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Background. Extensive physical activity (PA; ≥18 MET ∗ h/week, MET metabolic equivalent of tasks hours) postcancer diagnosis has shown favorable effects on colorectal cancer disease-free survival. However, the feasibility of introducing this high volume of PA in this patient group is unclear. Therefore, the aim of the F-PROTECT study was to evaluate the feasibility of extensive and prolonged PA (≥18 MET ∗ h/week over 12 months) in colorectal cancer patients with the primary objectives to (1) recruit 50 patients within 12 months and (2) reach an attendance rate of ≥70%. Methods. Single-armed, bicentric, prospective intervention study in colorectal cancer patients (≤80 years; UICC II/III Union for International Cancer Control) after histopathological confirmed R0-resection who were consecutively recruited from visceral surgery units of 10 clinics in Germany. Recruitment rates were calculated using screening logs. Intervention was a 12-month endurance-focused exercise program with supervised and home-based training. Attendance rates defined as ≥70% participation in training sessions were calculated by training diaries. Results. Out of 521 patients who were screened for eligibility, 50 (23 female; 59 ± 10 years, UICC 44% II, 56% III; adjuvant chemotherapy 60%) were recruited within 15 months. Mean duration between surgery and first training was 103 ± 57 days. Training attendance rate was 64% (including 9 dropouts). Six (12%) participants reached ≥18 MET ∗ h/week in ≥70% of training sessions between 4–12 months. 28 adverse events (n = 9 serious) occurred, however, were not assessed as training related. Conclusions. The present intervention involving a combination of supervised and home-based exercise training in postsurgical colorectal cancer patients was not feasible. Strategies specifically designed for this patient group must be developed and investigated to motivate long-term PA. Registration. The study was prospectively registered at clinicaltrials.gov (NCT01991847).

Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats).Experimental Design: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells.Results: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition.Conclusions: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival. Clin Cancer Res; 21(14); 3204–15. ©2015 AACR.

Supplementary tables S1-3 and figure legends. Supplementary Table S1. Antibodies and antibody dilution used for immunohistochemical analyses. Supplementary Table S2. Characterization of human HCC Supplementary Table S3. Number of tumors per analyzed animal of DEN and McA model.

Supplementary Fig. S4. Tumor vascularization and necrosis in human HCC.

The original version of this article unfortunately contained mistake. One of the author name was missspelled during revision and finalization of the manuscript. Dr. Kiran Polavarapu's surname "Polaparapu" should be spelled "Polavarapu". The original article has been corrected.

The chromosomes of the dogtooth characins, fish species of the family Cynodontidae, have only a relatively small amount of heterochromatin, including the terminal portion. Curiously, in the cynodontid Cynodon gibbus, the terminal portion is rich in repetitive DNAs, including transposable retroelements and microsatellite sequences. Given this, this study investigated the composition of the terminal portion of the chromosomes of two cynodontid species (Rhaphiodon vulpinus and Hydrolycus armatus), to compile a database for the evaluation of all three cynodontid genera, and in particular, verify the possible tendency for the accumulation of repetitive DNAs in the terminal portion of the chromosomes of C. gibbus, H. armatus, and R. vulpinus. The Rex1, Rex3, and Rex6 transposable retroelements and the (CA)15, (GA)15, (GATA)8, (GACA)8, (CAT)10, and (CAC)10 microsatellite motifs are found primarily in the terminal portion of the chromosomes of the species analyzed in this study, except R. vulpinus, which has no evidence of the presence of Rex1 or Rex3 through the fluorescent in situ hybridization technique. The mapping of the repetitive sequences, principally the microsatellite motifs, indicates a marked tendency for the accumulation of these sequences in the terminal portions of the chromosomes, which may have played a fundamental role in the differentiation of the three species.

Rovral® is a fungicide used to control pests that affect various crops and little is known regarding its effects on embryonic development of amniotes. Thus, this study aimed to determine the influe...

The study aims to investigate the rates of recidivism among prisoners on parole with a substance misuse disorder who participated in the Jerusalem halfway-house, which combines supervision, employment, and a comprehensive therapeutic program. The study population included all participants who have been treated in the halfway-house ( N = 125), whereas the comparison group included all prisoners with a substance misuse disorder who were released after serving their full sentences ( N = 321). To reduce possible selection biases, the Propensity Score Matching method was used. Findings show that prisoners, who were treated at the Jerusalem halfway-house, are characterized by higher and frequent rates of recidivism. However, when only completers of the halfway-house were evaluated, it was found that they had lower and slower rates of recidivism. Findings suggest that completing treatment contributes to desistance from crime in the critical post-release years among participants and indicates the importance of optimal diagnostic processes before admitting prisoners to a halfway-house.

The fish family Cynodontidae belongs to the superfamily Curimatoidea, together with the Hemiodontidae, Serrasalmidae, Parodontidae, Prochilodontidae, Chilodontidae, Curimatidae, and Anostomidae. The majority of the species of this superfamily that have been analyzed to date have a diploid chromosome number of 2n = 54. Differentiated sex chromosomes (with female heterogamety) have been observed only in the Prochilodontidae, Parodontidae, and Anostomidae. The present study provides the first description of differentiated sex chromosomes in the cynodontid species Cynodon gibbus, which has a ZZ/ZW system, and shows that repetitive DNA has played a fundamental role in the differentiation of these sex chromosomes.

Transposable elements have driven genome evolution and plasticity in many ways across a range of organisms. Different types of biotic and abiotic stresses can stimulate the expression or transposition of these mobile elements. Here, we cytogenetically analyzed natural fish populations of the same species living under different environmental conditions to test the influence and organization of transposable elements in their genome. Differential behavior was observed for the markers Rex 1, Rex 3, and Rex 6 in the chromosomes of individuals of the same species but coming from different environments (polluted and unpolluted). An increase in the number of Rex transposable elements in the chromosomes and their influence on the genome of populations living in a polluted environment indicates that they must be under constant adaptive evolution.

The synthesis of cytochrome c oxidase 2 (SCO₂) gene encodes for a mitochondrial located metallochaperone essential for the synthesis of the cytochrome c oxidase (COX) subunit 2. Recessive mutations in SCO₂ have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy. Here, we identified a homozygous pathogenic variant (c.361G > C; p.[Gly121Arg]) in SCO₂ in two brothers with isolated axonal motor neuropathy. To address pathogenicity of the amino acid substitution, biochemical studies were performed and revealed increased level of the mutant SCO₂-protein and dysregulation of COX subunits in leukocytes and moreover unraveled decrease of proteins involved in the manifestation of neuropathies. Hence, our combined data strengthen the concept of SCO₂ being causative for a very rare form of axonal neuropathy, expand its molecular genetic spectrum and provide first biochemical insights into the underlying pathophysiology.

Funder: Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein‐Westfalen; Id: http://dx.doi.org/10.13039/501100009591, Funder: Bundesministerium für Bildung und Forschung; Id: http://dx.doi.org/10.13039/501100002347, AIMS: MICU1 encodes the gatekeeper of the mitochondrial Ca2+ uniporter, MICU1 and biallelic loss-of-function mutations cause a complex, neuromuscular disorder in children. Although the role of the protein is well understood, the precise molecular pathophysiology leading to this neuropaediatric phenotype has not been fully elucidated. Here we aimed to obtain novel insights into MICU1 pathophysiology. METHODS: Molecular genetic studies along with proteomic profiling, electron-, light- and Coherent anti-Stokes Raman scattering microscopy and immuno-based studies of protein abundances and Ca2+ transport studies were employed to examine the pathophysiology of MICU1 deficiency in humans. RESULTS: We describe two patients carrying MICU1 mutations, two nonsense (c.52C>T; p.(Arg18*) and c.553C>T; p.(Arg185*)) and an intragenic exon 2-deletion presenting with ataxia, developmental delay and early onset myopathy, clinodactyly, attention deficits, insomnia and impaired cognitive pain perception. Muscle biopsies revealed signs of dystrophy and neurogenic atrophy, severe mitochondrial perturbations, altered Golgi structure, vacuoles and altered lipid homeostasis. Comparative mitochondrial Ca2+ transport and proteomic studies on lymphoblastoid cells revealed that the [Ca2+ ] threshold and the cooperative activation of mitochondrial Ca2+ uptake were lost in MICU1-deficient cells and that 39 proteins were altered in abundance. Several of those proteins are linked to mitochondrial dysfunction and/or perturbed Ca2+ homeostasis, also impacting on regular cytoskeleton (affecting Spectrin) and Golgi architecture, as well as cellular survival mechanisms. CONCLUSIONS: Our findings (i) link dysregulation of mitochondrial Ca2+ uptake with muscle pathology (including perturbed lipid homeostasis and ER-Golgi morphology), (ii) support the concept of a functional interplay of ER-Golgi and mitochondria in lipid homeostasis and (iii) reveal the vulnerability of the cellular proteome as part of the MICU1-related pathophysiology.

Simple summary: Intraductal tubulopapillary neoplasms (ITPN) have recently been described as rare precursor lesions of pancreatic ductal adenocarcinoma and cholangiocarcinoma. Despite a high number of associated invasive adenocarcinomas at the time of diagnosis, patients with ITPN tend to have a much better clinical outcome than those with classical pancreato-biliary adenocarcinoma. Furthermore, rare molecular studies of ITPN show an unexpected lack of hotspot mutations in common driver genes of pancreato-biliary adenocarcinoma, including KRAS. This article reports the first large comprehensive and comparative molecular study of pancreato-biliary ITPN. In the absence of KRAS mutations, we found a high genetic heterogeneity with enrichment in core signaling pathways, including putative actionable genomic targets in one-third of the cases. Whereas, pancreatic ITPN demonstrates a highly distinct genetic profile, differing from classical pancreatic carcinogenesis, biliary ITPN and classical cholangiocarcinoma share common alterations in key genes of the chromatin remodeling pathway, and therefore, appear more closely related than pancreatic ITPN and classical pancreatic ductal adenocarcinoma PDAC. The molecular carcinogenesis of intraductal tubulopapillary neoplasms (ITPN), recently described as rare neoplasms in the pancreato-biliary tract with a favorable prognosis despite a high incidence of associated pancreato-biliary adenocarcinoma, is still poorly understood. To identify driver genes, chromosomal gains and losses, mutational signatures, key signaling pathways, and potential therapeutic targets, the molecular profile of 11 biliary and 6 pancreatic ITPNs, associated with invasive adenocarcinoma in 14/17 cases, are studied by whole exome sequencing (WES). The WES of 17 ITPNs reveals common copy number variants (CNVs) broadly distributed across the genome, with recurrent chromosomal deletions primarily in 1p36 and 9p21 affecting the tumor suppressors CHD5 and CDKN2A, respectively, and gains in 1q affecting the prominent oncogene AKT3. The identified somatic nucleotide variants (SNVs) involve few core signaling pathways despite high genetic heterogeneity with diverse mutational spectra: Chromatin remodeling, the cell cycle, and DNA damage/repair. An OncoKB search identifies putative actionable genomic targets in 35% of the cases (6/17), including recurrent missense mutations of the FGFR2 gene in biliary ITPNs (2/11, 18%). Our results show that somatic SNV in classical cancer genes, typically associated with pancreato-biliary carcinogenesis, were absent (KRAS, IDH1/2, GNAS, and others) to rare (TP53 and SMAD4, 6%, respectively) in ITPNs. Mutational signature pattern analysis reveals a predominance of an age-related pattern. Our findings highlight that biliary ITPN and classical cholangiocarcinoma display commonalities, in particular mutations in genes of the chromatin remodeling pathway, and appear, therefore, more closely related than pancreatic ITPN and classical pancreatic ductal adenocarcinoma., German Research Foundation (DFG)

Mit dieser Ubersicht erhalten Sie einen kurzen Uberblick uber den aktuellen Stand und alle wichtigen Aspekte der Pathologie des duktalen Adenokarzinoms des Pankreas (PDAC). Die Ubersicht soll alle behandelnden Arzte in die Lage versetzen, den Pathologiebefund zum PDAC interpretieren zu konnen.

In recent years, a number of translational tools have been developed in policing to make the growing research evidence base more accessible and useful for practitioners and policymakers. He...

Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with a distinct clinical and biochemical phenotype of recurrent metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, and encephalopathy with cognitive decline. We report nine subjects from seven independent families, and we studied muscle histology, respiratory chain enzyme activities in skeletal muscle and proteomic signature of fibroblasts. All nine subjects carried autosomal recessive TANGO2 mutations. Two carried the reported deletion of exons 3 to 9, one homozygous, one heterozygous with a 22q11.21 microdeletion inherited in trans. The other subjects carried three novel homozygous (c.262C>T/p.Arg88*; c.220A>C/p.Thr74Pro; c.380+1G>A), and two further novel heterozygous (c.6_9del/p.Phe6del); c.11‐13delTCT/p.Phe5del mutations. Immunoblot analysis detected a significant decrease of TANGO2 protein. Muscle histology showed mild variation of fiber diameter, no ragged‐red/cytochrome c oxidase‐negative fibers and a defect of multiple respiratory chain enzymes and coenzyme Q10 (CoQ10) in two cases, suggesting a possible secondary defect of oxidative phosphorylation. Proteomic analysis in fibroblasts revealed significant changes in components of the mitochondrial fatty acid oxidation, plasma membrane, endoplasmic reticulum‐Golgi network and secretory pathways. Clinical presentation of TANGO2 mutations is homogeneous and clinically recognizable. The hemizygous mutations in two patients suggest that some mutations leading to allele loss are difficult to detect. A combined defect of the respiratory chain enzymes and CoQ10 with altered levels of several membrane proteins provides molecular insights into the underlying pathophysiology and may guide rational new therapeutic interventions., Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Grant/Award Number: 2014: SGR 393; Association Française contre les Myopathies (FR), Grant/Award Number: 21644; CERCA Programme/ Generalitat de Catalunya, the Hesperia Foundation, the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia, Grant/Award Number: [2017SGR1206]; European Research Council, Grant/Award Number: 309548; FEuropean Union Seventh Framework Programme, Grant/Award Number: (FP7/2007‐2013); Instituto de la Marató de TV3, Grant/Award Number: 345/C/2014rm Care (CA); Instituto de Salud Carlos III, Grant/Award Number: grants PI17‐01286, PI17/00109, PI16/00579, PI16/01048, PI14/00581 and CP09/00011; Medical Research Council, Grant/Award Number: MR/N025431/1; Mitochondrial Disease Patient Cohort (UK) , Grant/Award Number: (G0800674); National Institute for Health Research (NIHR) doctoral fellowship, Grant/Award Number: NIHR‐HCS‐D12‐03‐04; Newton Fund, Grant/Award Number: MR/N027302/1; Wellcome Centre for Mitochondrial Research, Grant/Award Number: (203105/Z/16/Z); Wellcome Investigator fund, Grant/Award Number: 109915/Z/15/Z; Wellcome Trust Pathfinder Scheme, Grant/Award Number: 201064/Z/16/Z

The Amazon aquatic ecosystems have been modified by the human population growth, going through changes in their water bodies and aquatic biota. The spectacled alligator (Caiman crocodilus crocodilus) has a wide distribution and adaptability to several environments, even those polluted ones. This study aimed to investigate if a Caiman species living in urban streams of Manaus city (Amazonas State, Brazil) is affected by environmental pollution. For that, it was used classical and molecular cytogenetic procedures, in addition to micronucleus and comet assays. Although the karyotype macrostructure remains unaltered (2 n = 42 chromosomes; 24 t + 18 m/sm; NF = 60), the genotoxic analysis and the cytogenetic mapping of repetitive DNA sequences demonstrated that polluted environments alter the genome of the specimens, affecting both the chromosomal organization and the genetic material.

Item does not contain fulltext The widespread promotion of management ideas, their regular inclusion in textbooks and business school curricula and their use in organizational change programs has engendered debates about the impact of these ideas on management and organizational practice. Based on analyses of managerial audience members' activities and related meaning-making prior to, during and after guru events with leading management thinkers, this book sheds new light on how management practitioners come to use management ideas in the different relevant contexts of their working lives. The authors argue that a broader, more differentiated and more dynamic view of managerial audiences is essential in understanding the impact of management ideas as well as the nature of contemporary managerial work. For scholars and students in organisation studies, knowledge management and management consultancy, as well as reflective management practitioners. 234 p.

Cytogenetic characterization was performed on three wandering spiders: Ctenus amphora Mello-Leitão, 1930, C. crulsi Mello-Leitão, 1930 and C. villasboasi Mello-Leitão, 1949. The three species had similar karyotypes, with 2n = 28 (26 + X1X20) in males, with sex chromosomes exhibiting positive heteropicnosis in meiotic cells. 18S rDNA mapping revealed gene sites at the terminal region of one chromosomal pair for all species, with one C. crulsi individual, showing markings in two pairs. C. villasboasi showed markers only in the pachytene phase. The distribution pattern of constitutive heterochromatin was found to be characteristic for the genus, with markings in the centromeric region of all chromosomes, suggesting an acrocentric morphology for all chromosomes of the three analysed species. The results support the fusion of sex chromosomes as an evolutionary tendency for this spider group.

Sozialtherapeutische Anstalten und Abteilungen („Sothas“) wurden als spezielle Behandlungseinrichtungen insbesondere fur Sexual- und Gewaltstraftater im deutschen Strafvollzug in den letzten Jahrzehnten stark ausgebaut. Sie sind entsprechend den dafur formulierten „Mindestanforderungen“ personell und raumlich besser ausgestattet als der normale Strafvollzug und dienen der Ruckfallpravention durch kriminaltherapeutische Interventionen. Der Beitrag beschreibt ausfuhrlich den typischen Ablauf der sozialtherapeutischen Behandlung, von der Indikationsstellung (hinsichtlich Behandlungsbedurftigkeit und -fahigkeit) uber Motivierung, Beziehungsaufbau und Formulierung von Behandlungszielen, Durchfuhrung von speziellen Behandlungsprogrammen bis hin zu Entlassungsvorbereitung, Ubergangsmanagement und Nachbetreuung. Vertieft eingegangen wird auf die Problematik der Deliktbearbeitung sowie auf Behandlungsschwierigkeiten und die Ursachen von Behandlungsabbruchen. Die Forschung zur Evaluation der Sozialtherapie liefert Hinweise auf ruckfallpraventive Effekte, lasst aber noch viele Fragen offen.

Translational criminology—the practice and process of bringing research evidence into strategies and decision-making in the criminal justice field—is growing in importance. However, there remain significant barriers to the development and sustainability of evidence-based policy and practice. In the United States, federal funding initiatives like the Bureau of Justice Assistance’s Byrne Criminal Justice Innovation (BCJI) program have provided the impetus to further translational criminology efforts by promoting sustainable, data-driven partnerships between researchers, police and local government agencies, community organizations, and residents. In this chapter, we describe the factors needed to develop a successful partnership through a case study of the Seattle, WA BCJI program, Rainier Beach: A Beautiful Safe Place for Youth (ABSPY). We begin with a discussion of the literature on translational criminology, including barriers to and facilitators of successful translation. We then describe the history, characteristics, and key stakeholders of ABSPY and how we built an approach that reflects best practices in researcher-practitioner partnerships. We conclude with lessons learned and recommendations for sustaining similar efforts in collaborations between communities, local governments, and academics.

PurposeThe purpose of this paper is to describe a case study of a pilot program in which a collaborative problem-solving approach was implemented at hot spots of juvenile and youth crime in downtown Seattle, Washington.Design/methodology/approachTwo matched pairs of youth crime hot spots were allocated at random to treatment (“non-enforcement problem-solving”) or comparison (“policing-as-usual”) conditions within matched pairs. In the treatment condition, police collaborated with community and local government partners to develop problem-solving strategies that deemphasized arrests and other traditional law enforcement approaches. Impacts on crime incidents, calls for service, and police activity were assessed using difference-in-differences Poisson regression with robust standard errors.FindingsNo significant impact on crime or calls for service was observed at one site, where several problem-solving approaches were successfully implemented. However, crime and calls for service were significantly lower at the other site, where some enforcement activity took place but non-enforcement problem-solving was limited.Research limitations/implicationsThe authors find mixed support for non-enforcement problem-solving at hot spots. The enforcement may be necessary for stabilization, and must be balanced with the risks of justice system involvement for youth. Political support at the city level is necessary for collaboration. Limitations include the small number of sites in this pilot study and key differences between treatment and comparison locations.Originality/valueThis study is one of the first to assess the impact of primarily non-enforcement problem-solving specifically at youth crime hot spots.

The chromosomes of 2 flea beetle species from central Amazonia, Omophoita abbreviata and O. aequinoctialis (Alticini), were investigated through analysis of meiotic and mitotic cells. These species belong to the subtribe Oedionychina, a taxon that has unique cytogenetic features, such as giant sex chromosomes which are aligned at a distance during meiosis I (asynaptic). O. abbreviata and O. aequinoctialis have a meiotic formula of 10II + X + y, which is predominant in this subtribe. While the species of the genus Omophoita possess a relatively stable karyotype, a typical feature for Oedionychina, the present study identified inter- and intrapopulational variation in chromosome morphology, constitutive heterochromatin, and the presence and number of B chromosomes in O. aequinoctialis. In addition, FISH mapping of telomeric sequences revealed signals in the collochores, raising several questions on the chromosomal evolution in this group.

Species in the subgenus Artibeus Leach, 1821 are widely distributed in Brazil. Conserved karyotypes characterize the group with identical diploid number and chromosome morphology. Recent studies suggested that the heterochromatin distribution and accumulation patterns can vary among species. In order to assess whether variation can also occur within species, we have analyzed the chromosomal distribution of constitutive heterochromatin in A. planirostris (Spix, 1823) and A. lituratus (Olfers, 1818) from Central Amazon (North Brazil) and contrasted our findings with those reported for other localities in Brazil. In addition, Ag-NOR staining and FISH with 18S rDNA, telomeric, and LINE-1 probes were performed to assess the potential role that these different repetitive markers had in shaping the current architecture of heterochromatic regions. Both species presented interindividual variation of constitutive heterochromatin. In addition, in A. planirostris the centromeres of most chromosomes are enriched with LINE-1, colocated with pericentromeric heterochromatin blocks. Overall, our data indicate that amplification and differential distribution of the investigated repetitive DNAs might have played a significant role in shaping the chromosome architecture of the subgenus Artibeus. © érica M. Silva de Souza.

Saguinus is the largest and most complex genus of the subfamily Callitrichinae, with 23 species distributed from the south of Central America to the north of South America with Saguinus midas having the largest geographical distribution while Saguinus bicolor has a very restricted one, affected by the population expansion in the state of Amazonas. Considering the phylogenetic proximity of the two species along with evidence on the existence of hybrids between them, as well as cytogenetic studies on Saguinus describing a conserved karyotypic macrostructure, we carried out a physical mapping of DNA repeated sequences in the mitotic chromosome of both species, since these sequences are less susceptible to evolutionary pressure and possibly perform an important function in speciation. Both species presented 2n = 46 chromosomes; in S. midas, chromosome Y is the smallest. Multiple ribosomal sites occur in both species, but chromosome pairs three and four may be regarded as markers that differ the species when subjected to G banding and distribution of retroelement LINE 1, suggesting that it may be cytogenetic marker in which it can contribute to identification of first generation hybrids in contact zone. Saguinus bicolor also presented differences in the LINE 1 distribution pattern for sexual chromosome X in individuals from different urban fragments, probably due to geographical isolation. In this context, cytogenetic analyses reveal a differential genomic organization pattern between species S. midas and S. bicolor, in addition to indicating that individuals from different urban fragments have been accumulating differences because of the isolation between them.

The genus Colomesus is the sole representative of the family Tetraodontidae in the Amazon region. Here, Colomesus asellus was analyzed using conventional and molecular cytogenetic protocols. Its diploid chromosome number is 2n = 46 with 12 meta-, 10 submeta-, 16 subtelo-, and 8 acrocentric chromosomes and a fundamental number of FN = 84. An XX/XY sex chromosome system was identified. Mapping of 18S rDNA correlated with the nucleolus organizer regions (Ag-NORs) in the short arms of the 2 X chromosomes in females and in the Y chromosome in males. C-banding revealed heterochromatin in the centromeric regions of all chromosomes, except for pair 3. Prominent sex chromosome-specific heterochromatin amplification was observed, covering the short arms of the Y chromosome almost entirely. FISH with telomeric and tropomyosin (tpm1) sequences, respectively, revealed terminal signals in all chromosomes. The analysis of extended DNA fibers confirmed the colocalization and the interspersed pattern of the telomeric and tpm1 sequences. Thus, this study highlights the remarkable evolutionary dynamism presented by the Amazonian puffer fish regarding the differentiation of a heteromorphic XY sex chromosome system and a particular sex-specific amplification of rDNA sites. This is the first record of such an association in the Tetraodontidae family.

Transforming growth factor beta 3 (TGF&beta, 3) promotes tenogenic differentiation and may enhance tendon regeneration in vivo. This study aimed to apply TGF&beta, 3 absorbed in decellularized equine superficial digital flexor tendon scaffolds, and to investigate the bioactivity of scaffold-associated TGF&beta, 3 in an in vitro model. TGF&beta, 3 could effectively be loaded onto tendon scaffolds so that at least 88% of the applied TGF&beta, 3 were not detected in the rinsing fluid of the TGF&beta, 3-loaded scaffolds. Equine adipose tissue-derived multipotent mesenchymal stromal cells (MSC) were then seeded on scaffolds loaded with 300 ng TGF&beta, 3 to assess its bioactivity. Both scaffold-associated TGF&beta, 3 and TGF&beta, 3 dissolved in the cell culture medium, the latter serving as control group, promoted elongation of cell shapes and scaffold contraction (p &lt, 0.05). Furthermore, scaffold-associated and dissolved TGF&beta, 3 affected MSC musculoskeletal gene expression in a similar manner, with an upregulation of tenascin c and downregulation of other matrix molecules, most markedly decorin (p &lt, 0.05). These results demonstrate that the bioactivity of scaffold-associated TGF&beta, 3 is preserved, thus TGF&beta, 3 application via absorption in decellularized tendon scaffolds is a feasible approach.

Contains fulltext : 203531pub.pdf (Publisher’s version ) (Open Access) Multi-level marketing companies (MLMs) such as Amway, Herbalife or Tupperware differ from most other companies. They market their products and services by means of self-employed distributors who typically work from home, sell products to end consumers, and recruit, motivate and educate new distributors to do the same. Although the industry’s growth seems to illustrate the attractiveness of MLMs, the industry has been facing several legal and ethical problems. In this paper, we focus on these problems and argue that an extended MLM model may help us to understand why such problems continue to occur, despite the countermeasures that have been implemented. By explicating how problems relate to a specific but often overlooked characteristic of MLMs, i.e. the so-called distributor network (DN), we provide an extended understanding of (a) MLMs’ mode of operation, (b) the sources of their legal and ethical problems, and (c) the reason that currently implemented and suggested countermeasures may not suffice. Moreover, based on our extended understanding of MLMs and their problems, we propose additional countermeasures. 12 mei 2017

The taxonomy of Satanoperca spp. is still unresolved, especially because coloring, one of the main diagnostic characters, is variable among species of this genus. Thus, the aim of this study was to elucidate the relationship between the genome and the organization of the chromosome in two Satanoperca species. Our main goal was to develop a method to better differentiate taxa and understand the evolution of Satanoperca jurupari and Satanoperca lilith karyotypes, which we analyzed with classical and molecular cytogenetics. Both species have the same diploid number (2n) of 48 and location of 5S rDNA sites on pair 5. Nonetheless, the distribution of heterochromatin and 18S rDNA sites followed a species-specific pattern. The interstitial telomeric sites were not highlighted in either species. Regardless, a single B chromosome was identified in some metaphases of S. lilith. These data show that Satanoperca species harbor chromosomal features that can be used to identify the two species of Satanoperca studied here, allowing for the use of cytogenetic markers to make taxonomic inferences within the genus.

We provide an efficient protocol for obtaining mitotic chromosomes with well-defined morphology in 17 different taxa of the class Reptilia. We also show that there is no need for adjustments among taxa and no need to sacrifice the animals studied.

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.

In magnetic resonance imaging (MRI) examinations, moderate to severe changes of the distal sesamoidean impar ligament (DSIL) were found in horses with lameness localized to their feet. Histologic abnormalities were detected more commonly in lame horses. Because of its heterogeneity and small thickness, evaluation of the DSIL in MRI can be challenging. The aim of the study was to determine the optimal sequence and the ideal transverse perpendicular angle for visualization of the DSIL before and after arthrography of the distal interphalangeal joint (DIPJ). Twenty-five cadaver forelimbs were examined with low-field MRI. Sagittal, frontal, and three different angled transverse planes were obtained before and after arthrography of the DIPJ. All planes were acquired in T1w (weighted) Gradient Recall Echo (GRE), T2∗w GRE, T2w Fast Spin Echo (FSE), and Short Tau Inversion Recovery (STIR) FSE and visualization of the DSIL was scored by two observers. Visualization of the DSIL was best on sagittal T2w FSE and STIR FSE images. All transverse planes were inferior compared with sagittal sequences. After arthrography of the DIPJ, visualization of the DSIL origin improved in sagittal T2w FSE sequences, and agreement between observers increased for sagittal T2w FSE and STIR FSE images. Sagittal T2w FSE and STIR FSE images allowed good visualization of the DSIL in low-field MRI. Visualization of the DSIL did not improve for altered angled transverse sequences but increased with arthrography of the DIPJ. Subjective influence between different observers was found but decreased with DIPJ arthrography.

Pollution is a growing environmental problem throughout the world, and the impact of human activities on biodiversity and the genetic variability of natural populations is increasingly preoccupying, given that adaptive processes depend on this variability, in particular that found in the repetitive DNA. In the present study, the mitochondrial DNA (COI) and the distribution of repetitive DNA sequences (18S and 5S rDNA) in the fish genome were analysed in fish populations inhabiting both polluted and unpolluted waters in the northern Amazon basin. The results indicate highly complex ribosomal sequences in the fish genome from the polluted environment because these sequences are involved primarily in the maintenance of genome integrity, mediated by a systematic increase in the number of copies of the ribosomal DNA in response to changes in environmental conditions.