Paca Research Articles

Vitamin D Deficiency and Molecular Changes in Circulating MicroRNAs in Older Adults with Lower Back Pain.

Background MicroRNAs play an essential role in regulating pain processing within a wide range of clinical pain disorders. Objectives The present study aimed to evaluate the role of circulating miRNAs as biomarkers of lower back pain in older adults. In addition, the correlation between miRNAs and other related cofounders such as muscle function, adiposity, malnutrition, and Ca and vitamin D intake was assessed. Methods A total of 110 older subjects with an age range of 40–60 years were included in this study. The participants were classified according to a modified Oswestry lower back pain disability questionnaire (OSW) into subjects with minimal LBP (n = 40; LBP score: 0–20%), moderate LBP (n = 35; LBP score: 20–40%), and severe LBP (n = 35; LBP score: 41–60%). RT-PCR and immunoassays were used to study the circulating miRNA profile, vitamin D status, and CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX levels. In addition, malnutrition and muscle performance were estimated in all subjects as other factors related to LBP. Results In this study, normal LBP-OSW cutoff values (8.96 ± 3.6) were reported in 36.4% of the total population, whereas 63.6% of the population had higher LBP-OSW scores, classified as follows: 31.8% with moderate LBP (LBP-OSW score: 31.4 ± 9.1) and 31.8% with severe LBP (LBP-OSW score: 54.9 ± 14.6). Four circulating miRNAs, namely, miR-146a, miR-558, miR-155, and miR-124a, as biomarkers of the intensity of back pain were identified in all participants. In subjects with moderate to severe LBP, the expression levels of miR-146a and miR-558 were significantly reduced and those of miR-155 and miR-124a were significantly increased compared to subjects with minimal LBP scores. Subjects with moderate to severe LBP showed a significant increase in adiposity markers, lower PA, muscle performance, malnutrition, and lower Ca and vitamin D intake compared to normal controls. In addition, serum levels of vitamin D and circulated plasma markers of inflammation and bone metabolism such as CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX were significantly reduced in severe LBP cases compared to those with minimal LBP scores. The expressed circulating miRNAs were significantly associated with the measured muscle performance, adiposity, PA score, inflammation, and bone metabolism cofounders in subjects with higher LBP-OSW scores. The expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9–86.4% of the incidence of LBP in older adults. Conclusions In older adults with vitamin D deficiency, the severity of LBP was significantly associated with the expression of circulating miRNAs, adiposity, bone metabolism, inflammation, and muscle performance. In addition, the expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9–86.4% of the incidence of LBP in older adults. These results suggest the possibility of using microRNAs as therapeutics to alleviate established pain and as biomarkers in old adults with painful conditions.

Novel cyphelloid fungi in Glabrocyphella, Heteroscypha, and Rectipilus from Brazil

New records of cyphelloid fungi from Brazil are presented, based on specimens collected and identified by J. Rick and conserved at Herbarium PACA (São Leopoldo, Rio Grande do Sul). Glabrocyphella cyathiformis sp. nov. is characterized by small (0.1–0.5 mm diam.), pale yellow, turbinate basidiomes and ellipsoid to fusoid basidiospores (5–6 × 2–2.5 μm). Flagelloscypha malmei is recombined as Heteroscypha malmei comb. nov., and Rectipilus natalensis is reported for the first time from the Americas. Descriptions, photographs, and illustrations are presented for the three species.

New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile, antimicrobial and cytotoxic activity

New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o‒vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, 1H & 13C NMR, ESI−MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C30H22CuN5O7S2], [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H22N4O4S2Zn], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn], with CT‒DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by Kb and Ksv values which gave higher binding propensity for chloro-substituted Cu(II) [C30H20Cl2CuN5O7S2] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn] were evaluated against five human cancer cell lines viz., MCF‒7 (breast), MIA‒PA‒CA‒2 (pancreatic), HeLa (cervix) and Hep‒G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C30H20Cl2CuN5O7S2] complex, exhibited pronounced specific cytotoxicity with GI50 value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.

Restos de mamíferos encontrados en una cueva de Valle Nacional, Oaxaca, México

A list is given of the species of mammals represented among the remains found at the archeological site of Monte Flor Cave, Oaxaca. The list comprises Pteronotus rubiginosus, Canis latrans, Heteromys cf. lepturus, Agouti paca, Dasyprocta mexicana, and D. cE. punctata. The latter four are range extensions for the species in question.

Nicotine mediated activation of Pak1/NFkB cascade in pancreatic cancer cells – A pilot study

BackgroundTobacco smoking is a major established risk factor for pancreatic cancer (PC), increasing the incidence up to six fold depending on the duration and intensity of smoking. Nicotine is a key toxin in tobacco and cigarette, which may contribute to development of pancreatitis and PC. Our previous studies revealed an aberrant expression of Pak1 in PC as compared to normal pancreas and its association with cancer progression, tumor angiogenesis, drug resistance and metastasis. Here, we explore a potential link between Pak1 expression and smoking-mediated PC pathogenesis and the use of Pak1 inhibitors to curtail this association. MethodsMia Pa Ca 2 cell line was obtained from NCCS, Pune and grown in the presence and absence of 0.5μM (0.112μg/ml) nicotine hemisulphate salt (5h) and further nicotine exposed cells were treated with Pak1 inhibitor, IPA-3 (1h). Protein, mRNA and kinase activity of Pak1 were evaluated. Using human pancreatic cancer tissue, mRNA from smokers (n = 10) and non –smokers (n = 10) were assessed for Pak1 expression. ResultsNicotine significantly enhanced the expression and kinase activity of Pak1, with subsequent activation of NF-κB signalling cascade in cooperation with other pathways, this effect was blocked by IPA-3. Also, it was observed that pharmacological blockage or silencing of α7-nAChR abrogated nicotine mediated activation of Pak1/NF-κB. Additionally, we demonstrated up-regulated Pak1 mRNA expression in tissue sample from smokers compared to non-smokers. ConclusionOur findings suggest probable mechanism of action of nicotine through Pak1 signalling on PC pathogenesis and this could be targeted using Pak1 inhibitors for PC treatment.

Spermatogonia types in tepezcuintle (Cuniculus paca). Ultrastructural study

Ultrastructural studies of different types of spermatogonia by thin section techniques and transmission electron microscopy showed that Cuniculus paca has two types of Type A spermatogonia (A-O and A-1). Samples were taken at different stages of the cycle in the seminiferous tubule epithelium presented a similar pattern as those of other rodents. Type B spermatogonia are similar to those of the rat, the difference being that the heterochromatic zones are larger and more numerous. Both characteristics differentiate them from preleptotenic spermatocytes.

Report on the two‐phase public consultation on the draft EFSA scientific opinion on bisphenol A (BPA)

Report on the two‐phase public consultation on the draft EFSA scientific opinion on bisphenol A (BPA)

Light microscope observations on the epididymis of paca (Agouti paca).

The features of paca epididymis, based on its appearance in light microscope, is described in this paper. The cellular population of the epithelial lining comprises principal cells, basal cells, apical cells, narrows cells, and hallo cells. The epididymis is divided in five distinct and continuous regions, Zone I, or initial segment, and zone II, are both localized into the head. Zone III comprises the distal head and all the body. Zones IV and V are restricted to the tail, in the proximal and distal cauda epididymis respectively. Each zone can be readily distinguished on the basis of morphological characteristics. The height of epididymal epithelium is greater in zone I. There is a progressive increase in the diameter of the tubular lumen through the different areas, with the maximum in the zone V. The presence of a high epithelium, and the virtual absence of sperm in zone I suggest fast transit of spermatozoa in this region. Zone V comprises the distal tail, has smaller epithelial lining, greater luminal diameter, shorter stereocilia than the other zones, and contains spermatozoa packed inside the lumen, that characterizes this zone as a place of sperm storage. The findings are compared with other reports in rodents and other domestic animals, to contribute to the understanding of epididymal morphophysiology.

Abundancia de tepezcuintle (Cuniculus paca) y su relación con la presencia de competidores y depredadores en una selva tropical

El tepezcuintle (Cuniculus paca) es uno de los roedores vivientes mas grandes de America Latina. En muchas comunidades rurales e indigenas es el mamifero silvestre mas consumido por sus pobladores, por lo que se ejerce en ella una fuerte presion por la caceria, ademas hay que considerar el efecto por la alteracion y eliminacion de su habitat. En este estudio se estima la densidad poblacional del tepezcuintle y sus variaciones temporales en una selva alta perennifolia en el este del estado de Oaxaca, Mexico. Se utiliza fototrampeo y el modelo de gas ideal, asi como la relacion entre su presencia y la de sus mamiferos depredadores y competidores. La densidad poblacional promedio mensual se estimo en 0.492 ± 0.361 individuos por hectarea, y sus variaciones probablemente se deban en ultima instancia a las fluctuaciones en la precipitacion. La presencia del tepezcuintle tuvo una relacion estadisticamente significativa e inversa con la de sus competidores (serete) y depredadores (ocelote y jaguar). Los tepezcuintles estan activos principalmente entre las 18:00 y las 02:00, mientras que los seretes son de habitos diurnos

La modélisation du risque d'inondation en région PACA : une analyse économique et technique

Les plus récentes catastrophes d’origines naturelles ont un impact économique régional significativement important. Plus particulièrement les inondations, dont les occurrences tendent à s’amplifier en région Provence-Alpes-Côte d’Azur. Leurs effets dévastateurs sur la région peuvent être désormais estimés, de manière très locale, à l’aide de modèles techniques. Un modèle technique construit ex-ante peut fournir une évaluation des pertes économiques subies par la zone inondée. Les résultats peuvent ensuite être intégrés à un modèle économique. Cette démarche d’orientation macroéconomique permet non seulement la validation des estimations après analyse technique mais offre également une vision régionale du problème de crues. Cet article propose une évaluation monétaire de la vulnérabilité économique de la région PACA. En retenant comme événement de référence l’inondation historique de décembre 2003, nous illustrerons la méthodologie sur deux départements de la région PACA.

Dispositifs de connaissance et action publique en région : les Observatoires régionaux de l'emploi et de la formation. Provence-Alpes-Côte d'Azur versus Rhône-Alpes

Résumé Depuis 1982, en France, la décentralisation de la formation professionnelle de l’État aux Régions est en cours. Ce processus s’accompagne de transformations des modes de production, puis de mobilisation dans l’action publique, des connaissances concernant les liens entre formation et emploi. Ces transformations sont ici analysées dans une perspective socio-historique basée sur une comparaison entre deux régions (PACA et RA). Cette comparaison souligne une évolution profonde de l’activité des deux observatoires de l’emploi et de la formation étudiés. Ils sont progressivement passés de la figure du dossier statistique descriptif rassemblant (à l’échelle d’une branche, d’un groupe professionnel ou encore d’un territoire) des informations issues de producteurs différenciés et peu coordonnés, à la figure du diagnostic dégageant des enjeux stratégiques et ouvrant sur des préconisations pour l’action publique.

Application of serum protein profiling in diagnosis, prognosis and evaluation of curative effect of pancreatic adenocarcinoma

To establish decision tree and logistic regression classification models for diagnosing pancreatic adenocarcinoma (PaCa) and for screening serum biomarkers related to evaluation of different stages and curative effects. Serum samples obtained from subjects with pancreatic adenocarcinoma (n = 58) and normal pancreas (n = 51) were applied to strong anion exchange chromatography (SAX2) chips for protein profiling by SELDI-TOF-MS to screen multiple serum biomarkers. Biomarker Wizard software and several statistical methods including algorithm of decision tree, logistic regression and ROC curves were used to construct the decision tree or logistic regression classification models. Average of 61 mass peaks were detected at the molecular range of 2000-30,000, ten decision trees with the highest cross validation rate were chosen to construct the classification models, which can differentiate PaCa from normal pancreas with a sensitivity of 83.3% and a specificity of 100%. Logistic regression was used to achieve the AUC (0.976 +/- 0.011, P < 0.001) with a sensitivity of 77.6% - 91.4% and a specificity of 92.2% - 100%. Six mass peaks were combined by logistic regression to achieve the AUC 0.897 +/- 0.054, 0.978 +/- 0.021 and 0.792 +/- 0.107 (P < 0.05) in the three groups (patients at stage I and II, stage II and III, stage III and IV). One mass peak (M/Z 4,016) was screened (P < 0.05) significantly between the preoperative and postoperative PaCa samples and the intensity decreased weeks after operation. Decision tree and logistic regression classification models of the mass peaks screened by SELDI-TOF-MS serum profiling can be used to differentiate pancreatic adenocarcinoma from normal pancreas, and is superior to CA 199. The detected mass peaks are helpful for the evaluation of curative effect and prognosis of pancreatic adenocarcinoma.

Expression of neuropilin-1 in human pancreatic ductal carcinoma and MIA PaCa- II cell lines

Objective To investigate the expression of Neuropilin-1 in human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. Methods Expression and distribution of Neuropilin-1 were detected in operation tissue specimens of human pancreatic ductal adenocarcinoma with HE, immunohistochemistry and RT-PCR. Results Immunohistochemical analysis revealed that Neuropilin-1 were expressed in human pancreatic adenocarcinoma specimens, precancerous tissue and MIA PaCa-Ⅱ cell lines, but was absent in normal pancreatic tissue, mRNA of Neuropilin-1 could also be detected the in human pancreatic adenocarcinoma specimens, precancerous tissue and MIA PaCaⅡ cell Lines, while could not be detected in normal pancreatic tissue. Neuropilin-1 expression in pancreatic adenocarcinoma were higher than that in normal pancreas, and the differences were significant( P < 0. 01 ). Conclusions Neuropilin-1 might play an potential role in carcinogenesis for pancreatic cancer. Neuropilin-1 may be relevant to perineural invasion of pancreatic carcinoma by some signal transduction. Key words: Neuropilin-l/Bl; Pancreatic neoplasms/ME

Establishment of animal model of in situ transplanted tumor of human pancreatic cancer MIA PaCa II cells with activity of nervous invasion

Objective To establish the nude mice model of in situ transplanted tumor of human pancreatic cancer MIA PaCa Ⅱ cells and observe its activity of nervous invasion to provide experimen-tal basis and condition for study the occurrence and development of the nervous invasion by pancreatic cancer. Methods The human pancreatic cancer MIA PaCa Ⅱ cells were implanted on back of nude mice to establish the subcutaneous model of transplanted tumor of pancreatic cancer with high activity of metastasis in nude mice. Then the tumor was implanted in situ in the pancreas of the nude mice.The nude mice was sacrificed in 4, 6 and 8 weeks for anatomy and pathological examination of the transplanted tumor as well as determination of its size and weight. Furthermore, HE staining and sil-ver staining were employed to observe its activity of nervous invasion. Results During the establish-ment of subcutaneous model, the successful rate of implantation was 100% (10/10). The subcutane-ous transplanted tumor had limited growth and there was no metastasis to organs and nerves. In 4, 6 and 8 weeks after the in situ pancreatic implantation, the successful implantation rate was 100% (10/ 10). The rate of nervous invasion was 50% (5/10), 80% (8/10) and 60% (6/10), respectively.Meanwhile, there were metastases of the tumor in various organs. Conclusion The in situ transplan-ted tumor model was successfully established in nude mice and its nervous invasion observed. This model is a fairly optimal model for study of nervous invasion by pancreatic cancer. Key words: Pancreatic neoplasms; Model; Nerve; Metastasis

13α–Hydroxylucilactaene and Other Metabolites of an Endophytic Strain of Fusarium acuminatum

A liquid fermentation culture of Fusarium acuminatum, endophytic in the root of Larrea tritentata, afforded a new furanopyrrolidone, 13α–hydroxylucilactaene (1), together with four known metabolites, NG–391 (2), NG–393 (3), enniatin A (4), and enniatin B (5). The structure and relative stereochemistry of 1 was established by extensive NMR spectral analysis and the known compounds 2 – 5 were identified by comparison of their spectroscopic data with those reported in the literature. The cytotoxicity of all compounds was evaluated in a panel of five human cancer cell lines [NCI–H460 (non-small cell lung), MCF–7 (breast), SF–268 (CNS glioma), MIA Pa Ca–2 (pancreatic carcinoma), PC-3M (metastatic prostate cancer)] and normal human fibroblast (WI–38) cells, and only enniatins A (4) and B (5) were shown to have significant cytotoxic activity.

A dual-pathway ultrastructural model for the tight junction of rat proximal tubule epithelium.

A dual-pathway model is proposed for transport across the tight junction (TJ) in rat proximal tubule: large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores, with spacing similar to that of claudin-2. This dual-pathway model is developed in the context of a proximal tubule model (Weinstein AM. Am J Physiol Renal Fluid Electrolyte Physiol 247: F848-F862, 1984) to provide an ultrastructural view of solute and water fluxes. Tubule model paramters (TJ reflection coefficient and water permeability), plus the measured epithelial NaCl and sucrose permeabilities, provide constraints for the dual-pathway model, which yields the small-pore radius and spacing and large slit height and area. For a small-pore spacing of 20.2 nm, comparable to the distance between adjacent particle pairs in apposing TJ strands, the small-pore radius is 0.668 nm and the large slit breaks have a height of 19.6 nm, occupying 0.04% of the total TJ length. This pore/slit geometry also satisfies the measured permeability for mannitol. The numerous small circular pores account for 91.25% of TJ NaCl permeability but only 5.0% of TJ water permeability. The infrequent large slit breaks in the TJ account for 95.0% of TJ water permeability but only 8.7% of TJ NaCl permeability. Sucrose and mannitol (4.6- and 3.6-A radius) can pass through both the large slit breaks and the small pores. For sucrose, 78.3% of the flux is via the slits and 21.7% via the pores; for mannitol, the flux is split nearly evenly between the two pathways, 50.8 and 49.2%. In this ultrastructural model, the TJ water permeability is 21.2% of the entire transepithelial water permeability and thus an order of magnitude greater than that predicted by the single-pore/slit theory (Preisig PA and Berry CA. Am J Physiol Renal Fluid Electrolyte Physiol 249: F124-F131, 1985).

Intestinal parasites of Agouti paca (Rodentia: Dasyproctidae) in Costa Rica

In a sample of 23 breeding places of pacas (Agouti paca) in Costa Rica, the following parasites were found: Eimeria agoutii, Balantidium coli, Capillaria sp., Trichuris sp., Taenia sp., Strongyloides sp., and members of the superfamilies Strongyloidea and Ascaroidea.

20: WILLIAM PACA, Signer of the Declaration of Independence

20: WILLIAM PACA, Signer of the Declaration of Independence

The Systematics of the Subfamily Ornithodorinae (Acarina: Argasidae). V. a Revised Key to Larval Argasidae of the Western Hemisphere and Description of Seven New Species of Ornithodoros

Described as new, from larvae only, are: Ornithodoros (Alectorobius) casebeeri from the rodent, Ototylomys sp., in Costa Rica; O. (A.) chironectes from water opossum, Chironectcs minimus, and cotton rat, Sigmodon hispidus griseus, in Nicaragua; O. (A.) clarki from bats, Pteronotus davyi fulvus and P. suapurensis, in Nicaragua; O. (A.) knoxjonesi from bat, Balantiopteryx p. plicata, in Nicaragua; O. (A.) marmosae from murine opossum, Marmosa robinsoni, and mouse, Rhipidomys sp., in Venezuela and Colombia; O. (A.) tiptoni from bat, Noctilio leporinus, from Venezuela and O. (A.) tuttlei from paca, Agouti paca, and tapir, Tapirus terrestris, in Venezuela. In addition, the following species described by Kohls, Clifford, and Jones are now placed in the subgenus Alectorobius: O. setosus, O. eptesicus, O. peruvianus, O. peropteryx, O. mimon, and O. echimys.

Switching of Techniques and Consumption Per Head

The analysis of reswitching of techniques enables us to show that if stationary states are compared, low rates of interest do not necessarily go together with a high consumption per head. If a stationary state with a high rate of interest gives way to one with a low rate of interest, the corresponding switch need not necessarily be from a technique with a low consumption per head to one with a high consumption per head. It may also be from a technique with a high to one with a low consumption per head. What has not been sufficiently emphasized in the literature, however, is that whether the former or the latter is the case may depend not only on which technique replaces which but also on what is the pattern of consumption. M. Bruno, E. Burmeister, and E. Sheshinski assert I that this is not so. They argue that the hyperplanes representing the opportunity sets of consumption for the techniques which are optimal at different rates of interest never intersect, and that whatever the pattern of consumption the respective point on one hyperplane must always be above, or always below, that on the other plane. The purpose of the present note is to show by means of a numerical example that this assertion is not correct. Consider a circulating-capital model with a generalized Leontief technology. There is no joint production in it; the same goods may be used either as inputs or as consumer goods; alternative methods of production are available for each of them; and labor is the only primary factor of production. Let wages be paid at the end of the period, and all other inputs at the beginning of it. The technique actually used is then that which minimizes prices subject to the constraint that at the given wage and the given rate of interest no production processes are run at a loss. This means that if a is the optimal technique, the vector of prices may be written as (A) pa(r) =wao[I(l+r)a]'where w is the wage, r is the rate of interest, a is the matrix of input coefficients for technique a, and ao is the corresponding vector of labor coefficients. The consumption hyperplane is then L=wao [I-a] -lCa=Pa(O)Ca