Human small EDRK-rich factor protein SERF2 is a cellular driver of protein amyloid formation, a process that has been linked to neurodegenerative diseases including Alzheimer\'s and Parkinson\'s disease. SERF2 is a 59 amino acid protein, highly charged, and well conserved whose structure and physiological function is unclear. SERF family proteins including human SERF2 have shown a tendency to form fuzzy complexes with misfolded proteins such as α-Synuclein which has been linked to Parkinson\'s disease. SERF family proteins have been recently identified to bind nucleic acids, but the binding mechanism(s) remain enigmatic. Here, using multidimensional solution NMR, we report the 1H, 15N, and 13C chemical shift assignments (~ 86% of backbone resonance assignments) for human SERF2. TALOS-N predicted secondary structure of SERF2 showed three very short helices (3-4 residues long) in the N-terminal region of the protein and a long helix in the C-terminal region spanning residues 37-46 which is consistent with the helical content indicated by circular dichroism spectroscopy. Paramagnetic relaxation enhancement NMR analysis revealed that a short C-terminal region E53-K55 is in the proximity of the N-terminus. Having the backbone assignment of SERF2 allowed us to probe its interaction with α-Synuclein and to identify the residues in SERF2 binding interfaces that likely promote α-Synuclein aggregation.

The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark of Parkinson\'s disease. Under stress or other pathological conditions, the accumulation of α-Syn oligomers is the main contributor to the cytotoxicity. A potential approach for treating Parkinson\'s disease involves preventing the accumulation of these α-Syn oligomers. In this study, we present a novel mechanism involving a conserved group of disorderly proteins known as small EDRK-rich factor (SERF), which promotes the aggregation of α-Syn through a cophase separation process. Using diverse methods like confocal microscopy, fluorescence recovery after photobleaching assays, solution-state NMR spectroscopy, and Western blot, we determined that the N-terminal domain of SERF1a plays a role in the interactions that occur during cophase separation. Within these droplets, α-Syn undergoes a gradual transformation from solid condensates to amyloid fibrils, while SERF1a is excluded from the condensates and dissolves into the solution. Notably, in vivo experiments show that SERF1a cophase separation with α-Syn significantly reduces the deposition of α-Syn oligomers and decreases its cellular toxicity under stress. These findings suggest that SERF1a accelerates the conversion of α-Syn from highly toxic oligomers to less toxic fibrils through cophase separation, thereby mitigating the biological damage of α-Syn aggregation.

The abnormal aggregation of proteins is a significant pathological hallmark of diseases, such as the amyloid formation associated with fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Understanding which cellular components and how these components regulate the process of abnormal protein aggregation in living organisms is crucial for the prevention and treatment of neurodegenerative diseases. MOAG-4/SERF is a conserved family of proteins with rich positive charged residues, which was initially identified as an enhancer for the formation of amyloids in C. elegans. Knocking out SERF impedes the amyloid formation of various proteins, including α-synuclein and β-amyloid, which are linked to Parkinson\'s and Alzheimer\'s diseases, respectively. However, recent studies revealed SERF exhibited dual functions, as it could both promote and inhibit the fibril formation of the neurodegenerative disease-related amyloidogenic proteins. The connection between functions and structure basis of SERF in regulating the amyloid formation is still unclear. This review will outline the hallmark proteins in neurodegenerative diseases, summarize the contradictory role of the SERF protein family in promoting and inhibiting the aggregation of neurodegenerative proteins, and finally explore the potential structural basis and functional selectivity of the SERF protein.

Machine learning (ML) is an effective tool to interrogate complex systems to find optimal parameters more efficiently than through manual methods. This efficiency is particularly important for systems with complex dynamics between multiple parameters and a subsequent high number of parameter configurations, where an exhaustive optimisation search would be impractical. Here we present a number of automated machine learning strategies utilised for optimisation of a single-beam caesium (Cs) spin exchange relaxation free (SERF) optically pumped magnetometer (OPM). The sensitivity of the OPM (T/Hz), is optimised through direct measurement of the noise floor, and indirectly through measurement of the on-resonance demodulated gradient (mV/nT) of the zero-field resonance. Both methods provide a viable strategy for the optimisation of sensitivity through effective control of the OPM\'s operational parameters. Ultimately, this machine learning approach increased the optimal sensitivity from 500 fT/Hz to <109fT/Hz. The flexibility and efficiency of the ML approaches can be utilised to benchmark SERF OPM sensor hardware improvements, such as cell geometry, alkali species and sensor topologies.

Amyloid formation is a misfolding process that has been linked to age-related diseases, including Alzheimer\'s and Huntington\'s. Understanding how cellular factors affect this process in vivo is vital in realizing the dream of controlling this insidious process that robs so many people of their humanity. SERF (small EDRK-rich factor) was initially isolated as a factor that accelerated polyglutamine amyloid formation in a C. elegans model. SERF knockouts inhibit amyloid formation of a number of proteins that include huntingtin, α-synuclein and β-amyloid which are associated with Huntington\'s, Parkinson\'s and Alzheimer\'s disease, respectively, and purified SERF protein speeds their amyloid formation in vitro. SERF proteins are highly conserved, highly charged and conformationally dynamic proteins that form a fuzzy complex with amyloid precursors. They appear to act by specifically accelerating the primary step of amyloid nucleation. Brain-specific SERF knockout mice, though viable, appear to be more prone to deposition of amyloids, and show modified fibril morphology. Whole-body knockouts are perinatally lethal due to an apparently unrelated developmental issue. Recently, it was found that SERF binds RNA and is localized to nucleic acid-rich membraneless compartments. SERF-related sequences are commonly found fused to zinc finger sequences. These results point towards a nucleic acid-binding function. How this function relates to their ability to accelerate amyloid formation is currently obscure. In this review, we discuss the possible biological functions of SERF family proteins in the context of their structural fuzziness, modulation of amyloid pathway, nucleic acid binding and their fusion to folded proteins.

While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that MOAG-4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation-prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age-related protein toxicity.

We have developed a pulsed optically pumped magnetometer (OPM) array for detecting magnetic field maps originated from an arbitrary current distribution. The presented magnetic source imaging (MSI) system features 24 OPM channels, has a data rate of 500 S/s, a sensitivity of 0.8 p T / H z , and a dynamic range of 72 dB. We have employed our pulsed- OPM MSI system for measuring the magnetic field map of a test coil structure. The coils are moved across the array in an indexed fashion to measure the magnetic field over an area larger than the array. The captured magnetic field maps show excellent agreement with the simulation results. Assuming a 2D current distribution, we have solved the inverse problem, using the measured magnetic field maps, and the reconstructed current distribution image is compared to that of the simulation.

Conventional approaches to identify a telomere motif in a new genome are laborious and time-intensive. An efficient new methodology based on next-generation sequencing (NGS), de novo sequence repeat finder (SERF) and fluorescence in situ hybridization (FISH) is presented. Unlike existing heuristic approaches, SERF utilizes an exhaustive analysis of raw NGS reads or assembled contigs for rapid de novo detection of conserved tandem repeats representing telomere motifs. SERF was validated using the NGS data from Ipheion uniflorum and Allium cepa with known telomere motifs. The analysis program was then used on NGS data to investigate the telomere motifs in several additional plant species and together with FISH proved to be an efficient approach to identify as yet unknown telomere motifs.

As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under certain conditions these disease proteins can undergo structural rearrangements resulting in misfolded proteins that can lead to the formation of aggregates with a fibrillar amyloid-like structure. Cells have different mechanisms to deal with this protein aggregation, where the molecular chaperone machinery constitutes the first line of defense against misfolded proteins. Proteins that cannot be refolded are subjected to degradation and compartmentalization processes. Amyloid formation has traditionally been described as responsible for the proteotoxicity associated with different neurodegenerative disorders. Several mechanisms have been suggested to explain such toxicity, including the sequestration of key proteins and the overload of the protein quality control system. Here, we review different aspects of the involvement of amyloid-forming proteins in disease, mechanisms of toxicity, structural features, and biological functions of amyloids, as well as the cellular mechanisms that modulate and regulate protein aggregation, including the presence of enhancers and suppressors of aggregation, and how aging impacts the functioning of these mechanisms, with special attention to the molecular chaperones.

With the rapid development of modern physics, atomic gyroscopes have been demonstrated in recent years. There are two types of atomic gyroscope. The Atomic Interferometer Gyroscope (AIG), which utilizes the atomic interferometer to sense rotation, is an ultra-high precision gyroscope; and the Atomic Spin Gyroscope (ASG), which utilizes atomic spin to sense rotation, features high precision, compact size and the possibility to make a chip-scale one. Recent developments in the atomic gyroscope field have created new ways to obtain high precision gyroscopes which were previously unavailable with mechanical or optical gyroscopes, but there are still lots of problems that need to be overcome to meet the requirements of inertial navigation systems. This paper reviews the basic principles of AIG and ASG, introduces the recent progress in this area, focusing on discussing their technical difficulties for inertial navigation applications, and suggests methods for developing high performance atomic gyroscopes in the near future.