Transcriptional networks of transient cell states during human prefrontal cortex development

The human brain is divided into various anatomical regions that control and coordinate unique functions. The prefrontal cortex (PFC) is a large brain region that comprises a range of neuronal and non-neuronal cell types, sharing extensive interconnections with subcortical areas, and plays a critical role in cognition and memory. A timely appearance of distinct cell types through embryonic development is crucial for an anatomically perfect and functional brain. Direct tracing of cell fate development in the human brain is not possible, but single-cell transcriptome sequencing (scRNA-seq) datasets provide the opportunity to dissect cellular heterogeneity and its molecular regulators. Here, using scRNA-seq data of human PFC from fetal stages, we elucidate distinct transient cell states during PFC development and their underlying gene regulatory circuitry. We further identified that distinct intermediate cell states consist of specific gene regulatory modules essential to reach terminal fate using discrete developmental paths. Moreover, using in silico gene knock-out and over-expression analysis, we validated crucial gene regulatory components during the lineage specification of oligodendrocyte progenitor cells. Our study illustrates unique intermediate states and specific gene interaction networks that warrant further investigation for their functional contribution to typical brain development and discusses how this knowledge can be harvested for therapeutic intervention in challenging neurodevelopmental disorders

Fuzzy Closure Spaces vs. Fuzzy Rough Sets

AbstractThis paper investigates the relationship among fuzzy rough sets, fuzzy closure spaces and fuzzy topology. It is shown that there exists a bijective correspondence between the set of all fuzzy reflexive approximation spaces and the set of all quasi-discrete fuzzy closure spaces satisfying a certain extra condition. Similar correspondence is also obtained between the set of all fuzzy tolerance approximation spaces and the set of all symmetric quasi-discrete fuzzy closure spaces satisfying a certain extra condition

Circular Patch Antenna with Defected Ground for UWB Communication with WLAN Band Rejection

The design and performance of coplanar waveguide fed modified circular patch antenna for possible application in ultra wideband communication systems with band rejection for upper wireless local area network band (5.15 GHz - 5.85 GHz) is reported. This antenna is designed on glass epoxy FR4 substrate having size 30 mm × 20 mm × 1.59 mm. The coplanar waveguide fed circular patch antenna is modified by introducing L shaped slits in ground plane and U shaped slot in patch and performance analysis of antenna is simulated by applying CST microwave studio simulation software. Different designed antennas were tested with available experimental facilities. The developed end product shows a nice matching with feed network at frequencies 2.62 GHz, 3.94 GHz and 8.50 GHz and provides 10.38 GHz (3.33 GHz - 13.71 GHz) impedance bandwidth with wireless local area network 5.5 GHz (4.74 GHz - 6.15 GHz) band rejection. The co and cross polar patterns in elevation and azimuth planes at two frequencies namely 2.62 GHz and 3.94 GHz are obtained which dictate that co-polar patterns are significantly better than cross polar patterns. The simulated peak gain of antenna is close to 3.86 dBi and gain variation with frequency shows a sharp gain decrease in the frequency range 4.74 GHz to 6.15 GHz.

Polimorfizam gena za adiponektin (ADIPOQ) i njegova povezanost s proizvodnim i rasplodnim svojstvima indijskog mliječnog goveda

The present investigation was performed to explore the SNP in the promoter of the adiponectin (ADIPOQ) gene and its association with production and reproduction traits in Indian Sahiwal cows. A portion of the promoter (ADIPOQ) region of the ADIPOQ gene was amplified which revealed a 977 bp amplicon, and its PCR-RFLP assay with the restriction enzyme TasI revealed three genotypes, in which the CT genotype was the most frequent (62.32%), followed by CC (24.64%) and TT (13.04%). The frequency of the C and T alleles was 0.558 and 0.442, respectively. The ADIPOQ/TasI genotypes revealed a significant association with calving interval (CI) in the first and fourth lactations, in which the CC genotype showed a significantly (P<0.05) longer CI compared to the TT genotype, while in the fourth lactation the TT genotype showed a longer CI compared to the CC genotype. In the fourth lactation, the TT genotype showed a significantly (P<0.05) longer lactation period (LP) and greater total milk yield (TMY) as compared to CC and CT genotypes. In conclusion, the SNP identified in the promoter of the ADIPOQ gene and its association with production and reproduction traits suggests that this gene might serve as a candidate genetic marker for selection of dairy cattle with better milk yield. However, further studies are needed to explore these SNPs in other regions of this gene, and in other breeds and populations.Cilj ovoga rada bio je istražiti polimorfizam pojedinačnog nukleotida (SNP) u promotoru gena za adiponektin (ADIPOQ) i njegovu povezanost s proizvodnim i rasplodnim svojstvima indijskog goveda Sahiwal pasmine. Dio promotora (ADIPOQ) regije gena ADIPOQ je umnožen i prikazan produktom 977 bp, a PCR-RFLP metodom s restrikcijom enzimom TasI dobivena su tri genotipa. Među njima najčešći je bio CT genotip (62,32 %), zatim CC (24,64 %) i TT (13,04 %). Učestalost C-alela bila je 0,558, a T-alela 0,442. ADIPOQ/TasI genotipovi su pokazali znakovitu povezanost s međutelidbenim intervalom (CI) u prvoj i četvrtoj laktaciji u kojima je CC genotip pokazao znakovito duži interval između teljenja (P<0,05) u usporedbi s TT genotipom, dok je u četvrtoj laktaciji TT genotip pokazao duži interval teljenja u usporedbi s CC genotipom. U četvrtoj laktaciji TT genotip pokazao je znakovito duže trajanje laktacije (LP) (P<0,05) i ukupan prinos mlijeka (TMY) u usporedbi s CC i CT genotipovima. Zaključno, SNP identificiran u promotoru gena ADIPOQ i njegova povezanost s proizvodnim i reproduktivnim svojstvima upućuju na to da ovaj gen može poslužiti kao kandidatni genski biljeg za selekciju mliječnih krava s većim prinosom mlijeka. Potrebna su daljnja istraživanja polimorfizama pojedinačnih nukleotida u drugim regijama ovoga gena kao i u drugih pasmina i populacija

Antigiardial activity of novel triazolyl-quinolone-based chalcone derivatives:when oxygen makes the difference

Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an ‘anaerobic pathogen,’ G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100- fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds

The effect of lauric arginate on the thermal inactivation of starved Listeria monocytogenes in sous-vide cooked ground beef

The aim of this study was to examine the efficacy of lauric arginate (LAE, 1000 ppm – 3000 ppm) as an assisting tool to reduce starved Listeria monocytogenes population in ground beef following sous-vide processing at different temperatures (55–62.5 °C). Ground beef mixed with LAE was vacuum sealed and a laboratory water bath was used for sous-vide cooking. Loglinear and Weibull models were fit to the survival microbial population and the D and Z-values were determined at 55–62.5 °C. Calculated D-values ranged from 33.62 to 3.22 min at temperature 55–62.5 °C. LAE at higher concentration is an effective antimicrobial to increase the inactivation of the pathogen in sous-vide cooking. With the addition of LAE, D-values at 55 and 62.5 °C determined by the Loglinear model decreased from 31.86 to 2.28 min (LAE 1000 ppm) and 16.71 to 0.56 min (LAE 3000 ppm), respectively; whereas the D-values at 55 to 62.5 °C determined by the Weibull model were 44.26 and 2.09 min (LAE 1000 ppm) and 22.71 and 1.60 min (LAE 3000 ppm), respectively. This study shows that sous-vide processing of ground beef supplemented with higher concentration of LAE effectively inactivates L. monocytogenes and thus, helps increase the microbiological safety and product quality

A membrane protein of the rice pathogen Burkholderia glumae required for oxalic acid secretion and quorum sensing

Bacterial panicle blight is caused by Burkholderia glumae and results in damage to rice crops worldwide. Virulence of B. glumae requires quorum sensing (QS)-dependent synthesis and export of toxoflavin, responsible for much of the damage to rice. The DedA family is a conserved membrane protein family found in all bacterial species. B. glumae possesses a member of the DedA family, named DbcA, which we previously showed is required for toxoflavin secretion and virulence in a rice model of infection. B. glumae secretes oxalic acid as a “common good” in a QS-dependent manner to combat toxic alkalinization of the growth medium during the stationary phase. Here, we show that B. glumae ΔdbcA fails to secrete oxalic acid, leading to alkaline toxicity and sensitivity to divalent cations, suggesting a role for DbcA in oxalic acid secretion. B. glumae ΔdbcA accumulated less acyl-homoserine lactone (AHL) QS signalling molecules as the bacteria entered the stationary phase, probably due to nonenzymatic inactivation of AHL at alkaline pH. Transcription of toxoflavin and oxalic acid operons was down-regulated in ΔdbcA. Alteration of the proton motive force with sodium bicarbonate also reduced oxalic acid secretion and expression of QS-dependent genes. Overall, the data show that DbcA is required for oxalic acid secretion in a proton motive force-dependent manner, which is critical for QS of B. glumae. Moreover, this study supports the idea that sodium bicarbonate may serve as a chemical for treatment of bacterial panicle blight

PcG Proteins, DNA Methylation, and Gene Repression by Chromatin Looping

Many DNA hypermethylated and epigenetically silenced genes in adult cancers are Polycomb group (PcG) marked in embryonic stem (ES) cells. We show that a large region upstream (∼30 kb) of and extending ∼60 kb around one such gene, GATA-4, is organized—in Tera-2 undifferentiated embryonic carcinoma (EC) cells—in a topologically complex multi-loop conformation that is formed by multiple internal long-range contact regions near areas enriched for EZH2, other PcG proteins, and the signature PcG histone mark, H3K27me3. Small interfering RNA (siRNA)–mediated depletion of EZH2 in undifferentiated Tera-2 cells leads to a significant reduction in the frequency of long-range associations at the GATA-4 locus, seemingly dependent on affecting the H3K27me3 enrichments around those chromatin regions, accompanied by a modest increase in GATA-4 transcription. The chromatin loops completely dissolve, accompanied by loss of PcG proteins and H3K27me3 marks, when Tera-2 cells receive differentiation signals which induce a ∼60-fold increase in GATA-4 expression. In colon cancer cells, however, the frequency of the long-range interactions are increased in a setting where GATA-4 has no basal transcription and the loops encompass multiple, abnormally DNA hypermethylated CpG islands, and the methyl-cytosine binding protein MBD2 is localized to these CpG islands, including ones near the gene promoter. Removing DNA methylation through genetic disruption of DNA methyltransferases (DKO cells) leads to loss of MBD2 occupancy and to a decrease in the frequency of long-range contacts, such that these now more resemble those in undifferentiated Tera-2 cells. Our findings reveal unexpected similarities in higher order chromatin conformation between stem/precursor cells and adult cancers. We also provide novel insight that PcG-occupied and H3K27me3-enriched regions can form chromatin loops and physically interact in cis around a single gene in mammalian cells. The loops associate with a poised, low transcription state in EC cells and, with the addition of DNA methylation, completely repressed transcription in adult cancer cells

Mapping of Quantitative Trait Loci for Grain Iron and Zinc Concentration in Diploid A Genome Wheat

Micronutrients, especially iron (Fe) and zinc (Zn), are deficient in the diets of people in underdeveloped countries. Biofortification of food crops is the best approach for alleviating the micronutrient deficiencies. Identification of germplasm with high grain Fe and Zn and understanding the genetic basis of their accumulation are the prerequisites for manipulation of these micronutrients. Some wild relatives of wheat were found to have higher grain Fe and Zn concentrations compared with the cultivated bread wheat germplasm. One accession of Triticum boeoticum (pau5088) that had relatively higher grain Fe and Zn was crossed with Triticum monococcum (pau14087), and a recombinant inbred line (RIL) population generated from this cross was grown at 2 locations over 2 years. The grains of the RIL population were evaluated for Fe and Zn concentration using atomic absorption spectrophotometer. The grain Fe and Zn concentrations in the RIL population ranged from 17.8 to 69.7 and 19.9 to 64.2 mg/kg, respectively. A linkage map available for the population was used for mapping quantitative trait loci (QTL) for grain Fe and Zn accumulation. The QTL analysis led to identification of 2 QTL for grain Fe on chromosomes 2A and 7A and 1 QTL for grain Zn on chromosome 7A. The grain Fe QTL were mapped in marker interval Xwmc382-Xbarc124 and Xgwm473-Xbarc29, respectively, each explaining 12.6% and 11.7% of the total phenotypic variation and were designated as QFe.pau-2A and QFe.pau-7A. The QTL for grain Zn, which mapped in marker interval Xcfd31-Xcfa2049, was designated as QZn.pau-7A and explained 18.8% of the total phenotypic variatio