A Pneumatic-based Mechanism for Inserting a Flexible Microprobe into the Brain

Insertion of flexible microprobes into the brain requires withstanding the compressive penetration force by the microprobes. To aid the insertion of the microprobes, most of the existing approaches employ pushing mechanisms to provide temporary stiffness increase for the microprobes to prevent buckling during insertion into the brain. However, increasing the microprobe stiffness may result in acute neural tissue damage during insertion. Moreover, any late or premature removal of the temporary stiffness after insertion may lead to further tissue damage due to brain micromotion, or inaccuracy in the microprobe positioning. In this study, a novel pneumatic-based insertion mechanism is proposed which simultaneously pulls and pushes a flexible microprobe towards the brain. As part of the brain penetration force in the proposed mechanism is supplied by the tensile force, the applied compressive force, which the microprobe must withstand during insertion, is lower compared to the existing approaches. Therefore, the microprobes with a critical buckling force less than the brain penetration force can be inserted into the brain without buckling. Since there is no need for temporary stiffness increment, the neural tissue damage during the microprobe insertion will be much lower compared to the existing insertion approaches. The pneumatic-based insertion mechanism is modelled analytically to investigate the effects of the microprobe configuration and the applied air pressure on the applied tensile and compressive forces to the microprobe. Next, finite element modelling is conducted, and its analysis results not only validate the analytical results but also confirm the efficiency of the mechanism.

Electrophilic Sulfur Reagent Design Enables Catalytic syn-Carbosulfenylation of Unactivated Alkenes

A multi-component approach to structurally complex organosulfur products is described via the nickel-catalyzed 1,2-carbosulfenylation of unactivated alkenes with organoboron nucleophiles and tailored organosulfur electrophiles. Key to the development of this transformation is the identification of a modular N-alkyl-N-(arylsulfenyl)arenesulfonamide family of sulfur electrophiles. Tuning the electronic and steric properties of the leaving group in these reagents controls pathway selectivity, favoring three-component coupling and suppressing side reactions, as examined via computational studies. The unique syn-stereoselectivity differs from traditional electrophilic sulfenyl transfer processes involving a thiiranium ion intermediate and arises from the directed arylnickel(I) migratory insertion mechanism, as elucidated through reaction kinetics and control experiments. Reactivity and regioselectivity are facilitated by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, alcohols, amines, amides, and azaheterocycles.

The ER transmembrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria

Two multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): The guided entry of tail anchor proteins (GET) complex and ER membrane complex (EMC). The structures of both of their hydrophobic core subunits, that are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2 as well as of nuclear encoded inner membrane proteins though was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.

The Relevance of Plant-Derived Se Compounds to Human Health in the SARS-CoV-2 (COVID-19) Pandemic Era

Dietary selenium (Se)-compounds accumulated in plants are essential for human metabolism and normal physiological processes. Inorganic and organic Se species can be readily absorbed by the human body, but are metabolized differently and thus exhibit distinct mechanisms of action. They can act as antioxidants or serve as a source of Se for the synthesis of selenoproteins. Selenocysteine, in particular, is incorporated at the catalytic center of these proteins through a specific insertion mechanism and, due to its electronic features, enhances their catalytic activity against biological oxidants. Selenite and other Se-organic compounds may also act as direct antioxidants in cells due to their strong nucleophilic properties. In addition, Se-amino acids are more easily subjected to oxidation than the corresponding thiols/thioethers and can bind redox-active metal ions. Adequate Se intake aids in preventing several metabolic disorders and affords protection against viral infections. At present, an epidemic caused by a novel coronavirus (SARS-CoV-2) threatens human health across several countries and impacts the global economy. Therefore, Se-supplementation could be a complementary treatment to vaccines and pharmacological drugs to reduce the viral load, mutation frequency, and enhance the immune system of populations with low Se intake in the diet.