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The article cites a research study that examines the role of MiR- Par3L axis in breast cancer progression. It examined normal tissues and Par3L expressions in breast cancer tissues and cells. Par3L was found to be frequently down-regulated in human breast cancer cells and tissues and Par3L low-expression was associated with aggressive clinicopathological features and poor clinical outcome of breast cancer patients.

Although effluent treatment systems within pulp and paper mills remove many toxicants and improve wastewater quality, there is a need to understand and quantify the effectiveness of the treatment process. At a combined news and kraft pulp and paper mill in northwestern Ontario, Canada, fathead minnow (FHM) reproduction and physiology were examined before, during, and after a short-term (6-d) exposure to 10% (v/v) untreated kraft mill effluent (UTK), 25% (v/v) secondary treated kraft mill effluent (TK), and 100% (v/v) combined mill outfall (CMO). Although UTK exposure significantly decreased egg production, neither TK nor CMO caused any reproductive changes. The expression of six genes responsive to endocrine-disrupting compounds, stress, or metals was then examined in livers of these fish using real-time polymerase chain reaction. In female FHMs, none of the three effluents induced significant expression changes in any genes investigated. By contrast, in males there were significant increases in the mRNA levels of androgen receptor, estrogen receptor (ER) β, and cytochrome P4501A (CYP1A) upon UTK and TK exposure but no changes in ERα or vitellogenin (VTG) gene expression, whereas CMO exposure significantly increased the mRNA levels of ERα, VTG, and CYP1A. Together, these results suggest that kraft effluent before and after biological treatment contained compounds able to induce androgenic effects in FHMs, and that combination of kraft and newsmill effluents eliminated the androgenic compounds while inducing distinct and significant patterns of gene expression changes that were likely due to estrogenic compounds produced by the newsmill. Environ. Toxicol. Chem. 2010;29:430–439. © 2009 SETAC [ABSTRACT FROM AUTHOR]

Terminal B-cell differentiation is a multi-step process, from short-lived plasmablasts to mature long-lived plasma cells (PC). The anti-apoptotic Bcl-2 family member Bfl-1/A1 plays a critical role in the survival of mature B cells. However, its potential involvement at the later stages of B-cell development remains highly controversial. Our aim was thus to clarify the place of Bfl-1/A1 in the biology of normal PC and in the pathogenesis of multiple myeloma (MM), the major PC dyscrasia. Using gene expression profiling and quantifiable reverse transcription polymerase chain reaction experiments, we found a similar down-regulation of Bfl-1/A1 in both normal immature plasmablasts and mature PC when compared with B cells. In myeloma cells, the level of Bfl-1/A1 was low and Bfl-1/A1 was not a nuclear factor κB-inducible gene. Collectively, these data demonstrate that Bfl-1/A1 is not involved in the prolonged survival of normal mature PC, and that Bfl-1/A1 deregulation is not a common oncogenic event in MM. However, overexpression of Bfl-1/A1 by retroviral transduction promoted autonomous survival of an interleukin-6-dependent myeloma cell line and rendered it less sensitive to dexamethasone. Thus, Bfl-1/A1 transduction could be an interesting tool to obtain myeloma cell lines from primary samples and to favour the in vitro generation of antibody-secreting, long-lived normal PC. [ABSTRACT FROM AUTHOR]

Different transformation mechanisms have been proposed for elderly acute myeloid leukaemia (AML) and secondary AML (sAML) when compared with de novo AML or AML of younger patients. However, little is known regarding differences in the immunophenotypic profile of blast cells in these diseases. We systematically analysed, by flow cytometry, 148 patients affected by de novo (100 cases) or sAML (48 cases). By defining a cut-off level of 20% of CD34+ cells co-expressing CD90, the frequency of CD90+ cases was higher in sAML (40%) versus de novo AML (6%, P < 0·001), elderly AML (>60 years) (24%) versus AML of younger patients (10%, P = 0·010) and poor- versus good-risk karyotypes (according to the Medical Research Council classification, P < 0·001). The correlation between CD90 expression, sAML and unfavourable karyotypes was confirmed by analysing the subset of CD34+ AML cases alone (91/148). Consistently, univariate analysis showed that expression of CD90 was statistically relevant in predicting a shorter survival in CD90+ AML patients ( P = 0·042). Our results, demonstrating CD90 expression in AML with unfavourable clinical and biological features, suggest an origin of these diseases from a CD90-expressing haemopoietic progenitor and indicate the use of CD90 as an additional marker of prognostic value in AML. [ABSTRACT FROM AUTHOR]

Bispecific antibodies offer the possibility of improving effector-cell recruitment for antibody therapy. For this purpose, a recombinant bispecific single-chain Fv antibody (bsscFv), directed against Fc γRIII (CD16) and human leucocyte antigen (HLA) class II, was constructed and tested in functional assays. RNA from the hybridomas 3G8 and F3.3, reacting with CD16 and HLA class II, respectively, was used to generate phage display libraries. From these libraries, reactive phages were isolated and the bsscFv was constructed by connecting both single-chain Fv components through a 20 amino acid flexible linker. After expression in SF21 insect cells and chromatographic purification, the bsscFv bound specifically and simultaneously to both antigens. The affinities of the anti-CD16 and the anti-HLA class II scFv components of the bsscFv were 8·6 × 10−8 mol/l and 13·7 × 10−8 mol/l, respectively, which was approximately sevenfold lower than the F(ab) fragments of the parental antibodies. In antibody-dependent cellular cytotoxicity experiments with human mononuclear cells as effectors, the bsscFv-mediated specific lysis of both HLA class II-positive, malignant human B-lymphoid cell lines and primary cells from patients with chronic B-cell lymphocytic leukaemia. Optimal lysis was obtained at bsscFv concentrations of approximately 400 ng/ml, similar to the concentration required for maximum lysis by the corresponding chemically linked bispecific antibody. Thus, this recombinant bsscFv-antibody is an efficient molecule for effector-cell mediated lysis of malignant human B-lymphoid cells. [ABSTRACT FROM AUTHOR]

The mechanisms by which mutations within the 5′ untranslated region (UTR) of the human β-globin gene ( HBB) cause thalassaemia are currently not well understood. We present here the first comprehensive comparative functional analysis of four ‘silent’ mutations in the human β-globin 5′UTR, namely: +10(−T), +22(G → A), +33(C → G) and +(40–43)(−AAAC), which are present in patients with β-thalassaemia intermedia. Expression of these genes under the control of the β-globin locus control region in stable transfected murine erythroleukaemia cells showed that all four mutations decreased steady state levels of mRNA to 61·6%, 68%, 85·2% and 70·6%, respectively, compared with the wildtype gene. These mutations did not interfere with either mRNA transport from the nucleus to the cytoplasm, 3′ end processing or mRNA stability. Nuclear run-on experiments demonstrated that mutations +10(−T) and +33(C → G) reduced the rate of transcription to a degree that fully accounted for the observed lower level of mRNA accumulation, suggesting a disruption of downstream promoter sequences. Interestingly, mutation +22(G → A) decreased the rate of transcription to a low degree, indicating the existence of a mechanism that acts post-transcriptionally. Generally, our data demonstrated the significance of functionally analysing mutants of this type in the presence of a full complement of transcriptional regulatory elements within a stably integrated chromatin context in an erythroid cell environment. [ABSTRACT FROM AUTHOR]

Neutrophils from patients with chronic myeloid leukaemia (CML) have an aberrant expression of leukotriene (LT)C4 synthase. In order to learn more about the regulation of this abnormality, LTC4 synthase mRNA expression was determined by reverse transcription polymerase chain reaction. A digoxigenin (DIG)-labelled LTC4 synthase RNA was synthesized and incubated in cytsolic extracts from CML neutrophils, normal neutrophils and eosinophils. LTC4 synthase mRNA was detected in total but not cytoplasmic RNA from normal neutrophils. In contrast, LTC4 synthase mRNA was found in the cytoplasm of CML neutrophils and in normal eosinophils, which also express the enzyme. The DIG-labelled LTC4 synthase RNA was, as opposed to normal neutrophils, degraded in cytosolic extracts from CML neutrophils. The degradation was time dependent and cell concentration dependent. Degradation was also seen in eosinophils, indicating that degradation of LTC4 synthase RNA was correlated to the expression of the protein. This study showed that the difference in expression of LTC4 synthase in normal and CML neutrophils was not because of a total lack of LTC4 synthase mRNA in normal neutrophils. However normal neutrophils lack, in contrast to CML neutrophils, LTC4 synthase mRNA in the cytoplasm. This discrepancy is not caused by a stabilized LTC4 synthase RNA in the cytosol of CML neutrophils. Instead an abnormal degradation of LTC4 synthase RNA was found in the cytosol of CML neutrophils. [ABSTRACT FROM AUTHOR]

Budd–Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently associated with polycythaemia vera (PV). In an attempt to elucidate the mechanisms of BCS/PVT secondary to PV (T-PV), CD11b neutrophil expression, neutrophil oxidative burst and platelet–neutrophil complexes (PNC) were assessed in 17 such patients. Three groups served as controls: BCS/PVT not secondary to PV (T-nPV; n = 20), PV without thrombosis (PV-nT; n = 16), and healthy controls (HC; n = 20). Baseline CD11b expression (in mean fluorescence intensity units) was 101 [95% confidence interval (CI): 79–128] in T-PV patients, versus 25 (95% CI: 18–35) in T-nPV, 59 (95% CI: 43–80) in PV-nT, and 34 (95% CI: 25–48) in HC ( P < 0·001). After N-formyl- L-methionyl- L-leucyl- L-phenylalanine activation, T-PV patients also showed higher CD11b values: 190 (95% CI: 151–238), versus 55 (95% CI: 41–72) in T-nPV, 111 (95% CI: 81–153) in PV-nT, and 77 (95% CI: 63–95) in HC ( P < 0·001). In BCS/PVT, CD11b neutrophil expression had 90% specificity and 100% sensitivity for the association with PV. Finally, PV patients had higher oxidative burst and PNC than T-nPV patients or HC ( P < 0·05). These results support a role for neutrophils in BCS/PVT secondary to PV and indicate that neutrophil CD11b expression could be of use for PV screening in BCS/PVT patients. [ABSTRACT FROM AUTHOR]

Sir2 is an NAD-dependent histone deacetylase that functions in longevity, gene silencing, heterochromatin formation, DNA repair, and suppression of DNA recombination in yeast. The mammalian homolog Sir2α (SIRT1) has been shown to inhibit p53-dependent apoptosis, but its physiological roles are still not known. We found that the level of Sir2α expression during embryogenesis was high. The highest Sir2α mRNA expression was detected as early as embryonic day (E) 4.5. Although the level was down-regulated during embryogenesis, a high level of expression was still found in the late embryonic stage (E18.5). In embryos, Sir2α was expressed at high levels in the heart, brain, spinal cord, and dorsal root ganglia. The expression levels in these organs were high on E10.5–E13.5 and low on E16.5. Quantitative reverse transcription polymerase chain reaction showed a 60% reduction in Sir2α mRNA content in the heart between E12.5 and E14.5. After E14.5, the expression level in the heart remained constant up to 27 months of age. The expression pattern of Sir2α protein in embryonic hearts was consistent with that of mRNA. These results suggest new roles of Sir2α not only in early embryogenesis but also in cardiogenesis and neurogenesis with a stage-specific manner. [Copyright &y& Elsevier]

In contrast to the human genome, the mouse genome contains two HEPC genes encoding hepcidin, a key regulator of iron homeostasis. Here we report a comparative analysis of sequence, genomic structure, expression and iron regulation of mouse HEPC genes. The predicted processed 25 amino acid hepcidin 2 peptide share 68% identity with hepcidin 1 with perfect conservation of eight cysteine residues. Both HEPC1 and HEPC2 genes have similar genomic organization and have probably arisen from a recent duplication of chromosome 7 region, including the HEPC ancestral gene and a part of the adjacent USF2 gene. Insertion of a retroviral intracisternal A-particle element was found upstream of the HEPC1 gene. Both genes are highly expressed in the liver and to a much lesser extent in the heart. In contrast to HEPC1, a high amount of HEPC2 transcripts was detected in the pancreas. Expression of both genes was increased in the liver during carbonyl–iron and iron–dextran overload. Overall our data suggest that both HEPC1 and HEPC2 genes are involved in iron metabolism regulation but could exhibit different activities and/or play distinct roles. [Copyright &y& Elsevier]

Objective: To evaluate the impact of early treatment and IL1RN genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (JIA). Methods: Response to anakinra was defined as achievement of clinically inactive disease (CID) at 6 months without glucocorticoid treatment. Demographic, clinical, and laboratory characteristics of 56 patients were evaluated in univariate and multivariate analyses as predictors of response to treatment. Six single‐nucleotide polymorphisms (SNPs) in the IL1RN gene, previously demonstrated to be associated with a poor response to anakinra, were genotyped by quantitative polymerase chain reaction (qPCR) or Sanger sequencing. Haplotype mapping was performed with Haploview software. IL1RN messenger RNA (mRNA) expression in whole blood from patients, prior to anakinra treatment initiation, was assessed by qPCR. Results: After 6 months of anakinra treatment, 73.2% of patients met the criteria for CID without receiving glucocorticoids. In the univariate analysis, the variable most strongly related to the response was disease duration from onset to initiation of anakinra treatment, with an optimal cutoff at 3 months (area under the curve 84.1%). Patients who started anakinra treatment ≥3 months after disease onset had an 8‐fold higher risk of nonresponse at 6 months of treatment. We confirmed that the 6 IL1RN SNPs were inherited as a common haplotype. We found that homozygosity for ≥1 high‐expression SNP correlated with higher IL1RN mRNA levels and was associated with a 6‐fold higher risk of nonresponse, independent of disease duration. Conclusion: Our findings on patients with systemic JIA confirm the important role of early interleukin‐1 inhibition and suggest that genetic IL1RN variants predict nonresponse to therapy with anakinra. [ABSTRACT FROM AUTHOR]

Details a study which examined the accumulation of H2O2 within the leaf mesophyll of Populus tremuloides aspen genotypes and seedlings of paper birch Betula papyrifera. Gene expression of catalase; Effects of ozone and carbon dioxide on the structure of ozone-tolerant aspen; Correlation between aspen clones, elevated ozone, birch and peroxisomes levels.

The use of artificial zinc finger chimeras to manipulate the expression of a gene of interest is a promising approach because zinc finger proteins can be engineered to bind any given DNA sequence in the genome. We have previously shown that a zinc finger chimera with a VP16 activation domain can activate a reporter gene in transgenic Arabidopsis thaliana (Sánchez, J.P., Ullman, C., Moore, M., Choo, Y. and Chua, N.H. (2002) Regulation of gene expression in Arabidopsis thaliana by artificial zinc finger chimeras. Plant Cell Physiol. 43, 1465–1472). Here, we report the use of artificial zinc finger chimeras to specifically regulate the 4-coumarate:coenzyme-A ligase-1 ( At4CL1) gene in A. thaliana. At4CL1 is a key enzyme in lignin biosynthesis and the down-regulation of At4CL1 can lead to a decrease in lignin content, which has a significant commercial value for the paper industry. To this end, we designed zinc finger chimeras containing either an activation or a repression domain, which bind specifically to the At4CL1 promoter region. Transgenic lines expressing a zinc finger chimera with the VP16 activation domain showed an increase in At4CL1 expression and enzyme activity. In contrast, transgenic lines expressing a chimera with the KOX (KRAB) repression domain displayed repression of At4CL1 expression and enzyme activity. The activation of At4CL1 expression produced an increase in lignin content, and transgenic plant stems showed ectopic lignin distribution. Repression of the At4CL1 gene resulted in reduced lignin content, and lignin distribution in transgenic stems was severely diminished. Our results confirm and extend previous studies of gene regulation using various artificial zinc finger chimeras in animal and plant systems, and show that this system can be used to up- and down-regulate the expression of an endogenous plant gene such as At4CL1. [ABSTRACT FROM AUTHOR]

During its first decade of life, Physiological Reports has become a home for well‐conceived and rigorously performed exercise physiology and metabolism studies. The breadth of research within this area is impressive, covering exercise‐induced increases in skeletal muscle gene expression to the effects of exercise on the gut microbiome. The purpose of the current review is to highlight some of the impactful exercise physiology and metabolism papers published in the journal and to look ahead to what areas exercise physiology publications might address in the next 10 years. [ABSTRACT FROM AUTHOR]

Hundreds of microbiota gene expressions are significantly different between healthy and diseased humans. The "bottleneck" preventing a mechanistic dissection of how they affect host biology/disease is that many genes are encoded by nonmodel gut commensals and not genetically manipulatable. Approaches to efficiently identify their gene transfer methodologies and build their gene manipulation tools would enable mechanistic dissections of their impact on host physiology. This paper will introduce a step‐by‐step protocol to identify gene transfer conditions and build the gene manipulation tools for nonmodel gut microbes, focusing on Gram‐negative Bacteroidia and Gram‐positive Clostridia organisms. This protocol enables us to identify gene transfer methods and develop gene manipulation tools without prior knowledge of their genome sequences, by targeting bacterial 16s ribosomal RNAs or expanding their compatible replication origins combined with clustered regularly interspaced short palindromic repeats machinery. Such an efficient and generalizable approach will facilitate functional studies that causally connect gut microbiota genes to host diseases. Highlights: A protocol introducing a step‐by‐step genetic manipulation method would facilitate the investigation of those functional genes encoded by nonmodel gut commensals.The gene‐editing tools could be established in nonmodel gut Bacteroidia and Clostridia without prior knowledge of their genome information.The genetic manipulation pipeline may serve as a high‐throughput genetics screening and manipulating platform for human gut microbes. [ABSTRACT FROM AUTHOR]

In biological systems, impulses are often used to model mutations in gene expression. In order to describe the instantaneity of the impulse, this paper employs a hybrid‐index model of impulsive Boolean networks with state‐triggered impulses. Based on this model, the time‐domain output controllability is investigated. Using the quotient mapping method, the hybrid‐domain solutions of this model are mapped to the time‐domain solutions, mathematically. Then a necessary and sufficient condition for output controllability in the time domain is presented. Finally, an example is given to demonstrate the correctness and effectiveness of the obtained results. [ABSTRACT FROM AUTHOR]

Lists the forthcoming research articles published in the September 15, 1992 issue of the "European Journal of Biochemistry." "Stoichiometry of interaction between interferon y and its receptor" by M. Fountoulakis, M. Zulauf, A. Lustig and G. Garotta; "Leukotriene uptake by hepatocytes and hepatoma cells" by I. Leier, M. Muller, G. Jedlitschky and D. Keppler; "Regulation of insulin-like-growth-factor-II gene expression in rat liver cells" R. Zarrilli, V. Colantouni and C. B. Bruni; "NMR study of the solution conformation of actionmycin D," by C. Yu, Y.-Y. Tseng.

Background: It has been reported that programmed death‐ligand 1 (PD‐L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD‐L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD‐L1 in condyloma acuminatum. Methods: The expression of PD‐L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11‐E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD‐L1. The successfully constructed HPV11‐E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit‐8 (CCK‐8) assays. Results: PD‐L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11‐E7 could upregulate the expression of PD‐L1 in HaCaT cells. Furthermore, HPV11‐E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD‐1/PD‐L1 signalling pathway. Conclusions: HPV infection may upregulate PD‐L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T‐cell function. [ABSTRACT FROM AUTHOR]

Background: Sea urchins are model organisms for studying the spatial‐temporal control of gene activity during development. The Southern California species, Lytechinus pictus, has a sequenced genome and can be raised in the laboratory from egg to egg in 4 to 5 months. Results: Here, we present new techniques for generating parthenogenetic larvae of this species and include a gallery of photomicrographs of morphologically abnormal larvae that could be used for transcriptomic analysis. Conclusions: Comparison of gene expression in parthenogenotes to larvae produced by fertilization could provide novel insights into gene expression controls contributed by sperm in this important model organism. Knowledge gained from transcriptomics of sea urchin parthenogenotes could contribute to parthenogenetic studies of mammalian embryos. Key Findings: Our paper reintroduces the potential value of studying parthenogenotes since the last such paper was published 46 years ago, before transcriptomics existed.This paper describes the simple culture of Lytechinus pictus in petri plates in the absence of large quantities of seawater and continuous stirring motors.This paper provides the first photomicrographs of parthenogenetic sea urchin larvae in the developmental biology literature.Studying transcriptomics in these parthenogenotes might illuminate controls the sperm genome contributes to gene activation during development.Processes such as the activation of protein and DNA synthesis would also be interesting to study in parthenogenote sea urchin embryos and larvae. [ABSTRACT FROM AUTHOR]

Lists forthcoming papers published on the January 12, 1990 issue of the "European Journal of Biochemistry." "Distance between the substrate and regulatory reduced coenzyme binding sites of bovine liver glutamate dehydrogenase by resonance energy transfer," by R. H. Lark and R. F. Colman; Mechanism of glucocorticoid regulation of alkaline phosphatase gene expression in osteoblast-like cells," by E. Green, B. Todd and D. Heath; "Use of fragments of hirudin to investigate thrombin-hirudin interaction," by S. Dennis, A. Wallace, J. Hofsteenge and S. R. Stone; "Acute stimulation by lutropin of mitochondrial protein synthesis in small luteal cells," by H. Mittre, P. Aunai, A. Benhaim and P. Leymarie.

Lists papers to be published in the "European Journal of Biochemistry" after January 1987. "Expression of bovine pancreatic ribonuclease A in Escherichia coli," by K.P. Nambiar, et al; "Phenobarbital-mediated modulation of gene expression in rat liver — Analysis of cDNA clones; "Complete amino-acid sequence of the natural ATPase inhibitor from the mitochondria of the yeast Candida utilis.

Nourishment can have profound effects on social behaviour, including aggressive interactions between individuals. The prevailing theoretical and empirical understanding is that when nutritional resources are limited, inter‐individual competition and aggression will increase. Alternatively, studies from some group‐living species suggest limited nutrition can lead to increased cooperation, including by a reduction in inter‐individual aggression. Thus, a general model for understanding how and why nutritional resource limitation affects aggressive behaviour remains elusive.We suggest that the link between nourishment and future reproductive potential may be a key missing element of models that predict how nutritional resource availability affects inter‐individual aggression in social animals.We investigated how nourishment influenced intra‐colony aggression and its molecular correlates in colonies of the social paper wasp Polistes fuscatus, which contain workers that maintain flexible reproductive potential as adults. We subjected colonies to either a high or low feeding treatment, and examined subsequent effects on behaviour, nutritional/reproductive physiology and brain gene expression.We found that nutritional restriction reduced aggressive interactions. Thus, resource limitation was linked to reduced intra‐group conflict. Thus, individual worker paper wasps appear to have the capacity to adjust their behaviour (e.g. reduced aggression) in response to nutritional stress; this suggests they may invest nutritional resources in the colony when resources are limiting, and in the self (and possible future reproduction) when resources are abundant.Differential brain gene expression results implicate two well‐known neuropeptides associated with aggression and/or nutrient signalling across taxa, Tachykinin and Neuropeptide F, as possible mediators of nutritionally dependent intra‐colony aggression. This adds to a growing understanding that deeply conserved genes associated with core, conserved behaviours such as feeding and aggression in solitary insects can play a role in the regulation of social plasticity in more highly social species. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Neurosteroidogenesis in astrocytes is crucial for the proper development and functioning of the brain. During this process, key neurohormones such as progesterone (P4), testosterone (T), and estradiol (E2) are produced. Proper production and release of neurosteroids can be affected by substances referred to as endocrine‐disrupting compounds (EDCs). Tris‐(2,3‐dibromopropyl)isocyanurate (TBC) is a representative of novel brominated flame retardants used to stop ignition or reduce fire‐related property damage to plastics, polyolefin, polyphenyl alkene, unsaturated polyester, synthetic rubber, and fibers. Interestingly, previous studies have shown that TBC can enhance the proliferation of estradiol‐sensitive breast cancers in vitro, which suggests that TBC has EDC properties. Therefore, given the suspected endocrine‐disrupting properties of TBC, the aim of the present study was to determine the impact of TBC on the neurosteroid (P4, T, and E2) production and secretion as well as the mRNA expression of key enzymes involved in its production in mouse astrocytes in vitro. Our paper shows that TBC increases P4 production with a strong decrease in T production, which is accompanied by a decrease in Cyp17a1 mRNA expression, that is, the main enzyme metabolizing P4 to T. Moreover, TBC in both studied concentrations increases P4 secretion in the culture medium. Finally, our studies have demonstrated an increase in the expression of Cyp19a1 mRNA, an enzyme metabolizing T to E2, with a simultaneous increase in the amount of E2 in cells. Our data clearly show that TBC in an in vitro environment acts as EDCs, which may lead to serious consequences for the proper development and functioning of the brain. The aim of the present study was to determine the impact of tris‐(2,3‐dibromopropyl)isocyanurate on the neurosteroid production and secretion as well as the mRNA expression of key enzymes of steroidogenesis. Our paper shows that tris‐(2,3‐dibromopropyl)isocyanurate increases progesterone production with a decrease in testosterone production, which is accompanied by a decrease in Cyp17a1 mRNA expression. Tris‐(2,3‐dibromopropyl)isocyanurate increases progesterone secretion in the culture medium. Tris‐(2,3‐dibromopropyl)isocyanurate increases the expression of Cyp19a1 mRNA with a simultaneous increase in the amount of estradiol in cells. [ABSTRACT FROM AUTHOR]

GRAPH Tom is a Guest Coeditor of this special issue on gene regulatory network evolution. My PhD research was done under the mentorship of Dr. Jeffrey Innis and focused on Hox genes in human disease and in a gene regulatory network responsible for mouse limb development. CREs far outnumber the genes in animal genomes and allow genes to be expressed in multiple cell types, different life stages, and even varied ecological contexts. [Extracted from the article]

The article titled "Corrigendum to: A Hill type equation can predict target gene expression driven by p53 pulsing" contains an error in Equation 18. The corrected equation is provided in the document. It is important to note that this change does not impact the results of the paper. [Extracted from the article]

Various reviews and meta‐analyses have shown the positive effects of mindfulness‐based interventions (MBIs) on the mental health of cancer patients and survivors. Some studies have also investigated the impact of MBIs on physiological markers of health in oncology, but a systematic review has not been conducted in this field. The current paper aims to fill this gap in the literature. Following preferred reporting items for systematic reviews and meta‐analyses 2020 guidelines, data were obtained from the databases of Pubmed, Scopus, Web of Science in May 2022. Twenty‐five studies were included. Globally, 35 biomarkers were employed in these studies and were categorized 8 groups (cortisol; blood pressure (BP), heart rate, and respiratory rate; C‐reactive protein; telomere length and telomerase activity (TA); genetic signature; cytokines and hormones; leucocyte activation; leucocyte count and cell subpopulation analysis). In seven of these categories of biomarkers, positive effects of MBIs were observed. The most promising results were obtained for cortisol, BP, TA and pro‐inflammatory gene expression. However, the generally low number of studies per single biomarker limits the possibility to draw reliable conclusions. The present review presents a comprehensive state‐of‐the‐art for MBIs in oncology on biomarkers, confirming MBIs' potential for improving physiological health in cancer patients and survivors besides those already shown in literature on psychological well‐being. [ABSTRACT FROM AUTHOR]

The hedgehog signaling pathway plays an important role in early development and growth of most vertebrates. Sonic hedgehog (shh) gene is a critical regulator of embryonic development in many species, including humans. However, it is not clear what roles shh can play in the development of fish. In this paper, shh gene was cloned from Pseudopleuronectes yokohamae. The full‐length complementary DNA (cDNA) of P. yokohamae sonic hedgehog gene (Pyshh) comprises 3194 bp, with a 1317‐bp open reading frame (ORF) that encodes a polypeptide of 438 amino acids with a typical HH‐signal domain and Hint‐N domain. The conserved sequences of the protein among species were predicted by using multiple sequence comparison. The phylogenetic tree construction showed that PySHH is clustered in a branch of Pleuronectidae. To explore the expression of Pyshh gene in various tissues of P. yokohamae, we used real‐time fluorescence quantitative PCR technology to detect it. The results showed that Pyshh gene is widely distributed in various tissues of P. yokohamae juveniles, different tissues of adult males and females, and is particularly expressed in immune organs. The Pyshh gene expression was higher in the muscle and brain of juvenile fish, and higher in bone, gill, and skin of male fish than that of female fish, suggesting that Pyshh might be involved in the formation of immune organs of P. yokohamae. The expression of Pyshh gene significantly upregulated from the gastrula stage to the hatching stage. Western blotting of the expression levels of PySHH during different embryonic development stages revealed that PySHH levels increased gradually during development stages from oosperm stage to hatching stage. These results indicate that Pyshh is highly conserved among species and plays a critical role in the complex process of embryonic development. Its precise regulation is essential for the proper formation of many organs and tissues in the body, and disruptions in its function may have serious consequences for the formation of immune organs in fish. [ABSTRACT FROM AUTHOR]

Objective: This narrative review illuminates on the application of single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST) in periodontitis and highlights the probability of relating cell population and gene signatures to the pathogenesis of the disease for a better diagnosis. Methods: An electronic search of the literature in the PubMed database for the keywords, "single cell sequencing" OR "spatial transcriptomics" and "periodontitis" OR "gingiva" OR "oral mucosa" yielded 486 research articles and reviews. After filtering duplicates and careful curation, 22 papers conducted in humans were retained. Results: The molecular mechanisms underlying periodontitis are complex and involve the interaction of multiple cells and various gene expressions. Most residing cells in periodontal tissues participate in maintaining homeostasis and health, while in addition to infiltrating immune cells contribute to the fight against the bacterial insult. Conclusion: scRNA‐seq and ST have provided new insights into the cellular and molecular changes associated with periodontitis for a better diagnosis and clinical outcome. New functions of cells and genes are revealed with these techniques; however, no cells or gene signatures are attributed to periodontitis so far. [ABSTRACT FROM AUTHOR]

Lists articles about biochemistry. "A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1, " by M.S. Erard et al; "A mathematical model of the Calvin photosynthesis cycle," by G. Pettersson et al; Import of proteins into mitochondria: a multi-step process," by N. Pfanner et al; "Hyper-regulation of pyr gene expression in Escherichia coli cells with slow ribosomes-Evidence for RNA polymerase pausing in vivo?" by K.F. Jensen; "Effect of intracellular pH and potassium ions on a primary transport system for glutamate aspartate in Streptococcus mutans," by S. Noji et al; Others.

Accurate cancer diagnosis especially early diagnosis is of great importance for prompt therapy and elevated survival rate. mRNAs are widely used as biomarkers for cancer identification and treatment. mRNA expression levels are highly associated with cancer stage and malignant progression. Nevertheless, single type mRNA detection is insufficient and unreliable. Herein, we developed a DNA nano‐windmill probe for in situ multiplexed mRNAs detection and imaging in this paper. The probe is designed to simultaneously target four types of mRNA through wind blades. Importantly, recognition of targets is independent from each other, which further facilitate cell type discrimination. The probe can specifically distinguish cancer cell lines from normal cells. In addition, it can identify changes in mRNA expression levels in living cells. The current strategy enriches the toolbox for improving the accuracy of cancer diagnosis and therapeutic solutions. [ABSTRACT FROM AUTHOR]

Summary: Circadian clocks are 24‐h endogenous oscillators in physiological and behavioral processes. Though recent transcriptomic studies have been successful in revealing the circadian rhythmicity in gene expression, the power calculation for omics circadian analysis have not been fully explored. In this paper, we develop a statistical method, namely CircaPower, to perform power calculation for circadian pattern detection. Our theoretical framework is determined by three key factors in circadian gene detection: sample size, intrinsic effect size and sampling design. Via simulations, we systematically investigate the impact of these key factors on circadian power calculation. We not only demonstrate that CircaPower is fast and accurate, but also show its underlying cosinor model is robust against variety of violations of model assumptions. In real applications, we demonstrate the performance of CircaPower using mouse pan‐tissue data and human post‐mortem brain data, and illustrate how to perform circadian power calculation using mouse skeleton muscle RNA‐Seq pilot as case study. Our method CircaPower has been implemented in an R package, which is made publicly available on GitHub (https://github.com/circaPower/circaPower). [ABSTRACT FROM AUTHOR]

Feature screening is a useful and popular tool to detect informative predictors for ultrahigh‐dimensional data before developing statistical analysis or constructing statistical models. While a large body of feature screening procedures has been developed, most methods are restricted to examine either continuous or discrete responses. Moreover, even though many model‐free feature screening methods have been proposed, additional assumptions are imposed in those methods to ensure their theoretical results. To address those difficulties and provide simple implementation, in this paper we extend the rank‐based coefficient of correlation to develop a feature screening procedure. We show that this new screening criterion is able to deal with continuous and binary responses. Theoretically, the sure screening property is established to justify the proposed method. Simulation studies demonstrate that the predictors with nonlinear and oscillatory trajectories are successfully retained regardless of the distribution of the response. Finally, the proposed method is implemented to analyze two microarray datasets. [ABSTRACT FROM AUTHOR]

Epigallocatechin‐3‐gallate (EGCG) is a major bioactive compound in tea polyphenol extract. After ingestion, EGCG reaches the intestine and may commence anti‐inflammation in the intestinal organ. Thus, in this paper, the anti‐inflammatory effect of EGCG was studied using lipopolysaccharide (LPS)‐induced inflammation in RAW 264.7 cells. LPS induction instigated morphological deformation extensively which was normalized by EGCG. In LPS‐induced macrophage cells, EGCG was found to lower cellular nitric oxide (32% of LPS group) and intercellular ROS level (45.4% of LPS group). It also suppressed the expression of IL‐1β (LPS 132.6 ± 14.6, EGCG 10.67 ± 3.65), IL‐6 (LPS 2994.44 ± 178.5, EGCG 408.33 ± 52.34), TNF‐α (LPS 27.11 ± 2.84, EGCG 1.22 ± 0.03), and iNOS (LPS 40.45 ± 11.17, EGCG 10.24 ± 0.89). The GO function analysis identified that these differential genes involved 24 biological processes, 18 molecular functions, and 19 cellular component‐related processes. KEGG pathway enrichment analysis revealed that LPS significantly affects NF‐κB, TNF, and TLR signaling pathways. Western blotting revealed that EGCG diminished P‐IκB/IκB ratio by 75% and p‐p65/p65 by 50% compared to the LPS group. Finally, Arg‐1 and CD‐206 mRNA expression were determined by RT‐PCR, which was consistent with the RNA‐Seq result. These findings indicate that EGCG exerts an anti‐inflammatory effect by reducing NO and ROS production, suppressing TLR4 protein expression, and inhibiting IκB and p65 phosphorylation. [ABSTRACT FROM AUTHOR]

Bone formation is regulated by numerous factors, such as transcription factors, cytokines, and extracellular matrix molecules. Human hormone nuclear receptors (hHNR) are a family of ligand‐regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various lipid‐soluble signals, including retinoic acid, oxysterols, and thyroid hormone. We found that an hHNR called NR4A1 was the most highly expressed after human MSC differentiation into osteoblasts by whole‐genome microarray. NR4A1 knockout decreased the osteoblastic differentiation of hMSCs in terms of ALPL expression and key marker gene expression. Whole‐genome microarray analysis further confirmed the decrease in key pathways when we knocked down NR4A1. Further studies with small molecule activators identified a novel molecule called Elesclomol (STA‐4783), which could activate and enhance osteoblast differentiation. Elesclomol activation of hMSCs also induced the gene expression of NR4A1 and rescued the phenotype of NR4A1 KD. In addition, Elesclomol activated the TGF‐ß pathway by regulating key marker genes. In conclusion, we first identified the role of NR4A1 in osteoblast differentiation and that Elesclomol is a positive regulator of NR4A1 through activation of the TGF‐ß signalling pathway. Significance statement: This paper investigates the role of the human hormone nuclear receptor (hHNR) NR4A1 in osteoblast differentiation and the effect of the small molecule activator Elesclomol (STA‐4783) on NR4A1 activation. This study found that NR4A1 plays a crucial role in osteoblast differentiation, with knockdown decreasing ALPL expression and key marker gene expression. This study further identified Elesclomol as a positive regulator of NR4A1 through the activation of the TGF‐ß signalling pathway. The temporal expression of NR4A1 during osteoblast differentiation was also studied, showing sporadic expression. This study provides valuable insights into the molecular mechanisms of osteoblast differentiation and potential therapeutic targets for bone‐related diseases. [ABSTRACT FROM AUTHOR]

Background: The fundamental initial step in the metabolic process of fatty acids (FA) is facilitated by Acyl‐coenzyme A synthetase (ACS). ACS enables FAs to engage in both anabolic and catabolic pathways by creating thioester bonds with CoA, thus triggering their activation. This paper demonstrated the effect of in vitro cells on the ACS family of key enzymes in FA metabolism in response to inflammatory or lipid stimulating factors and provided insight into the relevant metabolic mechanisms. Methods: The expression levels of 27 ACS family members were assessed across various lung epithelial cell lines, such as HBE, SPC‐1A, or NCI‐H460, in response to external challenges including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and interference with the ACSL5 gene in response to FASN, CPT1A inhibitors. Results: Our data showed that ACSF2 was highly expressed in SPC‐A1 and NCI‐H460 cells compared with HBE cell, while ACSL4 and ACSVL4 were lower expressed. The 27 ACS family genes associated with FA metabolism varied under several different exogenous stimuli. [ABSTRACT FROM AUTHOR]

Analysis pipelines in genomics, transcriptomics, and proteomics commonly produce lists of genes, e.g., differentially expressed genes. Often these lists overlap only partly or not at all and contain too many genes for manual comparison. However, using background knowledge, such as the functional annotations of the genes, the lists can be abstracted to functional terms. One approach is to run Gene Ontology (GO) enrichment analyses to determine over‐ and/or underrepresented functions for every list of genes. Due to the hierarchical structure of the Gene Ontology, lists of enriched GO terms can contain many closely related terms, rendering the lists still long, redundant, and difficult to interpret for researchers. In this paper, we present GO‐Compass (Gene Ontology list comparison using Semantic Similarity), a visual analytics tool for the dispensability reduction and visual comparison of lists of GO terms. For dispensability reduction, we adapted the RE‐VIGO algorithm, a summarization method based on the semantic similarity of GO terms, to perform hierarchical dispensability clustering on multiple lists. In an interactive dashboard, GO‐Compass offers several visualizations for the comparison and improved interpretability of GO terms lists. The hierarchical dispensability clustering is visualized as a tree, where users can interactively filter out dispensable GO terms and create flat clusters by cutting the tree at a chosen dispensability. The flat clusters are visualized in animated treemaps and are compared using a correlation heatmap, UpSet plots, and bar charts. With two use cases on published datasets from different omics domains, we demonstrate the general applicability and effectiveness of our approach. In the first use case, we show how the tool can be used to compare lists of differentially expressed genes from a transcriptomics pipeline and incorporate gene information into the analysis. In the second use case using genomics data, we show how GO‐Compass facilitates the analysis of many hundreds of GO terms. For qualitative evaluation of the tool, we conducted feedback sessions with five domain experts and received positive comments. GO‐Compass is part of the Tue‐Vis Visualization Server as a web application available at https://go‐compass‐tuevis.cs.uni‐tuebingen.de/ [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) treatment has been widely explored as a therapy for myocardial infarction, peripheral ischemic vascular diseases, dilated cardiomyopathy, and pulmonary hypertension. Latest in vitro studies suggest that MSCs can differentiate into contractile cardiomyocytes. One of the best‐characterized MSCs products are MSCs‐derived extracellular vesicles (EVs). EVs are crucial paracrine effectors of MSCs. Based on previous works, paracrine effects of MSCs play a primary role in the regenerative ability. Hence, in the current paper, we focused our attention on an alternative approach, exploiting products derived from human dental pulp stem cells (hDPSCs) rather than MSCs themselves, which may denote a cost‐effective and safer approach. The focus has been on EVs and the bioactive molecules they contain to evaluate their ability to influence the differentiation process toward cardiomyogenic lineage. The expression of GATA4, ACTC1, CX43, and Nkx2.5 was evaluated using Immunofluorescence, real time‐PCR, and Western blotting analyses. Furthermore, the expression profiling analysis of the microRNA hsa‐miR‐200c‐3p, targeting the GATA4 gene, was studied. The hsa‐miR‐200c‐3p was found significantly down‐regulated in both c‐hDPSCs + EVs‐hDPSCs and c‐hDPSCs + EVs‐HL‐1 compared to untreated c‐hDPSCs underlying a possible epigenetic mechanism behind the prevalent up‐regulation of its targeted GATA4 gene. The aim of the present work was to develop an in vitro model of hDPSCs able to differentiate into cardiomyocytes in order to investigate the role of EVs derived from hDPSCs and derived from HL‐1 cardiomyocyte cell line in modulating the differentiation process toward cardiomyogenic lineage. [ABSTRACT FROM AUTHOR]

With the increasing availability of biomedical data from multiple platforms of the same patients in clinical research, such as epigenomics, gene expression, and clinical features, there is a growing need for statistical methods that can jointly analyze data from different platforms to provide complementary information for clinical studies. In this paper, we propose a two‐stage hierarchical Bayesian model that integrates high‐dimensional biomedical data from diverse platforms to select biomarkers associated with clinical outcomes of interest. In the first stage, we use Expectation Maximization‐based approach to learn the regulating mechanism between epigenomics (e.g., gene methylation) and gene expression while considering functional gene annotations. In the second stage, we group genes based on the regulating mechanism learned in the first stage. Then, we apply a group‐wise penalty to select genes significantly associated with clinical outcomes while incorporating clinical features. Simulation studies suggest that our model‐based data integration method shows lower false positives in selecting predictive variables compared with existing method. Moreover, real data analysis based on a glioblastoma (GBM) dataset reveals our method's potential to detect genes associated with GBM survival with higher accuracy than the existing method. Moreover, most of the selected biomarkers are crucial in GBM prognosis as confirmed by existing literature. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. Methods: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H‐index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. Results: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H‐index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih‐hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high‐frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR‐146a and miR‐155. Conclusions: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR‐146a and miR‐155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose: Early detection of healing complications after placement of dental implants is a pressing but elusive goal. This paper proposes a non-invasive diagnostic tool for monitoring healing- and peri-implant disease specific genes, complementary to clinical evaluations. Material and Methods: Eighteen partially edentulous patients were recruited to this pilot study. Three Brånemark TiUnite® implants/patient (Nobel Biocare) were placed in a one-stage procedure. Abutments with smooth or rough (TiUnite®) surface were placed. The test group ( n = 9) received fixed bridges (immediate loading), whereas the control group ( n = 9) implants were loaded 3 months after surgery. In addition to clinical measurements, crevicular fluid was collected using paper strips at the implant abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and converted to cDNA. Quantitative PCR assays for IL-1β, TNF-α, Osteocalcin (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene expression levels were calculated. Results: One implant was lost in the control group and three in the test group. In one test patient, one implant showed lowered stability after 2 to 4 weeks and was unloaded. Later implant stability improved which allowed for loading after 3 to 4 months. TNF-α and ALP most commonly showed correlation with clinical parameters followed by IL-1β and OC. The strongest correlation was found for TNF-α with clinical complications at 2 and 14 days ( p = .01/ r = −048, and p = .0004/r = −0.56, respectively; test and control groups together). In some cases, gene expression predicted clinical complications (TNF-α, ALP, CK). Conclusion: This study is based on samples from few individuals; still, some genes showed correlation with clinical findings. Further studies are needed to refine and optimize the sampling process, to find the appropriate panel, and to validate gene expression for monitoring implant healing. [ABSTRACT FROM AUTHOR]

Cancer development is a complex process involving both genetic and epigenetic changes. The SWI/SNF (switch/sucrose non‐fermentable) chromatin remodelling complex, one of the most studied ATP‐dependent complexes, plays an important role in coordinating chromatin structural stability, gene expression and post‐translational modifications. The SWI/SNF complex can be classified into BAF, PBAF and GBAF according to their constituent subunits. Cancer genome sequencing studies have shown a high incidence of mutations in genes encoding subunits of the SWI/SNF chromatin remodelling complex, with abnormalities in one or more of these genes present in nearly 25% of all cancers, which indicating that stabilizing normal expression of genes encoding subunits in the SWI/SNF complex may prevent tumorigenesis. In this paper, we will review the relationship between the SWI/SNF complex and some clinical tumours and its mechanism of action. The aim is to provide a theoretical basis to guide the diagnosis and treatment of tumours caused by mutations or inactivation of one or more genes encoding subunits of the SWI/SNF complex in the clinical setting. [ABSTRACT FROM AUTHOR]

The chromatin structure is generally regulated by chromatin remodelers and histone modifiers, which affect DNA replication, repair, and levels of transcription. The first identified histone acetyltransferase was Hat1/KAT1, which belongs to lysine (K) acetyltransferases. The catalytic subunit Hat1 and the regulatory subunit Hat2 make up the core HAT1 complex. In this study, the results of tandem affinity purification and mass spectrometry and bimolecular fluorescence complementation proved that the Penicillium oxalicum PoHat1‐Hat2 is the transcriptional cofactor of the sequence‐specific transcription factor PoAmyR, a transcription activator essential for the transcription of amylase gene. ChIP‐qPCR results demonstrated that the complex PoHat1‐Hat2 is recruited by PoAmyR to the promoters of prominent amylase genes Poamy13A and Poamy15A and performs histone H4 lysine12 acetylation. The result of the yeast two‐hybrid test indicated that PoHat2 is the subunit that directly interacts with PoAmyR. PoHat1‐Hat2 acts as the molecular brake of the PoAmyR‐regulating transcription of amylase genes. A putative model for amylase gene regulation by PoAmyR‐Hat2‐Hat1 was constructed. Our paper is the first report that the Hat1‐Hat2 complex acts as a cofactor for sequence‐specific TF to regulate gene expression and explains the mechanism of TF AmyR regulating amylase genes expression. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are functional RNAs in the development and metabolism of non‐small cell lung cancer (NSCLC). Therein, this paper particularly elucidated the circRNA SEC61 subunit alpha isoform 1 (circSEC61A1) in NSCLC has not been fully elucidated. Clinical analysis of circSEC61A1 expression was performed on specimens collected from 51 patients with primary NSCLC, together with patients' survival. Cell experiments were performed after interfering with circSEC61A1, microRNA (miR)‐513a‐5p, and peroxisomal biogenesis factor 5 (PEX5) expression, respectively, and cell malignant phenotypes and aerobic glycolysis were evaluated, as well as epithelial‐to‐mesenchymal transition (EMT)‐related markers and Wnt/β‐catenin pathway. Xenografts experiments studied the performance of circSEC61A1 in vivo. The downstream molecules of circSEC61A1 were searched. Our data demonstrated that circSEC61A1 was upregulated in NSCLC patients, showing an association with poorer survival outcomes. In cell experiments, circSEC61A1 overexpression promoted NSCLC malignant phenotypes, glycolysis, EMT, and Wnt/β‐catenin pathway activation, whereas circSEC61A1 underexpression did the opposite. Knockdown of circSEC61A1 limited tumor growth and metastasis. Furthermore, circSEC61A1 could regulate PEX5 expression through competitive absorption of miR‐513a‐5p. Generally, circSEC61A1 is a potential biomarker for NSCLC, and circSEC61A1 serves tumor‐promoting action in the progression of NSCLC. [ABSTRACT FROM AUTHOR]

Klotho, as an antiaging protein, is involved in the maintenance and differentiation of neuronal or glial cells and, therefore, has been noticed as a potential therapeutic target for neurodegenerative disorders. Expression of Klotho has been examined in different cells and organs, however, our information about the developmental pattern of this protein during differentiation of mesenchymal stem cells (MSCs) into neuron‐like cells is limited. In this study, we conducted neural differentiation of mouse bone marrow‐derived‐MSCs and monitored the expression of Klotho together with selected neuron‐specific genes at messenger RNA (mRNA) on days 7 and 14 of differentiation using quantitative real‐time PCR. In addition, Klotho status at protein level was evaluated by immunocytochemistry. The results showed a significant change in the morphology of MSCs towards neuron‐like cells. These changes were observed with progressive growth and formation of cell connections towards the formation of a chain of neuron‐like cells which occurred in the second week of differentiation. Morphological changes were associated with a significant increase in the expression of neuron‐specific genes like pax‐6, neuN and, neurofilaments (NfL). Likewise, there was an increased expression of Klotho mRNA, and accumulation of Klotho protein in neuronal cell bodies, during the cellular differentiation of MSCs. These findings provided new evidence that neuronal differentiation from the MSCs is associated with increased expression of Klotho. These data may provide insight into the importance of Klotho protein in stem cell differentiation and regeneration in response to cell death in the central nervous system. Significance: Neuronal development is a complicated process. Specific growth factors have been identified to play role in this process. In this paper, we provide experimental evidences showing that in vitro differentiation of neuron cells from mouse bone marrow mesenchymal stem cells (MSCs) is associated with increased expression of Klotho, an anti‐ageing protein. This finding was confirmed by showing that morphological changes were associated with a significant increase in the expression of a panel of neuron‐specific genes Pax‐6, neuN, and, Nefl in the cells. During this process, klotho expression at mRNA level was increased, which was corroborated with klotho accumulation in cell bodies. These findings suggest that klotho contribute to neuronal cell differentiation and regeneration of these cells. [ABSTRACT FROM AUTHOR]

Remove unwanted variation (RUV) is an estimation and normalization system in which the underlying correlation structure of a multivariate dataset is estimated from negative control measurements, typically gene expression values, which are assumed to stay constant across experimental conditions. In this paper we derive the weight matrix which is estimated and incorporated into the generalized least squares estimates of RUV‐inverse, and show that this weight matrix estimates the average covariance matrix across negative control measurements. RUV‐inverse can thus be viewed as an estimation method adjusting for an unknown experimental design. We show that for a balanced incomplete block design (BIBD), RUV‐inverse recovers intra‐ and interblock estimates of the relevant parameters and combines them as a weighted sum just like the best linear unbiased estimator (BLUE), except that the weights are globally estimated from the negative control measurements instead of being individually optimized to each measurement as in the classical, single measurement BIBD BLUE. [ABSTRACT FROM AUTHOR]

The article presents papers to be published in the forthcoming issues of the "British Journal of Haematology." Some of the papers to be included are: "Cryoglobulinaemia As an Acute Presentation of Waldenstroms's Macroglobulinaemia," by A. B. Michael, M. Lawes, M. Kamalarajan, A. Huissoon and G. Pratt, "Gene Expression Profiling and Its Application in Studies of Haematological Malignancy," by M. Hubank, "Association Between Thrombin Activatable Fibrinolysis Inhibitor Genotype and Levels in Plasma: Comparison of Different Assays," by A. H. C Guimaraes, N. H. van Tilburg, H. L. Vos, R. M. Bertina and D. C Rijken.

In the paper, we propose two gene expression programming (GEP)‐based ensemble classifiers with different drift detection mechanisms. In the related work section, we briefly review GEP as a classification tool, incremental classifiers, and concept drift detectors. Next, the structure of our two‐level GEP ensemble with metagenes is described. Further on, two integrated classifiers with drift detection algorithm and Wilcoxon rank sum test drift detector are proposed. The approach is validated in the computational experiment in which several real‐life and artificial datasets with concept drift have been used. Experiment confirmed that the proposed approach can be competitive to existing solutions. In the conclusion section, we briefly outline directions for future research. [ABSTRACT FROM AUTHOR]

In their paper, using zebrafish models, Gioacchino et al. have demonstrated the GATA2 haploinsufficiency, the genetic hallmark of GATA2 deficiency syndrome, promotes erythroid and myeloid cytopenia, and have discovered a self‐regulatory mechanism to compensate GATA2 levels and protein function. Commentary on: Gioacchino et al. GATA2 heterozygosity causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasia. Br J Haematol 2024;205:580‐593. [ABSTRACT FROM AUTHOR]

Aim: Platinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer. Methods: We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature. Results: Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer. Conclusions: There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment. [ABSTRACT FROM AUTHOR]

Pfu DNA polymerase is a vital enzyme in PCR‐related experiments. However, it is not easy to achieve high‐level expression and high purity through one‐step purification. This paper illustrates the method to acquire the full‐length open reading frame of Pfu DNA polymerase. Without altering its amino acids, we have modified the codon usage, based on that of the enhanced green fluorescence protein (eGFP), and named it rPfu. The synthesized rPfu gene has been subcloned into the pET28a plasmid and expressed in four Escherichia coli strains without the pLysS plasmid. Three strains have expressed a high level of soluble Pfu DNA polymerase. With the aid of Ni‐NTA His•Bind® resin, we could obtain high purity (>95%) soluble recombinant protein. Compared with the commercial, proofreading DNA polymerase, rPfu's bioactivity was 12,987 U/mg; that is, 88,311 U of rPfu could be obtained from 50 mL cultured E. coli. The purified rPfu was able to amplify the length of DNA fragments at least 5.5 kb. The method of increasing soluble protein's yield using the eGFP codon usage may introduce a new possibility to the expression of other soluble recombinant proteins. [ABSTRACT FROM AUTHOR]