From Beads on a String to the Pearls of Regulation: the Structure and Dynamics of Chromatin

The assembly of eukaryotic chromatin, and the bearing of its structural organization on the regulation of gene expression, were the central topics of a recent conference organized jointly by the Biochemical Society and Wellcome Trust. A range of talks and poster presentations covered topical aspects of this research field and illuminated recent advances in our understanding of the structure and function of chromatin. The two-day meeting had stimulating presentations complemented with lively discourse and interactions of participants. In the present paper, we summarize the topics presented at the meeting, in particular highlighting subjects that are reviewed in more detail within this issue of Biochemical Society Transactions. The reports bring to life the truly fascinating molecular and structural biology of chromatin

Machines on Genes: Enzymes that Make, Break and Move DNA and RNA

As the vital information repositories of the cell, the nucleic acids DNA and RNA pose many challenges as enzyme substrates. To produce, maintain and repair DNA and RNA, and to extract the genetic information that they encode, a battery of remarkable enzymes has evolved, which includes translocases, polymerases/replicases, helicases, nucleases, topoisomerases, transposases, recombinases, repair enzymes and ribosomes. An understanding of how these enzymes function is essential if we are to have a clear view of the molecular biology of the cell and aspire to manipulate genomes and gene expression to our advantage. To bring together scientists working in this fast-developing field, the Biochemical Society held a Focused Meeting, ‘Machines on Genes: Enzymes that Make, Break and Move DNA and RNA’, at Robinson College, University of Cambridge, U.K., in August 2009. The present article summarizes the research presented at this meeting and the reviews associated with the talks which are published in this issue of Biochemical Society Transactions

Dynamical description of vesicle growth and shape change

We systematize and extend the description of vesicle growth and shape change using linear nonequilibrium thermodynamics. By restricting the study to shape changes from spheres to axisymmetric ellipsoids, we are able to give a consistent formulation which includes the lateral tension of the vesicle membrane. This allows us to generalize and correct a previous calculation. Our present calculations suggest that, for small growing vesicles, a prolate ellipsoidal shape should be favored over oblate ellipsoids, whereas for large growing vesicles oblates should be favored over prolates. The validity of this prediction is examined in the light of the various assumptions made in its derivation.Comment: 6 page

A spatial model of autocatalytic reactions

Biological cells with all of their surface structure and complex interior stripped away are essentially vesicles - membranes composed of lipid bilayers which form closed sacs. Vesicles are thought to be relevant as models of primitive protocells, and they could have provided the ideal environment for pre-biotic reactions to occur. In this paper, we investigate the stochastic dynamics of a set of autocatalytic reactions, within a spatially bounded domain, so as to mimic a primordial cell. The discreteness of the constituents of the autocatalytic reactions gives rise to large sustained oscillations, even when the number of constituents is quite large. These oscillations are spatio-temporal in nature, unlike those found in previous studies, which consisted only of temporal oscillations. We speculate that these oscillations may have a role in seeding membrane instabilities which lead to vesicle division. In this way synchronization could be achieved between protocell growth and the reproduction rate of the constituents (the protogenetic material) in simple protocells.Comment: Submitted to Phys. Rev.

Formas de nitrogênio e níveis de potássio sobre a absorção de fósforo por milho

A study, was made on the effects of N-sources (N1 - 100 ppm N-NO3 x N2 = 100 ppm NH4) and K levels (32 and 64 ppm) on dry matter accumulation, P-uptake, root volume, and rhizocylinder pH (pHr) of corn (Zea mays L.). Plants (cv. Centralmex) were grown in 5 liter pots, and harvested at 15, 30 and 45 days after-emergence. NH4 - plants showed reduced growth at the first harvest, K overcame that effect. This effect of NH4 was attributed either to soluble-N accumulation in tissues or to NH4 - phosphate complexes in the soil. The beneficial effect of K on plant growth should then be due to development of K-NH4 - phosphate complexes. NO3 and K affected positively root volume. There was a decrease in pHr between 15 and 45 days, and NH4-N pots had the lowest pH. In the NO3-N treatments, decrease in pHr could be attributed to the small N + P/K relationships (0,8 for N1 plants and 0,66- 0,90 for N1K1 plants at 30 and 45 days). There was a negative relationship between pH and P-uptake (except for NH4 - only treatments).Foi estudado o efeito de formas de N (N1 - 100 ppm N-NO3 x N2 = 100 ppm N-NH4 ) e doses de K (32 e 64 ppm) sobre a acumulação de matéria seca, volume de raízes, pH do rizocilindro (PHr) e absorção de fósforo (P) por milho (Zea mays L.) (cv. Centralmex), aos 15, 30 e 45 dias após a emergência. Houve um efeito inicial negativo do N-NH4 sobre o crescimento. K corrige o efeito negativo do NH4. Os efeitos negativos do N-NH4 podem ter sido causados pelo acúmulo de N solúvel em detrimento do N protéico, ou pela formação de complexos NH4 -fosfato, reduzindo a disponibilidade de P na solução do solo. O efeito positivo do K seria através da formação de complexos K-NH4 -fosfatos. Houve acidificação do rizocilindro (PHr) no período de 15 a 45 dias em todos os tratamentos, com menor pH nos tratamentos que receberam N-NH4. A queda de pHr nos tratamentos sob NO3 explica-se pela relação N + P/K (0,8 para o tratamento N1 e 0,66-0,99 para os tratamentos N1K1, aos 30 e 45 dias, respectivamente). Houve uma correlação negativa entre pHr e acumulação de P na parte aérea (exceto para os tratamentos N2)

On RAF Sets and Autocatalytic Cycles in Random Reaction Networks

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as reflexively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the difficulties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.Comment: pp 113-12

The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations

Objective To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series. Methods Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000\u20132014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed. Results Out of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20 years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or d\ue9j\ue0-vu). Tonic\u2013clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory. By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group. Significance Heterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations