Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced SLC27A2 induces cisplatin resistance in lung cancer stem cells by negatively regulating Bmi1‐ABCG2 signaling

Platinum‐based chemotherapies have long been used as a standard treatment in non‐small cell lung cancer (NSCLC). However, cisplatin resistance is a major problem that restricts the use of cisplatin. Lung cancer stem cells (LCSCs) represent a subpopulation that is responsible for chemo‐resistance. We aim to investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo‐resistance to cisplatin in LCSCs. Here, our findings testified that CD166+ cells which were derived from fresh primary NSCLC samples displayed stem cell‐like features and were resistant to chemotherapy drug cisplatin. In patient cohort, we found the presence of a variable fraction of CD166+ cells in 24 out of 25 primary NSCLC samples. Significantly, SLC27A2 expression was reduced in CD166+ LCSCs. Reduced SLC27A2 correlated chemo‐response and poor patient survival. Our results indicated that enhanced SLC27A2 expression sensitized CD166+ LCSCs to cisplatin by in vitro and in vivo experiments. Microarray profiling showed that the expression of Bmi1 and ABCG2 was enhanced in p‐SLC27A2‐LCSCs compared with that in pc3.1DNA‐LCSCs. Furthermore, we demonstrated that reduced SLC27A2 induced chemo‐resistance in CD166+ LCSCs by negatively regulating Bmi1‐ABCG2 signaling, and ABCG2 was a direct transcriptional target of Bmi1. Thus, this study widens the window for identification and targeting of a cisplatin‐resistant population and contributes to the development of potential therapeutics to improve the current treatment modalities in NSCLC. © 2015 Wiley Periodicals, Inc.
Recapitulating emotional context: activity of amygdala, hippocampus and fusiform cortex during recollection and familiarity

The amygdala is thought to enhance long‐term memory for emotionally arousing events by modulating memory formation and storage in the hippocampus and in neocortical areas. Recent animal studies have raised the possibility that cooperativity between amygdala and hippocampus contributes to the retrieval of fear memories. The functional contributions of the amygdala to the retrieval of emotional memories in humans are less well known. Here, in a functional magnetic resonance imaging experiment, 20 healthy subjects studied neutral words in the context of a fearful or a neutral human face. In a subsequent test, they made ‘remember’ (conscious recollection of the study context), ‘know’ (familiarity in the absence of conscious recollection) and ‘new’ judgements on the studied and newly presented neutral words, in the absence of face stimuli. At test, bilateral amygdala, hippocampus and fusiform face area (FFA) were more strongly activated during recollection than during familiarity. Higher activity for fearful than for neutral study context was found in bilateral FFA during recollection but not during familiarity. This difference recapitulated higher activity for fearful than for neutral context in the FFA during study. These data suggest that the amygdalae and hippocampi contribute to the retrieval of emotion‐laden context memories by coordinating the reactivation of stored representations in neocortical areas, such as the FFA. However, there also was a recapitulation of emotional study context in the right amygdala during familiarity only, which might therefore be related to affective implicit memory.
Natural hybridization between a deciduous (Nothofagus antarctica, Nothofagaceae) and an evergreen (N. dombeyi) forest tree species: evidence from morphological and isoenzymatic traits.

BACKGROUND AND AIMS Trees with a partial leaf-shedding pattern and other morphological features a priori considered intermediate between those of the deciduous Nothofagus antarctica (G. Forster) Oersted and the evergreen N. dombeyi (Mirb.) Oersted (Nothofagaceae) were found in natural stands. The hybridization between a deciduous and an evergreen species of Nothofagus has not been reported so far in natural communities. METHODS The putative hybrids and the two presumed parental species were compared using 14 enzyme systems as well as shoot, leaf and reproductive morphology. KEY RESULTS Six enzyme systems showed good resolution (MDH-B, IDH, SKDH, 6-PGDH, GOT and PGI) and in four of them (PGI, MDH-B, SKDH and 6-PGDH) the putative hybrids showed intermediate zymogram patterns between N. antarctica and N. dombeyi. Both principal coordinates analysis on isozyme data and principal components analysis (PCA) on quantitative morphological traits of shoots and leaves separated both parental species and located the putative hybrids closer to N. antarctica than to N. dombeyi. In the PCA, the number of basal cataphylls and the length : width ratio of leaves were the variables most discriminating among shoots of the three entities. The putative hybrids were intermediate between both species regarding leaf vernation, outline and venation, variation in leaf shape (length/width) with position on the parent shoot and in staminate inflorescence and cupule morphology. For other morphological traits, the putative hybrids resembled one of the parental species or differed from both species (e.g. valve morphology). CONCLUSIONS Isoenzymatic and morphological data sets support the idea of the hybrid nature (probably F1 generation) of the semi-deciduous trees found. Nothofagus antarctica and N. dombeyi are probably more closely related than previously assumed. The relevance of pollen type in revealing evolutionary relationships between Nothofagus species is supported, and that of leaf-shedding pattern is rejected.
Identification of Pax5 Target Genes in Early B Cell Differentiation1

The transcription factor Pax5 is essential for B cell commitment in the mouse, where it represses lineage-inappropriate gene expression while simultaneously activating the B cell gene expression program. In this study we have performed a global gene expression screen of wild-type and Pax5-deficient pro-B cells in an attempt to identify the crucial Pax5 targets in early B lymphopoiesis. These studies have identified 109 Pax5 targets comprising 61% activated and 39% repressed genes. Interestingly, Pax5 directly regulates the genes encoding a number of transcription factors that are required at the pre-B cell stage of differentiation, including Irf8, Spib, and Ikzf3 (Aiolos), suggesting that a key function of Pax5 is to activate secondary transcription factors that further reinforce the B cell program. Pax5 is also required for the expression of many genes known to be involved in adhesion and signaling, indicating that Pax5 modulates the homing and or migration properties of B cell progenitors. Finally, Pax5 also represses a cohort of genes that are involved in multiple biological processes, many of which are not typically associated with B cells. These include the repression of the adhesion molecule Embigin, which is expressed in bone marrow progenitors, T cells, and myeloid cells but is specifically repressed by Pax5 in B cells.
Precocious Puberty – A Case Report

The parents of a 04-year-old girl bring her to a Gynaecologist because of breast development, appearance of pubic hair and periodic per vaginal bleeding. Her medical history is unremarkable. The parents are of average height, and the mother reports first menstruating when she was 11 years old. At physical examination, the girl is 100 cm tall , weighs 17 kg, and has a bodymass index of 17. Her pubertal development is classified as Tanner stage 3 breast development and Tanner stage 2 pubic hair development. She was diagnosed as a case of precocious puberity. Appearance of secondary sexual development before the age of 9 in a male child and before the age of 8 in a female child is called precocious puberty. When the cause of precocious puberty is premature activation of the hypothalamic-pituitary axis, it is called central or complete precocious puberty and she was a case of central precocious puberty. After proper consult she was treated by GnRHa suppressor of pituitary till 11 years of age. Bangladesh J Obstet Gynaecol, 2015; Vol. 30(2) : 109-112
Epigenetic dysregulation of Insulin-like growth factor (IGF)-related genes and adverse pregnancy outcomes: a systematic review

Abstract Objectives: Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) are leading causes of neonatal mortality and morbidity around the world. Epigenetic alterations of the human genome may be involved in the causal chain of adverse pregnancy outcomes. In this systematic review we investigated whether PTB, LBW and SGA are associated with epigenetic dysregulation of insulin-like growth factor-related genes (IGF). Methods: We searched MEDLINE and EMBASE for peer-reviewed articles about IGF and PTB, LBW and SGA published up to February 2015. Two independent reviewers selected original, controlled, human studies published in any language and graded them using the Newcastle–Ottawa Quality Assessment Scale. Disagreements were resolved by consensus with a third reviewer. Results: Eighteen observational studies of low-to-moderate quality met the eligibility criteria out of 210 unique studies. There was substantial heterogeneity across studies. Most studies reported no, limited or borderline association between epigenetic changes (methylation or imprinting) of IGF-related genes and LBW or SGA. There were no IGF-related epigenetic studies of PTB. Conclusions: Overall, evidence of an association between epigenetic abnormalities of IGF-related genes and LBW or SGA was weak and inconsistent. Methodological concerns limited results validity.
The incidence of venous thromboembolism in patients with overt hyperthyroidism

Summary Hyperthyroidism is associated with several changes in the haemostatic system resulting in a hypercoagulable state. It is uncertain at this stage whether this leads to an increased risk of venous thromboembolism (VTE). The aim of this retrospective cohort study was to determine the risk of VTE in all patients with overt hyperthyroidism and to compare this to the risk of VTE in the general population. In three hospitals in the Netherlands, patients with biochemically confirmed hyperthyroidism caused by Graves’ disease, multinodular goiter or toxic adenoma were included. All available electronic and handwritten records were examined. Primary outcome was the occurrence of VTE within six months before and until six months after the diagnosis of hyperthyroidism. We included a total of 587 patients. Five patients experienced a VTE during the study period, resulting in an incidence rate of 8.7 (95% CI 2.8 – 20.2) per 1,000 person-years. Three of these five patients had a first VTE (incidence rate for first VTE was 5.3 [95% CI 1.1 – 15.6] per 1,000 person-years). Incidence rates of VTE in the general population are between 0.6 and 1.6 per 1,000 person-years for first VTE and 0.7 and 1.8 per 1,000 person-years for all VTE. In conclusion, the incidence rate of VTE in patients with hyperthyroidism appears to be high. Future prospective studies are needed to further explore this possible association and to address its clinical implications.
Deficient Post-error Slowing in Children with ADHD Is Limited to the Inattentive Subtype

Abstract Post-error slowing (i.e., slowing of a response on correct trials following an error) is thought to reflect adaptive behavior that may be impaired in Attention-Deficit/Hyperactivity Disorder (ADHD). The current study examined post-error slowing in children with ADHD and typically developing controls on two cognitive tasks. Fifty-one ADHD-Combined type, 53 ADHD-Inattentive type, and 47 controls completed a Choice Discrimination and Stop Signal Task with incentive and event rate manipulations. Linear mixed models were used to examine reaction times surrounding errors (trial-by-trial). Pre-error speeding and pre- to post-error slowing occurred on both tasks. Impaired post-error slowing was only present on the Choice Discrimination Task for the ADHD-Inattentive type. Post-error slowing is impaired in children with ADHD-Inattentive type, but not ADHD-Combined type, on a simple attention task. These findings highlight the importance of considering task demands and ADHD subtype when examining post-error slowing and also provide a novel approach to quantifying post-error slowing. (JINS, 2012, 18, 612–617)
Ammonia as a source of gastric hypoacidity in patients with uremia.

Ammonia is produced when urea passes from the blood into gastric secretion, a reaction catalyzed by a urease, present in the gastric mucosa of man and several animals (1-14). Fitzgerald and Murphy (15) have suggested that the ammonia formed in this process may have an important protective function by neutralizing gastric acidity. This concept was based on the observation in man that administration of urea in amounts sufficient to raise temporarily the blood urea level by 12 mg. per cent was followed by a decrease of gastric acidity. Burke and Page (16) were unable to confirm these findings, and Kornberg, Davies and Wood (17-19) presented evidence which suggested that, at least in the cat, the urease found in the stomach is of bacterial origin and does not influence gastric acid secretion. This paper compares gastric ammonia and acid contents in normal and uremic subjects, the latter known to exhibit an elevated gastric ammonia concentration (20-22). Because of the influence of antibiotics on intestinal ammonia production (23-25), their effects on gastric ammonia and acid concentration were studied.
Effects of Prepregnancy Body Mass Index and Gestational Weight Gain on Pregnancy Outcomes

To investigate the single and joint effects of prepregnancy body mass index (BMI) and gestational weight gain (GWG) on pregnancy outcomes, electronic medical records of 14 196 women who delivered singleton live infant at a maternal and child health hospital in Beijing, China, in 2012 were reviewed. Logistic regression was used to assess the associations, adjusting for maternal age, height, education, parity, and offspring sex. Women of high prepregnancy BMI or excessive GWG had higher risks of gestational diabetes mellitus, hypertensive disorders in pregnancy, postpartum hemorrhage, caesarean delivery, macrosomia, and large for gestational age infant, while women of inadequate GWG had higher risks of preterm delivery, low birth weight, and small for gestational age infant. Findings suggest that antenatal care providers should help pregnant women control their GWG to normal.
Improving the productivity of tropical sheep.

Sheep of Merino (Peppin, non-Peppin and South Australian) and nonMerino origin (Suffolk, Poll Dorset, Border Leicester and Wiltshire Horn) were screened for environmental adaptation traits after a season of acclimatisation. Measurements of rectal temperature, respiration rate and water turnover have been used as a guide to initial screening tests (Hopkins, Knights and Le Feuvre 1977). Subsequent measurements of reproductive performance, wool growth, liveweight gains and mature body size have been made.
Multiple role of reactive oxygen species in the arterial wall

Increased oxidative stress plays an important role in vascular dysfunction and atherogenesis. Both systemic factors, such as hypercholesterolemia and hyperglycemia, and local factors, such as activation of macrophages and T cells, may contribute to oxidative stress. Oxidation of lipids in lipoproteins and cell membranes leads to functionally important modifications of proteins that affect their recognition by cell surface receptors and protein–protein interactions within the cell, including DNA binding. Oxidized LDL and extracellular oxidation modulate oxidation‐sensitive signaling pathways, but it is not clear to what extent this results from receptor‐mediated activation or from direct effects on the intracellular redox‐balance. Extensive evidence indicates that reactive oxygen species (ROS) regulate gene expression by modulating a large number of transcription factors, including the nuclear transcription factor kappa B (NFκB), the peroxisome proliferator activated receptorγ (PPARγ), and pathways linked to apoptosis. It is also increasingly recognized that cell differentiation and proliferation, cytokine expression, and programmed cell death are determined by the interactions between oxidation‐sensitive regulatory pathways previously thought to lead to distinct outcomes. Because hypercholesterolemia exerts pro‐oxidant effects both intra‐ and extracellularly and because increased ROS formation affects vascular reactivity and atherogenesis by modulating multiple signaling pathways and transcriptional events, future investigations of its atherogenic mechanisms should place greater emphasis on the net effect of such modulation on the expression of a large spectrum of genes. One way of doing this will be by defining clusters of genes responding to hypercholesterolemic stimuli—or interventions with structurally unrelated antioxidants—in analogous ways, irrespective of what regulatory pathway they are controlled by. Microarray technologies that allow simultaneous assessment of large numbers of genes may provide a tool for this approach. J. Cell. Biochem. 82: 674–682, 2001. © 2001 Wiley‐Liss, Inc.
Presynaptic inhibition of transmitter release from rat sympathetic neurons by bradykinin

Bradykinin is known to stimulate neurons in rat sympathetic ganglia and to enhance transmitter release from their axons by interfering with the autoinhibitory feedback, actions that involve protein kinase C. Here, bradykinin caused a transient increase in the release of previously incorporated [3H] noradrenaline from primary cultures of dissociated rat sympathetic neurons. When this effect was abolished by tetrodotoxin, bradykinin caused an inhibition of tritium overflow triggered by depolarizing K+ concentrations. This inhibition was additive to that caused by the α2‐adrenergic agonist UK 14304, desensitized within 12 min, was insensitive to pertussis toxin, and was enhanced when protein kinase C was inactivated. The effect was half maximal at 4 nm and antagonized competitively by the B2 receptor antagonist Hoe 140. The cyclooxygenase inhibitor indomethacin and the angiotensin converting enzyme inhibitor captopril did not alter the inhibition by bradykinin. The M‐type K+ channel opener retigabine attenuated the secretagogue action of bradykinin, but left its inhibitory action unaltered. In whole‐cell patch‐clamp recordings, bradykinin reduced voltage‐activated Ca2+ currents in a pertussis toxin‐insensitive manner, and this action was additive to the inhibition by UK 14304. These results demonstrate that bradykinin inhibits noradrenaline release from rat sympathetic neurons via presynaptic B2 receptors. This effect does not involve cyclooxygenase products, M‐type K+ channels, or protein kinase C, but rather an inhibition of voltage‐gated Ca2+ channels.
Photodynamic therapy may worsen the prognosis of highly myopic choroidal neovascularisation treated by intravitreal bevacizumab

Myopic maculopathy is the main cause of vision loss among highly myopic patients, and the leading aetiology of subfoveal choroidal neovascularisation (CNV) among patients <50 years old. Different therapeutic approaches have been used to treat myopic CNV, including argon laser photocoagulation, surgery and photodynamic therapy (PDT). New anti-angiogenic drugs have been used to treat subfoveal CNV secondary to high myopia.1 2 The purpose of this study is to report the influence of previous PDT on the visual outcome of subfoveal and juxtafoveal CNV in highly myopic patients treated by intravitreal bevacizumab (IB). Twenty-nine eyes from 28 highly myopic patients with subfoveal and juxtafoveal CNV were treated by three-monthly intravitreal injections of 1.25 mg bevacizumab. Patients on treatment by PDT were started on IB if they were losing visual acuity or CNV did not respond to PDT. Best …
GABA‐mediated control of hypocretin‐ but not melanin‐concentrating hormone‐immunoreactive neurones during sleep in rats

The perifornical‐lateral hypothalamic area (PF‐LHA) has been implicated in the regulation of behavioural arousal. The PF‐LHA contains several cell types including neurones expressing the peptides, hypocretin (HCRT; also called orexin) and melanin‐concentrating hormone (MCH). Evidence suggests that most of the PF‐LHA neurones, including HCRT neurones, are active during waking and quiescent during non‐rapid eye movement (non‐NREM) sleep. The PF‐LHA contains local GABAergic interneurones and also receives GABAergic inputs from sleep‐promoting regions in the preoptic area of the hypothalamus. We hypothesized that increased GABA‐mediated inhibition within PF‐LHA contributes to the suppression of neuronal activity during non‐REM sleep. EEG and EMG activity of rats were monitored for 2 h during microdialytic delivery of artificial cerebrospinal fluid (aCSF) or bicuculline, a GABAA receptor antagonist, into the PF‐LHA in spontaneously sleeping rats during the lights‐on period. At the end of aCSF or bicuculline perfusion, rats were killed and c‐Fos immunoreactivity (Fos‐IR) in HCRT, MCH and other PF‐LHA neurones was quantified. In response to bicuculline perfusion into the PF‐LHA, rats exhibited a dose‐dependent decrease in non‐REM and REM sleep time and an increase in time awake. The number of HCRT, MCH and non‐HCRT/non‐MCH neurones exhibiting Fos‐IR adjacent to the microdialysis probe also increased dose‐dependently in response to bicuculline. However, significantly fewer MCH neurones exhibited Fos‐IR in response to bicuculline as compared to HCRT and other PF‐LHA neurones. These results support the hypothesis that PF‐LHA neurones, including HCRT neurones, are subject to increased endogenous GABAergic inhibition during sleep. In contrast, MCH neurones appear to be subject to weaker GABAergic control during sleep.
Topographical and Cytological Evolution of the Glial Phase During Prenatal Development of the Human Brain: Histochemical and Electron Microscopic Study

An ultrastructural analysis of prenatal gliogenesis and neuronal-glial relationships in the developing fetal brain was carried out using reduced osmium and periodic acid-thiocarbohydrazide-silver proteinate to stain selectively the glycogen content of the glial population. Gliophilic neuronal migration was confirmed in the human fetus, with radial glial fibers (RGF) acting as obligatory corridors for neuronal migration in the prospective neocortex and underlying intermediate zone (IZ). With this method, the entire glial phase was differentiated from neuronal elements; this permitted a description of the evolutionary distribution pattern of RGF: in the cortical plate, glial fascicles fully dissociate by 18 weeks gestation, whereas in the IZ, they remain grouped in fascicles until their transformation into astrocytes. The most conspicuous and constant developmental feature observed in the maturing glial cytoplasm between 21 and 30 weeks gestation was a radical enhancement in the abundance and activity of the lysosomal apparatus and autophagic vacuoles observed in the RGF, a cytological basis for the transformation of radial glial cells into astrocytes. These data have implications for the understanding of the ontogenesis of the neocortical vertical modules in the human brain and for the phylogenetic analysis of the vertical cortical units in terms of comparative mammalian anatomy.