Animal

Navigation requires a network of neurons processing inputs from internally generated cues and external landmarks. Most studies on the neuronal basis of navigation in vertebrates have focused on rats and mice and the canonical senses vision, hearing, olfaction, and somatosensation. Some animals have evolved the ability to sense the Earth's magnetic field and use it for orientation. It can be expected that in these animals magnetic cues are integrated with other sensory cues in the cognitive map. We provide an overview of the behavioral evidence and brain regions involved in magnetic sensing in support of this idea, hoping that this will guide future experiments...

IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2...

BACKGROUND AND OBJECTIVES: Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease...

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, causing a substantive threat to the public, which receives global concern. However, there are limited drugs targeting the treatment of DN. Owing to this, it is highly crucial to investigate the pathogenesis and potential therapeutic targets of DN. The process of ferroptosis is a type of regulated cell death (RCD) involving the presence of iron, distinct from autophagy, apoptosis, and pyroptosis. A primary mechanism of ferroptosis is associated with iron metabolism, lipid metabolism, and the accumulation of ROS...

OBJECTIVES: The aim of the present study was to assess the accuracy of weight estimation in cats provided by pet owners, veterinary technicians, house officers (interns and residents) and attending clinicians in an emergency room (ER). An additional objective was to determine whether carrying the cat contributed to a more accurate weight estimate. METHODS: A total of 72 cats presented to an ER and were enrolled in the study. Pet owners, veterinary technicians, house officers and attending clinicians were asked to record the cats' estimated weights on individual data collection cards...

Many cancer patients are at risk of developing cognitive symptoms that often become evident during or after cancer-directed therapy and may involve difficulties with attention, concentration, multitasking, executive function, and memory. Despite recent advances in identifying potential molecular and cellular mechanisms underlying cancer and chemotherapy-related cognitive impairment, there is generally a lack of effective treatment strategies, and the development of novel therapeutic interventions represents a major unmet medical need in clinical practice...

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression. This study aimed to explore the roles of CAFs-derived Fibroblast growth factor 9 (FGF9) and Neuro-oncological ventral antigen 1 (NOVA1) in triple negative breast cancer (TNBC) progression. MDA-MB-231 and BT-549 cells were cocultured with CAF conditioned-medium (CAF-CM) or normal fibroblasts conditioned-medium (NF-CM). MTT, EdU, colony formation, wound healing, transwell migration, and invasion assays were employed to determine cell proliferation, migration and invasion, respectively...

Animals are much better at running than robots. The difference in performance arises in the important dimensions of agility, range, and robustness. To understand the underlying causes for this performance gap, we compare natural and artificial technologies in the five subsystems critical for running: power, frame, actuation, sensing, and control. With few exceptions, engineering technologies meet or exceed the performance of their biological counterparts. We conclude that biology's advantage over engineering arises from better integration of subsystems, and we identify four fundamental obstacles that roboticists must overcome...

Advances in engineering enable wheeled-legged hybrid locomotion, an achievement not feasible in biological systems.

Polycomb group (PcG) proteins mediate epigenetic silencing of important developmental genes by modifying histones and compacting chromatin through two major protein complexes, PRC1 and PRC2. These complexes are recruited to DNA by CpG islands (CGIs) in mammals and Polycomb response elements (PREs) in Drosophila . When PcG target genes are turned OFF, PcG proteins bind to PREs or CGIs, and PREs serve as anchors that loop together and stabilize gene silencing. Here, we address which PcG proteins bind to PREs and whether PREs mediate looping when their targets are in the ON transcriptional state...

Myotendinous junction (MTJ) injuries are prevalent in clinical practice, yet the treatment approaches are limited to surgical suturing and conservative therapy, exhibiting a high recurrence rate. Current research on MTJ tissue engineering is scarce and lacks in vivo evaluation of repair efficacy. Here, we developed a three-dimensional-printed bioactive fiber-reinforced hydrogel containing mesenchymal stem cells (MSCs) and Klotho for structural and functional MTJ regeneration. In a rat MTJ defect model, the bioactive fiber-reinforced hydrogel promoted the structural restoration of muscle, tendon, and muscle-tendon interface and enhanced the functional recovery of injured MTJ...

T helper 17 (TH 17) cells are implicated in autoimmune diseases, and several metabolic processes are shown to be important for their development and function. In this study, we report an essential role for sphingolipids synthesized through the de novo pathway in TH 17 cell development. Deficiency of SPTLC1, a major subunit of serine palmitoyl transferase enzyme complex that catalyzes the first and rate-limiting step of de novo sphingolipid synthesis, impaired glycolysis in differentiating TH 17 cells by increasing intracellular reactive oxygen species (ROS) through enhancement of nicotinamide adenine dinucleotide phosphate oxidase 2 activity...

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina...

Sex-limited polymorphism has evolved in many species including our own. Yet, we lack a detailed understanding of the underlying genetic variation and evolutionary processes at work. The brood parasitic common cuckoo ( Cuculus canorus ) is a prime example of female-limited color polymorphism, where adult males are monochromatic gray and females exhibit either gray or rufous plumage. This polymorphism has been hypothesized to be governed by negative frequency-dependent selection whereby the rarer female morph is protected against harassment by males or from mobbing by parasitized host species...

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia...

Pronounced differences in neurotransmitter release from a given presynaptic neuron, depending on the synaptic target, are among the most intriguing features of cortical networks. Hippocampal pyramidal cells (PCs) release glutamate with low probability to somatostatin expressing oriens-lacunosum-moleculare (O-LM) interneurons (INs), and the postsynaptic responses show robust short-term facilitation, whereas the release from the same presynaptic axons onto fast-spiking INs (FSINs) is ~10-fold higher and the excitatory postsynaptic currents (EPSCs) display depression...

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment...

Recent evidence has demonstrated that the transsynaptic nanoscale organization of synaptic proteins plays a crucial role in regulating synaptic strength in excitatory synapses. However, the molecular mechanism underlying this transsynaptic nanostructure in inhibitory synapses still remains unclear and its impact on synapse function in physiological or pathological contexts has not been demonstrated. In this study, we utilized an engineered proteolysis technique to investigate the effects of acute cleavage of neuroligin-2 (NL2) on synaptic transmission...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens (Fra-) 1 and 2 is unknown. Here, we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2hep mice...

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells...