History of Small for Gestational Age at Birth With Verbal and Non-verbal Intelligence: A Case-Control Study Among Preschool Children.

Objective: Advances in technology and treatments have improved the survival rate of small for gestational age (SGA) infants that need more concern for their neurodevelopmental outcomes. In the present study, we hypothesized that a history of SGA may affect verbal and non-verbal intelligence indices among pre-school children. Materials and methods: A case-control study was conducted at the Tehran University of Medical Sciences (Tehran-Iran, 2020). Totally 232 children entered the study. An expert pediatrician examined all included subjects. Based on birth weight (extracted from medical records), participants were divided into the case (born SGA) and control (born Appropriate for gestational age (AGA)) groups. Wechsler Intelligence Scale (WISC) and Conners tests were implemented to assess intelligence quotient (IQ), verbal, attention, development, and executive functions. Finally, total scores were compared between groups. Results: Totally, 232 preschool children were included in the study. Of all, 114 (49.1%) and 118 (50.9%) subjects had the history of born SGA and AGA, respectively. The results related to WISC scores showed that the mean WISC-verbal score among children born SGA was significantly higher than children born AGA; (114.288±18.130 vs. 108.898±20.145; P=0.024). This significant difference was associated with Vocabulary (13.531±2.843 vs. 12.745±3.242; p=0.046) and Similarities (14.054±3.630 vs. 13.279±4.898; p=0.048) domains between the groups. The results related to different domains of the Conners test also showed that the mean scores of Inattention (B) and attention deficit hyperactive disorder score (D) in the case group were higher than these scores in the control group; however, these differences were not significant (4.929±3.511 vs. 4.906±4.300; p=0.495 &10.371±5.867 vs. 10.093±7.588; p=0.211). Conclusion: Our results indicated that the development of non-verbal intelligence in children born with SGA had been delayed. This finding shows that these children may need more consideration during the preschool period and after that.

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents.

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a-o was carried out using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a-o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 752.0 ± 2.0 µM). Structure-activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

Synthesis and in vitro urease inhibitory activity of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides, in silico and kinetic studies.

A series of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides were rationally designed and synthesized. All synthetic compounds were evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC50 values in the range of 0.94 - 6.78 µM as compared to the standard thiourea (IC50 = 22.50 µM). Compound 8g (IC50 = 0.94 µM) with a thiophene substituent at the R2 position was found to be the most active member of the series. Kinetic studies exhibited that the compound 8g was a non-competitive inhibitor. In silicostudy showed the critical interactions of potent inhibitors with the active site of the enzyme. These newly identified inhibitors of the urease enzyme can serve as leads for further research and development.

The Benefits of Unnatural Amino Acid Incorporation as Protein Labels for Single Molecule Localization Microscopy.

Single Molecule Localization Microscopy (SMLM) is an imaging method that allows for the visualization of structures smaller than the diffraction limit of light (~200 nm). This is achieved through techniques such as stochastic optical reconstruction microscopy (STORM) and photoactivated localization microscopy (PALM). A large part of obtaining ideal imaging of single molecules is the choice of the right fluorescent label. An upcoming field of protein labeling is incorporating unnatural amino acids (UAAs) with an attached fluorescent dye for precise localization and visualization of individual molecules. For this technique, fluorescent probes are conjugated to UAAs and are introduced into the protein of interest (POI) as a label. Here we contrast this labeling method with other commonly used protein-based labeling methods such as fluorescent proteins (FPs) or self-labeling tags such as Halotag, SNAP-tags, and CLIP-tags, and highlight the benefits and shortcomings of the site-specific incorporation of UAAs coupled with fluorescent dyes in SMLM.

A newly identified prophage-encoded gene, ymfM, causes SOS-inducible filamentation in Escherichia coli.

Rod-shaped bacteria such as Escherichia coli can regulate cell division in response to stress, leading to filamentation, a process where cell growth and DNA replication continues in the absence of division, resulting in elongated cells. The classic example of stress is DNA damage which results in the activation of the SOS response. While the inhibition of cell division during SOS has traditionally been attributed to SulA in E. coli, a previous report suggests that the e14 prophage may also encode an SOS-inducible cell division inhibitor, previously named SfiC. However, the exact gene responsible for this division inhibition has remained unknown for over 35 years. A recent high-throughput over-expression screen in E. coli identified the e14 prophage gene, ymfM, as a potential cell division inhibitor. In this study, we show that the inducible expression of ymfM from a plasmid causes filamentation. We show that this expression of ymfM results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in E. coli, SulA, SlmA and MinC. We confirm that ymfM is the gene responsible for the SfiC phenotype as it contributes to the filamentation observed during the SOS response. This function is independent of SulA, highlighting that multiple alternative division inhibition pathways exist during the SOS response. Our data also highlight that our current understanding of cell division regulation during the SOS response is incomplete and raises many questions regarding how many inhibitors there actually are and their purpose for the survival of the organism.Importance:Filamentation is an important biological mechanism which aids in the survival, pathogenesis and antibiotic resistance of bacteria within different environments, including pathogenic bacteria such as uropathogenic Escherichia coli Here we have identified a bacteriophage-encoded cell division inhibitor which contributes to the filamentation that occurs during the SOS response. Our work highlights that there are multiple pathways that inhibit cell division during stress. Identifying and characterising these pathways is a critical step in understanding survival tactics of bacteria which become important when combating the development of bacterial resistance to antibiotics and their pathogenicity.

The novel E. coli cell division protein, YtfB, plays a role in eukaryotic cell adhesion.

Characterisation of protein function based solely on homology searches may overlook functions under specific environmental conditions, or the possibility of a protein having multiple roles. In this study we investigated the role of YtfB, a protein originally identified in a genome-wide screen to cause inhibition of cell division, and has demonstrated to localise to the Escherichia coli division site with some degree of glycan specificity. Interestingly, YtfB also shows homology to the virulence factor OapA from Haemophilus influenzae, which is important for adherence to epithelial cells, indicating the potential of additional function(s) for YtfB. Here we show that E. coli YtfB binds to N'acetylglucosamine and mannobiose glycans with high affinity. The loss of ytfB results in a reduction in the ability of the uropathogenic E. coli strain UTI89 to adhere to human kidney cells, but not to bladder cells, suggesting a specific role in the initial adherence stage of ascending urinary tract infections. Taken together, our results suggest a role for YtfB in adhesion to specific eukaryotic cells, which may be additional, or complementary, to its role in cell division. This study highlights the importance of understanding the possible multiple functions of proteins based on homology, which may be specific to different environmental conditions.

High-throughput sequencing of sorted expression libraries reveals inhibitors of bacterial cell division.

BACKGROUND: Bacterial filamentation occurs when rod-shaped bacteria grow without dividing. To identify genetically encoded inhibitors of division that promote filamentation, we used cell sorting flow cytometry to enrich filamentous clones from an inducible expression library, and then identified the cloned DNA with high-throughput DNA sequencing. We applied the method to an expression library made from fragmented genomic DNA of uropathogenic E. coli UTI89, which undergoes extensive reversible filamentation in urinary tract infections and might encode additional regulators of division. RESULTS: We identified 55 genomic regions that reproducibly caused filamentation when expressed from the plasmid vector, and then further localized the cause of filamentation in several of these to specific genes or sub-fragments. Many of the identified genomic fragments encode genes that are known to participate in cell division or its regulation, and others may play previously-unknown roles. Some of the prophage genes identified were previously implicated in cell division arrest. A number of the other fragments encoded potential short transcripts or peptides. CONCLUSIONS: The results provided evidence of potential new links between cell division and distinct cellular processes including central carbon metabolism and gene regulation. Candidate regulators of the UTI-associated filamentation response or others were identified amongst the results. In addition, some genomic fragments that caused filamentation may not have evolved to control cell division, but may have applications as artificial inhibitors. Our approach offers the opportunity to carry out in depth surveys of diverse DNA libraries to identify new genes or sequences encoding the capacity to inhibit division and cause filamentation.

Analysis of stress distribution on fixation of bilateral sagittal split ramus osteotomy with resorbable plates and screws using the finite-element method.

PURPOSE: To determine the most appropriate stress distribution in fixation with resorbable screws and plates after bilateral sagittal split ramus osteotomy using the finite-element method. MATERIALS AND METHODS: This experimental study was performed on simulated human mandibles using computer software. The osteotomy line was applied to the simulated model and experimental loads of 75, 135, and 600 N were exerted on the model in accordance with the vector of occlusal force. The distribution pattern of stress was assessed and compared in 8 fixation methods: 1 resorbable screw, 2 resorbable screws in a vertical pattern, 2 resorbable screws in a horizontal pattern, 3 resorbable screws in an L pattern, 3 resorbable screws in a backward-L pattern, 1 miniplate with 2 screws, 1 miniplate with 4 screws, and 2 parallel miniplates with 4 screws each. RESULTS: Among the simulated fixations, 2 parallel miniplates showed the greatest primary stability and the single screw and the 2-hole miniplate showed the least tolerance to posterior forces. CONCLUSIONS: This study showed the 2-miniplate/4-hole plate pattern was the strongest and the single-screw and 2-hole plate patterns were the weakest of fixations in this bilateral sagittal split ramus osteotomy model. The finite-element method showed that polymer-based resorbable screws and plates (polyglycolic acid and d,l-polylactide acid) provide satisfactory primary stability in this model.