patients, and was well rehabilitated with cochlear implantation. A thorough genotype-phenotype correlation is difficult because of the small number of affected patients and the limited clinical data of these patients. More clinical data on DFNA3 families need to be published in order to create a reliable and precise phenotype characterization.
Purification and properties of 4-hydroxybenzoate 1-hydroxylase (decarboxylating), a novel flavin adenine dinucleotide-dependent monooxygenase from Candida parapsilosis CBS604

A novel flavoprotein monooxygenase, 4-hydroxybenzoate 1-hydroxylase (decarboxylating), from Candida parapsilosis CBS604 was purified to apparent homogeneity. The enzyme is induced when the yeast is grown on either 4-hydroxybenzoate, 2,4-dihydroxybenzoate, or 3,4-dihydroxybenzoate as the sole carbon source. The purified monooxygenase is a monomer of about 50 kDa containing flavin adenine dinucleotide as weakly bound cofactor. 4-Hydroxybenzoate 1-hydroxylase from C. parapsilosis catalyzes the oxidative decarboxylation of a wide range of 4-hydroxybenzoate derivatives with the stoichiometric consumption of NAD(P)H and oxygen. Optimal catalysis is reached at pH 8, with NADH being the preferred electron donor. By using (18)O2, it was confirmed that the oxygen atom inserted into the product 1,4-dihydroxybenzene is derived from molecular oxygen. 19F nuclear magnetic resonance spectroscopy revealed that the enzyme catalyzes the conversion of fluorinated 4-hydroxybenzoates to the corresponding hydroquinones. The activity of the enzyme is strongly inhibited by 3,5-dichloro-4-hydroxybenzoate, 4-hydroxy-3,5-dinitrobenzoate, and 4-hydroxyisophthalate, which are competitors with the aromatic substrate. The same type of inhibition is exhibited by chloride ions. Molecular orbital calculations show that upon deprotonation of the 4-hydroxy group, nucleophilic reactivity is located in all substrates at the C-1 position. This, and the fact that the enzyme is highly active with tetrafluoro-4-hydroxybenzoate and 4-hydroxy-3-nitrobenzoate, suggests that the phenolate forms of the substrates play an important role in catalysis. Based on the substrate specificity, a mechanism is proposed for the flavin-mediated oxidative decarboxylation of 4-hydroxybenzoate.
The dlt operon in the biosynthesis of D-alanyl-lipoteichoic acid in Lactobacillus casei.

The D-alanine incorporation system allows Lactobacillus casei to modulate the chemical properties of lipoteichoic acid (LTA) and hence control its proposed functions, i.e., regulation of autolysin action, metal ion binding, and the electromechanical properties of the cell wall. The system requires the D-alanine-D-alanyl carrier protein ligase (Dcl) and the D-alanyl carrier protein (Dcp). Our results indicate that the genes for these proteins are encoded in the dlt operon and that this operon contains at least 2 other genes, dltB and dltD. The aim of this paper is to describe the genetic organization of the operon, the role of the D-alanyl carrier protein, and the function of the putative protein encoded by dltB in the intramembranal translocation of the activated D-alanine.
Telemedicine for diabetes care: An Indian perspective - feasibility and efficacy

Diabetes is a chronic and costly disease. In India, the usual practice among patients is to visit the doctor once in every 2–3 months to get advice on changes in the dosages of medications. The Diabetes Tele Management System (DTMS®) is a telemedicine based follow-up program originally introduced at Jothydev's Diabetes Research Centre at Trivandrum South India in 1998. It is a chronic disease management system which enables patient to interact lively with a professionally trained multidisciplinary team comprising of diabetes educators, nurses, dieticians, pharmacists, psychologists, physicians, etc., in modifying the dosages of medications, diet, and physical activity either through telephone/email/secure website. The uniquely designed software and the trained multidisciplinary team overcomes the globally recognized major barriers to diabetes management namely fear of hypoglycemia, polypharmacy, discontinuation of stains, and antihypertensives or wrong injection techniques. DTMS is designed to provide individualized therapy advices on glycosylated hemoglobin, blood pressure, and low density lipoprotein customized to multiple patient characteristics which help attain goals of therapy. The system has been tested on various platforms over a decade and was shown to be a patient friendly approach with successful outcomes due to a live “round-the-clock” interactive communication in contrast to text or recorded messages. The major challenge to the widespread use of DTMS® is seeking a source of funding this unique telemedicine program.
Resuscitating the heart but losing the brain

Objectives: Many survivors of cardiac arrest are left with considerable long-term impairments due to a transient ischemic state of the brain. Neuropsychologists identified a wide range of neuropsychological deficits in these patients besides the well-known amnesic syndrome. To date, there is no complete and unbiased documentation of the affected brain areas in vivo. We aimed to identify the brain tissue atrophy underlying the observed neuropsychological deficits in a case-control study. Methods: We measured gray matter loss by voxel-based morphometry of 3-T structural magnetic resonance images in a sample of 12 patients who had had cardiac arrest with successful subsequent resuscitation in comparison with 12 individually age- and sex-matched control subjects. Such data are rare because many of these patients wear cardiac pacemakers. Results: We found extensive reductions of gray matter volumes in the anterior, medial, and posterior cingulate cortex, the precuneus, the insular cortex, the posterior hippocampus, and the dorsomedial thalamus in tight correlation with neuropsychological impairments, namely, amnestic deficits and apathy. Conclusion: The identified neuroanatomical pattern of brain tissue loss substantiates the reports of wide-ranging neuropsychological impairments in patients after cardiac arrest.
Disseminated nocardiosis in an immunocompetent child

Abstract We report a 2-month-old child with a disseminated Nocardia farcinica infection that presented with suppurative lymphatic abscess. The child did not have any predisposing factors and responded to treatment with co-trimoxazole and amikacin. This is first case report of disseminated nocardiosis caused by Nocardia farcinica in an immunocompetent child.
Rauchverhalten und Einstellung zum Rauchen von zahnärztlichem Personal

Das Ziel der Arbeit war es, zahnarztliches Personal aus Jena und Erfurt uber ihre Einstellung zum Rauchen, ihr Rauchverhalten und ihre Bereitschaft zur Teilnahme an Raucherentwohnungsmasnahmen in der Praxis zu befragen. Die Antworten von 154 zahnarztlichen Helferinnen (Jena n = 41, Erfurt n = 113) aus 146 Zahnarztpraxen (Jena n = 39, Erfurt n = 107) konnten ausgewertet werden, der Nichtraucheranteil lag bei 73 %. Die Beziehungen zwischen Rauchen und der Entstehung von Allgemeinkrankheiten wie Lungenkrebs, Herzerkrankungen, Kehlkopfkarzinom und peripheren arteriellen Erkrankungen waren bekannt, im Gegensatz dazu stand das niedrige Wissen der Helferinnen uber Auswirkungen des Rauchens auf die orale Gesundheit (Komplikationen bei Implantaten, Leukoplakie und orale Candidose). Barrieren fur Aktivitaten gegen das Rauchen hatten 64 % der Helferinnen, zudem wollten sich nur 52 % an einer Kampagne beteiligen, die rauchende Patienten uber die Vorteile der Rauchabstinenz aufklart. Die Raucheraufklarung in den Praxen nimmt noch einen zu niedrigen Stellenwert ein, deshalb sollte durch gezielte Aufklarungs- und Weiterbildungsmasnahmen zur Schadlichkeit des Rauchens diese Situation in Zukunft verbessert werden, um Patienten uberhaupt und effizient zum Aufgeben des Rauchens motivieren zu konnen.
Subcutaneous and intravenous administration of analgesics in palliative medicine

Pain is one of the most frequent complaints reported by cancer patients. In their terminal periods, the proportion of patients suffering from pain reaches 75%. Even, the most convenient route of administration of medicines is the oral route, not every clinical situation permits the oral therapy. Alternative routes of administration of medicines, especially in palliative medicine, involve multiple injections or continuous infusions, both subcutaneous and intravenous. Most opioids (morphine, diamorphine in small doses, oxycodon, pethidine, fentanyl, tramadol) can be administered subcutaneously. There are no significant differences between the subcutaneous and intravenous ( i.v. ) application of medicines in terms of their absorption, efficacy and the frequency of side effects. The titration of i.v. opioids is not only an effective and rapid method of pain relief, but also is safe and unrelated to increased risk of respiratory centre depression. The role of intravenous administration of medicines increase especially at the terminal stages of cancer patients’ life. An appropriate choice of administration route or its exchange to an alternative one may in a number of cases improve the comfort and quality of life of patients receiving palliative care.
Serum Beta2-Microglobulin in Malignant Lymphoproliferative Disorders

Beta2-microglobulin (B2m) was measured on serum samples in 274 patients with acute and chronic lymphoproliferative disorders (85 non-Hodgkin lymphomas - NHL, 30 Hodgkin lymphomas - HL, 34 B-cell chronic lymphocytic leukemias - B-CLL, 8 Waldenström macro-globulinemias - WM, 76 multiple myelomas - MM, 31 acute lymphoblastic leukemias - ALL, 10 hairy cell leukemias - HCL). Two hundred and four patients were studied at the time of diagnosis, and results were correlated to clinical stage, and histologic subtype in NHL, immunoglobulin type in MM, and immunologic phenotype in ALL. Moreover, B2m was tested during and after chemo- and/or radiotherapy, and results were correlated to response, progression or relapse. Elevated pretreatment B2m values were found in widespread forms of NHL and HL, in patients with B symptoms and in the unfavorable histologic subgroups of NHL. Rapid falls in levels followed therapy institution. In B-CLL and in MM a close relationship between B2m and cell mass was found. A significant B2m level reduction followed treatment, whereas its increase could detect a relapse. In ALL, serum B2m was only slightly above the normal range. B2m seems to reflect the total burden of malignant cells mainly in MM and B-CLL; in other lymphoproliferative disorders it provides less prognostic information.
Symptoms of depression, sadness and sense of coherence (coping) among cognitively intact older people with cancer living in nursing homes—a mixed-methods study

Background: Symptoms of depression are often reported among patients with a cancer diagnosis. Strong sense of coherence (SOC) is shown to be associated with less depression in the general older population and among nursing homes (NH) residents in particular. Knowledge about mixed-methods perspectives that examine symptoms of depression and SOC among cognitively intact NH residents with cancer is scarce. Aim: To investigate symptoms of depression and SOC among NH residents who are cognitively intact and have cancer. Methods: We used a quantitatively driven mixed-methods design with sequential supplementary qualitative components. We facilitated the collection of quantitative survey data of 60 NH residents (≥ 65 years) with cancer using the Geriatric Depression Scale (GDS) and SOC scale. The supplementary psychosocial component comprised qualitative research interviews about experiences related to depression with nine respondents from the same cohort. Results: In fully adjusted multiple regression analysis of the sociodemographic variables, the GDS was significantly correlated with SOC (P < 0.001). The experience of sadness was identified by the following theme: sadness. Coping with the experience of symptoms of depression was dominated by coping with sadness. Conclusion: More than half the NH residents reported symptoms of depression, and the SOC was associated with reduced symptoms. A mixed-methods design contributed to nuanced and detailed information about the meaning of depression, and the supplementary component informs and supports the core component. To improve the situation of NH residents with cancer, more attention should be paid to the residents’ experience of symptoms of depression and their SOC.
B10 cell regulation of health and disease

While B cells are traditionally regarded as promoters of the immune response via antibody secretion and pro‐inflammatory cytokine production, recent studies have also confirmed an important role for B‐cell‐mediated negative regulation of immunity. Tremendous advances in the characterization of the mechanisms by which regulatory B cells function has led to the identification of a novel subset of regulatory B cells known as B10 cells, which regulate immune responses through the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10). B10 cells are best defined by their functional ability to produce IL‐10, as they are not confined to any particular phenotypic subset. B10 cells function in an antigen‐specific manner that requires cognate interactions with T cells in vivo to regulate immune responses and have been demonstrated to be potent regulators of allergic and autoimmune disease, cancer, infection, and transplant rejection. Importantly, the recent discovery of human B10 cells has accelerated this field to the forefront of clinical research where the possibility of harnessing the regulatory potential of B10 cells for treatment of aberrant immune responses and diseases may become feasible.
A Comparison of Drug use and Dependence Between Blunt Smokers and Other Cannabis Users

Ethnographic studies have suggested that blunt smokers represent a subculture of cannabis users whose drug use is moderated by social norms. The objective of this study was to compare rates of cannabis dependence/abuse and nicotine dependence between blunt and other cannabis smokers. The sample included adolescents and young adults (n = 4348) who reported some form of past-month cannabis use in the 2004 National Survey on Drug Use and Health. Compared to smokers who never used blunts, blunt smokers had significantly greater odds of being dependent on cannabis and tobacco. Associations with cannabis dependence/abuse remained statistically significant with adjustment for smoking frequency and demographic characteristics. These findings highlight the need for differentiating types of cannabis users in epidemiologic studies. The study's limitations are noted.
Bacteriological Quality Assessment of Raw Beef Sold in Sylhet Sadar

This study was conducted to assess the bacteriological quality of fresh raw beef sold in different markets of Sylhet Sadar. A total of seventy five (75) fresh raw beef samples were randomly collected from seven major markets (Shibgonj, Mirabazar, Kazitula, Ambarkhana, Madina market, Bandar bazar and Sheikh ghat) of Sylhet Sadar. Total Viable Count of the samples ranged between 2.5 × 10 5 to 2.25 × 10 8 cfu/g. Acceptability for consumption of these samples as satisfactory, acceptable and rejected were 40, 32 and 28%, respectively. A total of 115 bacterial isolates of 5 genera were identified including gram negative Escherichia coli [15(10%)], Salmonella spp. [20(13.33%)], Klebsiella spp. [30(20%)], Enterobacter spp. [10(6.67%)] and gram positive Staphylococcus spp. [40(26.67%)]. The presence of these organisms in fresh meat from conventional beef is alarming. DOI: http://dx.doi. org/10.3329/agric.v13i2. 26654 The Agriculturists 2015; 13(2) 09-16