Physiological properties of Cantor coding-like iterated function system in the hippocampal CA1 network

Cantor coding provides an information coding scheme for temporal sequences of events. In the hippocampal CA3–CA1 network, Cantor coding-like mechanism was observed in pyramidal neurons and the relationship between input pattern and recorded responses could be described as an iterated function system. However, detailed physiological properties of the system in CA1 remain unclear. Here, we performed a detailed analysis of the properties of the system related to the physiological basis of learning and memory. First, we investigated whether the system could be simply based on a series of on–off responses of excitatory postsynaptic potential (EPSP) amplitudes. We applied a series of three spatially distinct input patterns with similar EPSP peak amplitudes. The membrane responses showed significant differences in spatial clustering properties related to the iterated function system. These results suggest that existence of some factors, which do not simply depend on a series of on–off responses but on spatial patterns in the system. Second, to confirm whether the system is dependent on the interval of sequential input, we applied spatiotemporal sequential inputs at several intervals. The optimal interval was 30 ms, similar to the physiological input from CA3 to CA1. Third, we analyzed the inhibitory network dependency of the system. After GABA_A receptor blocker (gabazine) application, quality of code discrimination in the system was lower under subthreshold conditions and higher under suprathreshold conditions. These results suggest that the inhibitory network increase the difference between the responses under sub- and suprathreshold conditions. In summary, Cantor coding-like iterated function system appears to be suitable for information expression in relation to learning and memory in CA1 network.     

Murburn posttranslational modifications of proteins: Cellular redox processes and murzyme-mediated metabolo-proteomics

Murburn concept constitutes the thesis that diffusible reactive species or DRS are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn posttranslational modifications (PTMs) result because murburn/murzyme functionalism is integral to cellular existence. Cells must incorporate the inherently stochastic nature of operations mediated by DRS. Due to the earlier/inertial stigmatic perception that DRS are mere agents of chaos, several such outcomes were either understood as deterministic modulations sponsored by house-keeping enzymes or deemed as unregulated nonenzymatic events resulting out of “oxidative stress”. In the current review, I dispel the myths around DRS-functions, and undertake systematic parsing and analyses of murburn modifications of proteins. Although it is impossible to demarcate all PTMs into the classical or murburn modalities, telltale signs of the latter are evident from the relative inaccessibility of the locus, non-specificities and mechanistic details. It is pointed out that while many murburn PTMs may be harmless, some others could have deleterious or beneficial physiological implications. Some details of reversible/irreversible modifications of amino acid residues and cofactors that may be subjected to phosphorylation, halogenation, glycosylation, alkylation/acetylation, hydroxylation/oxidation, etc. are listed, along with citations of select proteins where such modifications have been reported. The contexts of these modifications and their significance in (patho)physiology/aging and therapy are also presented. With more balanced explorations and statistically verified data, a definitive understanding of normal versus pathological contexts of murburn modifications would be obtainable in the future.     

Genome-wide histone modifications: gaining specificity by preventing promiscuity

More than 20 residues within the four core histone proteins of the nucleosome are potential sites of post-translational modifications, such as methylation, acetylation, ubiquitination and phosphorylation. It has been hypothesized that specific patterns of these modifications on the nucleosome facilitate recruitment of non-histone proteins to chromatin. When such modifications are restricted to particular regions of the genome, they seem to play an important role in creating specific chromatin domains. However, more recent results suggest that some histone modifications, particularly those that exist on a genome-wide scale, act to reduce nonspecific binding by chromatin proteins involved in silencing. This decrease of promiscuous binding ensures that the silent chromatin proteins are not titrated away from their normal locations on chromosomes. We suggest that preventing such promiscuous binding of chromatin proteins is an important part of generating specificity to create chromatin domains and overall chromosome organization.     

The human serum albumin gene: structure of a unique locus

The entire gene for human serum albumin (HSA) has been isolated from a genomic DNA library, carried in the lambda Charon 4A vector. Six independent isolates have been found to hybridize to a cloned HSA cDNA probe, and all six clones share restriction site sequence homology in the overlapping portion of their DNA. These results seem to indicate that the albumin gene is single-copy, or unique, within the human haploid genome. Measuring from the "CAP" site to the "poly(A)" addition site, albumin gene comprises 16.5 kb of DNA.     

Molecular determinants for α-tubulin methylation by SETD2

Post-translational modifications to tubulin are important for many microtubule-based functions inside cells. It was recently shown that methylation of tubulin by the histone methyltransferase SETD2 occurs on mitotic spindle microtubules during cell division, with its absence resulting in mitotic defects. However, the catalytic mechanism of methyl addition to tubulin is unclear. We used a truncated version of human wild type SETD2 (tSETD2) containing the catalytic SET and C-terminal Set2–Rpb1–interacting (SRI) domains to investigate the biochemical mechanism of tubulin methylation. We found that recombinant tSETD2 had a higher activity toward tubulin dimers than polymerized microtubules. Using recombinant single-isotype tubulin, we demonstrated that methylation was restricted to lysine 40 of α-tubulin. We then introduced pathogenic mutations into tSETD2 to probe the recognition of histone and tubulin substrates. A mutation in the catalytic domain (R1625C) allowed tSETD2 to bind to tubulin but not methylate it, whereas a mutation in the SRI domain (R2510H) caused loss of both tubulin binding and methylation. Further investigation of the role of the SRI domain in substrate binding found that mutations within this region had differential effects on the ability of tSETD2 to bind to tubulin versus the binding partner RNA polymerase II for methylating histones in vivo, suggesting distinct mechanisms for tubulin and histone methylation by SETD2. Finally, we found that substrate recognition also requires the negatively charged C-terminal tail of α-tubulin. Together, this study provides a framework for understanding how SETD2 serves as a dual methyltransferase for both histone and tubulin methylation.     

Experimental investigation of the origin of fynbos plant community structure after fire

Background and aims

Species in plant communities segregate along fine-scale hydrological gradients. Although this phenomenon is not unique to fynbos, this community regenerates after fire and therefore provides an opportunity to study the ecological genesis of hydrological niche segregation.

Methods

Following wildfires at two field sites where we had previously mapped the vegetation and monitored the hydrology, seeds were moved experimentally in >2500 intact soil cores up and down soil-moisture gradients to test the hypothesis that hydrological niche segregation is established during the seedling phase of the life cycle. Seedling numbers and growth were then monitored and they were identified using DNA bar-coding, the first use of this technology for an experiment of this kind.

Key Results

At the site where niche segregation among Restionaceae had previously been found, the size of seedlings was significantly greater, the wetter the location into which they were moved, regardless of the soil moisture status of their location of origin, or of the species. Seedling weight was also significantly greater in a competition treatment where the roots of other species were excluded. No such effects were detected at the control site where niche segregation among Restionaceae was previously found to be absent.

Conclusions

The finding that seedling growth on hydrological gradients in the field is affected by soil moisture status and by root competition shows that hydrological niche segregation could potentially originate in the seedling stage. The methodology, applied at a larger scale and followed-through for a longer period, could be used to determine whether species are differently affected by soil moisture.     

Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics

Posttranslational modifications of proteins have profound effects on many aspects of their function and have received much attention due to the importance of these processes in epigenetic regulation. In this study, we report that deleted azoospermia associated protein 1 (DAZAP1)/proline-rich RNA binding protein (Prrp), a multifunctional RNA binding protein which is essential for spermatogenesis and normal cell growth, is acetylated at Lysine 150 within its RNA binding domain. The acetylation is predominantly observed in nuclear Prrp, and the nonacetylated form is in cytoplasm. Considering that Prrp is a shuttling protein, we suggest that the acetylation cycle at Prrp K150 regulates nucleocytoplasmic transport in cells.     

Mapping QTLs and candidate genes for iron and zinc concentrations in unpolished rice of Madhukar×Swarna RILs

Identifying QTLs/genes for iron and zinc in rice grains can help in biofortification programs. 168 F(7) RILs derived from Madhukar×Swarna were used to map QTLs for iron and zinc concentrations in unpolished rice grains. Iron ranged from 0.2 to 224ppm and zinc ranged from 0.4 to 104ppm. Genome wide mapping using 101 SSRs and 9 gene specific markers showed 5 QTLs on chromosomes 1, 3, 5, 7 and 12 significantly linked to iron, zinc or both. In all, 14 QTLs were identified for these two traits. QTLs for iron were co-located with QTLs for zinc on chromosomes 7 and 12. In all, ten candidate genes known for iron and zinc homeostasis underlie 12 of the 14 QTLs. Another 6 candidate genes were close to QTLs on chromosomes 3, 5 and 7. Thus the high priority candidate genes for high Fe and Zn in seeds are OsYSL1 and OsMTP1 for iron, OsARD2, OsIRT1, OsNAS1, OsNAS2 for zinc and OsNAS3, OsNRAMP1, Heavy metal ion transport and APRT for both iron and zinc together based on our genetic mapping studies as these genes strictly underlie QTLs. Several elite lines with high Fe, high Zn and both were identified.     

Enhancing students’ experimental planning competences by introducing and evaluating the IS4O teaching approach

ABSTRACT

We herein report the introduction of the IS⁴O (Improving Students’ Scientific Skills by Using Scaffolding Outlines) teaching approach and its implementation to successfully empower students with initial minor planning competences in mastering complex scientific challenges in the course of Germany’s most-renowned scientific competitions. The IS⁴O teaching approach itself comprises the unique combination of the differentiating teaching methods Backward Planning and Project Mapping as core teaching elements. The beneficial effect of the IS⁴O teaching approach on the enhancement of the students planning competences is also discussed. Based on the given results, this teaching approach is mandatory to empower students with initial minor competences in completing a scientific competition successfully with very high assignment of tasks.