Expression Domains Research Articles

Speech and Language Profiling of a Young Adolescent Diagnosed with Moya-Moya Disease

Background: Moya-Moya disease is leading condition of stroke in children and can affect children as young as 2 years to middle aged adults. Aim: Speech language profiling was carried out in the client after eliciting detailed on Neuro-imaging and intervention. The client reported difficulty on the expression domain and reduced clarity of speech. Western Aphasia Battery, a diagnostic test to diagnose Aphasia (verbal impairment associated with stroke/trauma/tumour) was administered and the diagnosis of Broca’s aphasia was made. Following this treatment was provided for a period of 3 months. Though the client dropped out from therapy, he showed considerable improvement and was able to sustain the progress after the period of 3 years also.

Poslijepandemijska sveučilišna kultura iz studentske perspektive

Culture of an educational institution encompasses a set of norms, beliefs and behaviours evident in a powerful network of rituals and traditions, norms and values that affect every corner of the organization. In the university context, it is perceived as the way of living that is co-created by the community members - their opinions, ideas and habits. The period of the forced social isolation has made many students struggle with developing personal connections and brought them in danger of developing a sense of isolation and disconnection. When moving forward from the lessons learnt in the online university courses,building a sense of community has proven to be one of the greatest challenges. Therefore, this qualitative study aimed to explore how students in their freshman year tend to perceive the university culture after joining the on site classes. For that purpose, Hargreaves’s model of institutional culture, which describes culture in terms of its expressive domain and instrumental domain, was adapted to the context of higher education and applied in focus groups discussions among students of Pedagogy and Psychology (University of Tuzla, Bosnia and Herzegovina). The results show that students recognize the need to increase social cohesion at the university courses while providing engaging and innovative teaching methods that would facilitate learning and create supporting personal relations between students (and the teaching staff).

Cultural and linguistic applicability of the English PEDS tools in a low-income community: A caregiver perspective

Background. Regular developmental surveillance using structured developmental screening tools is a proven way to effectively identify developmental delays and disabilities. Most screening tools are developed and standardised in high-income countries and then adapted and translated for low-and middle-income countries. However, cultural differences and viewpoints make it challenging to translate and adapt developmental screening tools for low-income communities.Objectives. To determine caregivers’ perspectives on linguistic and cultural appropriateness of the Parents’ Evaluation of Developmental Status (PEDS) and the PEDS: Developmental Milestones (DM) as a first step in the adaptation process for low-income communities in South Africa.Method. Participants (N=102) were selected using convenience sampling at an immunisation clinic. We employed a survey researchdesign. Quantitative data were analysed using descriptive statistics and qualitative survey feedback survey was analysed using data-driven inductive methodology.Results. On the PEDS questionnaire, 38.2% of participants indicated the term ‘development’ on question 1 was not suitable; and 51%preferred the phrase ‘sometimes worry’ more than the phrase ‘have any concerns’ for questions 2 - 9. On the PEDS:DM, 58 of the 124questions were deemed difficult. Most questions were problematic owing to cultural or linguistic differences (49 questions), while 9questions were too difficult for the child’s age. The expressive language developmental domain had the most challenges.Conclusion. The present study relied on robust community participation, enabling community-led adaptation of the PEDS tools. Items on the tools were viewed solely from a community perspective, empowering the community to be ‘experts’ in this process, ensuring greater contextual relevance and applicability of the tools, as well as generalisability to similar low-income communities.

Cultivating Insight: Detecting Autism Spectrum Disorder through Residual Attention Network in Facial Image Analysis

Revolutionizing Autism Spectrum Disorder Identification through Deep Learning: Unveiling Facial Activation Patterns. In this study, our primary objective is to harness the power of deep learning algorithms for the precise identification of individuals with autism spectrum disorder (ASD) solely from facial image datasets. Our investigation centers around the utilization of face activation patterns, aiming to uncover novel insights into the distinctive facial features of ASD patients. To accomplish this, we meticulously examined facial imaging data from a global and multidisciplinary repository known as the Autism Face Imaging Data Exchange. Autism spectrum disorder is characterized by inherent social deficits and manifests in a spectrum of diverse symptomatic scenarios. Recent data from the Centers for Disease Control (CDC) underscores the significance of this disorder, indicating that approximately 1 in 54 children are impacted by ASD, according to estimations from the CDC's Autism and Developmental Disabilities Monitoring Network (ADDM). Our research delved into the intricate functional connectivity patterns that objectively distinguish ASD participants, focusing on their facial imaging data. Through this investigation, we aimed to uncover the latent facial patterns that play a pivotal role in the classification of ASD cases. Our approach introduces a novel module that enhances the discriminative potential of standard convolutional neural networks (CNNs), such as ResNet-50, thus significantly advancing the state-of-the-art. Our model achieved an impressive accuracy rate of 99% in distinguishing between ASD patients and control subjects within the dataset. Our findings illuminate the specific facial expression domains that contribute most significantly to the differentiation of ASD cases from typically developing individuals, as inferred from our deep learning methodology. To validate our approach, we conducted real-time video testing on diverse children, achieving an outstanding accuracy score of 99.90% and an F1 score of 99.67%. Through this pioneering work, we not only offer a cutting-edge approach to ASD identification but also contribute to the understanding of the underlying facial activation patterns that hold potential for transforming the diagnostic landscape of autism spectrum disorder.

Normocephalic Children Exposed to Maternal Zika Virus Infection Do Not Have a Higher Risk of Neurodevelopmental Abnormalities around 24 Months of Age than Unexposed Children: A Controlled Study.

Although very few controlled studies are available, in utero Zika virus (ZIKV)-exposed children are considered at risk for neurodevelopmental abnormalities. We aimed to identify whether there is an excess risk of abnormalities in non-microcephalic children born to mothers with confirmed ZIKV infection compared with ZIKV-unexposed children from the same population. In a cross-sectional study nested in two larger cohorts, we compared 324 ZIKV-exposed children with 984 unexposed controls. Outcomes were assessed using the Bayley Screening Test III applied around 24 months of age. Relative risks for classifying children as emergent or at-risk for neurodevelopmental delay in at least one of five domains were calculated, adjusting for covariates. In four of the five domains, few children were classified as emergent (4-12%) or at-risk (0.3-2.16%) but for the expressive communication domain it was higher for emergent (19.1-42.9%). ZIKV-exposed children were half as frequently classified as emergent, including after adjusting for covariates [RR = 0.52 (CI 95% 0.40; 0.66)]. However, no difference was detected in the at-risk category [RR = 0.83 (CI 95% 0.48; 1.44)]. Normocephalic children exposed to the Zika virus during pregnancy do not have a higher risk of being classified as at risk for neurodevelopmental abnormalities at two years of age.

A double-negative feedback loop between miR319c and JAW-TCPs establishes growth pattern in incipient leaf primordia in Arabidopsis thaliana.

The microRNA miR319 and its target JAW-TCP transcription factors regulate the proliferation-to-differentiation transition of leaf pavement cells in diverse plant species. In young Arabidopsis leaf primordia, JAW-TCPs are detected towards the distal region whereas the major mRNA319-encoding gene MIR319C, is expressed at the base. Little is known about how this complementary expression pattern of MIR319C and JAW-TCPs is generated. Here, we show that MIR319C is initially expressed uniformly throughout the incipient primordia and is later abruptly down-regulated at the distal region, with concomitant distal appearance of JAW-TCPs, when leaves grow to ~100 μm long. Loss of JAW-TCPs causes distal extension of the MIR319C expression domain, whereas ectopic TCP activity restricts MIR319C more proximally. JAW-TCPs are recruited to and are capable of depositing histone H3K27me3 repressive marks on the MIR319C chromatin. JAW-TCPs fail to repress MIR319C in transgenic seedlings where the TCP-binding cis-elements on MIR319C are mutated, causing miR319 gain-of-function-like phenotype in the embryonic leaves. Based on these results, we propose a model for growth patterning in leaf primordia wherein MIR319C and JAW-TCPs repress each other and divide the uniformly growing primordia into distal differentiation zone and proximal proliferation domain.

GH3-mediated auxin inactivation attenuates multiple stages of lateral root development.

Lateral root (LR) positioning and development rely on the dynamic interplay between auxin production, transport but also inactivation. Nonetheless, how the latter affects LR organogenesis remains largely uninvestigated. Here, we systematically analyze the impact of the major auxin inactivation pathway defined by GRETCHEN HAGEN3-type (GH3) auxin conjugating enzymes and DIOXYGENASE FOR AUXIN OXIDATION1 (DAO1) in all stages of LR development using reporters, genetics and inhibitors in Arabidopsis thaliana. Our data demonstrate that the gh3.1/2/3/4/5/6 hextuple (gh3hex) mutants display a higher LR density due to increased LR initiation and faster LR developmental progression, acting epistatically over dao1-1. Grafting and local inhibitor applications reveal that root and shoot GH3 activities control LR formation. The faster LR development in gh3hex is associated with GH3 expression domains in and around developing LRs. The increase in LR initiation is associated with accelerated auxin response oscillations coinciding with increases in apical meristem size and LR cap cell death rates. Our research reveals how GH3-mediated auxin inactivation attenuates LR development. Local GH3 expression in LR primordia attenuates development and emergence, whereas GH3 effects on pre-initiation stages are indirect, by modulating meristem activities that in turn coordinate root growth with LR spacing.

BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians.

Adult regeneration restores patterning of orthogonal body axes after damage in a post-embryonic context. Planarians regenerate using distinct body-wide signals primarily regulating each axis dimension: anteroposterior Wnts, dorsoventral BMP, and mediolateral Wnt5 and Slit determinants. How regeneration can coordinate perpendicular tissue axes without symmetry-breaking embryonic events is not fully understood. Here, we report that the planarian dorsoventral regulator bmp4 suppresses the posterior determinant wnt1 to provide patterning input to the anteroposterior axis. Double-FISH identified distinct anteroposterior domains within dorsal midline muscle that express either bmp4 or wnt1. Homeostatic inhibition bmp4 and smad1 expanded the wnt1 expression anteriorly, while elevation of BMP signaling through nog1;nog2 RNAi reduced the wnt1 expression domain and elevated bmp4 expression. Homeostatic BMP signal perturbation broadly affected anteroposterior identity as measured by expression of posterior Wnt pathway factors, and caused mislocalization of AP-regionalized pharynx progenitors, without strongly affecting expression domains of anterior regulators. Additionally, wnt1 inhibition elevated bmp4 expression in the tip of the tail. Therefore, dorsal BMP signals and posterior wnt1 mutually antagonize for patterning the tail. Furthermore, homeostatic bmp4 RNAi caused medial expansion of the lateral determinant wnt5 and reduced expression of the medial regulator slit. By contrast, nog1;nog2 RNAi restricted wnt5 expression. Double RNAi of bmp4 and wnt5 resulted in lateral ectopic eye phenotypes, suggesting bmp4 acts upstream of wnt5 to pattern the mediolateral axis. These results indicate bmp4 controls dorsoventral information and also, through suppression of Wnt signals, influences anteroposterior and mediolateral identity. Based on related functions across vertebrates and Cnidarians, Wnt and BMP cross-regulation could form an ancient mechanism for coordinating orthogonal axis patterning.

Evolution of the expression and regulation of the nuclear hormone receptor ERR gene family in the chordate lineage

The Estrogen Related Receptor (ERR) nuclear hormone receptor genes have a wide diversity of roles in vertebrate development. In embryos, ERR genes are expressed in several tissues, including the central and peripheral nervous systems. Here we seek to establish the evolutionary history of chordate ERR genes, their expression and their regulation. We examine ERR expression in mollusc, amphioxus and sea squirt embryos, finding the single ERR orthologue is expressed in the nervous system in all three, with muscle expression also found in the two chordates. We show that most jawed vertebrates and lampreys have four ERR paralogues, and that vertebrate ERR genes were ancestrally linked to Estrogen Receptor genes. One of the lamprey paralogues shares conserved expression domains with jawed vertebrate ERRγ in the embryonic vestibuloacoustic ganglion, eye, brain and spinal cord. Hypothesising that conserved expression derives from conserved regulation, we identify a suite of pan-vertebrate conserved non-coding sequences in ERR introns. We use transgenesis in lamprey and chicken embryos to show that these sequences are regulatory and drive reporter gene expression in the nervous system. Our data suggest an ancient association between ERR and the nervous system, including expression in cells associated with photosensation and mechanosensation. This includes the origin in the vertebrate common ancestor of a suite of regulatory elements in the 3’ introns that drove nervous system expression and have been conserved from this point onwards.

An ancient pan-cnidarian microRNA regulates stinging capsule biogenesis in Nematostella vectensis

An ancient evolutionary innovation of a novel cell type, the stinging cell (cnidocyte), appeared >600 million years ago in the phylum Cnidaria (sea anemones, corals, hydroids, and jellyfish). A complex bursting nano-injector of venom, the cnidocyst, is embedded in cnidocytes and enables cnidarians to paralyze their prey and predators, contributing to this phylum's evolutionary success. In this work, we show that post-transcriptional regulation by a pan-cnidarian microRNA, miR-2022, is essential for biogenesis of these cells in the sea anemone Nematostella vectensis. By manipulation of miR-2022 levels in a transgenic reporter line of cnidocytes, followed by transcriptomics, single-cell data analysis, prey paralysis assays, and cell sorting of transgenic cnidocytes, we reveal that miR-2022 enables cnidocyte biogenesis in Nematostella, while exhibiting a conserved expression domain with its targets in cnidocytes of other cnidarian species. Thus, here we revealed a functional basis to the conservation of one of nature's most ancient microRNAs.

Acute and Long-Term Consequences of Co-opted doublesex on the Development of Mimetic Butterfly Color Patterns.

Novel phenotypes are increasingly recognized to have evolved by co-option of conserved genes into new developmental contexts, yet the process by which co-opted genes modify existing developmental programs remains obscure. Here, we provide insight into this process by characterizing the role of co-opted doublesex in butterfly wing color pattern development. dsx is the master regulator of insect sex differentiation but has been co-opted to control the switch between discrete nonmimetic and mimetic patterns in Papilio alphenor and its relatives through the evolution of novel mimetic alleles. We found dynamic spatial and temporal expression pattern differences between mimetic and nonmimetic butterflies throughout wing development. A mimetic color pattern program is switched on by a pulse of dsx expression in early pupal development that causes acute and long-term differential gene expression, particularly in Wnt and Hedgehog signaling pathways. RNAi suggested opposing, novel roles for these pathways in mimetic pattern development. Importantly, Dsx co-option caused Engrailed, a primary target of Hedgehog signaling, to gain a novel expression domain early in pupal wing development that is propagated through mid-pupal development to specify novel mimetic patterns despite becoming decoupled from Dsx expression itself. Altogether, our findings provide multiple views into how co-opted genes can both cause and elicit changes to conserved networks and pathways to result in development of novel, adaptive phenotypes.

Characterization of the Abracl-Expressing Cell Populations in the Embryonic Mammalian Telencephalon.

Abracl (ABRA C-terminal-like protein) is a small, non-typical winged-helix protein that shares similarity with the C-terminal domain of the protein ABRA (Actin-Binding Rho-Activating protein). The role of Abracl in the cell remains elusive, although in cancer cells, it has been implicated in proliferation, migration and actin dynamics. Our previous study showed that Abracl mRNA was expressed in the dividing cells of the subpallial subventricular zone (SVZ), in the developing cortical plate (CP), and in the diencephalic SVZ; however, the molecular identities of the Abracl-expressing cell populations were not defined in that work. In this study, we use double immunofluorescence to characterize the expression of Abracl on sections of embryonic murine (E11.5-E18.5) and feline (E30/31-E33/34) telencephalon; to this end, we use a battery of well-known molecular markers of cycling (Ki67, Ascl1, Dlx2) or post-mitotic (Tubb3, Gad65/67, Lhx6 and Tbr1) cells. Our experiments show that Abracl protein has, compared to the mRNA, a broader expression domain, including, apart from proliferating cells of the subpallial and diencephalic SVZ, post-mitotic cells occupying the subpallial and pallial mantle (including the CP), as well as subpallial-derived migrating interneurons. Interestingly, in late embryonic developmental stages, Abracl was also transiently detected in major telencephalic fiber tracts.

The sulfotransferase XB5850668.L is required to apportion embryonic ectodermal domains.

Members of the sulfotransferase superfamily (SULT) influence the activity of a wide range of hormones, neurotransmitters, metabolites and xenobiotics. However, their roles in developmental processes are not well characterized even though they are expressed during embryogenesis. We previously found in a microarray screen that Six1 up-regulates LOC100037047, which encodes XB5850668.L, an uncharacterized sulfotransferase. Since Six1 is required for patterning the embryonic ectoderm into its neural plate, neural crest, preplacodal and epidermal domains, we used loss- and gain-of function assays to characterize the role of XB5850668.L during this process. Knockdown of endogenous XB5850668.L resulted in the reduction of epidermal, neural crest, cranial placode and otic vesicle gene expression domains, concomitant with neural plate expansion. Increased levels had minimal effects, but infrequently expanded neural plate and neural crest gene domains, and infrequently reduced cranial placode and otic vesicle gene domains. Mutation of two key amino acids in the sulfotransferase catalytic domain required for PAPS binding and enzymatic activity tended to reduce the effects of overexpressing the wild-type protein. Our analyses indicates that XB5850668.L is a member of the SULT2 family that plays important roles in patterning the embryonic ectoderm. Some aspects of its influence likely depend on sulfotransferase activity.

The relationship between negative symptoms and MATRICS neurocognitive domains: A meta-analysis and systematic review

BackgroundNegative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations between neurocognitive domains and NS severity. Thus, one promising area in understanding NS is in relation to neurocognition. Currently, the specificity of the relationship between NS and neurocognition is unknown, meaning that there is no consensus regarding which neurocognitive domain is most strongly associated with NS. There is a need to systematically examine the relationship between NS and various neurocognitive domains within study samples. MethodsA systematic search of Ovid PsycINFO, Ovid MEDLINE and Web of Science was performed for articles published since 2004 (year of MATRICS Consensus publication). Inclusion criteria were: 1) individuals with schizophrenia spectrum disorders, first episode psychosis or clinical high risk 2) assessed all six MATRICS neurocognitive domains (processing speed, attention, working memory, verbal learning & memory, visual learning & memory, reasoning & problem solving), 3) reported correlations between all six MATRICS neurocognitive domains and global NS. A three-level random effects hierarchical meta-analysis was performed to assess the relationship between NS (global, expressive, and experiential dimensions) and the six MATRICS neurocognitive domains. Results21 studies were included in the review (n = 3619). All MATRICS neurocognitive domains had small significant correlations with global NS (r = −0.16 to −0.20, p < 0.0001). This relationship was significantly moderated by diagnosis and the moderating effect of sex/ gender trended on significance. Analysis of a subset of the studies revealed that MATRICS neurocognitive domains also had small significant correlations with the two NS dimensions, expressive and experiential. Correlations were stronger with the expressive NS dimension. ConclusionsThis review is novel in assessing the relationship between multiple neurocognitive domains and NS within the same sample, by synthesizing close to two decades of research. Our results suggest that there is a non-specific relationship between neurocognition and NS, and that expressive NS may have a stronger relationship with neurocognitive functioning-based on the MATRICS classification of neurocognition and the neurocognitive assessments used in the included studies. This has implications on our understanding of NS and neurocognition, as well as their treatments. As we gain better understanding of the directionality of the NS-cognition relationship, it could suggest that NS, particularly in the expressive domain, could be improved by targeting cognition globally or that neurocognitive treatments could be more effective if NS are addressed first. Further implications of these results are discussed.

From transgressors to authors: promoting EFL writing through academic integrity integrated instruction

The relationship between academic integrity and plagiarism has been shaped by two governing pedagogies. The first one stipulates imposing sanctions on students who plagiarise. In this case, students are seen as moral slackers, habituated to cheating. The second pedagogy approaches plagiarism as a matter of intertextual issue and highlights the importance of teaching the ethics of intertextual writing through developing pedagogies that offer positive practices. In this approach, students are seen as authors, not transgressors. This study aimed to investigate the effectiveness of a writing instruction, which emphasizes the importance of teaching mechanical, ethical, and rhetorical intertextuality skills along with its role in mitigating plagiarism incidents and enhancing the EFL writing development of secondary school students. A mixed-method time series design was employed to collect data, and the results indicate that teaching intertextuality skills was effective in reducing plagiarism incidents in student papers and enhancing the content, organisation, style, and expression domains in their papers. Such an implementation makes it evident that in approaching student writing in general, plagiarism in particular, we need to shift our writing pedagogy from policing students to engaging them.

Impact of cognitive performance and negative symptoms on psychosocial functioning in Czech schizophrenia patients

Schizophrenia has a profound influence on the real-life functioning of patients. There are several factors inherent to the disease course affecting the level of psychosocial functioning. Our study focused on the impact of cognitive deficit and severity of negative symptoms (i.e., the experiential domain (avolition, asociality, and anhedonia) and the expressive domain (blunted affect and alogia)) to explore psychosocial functioning in schizophrenia. Schizophrenia patients (n = 211) were tested for the presence of cognitive impairment using the NIMH-MATRICS: Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Cattery (MCCB; MATRICS Consensus Cognitive Battery) and the extent of negative symptoms using the PANSS (PANSS; Positive and Negative Syndrome Scale—selected items). The level of psychosocial functioning was measured with the Personal and Social Performance Scale (PSP). The path analysis using three regression models was used to analyse variables influencing psychosocial functioning (PSP). One of these models analyzed influence of cognitive functioning (MCCB) and negative schizophrenia symptoms (PANSS selected items reflecting expressive and experiential deficits) as predictors and NART/CRT and disease length as confounders. R2 was 0.54. The direct effect of the MCCB (β = 0.09) on the PSP was suppressed by the strong effect of the negative symptoms (β = −0.64). The presence of cognitive deficits and negative symptoms in our sample of schizophrenia patients significantly influences the level of their psychosocial functioning, a key factor in remission and recovery.

How enhancers regulate wavelike gene expression patterns.

A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called 'enhancers.' Much of our models of how enhancers work rely on the assumption that genes are activated de novo as stable domains across embryonic tissues. Such a view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of the Drosophila embryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expression patterns in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetle Tribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here, we establish the AP patterning of the short-germ beetle Tribolium as a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system in Tribolium based on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered several Tribolium enhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expression patterns (that we call 'dynamic enhancers') and enhancers that stabilize gene expression patterns (that we call 'static enhancers'). However, more data is needed for a strong support for this or any other alternative models.

Fibroblast Growth Factor 11 Inhibits Hepatitis B Virus Gene Expression Through FXRα Suppression

Fibroblast growth factor 11 (FGF11) is a member of the intracellular FGF family, which shows different signal transmission compared with other FGF superfamily members. The molecular function of FGF11 is not clearly understood. In this study, we identified the inhibitory effect of FGF11 on hepatitis B virus (HBV) gene expression through transcriptional suppression. FGF11 decreased the mRNA and protein expression of HBV genes in liver cells. While the nuclear receptor FXRα1 increased HBV promoter transactivation, FGF11 decreased the FXRα-mediated gene induction of the HBV promoter by the FXRα agonist. Reduced endogenous levels of FXRα by siRNA and the dominant negative mutant protein (aa 1–187 without ligand binding domain) of FXRα expression indicated that HBV gene suppression by FGF11 is dependent on FXRα inhibition. In addition, FGF11 interacts with FXRα protein and reduces FXRα protein stability. These results indicate that FGF11 inhibits HBV replicative expression through the liver cell-specific transcription factor, FXRα, and suppresses HBV promoter activity. Our findings may contribute to the establishment of better regimens for the treatment of chronic HBV infections by including FGF11 to alter the bile acid mediated FXR pathway.

Molecular mechanism of synovial joint site specification and induction in developing vertebrate limbs.

The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.

Levels of APE1 Repair Gene and CLEC4M in Lung Cancer Patients Receiving Cisplatin Chemotherapy.

This study aimed to detect the levels of apurinic/apyrimidinic endonuclease 1 (APE1) gene expression and C-type lectin domain family 4 member M (CLEC4M) and their association with cisplatin chemotherapy in lung cancer patients. Overall, 105 individuals who attended the Al-Amal National Hospital for Cancer Management, Baghdad, Iraq, were enrolled in the study and divided into three equal groups. The groups included the patients newly diagnosed with lung cancer, cancer patients who received cisplatin, and the healthy control group. All study groups were subjected to the sampling of the venous blood for molecular analysis by real-time polymerase chain reaction (RT-PCR) to detect the APE1 gene and enzyme-linked immunosorbent assay (ELISA) for serological testing to measure the concentration of CLEC4M protein. Significantly, the values of both cancer groups were higher than those reported in the control group. The relative index revealed a significant difference in the mean fold change level of APE1 in the newly diagnosed group (3 fold) and cisplatin therapy patients group (2 fold), compared to the control group (P=0.005). No significant differences were detected between the two cancer groups in terms of fold change mean of expression, demographic characteristics, and cancer histological type. Regarding human CLEC4M protein level, cases receiving cisplatin (139.2±25.9) and newly diagnosed patients (331.0±38.1) had a highly significant difference with the control group (100.3±47.5, P<0.001). There was no significant difference between the concentration level of CLEC4M and all parameters in demographic characteristics and cancer histological type. This was the first study to demonstrate that higher expression levels of new APE1, CLEC4M, and glutathione, especially after chemotherapy, are beneficial as diagnostic and prognostic markers for resistance to platinum chemotherapy in Iraqi lung cancer patients.