Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials’ development. Existing peptide-based catalysts exhibit low catalytic efficiency ...compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. For this purpose, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique and well-defined mechanisms. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. Moreover, fragmentation schemes of the primary sequence of selected enzymes alongside the study of their amino acid frequencies, composition, and physicochemical properties are proposed. The results showed highly conserved catalytic sites with distinct positional patterns and chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts.
This article deals mostly with land registers. It demonstrates clearly what is the significance of this legal element in continental European legal systems especially those who follow Germanic legal ...tradition (like Croatia). As such, land registers provide legal certainty and transparency which are highly desired and valued among potential business investors. Therefore, we may rightly award it with cornerstone status within the law of real property.
- A young woman with breast cancer is considered to be a woman younger than 40. According to the literature, breast cancer in the population of young women usually is of a higher histologic grade, ...unfavorable hormonal status, and overall higher mortality rate when compared with breast cancer occurring in older population. We compared pathologic and immunohistochemical features of breast carcinoma in women under 40 years of age with the respective features in women over 60 years of age. The following parameters were observed in these two groups: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2/neu status, and histologic type of the tumor. Early onset breast carcinoma was found to have a higher frequency of tumor grade 3 (29%
. 17%) and estrogen receptor negativity (45%
. 23%). In the group of young women, breast carcinoma was mostly multicentric (23%
. 5%), triple-negative (32%
. 10%), and was found to have higher proliferation index Ki-67 (25%
. 10%). Our results confirmed differences between the young and older groups of patients. In the group of young women, we found predominantly unfavorable prognostic parameters of the disease.
The sequence-to-function relationship of peptide-based catalysts remains a challenge, as even subtle modifications at the sequence level can alternate their catalytic activity. A set of linear and ...cyclic histidine-rich peptides was synthesized to assess the impact of amino acid disposition, cyclization, and incorporation of
d
-amino acids on their ability to self-assemble, coordinate Zn
2+
ions, and show intrinsic hydrolase-like activity. Self-assembly into β-sheets was confirmed for both linear peptides and one cyclic analogue (cy-hh) by FTIR, ThT binding, CD, and AFM. Interestingly, only peptide A demonstrated efficient ester hydrolysis of
p
-NPA,
p
-NPB and
p
-NPO substrates, indicative of its effective Zn
2+
coordination. Our findings highlight that increased rigidity of the peptide can hinder metal ion coordination by limiting the necessary conformational adjustments for optimal Zn
2+
binding. These insights into the structural changes underlying the function of short peptides offer valuable knowledge for the design of metal-dependent peptide-based catalysts.
Understanding how sequence modification, self-assembly, stereochemistry and affinity for zinc ions contribute to catalytic function of histidine-rich metal-dependent peptides.
Political extremism (and particularly right wing political extremism) remains relatively insufficiently explored due to the fact that the phenomenon is controversial and hard to define. Its ambiguity ...and variability depending on time and spatial point of view further complicates its definition. Its structure is amorphous and eclectic as it often includes elements from different ideologies and connects incompatible ideas. A multidimensional conceptualization and an interdisciplinary approach - sociological, social, psychological and historical, are the Author’s tools in explaining the phenomenon of political extremism in Serbia, hopefully contributing to its clarification and laying a foundation for its furtherexplanatory theoretical studies.
Commercial law embraces different types of relations in exchanging goods and services, among which the most prominent place is taken by contract law with its trans-border and international features. ...Unlike in other private law branches, dispositive norms play a more significant role in commercial law, in particular business customs and codified commercial practices (usage of trade). However, a new field has recently come into view -- consumer protection law which (not only in the European legal area) imposes peremptory norms aimed at protecting health, providing better information and strengthening competitiveness between commercial entities. Accordingly, the responsibility of traders in that field has also intensified. The issues related to competition law, however, also have a broader meaning within the framework of harmonisation of the Croatian law with the new European private law. In that light there are issues related to terminology, conceptual clarity and systematic classification of law.
Breast cancer is the most common malignancy in the population of women under 40 years of age. Young age is an independent factor for poor prognosis. In this research, we tried to establish other ...factors for poor prognosis in stage I-III breast cancer. The following parameters were observed: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2 neu status, histologic type of the tumor, local recurrence and metastases. Logistic regression was used to evaluate the effect of specific factors on the probability of lethal outcome and development of distant metastases. Our patients showed a predominance of T1 tumor (49.4%), had positive lymph nodes (62%) and most of them were pN1 (61.2%). Up to one-third of patients had triple negative status. Ki-67 proliferation index was high (25%). Multicentric tumor was detected in 23% of patients. There was no difference in overall survival between the two types of surgical procedures. Patients with pN0 status had better overall survival. Breast cancer in the population of young women has a more aggressive nature. Study results indicated positive lymph node status as an independent factor for poor prognosis of stage I-III breast cancer.
Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in the
(
gene. Individuals with this syndrome present with multiple congenital anomalies, ...as well as a delay in development and intellectual disability. Herein, we report the case of a newborn male patient with a novel de novo pathogenic variant in the Guanine Nucleotide-Binding Protein, Alpha Stimulating (
) gene, which was identified by whole-exome sequencing. Our patient suffered from a large open spinal dysraphism which was treated surgically immediately after birth. During the follow-up, facial dysmorphism, bladder and bowel incontinence, and mildly delayed motor and speech development were observed. Congenital central nervous system disorders were also confirmed radiologically. In this case report, we present our diagnostic and treatment approaches to this patient. To our knowledge, this is the first reported case of Gabriele-de Vries syndrome presenting with spinal dysraphism. Extensive genetic evaluation is the cornerstone in treatment of patients with suspected Gabriele-de Vries syndrome. However, in cases with potentially life-threatening conditions, surgery should be strongly considered.
Highlights • long-term GH therapy has positive influence on craniofacial development in TS. • mandibular ramus and posterior face height are especially responsive. • development of acromegalic ...features is not a concern. • effects of GH therapy do not overcome craniofacial characteristics related to TS.
Despite the fact that Macedonia achieved independence in a peaceful manner in 1991, its position has been continuously challenged in political, economic and security dimensions ever since. One of ...them is Islamic fundamentalism. In a country with over 1/3 of the population being Muslims (and still growing) this issue becomes a potential danger in the security dimension. Using a descriptive analysis method, the Author aims to highlight the specificity of Islam in Macedonia and to define the potential or real danger of Islamic fundamentalism in the country.
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