Unraveling evolutionary constraints: A heterogeneous conservation in dynamics of the titin Ig domains

The giant protein titin, which comprises immunoglobulin (Ig) domains, acts as a bidirectional spring in muscle. The unfolding of Ig domains has been extensively studied, but their dynamics under native states have not been well-characterized. We performed molecular dynamics simulation on a single titin Ig domain and multi-domains. Mobile regions displaying concerted motions were identified. The dynamics of Ig domains are constrained by evolutionary pressures, in such a way that global dominant motion is conserved, yet different flexibilities within Ig domains and in linkers connecting neighbouring domains were observed. We explain these heterogeneous conserved dynamics in relation to sequence conservation across species and the sequence diversity among neighbouring Ig domains.     

TRIM family proteins: roles in proteostasis and neurodegenerative diseases

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration of the structure and function of the central or peripheral nervous systems. One of the major features of NDs, such as Alzheimer''s disease (AD), Parkinson''s disease (PD) and Huntington''s disease (HD), is the aggregation of specific misfolded proteins, which induces cellular dysfunction, neuronal death, loss of synaptic connections and eventually brain damage. By far, a great amount of evidence has suggested that TRIM family proteins play crucial roles in the turnover of normal regulatory and misfolded proteins. To maintain cellular protein quality control, cells rely on two major classes of proteostasis: molecular chaperones and the degradative systems, the latter includes the ubiquitin-proteasome system (UPS) and autophagy; and their dysfunction has been established to result in various physiological disorders including NDs. Emerging evidence has shown that TRIM proteins are key players in facilitating the clearance of misfolded protein aggregates associated with neurodegenerative disorders. Understanding the different pathways these TRIM proteins employ during episodes of neurodegenerative disorder represents a promising therapeutic target. In this review, we elucidated and summarized the diverse roles with underlying mechanisms of members of the TRIM family proteins in NDs.     

Culture and mental disorder: The case of bebainan in Bali

This is an investigation of bebainan, a disorder which Balinese believe to be caused by sorcery. Most attacks are brief, lasting % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaSGaaeaaca% aIXaaabaGaaGinaaaaaaa!3778!\[{\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 4}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{$4$}}\]–1 hour. The most common symptoms are sudden feelings of confusion, crying, screaming and shouting, followed by inability of the sufferer to control his or her actions. Most sufferers are aware of their behavior during an attack, and remember the occurrence afterwards.The investigator interviewed all the members (296 persons) in the compound of the descendants of the former royal family of Klungkung, among whom 27 people had suffered bebainan attacks. The victims, mostly females, offspring of endogamous marriges, experienced their first attack between the ages of 16 and 30. Analysis of the psychological and social pressures acting on these women suggests that bebainan attacks provide sufferers with an opportunity to release feelings of frustration and anger without risk of widespread disapprobation or stigmatization. However, bebainan is not instrumental in altering access to resources within the restricted environment of the royal compound, nor does it empower the victim within this environment in any but the most transitory ways. Bebainan cannot be regarded as a form of psychosis, even of the reactive or atypical type, it is neither an organic mental disorder, nor a form of neurosis. Instead bebainan can be considered a form of dissociation which is only understandable in the local context of Balinese culture.     

Iron in blood cells: Function,relation to disease,and potential for magnetic separation

Iron in blood cells has several physiological functions like transporting oxygen to cells and maintaining iron homeostasis. Iron is primarily contained in red blood cells (RBCs), but monocytes also store iron as these cells are responsible for the recycling of senescent RBCs. Iron also serves an important role related to the function of different leukocytes. In inflammation, iron homeostasis is dependent on cytokines derived from T cells and macrophages. Fluctuations of iron content in the body lead to different diseases. Iron deficiency, which is also known as anemia, hampers different physiological processes in the human body. On the other hand, genetic or acquired hemochromatosis ultimately results in iron overload and leads to the failure of different vital organs. Different diagnoses and treatments are developed for these kinds of disorders, but the majority are costly and suffer from side effects. To address this issue, magnetophoresis could be an attractive technology for the diagnosis (and in some cases treatment) of these pathologies due to the paramagnetic character of the cells containing iron. In this review, we discuss the main functions of iron in blood cells and iron-related diseases in humans and highlight the potential of magnetophoresis for diagnosing and treating some of these disorders.     

Tandemly repeated pentanucleotides in DNA sequences of eucaryotes.

Genetic sequence data banks were scanned in order to retrieve tandemly repeated pentanucleotides (pnts). It was found that among 102 (=(1024-4)/2/5) possible distinct pnts roughly each fourth is involved in tandem repeats. It is shown that tandemly repeated pnts are composed of frequently occurring di- and trinucleotides and that those pnts which occur frequently in the form of mono- or di-pnts form also tandem repeats either in the form of satellites or in the form of shorter tandem repeats. Human satellite III is taken as a specific example. It is shown that the first guanine within GG-AAT pnt exhibits the highest mutability. Sequential distribution of base changes gives evidence that the mutations do not occur at random positions but in a correlated fashion so that long stretches of original pnts remain intact. It is found that pnts related to the satellite III are present in introns and flanking regions of some structural genes, but are not preserved between orthologous genes of related species. The results corroborate the most plausible mechanism of their evolution--rapid amplification followed by successive divergence of repeat units by various mutational processes.