Master regulators of the epithelial-mesenchymal transition such as Twist1 and Snail1 have been implicated in invasiveness and the generation of cancer stem cells, but their persistent activity ...inhibits stem-cell-like properties and the outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show that Twist1 activation primes a subset of mammary epithelial cells for stem-cell-like properties, which only emerge and stably persist following Twist1 deactivation. Consequently, when cells undergo a mesenchymal-epithelial transition (MET), they do not return to their original epithelial cell state, evidenced by acquisition of invasive growth behavior and a distinct gene expression profile. These data provide an explanation for how transient Twist1 activation may promote all steps of the metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites.
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•Transient Twist1 activation primes cells for stem-cell-like traits•Stable stem-cell-like traits arise after Twist1 deactivation•Transient, not continuous, Twist1 activity promotes invasive growth•Transient Twist1 elicits a stably altered plastic epithelial cell state
Schmidt et al. show that Twist1, a master regulator of the epithelial-mesenchymal transition, primes mammary epithelial cells for stem-cell-like properties. Following transient Twist1 activation, cells display an altered, epithelial cell state characterized by invasive growth, plasticity, and a unique gene expression profile.
We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix ...environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.
The development of well-adhering, easily producible photonic reflective coatings is still a challenge. Here, an easy-to-produce, industrial viable process is reported that uses a primer layer of the ...so-called type II photoinitiator to obtain an excellent adhesion between a plastic substrate and one-dimensional (1D) photonic liquid crystalline coatings. Furthermore, a good alignment of the reactive cholesteric liquid crystal mixture is obtained using a bar-coating process, without alignment layers or surfactants. After photopolymerization, cross-hatch tape tests show a good adhesion of the photonic coating having a reflection band of 50% transmission with almost no scattering. Additionally, we demonstrate the ability to create well-adhering ∼100% reflective coatings by coating double layers and the ability to create single-layered cholesteric broadband reflectors using solely a reactivity gradient created by the primer layer. Our new interfacial method gives new opportunities to use reflecting 1D photonic coatings in industrial processes and applications and allows the bonding of almost any polymer to a plastic substrate.
To investigate the current practice of enucleation with or without orbital implant for retinoblastoma in countries across the world.
A digital survey identifying operation techniques and material ...used for orbital implants after enucleation in patients with retinoblastoma.
We received a response of 58 surgeons in 32 different countries. A primary artificial implant is routinely inserted by 42 (72.4%) surgeons. Ten (17.2%) surgeons leave the socket empty, three (5.2%) decide per case. Other surgeons insert a dermis fat graft as a standard primary implant (n=1), or fill the socket in a standard secondary procedure (n=2; one uses dermis fat grafts and one artificial implants). The choice for porous implants was more frequent than for non-porous implants: 27 (58.7%) and 15 (32.6%), respectively. Both porous and non-porous implant types are used by 4 (8.7%) surgeons. Twenty-five surgeons (54.3%) insert bare implants, 11 (23.9%) use separate wrappings, eight (17.4%) use implants with prefab wrapping and two insert implants with and without wrapping depending on type of implant. Attachment of the muscles to the wrapping or implant (at various locations) is done by 31 (53.4%) surgeons. Eleven (19.0%) use a myoconjunctival technique, nine (15.5%) suture the muscles to each other and seven (12.1%) do not reattach the muscles. Measures to improve volume are implant exchange at an older age (n=4), the use of Restylane SQ (n=1) and osmotic expanders (n=1). Pegging is done by two surgeons.
No (worldwide) consensus exists about the use of material and techniques for enucleation for the treatment of retinoblastoma. Considerations for the use of different techniques are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The fabrication of temperature responsive photonic polymers remains a challenge. Here, we report the fabrication of humidity-gated temperature-responsive infrared reflective photonic coatings using ...an easy-to-process bar-coating technique. At high humidity the hydroscopic cholesteric liquid crystalline polymer is able to absorb water vapour from the air causing swelling of the photonic coating. By increasing the temperature, water is desorbed from the coating, resulting in a reversible 420 nm shift of the photonic reflection band. In particular, it is shown that temperature-responsive single-layered broadband IR reflective coatings, prepared by creation of a pitch gradient of the cholesteric liquid crystals, might be suitable for smart window applications in high relative humidity environments such as greenhouses.
Postoperative cognitive dysfunction (POCD) is being recognized as a complication contributing to perioperative morbidity and mortality of the elderly. We hypothesized that the use of the ...shorter-acting volatile anaesthetic desflurane would be associated with less incidence of POCD when compared with sevoflurane.
Approved by the local ethical committee, 80 patients (aged 65–75 yr) were enrolled in this randomized, double-blinded study. Patients were allocated to either the desflurane (n=40) or the sevoflurane (n=40) group. The primary outcome was the cognitive Test for Attentional Performance with its subtests Alertness, Divided Attention, Visual Scanning, Working Memory, and Reaction Change. In addition, Paper–Pencil Tests Well-being Test BF-S, Recall of Digit Span (DST), Digit-Symbol-Substitution Test, Trail Making Tests A and B, and Spielberg State-Trait Anxiety Inventory were measured. After baseline assessment 12–24 h before operation, patients were followed up 6–8 and 66–72 h after operation. Among other outcome parameters, emergence times from anaesthesia and modified Aldrete scores were recorded.
There was no difference in the incidence of POCD. However, according to the Paper–Pencil Tests, significant improvements for the desflurane group could be detected (Well-being Test at 6–8 h, DST at 6–8 h, and Trail Making Test at 66–72 h). Emergence was significantly faster in the desflurane group for ‘time to open eyes’ and ‘time to extubation’.
The total incidence of POCD showed no differences between the desflurane and the sevoflurane groups. However, the tests Well-being scale, DST, and Trail Making Test, emergence times, and patients’ satisfaction were in favour of desflurane.
We update the results of cloud imaging sequences from the Mars Science Laboratory (MSL) rover Curiosity to complete two Mars years of observations (LS=160° of Mars year (MY) 31 to LS=160° of MY 33). ...Relatively good seasonal coverage is achieved within the study period, with just over 500 observations obtained, averaging one observation every 2–3 sols. Cloud opacity measurements are made using differential photometry and a simplified radiative transfer method. These opacity measurements are used to assess the interannual variability of the aphelion cloud belt (ACB) for MY 32 and 33. Upon accounting for a statistical bias in the data set, the variation is found to be <30% within uncertainty. Diurnal variation of the ACB is also able to be examined in MY 33 owing to an increased number of early morning observations in this year. Although a gap in data around local noon prevents a complete assessment, we find that cloud opacity is moderately increased in the morning hours (07:00–09:00) compared to the late afternoon (15:00–17:00).
Key Points
Interannual variability of the ACB is estimated to be <30% between MY 32 and 33
Cloud opacity is increased in the morning compared to the late afternoon
In this retrospective study, a technique consisting in neurolysis of the lateral retinacular nerve combined with a partial release through elliptic excision of the iliotibial band (ITB) is evaluated ...for efficacy in recalcitrant ITB friction syndrome and compared with results from other techniques reported in literature. From April 2014 to December 2017, 21 patients suffering from recalcitrant ITB friction syndrome were surgically treated with the aforementioned technique. 15 patients (15 knees) were available for a written retrospective reassessment after completion of a follow-up period of at least 12 months. Residual pain was scored using the Visual Analogue Scale (VAS). The functional outcome was evaluated by two patient reported outcome measurement scales (PROMs), the Lysholm and the International Knee Documentation Committee (IKDC) score. Return to sport was analysed by duration of the inactivity period as well as by the Tegner score. Overall satisfaction was evaluated using a modified Boyden scale. At final follow-up of one year, the performed intervention resulted in a pain reduction (VAS 4.2 (1-8) to 1.4 (0-6)) and improved knee function (Lysholm 59.53 to 87.73, IKDC 75) with return to sport (Tegner 4.3 to 5.4) after a median of 23.8 weeks (6 to 52). Twelve patients reported good or excellent results (80%) at final follow-up, and 12 patients (80%) would undergo surgery again, if necessary. The treatment of recalcitrant ITB friction syndrome by combining neurectomy of the lateral retinacular nerve with elliptic excision of the ITB resulted in good to excellent results in 80% of treated cases with return to sport in 93%.
Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as ...metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers. By contrast, TGFBR1-activation directs Twist1 to induce stable mesenchymal transdifferentiation through EMT, thereby generating cells that display single-cell invasion, but lose their proliferative capacity. In conclusion, preventing Twist1-induced EMT by inhibiting TGFβ-signaling does not generally block acquisition of invasion, but switches mode from single-cell/non-proliferative to collective/proliferative. Together, these data reveal that transient Twist1-activation induces distinct cell states depending on signaling context and caution against the use of TGFβ-inhibitors as a therapeutic strategy to target invasiveness.
Cosmetic dissatisfaction, pain, and chronic discharge may present months till years after enucleation in patients operated because of retinoblastoma. If noninvasive treatment modalities are ...insufficient, socket reconstruction can be considered. In this study, we discuss the results of dermis-fat exchange to treat these problems.
Four patients with late onset post enucleation socket problems with a request for treatment were included in this prospective study. Socket inspection was documented and pictures at baseline and at a follow-up of at least 6 months were taken. To quantify the problem 'pain', a VAS score at baseline and at follow up was used. For the problem 'cosmetic dissatisfaction' standardized questionnaires were used.
Two patients were included because of cosmetic dissatisfaction; one was included with chronic pain and one with chronic discharge. Reconstruction of the socket using autologous dermis-fat insertion was done in all four. In one of them, severe shrinking of the fat developed. This patient was treated with additional injectable fillers. Both of them, ultimately, had satisfactory results. Autologous fat transplantation also solved the problem of chronic discharge and pain in the two other patients.
Socket reconstruction by autologous dermis-fat exchange may solve different post enucleation socket problems. However, shrinking of the transplanted fat may occur and require additional procedures.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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