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Common dolphins, Delphinus sp., are one of the marine mammal species tourism operations in New Zealand focus on. While effects of cetacean-watching activities have previously been examined in coastal regions in New Zealand, this study is the first to investigate effects of commercial tourism and recreational vessels on common dolphins in an open oceanic habitat. Observations from both an independent research vessel and aboard commercial tour vessels operating off the central and east coast Bay of Plenty, North Island, New Zealand were used to assess dolphin behaviour and record the level of compliance by permitted commercial tour operators and private recreational vessels with New Zealand regulations. Dolphin behaviour was assessed using two different approaches to Markov chain analysis in order to examine variation of responses of dolphins to vessels. Results showed that, regardless of the variance in Markov methods, dolphin foraging behaviour was significantly altered by boat interactions. Dolphins spent less time foraging during interactions and took significantly longer to return to foraging once disrupted by vessel presence. This research raises concerns about the potential disruption to feeding, a biologically critical behaviour. This may be particularly important in an open oceanic habitat, where prey resources are typically widely dispersed and unpredictable in abundance. Furthermore, because tourism in this region focuses on common dolphins transiting between adjacent coastal locations, the potential for cumulative effects could exacerbate the local effects demonstrated in this study. While the overall level of compliance by commercial operators was relatively high, non-compliance to the regulations was observed with time restriction, number or speed of vessels interacting with dolphins not being respected. Additionally, prohibited swimming with calves did occur. The effects shown in this study should be carefully considered within conservation management plans, in order to reduce the risk of detrimental effects on common dolphins within the region.

Sources of magnetic fields-magnetic monopoles-have so far proven elusive as elementary particles. Condensed-matter physicists have recently proposed several scenarios of emergent quasiparticles resembling monopoles. A particularly simple proposition pertains to spin ice on the highly frustrated pyrochlore lattice. The spin-ice state is argued to be well described by networks of aligned dipoles resembling solenoidal tubes-classical, and observable, versions of a Dirac string. Where these tubes end, the resulting defects look like magnetic monopoles. We demonstrated, by diffuse neutron scattering, the presence of such strings in the spin ice dysprosium titanate (Dy2Ti2O7). This is achieved by applying a symmetry-breaking magnetic field with which we can manipulate the density and orientation of the strings. In turn, heat capacity is described by a gas of magnetic monopoles interacting via a magnetic Coulomb interaction.

Complementary resource use is considered an important mechanism in the study of biodiversity effects. Here we explore how species identity, species mixture and tree size influence the vertical partitioning of soil water among canopy trees during a soil desiccation period. In the Hainich Forest, Germany, the species Fagus sylvatica, Tilia sp. and Fraxinus excelsior were studied in single- and three-species mixed clusters, each consisting of three co-dominant trees situated within a larger mixed forest stand. Vertical soil water uptake depth was assessed by analyzing the hydrogen stable isotope composition (deuterium, δD) of water from depth intervals throughout the soil profile and in tree xylem water. For single species clusters, a mixing model suggested that Fagus distinctively drew water from soil depths of 0.3–0.5 m, Tilia from 0.3–0.5 m and 0.5–0.7 m and Fraxinus mainly used water from 0.5–0.7 m. In mixed clusters, the uptake patterns of Fagus and Tilia were similar to those of the single-species clusters (mainly uptake form 0.3–0.5 m), but Fraxinus showed a different uptake pattern. Fraxinus in mixture had a somewhat homogenously distributed uptake over the soil depths 0.2–0.7 m. For single species clusters, there was no correlation between main soil water uptake depth and tree diameter, irrespective of variations in tree size. In contrast, for mixed clusters there was a significant decrease in the main uptake depth with increasing tree size (P<0.001, R2adj = 0.73), irrespective of species mix. In consequence, soil water partitioning was strongest where species were mixed and tree size varied. We further analyzed whether single and mixed-species clusters differed in the level of water uptake, e.g. due to complementarity, but our soil water budgeting did not indicate any such differences. A possible explanation might be that the volume of water used is predominantly governed by properties at the stand level, such as aerodynamic roughness, rather than by processes acting at the meter scale between neighbouring trees. With respect to application, we assume that the upcoming close-to-nature forestry approach for the area, which fosters mixed stands of heterogonous diameters, may result in enhanced complementarity in soil water uptake among canopy trees.

Androgenetic alopecia is the most common cause of hair loss for women and men. Current treatments for androgenetic alopecia, such as those based on drugs like Minoxidil, Finasteride, or Dutasteride, have been associated with a variety of side effects, such as irritation, contact dermatitis, scalp pruritus, burning, etc. In this regard, plant extracts have emerged as promising alternatives to available chemical-based treatments for androgenetic alopecia given their efficacy, customer acceptability, and potentially minimized side effects. In this study, we evaluated the efficacy of Kyoh®, an extract from rocket leaves, as a treatment to improve the signs of androgenetic alopecia. We found that Kyoh® contained 2.1% total flavonoids, with kaempferol, quercetin, and isorhamnetin diglucosides being the most abundant. Additionally, Kyoh® showed a stimulating effect on the growth of human dermal follicle papilla cells in laboratory conditions. Most importantly, Kyoh® enhanced the gene expression of the hair growth-associated growth factors VEGF (Vascular Endothelial Growth Factor) and FGF7 (Fibroblast Growth Factor 7). Specifically, VEGF expression increased by 60.7% after 4 h and 267.3% after 24 h, while FGF7 expression increased by 50.3% after 4 h and 244.3% after 24 h, indicating both a rapid induction of gene expression and a sustained effect lasting at least one day. Moreover, Kyoh® increased the gene expression of NRF2 (Nuclear factor erythroid 2-related factor 2) by 71.2%, which encodes for a protein participating in the antioxidant response. Overall, our study shows that flavonol-rich rocket extract (Kyoh®) is a promising treatment for promoting hair growth, demonstrated by its proliferation-promoting effect, potential antioxidant priming, and induction of the expression of growth factors associated with hair growth and health.

T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling. However, the role of spectrin in IS formation has not been explored. We used molecular, imaging and cellular approaches to show that nonerythroid αII-spectrin redistributes to the IS during T-cell activation. The redistribution of spectrin coincides with the relocation of CD45 and LFA-1, two components essential for IS formation and stability. We assessed the role of spectrin by shRNA-mediated depletion from Jurkat T cells and show that spectrin-depleted cells exhibit decreased adhesion and are defective in forming lamellipodia and filopodia. Importantly, IS formation is impaired in spectrin-depleted cells. Thus, spectrin may be engaged in regulation of distinct events necessary for the establishment and maturity of the IS: besides the involvement of spectrin in the control of CD45 and LFA-1 surface display, spectrin acts in the establishment of cell-cell contact and adhesion processes during the formation of the IS.

BackgroundImmune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients.MethodsWe analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded.ResultsOverall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR.ConclusionOur results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

Skin irritation and itching, often intense, are common consequences of mosquito bites. Interest in cosmetics formulated with natural ingredients has markedly increased among consumers, perceiving them as healthier, safer and more sustainable. We developed a natural formulation based on botanical ingredients for the treatment of mosquito bites. In this work, we tested the physicochemical and microbiological stability of this novel formulation, as well as its skin tolerance. Moreover, we performed an in vitro test to assess its soothing efficacy in comparison with an ammonia-based product. According to our findings, the natural formulation resulted in a stable oil-in-water emulsion, with an appealing texture and good skin tolerance; no cases of erythema or edema were observed in any of the volunteers with sensitive skin after product application. In addition, an in vitro test performed on a keratinocytes cell line showed that our formulation significantly reduced IL-1α levels, with a displayed efficacy comparable to the ammonia-based product. This study emphasizes the promising potential of botanical ingredients in the field of cosmetic dermatology, offering high-performance, well-tolerated skincare products suitable for the treatment of common skin irritations, such as mosquito bites.

Background/Objectives: Magnesium (Mg)-based food supplements contribute to the maintenance of adequate levels of Mg that are essential for overall health and well-being. The aim of this double-blind, randomized, cross-over clinical study was to assess the plasma Mg levels in volunteers following the oral administration of a magnesium-based nutraceutical ingredient, MAGSHAPETM microcapsules (Mg-MS), in comparison to other commonly used magnesium sources, including the following: Mg Oxide (MgO), Mg Citrate (Mg-C), and Mg bisglycinate (Mg-BG). Methods: A total of 40 healthy women and men were put on a low-Mg diet for 7 days, and after 8 h of fasting, a blood sample was taken from a digital puncture before (0 h) and 1 h, 4 h, and 6 h after the oral intake of each product. Results: Our results showed that the blood plasma levels of Mg increased significantly at all tested time-points after the oral intake of Mg-MS, while the blood plasma levels of Mg increased significantly only after 1 and 4 h of the oral intake of MgO and Mg-C, respectively. However, no significant increase in Mg levels was observed upon the intake of Mg-BG. Interestingly, the Mg-MS microencapsulation technology was observed to enable a sustained increase in plasma Mg levels over the duration of this study, i.e., 1, 4, and 6 h after oral intake. A direct comparison of the increase in plasma Mg levels over the 6 h period revealed that the Mg-MS microencapsulation technology significantly increased Mg bioavailability compared to the non-microencapsulated MgO. Our study also showed that, compared to the other Mg sources tested, the Mg-MS microencapsulation technology reduced adverse side effects commonly associated with Mg supplementation, specifically with regard to increased intestinal motility and sensations of gastric heaviness following oral administration. Conclusions: Altogether, this clinical study introduced MAGSHAPETM microcapsules as a bioavailable and well-tolerated alternative to existing Mg-based ingredients used in food supplements.

Land cover mapping can be seen as a key element to understand the spatial distribution of habitats and thus to sustainable management of natural resources. Multi-temporal remote sensing data are a valuable data source for land cover mapping. However, the increased amount of data requires effective machine learning algorithms and data compression approaches. In this study, the Random Forest and C 5.0 classification algorithms were applied to (1) a multi-temporal Tasselled-Cap-transformed, (2) top of atmosphere and (3) surface reflectance RapidEye time-series. The overall accuracies ranged from 91.44% to 91.80%, with only minor differences between algorithms and datasets. The McNemar test showed, however, significant differences between the Tasselled-Cap-transformed and untransformed mapping results in most cases. The temporal profiles for the Tasselled-Cap-transformed RapidEye data indicated a good separability between considered classes. The phenological profiles of vegetated surfaces followed a typical green-up curve for the Greenness Tasselled-Cap-index. A permutation-based variable importance measure indicated that late autumn should be considered as most important phenological phase contributing to the classification model performance. The results suggested that the RapidEye Tasselled Cap Transformation, which was designed for agricultural applications, can be an effective data compression tool, suitable to map heterogeneous landscapes with no measurable negative impact on classification accuracy.