Thallium contamination in the Raibl Mine Site stream drainage system (Eastern Alps, Italy)

The Raibl mine (Cave del Predil village, northern Italy) belongs to the Pb–Zn minerogenetic district in the southeastern Alps, hosted in Middle Triassic carbonates. The drainage water quality reflects the high acid-buffering capacity of the carbonate rocks, which controls the mobility of most metals. In particular, Fe is non-detectable in solution, having formed hydrous-oxides precipitates. Molybdenum, Ni, Zn, Cd, Pb, and Tl are present, and the Pb, Tl, and Zn concentrations sometimes exceed the Italian regulatory thresholds. Thallium concentrations substantially exceed the 2 µg/L limit at some sampling stations, ranging between 12 and 30 µg/L in the mine drainage, and reaching 5 µg/L downstream of the mine site, despite strong dilution. The data indicate that Tl behaves almost conservatively and is not significantly scavenged by the Fe precipitates. The elevated Tl represents a potential risk for the stream ecosystem. Although Tl is not regulated in drinking water in Italy or the European Community, its distribution in natural waters may help to determine if health actions should be taken

SCD5 restored expression favors differentiation and epithelial-mesenchymal reversion in advanced melanoma

Our previous data supported a role for the Stearoyl-CoA desaturase (SCD5) in protection against malignancy, whereby it appears to functionally modify tumor stroma impairing tumor spread. SCD5 is significantly expressed in primary melanoma, but becomes barely detectable at tumor advanced stages. Looking for the regulatory mechanisms underlying SCD5 reduced expression during melanoma progression, we demonstrated a significantly lower stability of SCD5 protein as well as the direct targeting of SCD5 mRNA by the oncogenic miR-221 & 222 in metastatic cell lines. Moreover, our results indicated the existence of a negative feedback loop between SCD5 and miR-221 & 222, in good agreement with their opposite functions. Also, we showed how SCD5 re-expression and the direct supplementation of its main product oleic acid (OA) can drive advanced melanoma cell lines toward differentiation and reversion of the epithelial-mesenchymal (EMT)-like process, eventually inducing a less malignant phenotype. Indeed, SCD5 re-established the sensitivity to all-trans retinoic acid in A375M metastatic melanoma, associated with increased levels of Tyrosinase, melanin production and reduced proliferation. As evidenced by the correct modulation of some key transcription factors, SCD5 managed by favoring a partial mesenchymal-to-epithelial (MET) transition in in vitro studies. Interestingly, a more complete MET, including E-cadherin re-expression correctly localized at cell membranes, was obtained in in vivo xenograft models, thus indicating the requirement of direct contacts between tumor cells and the surrounding microenvironment as well as the presence of some essential factors for SCD5 complete function

Soil microarthropod communities from Mediterranean forest ecosystems in Central Italy under different disturbances

The aim of this study is to assess soil quality in Mediterranean forests of Central Italy, from evergreen to deciduous, with different types of management (coppice vs. high forest vs. secondary old growth) and compaction impacts (machinery vs. recreational). Soil quality was evaluated studying soil microarthropod communities and applying a biological index (QBS-ar) based on the concept that the higher is the soil quality, the higher will be the number of microarthropod groups well adapted to the soil habitat. Our results confirm that hardwood soils are characterised by the highest biodiversity level among growth) and compaction impacts (machinery vs. recreational). terrestrial communities and by a well-structured and mature microarthropod community, which is typical of stable ecosystems (QBS value, >200). While silvicultural practices and forest composition do not seem to influence QBS-ar values or microarthropod community structure, the index is very efficient in detecting soil impacts (soil compaction due to logging activities). Several taxa (Protura, Diplura, Coleoptera adults, Pauropoda, Diplopoda, Symphyla, Chilopoda, Diptera larvae and Opiliones) react negatively to soil compaction and degradation (QBS value, <150). In particular, Protura, Diplura, Symphyla and Pauropoda, are taxonomic groups linked to undisturbed soil. This index could also be a useful tool in monitoring soil biodiversity in protected areas and in urban forestry to prevent the negative effects of trampling. QBS-ar is a candidate index for biomonitoring of soil microarthropod biodiversity across the landscape to provide guidance for the sustainable management of renewable resource and nature conservation

HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line

BACKGROUND: Homeobox (HOX) genes deregulation has been largely implicated in the development of human leukemia. Among the HOXB cluster, HOXB1 was silent in a number of analyzed acute myeloid leukemia (AML) primary cells and cell lines, whereas it was expressed in normal terminally differentiated peripheral blood cells. METHODS: We evaluated the biological effects and the transcriptome changes determined by the retroviral transduction of HOXB1 in the human promyelocytic cell line HL60. RESULTS: Our results suggest that the enforced expression of HOXB1 reduces cell growth proliferation, inducing apoptosis and cell differentiation along the monocytic and granulocytic lineages. Accordingly, gene expression analysis showed the HOXB1-dependent down-regulation of some tumor promoting genes, paralleled by the up-regulation of apoptosis- and differentiation-related genes, thus supporting a tumor suppressor role for HOXB1 in AML. Finally, we indicated HOXB1 promoter hypermethylation as a mechanism responsible for HOXB1 silencing. CONCLUSIONS: We propose HOXB1 as an additional member of the HOX family with tumour suppressor properties suggesting a HOXB1/ATRA combination as a possible future therapeutic strategy in AML

Psychic euosmia among obsessive-compulsive personality disorder patients : a case control study

BACKGROUND: Psychic euosmia (PE) has been described as a supposed psychological predisposition for which pleasant smells elicit an immediate sense of pleasure, order and calmness in obsessive-compulsive personality disorder (OCPD). In this study we tried to verify the interpretation that PE is the counterpart of disgust that has been associated to contamination and moral purity. Disgust and morality are significantly associated in people with obsessive-compulsive personality traits. We expected that OCPD patients would experience higher levels of PE. AIM: To investigate the PE frequency in OCPD patients and healthy controls (HC) and to evaluate the relationship between PE and disgust. METHODS: A single-center, case-control study was conducted in an outpatient service for obsessive-compulsive and related disorders. The sample consisted of 129 subjects: 45 OCPD patients and 84 HC. In both groups we submitted the Disgust Scale Revised (DS-R) and the self-report Structured Clinical Interview for DSM-5 Screening Personality Questionnaire to which we added an additional yes or no question to investigate the presence of PE. In order to verify differences between groups, t-test was employed for continuous variables and t-test for categorical variable; odds ratio was employed to analyze group differences in the PE survey. Correlation was explored with Pearson r correlations. RESULTS: No differences were observed between groups in gender composition or education. A slight significant difference was found in mean age (t = 1.988; P = 0.049). The present study revealed significantly higher proportions of PE among OCPD patients when compared to HC (OR: 5.3, 2.28-12.46). Patients with OCPD were more likely to report PE (n = 36; 80%) whereas a much lower proportion endorsed PE in the HC group (n = 36; 42.9%). Interestingly, no differences were observed between groups in mean score for the Disgust Scale. There was also no difference between the two groups in any of the Disgust Scale Revised subscales. Moreover, no significant correlations were observed in the OCPD group between PE and Disgust Scale Revised subscales. CONCLUSION: Results suggested that PE might be part of the clinical spectrum of OCPD, and it does not reflect the counterpart of disgust. This could also indicate that this phenomenon is a manifestation of orderliness or incompleteness. Further studies will need to be undertaken to better understand PE and its significance in OCPD

Tympanic Membrane Collagen Expression by Dynamically Cultured Human Mesenchymal Stromal Cell/Star-Branched Poly(ε-Caprolactone) Nonwoven Constructs

The tympanic membrane (TM) primes the sound transmission mechanism due to special fibrous layers mainly of collagens II, III, and IV as a product of TM fibroblasts, while type I is less represented. In this study, human mesenchymal stromal cells (hMSCs) were cultured on star-branched poly("-caprolactone) (*PCL)-based nonwovens using a TM bioreactor and proper dierentiating factors to induce the expression of the TM collagen types. The cell cultures were carried out for one week under static and dynamic conditions. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to assess collagen expression. A Finite Element Model was applied to calculate the stress distribution on the scaolds under dynamic culture. Nanohydroxyapatite (HA) was used as a filler to change density and tensile strength of *PCL scaolds. In dynamically cultured *PCL constructs, fibroblast surface marker was overexpressed, and collagen type II was revealed via IHC. Collagen types I, III and IV were also detected. Von Mises stress maps showed that during the bioreactor motion, the maximum stress in *PCL was double that in HA/*PCL scaolds. By using a *PCL nonwoven scaold, with suitable physico-mechanical properties, an oscillatory culture, and proper dierentiative factors, hMSCs were committed into fibroblast lineage-producing TM-like collagens

Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease

Atypical fibroblast growth factors (FGF) 21 and 19 play a central role in energy metabolism through the mediation of Klotho coreceptor. Contradictory findings are available about the association of FGF21 and FGF19 with nonalcoholic fatty liver disease (NAFLD) in humans. We investigated the association of serum FGF21, FGF19 and liver Klotho coreceptor with non-alcoholic steatohepatitis (NASH) and fibrosis in children with NAFLD. Serum FGF21 and FGF19 were measured in 84 children with biopsy-proven NAFLD and 23 controls (CTRL). The hepatic expression of Klotho coreceptor was measured in 7 CTRL, 9 patients with NASH (NASH+) and 11 patients without NASH (NASH-). FGF21 and FGF19 showed a tendency to decrease from CTRL (median FGF21 = 196 pg/mL; median FGF19 = 201 pg/mL) to NASH- (FGF21 = 89 pg/mL; FGF19 = 81 pg/mL) to NASH+ patients (FGF21 = 54 pg/mL; FGF19 = 41 pg/mL) (p&lt;0.001 for all comparisons) and were inversely associated with the probability of NASH and fibrosis in children with NAFLD. The hepatic expression of Klotho coreceptor was inversely associated with NASH (R2 = 0.87, p&lt;0.0001) and directly associated with serum FGF21 (R2 = 0.57, p&lt;0.0001) and FGF19 (R2 = 0.67, p&lt;0.0001). In conclusion, serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD and these findings may have important implications for understanding the mechanisms of NAFLD progression. © 2013 Alisi et al

Growing bone tissue-engineered niches with graded osteogenicity: an in vitro method for biomimetic construct assembly

The traditional bone tissue-engineering approach exploits mesenchymal stem cells ( MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence, differentiated for a certain period of time and resulting in a homogeneous osteoblast population at the endpoint. However, after achieving terminal osteodifferentiation, cell viability is usually markedly compromised. On the other hand, naturally occurring osteogenesis results from the coexistence of MSC progenies at distinct differentiative stages in the same microenvironment. This diversification also enables long-term viability of the mature tissue. We report an easy and tunable in vitro method to engineer simple osteogenic cell niches in a biomimetic fashion. The niches were grown via periodic reseeding of undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing osteogenic commitment. Timefractioning of the seeded cell number during differentiation time of the constructs allowed graded osteogenic cell populations to be grown together on the same scaffolds (i.e., not only terminally differentiated osteoblasts). In such cell-dynamic systems, the overall differentiative stage of the constructs could also be tuned by varying the cell density seeded at each inoculation. In this way, we generated two different biomimetic niche models able to host good reservoirs of preosteoblasts and other osteoprogenitors after 21 culture days. At that time, the niche type resulting in 40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts showed a calcium content comparable to the constructs obtained with the traditional culture method (i.e., 100.03 – 29.30 vs. 78.51 – 28.50 pg/cell, respectively; p = not significant), the latter colonized only by fully differentiated osteoblasts showing exhausted viability. This assembly method for tissue-engineered constructs enabled a set of important parameters, such as viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity, which are more complex and reliable than those currently used by tissue engineers

The recurrent pathogenic Pro890Leu substitution in CLTC causes a generalized defect in synaptic transmission in Caenorhabditis elegans

De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c.2669C &gt; T (p.P890L) substitution, which is associated with a relatively mild ID/MD phenotype. Primary fibroblasts endogenously expressing the mutated protein show reduced transferrin uptake compared to fibroblast lines obtained from three unrelated healthy donors, suggesting defective clathrin-mediated endocytosis. In vitro studies also reveal a block in cell cycle transition from G0/G1 to the S phase in patient's cells compared to control cells. To demonstrate the causative role of the p.P890L substitution, the pathogenic missense change was introduced at the orthologous position of the Caenorhabditis elegans gene, chc-1 (p.P892L), via CRISPR/Cas9. The resulting homozygous gene-edited strain displays resistance to aldicarb and hypersensitivity to PTZ, indicating defective release of acetylcholine and GABA by ventral cord motor neurons. Consistently, mutant animals show synaptic vesicle depletion at the sublateral nerve cords, and slightly defective dopamine signaling, highlighting a generalized deficit in synaptic transmission. This defective release of neurotransmitters is associated with their secondary accumulation at the presynaptic membrane. Automated analysis of C. elegans locomotion indicates that chc-1 mutants move slower than their isogenic controls and display defective synaptic plasticity. Phenotypic profiling of chc-1 (+/P892L) heterozygous animals and transgenic overexpression experiments document a mild dominant-negative behavior for the mutant allele. Finally, a more severe phenotype resembling that of chc-1 null mutants is observed in animals harboring the c.3146 T &gt; C substitution (p.L1049P), homologs of the pathogenic c.3140 T &gt; C (p.L1047P) change associated with a severe epileptic phenotype. Overall, our findings provide novel insights into disease mechanisms and genotype-phenotype correlations of CLTC-related disorders