Miracle-dz/UniFAR-FTUs huggingface dataset:
The development of the subplate and thalamocortical connections in the human foetal brain

The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the ‘waiting’ period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory‐driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness.
In Vivo Autoxidation of Dopamine in Guinea Pig Striatum Increases with Age

Catechols are known to react readily with molecular oxygen to form the corresponding quinones together with reduced oxygen species. These products have been shown to be toxic in in vivo and in vitro systems. 5‐S‐Cysteinyl adducts of catechols are believed to be formed through the spontaneous reaction between quinones and thiol‐containing compounds, like cysteine and glutathione (GSH). Thus, the brain levels of these adducts probably indicate the autoxidation rate of catechols in vivo. In the present study, the striatal concentrations of 5‐S‐cysteinyldopamine (5‐S‐cysteinyl‐DA), 5‐S‐cysteinyl‐3,4‐dihydroxyphenylalanine (5‐S‐cysteinyl‐DOPA), and 5‐S‐cysteinyl‐3,4‐dihydroxyphenylacetic acid (5‐S‐cysteinyl‐DOPAC) were determined in 2‐week‐, 2‐month‐and 3‐year‐old guinea pigs. In addition, brain levels of DA, the DA metabolite DOPAC, and GSH were assessed. The concentration of 5‐S‐cysteinyl‐DA increased markedly with age. The 3‐year‐old guinea pigs had the highest level, i.e., 248% of the concentration in the 2‐week‐old animals and 219% of the concentration in the 2‐month‐old animals. Furthermore, the striatal 5‐S‐cysteinyl‐DOPA level in the 3‐year‐old group was 68% higher than in the 2‐week‐old group and 46% higher than in the 2‐month‐old group. No age difference in the striatal concentration of DA was found. In contrast, the concentration of DOPAC increased with age: The DOPAC level in the 3‐year‐old animals was 153% of the level in the 2‐week‐old animals and 116% of the level in the 2‐month‐old animals. A slight decrease in brain GSH content was observed between 2 weeks and 2 months, whereas the level in the 3‐year‐old animals was not significantly different from the concentration in the 2‐month‐old animals. Thus, the present study has shown an increase in 5‐S‐cysteinyl‐DA and 5‐S‐cysteinyl‐DOPA levels with age in guinea pig striatum. The rise in 5‐S‐cysteinyl‐DA content was larger than the increase in content of the DA metabolite DOPAC, a finding indicating that DA to a greater extent undergoes autoxidation with increasing age. This may be part of the mechanism underlying the loss of dopaminergic neurons in senescence and in Parkinson's disease.
Quality Control Trial for Human Immunodeficiency Virus Type 1 Drug Resistance Testing Using Clinical Samples Reveals Problems with Detecting Minority Species and Interpretation of Test Results

ABSTRACT Between January and March 2000, a quality control panel for human immunodeficiency virus (HIV) drug resistance testing was analyzed by 20 laboratories in five countries. The panel consisted of three clinical samples with different drug resistance genotypes and phenotypes and one HIV-negative plasma. Participants were asked to report the methods used for amplification and sequencing, a list of drug resistance-associated mutations that were detected in the protease and reverse transcriptase of each sample, and an interpretation concerning the susceptibility or resistance to 14 antiretroviral drugs. A total of 22 genotypic data sets were generated, which showed an overall good technical quality except for three participants, who failed to report key mutations for drug resistance. Problems were encountered in three respects: (i) resistant minorities of L90M in the protease, which were determined to about 12% by real-time amplification, were only detected by one-fourth of the participants; (ii) newly described resistance mutations were frequently not reported; and (iii) interpretations of drug resistance-associated mutations varied widely, in particular for protease inhibitors. In some cases, different interpretations were caused by differences in the detection of resistant minorities, but even for the same genotypic profile, interpretations varied considerably. Similar discrepancies were revealed if current Web-based interpretation systems were used to predict drug resistance for samples of the proficiency panel. This indicates that a consensus for the interpretation of drug resistance-associated mutations is urgently needed.
Impact of Hispanic or Asian Ethnicity on the Treatment Outcomes of Chronic Hepatitis C: Results From the WIN-R Trial

Background and Aims African American ethnicity is a well-described negative predictor of treatment outcome for chronic hepatitis C (CHC); however, less is known about the influence of Hispanic and Asian ethnicity. The aim of this subanalysis of the Weight-based Dosing of PegINterferon &agr;-2b and Ribavirin (WIN-R) study was to assess the impact of Asian (n=118), Hispanic (n=289), and white (n=3919) ethnicity on CHC treatment outcomes. Methods WIN-R was an investigator-initiated trial in which patients with CHC received pegylated interferon &agr;-2b (1.5 &mgr;g/kg/wk) plus a fixed ribavirin dose (800 mg/d) or a weight-based ribavirin dose (800 to 1400 mg/d) for 24 or 48 weeks. Results Sustained virologic response was higher in Asian patients than in white patients (56% vs 46%, P=0.041), and higher in Asian and white patients than in Hispanic patients (56% vs 35%, P=0.0001; and 46% vs 35%, P=0.0002, respectively). In genotype 1 patients, sustained virologic response was higher in white and Asian patients than in Hispanic patients (36% and 45% vs 25%, P<0.001 for both comparisons); however, in genotype 2/3 patients, there were no significant differences among ethnic groups. Psychiatric adverse events were less common and anemia was more common in Asians than in white or Hispanic patients. Ribavirin dose reductions were less frequent in Hispanic patients than in white patients, whereas pegylated interferon&agr;-2b dose reductions were more common in white patients than Hispanic patients. Conclusion These observations highlight the importance of ethnicity as an integral component of the tailored treatment approach to CHC.
The multiple nicotinamide nucleotide-binding subunits of bovine heart mitochondrial NADH:ubiquinone oxidoreductase (complex I).

Direct photoaffinity labeling of purified bovine heart NADH:ubiquinone oxidoreductase (complex I) with 32P-labeled NAD(H), NADP(H) and ADP has shown that five polypeptides become labeled, with molecular masses of 51, 42, 39, 30, and 18-20 kDa. The 51 and the 30-kDa polypeptides were labeled with either [32P]NAD(H), [32P]NADP(H) or [beta-32P]ADP. The 42-kDa polypeptide was labeled with [32P]NAD(H) and to a small extent with [beta-32P]ADP. It was not labeled with [32P]NADP(H). The 39-kDa polypeptide was labeled with [32P]NADPH and to a small extent with [beta-32P]ADP. Our previous studies had shown that this subunit also binds NADP, but not NAD(H) [Yamaguchi, M. , Belogrudov, G.I. & Hatefi, Y. (1998) J. Biol. Chem. 273, 8094-8098]. The 18-20-kDa polypeptide was labeled only with [32P]NADPH. Among these polypeptides, the 51-kDa subunit is known to contain FMN and a [4Fe-4S] cluster, and is the NAD(P)H-binding subunit of the primary dehydrogenase domain of complex I. The possible roles of the other nucleotide-binding subunits of complex I have been discussed.
The Relationship between Glycan Binding and Direct Membrane Interactions in Vibrio cholerae Cytolysin, a Channel-forming Toxin*

Background: Vibrio cholerae secretes a toxin that forms channels in host cells. Results: Our study provides a complete structure/function mapping of the toxin membrane-interacting surface. Conclusion: Membrane binding integrates glycan recognition and direct lipid and cholesterol interactions. Significance: Targeting membrane interactions may be a viable approach for treating infectious disease. Bacterial pore-forming toxins (PFTs) are structurally diverse pathogen-secreted proteins that form cell-damaging channels in the membranes of host cells. Most PFTs are released as water-soluble monomers that first oligomerize on the membrane before inserting a transmembrane channel. To modulate specificity and increase potency, many PFTs recognize specific cell surface receptors that increase the local toxin concentration on cell membranes, thereby facilitating channel formation. Vibrio cholerae cytolysin (VCC) is a toxin secreted by the human pathogen responsible for pandemic cholera disease and acts as a defensive agent against the host immune system. Although it has been shown that VCC utilizes specific glycan receptors on the cell surface, additional direct contacts with the membrane must also play a role in toxin binding. To better understand the nature of these interactions, we conducted a systematic investigation of the membrane-binding surface of VCC to identify additional membrane interactions important in cell targeting. Through cell-based assays on several human-derived cell lines, we show that VCC is unlikely to utilize high affinity protein receptors as do structurally similar toxins from Staphylococcus aureus. Next, we identified a number of specific amino acid residues that greatly diminish the VCC potency against cells and investigated the interplay between glycan binding and these direct lipid contacts. Finally, we used model membranes to parse the importance of these key residues in lipid and cholesterol binding. Our study provides a complete functional map of the VCC membrane-binding surface and insights into the integration of sugar, lipid, and cholesterol binding interactions.
Insulin/Insulin-like Growth Factor I Hybrid Receptors Have Different Biological Characteristics Depending on the Insulin Receptor Isoform Involved*

The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) have a highly homologous structure, but different biological effects. Insulin and IGF-I half-receptors can heterodimerize, leading to the formation of insulin/IGF-I hybrid receptors (Hybrid-Rs) that bind IGF-I with high affinity. As the IR exists in two isoforms (IR-A and IR-B), we evaluated whether the assembly of the IGF-IR with either IR-A or IR-B moieties may differently affect Hybrid-R signaling and biological role. Three different models were studied: (a) 3T3-like mouse fibroblasts with a disrupted IGF-IR gene (R− cells) cotransfected with the human IGF-IR and with either the IR-A or IR-B cDNA; (b) a panel of human cell lines variably expressing the two IR isoforms; and (c) HepG2 human hepatoblastoma cells predominantly expressing either IR-A or IR-B, depending on their differentiation state. We found that Hybrid-Rs containing IR-A (Hybrid-RsA) bound to and were activated by IGF-I, IGF-II, and insulin. By binding to Hybrid-RsA, insulin activated the IGF-I half-receptor β-subunit and the IGF-IR-specific substrate CrkII. In contrast, Hybrid-RsBbound to and were activated with high affinity by IGF-I, with low affinity by IGF-II, and insignificantly by insulin. As a consequence, cell proliferation and migration in response to both insulin and IGFs were more effectively stimulated in Hybrid-RA-containing cells than in Hybrid-RB-containing cells. The relative abundance of IR isoforms therefore affects IGF system activation through Hybrid-Rs, with important consequences for tissue-specific responses to both insulin and IGFs.
Granulocyte colony-stimulating factors in the management of chemotherapy-induced neutropenia: evidence based review

(1) Neutropenia is a frequent complication of chemotherapy associated with life-threatening infections, hospitalisation, and chemotherapy dose reductions and delays. (2) Primary prophylaxis with granulocyte colony-stimulating factors has been shown to reduce the incidence and duration of neutropenia, febrile neutropenia, infections, hospitalisation and antibiotic use. (3) Recent randomised clinical trials of filgrastim, lenograstim and pegfilgrastim showed variable results across patient groups at different risks of febrile neutropenia. (4) Pegfilgrastim is at least as effective as filgrastim in the prophylaxis of chemotherapy-induced neutropenia and has improved pharmacokinetics requiring reduced administration.
Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro.

AIM To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs) in vitro. METHODS BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot. RESULTS Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 mug/L, respectively. However, the expression of CK19 by BECs was not changed. CONCLUSION CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.
Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

ABSTRACT Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.
Total phalloplasty using a musculocutaneous latissimus dorsi flap

Authors from Serbia describe their experience of total phalloplasty in children and adults using a musculocutaneous latissimus dorsi free flap, finding that this method successfully allowed the creation of a neophallus, facilitating subsequent urethroplasty and the safe insertion of a penile prosthesis.
Strong tectonic andweak climatic control of the geomorphologic and geological features inwest kunlun

TheWest Kunlun Mountains forms the northwestern margin of the Tibetan Plateau and is one of the key regions for understanding the uplift history of the Plateau and the geological structure of central Asia. This paper tries to figure out the geomorphologic and geological features of this region qualitatively through studying the data of Shuttle Reader Topography Mission (SRTM) and topographic maps by digital elevation models (DEMs) and constructing profiles, aiming to make clear what functions the tectonics and climate exert on the topography of the West Kunlun Mountains. Our results demonstrate that the tectonics play an important role to the topographic form in West Kunlun Mountains.
Making transparent metals based on scattering cancellations

It is highly desirable to make a metal film transparent for light, owing to many application requests for transparent metals in optoelectronics devices such as solar cells. Extraordinary optical transmission (EOT) is one of the mechanisms to make an opaque metal transparent, but it typically requires the metallic film to be perforated with subwavelength openings such as holes [1] or slits [2]. In addition, to achieve a high transmission, strict periodicity is required for the opening array perforated on the metal film, which adds substantial fabrication difficulties. Based on theoretical analysis and full-wave simulations, we proposed a scheme [3] to make a continuous metal film transparent in optical regime, with light scattered from the metal film canceled by those from two composite layers consisting of metallic and dielectric stripes. Such a transparency does not sacrifice the conductivity of the target metal and is robust against incidence angle as well as structural disorder. As a proof of concept, we performed microwave experiments to verify all theoretical predictions.
Application on Minimizing Residual AM in DPSK UDWDM-PON ONU by Integrated Dual-EML

A monolithically integrated dual electroabsorption modulated laser (DEML), consisting of distributed feedback laser (DFB) and electroabsorption modulator (EAM) sections, is proposed as a transmitter in an optical network unit with phase-shift keying (PSK) modulation. The DFB is directly modulated in phase, and the EAM section is applied for mitigating the residual amplitude modulation. The DEML, as compared with external phase modulator, has advantages of low cost, simplified design, low footprint, and reasonable power consumption, thus making it attractive for an ultradense wavelength division multiplexing passive optical unit. The system is validated at 2.5 and 5 Gb/s with intradyne detection.
The compressive deformation of multicomponent microcapsules: Influence of size, membrane thickness, and compression speed

The clinical application of microcapsules for the immunoisolation of living tissue requires knowledge about the mechanical stability of polymer membranes. Microcapsules of 400-1000 μm in diameter were formed through the gelation of sodium alginate/sodium cellulose sulfate droplets through calcium chloride, with the membrane produced via complex coacervation between polyanions and poly(methylene-co-guanidine) hydrochloride. The deformation behavior of these multicomponent microcapsules was investigated by uniaxial compression experiments. Specifically, the influence of the deformation speed, capsule diameter, and membrane thickness on the mechanical properties was evaluated. The bursting force was found to be dependent on the deformation speed. Therefore, the measurement of the bursting work, a speed-independent value of the resistance to high stresses and deformations, was recommended as the most valid for capsule mechanical resistance. Furthermore, the bursting force was positively correlated with membrane thickness only for membrane-radius ratios up to 20%. For thicker membranes, the bursting event occurred because the opposite membranes touched each other, and not, because of insufficient strength. Indeed, the resistance to smaller deformations was positively correlated to the membrane thickness over the whole range of membrane-radius ratios. Moreover, the forces for constant deformation were linearly correlated to the total membrane volume, independently of capsule size and membrane thickness.
Empirical examination of current depression categories in a population-based study: symptoms, course, and risk factors.

OBJECTIVE Research studies on the validity of current diagnostic and subthreshold categories of depression that use a population-based follow-up design are rare. The authors examined the validity and utility of four current depression categories by examining subject transition between categories and the symptoms, course, and risk factors of each. METHOD A general population sample of 1,920 adults from the Baltimore Epidemiologic Catchment Area 13-year follow-up study were examined. Data on diagnoses, symptoms, course, and risk factors were collected by using the National Institute of Mental Health Diagnostic Interview Schedule, the Life Chart Interview, and an office visit. Polychotomous regression was used to examine the heterogeneity of four diagnostic categories: major depressive disorder, depressive syndrome, dysthymia, and a comorbid depression condition (major depressive disorder and dysthymia). RESULTS Transitions between the four depression categories occurred over the 13 years. Symptom profiles for the four categories were parallel but differed in severity. Course characteristics among the four categories slightly differed. Risk factor profiles showed significant differences. Family history was associated with both depressive syndrome and major depressive disorder. Stressful life events were most strongly associated with depressive syndrome. Female gender was most strongly associated with the comorbid depression category. CONCLUSIONS The evidence suggests that except for dysthymia, the depression categories are genetically homogeneous and environmentally heterogeneous. Stress is associated with mild depression, and gender is associated with severe depression. The apparent familial transmission of the subthreshold entity, depressive syndrome, needs further investigation.
Testosterone treatment to mimic hormone physiology in androgen replacement therapy

There is still considerable controversy concerning the issue of testosterone replacement therapy. This is because testosterone replacement therapy is not a ‘risk-free’ treatment and a randomized controlled trial to evaluate safety of prolonged testosterone replacement therapy is not available, nor is it likely to be in the near future. However, recent testosterone delivery systems, such as the 1% gel (Testogel®, Androgel® and Testim®), have proven to have a good physiologic profile, allowing constant monitoring of the possible complications and prompt discontinuation in the event of adverse effects. The aim of this paper is to provide a comprehensive review of the available testosterone preparations to treat male hypogonadism, with special interest in the treatment of ageing men and late-onset hypogonadism. In addition, the experimental and clinical data on the effect of testosterone on sexual function domains is reviewed along with the indication for the combination therapy of androgens with pro-erectile drugs, for example, type 5 phosphodiesterase inhibitors.