19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML).

26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3) were recently identified as prognostic biomarkers and potential therapeutic targets in chronic myeloid leukemia (CML) and multiple solid tumors. In the present study, we analyzed the expression of 19S proteasome subunits in acute myeloid leukemia (AML) patients with mutations in the FMS-like tyrosine kinase 3 (FLT3) gene and assessed their impact on overall survival (OS). High levels of PSMD3 but not PSMD1 expression correlated with a worse OS in FLT3-mutated AML. Consistent with an oncogenic role for PSMD3 in AML, shRNA-mediated PSMD3 knockdown impaired colony formation of FLT3+ AML cell lines, which correlated with increased OS in xenograft models. While PSMD3 regulated nuclear factor-kappa B (NF-κB) transcriptional activity in CML, we did not observe similar effects in FLT3+ AML cells. Rather, proteomics analyses suggested a role for PSMD3 in neutrophil degranulation and energy metabolism. Finally, we identified additional PSMD subunits that are upregulated in AML patients with mutated versus wild-type FLT3, which correlated with worse outcomes. These findings suggest that different components of the 19S regulatory complex of the 26S proteasome can have indications for OS and may serve as prognostic biomarkers in AML and other types of cancers.

Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism.

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug-resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase-independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2-/- ) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.

Cambios en las características clínicas y desenlaces de pacientes hospitalizados por COVID-19 durante dos años de pandemia: experiencia en un hospital venezolano / Changes in clinical characteristics and outcomes of patients hospitalized with COVID-19 during two years of the pandemic: experience in a venezuelan hospital

RESUMEN Objetivos. Determinar los cambios en las características clínicas y desenlaces intrahospitalarios de los pacientes hospitalizados por COVID-19 en un hospital privado de Caracas durante dos años de pandemia. Materiales y métodos. Estudio retrospectivo, observacional, de pacientes hospitalizados por COVID-19. Se investigó la correspondencia entre las olas de ingresos hospitalarios con las variantes circulantes del SARS-CoV-2 en la población general del Distrito Capital y estado Miranda. Resultados. Se incluyeron 1025 pacientes (569 hombres y 456 mujeres), con edad promedio de 62,9 DE: 16,2 años. Cuatro olas de ingresos hospitalarios fueron identificadas: primera (marzo-noviembre 2020) 150/1025 (14,6%) casos; segunda (diciembre-2020 a mayo-2021) 415/1025 (40,5%) casos; tercera (junio-diciembre 2021) 344/1025 (33,6%) casos; cuarta (enero-febrero 2022) 116/1025 (11,3%) casos. La edad promedio fue mayor en la cuarta ola (primera 64,0±15,7, segunda 61,4±15,8, tercera 62,1±16,5, y cuarta ola 68,5±16,4), mientras que la proporción de pacientes masculinos (primera 66,7%, segunda 58,8%, tercera 50,3%, y cuarta 44,8%), los pacientes con enfermedad grave-crítica (primera 65,3%, segunda 57%, tercera 51,7% y cuarta 44,8%), la estadía intrahospitalaria (primera 9,1±6,0, segunda 9,0±7,3, tercera 8,8±7,7, y cuarta 6,9±5,0 días), los ingresos a la UCI (primera 23,3%, segunda 15,7%, tercera 14,0%, y cuarta 11,2%; p=0,027) y la mortalidad (primera 21.8%, segunda 10,7%, tercera 9,1%, y cuarta 7,1%; p<0,001) disminuyeron progresivamente con el tiempo. Conclusiones. Los resultados muestran menor frecuencia de casos severos y mejoría de los desenlaces intrahospitalarios en dos años de pandemia. Es probable que los cambios en las variantes circulantes, las mejoras del manejo de la enfermedad y la vacunación hayan influido sobre estos resultados.

ABSTRACT Objectives. To determine changes in the clinical characteristics and in-hospital outcomes of patients hospitalized for COVID-19 in a private hospital in Caracas during two years of the pandemic. Materials and Methods. Retrospective, observational study of patients hospitalized for COVID-19. We evaluated the correspondence between waves of hospital admissions and circulating variants of SARS-CoV-2 in the general population of the Capital District and Miranda state. Results. A total of 1025 patients (569 men and 456 women) were included, with a mean age of 62.9 SD: 16.2 years. Four waves of hospital admissions were identified: first (March-November 2020) 150/1025 (14.6%) cases; second (December 2020 to May 2021) 415/1025 (40.5%) cases; third (June-December 2021) 344/1025 (33.6%) cases; fourth (January-February 2022) 116/1025 (11.3%) cases. The mean age was higher in the fourth wave (first: 64.0±15.7, second: 61.4±15.8, third: 62.1±16.5, and fourth wave: 68.5±16.4), while the proportion of male patients (first: 66.7%, second: 58.8%, third: 50.3%, and fourth wave: 44.8%), patients with severe-critical illness (first: 65.3%, second: 57%, third: 51.7%, and fourth wave: 44.8%), in-hospital stay (first: 9.1±6.0, second: 9.0±7.3, third: 8.8±7.7, and fourth wave: 6.9±5.0 days), ICU admissions (first: 23.3%, second: 15.7%, third: 14.0%, and fourth wave: 11.2%; p=0.027) and mortality (first: 21. 8%, second: 10.7%, third: 9.1%, and fourth wave: 7.1%; p<0.001) progressively decreased over time. Conclusions. The results show lower frequency of severe cases and improvement of in-hospital outcomes in two years of the pandemic. Changes in circulating variants, improvements in disease management and vaccination are likely to have influenced these results.

Septic Arthritis With Superimposed Acute Gouty Arthritis in a Rheumatoid Arthritis Patient.

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus (Streptococcus agalactiae) infection and monosodium urate crystals. A diagnosis of septic arthritis with superimposed acute gouty arthritis was made and the patient was treated accordingly. Management included surgical irrigation and debridement, antibiotic therapy, and systemic glucocorticoids which resulted in a significant improvement in the patient's clinical status.

The Role of Serial Imaging in Neurocysticercosis for Disease Resolution.

Neurocysticercosis (NCC), the most common parasitic infection of the CNS in humans, is a frequent cause of seizure disorders and epilepsy. The cystic larvae Taenia solium is endemic to developing countries where the population raises pigs as a reliable source of food, however, massive immigration has now forced the surge of the disease in developed areas making it a worldwide problem. Clinical presentation is affected by the size, number, and location of the lesions within the brain, with the most common manifestations being seizures, headaches, and increased intracranial pressure. The appearance of NCC on radiological imaging helps determine the stage of the disease, required for appropriate antiparasitic treatment. In this article, we detail the case of a patient who presented for recurrent seizures after reportedly undergoing treatment for NCC years prior.

FLT3 inhibitors in the treatment of acute myeloid leukemia: current status and future perspectives.

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene arise in 25-30% of all acute myeloid leukemia (AML) patients. These mutations lead to constitutive activation of the protein product and are divided in two broad types: internal tandem duplication (ITD) of the juxtamembrane domain (25% of cases) and point mutations in the tyrosine kinase domain (TKD). Patients with FLT3 ITD mutations have a high relapse risk and inferior cure rates, whereas the role of FLT3 TKD mutations still remains to be clarified. Additionally, growing research indicates that FLT3 status evolves through a disease continuum (clonal evolution), where AML cases can acquire FLT3 mutations at relapse - not present in the moment of diagnosis. Several FLT3 inhibitors have been tested in patients with FLT3-mutated AML. These drugs exhibit different kinase inhibitory profiles, pharmacokinetics and adverse events. First-generation multi-kinase inhibitors (sorafenib, midostaurin, lestaurtinib) are characterized by a broad-spectrum of drug targets, whereas second-generation inhibitors (quizartinib, crenolanib, gilteritinib) show more potent and specific FLT3 inhibition, and are thereby accompanied by less toxic effects. Notwithstanding, all FLT3 inhibitors face primary and acquired mechanisms of resistance, and therefore the combinations with other drugs (standard chemotherapy, hypomethylating agents, checkpoint inhibitors) and its application in different clinical settings (upfront therapy, maintenance, relapsed or refractory disease) are under study in a myriad of clinical trials. This review focuses on the role of FLT3 mutations in AML, pharmacological features of FLT3 inhibitors, known mechanisms of drug resistance and accumulated evidence for the use of FLT3 inhibitors in different clinical settings.

Prevalencia y factores asociados con la conducta suicida en adolescentes de Lima rural / Prevalence and associated factors with a suicidal behavior in adolescents of rural Lima

Objetivos: Identificar la prevalencia y los factores asociados con tendencias suicidas en adolescentes de Lima rural. Métodos: Se realizó un análisis secundario de un subconjunto de datos del Estudio Epidemiológico de Salud Mental en Lima Rural 2007, que incluye variables demográficas y socioeconómicas, aspectos generales de salud mental, trastornos clínicos y relaciones intrafamiliares. Resultados: La prevalencia de vida del deseo de morir y del pensamiento suicida en adolescentes fue 21,4% (IC: 16,6-27,1) y 7,4% (IC: 5,0-10,8), respectivamente; observándose según el análisis multivariado asociaciones estadísticamente significativas para el deseo de morir con: sexo femenino (OR=3,05), cuánto le importa si hiciera algo que avergonzara a su familia (OR=2,61), reglas y castigos del hogar injustos (OR=2,89), apoyo del hermano(a) (OR=2,98), tener amigo confidente (OR=2,85), importancia de Dios en la vida (OR=0,23), trastorno de ansiedad generalizada (OR=6,91) y depresión mayor (OR=7,5). En el análisis multivariado para el pensamiento suicida se observó asociaciones significativas con: contar con cancha de vóley (OR=6,29), cuánto le importa si hiciera algo que avergonzara a su familia (OR=3,49) y tener amigo o confidente (OR=2,38). Conclusiones: En los adolescentes de Lima rural, la prevalencia de deseos de morir fue alta, mientras que la de pensamiento suicida fue similar a la de otros países. Las asociaciones identificadas deberían ser evaluadas en estudios posteriores.

Objectives: To identify the prevalence of and factors associated with suicidal behavior in adolescents from a rural area of Lima. Methods: A secondary analysis of a subset of data from the Epidemiological Study on Mental Health in Rural Lima 2007 was made. Information about sociodemographic variables, general mental health, mental disorders and domestic relations was included. Results: The prevalence of desire to die and suicidal thoughts in adolescents was 21.4% (CI: 16.6 to 27.1) and 7.4% (CI: 5.0 to 10.8), respectively. Multivariate analysis shows statistically significant associations of the desire to die with female gender (OR=3.05), how much the subject cares if he did something that embarrassed his family (OR=2.61), unfair rules and punishments at home (OR=2.89), sibling support (OR=2.98), having a confident friend (OR=2.85), importance of God in life, (OR=0.23), generalized anxiety (OR=6.91), and major depression (OR=7.5). In addition, multivariate analysis showed statistically significant associations for the suicidal thoughts with having volleyball court (OR=6.29), how much the subject cares if he did something that embarrassed his family (OR: 3.49), having a confident friend (OR: 2.38). Conclusions: A high prevalence of the desire to die was found in adolescents of rural Lima, whereas that of suicidal thinking was similar to the prevalence levels in other countries. The associations thus identified should be evaluated in further studies.

Influence of Sorghum Kafirin on Serum Lipid Profile and Antioxidant Activity in Hyperlipidemic Rats (In Vitro and In Vivo Studies).

The aim of this study was to compare in vitro the antioxidant potential of sorghum kafirin and sorghum flour and their influence on lipids and antioxidant capacity in rats. The antioxidant activity in sorghum kafirin extract measured by the DPPH and TEAC methods was increased 30 and 65 times, respectively, compared to that of its counterpart, sorghum flour. According to electrophoresis assay, the kafirins tert-butanol extract showed a high proportion of α-kafirin monomers, and its amino acid composition revealed higher hydrophobic amino acid content such as alanine, isoleucine, leucine, tyrosine and phenylalanine than sorghum flour extract. Diets supplemented with sorghum kafirin extract have improved lipid metabolism and increased the serum antioxidant potential (67%) especially in rats fed with added cholesterol. The bioactive peptides generated from kafirin in vivo hydrolysis appear to be associated with the positive effect on serum lipids and antioxidant activity. According to these results, sorghum kafirin extract at the levels used in this study apparently could be used for prevention of atherosclerosis and other chronic diseases.

Rich bacterial assemblages from Maritime Antarctica (Potter Cove, South Shetlands) reveal several kinds of endemic and undescribed phylotypes / Una rica colección de bacterias marinas antárticas (Caleta Potter, islas Shetlands del Sur) revela diversos filotipos endémicos y previamente no descritos

.

Bacterial richness in maritime Antarctica has been poorly described to date. Phylogenetic affiliation of seawater free-living microbial assemblages was studied from three locations near the Argentinean Jubany Station during two Antarctic summers. Sixty 16S RNA cloned sequences were phylogenetically affiliated to Alphaproteobacteria (30/60 clones), Gammaproteobacteria(19/60 clones), Betaproteobacteria and Cytophaga-Flavobacteriia- Bacteroides (CFB), which were (2/60) and (3/60) respectively. Furthermore, six out of 60 clones could not be classified. Both, Alphaproteobacteria and Gammaproteobacteria, showed several endemic and previously undescribed sequences. Moreover, the absence of Cyanobacteria sequences in our samples is remarkable. In conclusion, we are reporting a rich sequence assemblage composed of widely divergent isolates among themselves and distant from the most closely related sequences currently deposited in data banks.

Assessment of mammographic density in postmenopausal women during long term hormone replacement therapy.

OBJECTIVE: To assess long-term effects of different hormone replacement therapy (HRT) regimens on mammographic density. METHODS: One hundred sixty-five postmenopausal women were treated with the same HRT during 5 years: 38 received transdermal estradiol, 78 cyclic combined therapy and 49 continuous combined therapy. Mammograms were obtained at baseline, at 1-year and 5-year treatment. Breast density changes were categorized as slight focal increased density, considerable focal increased density, slight diffuse increased density and considerable diffuse increased density. RESULTS: Mammographic density increased in 7.9% of women receiving estrogen alone versus 25.2% of women receiving combined therapy (p < 0.022) during 1 year, and in 7.9% of women versus 28.3% of women (p < 0.009) after 5 years of therapy, respectively. There were significant statistical differences in women treated with estrogen alone versus those treated with combined HRT after 1 and 5 years. After 5 years of HRT, breast density increased 21.8% in women receiving cyclic combined therapy versus 38.8% in those under continuous combined therapy (p < 0.039). CONCLUSION: An increase in breast density is significantly more frequent in women receiving combined estrogen-progestin therapy than in women receiving estrogen alone. There are differences between cyclic and continuous combined therapy at 5 years of treatment.

MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma.

Although specific microRNA (miRNA) signatures in classical Hodgkin lymphoma (cHL) have been proposed, their relationship with clinical outcome remains unclear. Despite treatment advances, a substantial subset of patients with advanced cHL are refractory to standard therapies based on adriamycin and its variants. Global miRNA expression data of 29 advanced cHL patients and five cHL-derived cell lines were used to identify profiles from Hodgkin-Reed-Sternberg (HRS) cells and their non-tumoural microenvironment. A cHL-miRNA signature was identified with 234 miRNAs differentially expressed. A subset of these miRNAs was associated with outcome and selected for study in an independent set of 168 cHL samples using quantitative reverse transcription polymerase chain reaction. Multivariate Cox regression analyses including cross-validation with failure-free survival (FFS) as clinical endpoint revealed a miRNA signature with MIR21, MIR30E, MIR30D and MIR92B* that identified two risk-groups with significant differences in 5-year FFS (81% vs. 35.7%; P < 0.001). Additionally, functional silencing of MIR21 and MIR30D in L428 cells showed increased sensitivity to doxorubicin-induced apoptosis, pointing towards abnormalities of mitochondrial intrinsic and TP53-CDKN1A pathways as related to miRNA deregulation in cHL. These results suggest that clinical outcome in cHL is associated with a specific miRNA signature. Moreover, functional analyses suggest a role for MIR21 and MIR30D in cHL pathogenesis and therapeutic resistance.

Partial suppression of Oxa1 mutants by mitochondria-targeted signal recognition particle provides insights into the evolution of the cotranslational insertion systems.

The biogenesis of hydrophobic membrane proteins involves their cotranslational membrane integration in order to prevent their unproductive aggregation. In the cytosol of bacteria and eukaryotes, membrane targeting of ribosomes that synthesize membrane proteins is achieved by signal recognition particles (SRPs) and their cognate membrane-bound receptors. As is evident from the genomes of fully sequenced eukaryotes, mitochondria generally lack an SRP system. Instead, mitochondrial ribosomes are physically associated with the protein insertion machinery in the inner membrane. Accordingly, deletion of ribosome-binding sites on the Oxa1 insertase and the Mba1 ribosome receptor in yeast leads to severe defects in cotranslational protein insertion and results in respiration-deficient mutants. In this study, we expressed mitochondria-targeted versions of the bacterial SRP protein Ffh and its receptor FtsY in these yeast mutants. Interestingly, Ffh was found to bind to the large subunit of mitochondrial ribosomes, and could relieve, to some degree, the defect of these insertion mutants. Although FtsY could also bind to mitochondrial membranes, it did not improve membrane protein biogenesis in this strain, presumably because of its inability to interact with Ffh. Hence, mitochondrial ribosomes are still able to interact physically and functionally with the bacterial SRP system. Our observations are consistent with a model according to which the protein insertion system in mitochondria evolved in three steps. The loss of genes for hydrophilic polypeptides (step 1) allowed the development of ribosome-binding sites on membrane proteins (step 2), which finally made the existence of an SRP-mediated system dispensable (step 3).

Rat dorsal prostate is necessary for vaginal adhesion of the seminal plug and sperm motility in the uterine horns

The rat prostate comprises dorsal, ventral and lateral lobes that are morphologically and biochemically distinct. Lesions to these structures are expected to affect the quality of the ejaculate and male fertility. In experiment 1, we analyzed ejaculate parameters of males that had chemical lesions of the dorsal or ventral lobes. At pre-lesion and at 5 and 20 days post-lesion males were mated, and after ejaculation, seminal fluid and seminal plug were obtained from the mated females. In experiment 2, the ventral lobes were ablated, and the ejaculate was analyzed. In experiment 3, the fertility of males with chemically-lesioned dorsal lobes or ablation of the ventral lobes was evaluated. Chemical lesion of the dorsal lobe prevented the adhesion of the seminal plug to vaginal walls. When these males were tested at 5-days postlesion, no sperm were found in uterus, and at 20-days post-lesion, the few sperm encountered showed slow progressive motility. None of the females that mated with dorsal lobe-lesioned males became pregnant. However, chemical lesion or ablation of the ventral lobes did not affect ejaculate or fertility. Our results indicate that the dorsal prostatic lobes are indispensable for reproductive success in males, and define parameters of ejaculate with which fertility can be estimated.

A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma.

Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease. Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022). This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).

Assessing fatal cardiovascular disease risk with the SCORE (Systematic Coronary Risk Evaluation) scale in post-menopausal women 10 years after different hormone treatment regimens.

OBJECTIVE: To assess fatal cardiovascular disease (FCD) risk among women in early post-menopausal years, as evaluated with the Systematic Coronary Risk Evaluation (SCORE) scale. DESIGN: This was a retrospective study of parallel cohorts. Two hundred seventy-three healthy post-menopausal women. Participants received one of the following hormone treatment (HT) regimens: transdermal estradiol (50 microg) (n = 99), sequential cyclic HT with transdermal estradiol (50 microg/day) plus 200 mg/day natural micronised oral progesterone (cycle days 12-25) (n = 63) and combined HT using transdermal estradiol (50 microg) plus 100 mg/day of micronised oral progesterone (n = 61). A group of women who elected not to use HT served as control group (n = 50). SCORE values were assessed before HT or follow up. RESULTS: Only one woman displayed a high-risk SCORE value both before and after 10 years of HT, the remaining had low risk values (<5%) for FCD. After 10 years, SCORE values increased significantly as compared to baseline among HT users (all three regimens) and controls. Although post-treatment SCORE values significantly differed among groups, values were all below the high risk cut-off (5%). There were no FCD events during the 10 year observation period. CONCLUSION: As assessed with the SCORE scale, FCD risk in young post-menopausal women (HT users and controls) had a slight significant increase after 10 years, being values in the low risk range.

Gene expression profiling of intestinal regeneration in the sea cucumber.

BACKGROUND: Among deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools.For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences. RESULTS: In the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p < 0.05 to 39% at p < 0.001. Clustering analyses show specific profiles of expression for early (first week) and late (second week) regeneration stages. We used semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) to validate the expression profile of fifteen microarray detected differentially expressed genes which resulted in over 86% concordance between both techniques. Most of the differentially expressed ESTs showed no clear similarity to sequences in the databases and might represent novel genes associated with regeneration. However, other ESTs were similar to genes known to be involved in regeneration-related processes, wound healing, cell proliferation, differentiation, morphological plasticity, cell survival, stress response, immune challenge, and neoplastic transformation. Among those that have been validated, cytoskeletal genes, such as actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration. CONCLUSION: Our findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes.

Inhomogeneous feed gas processing in industrial ozone generation.

The synthesis of ozone by means of dielectric barrier discharge (DBD) is extensively used in industry. Ozone generators available on the market differ in ozone production capacities, electrode arrangements and working parameters, but operate with a uniformly distributed filamentary discharge plasma pattern.In the presented work the benefits of inhomogeneous feed gas processing are explored. Causality between power induction, production efficiency and working parameters are investigated. Different electrode arrangements, evenly distributed within a given space parameter, were designed, simulated, manufactured and tested on a representative scale. A finite element model was utilized to simulate an inhomogeneous power induction pattern along the ozone generator tube. The simulation yielded the local power density, the local gas temperature gradient and the relative DBD packing density.Results show that the degree of filamentation turns out to be decisive, indicating a new potential by means of plasma tailoring. An arrangement with a pronounced power induction at the inlet of the ozone generator revealed several advantages over homogeneous plasma processing arrangements, for which an increase in robustness and a reduction in electrical power consumption are achieved.