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The spontaneous emergence of collective flows is a generic property of active fluids and often leads to chaotic flow patterns characterised by swirls, jets, and topological disclinations in their orientation field. However, the ability to achieve structured flows and ordered disclinations is of particular importance in the design and control of active systems. By confining an active nematic fluid within a channel, we find a regular motion of disclinations, in conjunction with a well defined and dynamic vortex lattice. As pairs of moving disclinations travel through the channel, they continually exchange partners producing a dynamic ordered state, reminiscent of Ceilidh dancing. We anticipate that this biomimetic ability to self-assemble organised topological disclinations and dynamically structured flow fields in engineered geometries will pave the road towards establishing new active topological microfluidic devices.

Consciousness can be defined by two major attributes: awareness of environment and self, and arousal, which reflects the level of awareness. The return of arousal after general anesthesia presents an experimental tool for probing the neural mechanisms that control consciousness. Here we have identified that systemic or intracerebral injection of the cannabinoid CB1 receptor (CB1R) antagonist AM281 into the dorsomedial nucleus of the hypothalamus (DMH) - but not the adjacent perifornical area (Pef) or the ventrolateral preoptic nucleus of the hypothalamus (VLPO) - accelerates arousal in mice recovering from general anesthesia. Anesthetics selectively activated endocannabinoid (eCB) signaling at DMH glutamatergic but not GABAergic synapses, leading to suppression of both glutamatergic DMH-Pef and GABAergic DMH-VLPO projections. Deletion of CB1R from widespread cerebral cortical or prefrontal cortical (PFC) glutamatergic neurons, including those innervating the DMH, mimicked the arousal-accelerating effects of AM281. In contrast, CB1R deletion from brain GABAergic neurons or hypothalamic glutamatergic neurons did not affect recovery time from anesthesia. Inactivation of PFC-DMH, DMH-VLPO, or DMH-Pef projections blocked AM281-accelerated arousal, whereas activation of these projections mimicked the effects of AM281. We propose that decreased eCB signaling at glutamatergic terminals of the PFC-DMH projection accelerates arousal from general anesthesia through enhancement of the excitatory DMH-Pef projection, the inhibitory DMH-VLPO projection, or both.

Purpose: To evaluate the effect of catheter-directed irreversible electroporation (iRE) on the integrity, patency, and function of the normal porcine ureter. Materials and Methods: A catheter-mounted electrode was used to perform fluoroscopy-guided IRE in 8 healthy pigs. Two unilateral ablations (90 pulses at 2,000 V, 100 mu s) were performed in each animal in the proximal and distal ureter. Serum creatinine measurements and contrast-enhanced computed tomography imaging were performed at 1, 7, 14, 21, and 28 days after IRE, and findings were compared with baseline values by Student t test. Two animals each were euthanized at 1, 7, 14, and 28 days after IRE for histologic assessment of treatment effects. Quantitative histologic analysis of regeneration and healing of the ureteral wall was graded on a five-point scale. Results: IRE was successfully performed in all animals. Preservation of ureteral wall integrity was confirmed by the leakage-free passage of contrast medium in the treated ureter of all animals through the observation period. Ureteral strictures and associated renal pelvicaliceal dilation were observed in all animals by study days 7 (P = .005) and 14 (P = .007) and did not resolve by day 28. Urothelial recovery was observed in tissue samples from day 7, with progressive replacement of the tunica muscularis with granulation tissue. Despite extensive scarring of the tunica muscularis, full recovery of the urothelium was observed by day 28. Conclusions: The normal porcine ureter retains lumen wall integrity and function following catheter-directed IRE. Scarring of the tunica muscularis in the treated ureter results in stricture formation and reduction of lumen patency.

Using a microfluidic trap, we study the behavior of individual phospholipid vesicles in contact with fatty acids. We show that spontaneous fatty acids insertion inside the bilayer is controlled by the vesicle size, osmotic pressure difference across the membrane and fatty acids concentration in the external bath. Depending on these parameters, vesicles can grow spherically or become unstable and fragment into several daughter vesicles. We establish the phase diagram for vesicle growth and we derive a simple thermodynamic model that reproduces the time evolution of the vesicle volume. Finally, we show that stable growth can be achieved on an artificial cell expressing a simple set of bacterial cytoskeletal proteins, paving the way toward artificial cell reproduction.

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the beta-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the beta-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

Systemic lupus erythematosus (SLE) is an incurable autoimmune disease characterized by autoantibody deposition in tissues such as kidney, skin and lungs. Notably, up to 75% of patients with SLE experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and, in rare cases, psychosis-collectively this is referred to as central nervous system (CNS) lupus(1-4). In some cases, certain autoantibodies, such as anti-NMDAR or anti-phospholipid antibodies(5,6), promote CNS lupus. However, in most patients, the mechanisms that underlie these symptoms are unknown. CNS lupus typically presents at lupus diagnosis or within the first year, suggesting that early factors contributing to peripheral autoimmunity may promote CNS lupus symptoms. Here we report behavioural phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signalling. Furthermore, we show that type I IFN stimulates microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. These findings and our observation of increased type I IFN signalling in post-mortem hippocampal brain sections from patients with SLE may instruct the evaluation of ongoing clinical trials of anifrolumab(7), a type I IFN-receptor antagonist. Moreover, identification of IFN-driven microglia-dependent synapse loss, along with microglia transcriptome data, connects CNS lupus with other CNS diseases and provides an explanation for the neurological symptoms observed in some patients with SLE.

How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to function. We therefore treat protein as learning amorphous matter that evolves towards such a mechanical function: Genes are binary sequences that encode the connectivity of the amino acid network that makes a protein. The gene is evolved until the network forms a shear band across the protein, which allows for long-range, soft modes required for protein function. The evolution reduces the high-dimensional sequence space to a low-dimensional space of mechanical modes, in accord with the observed dimensional reduction between genotype and phenotype of proteins. Spectral analysis of the space of 10(6) solutions shows a strong correspondence between localization around the shear band of both mechanical modes and the sequence structure. Specifically, our model shows how mutations are correlated among amino acids whose interactions determine the functional mode.

We study analytically the one-loop contribution to the chiral magnetic effect (CME) using lattice regularization with a Wilson fermion field. In the continuum limit, we find that the chiral magnetic current vanishes at nonzero temperature but emerges at zero temperature consistent with that found by Pauli-Villas regularization. For finite lattice size, however, the chiral magnetic current is nonvanishing at nonzero temperature. But the numerical value of the coefficient of CME current is very small compared with that extracted from the full QCD simulation for the same lattice parameters. The possibility of higher-order corrections from QCD dynamics is also assessed.

Type III CRISPR-Cas systems have a unique targeting mechanism that requires the transcription of the DNA target and results in the degradation of not only the genome of the invader but also its transcripts. Here we discuss the most recent studies describing dual DNA and RNA targeting by these systems, as well as the implications of this complex molecular mechanism for immunity in vivo.