Miracle-dz/UniFAR-FTUs huggingface dataset:
Interhemispheric connections of cortical sensory areas in tree shrews

Interhemispheric connections were studied in tree shrews (Tupaia belangeri) after multiple injections of horseradish peroxidase or horseradish peroxidase conjugated to wheat germ agglutinin into the cortex of one cerebral hemisphere. After an appropriate survival period, the areal pattern of connections was revealed by flattening the other hemisphere, cutting sections parallel to the cortical surface, and staining with tetramethylbenzidine. Architectonic boundaries were identified by using sections stained for myelinated fibers. Labeled cells and axon terminations formed largely overlapping distributions that covaried in density, although labeled cells appeared to be more evenly distributed than labeled terminations. Connections were concentrated along the border of area 17 (V‐I) with area 18 (V‐II). However, connections also extended as far as 2 mm into area 17 to include cortex representing parts of the visual field 10° or more from the zero vertical meridian. Clusters of dense connections spanned the width of area 18, where they alternated with regions of fewer connections. These clusters roughly corresponded in location to regions with heavier myelination. In the visually responsive temporal cortex, connections were also unevenly distributed. The organization of most of this cortex is not understood, but one subdivision, the temporal dorsal area (TD), has been identified on the basis of reciprocal connections with area 17. The central part of the TD had few interhemispheric connections, while most of the outer border had dense connections. The auditory cortex had dense and patchy connections throughout. The pattern in the primary somatosensory cortex (S‐I) varied according to the representation of body parts, so that the cortex related to the forepaw had sparse connections, while connections were dense but uneven over much of the representation of the face, nose, and mouth. A focus of connections was found at the border of the forepaw and face representations, where the myelination of S‐I cortex is interrupted. Dense, uneven connections also characterized the second somatosensory area, S‐II. The motor cortex was densely connected, with only slightly fewer terminations rostral to the forepaw region of S‐I. Other parts of frontal cortex had dense connections, The distribution of cortical connections varied with depth for at least some areas, so that clusters of cells and terminations were found in supragranular layers in S‐I, S‐II, and TD, while infragranular labeled cells were more evenly distributed.
Multiplex Ligation‐Dependent Probe Amplification for the Detection of 1p and 19q Chromosomal Loss in Oligodendroglial Tumors

Multiplex ligation‐dependent probe amplification (MLPA) is a new assay for the detection of multiple chromosomal deletions in tumor tissue in a single experiment. Since genotyping of gliomas with oligodendroglial features by the detection of 1p/19q chromosomal deletions became essential for treatment decisions, we developed and validated an MLPA‐ based assay to determine these losses in formalin fixed and paraffin embedded oligodendroglial tumors (OG). Nineteen OGs, and 10 control samples were analyzed by MLPA and the results were correlated with those obtained by fluorescent in situ hybridization (FISH). The MLPA results were reproducible in all samples in which repeated experiments were performed. In 18 of 19 OGs, MLPA and FISH were concordant for presence or absence of 1p deletion. In 3 OGs, MLPA detected a 19q deletion not shown by FISH. For the other 15 OGs, MLPA and FISH were concordant. In one sample with 50% to 75% of tumor, MLPA failed to detect the 1p/19q deletions revealed by FISH (though with borderline values of significance). We conclude that MLPA is a valid and reproducible method for the detection of 1p/19q chromosomal deletions in OGs stored on formalin fixed, paraffin embedded tissue.
A comprehensive survey on image-based computer aided diagnosis systems for skin cancer

Malignant melanoma is the deadliest form of skin cancer. In 2013 around 14,509 melanoma cases were found in the United Kingdom and the rate is increasing ever since. Melanoma can be easily treatable if detected in early stages. Clinical as well as automated methods are being used for melanoma diagnosis. Image-based computer aided diagnosis systems have great potential for early malignant melanoma detection. In this paper we review state of the art in computer aided diagnosis system and examine recent practices in different steps of these systems. Statistics and results from the most important and recent implementations are analyzed and reported. We compared the performance of recent work based on different parameters like accuracy, dataset, computational time, color space, machine learning technique etc. and summarized them in table format for better understanding of emergent researchers in the field of computer aided skin diagnosis systems. Research challenges regarding the different parts of computer aided skin cancer diagnosis systems are also highlighted.
Adhesion-dependent regulation of an A+U-rich element-binding activity associated with AUF1

Monocyte adherence results in the rapid transcriptional activation and mRNA stabilization of numerous mediators of inflammation and tissue repair. While the enhancer and promoter elements associated with transcriptional activation have been studied, mechanisms linking adhesion, mRNA stabilization, and translation are unknown. GROalpha and interleukin-1beta (IL-1beta) mRNAs are highly labile in nonadhered monocytes but stabilize rapidly after adherence. GROalpha and IL-1beta transcripts both contain A+U-rich elements (AREs) in the 3' untranslated region (UTR) which have been directly associated with rapid mRNA turnover. To determine if the GROalpha ARE region was recognized by factors associated with mRNA degradation, we carried out mobility gel shift analyses using a series of RNA probes encompassing the entire GROalpha transcript. Stable complexes were formed only with the proximal 3' UTR which contained the ARE region. The two slower-moving complexes were rapidly depleted following monocyte adherence but not direct integrin engagement. Deadherence reactivated the two largest ARE-binding complexes and destabilized IL-1beta transcripts. Antibody supershift studies demonstrated that both of these ARE RNA-binding complexes contained AUF1. The formation of these complexes and the accelerated mRNA turnover are phosphorylation-dependent events, as both are induced in adherent monocytes by the tyrosine kinase inhibitor genistein and the p38 MAP kinase inhibitor of IL-1beta translation, SK&F 86002. These results demonstrate that cell adhesion and deadhesion rapidly and reversibly modify both cytokine mRNA stability and the RNA-binding complexes associated with AUF1.
Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer

Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC‐PDE) catalyzes the degradation of GPC to free choline and glycerol‐3‐phosphate. The gene(s) encoding for the GPC‐PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here, we demonstrate for the first time that the GPC‐PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n = 8 and n = 10) and primary human breast tumor samples (n = 19) were studied with combined MRS and quantitative reverse transcription‐polymerase chain reaction to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Of the five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER–) compared with weakly malignant estrogen receptor positive (ER+) human breast cancer cells (p = 0.027) and breast tumors from patients (p = 0.015). GDPD5 showed significantly positive correlations with PC (p < 0.001), total choline (tCho) (p = 0.007) and PC/GPC (p < 0.001) levels in human breast tumors. GDPD5 showed a trend towards a negative correlation with GPC levels (p = 0.130). Human breast cancers with malignant choline metabolite profiles consisting of low GPC and high PC levels highly co‐expressed GDPD5, choline kinase alpha (CHKA) and phosphatidylcholine‐specific phospholipase D1 (PLD1), whereas cancers containing high GPC and relatively low PC levels displayed low co‐expression of GDPD5, CHKA and PLD1. GDPD5, CHKA and PLD1 were significantly overexpressed in highly malignant ER– tumors in our patient cohort. Our study identified GDPD5 as a GPC‐PDE that probably participates in the regulation of choline phospholipid metabolism in breast cancer, which possibly occurs in cooperation with CHKA and PLD1. Copyright © 2012 John Wiley & Sons, Ltd.
Audiovisual speech integration in autism spectrum disorders: ERP evidence for atypicalities in lexical‐semantic processing

In typically developing (TD) individuals, behavioral and event‐related potential (ERP) studies suggest that audiovisual (AV) integration enables faster and more efficient processing of speech. However, little is known about AV speech processing in individuals with autism spectrum disorders (ASD). This study examined ERP responses to spoken words to elucidate the effects of visual speech (the lip movements accompanying a spoken word) on the range of auditory speech processing stages from sound onset detection to semantic integration. The study also included an AV condition, which paired spoken words with a dynamic scrambled face in order to highlight AV effects specific to visual speech. Fourteen adolescent boys with ASD (15–17 years old) and 14 age‐ and verbal IQ‐matched TD boys participated. The ERP of the TD group showed a pattern and topography of AV interaction effects consistent with activity within the superior temporal plane, with two dissociable effects over frontocentral and centroparietal regions. The posterior effect (200–300? ms interval) was specifically sensitive to lip movements in TD boys, and no AV modulation was observed in this region for the ASD group. Moreover, the magnitude of the posterior AV effect to visual speech correlated inversely with ASD symptomatology. In addition, the ASD boys showed an unexpected effect (P2 time window) over the frontocentral region (pooled electrodes F3, Fz, F4, FC1, FC2, FC3, FC4), which was sensitive to scrambled face stimuli. These results suggest that the neural networks facilitating processing of spoken words by visual speech are altered in individuals with ASD. Autism Res2011,4:xxx–xxx. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.
Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine

Objective:HIV-1 persists indefinitely in memory CD4+ T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from 24 HIV-1 infected patients with detectable viremia. Design and methods:Blood and urine samples were obtained from 35 HIV-1 positive patients. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine-derived cell pellets, respectively, as well as from plasma and peripheral blood mononuclear cell from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter model. Results:We amplified and sequenced the full-length HIV-1 envelope (env) gene from 12 of the 24 individuals, indicating that 50% of the viremic HIV-1-positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four individuals with more than 15 urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those peripheral blood mononuclear cell and plasma-derived sequences, consistent with viral compartmentalization in the urine. Conclusion:Our results suggest the presence of a distinct HIV compartment in the genitourinary tract.
Chronic Effects of Coated Silver Nanoparticles on Marine Invertebrate Larvae: A Proof of Concept Study

Silver nanoparticles (AgNPs), owing to their unique physical and chemical properties, have become increasingly popular in consumer products. However, data on their potential biological effects on marine organisms, especially invertebrates, remain very limited. This proof of principle study reports the chronic sub-lethal toxicity of two coated AgNPs (oleic acid coated AgNPs and polyvinylpyrrolidone coated AgNPs) on marine benthic invertebrate larvae across three phyla (i.e., the barnacle Balanus Amphitrite, the slipper-limpet Crepidula onyx, and the polychaete Hydroides elegans) in terms of growth, development, and metamorphosis. Bioaccumulation and biodistribution of silver were also investigated. Larvae were also exposed to silver nitrate (AgNO3) in parallel to distinguish the toxic effects derived from nano-silver and the aqueous form of silver. The sub-lethal effect of chronic exposure to coated AgNPs resulted in a significant retardation in growth and development, and reduction of larval settlement rate. The larval settlement rate of H. elegans was significantly lower in the coated AgNP treatment than the AgNO3 treatment, suggesting that the toxicity of coated AgNPs might not be solely evoked by the release of silver ions (Ag+) in the test medium. The three species accumulated silver effectively from coated AgNPs as well as AgNO3, and coated AgNPs were observed in the vacuoles of epithelial cell in the digestive tract of C. onyx. Types of surface coatings did not affect the sub-lethal toxicity of AgNPs. This study demonstrated that coated AgNPs exerted toxic effects in a species-specific manner, and their exposure might allow bioaccumulation of silver, and affect growth, development, and settlement of marine invertebrate larvae. This study also highlighted the possibility that coated AgNPs could be taken up through diet and the toxicity of coated AgNPs might be mediated through toxic Ag+ as well as the novel modalities of coated AgNPs.
Idiopathic Microscopic Colitis of Rhesus Macaques: Quantitative Assessment of Colonic Mucosa

Idiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. While lesions may be absent at colonoscopy, the histopathologic evaluation of the biopsy specimens is consistent with human macroscopic colitis (MC). In this study, we developed an isotropic uniform random sampling method to evaluate macroscopic and microscopic changes and applied it on proximal ascending colon in monkeys. Colonic tissue and peripheral blood specimens were collected from six MC and six control juvenile macaques at necropsy. Uniform random samples were collected from the colon using punch biopsy tools. The volume of epithelium and lamina propria were estimated in thick (25 µm) sections using point probes and normalized to the area of muscularis mucosae. Our data suggests a significant increase of the Vs of the lamina propria (1.9‐fold, P = 0.02) and epithelium (1.4‐fold, P = 0.05) in subjects with MC. The average colonic surface mucosa area in the MC monkeys increased 1.4‐fold over the controls (P = 0.02). The volume of the proximal colon in animals with MC showed a 2.4‐fold increase over the non‐diarrhea control monkeys (P = 0.0001). Cytokine, chemokine, and growth factor levels in peripheral blood were found to be correlated with the volume estimate of the lamina propria and epithelium. We found that ICD in macaques has features which simulates human MC and can be used as a spontaneous animal model for human MC. Furthermore, this developed sampling method can be used for unbiased preclinical evaluation of therapeutics in this animal model. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.
Direct substitution and assisted dissociation pathways for turning off transcription by a MerR-family metalloregulator

Metalloregulators regulate transcription in response to metal ions. Many studies have provided insights into how transcription is activated upon metal binding by MerR-family metalloregulators. In contrast, how transcription is turned off after activation is unclear. Turning off transcription promptly is important, however, as the cells would not want to continue expressing metal resistance genes and thus waste energy after metal stress is relieved. Using single-molecule FRET measurements we studied the dynamic interactions of the copper efflux regulator (CueR), a Cu+-responsive MerR-family metalloregulator, with DNA. Besides quantifying its DNA binding and unbinding kinetics, we discovered that CueR spontaneously flips its binding orientation at the recognition site. CueR also has two different binding modes, corresponding to interactions with specific and nonspecific DNA sequences, which would facilitate recognition localization. Most strikingly, a CueR molecule coming from solution can directly substitute for a DNA-bound CueR or assist the dissociation of the incumbent CueR, both of which are unique examples for any DNA-binding protein. The kinetics of the direct protein substitution and assisted dissociation reactions indicate that these two unique processes can provide efficient pathways to replace a DNA-bound holo-CueR with apo-CueR, thus turning off transcription promptly and facilely.
Reduced Myocardial 123-Iodine Metaiodobenzylguanidine Uptake: A Prognostic Marker in Familial Amyloid Polyneuropathy

Background— Transthyretin familial amyloid polyneuropathy is a hereditary form of amyloidosis characterized by sensorimotor and autonomic neuropathy, cardiac conduction defects, and infiltrative cardiomyopathy. Previous studies have suggested that myocardial sympathetic denervation assessed by 123-iodine metaiodobenzylguanidine (MIBG) imaging occurs early in disease progression. However, its prognostic significance was never evaluated. We aimed to study the long-term prognostic value of myocardial sympathetic denervation detected by MIBG imaging in transthyretin familial amyloid polyneuropathy. Methods and Results— A total of 143 individuals with V30M transthyretin mutation underwent Holter, ambulatory blood pressure monitoring, echocardiography, and MIBG imaging. Time to all-cause death was compared with late heart-to-mediastinum MIBG uptake ratio (H/M; either in relation to the estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses were performed to test the prognostic accuracy of clinical, neurological, and cardiovascular parameters. During a median follow-up of 5.5 years, 32 (22%) patients died. Five-year mortality rate was 42% for late H/M <1.60 and 7% for late H/M ≥1.60 (hazard ratio, 7.19; P<0.001). Late H/M was identified as an independent prognostic predictor. Fifty-three patients were submitted to liver transplantation. In comparison with neurophysiological score–matched controls, transplanted patients had lower long-term mortality (hazard ratio, 0.32; P=0.012). Patients with late H/M<1.60 were at higher risk of unfavorable outcome but seemed to have benefited from liver transplantation. Conclusions— Cardiac sympathetic denervation as assessed by MIBG imaging is a useful prognostic marker in transthyretin familial amyloid polyneuropathy.
The Impact of Gestational Age at Delivery on Urologic Outcomes for the Fetus with Hydronephrosis

ABSTRACT Objective: Compare short-term urologic outcomes with delivery timing in fetuses with severe hydronephrosis. Methods: An ultrasound database was queried for severe hydronephrosis. Cases were categorized into late preterm/early term (36 0/7 - 38 6/7 weeks) and full term (39 0/7 weeks or greater) groups. Baseline characteristics were compared using standard statistical methods. Spearman's correlation analysis was performed for grade and severity of hydronephrosis on first postnatal ultrasound with gestational age at delivery. Results: Of 589 cases, 79 (33 late preterm/early term, 46 full term) met criteria. Baseline characteristics were similar between groups. Spearman's correlation coefficients (rs) indicated that increased postnatal Society for Fetal Urology grade, rs= −0.26 (95% CI [−.48, −.002]), and severity of hydronephrosis, rs= −0.39 (95% CI [−.59, −.14]), both correlated with earlier delivery. Conclusion: Late preterm/early term delivery resulted in worse short-term postnatal renal outcomes. Unless otherwise indicated, delivery for fetal hydronephrosis should be deferred until 39 weeks.
Retrobiosynthetic Approach Delineates the Biosynthetic Pathway and the Structure of the Acyl Chain of Mycobacterial Glycopeptidolipids*

Background: Precise chemical structure and biosynthetic pathway of the acyl chain of mycobacterial glycopeptidolipids (GPLs) is unknown. Results: Polyketide synthases dictate biosynthesis and determine hydroxylation at C-5 position of the GPL acyl chain. Conclusions: Retrobiosynthetic studies establish the role of bimodular polyketide synthase and fatty acyl-AMP-ligase in GPL biosynthesis. Significance: The long-standing ambiguity on the accurate structure and the biosynthetic mechanism of GPLs was resolved. Glycopeptidolipids (GPLs) are dominant cell surface molecules present in several non-tuberculous and opportunistic mycobacterial species. GPLs from Mycobacterium smegmatis are composed of a lipopeptide core unit consisting of a modified C26-C34 fatty acyl chain that is linked to a tetrapeptide (Phe-Thr-Ala-alaninol). The hydroxyl groups of threonine and terminal alaninol are further modified by glycosylations. Although chemical structures have been reported for 16 GPLs from diverse mycobacteria, there is still ambiguity in identifying the exact position of the hydroxyl group on the fatty acyl chain. Moreover, the enzymes involved in the biosynthesis of the fatty acyl component are unknown. In this study we show that a bimodular polyketide synthase in conjunction with a fatty acyl-AMP ligase dictates the synthesis of fatty acyl chain of GPL. Based on genetic, biochemical, and structural investigations, we determine that the hydroxyl group is present at the C-5 position of the fatty acyl component. Our retrobiosynthetic approach has provided a means to understand the biosynthesis of GPLs and also resolve the long-standing debate on the accurate structure of mycobacterial GPLs.