Transitions in replication timing in a 340 kb region of human chromosomal R-Band 1p36.1

DNA replication is initiated within a few chromosomal bands as normal human fibroblasts enter the S phase. In the present study, we determined the timing of replication of sequences along a 340 kb region in one of these bands, 1p36.13, an R band on chromosome 1. Within this region, we identified a segment of DNA (approximately 140 kb) that is replicated in the first hour of the S phase and is flanked by segments replicated 1-2 h later. Using a quantitative PCR-based assay to measure sequence abundance in size-fractionated (900-1,700 nt) nascent DNA, we mapped two functional origins of replication separated by 54 kb and firing 1 h apart. One origin was found to be functional during the first hour of S and was located within a CpG island associated with a predicted gene of unknown function (Genscan NT_004610.2). The second origin was activated in the second hour of S and was mapped to a CpG island near the promoter of the aldehyde dehydrogenase 4A1 (ALDH4A1) gene. At the opposite end of the early replicating segment, a more gradual change in replication timing was observed within the span of approximately 100 kb. These data suggest that DNA replication in adjacent segments of band 1p36.13 is organized differently, perhaps in terms of replicon number and length, or rate of fork progression. In the transition areas that mark the boundaries between different temporal domains, the replication forks initiated in the early replicated region are likely to pause or delay progression before replication of the 340 kb contig is completed.     

A novel repetitive DNA sequence in lemon [Citrus limon (L.) Burm.] and related species Bruna

Repetitive DNA sequences constitute a significant component of most eukaryotic genomes, and the isolation and characterization of such sequences provide an insight into the organization of the genome of interest. Here, we report the isolation and molecular characterization of a novel repetitive DNA sequence from the genome of Citrus limon. Digestion of C. limon DNA with MboI produced a prominent fragment of approximately 600 bp. Southern blotting revealed a ladder composed of DNA fragments that are multimers of the 600 bp Mbo I band. This suggests that MboI isolated a novel satellite, named C. limon satellite DNA 600 (CL600). Methylation analyses using Sau3AI-MboI isoschizomers demonstrated that most cytosine residues in the GATC sites of this element were methylated in C. limon. This sequence was also found in related citrus plants, like grapefruit and orange, and the hardiest close relatives of Citrus, such as kumquat and trifoliate orange.     

Synthesis and anti-HIV evaluation of new 2',3'-dideoxy-3'-thiacytidine prodrugs

A series of anti-HIV prodrugs possessing various polyaminated side arms have been developed. The incorporation of a N-Boc protected monoamine or diamine side arm into the backbone of the 2',3'-dideoxy-3'-thiacytidine 1 (BCH-189) provided an increase in antiviral potency, which could be several orders magnitude greater than the parent drug (1) depending on the cell culture systems used (MT-4 or MDMs). Twenty six 2',3'-dideoxy-3'-thiacytidine prodrugs which differ from each other by the length, the nature of the 5'-O function and the 5'-O or/and N-4 position on the nucleoside moiety were synthesized. Among this new series of prodrugs, several congeners (12c and 12a) were found to inhibit HIV-1 replication in cell culture with 50% effective concentrations EC50 of 10 and 50 nM respectively, in MT-4 cells. Compound 12c was found more active on infected MDMs cells with 50% effective concentration of 0.01 nM. The synthesis and the antiviral properties of these compounds are discussed.     

Roads Alter the Colonization Dynamics of a Keystone Herbivore in Neotropical Savannas1

Roads can facilitate the establishment and spread of both native and exotic species. Nevertheless, the precise mechanisms facilitating this expansion are rarely known. We tested the hypothesis that dirt roads are favorable landing and nest initiation sites for founding‐queens of the leaf‐cutter ant Atta laevigata. For 2 yr, we compared the number of attempts to found new nests (colonization attempts) in dirt roads and the adjacent vegetation in a reserve of cerrado (tree‐dominated savanna) in southeastern Brazil. The number of colonization attempts in roads was 5 to 10 times greater than in the adjacent vegetation. Experimental transplants indicate that founding‐queens are more likely to establish a nest on bare soil than on soil covered with leaf‐litter, but the amount of litter covering the ground did not fully explain the preference of queens for dirt roads. Queens that landed on roads were at higher risk of predation by beetles and ants than those that landed in the adjacent vegetation. Nevertheless, greater predation in roads was not sufficient to offset the greater number of colonization attempts in this habitat. As a consequence, significantly more new colonies were established in roads than in the adjacent vegetation. Our results suggest that disturbance caused by the opening of roads could result in an increased Atta abundance in protected areas of the Brazilian Cerrado.     

Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats

Neurochemical Research - Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia...     

Understanding genetic diversity,spatial genetic structure,and mating system through microsatellite markers for the conservation and sustainable use of <Emphasis Type="Italic">Acrocomia aculeata</Emphasis> (Jacq.) Lodd. Ex Mart.

Acrocomia aculeata is a native palm distributed widely throughout Brazil that is used in a diverse array of products from the food industry to biodiesel oil production. This study uses nine microsatellite loci to assess the genetic diversity, spatial genetic structure (SGS), and mating system of A. aculeata. A total of 200 samples were collected from four populations (Fusquinha—FU, Padre Josimo—PJ, Gleba XV-GB, and Amparo—AM), in São Paulo State, Brazil. We also collected fruits from 20 randomly selected seed trees in the FU population to assess mating patterns, for a total of 246 genotyped embryos. We identified a total of 103 alleles and all loci were polymorphic. The average observed heterozygosity (\({H_o}\)) ranged from 0.410 (AM) to 0.531 (FU) and expected heterozygosity (\({H_e}\)) ranged from 0.547 (PJ) to 0.615 (GB). The average fixation index (\(F\)) ranged from 0.043 to 0.254 for FU and AM populations, respectively. The coancestry coefficient (\({\theta _{xy}}\)) was significant up to 38 m in PJ the population and 71 m in AM. Individual palm outcrossing rates were predominantly high (\({t_m}\)?=?0.985) and the paternity correlation (\({r_{{p_{(m)}}}}\)?=?0.02) was significantly low, indicating a high probability of the occurrence of half-sibs. Compared to other palm species, the studied populations show high levels of genetic diversity. Our results confirm that A. aculeata is primarily allogamous, with no significant paternity correlation, and seeds should be harvested from at least 40 trees to ensure high levels of genetic diversity in seed collection programs.     

NMR spectroscopy and mass spectrometry in metabolomics analysis of <Emphasis Type="Italic">Salvia</Emphasis>

The interest in using the ‘-omics’ approach for nutrition, agriculture, food science and human health have seen an explosive growth in the last years. Particularly, metabolomics analysis is becoming an integral part of a system biological approach for investigating organisms. In this review, the limitations and advantages of NMR spectroscopy and mass spectrometry were discussed in details using the study reported in the literature on different Salvia species (S. hispanica, S. miltiorrhiza, S. officinalis, S. runcinata and S. stenophylla). Both approaches identify and quantify several classes of compounds but not the complete metabolite profile of the plant. A combined approach of these two powerful techniques provides better results allowing to determine both primary and secondary metabolites.     

Fruit production along roads and footpaths in an Atlantic rain forest area

Background: Pathways (footpaths and roads) in forests are associated with edge effects, affecting forest structure and composition and associated wildlife. However, little is known about how edge effects along pathways may impact the dynamics of fruit production and their availability for frugivores.

Aim: We related pathway width as a proxy for edge effects to fruit production. Our underlying hypothesis was that pathway width would be positively related to fruit production.

Methods: We observed fruit production along three pathways of different widths – 2, 10 and 20 m wide – and in a control area of undisturbed forest in an Atlantic rain forest stand monthly over a 2-year period.

Results: The number of species and individuals-bearing fruit was higher along the wider pathways than along the narrowest pathway and in the control area. The amount of zoochorous fruits was higher in the control area than along pathways, and the widest pathway had higher non-zoochorous fruits production. Fruiting peaks occurred along pathways, while fruiting in the control area was aseasonal.

Conclusions: Pathway width is related to fruit type and its quantity and temporal availability. These effects extend towards the forest interior beyond 35 m. The presence of paths affects food resources for frugivores and thus can contribute to reconfiguring the spatio-temporal distribution of the fauna.     

Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders

Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor—BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT). Since the incidence and clinical manifestations of neurodevelopmental disorders present significant sex-related differences, we sought to distinctly evaluate male and female mice. While on PN35, LPS-challenged male mice presented depressive, anxiety-like, repetitive behavior, and working memory deficits; on PN70, only depressive- and anxiety-like behaviors were observed. Conversely, females presented prepulse inhibition (PPI) deficits in both ages studied. Behavioral changes in periadolescence and adulthood were accompanied, in both sexes, by increased levels of interleukin (IL-4) (PFC, HC, and HT) and decreased levels of IL-6 (PFC, HC, and HT). BDNF levels increased in both sexes on PN70. LPS-challenged male mice presented, in both ages evaluated, increased HC myeloperoxidase activity (MPO); while when adult increased levels of interferon gamma (IFNγ), nitrite and decreased parvalbumin were observed. Alterations in innate immunity and parvalbumin were the main LPS-induced remarks between males and females in our study. We concluded that neonatal LPS challenge triggers sex-specific behavioral and neurochemical alterations that resemble autism spectrum disorder, constituting in a relevant model for the mechanistic investigation of sex bias associated with the development of this disorder.