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Early oligomerization of human islet amyloid polypeptide (hIAPP), which is accountable for β‐cell death, has been implicated in the progression of type 2 diabetes mellitus. Some researches have shown the connection between hIAPP and Alzheimer's disease as well. However, the mechanism of peptide accumulation and associated cytotoxicity remains unclear. Due to the unique properties and significant role of histidine in protein sequences, here for the first time, the tautomeric effect of histidine at the early stages of amylin misfolding was investigated via molecular dynamics simulations. Considering Tau and Pi tautomeric forms of histidine (Tau and Pi tautomers are denoted as ϵ and δ, respectively), simulations were performed on two possible isomers of amylin. Our analysis revealed a higher probability of transient α‐helix generation in the δ isomer in monomeric form. In dimeric forms, the δδ and δϵ conformations showed an elevated amount of α‐helix and lower coil in comparison to the ϵϵ dimer. Due to the significant role of α‐helix in membrane disruption and transition to β‐sheet structure, these results may imply a noticeable contribution of the δ isomer and the δδ and δϵ dimers rather than ϵ and ϵϵ conformations in the early stages of diabetes initiation. Our results may aid in elucidating the hIAPP self‐association process in the etiology of amyloidosis. [ABSTRACT FROM AUTHOR]

We have derived a simple expression to evaluate the amount of intramolecular charge transfer (ICT) of π-conjugate push–pull systems from the properties of electronegativity (χ) and polarizability (α) of the corresponding push and pull systems. This simple model is verified from ab initio calculations of disubstituted benzenes, stilbenes, and butadienes (push–pull systems) and their monosubstituted (push or pull) systems with various donors and acceptors. The bond length alternation (BLA) is often used as a good structural parameter to describe the amount of ICT; however, it is not a complete parameter because the amounts of ICT for the same sets of donor/acceptor pairs are different for different bridge systems. Here, we report a parameter composed of polarizability and electronegativity to give a consistent amount of ICT for different bridge systems. In particular, when a highly electropositive donor is used, the polarizability of an acceptor is the most determining factor for ICT. On the basis of this model, we find a very strong acceptor with large polarization effect, CH==C[sub 5]H[sub 4], which gives a large nonlinear optical (NLO) response when a highly electropositive donor is used. The model would be a very useful utility to design various types of new functional molecular systems involving ICT optimization. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Early oligomerization of human islet amyloid polypeptide (hIAPP), which is accountable for β-cell death, has been implicated in the progression of type 2 diabetes mellitus. Some researches have shown the connection between hIAPP and Alzheimer's disease as well. However, the mechanism of peptide accumulation and associated cytotoxicity remains unclear. Due to the unique properties and significant role of histidine in protein sequences, here for the first time, the tautomeric effect of histidine at the early stages of amylin misfolding was investigated via molecular dynamics simulations. Considering Tau and Pi tautomeric forms of histidine (Tau and Pi tautomers are denoted as ϵ and δ, respectively), simulations were performed on two possible isomers of amylin. Our analysis revealed a higher probability of transient α-helix generation in the δ isomer in monomeric form. In dimeric forms, the δδ and δϵ conformations showed an elevated amount of α-helix and lower coil in comparison to the ϵϵ dimer. Due to the significant role of α-helix in membrane disruption and transition to β-sheet structure, these results may imply a noticeable contribution of the δ isomer and the δδ and δϵ dimers rather than ϵ and ϵϵ conformations in the early stages of diabetes initiation. Our results may aid in elucidating the hIAPP self-association process in the etiology of amyloidosis., (© 2021 Wiley-VCH GmbH.)

Aim: To investigate the survival outcomes of secondary hepatectomy for recurrent colorectal liver metastases (CRLM)., Methods: From October 1994 to December 2009, patients with CRLM who underwent surgical treatment with curative intent were investigated. Patients were divided into two groups: patients who underwent primary hepatectomy (Group 1) and those who underwent secondary hepatectomy for recurrent CRLM (Group 2)., Results: Survival and prognostic factors were analyzed. A total of 461 patients were included: 406 patients in Group 1 and 55 patients in Group 2. After a median 39-mo (range, 3-195 mo) follow-up, there was a significant difference between Groups 1 and 2 in terms of disease-free survival (P=0.029) although there was no significant difference in overall survival (P=0.206). Secondary hepatectomy was less effective in patients with multiple recurrent CRLM than primary hepatectomy for initial CRLM (P=0.008). Multiple CRLM and radiofrequency ablation therapy were poor prognostic factors of secondary hepatectomy in multivariate Cox regression analysis (P=0.006, P=0.004, respectively)., Conclusion: Secondary hepatectomy for single recurrent CRLM is as effective as primary surgical treatment for single recurrent CRLM. However, secondary hepatectomy for multiple recurrent CRLM is less effective than that for single recurrent CRLM.