Transverse Spin Structure of the Nucleon through Target Single Spin Asymmetry in Semi-Inclusive Deep-Inelastic (e,e′π±)(e,e^\prime \pi^\pm) Reaction at Jefferson Lab

Jefferson Lab (JLab) 12 GeV energy upgrade provides a golden opportunity to perform precision studies of the transverse spin and transverse-momentum-dependent structure in the valence quark region for both the proton and the neutron. In this paper, we focus our discussion on a recently approved experiment on the neutron as an example of the precision studies planned at JLab. The new experiment will perform precision measurements of target Single Spin Asymmetries (SSA) from semi-inclusive electro-production of charged pions from a 40-cm long transversely polarized $^3$He target in Deep-Inelastic-Scattering kinematics using 11 and 8.8 GeV electron beams. This new coincidence experiment in Hall A will employ a newly proposed solenoid spectrometer (SoLID). The large acceptance spectrometer and the high polarized luminosity will provide precise 4-D ($x$, $z$, $P_T$ and $Q^2$) data on the Collins, Sivers, and pretzelocity asymmetries for the neutron through the azimuthal angular dependence. The full 2$\pi$ azimuthal angular coverage in the lab is essential in controlling the systematic uncertainties. The results from this experiment, when combined with the proton Collins asymmetry measurement and the Collins fragmentation function determined from the e$^+$e$^-$ collision data, will allow for a quark flavor separation in order to achieve a determination of the tensor charge of the d quark to a 10% accuracy. The extracted Sivers and pretzelocity asymmetries will provide important information to understand the correlations between the quark orbital angular momentum and the nucleon spin and between the quark spin and nucleon spin.Comment: 23 pages, 13 figures, minor corrections, matches published versio

35+1 challenges in materials science being tackled by PIs under 35(ish) in 2023

Here we highlight 35 (+1) global researchers approximately under the age of 35. The annual cohort was self-generated by initial seed invitations sent by the editorial team, with each contributor inviting the next in a self-selecting unrestricted (nominally supervised) manner. The final collection is an inspiring look at the challenges the current generation of materials researchers are tackling, demonstrating the interdisciplinarity of materials science

Lightweight Co-free eutectic high-entropy alloy with high strength and ductility by casting

We report a cast light-weight dual-phase eutectic high-entropy alloy (EHEA) of Ni49Fe28Al17V6 that comprises of alternating FCC and ordered B2 lamellae. Such lamellar EHEA exhibits a superior tensile strength of ∼ 1.3 GPa in combination with a large uniform elongation of ∼ 26%, well surpassing those of other state-of-the-art cast EHEAs. The high strength-ductility synergy originates largely from the extensive dislocation activities in both FCC and B2 lamellae. In addition, the martensitic transformation of the B2 lamellae during deformation further promotes the work hardening capability to enhance the tensile strength and ductility

Campylobacter colonization, environmental enteric dysfunction, stunting, and associated risk factors among young children in rural Ethiopia: A cross-sectional study from the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project

Livestock farming provides a possible mechanism by which smallholder farmers can meet their household need for animal source foods (ASF), which may reduce the risk of stunting. However, direct/indirect contacts with domestic animals may increase colonization b

A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression. Genetic loss or locally antagonizing IL-1β/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, and reduced exhausted CD8+ T cells and thereby extends the survival of tumor-bearing mice. In contrast to IL-1β, IL-1α exhibits antitumor effects. Genetic deletion of Il1a/b is associated with decreased recruitment of lymphoid cells and loss-of-interferon signaling in various immune populations and subsets of malignant cells and is associated with decreased survival time of PDGFB-driven tumor-bearing mice. In contrast to PDGFB-driven GBM, Nf1-silenced tumors have a constitutively active NF-κB pathway, which drives the expression of MCPs to recruit monocytes into tumors. These results indicate local antagonism of IL-1β could be considered as an effective therapy specifically for proneural GBM

LRP1 is a neuronal receptor for α-synuclein uptake and spread

BACKGROUND: The aggregation and spread of α-synuclein (α-Syn) protein and related neuronal toxicity are the key pathological features of Parkinson\u27s disease (PD) and Lewy body dementia (LBD). Studies have shown that pathological species of α-Syn and tau can spread in a prion-like manner between neurons, although these two proteins have distinct pathological roles and contribute to different neurodegenerative diseases. It is reported that the low-density lipoprotein receptor-related protein 1 (LRP1) regulates the spread of tau proteins; however, the molecular regulatory mechanisms of α-Syn uptake and spread, and whether it is also regulated by LRP1, remain poorly understood. METHODS: We established LRP1 knockout (LRP1-KO) human induced pluripotent stem cells (iPSCs) isogenic lines using a CRISPR/Cas9 strategy and generated iPSC-derived neurons (iPSNs) to test the role of LRP1 in α-Syn uptake. We treated the iPSNs with fluorescently labeled α-Syn protein and measured the internalization of α-Syn using flow cytometry. Three forms of α-Syn species were tested: monomers, oligomers, and pre-formed fibrils (PFFs). To examine whether the lysine residues of α-Syn are involved in LRP1-mediated uptake, we capped the amines of lysines on α-Syn with sulfo-NHS acetate and then measured the internalization. We also tested whether the N-terminus of α-Syn is critical for LRP1-mediated internalization. Lastly, we investigated the role of Lrp1 in regulating α-Syn spread with a neuronal Lrp1 conditional knockout (Lrp1-nKO) mouse model. We generated adeno-associated viruses (AAVs) that allowed for distinguishing the α-Syn expression versus spread and injected them into the hippocampus of six-month-old Lrp1-nKO mice and the littermate wild type (WT) controls. The spread of α-Syn was evaluated three months after the injection. RESULTS: We found that the uptake of both monomeric and oligomeric α-Syn was significantly reduced in iPSNs with LRP1-KO compared with the WT controls. The uptake of α-Syn PFFs was also inhibited in LRP1-KO iPSNs, albeit to a much lesser extent compared to α-Syn monomers and oligomers. The blocking of lysine residues on α-Syn effectively decreased the uptake of α-Syn in iPSNs and the N-terminus of α-Syn was critical for LRP1-mediated α-Syn uptake. Finally, in the Lrp1-nKO mice, the spread of α-Syn was significantly reduced compared with the WT littermates. CONCLUSIONS: We identified LRP1 as a key regulator of α-Syn neuronal uptake, as well as an important mediator of α-Syn spread in the brain. This study provides new knowledge on the physiological and pathological role of LRP1 in α-Syn trafficking and pathology, offering insight for the treatment of synucleinopathies

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration