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The apicoplast, a relic plastid organelle derived from secondary endosymbiosis, is crucial for many medically relevant Apicomplexa. While it no longer performs photosynthesis, the organelle retains several essential metabolic pathways. In this study, we examine the four primary metabolic pathways in the Toxoplasma gondii apicoplast, along with an accessory pathway, and identify conditions that can bypass these. Contrary to the prevailing view that the apicoplast is indispensable for T. gondii , we demonstrate that bypassing all pathways renders the apicoplast non-essential. We further show that T. gondii lacking an apicoplast ( T. gondii −Apico ) can be maintained indefinitely in culture, establishing a unique model to study the functions of this organelle. Through comprehensive metabolomic, transcriptomic, and proteomic analyses of T. gondii −Apico we uncover significant adaptation mechanisms following loss of the organelle and identify numerous putative apicoplast proteins revealed by their decreased abundance in T. gondii −Apico . Moreover, T. gondii −Apico parasites exhibit reduced sensitivity to apicoplast targeting compounds, providing a valuable tool for discovering new drugs acting on the organelle. The capability to culture T. gondii without its plastid offers new avenues for exploring apicoplast biology and developing novel therapeutic strategies against apicomplexan parasites. Here, Chen et al. bypass the critical metabolic pathways of the remnant plastid organelle of Toxoplasma gondii . A subsequent detailed characterization of parasites devoid of the apicoplast organelle provides unprecedented insights into its constituents, evolution and functions, uncovering new vulnerabilities.

The cell surface of Toxoplasma gondii is rich in glycoconjugates which hold diverse and vital functions in the lytic cycle of this obligate intracellular parasite. Additionally, the cyst wall of bradyzoites, that shields the persistent form responsible for chronic infection from the immune system, is heavily glycosylated. Formation of glycoconjugates relies on activated sugar nucleotides, such as uridine diphosphate N -acetylglucosamine (UDP-GlcNAc). The glucosamine-phosphate- N -acetyltransferase (GNA1) generates N -acetylglucosamine-6-phosphate critical to produce UDP-GlcNAc. Here, we demonstrate that downregulation of T . gondii GNA1 results in a severe reduction of UDP-GlcNAc and a concomitant drop in glycosylphosphatidylinositols (GPIs), leading to impairment of the parasite’s ability to invade and replicate in the host cell. Surprisingly, attempts to rescue this defect through exogenous GlcNAc supplementation fail to completely restore these vital functions. In depth metabolomic analyses elucidate diverse causes underlying the failed rescue: utilization of GlcNAc is inefficient under glucose-replete conditions and fails to restore UDP-GlcNAc levels in GNA1-depleted parasites. In contrast, GlcNAc-supplementation under glucose-deplete conditions fully restores UDP-GlcNAc levels but fails to rescue the defects associated with GNA1 depletion. Our results underscore the importance of glucosamine-6-phosphate acetylation in governing T . gondii replication and invasion and highlight the potential of the evolutionary divergent GNA1 in Apicomplexa as a target for the development of much-needed new therapeutic strategies.

Background Over the past two decades, most cancer vaccines have failed to be developed clinically. The lack of efficient priming with specific tumor antigens and/or weak adjuvants may explain this poor success rate. MVX-ONCO-1, a personalized cell-based vaccine, combines inactivated autologous tumor cells and encapsulated allogeneic human cells genetically engineered to produce granulocyte–macrophage colony stimulating factor (GM-CSF). This unique technology allows sustained local delivery of strong adjuvant at the vaccination site. The combination of inactivated autologous tumor cells and potent local adjuvant delivery addresses these two unmet critical steps and may recapitulate in patients the successful combination observed in experimental models. Methods The SAKK 11/16, a Phase IIa trial with Overall Survival (OS) as the primary endpoint was the first efficacy study evaluating MVX-ONCO-1. Patients with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) progressing after at least one line of systemic therapy were enrolled with 50% of patients alive at 26 weeks as the primary objective. Results In this hard-to-treat population, SAKK 11/16 met the primary endpoint, with 68.8% of patients alive at 6 months. The median OS was 11.4 months, with 32% of the patients alive after 18 months. Complete and partial responses were observed on MVX-ONCO-1 monotherapy. Moreover, all patients who developed a positive DTH reaction to their tumor cells upon vaccination survived at 12 months. Additionally, patients living for more than 12 months had higher circulating antibody titers against tumor-associated antigens. Explorative analysis looking at median OS from the start of anti-PD-1 therapy was 21.7 months. In addition, no new safety signals with no systemic adverse events (AE) related to the treatment and no manufacturing issues were observed in this multicenter trial. Conclusions These findings suggest that MVX-ONCO-1 can induce a coordinated immune response with clinical benefits as a standalone treatment, leading to prolonged survival. This effect may be enhanced by previous exposure to immune checkpoint inhibitors. Trial registration (ClinicalTrials.gov): NCT02999646.

Pyrite, also known as fool's gold is the thermodynamic stable polymorph of FeS\\(_2\\). It is widely considered as a promising d-band semiconductor for various applications due to its intriguing physical properties. Marcasite is the other naturally occurring polymorph of FeS\\(_2\\). Measurements on natural crystals have shown that it has similarly promising electronic, mechanical, and optical properties as pyrite. However, it has been only scarcely investigated so far, because the laboratory-based synthesis of phase-pure samples or high-quality marcasite single crystal has been a challenge until now. Here, we report the targeted phase formation via hydrothermal synthesis of marcasite and pyrite. The formation condition and phase purity of the FeS\\(_2\\) polymorphs are systematically studied in the form of a comprehensive synthesis map. We, furthermore, report on a detailed analysis of marcasite single crystal growth by a space-separated hydrothermal synthesis. We observe that single phase product of marcasite forms only on the surface under the involvement of H\\(_2\\)S and sulphur vapor. The availability of high-quality crystals of marcasite allows us to measure the fundamental physical properties, including an allowed direct optical bandgap of 0.76 eV, temperature independent diamagnetism, an electronic transport gap of 0.11 eV, and a room-temperature carrier concentration of 4.14 \\(\\) 10\\(^18\\) cm\\(^-3\\). X-ray absorption/emission spectroscopy are employed to measure the band gap of the two FeS\\(_2\\) phases. We find marcasite has a band gap of 0.73 eV, while pyrite has a band gap of 0.87 eV. Our results indicate that marcasite -- that is now synthetically available in a straightforward fashion -- is as equally promising as pyrite as candidate for various semiconductor applications based on earth abundant elements.

We report on the structural and superconducting properties of the intermetallic compound BaGaGe. We find that this material undergoes a structural second-order phase transition from the distorted AlB\\(_2\\)-type structure (1H, \\(a\\) = 4.3254(2) Å, \\(c\\) = 5.1078(3) Å, P6/mmm) into the CaIn\\(_2\\)-type structure (2H, \\(a\\) = 4.3087(3) Å, \\(c\\) = 10.2117(6) Å, P6\\(_3\\)/mmc) at a transition temperature of \\(T_ S\\) = 253 K. We find that the structural phase-transition corresponds to a coherent buckling of the honeycomb layers, which we can interpret as a disorder-to-order transition of the atoms located within this layer. We show that the 2H-BaGaGe phase becomes superconducting at a critical temperature of \\(T_ c\\) = 2.1 K. The bulk nature of the superconductivity in 2H-BaGaGe is confirmed by means of specific heat measurements, where we determine a value of \\( C\\)/\\( T_ c\\) = 1.59, which is close to the expected BCS value in the weak coupling limit.

We report on the discovery, structural analysis, and the physical properties of Nb\\(_4\\)SiSb\\(_2\\) -- a hitherto unknown compound crystallizing in the V\\(_4\\)SiSb\\(_2\\)-type structure with the tetragonal space group \\(I4/mcm\\) and unit cell parameters \\(a\\) = 10.3638(2) \\(A\\) and \\(c\\) = 4.9151(2) \\(A\\). We find Nb\\(_4\\)SiSb\\(_2\\) to be a metal undergoing a transition to a superconducting state at a critical temperature of \\(T_ c \\) 1.6 K. The bulk nature of the superconductivity in this material is confirmed by the observation of a well defined discontinuity in specific heat with a normalized specific heat jump of \\( C(T_ c)/ T_ c = 1.33\\, mJ\\, mol^-1\\, K^-2\\). We find that for Nb\\(_4\\)SiSb\\(_2\\), the unoccupied sites on the \\(4b\\) Wyckoff position can be partially occupied with Cu, Pd, or Pt. Low-temperature resistivity measurements show transitions to superconductivity for all three compounds at \\(T_ c \\, 1.2\\, K\\) for Nb\\(_4\\)Cu\\(_0.2\\)SiSb\\(_2\\), and \\(T_ c \\, 0.8\\, K\\) for Nb\\(_4\\)Pd\\(_0.2\\)SiSb\\(_2\\) as well as for Nb\\(_4\\)Pt\\(_0.14\\)SiSb\\(_2\\). The addition of electron-donor atoms into these void positions, henceforth, lowers the superconducting transition temperature in comparison to the parent compound.

It is a well-established fact that the physical properties of compounds follow their crystal symmetries. This has especially pronounced implications on emergent collective quantum states in materials. Specifically, the effect of crystal symmetries on the properties of superconductors is widely appreciated, although the clarification of this relationship is a core effort of on-going research. Emergent phenomena on honeycomb lattices are of special interest, as they can give rise to spectacular phenomenology, as manifested by the recent discovery of correlated states in magic-angle graphene, or by the high-temperature superconductivity in MgB\\(_2\\). Here, we report on the structural and microscopic superconducting properties of a class of ternary superconductors with Al/Si honeycomb layers, i.e. Ca\\(_1-x\\)Sr\\(_x\\)AlSi. We show that this solid solution is a remarkable model system with a highly tunable two-gap to single-gap superconducting system on a honeycomb lattice, where the superconductivity is enhanced by a subtle structural instability, i.e. the buckling of the Al/Si layers.

As a member of the Ruddlesden-Popper Ln\\(_n+1\\)Ni\\(_n\\)O\\(_3n+1\\) series rare-earth-nickelates, the Pr4Ni\\(_3\\)O\\(_10\\) consists of infinite quasi-two-dimensional perovskite-like Ni-O based layers. Although a metal-to-metal phase transition at Tpt = 157 K has been revealed by previous studies, a comprehensive study of physical properties associated with this transition has not yet been performed. We have grown single crystals of Pr4Ni3O10 at high oxygen pressure, and report on the physical properties around that phase transition, such as heat-capacity, electric-transport and magnetization. We observe a distinctly anisotropic behavior between in-plane and out-of-plane properties: a metal-to-metal transition at Tpt within the a-b plane, and a metal-to-insulator-like transition along the c-axis with decreasing temperature. Moreover, an anisotropic and anomalous negative magneto-resistance is observed at Tpt that we attribute to a slight suppression of the first-order transition with magnetic field. The magnetic-susceptibility can be well described by a Curie-Weiss law, with different Curie-constants and Pauli-spin susceptibilities between the high-temperature and the low-temperature phases. The single crystal X-ray diffraction measurements show a shape variation of the different NiO6 octahedra from the high-temperature phase to the low-temperature phase. This subtle change of the environment of the Ni sites is likely responsible for the different physical properties at high and low temperatures.