Uptake of macromolecules by cercariae during skin penetration and transformation to schistosomula (Schistosoma mansoni)

Here, we observed the uptake of membrane-impermeant molecules by cercariae as they penetrate the skin and are transformed into schistosomula. We propose that membrane-impermeant molecules, Lucifer Yellow, Propidium iodide and Hoechst 33258 enter the parasite through both thenephridiopore and the surface membrane and then diffuse throughout the body of the parasite. We present a hypothesis that the internal cells of the body of the schistosomulum represent a new host-parasite interface, at which skin-derived growth factors may stimulate receptors on internal membranes during transformation of the cercariae into the schistosomulum.

Chromosomal number aberrations and transformation in adult mouse retinal stem cells in vitro.

PURPOSE: The potential of stem cells (SCs) as a source for cell-based therapy on a wide range of degenerative diseases and damaged tissues such as retinal degeneration has been recognized. Generation of a high number of retinal stem cells (RSCs) in vitro would thus be beneficial for transplantation in the retina. However, as cells in prolonged cultivation may be unstable and thus have a risk of transformation, it is important to assess the stability of these cells. METHODS: Chromosomal aberrations were analyzed in mouse RSC lines isolated from adult and from postnatal day (PN)1 mouse retinas. Moreover, selected cell lines were tested for anchorage-dependent proliferation, and SCs were transplanted into immunocompromised mice to assess the possibility of transformation. RESULTS: Marked aneuploidy occurred in all adult cell lines, albeit to different degrees, and neonatal RSCs were the most stable and displayed a normal karyotype until at least passage 9. Of interest, the level of aneuploidy of adult RSCs did not necessarily correlate with cell transformation. Only the adult RSC lines passaged for longer periods and with a higher dilution ratio underwent transformation. Furthermore, we identified several cell cycle proteins that might support the continuous proliferation and transformation of the cells. CONCLUSIONS: Adult RSCs rapidly accumulated severe chromosomal aberrations during cultivation, which led to cell transformation in some cell lines. The culture condition plays an important role in supporting the selection and growth of transformed cells.

Existential values transformation in all organ transplantation: A qualitative prospective study.

Organ transplantation offers a treatment of choice for patients suffering from end stage illnesses. The aim of this IRB approved prospective qualitative study was to analyze patients’ psychological concerns from their inclusion on the waiting list for first organ transplantation (TX) (T1; N=71; kidney, K=30; liver, Li=11; lung, Lu=15; heart, H=15) and six months after TX (T2; N=49; K=15; Li=10; Lu=14; H=10). Semi-structured interviews were conducted at home or in a place selected by patients. Qualitative pattern analysis (QUAPA) of the verbatim transcriptions was applied. T1 (K) Patients maintained an apparent normality (87%), building emotional protection (23%), and developing a fatalist attitude towards life (43%). (Li) Physical limits were set to spare energy until TX (73%). Illness led to reevaluation of life values (66%). (Lu) Physical and psychological self-protection was prioritized when health declined (67%). Modified life values, fatalism (33%) and spirituality (27 %) were mentioned. (H) Patients husbanded physical (80%) and psychological (67%) resources and self-protection. Modified life values and fatalist attitude towards life were reported (40%). T2 (K) New perspective on life was described, with increase of empathy towards others (20%). (Li) Positive identity and life values modifications (60%), greater openness towards others, closeness to significant ones (30%) and a more self-centered attitude (30%) prioritizing the essential (20%) were reported. Lack of respect of life values generated anger (40%). (Lu) Setting existential priorities and increase in spirituality (64%), along with the development of new life values, greater openness to others (57%) and closeness to significant ones (21%) were underlined. Lack of respect of human values induced negative feelings (36%). Self-centered attitudes, setting limits to other people were mentioned (29%). (H) Change in life values with setting life priorities was reported (70%) with increase in spirituality, and the lack of respect of life values generated anger (50%). Self-centered attitudes were reported (60%). TX not only comes with positive physical benefits, but also with positive existential values and psychological transformation, and the development of a more altruistic attitude and humanistic values.

Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients.

Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in clinical findings, histology, and immunophenotype reminiscent of B-lymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations (CD79B, CCND3, CDK12). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease.

PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Organisational PSM Antecedents. Do HRM Practices Matter? Testing the Mediating Role of Job Satisfaction and Organisational Commitment

The present study aims to identify organisational antecedents of public service motivation (PSM). Numerous research has been devoted to the identification of socio-demographic PSM antecedents, or to its outcomes. However, organisational antecedents are understudied thus far. In order to fill this research gap, we question whether human resources management practices, whether intrinsic or extrinsic ones, might be related to PSM. Drawing on person-environment fit theoretical assumptions, we depart from the idea that PSM may be developed or sustained by HRM practices, which might contribute to create an environment allowing public employees to fulfill their needs or personal aspirations. Based upon a survey in an important Swiss municipality (N = 859), our findings surprisingly highlight that extrinsic HRM practices are significantly related to PSM, whereas intrinsic ones are not. Furthermore, when taking into account work-related outcomes, such as job satisfaction and organisational commitment, there is evidence of full mediation effects towards extrinsic HRM practices from organisational commitment. Astonishingly, neither job satisfaction nor intrinsic HRM practices are significantly related to PSM.

Luteinizing hormone (LH) and prolactin-releasing pituitary tumor: possible malignant transformation of the LH cell line.

A pituitary tumor was diagnosed in a prepubertal 13-yr-old girl, who had elevated plasma LH (58 mIU/ml) and PRL (93 ng/ml) levels; decreased GH, ACTH, and FSH secretion; and diabetes insipidus. After surgery, plasma LH and PRL declined, but not to normal levels. Conventional external radiotherapy to the pituitary was immediately followed by a decrease in LH to prepubertal values (0.7 mIU/ml), while PRL levels became normal only after a long course of bromocriptine therapy. The pituitary tumor was composed of two distinct cell types: small polygonal cells, which were PRL positive by immunohistochemistry, and clusters of pleomorphic large frequently mitotic polynucleated cells, which were LH positive, some of them also being positive for the alpha-subunit or beta LH but not for beta FSH. Four years after surgery and radiotherapy, the patient deteriorated neurologically. Computed tomographic scan showed widespread frontal and periventricular tumor, which had the histological features of a poorly differentiated carcinoma. No PRL, LH, or alpha- or beta-subunits were detectable on immunocytochemistry. While the PRL-positive cells of the pituitary tumor displayed the histological and clinical features of PRL adenomas, the morphological characteristics of LH cells and the sharp decline of plasma LH levels after radiotherapy were suggestive of malignant transformation. In this context, the later brain tumor could have been the result of subependymal spread of the pituitary tumor after it lost its hormone-secreting capacity.

Legal europeanization as legal transformation : some insights from Swiss 'outer Europe'

The "Europeanization" of non-EU countries' laws is predominantly seen as an "export" of the EU acquis, especially in the case of so-called "quasi-member" states such as Switzerland. Based on an examination of the Swiss experience, this paper highlights the flaws of this conceptualization: the Europeanization of Swiss Law is a highly differentiated phenomenon, encompassing several forms of approximation to EU Law. All of these forms fall short of an "export" of norms, and result in the creation of something new: a "Europeanized law" that is similar to, but qualitatively different from, EU Law. Another drawback of the "export" metaphor is the emphasis it places on the isomorphism of positive legislation. Europeanization goes deeper than that. As shown in this paper, it is a process of transformation involving not only positive law, but also legal thinking. The Swiss case demonstrates how significant such deeper transformations can be: the Europeanization of positive law has induced an alteration of the traditional canon of legal interpretation. It also demonstrates how problematic such transformations can be: the above-mentioned alteration has not given rise to a new and universally accepted canon of interpretation. This reflects the tension between the need for clear "rules of reference" for EU legal materials - which are required in order to restore coherence and predictability to an extensively Europeanized legal system - and the reluctance to give a legal value to foreign legal materials - which is rooted in a traditional understanding of the concept of "law". Such tension, in turn, shows what deep and difficult transformations are required in order to establish a viable model of legal integration outside supranational structures.

Organisational Values as "Attractors of Chaos": An Emerging Cultural Change to Manage Organisational Complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.