Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins

Mitochondrial carriers, which transport metabolites, nucleotides, and cofactors across the mitochondrial inner membrane, have six transmembrane α-helices enclosing a translocation pore with a central substrate binding site whose access is controlled by a cytoplasmic and a matrix gate (M-gate). The salt bridges formed by the three PX[DE]XX[RK] motifs located on the odd-numbered transmembrane α-helices greatly contribute to closing the M-gate. We have measured the transport rates of cysteine mutants of the charged residue positions in the PX[DE]XX[RK] motifs of the bovine oxoglutarate carrier, the yeast GTP/GDP carrier, and the yeast NAD+ transporter, which all lack one of these charged residues. Most single substitutions, including those of the non-charged and unpaired charged residues, completely inactivated transport. Double mutations of charged pairs showed that all three carriers contain salt bridges non-essential for activity. Two double substitutions of these non-essential charge pairs exhibited higher transport rates than their corre-sponding single mutants, whereas swapping the charged residues in these positions did not increase activity. The results demonstrate that some of the residues in the charged residue positions of the PX[DE]XX[KR] motifs are important for reasons other than forming salt bridges, probably for playing specific roles related to the substrate interaction-mediated conformational changes leading to the M-gate opening/closing

Effects of Force Level and Hand Dominance on Bilateral Transfer of a Fine Motor Skill

Our research is about bilateral transfer, a concept in motor learning where skills learned by one limb are "transferred", allowing the opposite limb to benefit from what was learned by the first limb. Previous research into bilateral transfer has raised questions about whether specific aspects of motor coordination are or are not transferred. We wanted to see whether learning to control pinch force by the thumb and index finger is transferable, and if it is, whether the learning transfers equally from either hand. We also want to look into the effects of different force levels on the degree of transfer. We designed a task using a program that takes force levels as inputs and has the participant trace shapes on a screen. By having participants perform with one hand, then practice with the other, and finally perform again with the initial hand, we can measure transfer as the difference in performance before and after practice with the other hand.Kinesiology and Health Educatio

New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions

Mitochondrial carriers (MCs) belong to a eukaryotic protein family of transporters that in higher organisms is called the solute carrier family 25 (SLC25). All MCs have characteristic triplicated sequence repeats forming a 3-fold symmetrical structure of a six-transmembrane α-helix bundle with a centrally located substrate-binding site. Biochemical characterization has shown that MCs altogether transport a wide variety of substrates but can be divided into subfamilies, each transporting a few specific substrates. We have investigated the intron positions in the human MC genes and their orthologs of highly diversified organisms. The results demonstrate that several intron positions are present in numerous MC sequences at the same specific points, of which some are 3-fold symmetry related. Many of these frequent intron positions are also conserved in subfamilies or in groups of subfamilies transporting similar substrates. The analyses of the frequent and conserved intron positions in MCs suggest phylogenetic relationships not only between close but also distant homologs as well as a possible involvement of the intron positions in the evolution of the substrate specificity diversification of the MC family members

Superconducting Superstructure for the TESLA Collider

We discuss the new layout of a cavity chain (superstructure) allowing, we hope, significant cost reduction of the RF system of both linacs of the TESLA linear collider. The proposed scheme increases the fill factor and thus makes an effective gradient of an accelerator higher. We present mainly computations we have performed up to now and which encouraged us to order the copper model of the scheme, still keeping in mind that experiments with a beam will be necessary to prove if the proposed solution can be used for the acceleration.Comment: 11 page

Favourable outcome of coronavirus disease 2019 in a patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer receiving alectinib

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Is transperitoneal laparoscopic adrenalectomy for pheochromocytoma really more challenging? A propensity score-matched analysis

Purpose Minimally invasive surgery is the gold standard treatment for adrenal masses, but it may be a challenging procedure in the case of pheochromocytoma (PHEO). The aim of the present study is to report the results of transperitoneal laparoscopic adrenalectomy (TLA) in cases of PHEO in comparison to other types of adrenal lesions. Methods From 1994 to 2021, 629 patients underwent adrenalectomy. Twenty-two and thirty-five patients, respectively, were excluded because they underwent bilateral and open adrenalectomy, leaving 572 patients for inclusion. Of these, 114 patients had PHEO (Group A), and 458 had other types of lesions (Group B). To adjust for potential baseline confounders, a propensity score matching (PSM) analysis was conducted. Results After PSM, 114 matched pairs of patients were identified from each group. Statistically significant differences were not observed when comparing the median operative time (85 and 90 min in Groups A and B, respectively, p = 0.627), conversion rate [6 (5.3%) in each group, p = 1.000], transfusion rate [4 (3.5%) and 3 (2.6%) in Groups A and B, respectively, p = 1.000], complication rate [7 (6.1%) and 9 (7.9%) in Groups A and B, respectively, p = 0.796), median postoperative hospital stay (3.9 and 3.6 days in Groups A and B, respectively, p = 0.110), and mortality rate [1 (0.9%) in each group, p = 1.000]. Conclusions Based on this analysis, the results of TLA for PHEO are equivalent to those of TLA for other types of adrenal lesions, but the fundamental requirements are multidisciplinary patient management and adequate surgeon experience. Further prospective studies are required to draw definitive conclusions

Cancer risk in adrenalectomy: are adrenal lesions equal or more than 4 cm a contraindication for laparoscopy?

none7openBalla A, Corallino D, Ortenzi M, Palmieri L, Meoli F, Guerrieri M, Paganini AMBalla, A; Corallino, D; Ortenzi, M; Palmieri, L; Meoli, F; Guerrieri, M; Paganini, A

High-Resolution Ultrasound Spectroscopy for the Determination of Phospholipid Transitions in Liposomal Dispersions

High-resolution ultrasound spectroscopy (HR-US) is a spectroscopic technique using ultrasound waves at high frequencies to investigate the structural properties of dispersed materials. This technique is able to monitor the variation of ultrasound parameters (sound speed and attenuation) due to the interaction of ultrasound waves with samples as a function of temperature and concentration. Despite being employed for the characterization of several colloidal systems, there is a lack in the literature regarding the comparison between the potential of HR-US for the determination of phospholipid thermal transitions and that of other common techniques both for loaded or unloaded liposomes. Thermal transitions of liposomes composed of pure phospholipids (dimyristoylphosphatidylcholine, DMPC; dipalmitoylphosphatidylcholine, DPPC and distearoylphosphatidylcholine, DSPC), cholesterol and their mixtures were investigated by HR-US in comparison to the most commonly employed microcalorimetry (mDSC) and dynamic light scattering (DLS). Moreover, tramadol hydrochloride, caffeine or miconazole nitrate as model drugs were loaded in DPPC liposomes to study the effect of their incorporation on thermal properties of a phospholipid bilayer. HR-US provided the determination of phospholipid sol-gel transition temperatures from both attenuation and sound speed that are comparable to those calculated by mDSC and DLS techniques for all analysed liposomal dispersions, both loaded and unloaded. Therefore, HR-US is proposed here as an alternative technique to determine the transition temperature of phospholipid membrane in liposomes