Miracle-dz/UniFAR-FTUs huggingface dataset:
Stochasticity and heterogeneity in growing bacterial populations

and Contributions In this joint theoretical and experimental project, we focussed on populations of two species with equal growth rates. This non-selective form of evolution has been previously studied, but only for the special case of fixed population size. It was shown usingWright-Fishermodels that, in this case of fixed populations, demographic fluctuations (genetic drift, see subsection 1.1.1) eventually lead to the fixation of one species, and thus to the loss of diversity in the population. Together with Karl Wienand and Erwin Frey, I studied the more general case of growing populations using a Pólya urn model approach (subsection 1.1.2). We found that, after a short initial genetic drift, the population composition “freezes” to a non-fixated steady state. Consequently, genetic diversity is maintained. Our theoretical results were experimentally verified by Felix Becker and Heinrich Jung. This joint work has been published in the research paper “Non-Selective Evolution of Growing Populations”, which is reprinted in section 1.5 (and is also reprinted in the PhD theses of Karl Wienand and Felix Becker).
Fragile tumor suppressors: dissection of signal pathways

Loss or decreased expression of the tumor suppressor, FHIT, occurs in many human cancers and is one of the earliest events in cancer development in some tissues. We demonstrated in this study that the expression level of cyclin D1, an oncogenic protein that is up-regulated in many human cancers, is modulated by Fhit protein in a variety of cells and experimental conditions: 1) the cyclin D1 protein level is lower in Fhit stably transfected human cancer-derived cells and normal mouse kidney epithelial cells, compared to matched Fhit negative cells; 2) over-expression of Fhit by Ad-FHIT viral infection of mouse kidney cells leads to reduced cyclin D1 level by 48 h post infection; 3) cyclin D1 positive nuclei are more frequent in Fhit-/mouse kidney than in wild type kidney tissue. We further found that Fhit down-modulates cyclin D1 largely through contributing to cyclin D1 protein degradation in a cell cycle/CDK-dependent fashion. These results suggest that Fhit may exert tumor suppressor function in part through inhibiting cyclin D1 over-expression by posttranslational control.
From Spinning Silk to Spreading Saliva: Mouthpart Remodeling in Manduca sexta (Lepidoptera: Sphingidae)

Abstract As a model organism, the tobacco hornworm Manduca sexta (Linnaeus 1763) has contributed much to our knowledge of developmental processes in insects, and major developmental changes between different larval instars are generally well understood. Second and later instars of M. sexta do not produce silk, and their spinneret and accessory labial glands (=Lyonet's glands), structures thought to be key players in silk production in other lepidopterans, are highly reduced. To our knowledge, mouthparts and labial gland morphology of the silk-producing first instar have never been described. In this study, we compared the mouthpart morphology and transcriptome profile of first and later instars of M. sexta to determine whether the loss of silk production correlates with changes in the structure of the spinneret and the labial glands, and with changes in expression of silk-related genes. We found that the first instar, unlike later instars, has a typical, silk-producing spinneret with a tube-like spigot and well developed Lyonet's glands. Moreover, three known silk protein genes are highly expressed in the first instar but exhibit little to no expression in the embryo or later instars. Thus, the changes in morphology and gene expression presented here, coinciding with changes in larval behavior from silk production to saliva spreading, further our understanding of the developmental processes underlying this transition in this model organism.
Mortality in the rockpool shrimp Palaemon elegans following long-term exposure to low doses of the anti-parasitic drug teflubenzuron

Anti-parasitic drugs used to control sea lice infestations in the salmonid aquaculture industry are a growing environmental concern due to their potential impacts on non-target crustacean species. This study examined the lethal effects of teflubenzuron, a common in-feed pharmaceutical drug used on Norwegian salmon farms, on a non-target species, rockpool shrimp Palaemon elegans, following an extended exposure period. The standard daily dose for treating salmon is 10 μg teflubenzuron g−1 fish. Adult shrimp were fed 1 of 6 low doses of teflubenzuron (0, 0.0025, 0.005, 0.05, 0.094, 0.188 and 1.88 μg g−1) twice a week for a period of 66 d. Cumulative mortality reached 15, 27, 82 and 100% amongst shrimp exposed to the highest treatment groups (0.05, 0.094, 0.188 and 1.88 μg g−1, respectively). Cumulative mortality amongst shrimp exposed to the 2 lowest teflubenzuron doses and control feed was low (5%). Dose response curves based on measured concentrations within the shrimp were used to calculate a series of lethal threshold concentrations (LCx). The LC5, LC50 and LC90 concentrations of teflubenzuron causing low, median and high levels of mortality in rockpool shrimp were estimated to be 1.2, 18.4 and 150.6 ng g−1, respectively. These concentrations are similar to those reported in wild crustacean species, including shrimp species in the vicinity of Norwegian fish farms, both during and after teflubenzuron medication, suggesting that exposure to low doses of this compound can pose a significant risk to wild shrimp populations.
Potpourri: An Epistasis Test Prioritization Algorithm via Diverse SNP Selection

Genome-wide association studies explain a fraction of the underlying heritability of genetic diseases. Investigating epistatic interactions between two or more loci help closing this gap. Unfortunately, sheer number of loci combinations to process and hypotheses to test prohibit the process both computationally and statistically. Epistasis test prioritization algorithms rank likely-epistatic SNP pairs to limit the number of tests. Yet, they still suffer from very low precision. It was shown in the literature that selecting SNPs that are individually correlated with the phenotype and also diverse with respect to genomic location, leads to better phenotype prediction due to genetic complementation. Here, we hypothesize that an algorithm that pairs SNPs from such diverse regions and carefully ranks the pairs can detect statistically more meaningful pairs and can improve prediction power. We propose an epistasis test prioritization algorithm which optimizes a submodular set function to select a diverse and complementary set of genomic regions that span the underlying genome. SNP pairs from these regions are then further ranked w.r. t. their co-coverage of the case cohort. We compare our algorithm with the state-of-the-art on three GWAS and show that (i) we substantially improve precision (from 0.003 to 0.652) while maintaining the significance of selected pairs, (ii) decrease the number of tests by 25 folds, and (iii) decrease the runtime by 4 folds. We also show that promoting SNPs from regulatory/coding regions improves the precision (up to 0.8). Potpourri is available at http://ciceklab.cs. bilkent.edu. tr/potpourri.
ALLEVIATING THE SALT STRESS EFFECTS IN Salvia splendens BY HUMIC ACID APPLICATION

Salt stress is a serious problem in urban landscape of arid and semi arid regions. To overcome the adverse impacts of salinity, the application of organic matter and plant nutrients in the growth media for improving of plant growth is essential. An experiment was conducted in order to determine the response of Salvia splendens to salinity levels and also the role of humic acid in the salt stress alleviation. In the current experiment five salinity (0, 20, 40, 60, and 80 mM NaCl) and three humic acid (0, 100, 500 and 1000 mg l−1) treatments were prepared. The effects of these treatments were investigated on some growth parameters, physiological characteristics and also biochemical compounds. The results indicated that the growth parameters decreased in saline-treated plants than control plants. Different salinity levels significantly affected relative water content, evaporation rate and also electrolyte leakage. Salinity caused the increase in proline, malondialdehyde, sugar content, DPPH, total phenol content and decrease in chlorophyll, compare to the control plants. Application of humic acid on Salvia splendens, decrease leaf area and plant height compared to the control plants. Thus, regarding the growth parameters, it is probable that the effect of humic acid on the biochemical compounds is similar to salinity effect. The findings suggest that Sage is a sensitive ornamental plant to salinity and humic acid (in the studied levels) could not alleviate the negative effects of salt stress on this plant.
A Cutaneous False Positive in Radioiodine Scintigraphy for Metastatic Thyroid Cancer

Contamination of external sites with secretions or excretory products can mimic metastases and yield false positives in radioiodine whole-body scintigraphy for thyroid cancer. We present a case of a 26-year-old woman with differentiated papillary thyroid carcinoma who received radioiodine 131 (I-131) for treatment of persistent upper mediastinal metastasis. Her post-treatment whole-body scintigraphy revealed an unexpected focus of increased uptake near the scalp in addition to the mediastinal lesion. Although the scalp is the most common site of cutaneous thyroid cancer metastasis, differentiated thyroid cancers rarely manifest with cutaneous thyroid cancer metastasis and thus it is prudent to consider etiologies of false positive I-131 uptake in such cases. Contamination of our patient’s hair from salivary secretions was confirmed on history and with coiffure repositioning during whole-body scintigraphy.
Assessing white matter pathway reproducibility from human whole-brain tractography clustering

Diffusion MRI, together with tractography techniques, is a non-invasive tool to investigate the brain’s structural pathways (tracts). These tracts join together different regions of the brain and tract identification often involves the use of manual ROIs or automated techniques such as clustering. By studying these connections, current understanding of the connectome can be improved and changes due to disease in patient populations may be identified. We developed a tool to automatically identify all pathways in the human brain, including the short-range, U-shaped tracts, and map quantitative scalar metrics along the pathway trajectory for subsequent analysis. Pathways are identified via a spectral clustering technique on two datasets: Human Connectome Project (intersubject) and MyConnectome Project (intrasubject) and the reliability of the extracted tract and scalar values are evaluated. Average Euclidean distances and volumetric overlap were computed and indicated good spatial reliability. Intraclass correlations of the fractional anisotropy value mapped along the tract was calculated and exhibited good reproducibility within each dataset. Additionally, these evaluation metrics, together with the coefficient of variation of the mean streamline count is used to determine reliably identified U-shaped tracts across the datasets. The developed tract identification tool is an additional resource to studying the human connectome with increased confidence in the results. The identified reliable U-shaped tracts contributes to the identification of common structural connections across individuals and aids in advancing our understanding of the brain’s short-range pathways.
Detecting (Un)seen Change: The Neural Underpinnings of (Un)conscious Prediction Errors

Detecting changes in the environment is fundamental for our survival. According to predictive coding theory, detecting these irregularities relies both on incoming sensory information and our top-down prior expectations (or internal generative models) about the world. Prediction errors (PEs), detectable in event-related potentials (ERPs), occur when there is a mismatch between the sensory input and our internal model (i.e., a surprise event). Many changes occurring in our environment may go unnoticed. Such changes can nevertheless be detected by the brain without emerging into consciousness. What remains unclear is how these changes are processed in the brain at the network level. Here, we developed a visual oddball paradigm, where participants engaged in a central letter task during electroencephalographic (EEG) recordings while presented with task-irrelevant high- or low-coherence background, random-dot motion. Critically, once in a while, the direction of the dots changed. After the EEG session, we confirmed that changes in motion direction at high- and low-coherence were visible and invisible, respectively, using psychophysical measurements. ERP analyses revealed that changes in motion direction elicited PE regardless of the visibility, but with distinct spatiotemporal patterns. To understand these responses, we applied Dynamic Causal Modelling (DCM) to the EEG data. Bayesian Model Averaging showed visible PE relied on a release from adaptation (repetition suppression) within bilateral MT+, whilst invisible PE relied on adaptation at bilateral V1 (and left MT+). Furthermore, while feedforward upregulation was present for invisible PE, the visible change PE also included downregulation of feedback between right MT+ to V1. Our findings reveal a complex interplay of modulation in the generative network models underlying visible and invisible motion changes.
Effects of hexanal dip on the postharvest shelf life and quality of papaya Carica papaya L fruit

The objective of this study was to evaluate the effects of hexanal on the post-harvest shelf life and quality of papaya (Carica papaya L.) in two agro-ecological zones (AEZs II and IV) among small-holder farmers in Kenya. Hexanal was tested at two concentrations, 1% and 2%, and applied as a dip for 2.5 minutes or 5 minutes on mature green Solo Sunrise and Mountain papaya cultivars. Water was used as control. The experiment was done in a randomized complete block design with three replications; means were compared by Analysis of Variance using GenStat Version 15. Untreated papaya fruits lasted for 9 days whereas papaya fruits dipped in 2% hexanal for 5 minutes lasted for 15 days with ethylene and respiratory peaks delayed by three days (p < 0.05). These hexanal-dipped fruits lost up to 19% of their cumulative physiological weight (p < 0.05) after the entire storage period of 15 days, whereas controls lost up to 35% of their physiological weight over the same period, and were firmer in texture by 37.4% (p < 0.05). Titratable acidity in papaya fruits gradually decreased with time during the ripening period with no significant difference between the treated and the untreated fruits (p <0.05). Total soluble solids, however, increased as the fruit ripened and then declined with no significant differences between the treatments (p <0.05). Dipping the papaya fruits in hexanal had no effect on beta-carotene content but decreased the rate of vitamin C decline with fruit ripening (p < 0.05). The results of this study indicate that the use of hexanal could be a novel and viable option for reducing post-harvest losses of papaya (Carica papaya L.) in Africa, benefitting small-scale farmers as well as large-scale farmers and traders through improved post-harvest maintenance of quality and longer shelf life.
The complete mitochondrial genome of wood-rotting fungus Xylaria hypoxylon

Abstract Xylaria hypoxylon is a noticeable black fungus, and also habitual to cluster on rotting wood. In this study, the high-quality whole-genome of X. hypoxylon strain SFY20170806 was sequenced on the Illumina sequencing platform. The complete mitochondrial genome of X. hypoxylon was assembled and annotated. The single circular structure of 129,366 bp length is the largest species found in the order Xylariales. The overall GC content is 29.7% and gene composition includes 13 protein-coding genes (PCGs), 30 transfer RNA genes(tRNA), 2 ribosomal RNA genes(rRNA) and 6 open reading frames (ORF). Phylogenetic tree was constructed to validate the evolutionary relationship based on the complete mitogenomes from twelve taxa of four species of Xylariales, four species of Hypocreales, two species of Helotiales, one species of Microascales and X. hypoxylon. Phylogenetic analysis demonstrated that X. hypoxylon has a special evolutionary status and close genetic relationship with Annulohypoxylon stygium.
Functional connectome analyses reveal a highly optimized human olfactory network

The olfactory system is uniquely heterogeneous, performing multifaceted functions (beyond basic sensory processing) across diverse, widely distributed neural substrates. While knowledge of human olfaction continues to grow, it remains unclear how the olfactory network is organized to serve this unique set of functions. Leveraging a large and high-quality resting-state functional magnetic resonance imaging (rs-fMRI) dataset of nearly 900 participants from the Human Connectome Project (HCP), we identified a human olfactory network encompassing cortical and subcortical regions across the temporal and frontal lobes. Highlighting its reliability and generalizability, the connectivity matrix of this olfactory network mapped closely onto that extracted from an independent rs-fMRI dataset. Graph theoretical analysis further explicated the organizational principles of the network. The olfactory network exhibits a functionally advantageous modular composition of three (i.e., the sensory, limbic, and frontal) subnetworks and demonstrates strong small-world properties, high in both global integration and local segregation (i.e., circuit specialization). This network organization thus ensures the segregation of local circuits, which are nonetheless integrated via connecting hubs (i.e., amygdala and anterior insula), thereby enabling the specialized, yet integrative, functions of olfaction. In particular, the degree of local segregation positively predicted olfactory discrimination performance in the independent sample. In sum, an olfactory functional network has been identified through the large HCP dataset, affording a representative template of the human olfactory functional neuroanatomy. Importantly, the topological analysis of the olfactory network provides network-level insights into the remarkable functional specialization and spatial segregation of the olfactory system. Significance Statement Olfaction is an intriguing multifunctional system, playing key roles in regulating emotions, autonomic tone, and feeding, beyond basic sensory perception. However, it is unclear how the neuroanatomy of olfaction is organized in humans to subserve these functions. Functional connectivity analysis of the HCP dataset combined with graph theoretical analysis revealed an optimized large-scale network consisting of three subnetworks—the sensory, limbic, and frontal subnetworks. Distributed across frontal and temporal lobes in well segregated fashion, these olfactory structures are also highly integrated, linked through hub nodes of the amygdala and anterior insula. Our independent dataset replicated the HCP-derived olfactory network and, importantly, highlighted a direct association between the degree of network segregation and olfactory perception.
Genome-wide characterization and expression patterns of chitinase genes in the pigeonpea (Cajanus cajan (L.) Millsp.) genome

Plant chitinases are involved in defense as well as a wide range of physiological functions in plants, including germination, embryogenesis, flowering, and senescence. This study was conducted to identify and annotate the chitinase-related genes from the pigeonpea genome version 2.0, their chromosomal localization and phylogenetic relationship with chitinase genes from 13 different plant species. Here, we report the identification of 34 putative chitinase genes in the pigeonpea genome. These 34 genes encode proteins belonging to two functional domain families, and are subdivided into four classes matching four of the five chitinase classes in Arabidopsis. These chitinase genes are present in clusters on the chromosome. We investigated the expression patterns of these chitinases in 29 different tissues at five developmental stages. There was clear clustering of the chitinase genes into three groups based on their expression patterns in tissues. We identified two chitinase genes C_caj-24 and C_caj-25 that were highly expressed in all tissues as well as other chitinase genes with tissue-specific expression, which suggests that they play important roles in plant defense at specific developmental stages. This information on pigeonpea chitinases could be useful for the development of pigeonpea varieties that are resistant to insect pests and fungal diseases.
Strategic Plan for Interdisciplinary Faculty Development: Arming the Nation's Health Professional Workforce for a New Approach to Substance Use Disorders

America today faces a host of new threats—the threat of bioterrorism, the possibility of chemical weapons, and the reality of war. This nation also continues to face a threat that is even more real for millions of citizens: substance use disorders (SUD). SUD accounts for more deaths, illnesses, and disabilities than does any other preventable health condition. In a recent survey conducted by the Center for Addiction and Substance Abuse at Columbia University (CASA), 23 states reported an increased demand for alcohol and drug treatment since September 11,2001. SUD are associated with many of this country's most serious and tragic problems, including violence, injury, human immunodeficiency virus infection, cardiovascular disease, and cancer. Of the more than 2 million deaths in the United States each year, approximately one in four is attributable to alcohol, tobacco, or illicit drug use. More than 400,000 deaths annually are attributed to tobacco, more than 100,000 to alcohol abuse, and some 16,000 to illicit drugs. These problems put an enormous strain on America's health care system and its economy. The total annual costs associated with SUD are currently estimated at more than $414 billion.