Fasting initiates a coordinated metabolic response to preserve energy balance. As glycogen stores are depleted, the body transitions to mobilizing fatty acids from adipose tissue and generating ketone bodies in the liver to sustain the function of vital organs. A network of hormonal signals and transcriptional programs coordinate these adaptations. Among these, the hepatokine fibroblast growth factor 21 (FGF21) is strongly upregulated during fasting and has been proposed as a key mediator of the fasting response. To investigate the physiological functions of FGF21, we study mice with hepatocyte-specific deletion of Fgf21. Although the liver is the primary source of circulating FGF21 during fasting, its absence in hepatocytes does not alter typical fasting-induced gene expression or key metabolic pathways such as hepatic gluconeogenesis, adipose tissue lipolysis, or ketone production. Instead, we uncover a distinct role for FGF21 in promoting protein appetite following a fast. These findings challenge the conventional view of hepatocyte-produced FGF21 as a fasting-acting hormone and reveal a more specialized function in guiding nutrient selection after energy depletion.
Replicating the native cellular density of tissues remains a critical bottleneck in bioprinting, as most techniques yield local concentrations orders of magnitude lower than physiological levels. Here, we report Micro-Injection Laser-Assisted Bioprinting (MI-LAB), a laser-assisted strategy that uniquely integrates in situ microspheroid formation with micrometer-scale deposition precision. Unlike conventional laser-assisted bioprinting (LAB), which relies on pre-fabricated spheroids, MI-LAB dynamically generates cellular aggregates during printing, achieving features as small as 30 & micro;m while reaching local cell concentrations in the range of 100 million cells/mL, comparable to native tissues. This dual capability bridges the gap between single-cell placement and multicellular assembly. As a proof of concept, we fabricated prevascularized constructs by sequentially depositing human umbilical vein endothelial cell aggregates within a methacrylated gelatin/collagen (GelMA/ColMA) matrix containing human skin fibroblasts. The engineered tissues exhibited guided vasculogenic sprouting and robust endothelial marker expression, validating the maturation of pre-microvascular networks. By enabling programmable microspheroid placement at native-like densities with microscale precision, MI-LAB establishes a disruptive biofabrication paradigm for pre-microvascularized tissues while offering a broadly applicable strategy for high-density, biomimetic tissue engineering.
This article traces the history of microbial culture collections to explore the evolution of microbial biodiversity conservation and biotechnological valorization between 1972 and 2022. It shows how a progressive assetization of microbial value led to an enclosure of the global microbial commons. Culture collections were enablers and victims of this change. Analyzing collections across Europe, the Americas, and Asia as well as the World Federation of Culture Collections (WFCC), the article reconstructs how culture collections functioned as a key infrastructure for the globalized take-off of the biotechnology industry. Biotechnological investment in microbial exploitation created important revenue streams amidst public funding cuts and collections' declining role as research hubs. However, pressure to control and generate income from microbial assets also shifted moral economies governing microbial exchange and led to commercial rivalry between collections. While biodiversity concerns prompted a reconceptualization of collections as microbial arks, the 1993 Convention on Biological Diversity's recognition of national sovereignty over bioresources further complicated microbial conservation. Actors such as the WFCC and Organisation for Economic Co-operation and Development (OECD) tried to reconcile access and benefit sharing (ABS) obligations and intellectual property (IP) via guidelines, networking, and accreditation. However, entrenched asymmetries in the global distribution of ex situ conservation infrastructures and microbial value generation remained unaddressed despite passage of the 2010 Nagoya protocol on ABS. Meanwhile, advances in sequencing and synthetic biology not only highlighted biases in existing collections, but also pointed to an era in which in silico approaches to biodiversity might supersede existing in vitro museums.
Implementing an inclusive school means that teachers should use exam accommodations to foster the participation of students with Special Educational Needs (SEN). However, due to the emphasis on merit in most school systems, this practice can create a dilemma between equality and equity that can notably influence teachers' perceived fairness of such accommodations. Three studies conducted in the French context with teachers, students and members of the public (i.e. convenience samples, N = 1,525) examined this dilemma. Results indicate a differentiated perception of accommodations in terms of fairness, but also comparability. Moreover, the more teachers believed assessment should support student learning, the more they perceived exam accommodations as facilitating comparisons of students' performance, and the fairer they perceived accommodations. These findings highlight a recurrent equality - equity tension in assessment and suggest that accommodations intended to promote equity may be viewed as less fair when they are perceived to undermine comparability.
BACKGROUND Liver transplantation (LT) in hyperimmunized recipients with pre-formed donor-specific antibodies (pDSA) or a positive crossmatch (CM) presents a significant immunological graft challenge. AIM To assess whether induction therapy with rabbit anti-T lymphocyte globulin (rATLG) and high-dose intravenous immunoglobulin (IVIG) reduces acute T-cell mediated rejection (TCMR), acute antibody-mediated rejection (aAMR), and graft loss in these patients. METHODS This retrospective case-control study, conducted between 2016 and 2022, compared the outcomes of two groups of LT recipients: Forty-six hyperimmunized patients (high-risk, pDSA and/or CM positive at time of LT) were matched with 46 non-immunized (low-risk) recipients. High-risk patients received anti-T lymphocyte globulin/IVIG induction therapy whereas the low-risk patients did not. Patient and graft survival were compared using Kaplan-Meier survival analysis. RESULTS The incidence of biopsy-proven TCMR was numerically lower in the high-risk group (19.6%) compared to the low-risk group (26.1%), with all cases classified as Banff mild or moderate. Of these, clinically significant rejections requiring treatment occurred in 10.9% of high-risk and 8.7% of low-risk recipients. A subset of the high-risk group (n = 4, 8.7%) developed aAMR vs none in the low-risk group. The one-year (high-risk: 83.6%, low-risk: 95.6%) and three-year (high-risk: 78.0%, low-risk: 91.2%) survival rates were comparable between the two groups (log-rank P = 0.051). Notably, no grafts were lost due to rejection in either group, and no adverse events were linked to the induction therapy used in the high-risk group. CONCLUSION Short course of rATLG and IVIG induction therapy can be a valuable strategy for mitigating early immunological risks in hyperimmunized recipients, leading to comparable outcomes to non-immunized patients.
