Critical transitions and evolutionary hysteresis in movement: Habitat fragmentation can cause abrupt shifts in dispersal that are difficult to revert

Under habitat fragmentation, plant species' survival hinges on the ability of individuals to disperse from one habitat patch to another. While there is evidence that severe habitat fragmentation leads to evolution of reduced dispersal ability and that such decreased mobility is generally detrimental for species' survival, it is unknown whether species adapt via a gradual loss in dispersal ability or via a sudden shift from frequent to infrequent dispersal between patches (i.e., a critical transition). Using both a spatially explicit deterministic and individual-based stochastic model of hydrochorous seed dispersal, we show that a small increase in inter-patch distance can generate an abrupt shift in plant seed dispersal strategy from long to short distances. Most importantly, we found that a substantial increase in connectivity between habitat fragments is required to reverse this loss of long-distance dispersal, due to an evolutionary hysteresis effect. Our theory prompts for re-consideration of the eco-evolutionary consequences of habitat fragmentation as restoring habitat connectivity may require restoration of much higher connectivity levels than currently assumed

Patterning in mussel beds explained by the interplay of multi-level selection and spatial self-organization

Cooperation, ubiquitous in nature, is difficult to explain from an evolutionary perspective. Many modeling studies strive to resolve this challenge, but their simplifying assumptions on population and interaction structure are rarely met in ecological settings. Here we use a modeling approach that includes more ecological detail to investigate evolution of cooperation in spatially self-organized mussel beds. Mussels cooperate with each other through aggregative movement and attachment using byssal threads. These cooperative behaviors shape the spatial structure of the mussel bed, which can range from scattered distributions to labyrinth-like patterns and dense mussel clumps. The spatial pattern in turn impacts an individual’s fitness at two levels: (i) proper attachment to neighboring individuals decreases predation risk, and (ii) attachment to a sufficiently large group prevents dislodgement by wave stress. Without this second level of selection, our simulations do typically not result in evolutionary attractors that lead to the labyrinth-like spatial patterns that are characteristic for natural mussel beds. Yet, when group-level selection is included, labyrinth-like patterns emerge under a wide range of conditions. Our model demonstrates that multiple selection factors working at different spatial scales – predation of individuals and dislodgement of entire mussel clumps – combinedly determine evolution of cooperative traits in mussels and thereby result in emergence of the labyrinth-like spatial patterns that we observe in natural mussel beds

Local abundances of terrestrial mammal and bird species around indigenous villages in Suriname

Hunting is an important threat to tropical wildlife, yet many people are dependent on forest fauna for protein provisioning. We analyzed abundances of terrestrial mammal and bird species around four indigenous villages in the south of Suriname, using camera trap data and the Royle–Nichols abundance model. We hypothesized that hunting pressure increases with decreasing distance to a village and with increasing village size (expressed as cropland area). We detected 24 animal species in all villages combined, including several rare species. For 11 of the 24 species, we were able to examine if and how distance to a village and village size related to local abundances and found a positive effect of distance to village on local abundances in five species, and a negative effect of village size in one species. Because villages, and thus hunting, affect local abundances of terrestrial bird and mammal species in our study, we recommend monitoring forest fauna in areas where people are highly dependent on animals for food provisioning

First-line palliative HER2-targeted therapy in HER2-positive metastatic breast cancer is less effective after previous adjuvant trastuzumab-based therapy

Background. Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-näive patients (TN-group) in order to investigate the possibility of trastuzumab resistance. Patients and Methods. Patients treated with first-line HER2-targeted- containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP-group. OS and TNT were estimated using Kaplan-Meier curves andmultivariable Cox proportional hazards models. Results. Between January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP-group and 387 were in the TN-group. Median OS and TNT were significantly worse in the TP-group compared with the TN-group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15-2.96], p5.01 and 7 vs. 13 months, adjusted HR 1.65 [1.06-2.58], p5.03) after adjustment for age, year of diagnosis, diseasefree interval, hormone receptor status, metastatic site, and cytotoxic regimens. Conclusion. First-line trastuzumab-containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab-näive patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2-targeted treatment lines need further investigation.</p

Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed n