Warming and higher nitrogen loading induced by increasing precipitation are expected scenarios in north temperate regions as consequence of global climate change, with potential effects on the ...functional traits of submerged macrophytes and periphyton. Using an experimental heating facility we investigated the responses of three-week growth of two submerged macrophytes (
Potamogeton crispus
Linn. and
Elodea canadensis
Michx.), and periphyton on these plants and their artificial mimics. Analysis was based on IPCC climate scenarios A2 (ca. + 3°C) and A2 + 50% (called A3 in our study) relative to ambient conditions, across warming in spring and early summer (summer showed higher nitrogen loading). Some functional traits of plants showed species-specific responses to warming: A3 promoted the growth of
E. canadensis
in both seasons, while for
P. crispus
warming reduced the leaf number in spring but enhanced the turion production in early summer. Periphyton biomass was lower in A3 in early summer, but not in spring. Our results further show that the growth of
E. canadensis
and the asexual reproduction of
P. crispus
might increase in a warmer future. Moreover, we found a complex response of periphyton to the temperature increase and substrate type, varying with season and nutrient state.
Purpose
The purpose of this paper is to explore leadership for diversity informed by intersectionality and radical politics. Surfacing the political character of intersectionality, the authors ...suggest that a leadership for diversity imbued with a commitment to political action is essential for the progress towards equality.
Design/methodology/approach
Drawing lessons from the grassroots, political organizing of the black and Indigenous activist groups Combahee River Collective and Idle No More, the authors explore how these groups relied on feminist alliances to address social justice issues. Learning from their focus on intersectionality, the authors consider the role of politically engaged leadership in advancing diversity and equality in organizations.
Findings
The paper finds that leadership for diversity can be developed by shifting towards a more radical and transversal politics that challenges social and political structures that enable intersectionality or interlocking oppressions. This challenge relies on critical alliances negotiated across multiple intellectual, social and political positions and enacted through flexible solidarity to foster a collective ethical responsibility and social change. These forms of alliance-based praxis are important for advancing leadership for diversity.
Originality/value
This paper contributes to studies of leadership and critical diversity studies by articulating an alliance-based praxis for leadership underpinned by intersectionality, radical democracy and transversal politics.
Warming, eutrophication, and increased omnivory by small-sized fish are global change processes that induce major effects on the food web structure and primary producers of shallow lakes. Despite the ...key relevance of phytoplankton and periphyton in freshwaters, the combined and potential synergistic effects of fish omnivory, warming and eutrophication, especially on periphyton, remains little addressed, particularly for subtropical shallow lakes. We experimentally tested the food web effects on phytoplankton and periphyton induced by small visually feeding omnivorous fish (Rhodeus ocellatus), high nutrient enrichment and warming (+4.5 °C) in thirty-two 1000 L-mesocosms simulating littoral conditions of subtropical shallow lakes. We aimed at analysing the mechanisms and responses of periphyton and phytoplankton to these experimental factors. All mesocosms included the submerged macrophytes Vallisneria denseserrulata and Potamogeton lucens and artificial plants at 50% plant volume inhabited, plankton and macroinvertebrates. Small-sized visually feeding omnivorous fish enhanced phytoplankton dominance and periphyton loss. These changes coincided with a decrease in zooplankton biomass and a diversity loss of both zooplankton and macroinvertebrates as well as an increase in snail abundance. Fish presence led to a collapse of cladocerans, thereby releasing the grazing pressure on phytoplankton, and predator and collector macroinvertebrates were replaced with small snails (Radix peregra < 0.5 cm) resulting in enhanced grazing on periphyton. Eutrophication reinforced the fish effects, while warming had weak or no effects. Our results indicate that omnivory by small-sized visually feeding fish may induce stronger effects on the food webs of shallow lakes, towards phytoplankton-dominated states, than the combined effect of nutrient enrichment and warming under the present experimental conditions.
Display omitted
•Fish omnivory and eutrophication enhanced phytoplankton growth and periphyton loss.•Fish decreased macroinvertebrates and zooplankton diversity.•Fish decreased zooplankton grazing by selectively consuming large-sized Cladocera.•Small-sized omnivorous fish promoted snails grazing on periphyton.•Fish omnivory fostered phytoplankton more than warming and eutrophication combined.
This paper describes mammary organoids with a basal‐in phenotype where the basement membrane is located on the interior surface of the organoid. A key materials consideration to induce this basal‐in ...phenotype is the use of a minimal gel scaffold that the epithelial cells self‐assemble around and encapsulate. When MDA‐MB‐231 breast cancer cells are co‐cultured with epithelial cells from day 0 under these conditions, cells self‐organize into patterns with distinct cancer cell populations both inside and at the periphery of the epithelial organoid. In another type of experiment, the robust formation of the basement membrane on the epithelial organoid interior enables convenient studies of MDA‐MB‐231 invasion in a tumor progression‐relevant direction relative to epithelial cell‐basement membrane positioning. That is, the study of cancer invasion through the epithelium first, followed by the basement membrane to the basal side, is realized in an experimentally convenient manner where the cancer cells are simply seeded on the outside of preformed organoids, and their invasion into the organoid is monitored. Interestingly, invasion is more prominent when tumor cells are added to day 7 organoids with less developed basement membranes compared to day 16 organoids with more defined ones.
This paper describes the basal‐in phenotype of organotypic structures formed from MCF10A cells, in which a cell‐produced basement membrane is located on the interior side of the organoid. Because of the conveniently located apical surface, represented by the region exposed to the media surrounding the organoid, this platform shows promise as a high‐throughput cancer invasion assay.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans. PCSK9 has also been shown to regulate the ...levels of additional membrane-bound proteins in vitro, including the very low-density lipoprotein receptor (VLDLR), apolipoprotein E receptor 2 (ApoER2) and the β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are all highly expressed in the CNS and have been implicated in Alzheimer's disease. To better understand the role of PCSK9 in regulating these additional target proteins in vivo, their steady-state levels were measured in the brain of wild-type, PCSK9-deficient, and human PCSK9 overexpressing transgenic mice. We found that while PCSK9 directly bound to recombinant LDLR, VLDLR, and apoER2 protein in vitro, changes in PCSK9 expression did not alter the level of these receptors in the mouse brain. In addition, we found no evidence that PCSK9 regulates BACE1 levels or APP processing in the mouse brain. In conclusion, our results suggest that while PCSK9 plays an important role in regulating circulating LDL cholesterol levels by reducing the number of hepatic LDLRs, it does not appear to modulate the levels of LDLR and other membrane-bound proteins in the adult mouse brain.
The treatment of enteric fever is complicated by the emergence of antimicrobial resistant Salmonella Typhi. Azithromycin is commonly used for first-line treatment of uncomplicated enteric fever, but ...the response to treatment may be sub-optimal in some patient groups when compared with fluoroquinolones.
We performed an analysis of responses to treatment with azithromycin (500mg once-daily, 14 days) or ciprofloxacin (500mg twice-daily, 14 days) in healthy UK volunteers (18-60 years) enrolled into two Salmonella controlled human infection studies. Study A was a single-centre, open-label, randomised trial. Participants were randomised 1:1 to receive open-label oral ciprofloxacin or azithromycin, stratified by vaccine group (Vi-polysaccharide, Vi-conjugate or control Men-ACWY vaccine). Study B was an observational challenge/re-challenge study, where participants were randomised to challenge with Salmonella Typhi or Salmonella Paratyphi A. Outcome measures included fever clearance time, blood-culture clearance time and a composite measure of prolonged treatment response (persistent fever ≥38.0°C for ≥72 hours, persistently positive S. Typhi blood cultures for ≥72 hours, or change in antibiotic treatment). Both trials are registered with ClinicalTrials.gov (NCT02324751 and NCT02192008).
In 81 participants diagnosed with S. Typhi in two studies, treatment with azithromycin was associated with prolonged bacteraemia (median 90.8 hours 95% CI: 65.9-93.8 vs. 20.1 hours 95% CI: 7.8-24.3, p<0.001) and prolonged fever clearance times <37.5°C (hazard ratio 2.4 95%CI: 1.2-5.0; p = 0.02). Results were consistent when studies were analysed independently and in a sub-group of participants with no history of vaccination or previous challenge. A prolonged treatment response was observed significantly more frequently in the azithromycin group (28/52 54.9%) compared with the ciprofloxacin group (1/29 3.5%; p<0.001). In participants treated with azithromycin, observed systemic plasma concentrations of azithromycin did not exceed the minimum inhibitory concentration (MIC), whilst predicted intracellular concentrations did exceed the MIC. In participants treated with ciprofloxacin, the observed systemic plasma concentrations and predicted intracellular concentrations of ciprofloxacin exceeded the MIC.
Azithromycin at a dose of 500mg daily is an effective treatment for fully sensitive strains of S. Typhi but is associated with delayed treatment response and prolonged bacteraemia when compared with ciprofloxacin within the context of a human challenge model. Whilst the cellular accumulation of azithromycin is predicted to be sufficient to treat intracellular S. Typhi, systemic exposure may be sub-optimal for the elimination of extracellular circulating S. Typhi. In an era of increasing antimicrobial resistance, further studies are required to define appropriate azithromycin dosing regimens for enteric fever and to assess novel treatment strategies, including combination therapies.
ClinicalTrials.gov (NCT02324751 and NCT02192008).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Osteoarthritis is a debilitating disease that results in pain and joint stiffness. Currently, steroidal and nonsteroidal anti-inflammatory drugs and supplements aimed at restoring lubrication to the ...affected joint are the most successful with respect to improving patient comfort. Due to the success in lubricating therapies, there exists a keen interest to develop better therapies that mimic how lubrication occurs naturally in the joint. Here we describe the results obtained using a chondroitin sulfate chain to which is conjugated peptides that bind to either hyaluronic acid (found in high concentrations in the synovial fluid) or collagen type II (present on the cartilage surface). Our study investigates the effect of binding to the cartilage surface and interacting with hyaluronic acid on lubrication at the cartilage surface. The results described here suggest that binding to the cartilage surface is critical to supporting lubrication and did not require the addition of hyaluronic acid to reduce friction.
Display omitted
•Glycosaminoglycan binding to the cartilage surface is critical to reducing friction.•Hyaluronic acid may not be required to reduce friction at the cartilage surface.•Peptide-glycosaminoglycan conjugates can reduce cartilage friction.
Introduction
Guidelines for perioperative systemic therapy administration in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are ...evolving. Decisions regarding adjuvant therapy are influenced by postoperative morbidity, which is common after pancreatoduodenectomy. We evaluated whether postoperative complications are associated with receipt of adjuvant therapy after pancreatoduodenectomy.
Methods
A retrospective analysis of patients undergoing pancreatoduodenectomy for PDAC or dCCA from 2015 to 2020 was conducted. Demographic, clinicopathologic, and postoperative variables were analyzed.
Results
Overall, 186 patients were included—145 with PDAC and 41 with dCCA. Postoperative complication rates were similar for both pathologies (61% and 66% for PDAC and dCCA, respectively). Major postoperative complications (MPCs), defined as Clavien–Dindo >3, occurred in 15% and 24% of PDAC and dCCA patients, respectively. Patients with MPCs received lower rates of adjuvant therapy administration, irrespective of primary tumor (PDAC: 21 vs. 72%,
p
= 0.008; dCCA: 20 vs. 58%,
p
= 0.065). Recurrence-free survival (RFS) was worse for patients with PDAC who experienced an MPC 8 months (interquartile range IQR 1–15) vs. 23 months (IQR 19–27),
p
< 0.001 or who did not receive any perioperative systemic therapy 11 months (IQR 7–15) vs. 23 months (IQR 18–29),
p
= 0.038. In patients with dCCA, 1-year RFS was worse for patients who did not receive adjuvant therapy (55 vs. 77%,
p
= 0.038).
Conclusion
Patients who underwent pancreatoduodenectomy for either PDAC or dCCA and who experienced an MPC had lower rates of adjuvant therapy and worse RFS, suggesting that clinicians adopt a standard neoadjuvant systemic therapy strategy in patients with PDAC. Our results propose a paradigm shift towards preoperative systemic therapy in patients with dCCA.
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