Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-chromosome paints in maize reveal rearrangements, nuclear domains, and chromosomal relationships

Significance Whole-chromosome oligo-FISH paints using synthetic oligonucleotide libraries that can be amplified and labeled were generated for all 10 chromosomes of maize, facilitating chromosome studies with high sensitivity and specificity for genetically diverse lines. Applications include visualization of simple or complex chromosomal aberrations, establishment of chromosomal domains, illustration of mitotic and meiotic behavior, and providing insights into chromosomal relationships. Whole-chromosome painting probes were developed for each of the 10 chromosomes of maize by producing amplifiable libraries of unique sequences of oligonucleotides that can generate labeled probes through transcription reactions. These paints allow identification of individual homologous chromosomes for many applications as demonstrated in somatic root tip metaphase cells, in the pachytene stage of meiosis, and in interphase nuclei. Several chromosomal aberrations were examined as proof of concept for study of various rearrangements using probes that cover the entire chromosome and that label diverse varieties. The relationship of the supernumerary B chromosome and the normal chromosomes was examined with the finding that there is no detectable homology between any of the normal A chromosomes and the B chromosome. Combined with other chromosome-labeling techniques, a complete set of whole-chromosome oligonucleotide paints lays the foundation for future studies of the structure, organization, and evolution of genomes.
Low-moisture food matrices as probiotic carriers

To exert a beneficial effect on the host, adequate doses of probiotics must be administered and maintaining their viability until consumption is thus essential. Dehydrated probiotics exhibit enhanced long-term viability and can be incorporated into low-moisture food matrices, which also possess high stability at refrigeration and ambient temperature. However, several factors associated with the desiccation process, the physicochemical properties of the matrix and the storage conditions can affect probiotic survival. In the near future, an increased demand for probiotics based on functionally dominant members of the gut microbiome ('next-generation probiotics', NGP) is expected. NGPs are very sensitive to oxygen and efficient encapsulation protocols are needed. Strategies to improve the viability of traditional probiotics and particularly of NGPs involve the selection of a suitable carrier as well as proper desiccation and protection techniques. Dehydrated probiotic microcapsules may constitute an alternative to improve the microbial viability during not only storage but also upper gastrointestinal tract passage. Here we review the main dehydration techniques that are applied in the industry as well as the potential stresses associated with the desiccation process and storage. Finally, low- or intermediate-moisture food matrices suitable as carriers of traditional as well as NGPs will be discussed.
Development and In Vivo Evaluation of a κ-Opioid Receptor Agonist as a PET Radiotracer with Superior Imaging Characteristics

Studies have shown κ-opioid receptor (KOR) abnormalities in addictive disorders, other central nervous system diseases, and Alzheimer’s disease. We have developed the first set of agonist 11C-GR103545 and antagonist 11C-LY2795050 radiotracers for PET imaging of KOR in humans. Nonetheless, 11C-GR103545 displays protracted uptake kinetics and is not an optimal radiotracer. Here, we report the development and evaluation of 11C-methyl-(R)-4-(2-(3,4-dichlorophenyl)acetyl)-3-((diethylamino)methyl)piperazine-1-carboxylate (11C-EKAP) and its comparison with 11C-GR103545. Methods: EKAP was synthesized and assayed for in vitro binding affinities and then radiolabeled. PET studies were performed on rhesus monkeys. Blocking studies were performed with naloxone and the selective KOR antagonists LY2795050 and LY2456302. Arterial input functions were generated for use in kinetic modeling. Brain TACs were analyzed with multilinear analysis 1 to derive binding parameters. Results: EKAP has high KOR affinity (inhibition constant, 0.28 nM) and good selectivity in vitro. 11C-EKAP was prepared in good radiochemical purity. 11C-EKAP rapidly metabolized in plasma and displayed fast and reversible kinetics in brain, with peak uptake at less than 20 min after injection. Preblocking with naloxone (1 mg/kg) or LY2795050 (0.2 mg/kg) produced 84%–89% receptor occupancy, whereas LY2456302 (0.05 and 0.3 mg/kg) dose-dependently reduced 11C-EKAP–specific binding, thus demonstrating its binding specificity and selectivity in vivo. Mean multilinear analysis 1–derived nondisplaceable binding potential values were 1.74, 1.79, 1.46, 0.80, and 0.77 for cingulate cortex, globus pallidus, insula, striatum, and frontal cortex, respectively, consistent with the known KOR distribution in primate brains. Conclusion: We have successfully developed 11C-EKAP as a KOR agonist tracer with dual attractive imaging properties of fast uptake kinetics and high specific binding in vivo.
Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells

Dopamine-synthesizing neurons located in the mammalian ventral midbrain are at the center stage of biomedical research due to their involvement in severe human neuropsychiatric and neurodegenerative disorders, most prominently Parkinson’s Disease (PD). The induction of midbrain dopaminergic (mDA) neurons depends on two important signaling centers of the mammalian embryo: the ventral midline or floor plate (FP) of the neural tube, and the isthmic organizer (IsO) at the mid-/hindbrain boundary (MHB). Cells located within and close to the FP secrete sonic hedgehog (SHH), and members of the wingless-type MMTV integration site family (WNT1/5A), as well as bone morphogenetic protein (BMP) family. The IsO cells secrete WNT1 and the fibroblast growth factor 8 (FGF8). Accordingly, the FGF8, SHH, WNT, and BMP signaling pathways play crucial roles during the development of the mDA neurons in the mammalian embryo. Moreover, these morphogens are essential for the generation of stem cell-derived mDA neurons, which are critical for the modeling, drug screening, and cell replacement therapy of PD. This review summarizes our current knowledge about the functions and crosstalk of these signaling pathways in mammalian mDA neuron development in vivo and their applications in stem cell-based paradigms for the efficient derivation of these neurons in vitro.
Vaccinomics approach for developing multi-epitope peptide pneumococcal vaccine

Abstract Streptococcus pneumoniae is a leading cause of some diseases such as pneumonia, sepsis, and meningitis mostly in children less than 5 years of age. Presently, two types of pneumococcal vaccine are available on the market: polysaccharide vaccines (PPV) that are based on capsular polysaccharides of at least 92 different serotypes, and protein-conjugated polysaccharide vaccine (PCV). The PPVs such as PPV23 do not stimulate efficient protective immunity in children under 2 years old, while the PCVs such as PCV7, PCV10, and PCV13 that cover 7, 10, and 13 serotypes, respectively, highly protect newborns, but have some disadvantages such as complications in manufacturing, costly production, and also requires refrigeration and multiple injections. Epitope-based vaccines, including varied mixtures of conserved virulence proteins, are a promising alternative to the existing capsular antigen vaccines. In this study, it has been tried to design an efficient subunit vaccine in order to elicit both CTL and HTL responses. The immunodominant epitopes from highly protective antigens of S. pneumoniae (PspA, CbpA, PiuA, and PhtD) were selected from different databanks, such as IEDB, PROPRED, RANKPEP, and MHCPRED. The PspA and CbpA were chosen as CTL epitope stimulants, and PhtD and PiuA were defined as helper epitopes. Because of low immunogenicity of epitope vaccines, PorB protein as a TLR2 agonist was employed to increase the immunogenicity of the vaccine. All the peptide segments were fused to each other by proper linkers, and the physicochemical, structural, and immunological characteristics of the construct were also evaluated. To achieve a high-quality 3 D structure of the protein, modeling, refinement, and validation of the final construct were done. Docking and molecular dynamics analyses demonstrated an appropriate and stable interaction between the vaccine and TLR2 during the simulation period. The computational studies suggested the designed vaccine as a novel construct, capable to elicit efficient humoral and cellular immunities, which are crucial for protection against S. pneumoniae. Communicated by Ramaswamy H. Sarma
A novel probiotic, Lactobacillus johnsonii 456, resists acid and can persist in the human gut beyond the initial ingestion period

ABSTRACT Probiotics are considered to have multiple beneficial effects on the human gastrointestinal tract, including immunomodulation, pathogen inhibition, and improved host nutrient metabolism. However, extensive characterization of these properties is needed to define suitable clinical applications for probiotic candidates. Lactobacillus johnsonii 456 (LBJ 456) was previously demonstrated to have anti-inflammatory and anti-genotoxic effects in a mouse model. Here, we characterize its resistance to gastric and bile acids as well as its ability to inhibit gut pathogens and adhere to host mucosa. While bile resistance and in vitro host attachment properties of LBJ 456 were comparable to other tested probiotics, LBJ 456 maintained higher viability at lower pH conditions compared to other tested strains. LBJ 456 also altered pathogen adhesion to LS 174T monolayers and demonstrated contact-dependent and independent inhibition of pathogen growth. Genome analyses further revealed possible genetic elements involved in host attachment and pathogen inhibition. Importantly, we show that ingestion of Lactobacillus johnsonii 456 over a one week yogurt course leads to persistent viable bacteria detectable even beyond the period of initial ingestion, unlike many other previously described probiotic species of lactic acid bacteria.
Environmental Tobacco Smoke and Cardiovascular Disease

Environmental tobacco smoke (ETS) and its sequelae are among the largest economic and healthcare burdens in the United States and worldwide. The relationship between active smoking and atherosclerosis is well-described in the literature. However, the specific mechanisms by which ETS influences atherosclerosis are incompletely understood. In this paper, we highlight the definition and chemical constituents of ETS, review the existing literature outlining the effects of ETS on atherogenesis and thrombosis in both animal and human models, and briefly outline the public health implications of ETS based on these data.
Estrogen-Induced Apoptosis in Breast Cancers Is Phenocopied by Blocking Dephosphorylation of Eukaryotic Initiation Factor 2 Alpha (eIF2α) Protein

Approximately 30% of aromatase-inhibitor–resistant, estrogen receptor–positive patients with breast cancer benefit from treatment with estrogen. This enigmatic estrogen action is not well understood and how it occurs remains elusive. Studies indicate that the unfolded protein response and apoptosis pathways play important roles in mediating estrogen-triggered apoptosis. Using MCF7:5C cells, which mimic aromatase inhibitor resistance, and are hypersensitive to estrogen as evident by induction of apoptosis, we define increased global protein translational load as the trigger for estrogen-induced apoptosis. The protein kinase RNA-like endoplasmic reticulum kinase pathway was activated followed by increased phosphorylation of eukaryotic initiation factor-2 alpha (eIF2α). These actions block global protein translation but preferentially allow high expression of specific transcription factors, such as activating transcription factor 4 and C/EBP homologous protein that facilitate apoptosis. Notably, we recapitulated this phenotype of MCF7:5C in two other endocrine therapy–resistant cell lines (MCF7/LCC9 and T47D:A18/4-OHT) by increasing the levels of phospho-eIF2α using salubrinal to pharmacologically inhibit the enzymes responsible for dephosphorylation of eIF2α, GADD34, and CReP. RNAi-mediated ablation of these genes induced apoptosis that used the same signaling as salubrinal treatment. Moreover, combining 4-hydroxy tamoxifen with salubrinal enhanced apoptotic potency. Implications: These results not only elucidate the mechanism of estrogen-induced apoptosis but also identify a drugable target for potential therapeutic intervention that can mimic the beneficial effect of estrogen in some breast cancers.
Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut–liver axis

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut–liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.
Interleukin 34 (IL-34) cell-surface localization regulated by the molecular chaperone 78-kDa glucose-regulated protein facilitates the differentiation of monocytic cells

Interleukin 34 (IL-34) constitutes a cytokine that shares a common receptor, colony-stimulating factor-1 receptor (CSF-1R), with CSF-1. We recently identified a novel type of monocytic cell termed follicular dendritic cell-induced monocytic cells (FDMCs), whose differentiation depended on CSF-1R signaling through the IL-34 produced from a follicular dendritic cell line, FL-Y. Here, we report the functional mechanisms of the IL-34–mediated CSF-1R signaling underlying FDMC differentiation. CRIPSR/Cas9-mediated knockout of the Il34 gene confirmed that the ability of FL-Y cells to induce FDMCs completely depends on the IL-34 expressed by FL-Y cells. Transwell culture experiments revealed that FDMC differentiation requires a signal from a membrane-anchored form of IL-34 on the FL-Y cell surface, but not from a secreted form, in a direct interaction between FDMC precursor cells and FL-Y cells. Furthermore, flow cytometric analysis using an anti–IL-34 antibody indicated that IL-34 was also expressed on the FL-Y cell surface. Thus, we explored proteins interacting with IL-34 in FL-Y cells. Mass spectrometry analysis and pulldown assay identified that IL-34 was associated with the molecular chaperone 78-kDa glucose-regulated protein (GRP78) in the plasma membrane fraction of FL-Y cells. Consistent with this finding, GRP78-heterozygous FL-Y cells expressed a lower level of IL-34 protein on their cell surface and exhibited a reduced competency to induce FDMC differentiation compared with the original FL-Y cells. These results indicated a novel GRP78-dependent localization and specific function of IL-34 in FL-Y cells related to monocytic cell differentiation.
A cross-sectional study on eruption timing of primary teeth in children of Mysore, Karnataka

Context: Eruption of first primary teeth is the most anxiously awaited developmental milestone in a child. However, primary teeth have shown wide variations in their eruption time among different population, ethnic, and racial groups. Aims: The present study was conducted with the aim to evaluate the time and sequence of eruption of primary teeth of children of Mysore. Settings and Design: A cross-sectional study design included 1392 participants aged 3 months to 36 months recruited by simple random sampling method. The variables such as age, gender, and number of erupted primary teeth were recorded. Subjects and Methods: Clinical examination was done under natural illumination. A tooth was considered erupted when any part of its crown had penetrated the gingiva and was visible in the oral cavity. Statistical Analysis Used: Probit regression analysis was performed to obtain the mean and median age of eruption of teeth. The significance of difference in the mean age of eruption across gender and arch was determined using paired t-test. Results and Conclusion: The first primary tooth to erupt was mandibular central incisor at 10.24 ± 2.47 months followed by maxillary central incisor at 11.06 ± 2.65 months. The duration of primary teeth eruption was 17.89 and 18.32 months in males, 18.54 months and 18.32 months in females for maxilla and mandible, respectively. Eruption of primary tooth is delayed among children of Mysore as compared to standard eruption chart. The results will provide information to health professional about contemporary tooth eruption time derived from an Indian population.
What Are You Waiting For? Real-Time Integration of Cues for Fricatives Suggests Encapsulated Auditory Memory

Speech unfolds over time, and the cues for even a single phoneme are rarely available simultaneously. Consequently, to recognize a single phoneme, listeners must integrate material over several hundred milliseconds. Prior work contrasts two accounts: (a) a memory buffer account in which listeners accumulate auditory information in memory and only access higher level representations (i.e., lexical representations) when sufficient information has arrived; and (b) an immediate integration scheme in which lexical representations can be partially activated on the basis of early cues and then updated when more information arises. These studies have uniformly shown evidence for immediate integration for a variety of phonetic distinctions. We attempted to extend this to fricatives, a class of speech sounds which requires not only temporal integration of asynchronous cues (the frication, followed by the formant transitions 150-350 ms later), but also integration across different frequency bands and compensation for contextual factors like coarticulation. Eye movements in the visual world paradigm showed clear evidence for a memory buffer. Results were replicated in five experiments, ruling out methodological factors and tying the release of the buffer to the onset of the vowel. These findings support a general auditory account for speech by suggesting that the acoustic nature of particular speech sounds may have large effects on how they are processed. It also has major implications for theories of auditory and speech perception by raising the possibility of an encapsulated memory buffer in early auditory processing.
Bariatric Surgery Alters microRNA Content of Circulating Exosomes in Patients with Obesity

Exosomal microRNAs (miRNAs) are potential biomarkers for obesity, in which they regulate biological processes. Bariatric surgery has health benefits for patients with obesity; however, the mechanisms of these benefits are not clear. This study attempted to identify the exosomal miRNA signature associated with obesity and how it changed after bariatric surgery.
At-speed testing of SOC ICs

This paper discusses the aspects and associated requirements of design and implementation of at-speed scan testing. It also demonstrates some important vector generation and implementation procedures based on a real design. An innovative method of scan pattern timing creation based on the results from static timing analysis is presented. The paper also describes the usage of a clock control module on J750 tester, which creates fast clock by combining two tester channels with high edge placement accuracy. These methods allow a short test pattern preparation time and the use of low-cost test equipment, while providing the high quality at-speed testing.
H2AFZ, RNF4 and NR4A1 loci are associated with boar semen quality by population association studies

Abstract Spermatogenesis is a complex process regulated by many genes. In this study, H2AFZ, RNF4 and NR4A1 genes were selected as candidate genes for boar semen quality traits based on their functions during spermatogenesis, and the associations of three loci (H2AFZ c.192 + 210–192 + 213delCGAT, RNF4 c.374 + 358 T > C and NR4A1 c.956 + 796 A > G) with sperm quality traits were analyzed in Duroc (n = 185), Large White (n = 87) and Landrace (n = 49) pig populations. The results showed H2AFZ c.192 + 210–192 + 213delCGAT AA boars produced 1.52% lower abnormal sperm rate (ASR) than AB boars in Landrace pigs (p < 0.05); RNF4 c.374 + 358 TC boars produced 0.31 × 108/ml higher sperm concentration (SCON) than CC boars (p < 0.05) in Large White pigs; NR4A1 c.956 + 796 A > G was associated with ASR in Duroc and Large White pigs and was associated with sperm motility (MOT) in Large White and Landrace pigs. This study indicated the H2AFZ, RNF4 and NR4A1 loci were the potential molecular markers for improving the semen quality traits in boars.
Cognitive emotional processing across mood disorders

While impairments in cognitive emotional processing are key to the experience of mood disorders, little is understood of their shared and distinct features across major depressive disorder (MDD) and bipolar disorder (BD). In this review, we discuss the similarities and differences in abnormal emotional processing associated with mood disorders across the cognitive domains of perception, attention, memory, and reward processing, with a particular focus on how these impairments relate to the clinical profile of the disorders. We consider behavioral and neuroimaging evidence, especially that of the growing consensus surrounding mood-congruent biases in cognition, in combination with state- and trait-related characteristics in an attempt to provide a more comprehensive and translational overview of mood disorders. Special consideration is given to the shared phenomenon of mood instability and its role as a potential transdiagnostic marker across the prodrome and maintenance of mood disorders.