Coexistence of Flexo- and Ferro-Electric Effects in an Ordered Assembly of BaTiO3 Nanocubes

It has been reported that the flexoelectric effect could be dominant in the nanoscale. The discrepancy between theory and experiments on the frequency dependence of the dielectric constant of an ordered assembly of BaTiO3 nanocubes is nearly resolved by assuming the coexistence of flexo- and ferro-electric effects. Although flexoelectric polarizations perpendicular to the applied alternating electric field contribute to the dielectric constant, those parallel to the electric field do not contribute because the magnitude of the flexoelectric polarization does not change due to the mismatch of strain at the interface of the nanocubes. On the other hand, some dielectric response is possible for the ferroelectric component of the polarization parallel to the electric field.

Biogenesis of a bacterial metabolosome for propanediol utilization

Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both 'Shell first' and 'Cargo first' assembly pathways, unlike the beta-carboxysome structural analog which only involves the 'Cargo first' strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.

Impaired trigeminal control of ingestive behavior in the Prrxl1- / - mouse is associated with a lemniscal-biased orosensory deafferentation

Although peripheral deafferentation studies have demonstrated a critical role for trigeminal afference in modulating the orosensorimotor control of eating and drinking, the central trigeminal pathways mediating that control, as well as the timescale of control, remain to be elucidated. In rodents, three ascending somatosensory pathways process and relay orofacial mechanosensory input: the lemniscal, paralemniscal, and extralemniscal. Two of these pathways (the lemniscal and extralemniscal) exhibit highly structured topographic representations of the orofacial sensory surface, as exemplified by the one-to-one somatotopic mapping between vibrissae on the animals’ face and barrelettes in brainstem, barreloids in thalamus, and barrels in cortex. Here we use the Prrxl1 knockout mouse model to investigate ingestive behavior deficits associated with disruption of the lemniscal pathway. The Prrxl1 deletion disrupts somatotopic patterning and axonal projections throughout the lemniscal pathway but spares patterning in the extralemniscal nucleus. Our data reveal an imprecise and inefficient ingestive phenotype with deficits that span timescales from milliseconds to months, tightly linking trigeminal input with ingestion, from moment-to-moment consummatory to long term appetitive control. We suggest that ordered assembly of trigeminal sensory information along the lemniscal pathway is critical for the rapid and precise modulation of motor circuits driving eating and drinking action sequences.

Structure-based Classification of Tauopathies

Ordered assembly of the tau protein into filaments characterizes multiple neurodegenerative diseases, which are called tauopathies. We previously reported that by electron cryo-microscopy (cryo-EM), tau filament structures from Alzheimer's disease, chronic traumatic encephalopathy (CTE), Pick's disease and corticobasal degeneration (CBD) are distinct. Here we show that the structures of tau filaments from typical and atypical progressive supranuclear palsy (PSP), the most common tauopathy after Alzheimer's disease, define a previously unknown, three-layered fold. Moreover, the tau filament structures from globular glial tauopathy (GGT, Types I and II) are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs from the above and resembles the four-layered CBD fold. The majority of tau filaments from aging-related tau astrogliopathy (ARTAG) also have the AGD fold. Surprisingly, tau protofilament structures from inherited cases with mutations +3/+16 in intron 10 of MAPT, the microtubule-associated protein tau gene, are identical to those from AGD, suggesting that a relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, tau filament structures from cases of familial British dementia (FBD) and familial Danish dementia (FDD) are the same as those from Alzheimer's disease and primary age-related tauopathy (PART). These structures provide the basis for a classification of tauopathies that also allows identification of new entities, as we show here for a case diagnosed as PSP, but with abundant spherical 4R tau inclusions in limbic and other brain areas. The structures of the tau fold of this new disease (Limbic-predominant Neuronal inclusion body 4R Tauopathy, LNT) were intermediate between those of GGT and PSP.

A Unique Junctional Interface at Contact Sites Between the Endoplasmic Reticulum and Lipid Droplets

Lipid droplets (LDs) constitute compartments dedicated to the storage of metabolic energy in the form of neutral lipids. LDs originate from the endoplasmic reticulum (ER) with which they maintain close contact throughout their life cycle. These ER–LD junctions facilitate the exchange of both proteins and lipids between these two compartments. In recent years, proteins that are important for the proper formation of LDs and localize to ER–LD junctions have been identified. This junction is unique as it is generally believed to invoke a transition from the ER bilayer membrane to a lipid monolayer that delineates LDs. Proper formation of this junction requires the ordered assembly of proteins and lipids at specialized ER subdomains. Without such a well-ordered assembly of LD biogenesis factors, neutral lipids are synthesized throughout the ER membrane, resulting in the formation of aberrant LDs. Such ectopically formed LDs impact ER and lipid homeostasis, resulting in different types of lipid storage diseases. In response to starvation, the ER–LD junction recruits factors that tether the vacuole to these junctions to facilitate LD degradation. In addition, LDs maintain close contacts with peroxisomes and mitochondria for metabolic channeling of the released fatty acids toward beta-oxidation. In this review, we discuss the function of different components that ensure proper functioning of LD contact sites, their role in lipogenesis and lipolysis, and their relation to lipid storage diseases.