2,782 research outputs found
Sommerfeld enhancement from Goldstone pseudo-scalar exchange
We point out that the exchange of a Goldstone pseudo-scalar can provide an
enhancement in the dark matter annihilation rate capable of explaining the
excess flux seen in high energy cosmic ray data. The mechanism of enhancement
involves the coupling of s and d waves through the tensor force that is very
strong and, in fact, singular at short distances. The results indicate that
large enhancements require some amount of fine tuning. We also discuss the
enhancement due to other singular attractive potentials, such as WIMP models
with a permanent electric dipole.Comment: 14 pages, 4 figures, v2 includes contact informatio
Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response
Dramatic rise of mutators has been found to accompany adaptation of bacteria
in response to many kinds of stress. Two views on the evolutionary origin of
this phenomenon emerged: the pleiotropic hypothesis positing that it is a
byproduct of environmental stress or other specific stress response mechanisms
and the second order selection which states that mutators hitchhike to fixation
with unrelated beneficial alleles. Conventional population genetics models
could not fully resolve this controversy because they are based on certain
assumptions about fitness landscape. Here we address this problem using a
microscopic multiscale model, which couples physically realistic molecular
descriptions of proteins and their interactions with population genetics of
carrier organisms without assuming any a priori fitness landscape. We found
that both pleiotropy and second order selection play a crucial role at
different stages of adaptation: the supply of mutators is provided through
destabilization of error correction complexes or fluctuations of production
levels of prototypic mismatch repair proteins (pleiotropic effects), while rise
and fixation of mutators occur when there is a sufficient supply of beneficial
mutations in replication-controlling genes. This general mechanism assures a
robust and reliable adaptation of organisms to unforeseen challenges. This
study highlights physical principles underlying physical biological mechanisms
of stress response and adaptation
The RNA polymerase II C-terminal domain-interacting domain of yeast Nrd1 contributes to the choice of termination pathway and couples to RNA processing by the nuclear exosome
The RNA polymerase II (RNApII) C-terminal domain (CTD)- interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CIDRtt103)) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist. Therefore, CTD-CID interactions target specific termination complexes to help choose an RNApII termination pathway. Interactions of Nrd1 with bothCTDand nascent transcripts contribute to efficient termination by the Nrd1 complex. Surprisingly, replacing the Nrd1 CID with that from Rtt103 reduces binding to Rrp6/Trf4, and RNA transcripts terminated by Nrd1(CIDRtt103) are predominantly processed by core exosome. Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome
Methods for reduced cost and lower sample prep volumes for genetic analysis applications
As the cost of NGS has decreased, the library preparation cost has become a larger portion of the total expenditure. This is especially true for high-throughput applications, such as single-cell analysis. Therefore, there is a need to develop methods that can not only study the transcriptomes of single cells, but can also feasibly analyze large numbers of single cells.
Miniaturizing the sample preparation volume provides the opportunity for significant cost savings. Using TTP Labtech’s mosquito liquid handlers, reagent and sample quantities can be scaled down to picogram values
Prevalence of Depression among Households in Three Capital Cities of Pakistan: Need to Revise the Mental Health Policy
BACKGROUND: Pakistan, among the other developing countries, has a higher prevalence rate of depression because of the current social adversities. There is, thus, a great need for systematic studies on prevalence of depression. The current study aims at exploring the prevalence of depression among households in three capital cities of Pakistan. METHODOLOGY AND PRINCIPAL FINDINGS: A sample of N = 820 was randomly selected, and a cross sectional telephone-based study was conducted for a duration of six months. It was found that there was a regional variation in prevalence rates for depression among the three cities. Lahore had the highest number of depressives (53.4%), as compared to Quetta (43.9%) and Karachi (35.7%). Middle age, female gender and secondary school level of education were significantly associated with depression among the study group. CONCLUSIONS/SIGNIFICANCE: The different rates of prevalence among the three cities could be attributed to local cultural influence, geographical locations and social adversities. There is a need for revision of existing health policy by the government
CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells
Sickle Cell Disease and beta-thalassemia, which are caused by defective or deficient adult beta-globin (HBB) respectively, are the most common serious genetic blood diseases in the world. Persistent expression of the fetal beta-like globin, also known gamma-globin, can ameliorate both disorders by serving in place of the adult beta-globin as a part of the fetal hemoglobin tetramer (HbF). Here we use CRISPR-Cas9 gene editing to explore a potential gamma-globin silencer region upstream of the delta-globin gene identified by comparison of naturally-occurring deletion mutations associated with up-regulated gamma-globin. We find that deletion of a 1.7 kb consensus element or select 350 bp sub-regions from bulk populations of cells increases levels of HbF. Screening of individual sgRNAs in one sub-region revealed three single guides that caused increases gamma-globin expression. Deletion of the 1.7 kb region in HUDEP-2 clonal sublines, and in colonies derived from CD34+ hematopoietic stem/progenitor cells (HSPCs), does not cause significant up-regulation of gamma-globin. These data suggest that the 1.7 kb region is not an autonomous gamma-globin silencer, and thus by itself is not a suitable therapeutic target for gene editing treatment of beta-hemoglobinopathies.Peer reviewe
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