抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Comprehensive Integration of Single-Cell Data.

A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?

Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

/pdf/long-non-coding-rna-hotair-reprograms-chromatin-state-to-5fx0t32kv1.pdf

Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

/pdf/correction-to-robust-hematopoietic-progenitor-cell-gr8b2112at.pdf

Correction to "Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue" [J. Cell Sci. 2015, 128, 3009-3017]

Measurements that involve averaging values from large numbers of cells can obscure the fact that processes such as gene expression are fundamentally dynamic and can vary greatly from cell to cell ( 1 ). Similarly, static snapshots of individual cells can reveal instantaneous differences between cells but cannot reveal often important changes over time; for example, it is impossible to tell whether a yellow light follows a green light using only static pictures of traffic lights. On pages 472 and 475 of this issue, Suter et al. ( 2 ) and Larson et al. ( 3 ) report on using a time-lapse approach to document the dynamics of a key cellular process, RNA transcription. Using carefully constructed experimental systems and sophisticated analyses, they tracked changes in RNA transcription in single live cells. Their results provide new details about the dynamics of key steps in transcription.

Time-Lapse Transcription

[1] Observations from SOHO, STEREO, and ACE during the declining phase of the solar cycle toward the deep minimum in 2008 are analyzed to establish the timing of corotating interaction region (CIR) activity. This analysis is then employed to synthesize signals of the z component of the interplanetary magnetic field (IMF) Bz, solar wind radial velocity vx, and solar wind proton density Np at 1 AU. The synthesized signals are used as a substitute for ACE measurements to represent solar wind forcing due to coronal hole driven CIR events occurring during multiple Bartel rotations (BR 2381 to BR 2393). The signals drive a low-order physics-based model of the magnetosphere called WINDMI, one of whose outputs is the ground-based measurement of the Dst index. Estimating the arrival of CIR events for future rotations using ACE and SOHO data during BR 2381 produced what we refer to as an uncalibrated yearly forecast. We next generated a video-calibrated estimate of the arrival times of CIR events in addition to information from BR 2381 using SOHO and STEREO images of the Sun in order to produce a simulated 3.5 day ahead forecast of possible geomagnetic activity. The time of arrival of CIR events is taken to be the travel time of density compressions as seen in a noninertial frame according to a radial solar wind speed of 500 km/s and a distance of 1 AU. We were able to forecast the timing of CIR-induced geomagnetic activity to within 12 h for 17 out of 28 events by using the expected recurrence of the events through multiple Bartel rotations together with SOHO and STEREO coronal hole sightings made 3.5 days before every event. The uncertainty in the IMF Bz led to a forecast of levels of geomagnetic activity on an ensemble basis, yielding a distribution of different possible Dst signatures. We used a 10-sample ensemble and a 50-sample ensemble to obtain typical representations of geomagnetic activity. Depending on the periodicity and intensity of fluctuations in Bz, we obtained higher or lower levels of activity and shorter or longer times for the recovery of the Dst to quiet levels.

https://agupubs.onlinelibrary.wiley.com/doi/pdf/10.1029/2011JA017018

Forecasting the Dst index during corotating interaction region events using synthesized solar wind parameters

Wetlands play a crucial role in the biosphere and provide numerous services. They performed multiple functions such as groundwater recharge, water purification, conservation of biological resources, act as a carbon sink and habitat of amphibians and birds. A Ramsar site-the Sambhar Lake is one of the largest inland saline wetland present in the arid region of Rajasthan, India has unique habitat suitability for the winter avifauna migrants like flamingoes and falcons. The occurrence of suitable climatic conditions and food availability like brine shrimps (Artemia salina) attracts flocks of migratory birds. From the last three decades, Sambhar Lake has been continuously facing degradation due to anthropogenic activities, which disturb Lake’s natural ecology and existence. These cause disturbances in habitat suitability of migratory birds in the Sambhar Lake, which leads to a reduction of population density of migratory birds. Therefore, this study aimed to assess the degradation and vulnerability of Sambhar Lake and the habitat suitability of migratory birds using Maxent Habitat Suitability model. This model provides a platform to integrate the bird’s occurrence data with the bioclimatic variables using remote sensing and Geographical Information System, and provides bird’s habitat suitability as well as predicts future bird’s occurrence scenarios. Landsat-5 and Sentinel-2 imagery for the year 1996 and 2019 respectively were used in this study. Four indicators such as LULC NDWI, MSI and SABI depicts the environmental condition of the Sambhar Lake. Output form Maxent model reveals that the Sambhar lake area with increasing anthropogenic activities has become unsuitable for flamingos. A remarkable loss of breeding sites of animal, particularly avian fauna (flamingos) is seen in the recent years due to different types of threats posed on the Ramsar site. Increase in Salt crust and Vegetation area from 36.8055 to 123.837 Sq. Km. and 26.5347 to 36.857 Sq. Km. respectively have taken place. While a decrease in saline water area from 88.8309 to 19.3256 Sq. Km has been observed, within the vicinity of Sambhar Lake as clearly shown through LULC map. The future prediction of the distribution of species in the region for the year 2050 shows that the most suitable regions will be near to Jhapok and nearby waters of Salt Lake City as the drains from the city opens in the lake where the flamingoes get Algae in the form of food. Active steps are needed for the lake conservation to reduce the risks of migratory bird’s population.

/pdf/a-maxent-modelling-with-a-geospatial-approach-for-the-436azl7kew.pdf

A Maxent modelling with a geospatial approach for the Habitat suitability of Flamingos in an Evanescing Ramsar site (Sambhar Lake, India) over the changing climatic scenarios

Extensive cell-to-cell variation exists even among putatively identical cells, and there is great interest in understanding how the properties of transcription relate to this heterogeneity. Differential expression from the two gene copies in diploid cells could potentially contribute, yet our ability to measure from which gene copy individual RNAs originated remains limited, particularly in the context of tissues. Here, we demonstrate quantitative, single molecule allele-specific RNA FISH adapted for use on tissue sections, allowing us to determine the chromosome of origin of individual RNA molecules in formaldehyde-fixed tissues. We used this method to visualize the allele-specific expression of Xist and multiple autosomal genes in mouse kidney. By combining these data with mathematical modeling, we evaluated models for allele-specific heterogeneity, in particular demonstrating that apparent expression from only one of the alleles in single cells can arise as a consequence of low-level mRNA abundance and transcriptional bursting.

https://www.biorxiv.org/content/biorxiv/early/2018/08/07/386359.full.pdf

Arjun Raj

Papers

Correction to "Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue" [J. Cell Sci. 2015, 128, 3009-3017]

Time-Lapse Transcription

Forecasting the Dst index during corotating interaction region events using synthesized solar wind parameters

A Maxent modelling with a geospatial approach for the Habitat suitability of Flamingos in an Evanescing Ramsar site (Sambhar Lake, India) over the changing climatic scenarios

Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting