Cryo-nanoscale chromosome imaging—future prospects

The high-order structure of mitotic chromosomes remains to be fully elucidated. How nucleosomes compact at various structural levels into a condensed mitotic chromosome is unclear. Cryogenic preservation and imaging have been applied for over three decades, keeping biological structures close to the native in vivo state. Despite being extensively utilized, this field is still wide open for mitotic chromosome research. In this review, we focus specifically on cryogenic efforts for determining the mitotic nanoscale chromatin structures. We describe vitrification methods, current status, and applications of advanced cryo-microscopy including future tools required for resolving the native architecture of these fascinating structures that hold the instructions to life

Engaging currently available tested and proven strategies to tackle hepatitis B viral epidemic: the HBV-4-pronged approach (HBV4PA)

Hepatitis B viral (HBV) infection is a major world problem and is a key contributing factor to the worldwide incidence of hepatocelullar carcinoma, especially in sub-Saharan Africa. However, although hepatitis B treatment is available and effective, it is out of the reach of the common person. Many have, because of cost of treatment, succumbed to the chronic effects of HBV infection, such as liver cirrhosis and primary liver cancer. In this article, we make a case for the provision of free antiviral drugs to chronically-infected HBV patients by expanding the current HIV services to HBV-infected individuals using the PMTCT model. This, when implemented, will save lives, prevent unnecessary and escalating health expenditure and ensure sustainable development

Psychopharmacological characterisation of the successive negative contrast effect in rats

Rationale Successive negative contrast (SNC) describes a change in the behaviour of an animal following a downshift in the quantitative or qualitative value of an expected reward. This behavioural response has been hypothesised to be linked to affective state, with negative states associated with larger and/or prolonged shifts in behaviour. Objective This study has investigated whether different psychopharmacological treatments have dissociable actions on the SNC effect in rats and related these findings to their actions on different neurotransmitter systems and affective state. Methods Animals were trained to perform a nose-poke response to obtain a high-value food reward (four pellets). SNC was quantified during devalue sessions in which the reward was reduced to one pellet. Using a within-subject study design, the effects of acute treatment with anxiolytic, anxiogenic, antidepressant and dopaminergic drugs were investigated during both baseline (four pellets) or devalue sessions (one pellet). Results The indirect dopamine agonist, amphetamine, attenuated the SNC effect whilst the D1/D2 antagonist, alpha-flupenthixol, potentiated it. The antidepressant citalopram, anxiolytic buspirone and anxiogenic FG7142 had no specific effects on SNC, although FG7142 induced general impairments at higher doses. The α2-adrenoceptor antagonist, yohimbine, increased premature responding but had no specific effect on SNC. Results for the anxiolytic diazepam were mixed with one group showing an attenuation of the SNC effect whilst the other showed no effect. Conclusions These data suggest that the SNC effect is mediated, at least in part, by dopamine signalling. The SNC effect may also be attenuated by benzodiazepine anxiolytics

Evolutionary Consequences of Dusty Tori in Active Galactic Nuclei

Deep surveys of {\em Chandra} and {\em HST} (Hubble Space Telescope) show that active galactic nucleus (AGN) populations are changing with hard X-ray luminosities. This arises an interesting question whether the dusty torus is evolving with the central engines. We assemble a sample of 50 radio-quiet PG quasars to tackle this problem. The covering factors of the dusty tori can be estimated from the multiwavelength continuum. We find they are strongly correlated with the hard X-ray luminosity. Interestingly this correlation agrees with the fraction of type II AGNs discovered by {\em Chandra} and {\em HST}, implying strong evidence for that the AGN population changing results from the evolution of the tori. We also find that the frequencies of the dips around 1$\mu$m in the continuum correlate with the covering factors in the present sample, indicating the dip frequencies are adjusted by the covering factors. In the scenario of fueling black hole from the torus, the covering factor is a good and the dip frequency is a potential indicator of the torus evolution.Comment: 4 pages in emulateapj5.sty. Accepted by ApJ Letter

Exercise Habits and Tobacco Use among Male Latino Farmworkers

Migrant farmworkers risk occupational injury and are at risk for developing chronic health conditions. Exercise may enhance health and help to reduce the risk of occupational injury and/or reduce the risk of developing a chronic health condition. Little is known, however, about the exercise habits of Latino migrant farmworkers. Male Latino migrant farmworkers completed an exercise and health habits questionnaire at health screening clinics. One hundred fifty-three (58.2%) subjects reported exercising during the week. There was no difference in age between those who reported exercising and those who did not (p = .78). Only 42 (16%) of all workers reported exercising for 3 or more hours a week. Seventeen percent of the subjects reported smoking and almost 10% reported chewing tobacco. A majority of subjects do not meet the Centers for Disease Control and Prevention (CDC) exercise guidelines. Tobacco use is highest among individuals who do not exercise. These findings suggest the need for health education interventions for this population. Additional studies are warranted to understand exercise and health habits of this population

HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch

Simulations on High-z Long Gamma-Ray Burst Rate

Since the launch of Swift satellite, the detections of high-z (z>4) long gamma-ray bursts (LGRBs) have been rapidly growing, even approaching the very early Universe (the record holder currently is z=8.3). The observed high-z LGRB rate shows significant excess over that estimated from the star formation history. We investigate what may be responsible for this high productivity of GRBs at high-z through Monte Carlo simulations, with effective Swif/BAT trigger and redshift detection probabilities based on current Swift/BAT sample and CGRO/BATSE LGRB sample. We compare our simulations to the Swift observations via log N-log P, peak luminosity (L) and redshift distributions. In the case that LGRB rate is purely proportional to the star formation rate (SFR), our simulations poorly reproduce the LGRB rate at z>4, although the simulated log N-log P distribution is in good agreement with the observed one. Assuming that the excess of high-z GRB rate is due to the cosmic metallicity evolution or unknown LGRB rate increase parameterized as (1+z)^delta, we find that although the two scenarios alone can improve the consistency between our simulations and observations, incorporation of them gives much better consistency. We get 0.2<epsilon<0.6 and delta<0.6, where epsilon is the metallicity threshold for the production of LGRBs. The best consistency is obtained with a parameter set (epsilon, delta)=(~0.4, ~0.4), and BAT might trigger a few LGRBs at z~14. With increasing detections of GRBs at z>4 (~15% of GRBs in current Swift LGRB sample based on our simulations), a window for very early Universe is opening by Swift and up-coming SVOM missions.Comment: 9 pages, including 8 figures and 1 table, one more figure added. Accepted for publication in MNRA

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing