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The corticospinal tract (CST) is clinically important for the recovery of motor functions after spinal cord injury. Despite substantial progress in understanding the biology of axon regeneration in the central nervous system (CNS), our ability to promote CST regeneration remains limited. Even with molecular interventions, only a small proportion of CST axons regenerate1. Here we investigate this heterogeneity in the regenerative ability of corticospinal neurons following PTEN and SOCS3 deletion with patch-based single cell RNA sequencing (scRNA-Seq)2,3, which enables deep sequencing of rare regenerating neurons. Bioinformatic analyses highlighted the importance of antioxidant response and mitochondrial biogenesis along with protein translation. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of antioxidant response, in CST regeneration. Applying Garnett4, a supervised classification method, to our dataset gave rise to a Regenerating Classifier (RC), which, when applied to published scRNA-Seq data, generates cell type- and developmental stage-appropriate classifications. While embryonic brain, adult dorsal root ganglion and serotonergic neurons are classified as Regenerators, most neurons from adult brain and spinal cord are classified as Non-regenerators. Adult CNS neurons partially revert to a regenerative state soon after injury, which is accelerated by molecular interventions. Our data indicate the existence of universal transcriptomic signatures underlying the regenerative abilities of vastly different neuronal populations, and further illustrate that deep sequencing of only hundreds of phenotypically identified CST neurons has the power to reveal new insights into their regenerative biology.

Electronic nematicity in iron pnictide materials is coupled to both the lattice and the conducting electrons, which allows both structural and transport observables to probe nematic fluctuations and the order parameter. Here we combine simultaneous transport and x-ray diffraction measurements with in-situ tunable strain (elasto-XRD) to measure the temperature dependence of the shear modulus and elastoresistivity above the nematic transition and the spontaneous orthorhombicity and resistivity anisotropy below the nematic transition, all within a single sample of $Ba(Fe_{0.96}Co_{0.04})_{2} As_{2}$. The ratio of transport to structural quantities is nearly temperature-independent over a 74 K range and agrees between the ordered and disordered phases. These results show that elasto-XRD is a powerful technique to probe the nemato-elastic and nemato-transport couplings, which have important implications to the nearby superconductivity. It also enables the measurement in the large strain limit, where the breakdown of mean field description reveals the intertwined nature of nematicity., Comment: Main text 10 pages, 4 figures

In most unconventional and high-temperature superconductors, superconductivity emerges as a nearby symmetry-breaking phase is suppressed by chemical doping or pressure1–7. This has led to the belief that the fluctuations associated with the symmetry-breaking phase are beneficial, if not responsible, for the superconducting pairing8,9. A direct test to verify this hypothesis is to observe a decrease of the superconducting critical temperature (Tc) by applying the symmetry-breaking conjugate field that suppresses the dynamic fluctuations of the competing order. However, most of the competing phases in unconventional superconductors break translational symmetry, requiring a spatially modulated conjugate field that is difficult to realize experimentally. Here, we show that anisotropic strain, the conjugate field of nematicity, reduces the Tc of an iron pnictide. For optimally doped samples we show a fivefold reduction of Tc with less than one per cent of strain. For underdoped samples, Tc becomes zero yielding a fully metallic ground state. In addition to providing direct evidence of the role played by the nematic fluctuations in the formation of the superconducting state, these results demonstrate tunable mechanical control of a high-temperature superconductor, an important step forward for technological applications of superconductivity. Using doped BaFe2As2, the authors test whether nematicity is linked to superconductivity in the iron pnictides by applying the conjugate field to nematicity—a specific form of strain—and observe that the critical temperature decreases.

As a hallmark of electronic correlation, spin-charge interplay underlies many emergent phenomena in doped Mott insulators, such as high-temperature superconductivity, whereas the half-filled parent state is usually electronically frozen with an antiferromagnetic order that resists external control. We report on the observation of a new positive magnetoresistance that probes the staggered susceptibility of a pseudospin-half square-lattice Mott insulator built as an artificial SrIrO3/SrTiO3 superlattice. Its size is particularly large in the high-temperature insulating paramagnetic phase near the N\'eel transition. This novel magnetoresistance originates from a collective charge response to the large longitudinal spin fluctuations under a linear coupling between the external magnetic field and the staggered magnetization enabled by strong spin-orbit interaction. Our results demonstrate a magnetic control of the binding energy of the fluctuating particle-hole pairs in the Slater-Mott crossover regime analogous to the BCS-to-Bose-Einstein condensation crossover of ultracold-superfluids., Comment: Accepted by Nature communications

Of all parent compounds of iron-based high-temperature superconductors, ${\mathrm{EuFe}}_{2}{\mathrm{As}}_{2}$ exhibits by far the largest magnetostructural coupling due to the sizable biquadratic interaction between Eu and Fe moments. While the coupling between Eu antiferromagnetic (AFM) order and Fe structural/AFM domains enables rapid field detwinning, this prevents simple magnetometry measurements from extracting the critical fields of the Eu metamagnetic transition. Here, we measure these critical fields by combining x-ray magnetic circular dichroism spectroscopy with in situ tunable uniaxial stress and applied magnetic field. The combination of two tuning knobs allows us to separate the stress detwinning of structural domains from the field-induced reorientation of Eu moments. Intriguingly, we find a spin-flip transition which can only result from a strongly anisotropic interaction between Eu planes. We argue that this anisotropic exchange is a consequence of the strong anisotropy in the magnetically ordered Fe layer, which presents a form of higher-order coupling between Eu and Fe magnetism.

Cardiac neural crest cells (cNCCs) are required for normal heart development. cNCCs are a multipotent and migratory cell lineage that differentiates into multiple cell types. cNCCs migrate into the developing heart to contribute to the septation of the cardiac outflow tract (OFT). Foxc1 and Foxc2 are closely related members of the FOX (Forkhead box) transcription factor family and are expressed in cNCC during heart development. However, the precise role of Foxc1 and Foxc2 in cNCCs has yet to be fully described. We found that compound NCC-specific Foxc1;Foxc2 mutant embryos exhibited persistent truncus arteriosus (PTA), ventricular septal defects (VSDs), and thinning of the ventricular myocardium. Loss of Foxc1/c2 expression in cNCCs resulted in abnormal patterns of cNCC migration into the OFT without the formation of the aorticopulmonary septum. Further, loss of Foxc1 expression in cNCCs resulted in normal OFT development but abnormal ventricular septal formation. In contrast, loss of Foxc2 expression in NCCs led to no obvious cardiac abnormalities. Together, we provide evidence that Foxc1 and Foxc2 in cNCCs are cooperatively required for proper cNCC migration, the formation of the OFT septation, and the development of the ventricles. Our data also suggests that Foxc1 expression may play a larger role in ventricular development compared to Foxc2.

Ruddlesden-popper type Srn+1IrnO3n+1 compound is a major focus of condensed matter physics where the subtle balance between electron-electron correlation, spin-orbit interaction and crystal field effect brings a host of emergent phenomena. While it is understandable that a canted antiferromagnetic (AFM) insulating state with an easy-plane anisotropy is developed in Sr2IrO4 as the 2D limit of the series, it is intriguing that bilayer Sr3Ir2O7, with slightly higher effective dimensionality, stabilizes c-axis collinear antiferromagnetism. This also renders Sr3Ir2O7 as a unique playground to study exotic physics near a critical spin transition point. However, the epitaxial growth of the Sr3Ir2O7 is still a challenging task because of the narrow growth window. In our research, we have studied the thermodynamic process during synthesis of Sr3Ir2O7 thin films. We successfully expanded the synthesis window by mapping out the relation between the thin film sample crystal structure and gas pressure. Our work thus provides a more accessible avenue to stabilize metastable materials., Accepted by Applied Physics Letters

As the security landscape evolves and InfoSec professionals work to keep apace, modern day instructors face the issue of adequately equipping a new generation for this dynamic landscape. Cyber security, as a discipline, is currently going through an unprecedented growth, bringing attention to issues that are growing in importance. Using static analysis tools such as FindBugs, and an add-on of this tool, Find Security Bugs, this project thoroughly analyzed Java source code in the textbooks used at a collegiate level. The analysis consisted of testing significant code snippets in the books with respect to Java Development Kit (JDK) 9/10. Through this static security-oriented analysis of programming examples exercised at the collegiate level, we determine whether currently taught fundamental programming practices are keeping pace with the dynamic landscape, and it will also guide the instructors to better shape teaching programming from a security perspective as cyber security affects every software component in any computing system.

Discoveries of intrinsic two-dimensional (2D) ferromagnetism in van der Waals (vdW) crystals provide an interesting arena for studying fundamental 2D magnetism and devices that employ localized spins

Medication related osteonecrosis of the jaw (MRONJ) is a disorder characterized by loss of blood supply to the jaws and death to the bone. In our previous work, we created a rat model of MRONJ by two injections of 60ug/Kg zoledronic acid (a powerful bisphosphonate abbreviated as ZA) via tail vein followed by extraction of a single first molar. We have shown in this model (ZA-treated rats plus molar extraction) a decrease in the vasculature of the jaws and a delay in bone healing beyond 4 weeks. Purpose: The current study identified angiogenic factors from the jaws of our MRONJ model where expression was altered independent of exposure to ZA alone. Methods: Using RT-PCR arrays containing 84 different gene sequences related to angiogenesis, we screened RNA isolated from the jaws of Control, ZA-treated rats, and our MRONJ rat model (ZA-treated plus first molar extraction), 3 and 6 weeks after extraction. Heat maps of gene expression were analyzed to identify genes where expression was either maximal or lost in MRONJ rats relative to ZA-treated rats without extraction. Results: Our study demonstrates the loss or gain of expression for 22 genes in the MRONJ rat model relative to rats treated with ZA alone. In MRONJ rats, the loss of expression was seen for 10 genes after 3 weeks and 3 additional genes (13 total) after 6 weeks where maximal expression was seen in rats treated with ZA-alone. This study also identified 5 genes that were maximally expressed in MRONJ rats after 3 weeks and an additional 4 genes (9 total) after 6 weeks that were not expressed in rats treated with ZA alone. Conclusions: Our study identifies genes that predict the transition from asymptomatic bisphosphonate exposure to MRONJ.

Recent discoveries of intrinsic two-dimensional (2D) ferromagnetism in insulating/semiconducting van der Waals (vdW) crystals open up new possibilities for studying fundamental 2D magnetism and devices employing localized spins. However, a vdW material that exhibits 2D itinerant magnetism remains elusive. In fact, the synthesis of such single-crystal ferromagnetic metals with strong perpendicular anisotropy at the atomically thin limit has been a long-standing challenge. Here, we demonstrate that monolayer Fe3GeTe2 is a robust 2D itinerant ferromagnet with strong out-of-plane anisotropy. Layer-dependent studies reveal a crossover from 3D to 2D Ising ferromagnetism for thicknesses less than 4 nm (five layers), accompanying a fast drop of the Curie temperature from 207 K down to 130 K in the monolayer. For Fe3GeTe2 flakes thicker than ~15 nm, a peculiar magnetic behavior emerges within an intermediate temperature range, which we show is due to the formation of labyrinthine domain patterns. Our work introduces a novel atomically thin ferromagnetic metal that could be useful for the study of controllable 2D itinerant Ising ferromagnetism and for engineering spintronic vdW heterostructures., Comment: 12 pages, 4 figures

Combinations of polymer conjugates affording in situ gelation hold promise for treatment of pathological cavities (e.g., arthritis) and sustained drug release. In particular, hyaluronic acid (HA) functionalized with reactive groups is regarded as an excellent biomaterial due to its tunable cross-linking kinetics and mechanical properties. HA-based reagents, however, can be irritating to surrounding tissues due to the reactivity of pendant groups, and their fast gelation kinetics can result in poor cavity filling. In this study, a biocompatible "click" reaction between cyanobenzothiazole (CBT) and d-cysteine (d-Cys) is employed to produce HA-based conjugates for in situ gelation. Rheological studies conducted on a gel obtained from the combination of HA-CBT and HA-d-Cys indicate optimal gelation time and mechanical properties. Further, in vitro studies on porcine skin demonstrate the ability of the gel to form in situ upon subcutaneous injection or topical application, and to act as a reservoir for sustained release of protein therapeutics. Finally, the safety of the HA-based conjugates is demonstrated on human keratinocytes. The presented results demonstrate the applicability of the binary mixture for in situ gelation and the potential of the proposed system for a variety of biomedical applications.

Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5α-reduction to form more potent androgens. We tested the hypothesis that trenbolone-enanthate (TREN) might prevent orchiectomy-induced losses in muscle and bone and visceral fat accumulation without increasing prostate mass or resulting in adverse hemoglobin elevations. Male F344 rats aged 3 mo underwent orchiectomy or remained intact and were administered graded doses of TREN, supraphysiological testosterone-enanthate, or vehicle for 29 days. In both intact and orchiectomized animals, all TREN doses and supraphysiological testosterone-enanthate augmented androgen-sensitive levator ani/bulbocavernosus muscle mass by 35–40% above shams ( P ≤ 0.001) and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses ( P < 0.05) and visceral fat accumulation ( P < 0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at sham levels in both intact and orchiectomized animals, whereas supraphysiological testosterone-enanthate and high-dose TREN elevated prostate mass by 84 and 68%, respectively ( P < 0.01). In summary, low-dose administration of the non-5α-reducible androgen TREN maintains prostate mass and hemoglobin concentrations near the level of shams while producing potent myotrophic actions in skeletal muscle and partial protection against orchiectomy-induced bone loss and visceral fat accumulation. Our findings indicate that TREN has advantages over supraphysiological testosterone and supports the need for future preclinical studies examining the viability of TREN as an option for androgen replacement therapy.

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents.