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Biology subjects

Yasmin, S.

Publications and source records attributed to Yasmin, S..

5 recordsLinked to original sources

Spatiotemporal profiling of T cell repertoires in Lynch syndrome reveals convergent immune responses through neoplastic progression

Surveillance of individuals with Lynch syndrome (LS), who are carriers of heterozygous inactivating mismatch repair (MMR) gene mutations that predispose to colorectal cancer, enables the study of tumour-immune coevolution during tumour initiation. Somatic loss of MMR activity in the LS colon leads to the accrual of cancer driver mutations, and also of neoantigens likely to generate an adaptive immune response. However, the spatial and temporal immune dynamics in colon and peripheral blood are uncharacterised. Here we show that the neoplastic evolution of mismatch repair deficient (MMRd) clones leads to large-scale and sustained reorganisation of the T-cell repertoire in colon and peripheral blood. We performed dense spatiotemporal profiling of T cell receptor (TCR) repertoires from 109 colonic biopsies (11 tumour samples, 98 normal bowel) from seven individuals, with eight matched blood repertoires. We additionally analysed 13 colorectal polyp repertoires from eight participants, 286 cross sectional blood repertoires from 242 participants (198 LS and 44 non-LS) and 52 longitudinal peripheral blood samples from 26 individuals with LS. We detected tumour-associated T cell clones, some of which were widely present in normal bowel tissue and also detectable in peripheral blood. Sequence similarity analysis revealed conserved TCR architectures across tissue compartments and recurrent clustering patterns between patients, that were not present in non-Lynch controls, consistent with convergent MMRd-associated antigen-driven immune selection. We identified systemic signatures associated with local tumour immune activity and revealed evidence of structured repertoire remodelling before overt malignancy. Longitudinal profiling revealed frequent turnover of low-abundance clonotypes, whereas highly abundant clonotypes persisted for several years. Collectively, our data defines the local and circulating TCR landscape associated with colonic neoplasia in LS, and provides a framework for LS blood-based immune monitoring, early interception and biomarker development.

immunology↗

The Effects of Speech Masking on Neural Tracking of Acoustic and Semantic Features of Natural Speech

Listening environments contain background sounds that mask speech and lead to communication challenges. Sensitivity to slow acoustic fluctuations in speech can help segregate speech from background noise. Semantic context can also facilitate speech perception in noise, for example, by enabling prediction of upcoming words. However, not much is known about how different degrees of background masking affect the neural processing of acoustic and semantic features during naturalistic speech listening. In the current electroencephalography (EEG) study, participants listened to engaging, spoken stories masked at different levels of multi-talker babble to investigate how neural activity in response to acoustic and semantic features changes with acoustic challenges, and how such effects relate to speech intelligibility. The pattern of neural response amplitudes associated with both acoustic and semantic speech features across masking levels was U-shaped, such that amplitudes were largest for moderate masking levels. This U-shape may be due to increased attentional focus when speech comprehension is challenging, but manageable. The latency of the neural responses increased linearly with increasing background masking, and neural latency change associated with acoustic processing most closely mirrored the changes in speech intelligibility. Finally, tracking responses related to semantic dissimilarity remained robust until severe speech masking (-3 dB SNR). The current study reveals that neural responses to acoustic features are highly sensitive to background masking and decreasing speech intelligibility, whereas neural responses to semantic features are relatively robust, suggesting that individuals track the meaning of the story well even in moderate background sound.

neuroscience↗

Neural activity in human brainstem adapts to sound-level statistics

Optimal perception requires adaptation to sounds in the environment. Adaptation involves representing the acoustic stimulation history in neural response patterns, for example, by altering response magnitude or latency as sound-level context change. Neurons in the auditory brainstem of rodents are sensitive to acoustic stimulation history and sound-level context (often referred to as sensitivity to stimulus statistics), but the degree to which the human brainstem exhibits such neural adaptation is unclear. In six electroencephalography experiments with over 125 participants, we demonstrate that the response latency of the human brainstem is sensitive to the history of acoustic stimulation over a few tens of milliseconds. We further show that human brainstem responses adapt to sound-level context in, at least, the last 44 ms, but that neural sensitivity to sound-level context decreases when the time window over which acoustic stimuli need to be integrated becomes wider. Our study thus provides evidence of adaptation to sound-level context in the human brainstem and of the timescale over which sound-level information affects neural responses to sound. The research delivers an important link to studies on neural adaptation in non-human animals.

neuroscience↗

Metagenomic Analysis of Bacterial Community Associated with Rhizosphere and Phyllosphere of Basmati Rice

Rice is one of the most important crops for feeding about more than half of the worlds population. Yield of rice crop is significantly hampered by various biotic and abiotic factors. Application of cost-effective and environment-friendly bioinoculant is a common practice to combat the yield losses of rice in this era. The rhizosphere and phyllosphere of rice plants provide specific habitats for various micro-organisms. In the present study, the bacterial population dwelling the rhizosphere and phyllosphere of Basmati rice were explored using metagenomic approach from rice growing areas of Punjab, Pakistan. The bacterial communities associated with the rice rhizosphere of different rice growing areas as well as phyllosphere/rhizosphere were compared. Out of 20,069 16S rRNA gene sequences retreived from rhizosphere soil, 6485 were originated from Faisalabad, 5174 from Gujranwala and 8410 from Sheikhupura. Data analyses revelead that Proteobactria was dominant phylum at all three sites. Choloflexi was second abundant phylum at Sheikhupura, while Actinobacteria and Firmicutes at Gujranwala and Faisalabad. In addition to dominant culturable PGPB Bacillus genus at all three sites, Nitrosospira, Gaiella, Marmoricola, Clostridium sensu stricto. Maximum geners were detected from Faisalabad (159), followed by Sheikhupura (146) and Gujranwala (131). Comparison of the common sequences at the genus-level revealed that maximum number of shared genera (101) were observed in Sheikhupura and Gujranwala. 50 genera were specifically related to Faisalabad, while 27 and 21 genera were detected for Sheikhupura and Gujranwala. In the phyllosphere, Proteobacteria (79.6%) was detected as dominant phylum followed by Firmicutes (9.8%), Bacteroidetes (8.6%), Chloroflexi (4.3%) and Actinobacteria (0.9%). Comparison of phyllosphere and rhizosphere showed less bacterial diversity in the phyllosphere but Bradyrhizobium, Sphingomonas, GP6, Pseudomonas, Bacillus are abuundant. Fifteen genera were detected at both compartments. Furthermore, we may select these strains for development of compatible inocula for application in the rhizosphere and phyllosphere of rice.

microbiology↗

Megacities as drivers of national outbreaks: the role of holiday travel in the spread of infectious diseases

Human mobility connects populations and can lead to large fluctuations in population density, both of which are important drivers of epidemics. Measuring population mobility during infectious disease outbreaks is challenging, but is a particularly important goal in the context of rapidly growing and highly connected urban centers in low and middle income countries, which can act to amplify and spread local epidemics nationally and internationally. Here, we combine estimates of population movement from mobile phone data for over 4 million subscribers in the megacity of Dhaka, Bangladesh, one of the most densely populated cities globally. We combine mobility data with epidemiological data from a household survey, to understand the role of population mobility on the spatial spread of the mosquito-borne virus chikungunya within and outside Dhaka city during a large outbreak in 2017. The peak of the 2017 chikungunya outbreak in Dhaka coincided with the annual Eid holidays, during which large numbers of people traveled from Dhaka to their native region in other parts of the country. We show that regular population fluxes around Dhaka city played a significant role in determining disease risk, and that travel during Eid was crucial to the spread of the infection to the rest of the country. Our results highlight the impact of large-scale population movements, for example during holidays, on the spread of infectious diseases. These dynamics are difficult to capture using traditional approaches, and we compare our results to a standard diffusion model, to highlight the value of real-time data from mobile phones for outbreak analysis, forecasting, and surveillance.

ecology↗