Bistable Soft Shells for Programmable Mechanical Logic.

Mechanical computing promises to integrate semiconductor-based digital logic in several applications, but it needs straightforward programmable devices for changing computing rules in situ. A methodology based on strain-governed, bistable soft shells that process digital information by interchanging their internal/external surfaces is proposed. This bistable behavior, explained via model-based design, safeguards robustness by working only once for each input pulse.

A Cost-Effective Integrated Methodology for Electromagnetic Actuation via Visual Feedback.

Electromagnetic actuation can support many fields of technology, such as robotics or biomedical applications. In this context, fully understanding the system behavior and proposing a low-cost package for feedback control is challenging. Modeling the electromagnetic force is particularly tricky because it is a nonlinear function of the actuated object's position and coil's current.

Mechanism-based and computational modeling of hydrogen sulfide biogenesis inhibition: interfacial inhibition.

Hydrogen sulfide (HS) is a gaseous signaling molecule that participates in various signaling functions in health and diseases. The tetrameric cystathionine γ-lyase (CSE) contributes to HS biogenesis and several investigations provide evidence on the pharmacological modulation of CSE as a potential target for the treatment of a multitude of conditions. D-penicillamine (D-pen) has recently been reported to selectively impede CSE-catalyzed HS production but the molecular bases for such inhibitory effect have not been investigated.

Persulfidation of DJ-1: Mechanism and Consequences.

DJ-1 (also called PARK7) is a ubiquitously expressed protein involved in the etiology of Parkinson disease and cancers. At least one of its three cysteine residues is functionally essential, and its oxidation state determines the specific function of the enzyme. DJ-1 was recently reported to be persulfidated in mammalian cell lines, but the implications of this post-translational modification have not yet been analyzed.

A Case of Advanced Tubal Ectopic Pregnancy after Emergency Contraception.

Ectopic pregnancy is a relatively common condition and an important cause of morbidity in women of childbearing age. The most frequent implantation site is the fallopian tube. Most cases are diagnosed in an early gestational period.

Molecular Basis for the Interaction of Catalase with d-Penicillamine: Rationalization of Some of Its Deleterious Effects.

d-Penicillamine (d-Pen) is a sulfur compound used in the management of rheumatoid arthritis, Wilson's disease (WD), and alcohol dependence. Many side effects are associated with its use, particularly after long-term treatment. However, the molecular basis for such side effects is poorly understood.

COVID-19 pandemic in an Italian obstetric department: sharing our experience.

Background And Aim Of The Work: The outbreak of the novel coronavirus (or SARS-CoV 2) has significantly struck the healthcare system worldwide. Over the course of a few weeks, hospitals reorganized their internal structure entirely at any level of care, from the Emergency rooms to Departments, including all the medical specialties.

Methods: In order to cope with the contingent state of emergency, the Gynecology and Obstetrics Unit of the University Hospital in Udine introduced new protocols and guidance for the usual standard of care, ensuring a safe environment for both healthcare providers and patients.

Orofacial Myofunctional Therapy in Obstructive Sleep Apnea Syndrome: A Pathophysiological Perspective.

Obstructive sleep apnea (OSA) syndrome is a multi-factorial disorder. Recently identified pathophysiological contributing factors include airway collapsibility, poor pharyngeal muscle responsiveness, a low arousal threshold, and a high loop gain. Understanding the pathophysiology is of pivotal importance to select the most effective treatment option.

Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide.

Reactivity of persulfides toward strained bicyclo[6.1.0]nonyne derivatives: relevance to chemical tagging of proteins.

Persulfides are an emerging class of cysteine oxidative post-translational modification. They react with the bioconjugation reagents bicyclo[6.1.

EFA6 controls Arf1 and Arf6 activation through a negative feedback loop.

Guanine nucleotide exchange factors (GEFs) of the exchange factor for Arf6 (EFA6), brefeldin A-resistant Arf guanine nucleotide exchange factor (BRAG), and cytohesin subfamilies activate small GTPases of the Arf family in endocytic events. These ArfGEFs carry a pleckstrin homology (PH) domain in tandem with their catalytic Sec7 domain, which is autoinhibitory and supports a positive feedback loop in cytohesins but not in BRAGs, and has an as-yet unknown role in EFA6 regulation. In this study, we analyzed how EFA6A is regulated by its PH and C terminus (Ct) domains by reconstituting its GDP/GTP exchange activity on membranes.

Electrophilic sulfhydration of 8-nitro-cGMP involves sulfane sulfur.

The formation of 8-SH-cGMP from the reaction between hydrogen sulfide and 8-nitro-guanosine-3',5'-cyclic monophosphate in the presence of thiols does not take place by nucleophilic attack of the hydrosulfide anion, as previously proposed, but first involves the formation of reactive species containing sulfane sulfur, like persulfides.

A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone.

Fidelity during cofactor assembly is essential for the proper functioning of metalloenzymes and is ensured by specific chaperones. MeaB, a G-protein chaperone for the coenzyme B12-dependent radical enzyme methylmalonyl-CoA mutase (MCM), uses the energy of GTP binding, hydrolysis or both to regulate cofactor loading into MCM, protect MCM from inactivation and rescue MCM that is inactivated during turnover. Typically, G proteins signal to client proteins using the conformationally mobile switch I and II loops.

High yield production of myristoylated Arf6 small GTPase by recombinant N-myristoyl transferase.

Small GTP-binding proteins of the Arf family (Arf GTPases) interact with multiple cellular partners and with membranes to regulate intracellular traffic and organelle structure. Understanding the underlying molecular mechanisms requires in vitro biochemical assays to test for regulations and functions. Such assays should use proteins in their cellular form, which carry a myristoyl lipid attached in N-terminus.

Giant dedifferentiated liposarcoma of the right hemifacial area involving the oral cavity.

Although liposarcoma is a reasonably common soft tissue sarcoma in adults, its occurrence within the head and neck region is very rare. The following report presents the case of a giant dedifferentiated liposarcoma initially located in the temporal region and then extending to the entire right maxillofacial region. Clinical as well as histopathological features and therapeutic approaches of dedifferentiated liposarcoma are discussed, and a literature review is presented.

Basaloid squamous cell carcinoma of the larynx: report of a early laryngeal cancer.

Basaloid squamous cell carcinoma is a recently recognized, rare and aggressive variant of squamous cell carcinoma with a predilection to occur in base of the tongue, hypopharynx and larynx (especially the supraglottic tract). It is usually diagnosed in advanced stage, frequently with distant metastases, requiring aggressive surgical intervention. The prognosis is remarkably poor even after the association of radiotherapy or chemotherapy.

A G-protein editor gates coenzyme B12 loading and is corrupted in methylmalonic aciduria.

The mechanism by which docking fidelity is achieved for the multitude of cofactor-dependent enzymes is poorly understood. In this study, we demonstrate that delivery of coenzyme B(12) or 5'-deoxyadenosylcobalamin by adenosyltransferase to methylmalonyl-CoA mutase is gated by a small G protein, MeaB. While the GTP-binding energy is needed for the editing function; that is, to discriminate between active and inactive cofactor forms, the chemical energy of GTP hydrolysis is required for gating cofactor transfer.

IcmF is a fusion between the radical B12 enzyme isobutyryl-CoA mutase and its G-protein chaperone.

Coenzyme B(12) is used by two highly similar radical enzymes, which catalyze carbon skeleton rearrangements, methylmalonyl-CoA mutase and isobutyryl-CoA mutase (ICM). ICM catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA and exists as a heterotetramer. In this study, we have identified >70 bacterial proteins, which represent fusions between the subunits of ICM and a P-loop GTPase and are currently misannotated as methylmalonyl-CoA mutases.

The tinker, tailor, soldier in intracellular B12 trafficking.

The recognition of eight discrete genetic complementation groups among patients with inherited cobalamin disorders provided early insights into the complexity of a cofactor-processing pathway that supports only two known B(12)-dependent enzymes in mammals. With the identification of all eight genes now completed, biochemical interrogations of their functions have started and are providing novel insights into a trafficking pathway involving porters that tinker with and tailor the active cofactor forms and editors that ensure the fidelity of the cofactor loading process. The principles of sequestration and escorted delivery of a rare and reactive organometallic cofactor that are emerging from studies on B(12) might be of general relevance to other cofactor trafficking pathways.

Ligand-binding by catalytically inactive mutants of the cblB complementation group defective in human ATP:cob(I)alamin adenosyltransferase.

MMAB (methylmalonic aciduria type B) is a mitochondrial enzyme involved in the metabolism of vitamin B(12). It functions as the ATP:cob(I)alamin adenosyltransferase for the generation of adenosylcobalamin (AdoCbl), the cofactor of methylmalonyl-CoA mutase (MCM). Impaired MMAB activity leads to the inherited disorder methylmalonic aciduria and is responsible for the cblB complementation group.

Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions.

In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H2S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H2S generation. CBS from both organisms shows a marked preference for H2S generation by beta-replacement of cysteine by homocysteine.

A rotary mechanism for coenzyme B(12) synthesis by adenosyltransferase.

Adenosyltransferases (ATRs) catalyze the synthesis of the reactive cobalt-carbon bond found in coenzyme B(12) or 5'-deoxyadenosylcobalamin (AdoCbl), which serves as a cofactor for a number of isomerases. The reaction involves a reductive adenosylation of cob(II)alamin in which an electron delivered by a reductase reduces cob(II)alamin to cob(I)alamin, which attacks the 5'-carbon of ATP to form AdoCbl and inorganic triphosphate. Of the three classes of ATRs found in nature, the PduO type, which is also the only one found in mammals, is the most extensively studied.

H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia.

Although there is a growing recognition of the significance of hydrogen sulfide (H(2)S) as a biological signaling molecule involved in vascular and nervous system functions, its biogenesis and regulation are poorly understood. It is widely assumed that desulfhydration of cysteine is the major source of H(2)S in mammals and is catalyzed by the transsulfuration pathway enzymes, cystathionine beta-synthase and cystathionine gamma-lyase (CSE). In this study, we demonstrate that the profligacy of human CSE results in a variety of reactions that generate H(2)S from cysteine and homocysteine.