Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model

BACKGROUND: Spinocerebellar ataxia 38 (SCA38) is a rare autosomal neurological disorder characterized by ataxia and cerebellar atrophy. SCA38 is caused by mutations of ELOVL5 gene. ELOVL5 gene encodes a protein, which elongates long chain polyunsaturated fatty acids (PUFAs). Knockout mice lacking Elovl5 recapitulate SCA38 symptoms, including motor coordination impairment and disruption of cerebellar architecture. We asked whether, in Elovl5 knockout mice (Elovl5(−/−)), a diet with both ω3 and ω6 PUFAs downstream Elovl5 can prevent the development of SCA38 symptoms, and at which age such treatment is more effective. Elovl5(−/−) mice were fed either with a diet without or containing PUFAs downstream the Elovl5 enzyme, starting at different ages. Motor behavior was assessed by the balance beam test and cerebellar structure by morphometric analysis. RESULTS: The administration from birth of the diet containing PUFAs downstream Elovl5 led to a significant amelioration of the motor performance in the beam test of Elovl5(−/−) mice, with a reduction of foot slip errors at 6 months from 2.2 ± 0.3 to 1.3 ± 0.2 and at 8 months from 3.1 ± 0.5 to 1.9 ± 0.3. On the contrary, administration at 1 month of age or later had no effect on the motor impairment. The cerebellar Purkinje cell layer and the white matter area of Elovl5(−/ −)mice were not rescued even by the administration of diet from birth, suggesting that the improvement of motor performance in the beam test was due to a functional recovery of the cerebellar circuitry. CONCLUSIONS: These results suggest that the dietary intervention in SCA38, whenever possible, should be started from birth or as early as possible

An autoregulatory loop controls the expression of the transcription factor NF-Y

The heterotrimeric NF-Y complex is a pioneer factor that binds to CCAAT-genes and regulates their transcription. NF-Y cooperates with multiple transcription factors and co-regulators in order to positively or negatively influence gene transcription. The recruitment of NF-Y to CCAAT box is significantly enriched in cancer-associated gene promoters loci and positively correlates with malignancy. NF-Y subunits, in particular the DNA-binding subunit NF-YA and the histone-fold subunit NF-YC, appear overexpressed in specific types of cancer. Here we demonstrate that NF-Y subunits expression is finely regulated through transcriptional and post-translational mechanisms thus allowing control over basal expression levels. NF-Y negatively regulates the transcription of the genes encoding for its subunits. DNA pull-down/affinity purification assay coupled with Mass Spectrometry identified putative co-regulators, such as Lamin A, involved in NF-YA gene transcription level. We also evidentiate how the stability of the complex is severely affected by the absence of one subunit. Our results identified for the first time one of the mechanisms responsible for NF-Y expression, which may be involved in the aberrant expression and activity observed in tumor cells and other pathological conditions

Oxytetracycline-Protein Complex: The Dark Side of Pet Food

Background: Worldwide antibiotic abuse represents a huge burden, which can have a deep impact on pet and human health through nutrition and medicalization representing another way of antibiotic resistance transmission. Objective: We aimed our research to determine a possible complex formation between biological bone substrates, such as proteins, and Oxytetracycline (OTC), an approved antibiotic for use in zootechny, which might determine a toxic effect on K562 cells. Method: Cell viability and HPLC-ESI/QqToF assays were used to assess potential toxicity of bone extract derived from OTC-treated chickens according to standard withdrawal times and from untreated chickens at 24, 48 and 72h of incubation. Results: Cell culture medium with ground bone from chickens reared in the presence of OTC (OTC-CCM) resulted significantly cytotoxic at every incubation time regardless of the bone concentration while cell culture medium with ground bone from chickens reared without OTC (BIO-CCM) resulted significantly cytotoxic only after 72h of incubation. HPLC-ESI/QqToF assay ruled out the possible presence of OTC main derivatives possibly released by bone within culture medium until 1 \u3bcg/mL. Conclusion: The presence of a protein complex with OTC is able to exert a cytotoxic effect once released in the medium after 24-48h of incubation

Quantitative comparison of the protein corona of nanoparticles with different matrices

: Nanoparticles (NPs) are paving the way for improved treatments for difficult to treat diseases diseases; however, much is unknown about their fate in the body. One important factor is the interaction between NPs and blood proteins leading to the formation known as the "protein corona" (PC). The PC, consisting of the Hard (HC) and Soft Corona (SC), varies greatly based on the NP composition, size, and surface properties. This highlights the need for specific studies to differentiate the PC formation for each individual NP system. This work focused on comparing the HC and SC of three NPs with different matrix compositions: a) polymeric NPs based on poly(lactic-co-glycolic) acid (PLGA), b) hybrid NPs consisting of PLGA and Cholesterol, and c) lipidic NPs made only of Cholesterol. NPs were formulated and characterized for their physico-chemical characteristics and composition, and then were incubated in human plasma. In-depth purification, identification, and statistical analysis were then performed to identify the HC and SC components. Finally, similar investigations demonstrated whether the presence of a targeting ligand on the NP surface would affect the PC makeup. These results highlighted the different PC fingerprints of these NPs, which will be critical to better understand the biological influences of the PC and improve future NP designs

Quantum Zeno and Anti-Zeno probes of noise correlations in photon polarisation

We experimentally demonstrate, for the first time, noise diagnostics by repeated quantum measurements. Specifically, we establish the ability of a single photon, subjected to random polarisation noise, to diagnose non-Markovian temporal correlations of such a noise process. In the frequency domain, these noise correlations correspond to colored noise spectra, as opposed to the ones related to Markovian, white noise. Both the noise spectrum and its corresponding temporal correlations are diagnosed by probing the photon by means of frequent, (partially-)selective polarisation measurements. Our main result is the experimental demonstration that noise with positive temporal correlations corresponds to our single photon undergoing a dynamical regime enabled by the quantum Zeno effect (QZE), while noise characterized by negative (anti-) correlations corresponds to regimes associated with the anti-Zeno effect (AZE). This demonstration opens the way to a new kind of noise spectroscopy based on QZE and AZE in photon (or other single-particle) state probing

Phase Noise in Real-World Twin-Field Quantum Key Distribution

We investigate the impact of noise sources in real-world implementations of Twin-Field Quantum Key Distribution (TF-QKD) protocols, focusing on phase noise from photon sources and connecting fibers. Our work emphasizes the role of laser quality, network topology, fiber length, arm balance, and detector performance in determining key rates. Remarkably, it reveals that the leading TF-QKD protocols are similarly affected by phase noise despite different mechanisms. Our study demonstrates duty cycle improvements of over 2x through narrow-linewidth lasers and phase-control techniques, highlighting the potential synergy with high-precision time/frequency distribution services. Ultrastable lasers, evolving toward integration and miniaturization, offer promise for agile TF-QKD implementations on existing networks. Properly addressing phase noise and practical constraints allows for consistent key rate predictions, protocol selection, and layout design, crucial for establishing secure long-haul links for the Quantum Communication Infrastructures under development in several countries.Comment: 18 pages, 8 figures, 2 table

Coherent phase transfer for real-world twin-field quantum key distribution

Quantum mechanics allows distribution of intrinsically secure encryption keys by optical means. Twin-field quantum key distribution is one of the most promising techniques for its implementation on long-distance fiber networks, but requires stabilizing the optical length of the communication channels between parties. In proof-of-principle experiments based on spooled fibers, this was achieved by interleaving the quantum communication with periodical stabilization frames. In this approach, longer duty cycles for the key streaming come at the cost of a looser control of channel length, and a successful key-transfer using this technique in real world remains a significant challenge. Using interferometry techniques derived from frequency metrology, we develop a solution for the simultaneous key streaming and channel length control, and demonstrate it on a 206 km field-deployed fiber with 65 dB loss. Our technique reduces the quantum-bit-error-rate contributed by channel length variations to <1%, representing an effective solution for real-world quantum communications