Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific Glycosylation of Membrane Proteins in Epithelial Ovarian Cancer Cell Lines: Glycan Structures Reflect Gene Expression and DNA Methylation Status *

Epithelial ovarian cancer is the fifth most common cause of cancer in women worldwide bearing the highest mortality rate among all gynecological cancers. Cell membrane glycans mediate various cellular processes such as cell signaling and become altered during carcinogenesis. The extent to which glycosylation changes are influenced by aberrant regulation of gene expression is nearly unknown for ovarian cancer and remains crucial in understanding the development and progression of this disease. To address this effect, we analyzed the membrane glycosylation of non-cancerous ovarian surface epithelial (HOSE 6.3 and HOSE 17.1) and serous ovarian cancer cell lines (SKOV 3, IGROV1, A2780, and OVCAR 3), the most common histotype among epithelial ovarian cancers. N-glycans were released from membrane glycoproteins by PNGase F and analyzed using nano-liquid chromatography on porous graphitized carbon and negative-ion electrospray ionization mass spectrometry (ESI-MS). Glycan structures were characterized based on their molecular masses and tandem MS fragmentation patterns. We identified characteristic glycan features that were unique to the ovarian cancer membrane proteins, namely the “bisecting N-acetyl-glucosamine” type N-glycans, increased levels of α 2–6 sialylated N-glycans and “N,N′-diacetyl-lactosamine” type N-glycans. These N-glycan changes were verified by examining gene transcript levels of the enzymes specific for their synthesis (MGAT3, ST6GAL1, and B4GALNT3) using qRT-PCR. We further evaluated the potential epigenetic influence on MGAT3 expression by treating the cell lines with 5-azacytidine, a DNA methylation inhibitor. For the first time, we provide evidence that MGAT3 expression may be epigenetically regulated by DNA hypomethylation, leading to the synthesis of the unique “bisecting GlcNAc” type N-glycans on the membrane proteins of ovarian cancer cells. Linking the observation of specific N-glycan substructures and their complex association with epigenetic programming of their associated synthetic enzymes in ovarian cancer could potentially be used for the development of novel anti-glycan drug targets and clinical diagnostic tools.
Manipulation of Female Parasitoid Age Enhances Laboratory Culture of LYSIPHLEBUS TESTACEIPES (hymenoptera: aphidiidae) Reared on TOXOPTERA CITRICIDA (Homoptera: aphididae)

Abstract Cultures of the endoparasitoid Lysiphlebus testaceipes Cresson (Hymenoptera: Aphidiidae) on the brown citrus aphid, Toxoptera citricida Kirkaldy (Homoptera: Aphididae), previously have been reported to be difficult to establish. In this study, L. testaceipes colonies were initiated from parasitized brown citrus aphids obtained from field-collected citrus foliage in Florida and successfully maintained for >25 generations in the laboratory. To enhance colony rearing methods, several aspects of the parasitoid’s biology were examined. An evaluation of foraging by single or multiple females determined that the presence of multiple females did not influence mean progeny yield per female. However, the mean number of progeny produced by mature (25-49 and 49-73 h) L. testaceipes females was higher than that produced by younger (1-25 h) females over a 24-h period. In all three parasitoid age classes, each reared on second-, third- or fourth-instar aphid hosts, significantly more mummies containing L. testaceipes formed on a paper coffee filter covering the soil surface compared to the number of mummies formed on citrus foliage. Mummy formation off foliage has not been reported for this aphid-parasitoid complex in citrus. Mated females of L. testaceipes with access to honey and water and without access to aphids or honeydew lived longer than females that had access to aphid hosts and honeydew. These data provide novel findings on the biology of L. testaceipes when parasitizing the brown citrus citrus, particularly on mummification sites, and allowed us to develop a protocol for routine large-scale rearing of L. testaceipes on brown citrus aphids on citrus.
Expressing Disagreement in the Council of the European Union

The Council of the European Union is the most important legislative body of the Union that decides upon approvals to legislation accordingly to the rule envisaged by the establishing treaties. Whereas most acts are approved by consensus, this article explores rare cases where a member state expresses its disagreeement with the final version. The author analyses the ways to express the disagreement, its frequency and reasoning.
Increasing western US forest wildfire activity: sensitivity to changes in the timing of spring

Prior work shows western US forest wildfire activity increased abruptly in the mid-1980s. Large forest wildfires and areas burned in them have continued to increase over recent decades, with most of the increase in lightning-ignited fires. Northern US Rockies forests dominated early increases in wildfire activity, and still contributed 50% of the increase in large fires over the last decade. However, the percentage growth in wildfire activity in Pacific northwestern and southwestern US forests has rapidly increased over the last two decades. Wildfire numbers and burned area are also increasing in non-forest vegetation types. Wildfire activity appears strongly associated with warming and earlier spring snowmelt. Analysis of the drivers of forest wildfire sensitivity to changes in the timing of spring demonstrates that forests at elevations where the historical mean snow-free season ranged between two and four months, with relatively high cumulative warm-season actual evapotranspiration, have been most affected. Increases in large wildfires associated with earlier spring snowmelt scale exponentially with changes in moisture deficit, and moisture deficit changes can explain most of the spatial variability in forest wildfire regime response to the timing of spring. This article is part of the themed issue ‘The interaction of fire and mankind’.
Epidemiology of melanoma: is it still epidemic? What is the role of the sun, sunbeds, Vit D, betablocks, and others?

The incidence of cutaneous malignant melanoma is continuously increasing worldwide, but only minimal changes in mortality have been observed. This phenomenon has brought into question whether this increased incidence reflects a true or apparent melanoma epidemic. The most recent data suggest that this epidemiological trend may be explained by the existence of a certain degree of melanoma overdiagnosis, especially of thin lesions, which probably would never progress to advanced disease if left untreated. However, acute sun exposure and widespread use of sunbeds may also justify the increase in melanoma incidence. Recently, both vitamin D and beta‐blocker use seem to play a beneficial role in melanoma progression.
Characterization of a family of gamma-ray-induced CHO mutants demonstrates that the ldlA locus is diploid and encodes the low-density lipoprotein receptor

The ldlA locus is one of four Chinese hamster ovary (CHO) cell loci which are known to be required for the synthesis of functional low-density lipoprotein (LDL) receptors. Previous studies have suggested that the ldlA locus is diploid and encodes the LDL receptor. To confirm this assignment, we have isolated a partial genomic clone of the Chinese hamster LDL receptor gene and used this and other nucleic acid and antibody probes to study a family of ldlA mutants isolated after gamma-irradiation. Our analysis suggests that there are two LDL receptor alleles in wild-type CHO cells. Each of the three mutants isolated after gamma-irradiation had detectable deletions affecting one of the two LDL receptor alleles. One of the mutants also had a disruption of the remaining allele, resulting in the synthesis of an abnormal receptor precursor which was not subject to Golgi-associated posttranslational glycoprotein processing. The correlation of changes in the expression, structure, and function of LDL receptors with deletions in the LDL receptor genes in these mutants directly demonstrated that the ldlA locus in CHO cells is diploid and encodes the LDL receptor. In addition, our analysis suggests that CHO cells in culture may contain a partial LDL receptor pseudogene.
Dementia associated with dorsal midbrain lesion

Abstract Although the dorsal midbrain has been implicated in cognitive processes in animals, its role in humans is unclear. We report the neuropsychological and postmortem neuropathological findings of a 52-yr-old university professor who developed a profound dementia in association with a focal dorsal midbrain lesion. The patient's disorder appeared to result from a tuberculous granuloma based on the clinical course and autopsy results. Neuropsychologically, he exhibited a generalized impairment across most of the cognitive domains assessed. His deficits were not explained by impaired arousal, specific sensory or motor defects, depression, or hydrocephalus. Although there are inherent limitations to a single-case investigation, our observations are consistent with animal studies that have demonstrated that focal dorsal midbrain lesions may result in cognitive impairment. We propose that the dorsal midbrain is involved in cognitive processing via modulation of thalamocortical networks. (JINS, 1996, 2, 359–367.)
Complex signal measurement bench based on a special spectrum super-resolution algorithm

This paper presents a new algorithm that allows the use of non-uniform multi-sines for CAD/CAE modeling and characterization procedures. The new measurement procedure explores the narrow bandwidth of the signals used to obtain a sparsely, possibly NON-uniformly sampled representation, from which the spectral coefficients can nevertheless be accurately estimated.
In vivo Serial Passaging of Human–Simian Immunodeficiency Virus Clones Identifies Characteristics for Persistent Viral Replication

We previously reported that a human immunodeficiency virus type 1 with a simian immunodeficiency virus vif substitution (HSIV-vifNL4-3) could replicate in pigtailed macaques (PTMs), demonstrating that Vif is a species-specific tropism factor of primate lentiviruses. However, infections did not result in high-peak viremia or setpoint plasma viral loads, as observed during simian immunodeficiency virus (SIV) infection of PTMs. Here, we characterized variants isolated from one of the original infected animals with CD4 depletion after nearly 4years of infection to identify determinants of increased replication fitness. In our studies, we found that the HSIV-vif clones did not express the HIV-1 Vpr protein due to interference from the vpx open reading frame (ORF) in singly spliced vpr mRNA. To examine whether these viral genes contribute to persistent viral replication, we generated infectious HSIV-vif clones expressing either the HIV-1 Vpr or SIV Vpx protein. And then to determine viral fitness determinants of HSIV-vif, we conducted three rounds of serial in vivo passaging in PTMs, starting with an initial inoculum containing a mixture of CXCR4-tropic [Vpr-HSIV-vifNL4-3 isolated at 196 (C/196) and 200 (C/200) weeks post-infection from a PTM with depressed CD4 counts] and CCR5-tropic HSIV (Vpr+ HSIV-vif derivatives based NL-AD8 and Bru-Yu2 and a Vpx expressing HSIV-vifYu2). Interestingly, all infected PTMs showed peak plasma viremia close to or above 105 copies/ml and persistent viral replication for more than 20weeks. Infectious molecular clones (IMCs) recovered from the passage 3 PTM (HSIV-P3 IMCs) included mutations required for HIV-1 Vpr expression and those mutations encoded by the CXCR4-tropic HSIV-vifNL4-3 isolate C/196. The data indicate that the viruses selected during long-term infection acquired HIV-1 Vpr expression, suggesting the importance of Vpr for in vivo pathogenesis. Further passaging of HSIV-P3 IMCs in vivo may generate pathogenic variants with higher replication capacity, which will be a valuable resource as challenge virus in vaccine and cure studies.
The Neuropeptide Substance P Activates p38 Mitogen-Activated Protein Kinase Resulting in IL-6 Expression Independently from NF-κB1

Substance P (SP), a member of the tachykinin peptide family, is a major mediator of neuroimmunomodulatory activities and neurogenic inflammation within the central and peripheral nervous system. SP has been shown to induce the expression of proinflammatory cytokines such as IL-6, which might be implicated in the etiopathology of several human brain disorders. We showed in a previous study that nanomolar concentrations of SP triggered activation of NF-κB, a transcription factor involved in the control of cytokine expression. However, activation of NF-κB was not involved in SP-induced expression of IL-6. Here, we describe p38 mitogen-activated protein kinase (p38 MAPK) as a signal transduction component that operates independently from NF-κB activation and that mediates SP-induced IL-6 expression in the human astrocytoma cell line U373 MG. SP induced the phosphorylation of p38 MAPK within 10 min, and this activation persisted up to 30 min and was independent from p42/44 MAPKs and protein kinase C activation, which all are induced after stimulation with SP. As shown by EMSA, p38 MAPK was not involved in SP-induced activation of NF-κB. p38 MAPK, however, mediated SP-induced IL-6 expression as shown by the use of specific inhibitors of this kinase. Our results suggest that activation of p38 MAPK is an important component controlling neurogenic inflammation within the CNS independently from NF-κB. Drugs targeting this MAPK may therefore interfere with SP-correlated neuropsychiatric disorders and may represent a therapeutic approach in these disorders.
Mammalian ECD Protein Is a Novel Negative Regulator of the PERK Arm of the Unfolded Protein Response

ABSTRACT Mammalian Ecdysoneless (ECD) is a highly conserved ortholog of the DrosophilaEcd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects, but the mechanisms by which ECD functions are largely unknown. Here we present evidence that ECD regulates the endoplasmic reticulum (ER) stress response. ER stress induction led to a reduced ECD protein level, but this effect was not seen in PKR-like ER kinase knockout (PERK-KO) or phosphodeficient eukaryotic translation initiation factor 2α (eIF2α) mouse embryonic fibroblasts (MEFs); moreover, ECD mRNA levels were increased, suggesting impaired ECD translation as the mechanism for reduced protein levels. ECD colocalizes and coimmunoprecipitates with PERK and GRP78. ECD depletion increased the levels of both phospho-PERK (p-PERK) and p-eIF2α, and these effects were enhanced upon ER stress induction. Reciprocally, overexpression of ECD led to marked decreases in p-PERK, p-eIF2α, and ATF4 levels but robust increases in GRP78 protein levels. However, GRP78 mRNA levels were unchanged, suggesting a posttranscriptional event. Knockdown of GRP78 reversed the attenuating effect of ECD overexpression on PERK signaling. Significantly, overexpression of ECD provided a survival advantage to cells upon ER stress induction. Taken together, our data demonstrate that ECD promotes survival upon ER stress by increasing GRP78 protein levels to enhance the adaptive folding protein in the ER to attenuate PERK signaling.
A Meta-Analysis of the Use of Nonsteroidal Antiinflammatory Drugs for Pediatric Postoperative Pain

BACKGROUND: Opioid side effects are a great concern during the postoperative period in children. Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to effectively decrease postoperative pain, but their opioid-sparing effect is still controversial. In this present meta-analysis, we investigated the postoperative opioid-sparing effect of NSAIDs in children. METHODS: A comprehensive literature search was conducted to identify clinical trials using NSAIDs and opioids as perioperative analgesic compounds in children and infants. Outcomes measured were opioid consumption, pain intensity, postoperative nausea and vomiting (PONV), and urinary retention. All outcomes were studied during postanesthesia care unit (PACU) stay and the first 24 postoperative hours. Data from each trial were combined to calculate the pooled odds ratios (ORs) or standardized mean difference (SMD) and their 95% confidence interval. RESULTS: Twenty-seven randomized controlled studies were analyzed. Perioperative administration of NSAIDs decreased postoperative opioid requirement (both in the PACU and during the first 24 postoperative hours; SMD = −0.66 [−0.84, −0.48] and −0.83 [−1.11, −0.55], respectively), pain intensity in the PACU (SMD = −0.85 [−1.24, −0.47]), and PONV during the first 24 postoperative hours (OR = 0.75 [0.57–0.99]). NSAIDs did not decrease pain intensity during the first 24 postoperative hours (OR = 0.56 [0.26–1.2]) and PONV during PACU stay (OR = 1.02 [0.73–1.44]). Subgroup analysis according to the timing of NSAID administration (intraoperative versus postoperative), type of surgery, or coadministration of paracetamol did not show any influence of these factors on the studied outcomes except the reduction of pain intensity and the incidence of PONV during the first 24 postoperative hours, which were influenced by the coadministration of paracetamol and the type of surgery, respectively. CONCLUSION: This meta-analysis shows that perioperative NSAID administration reduces opioid consumption and PONV during the postoperative period in children.
Fast TCP flow control with differentiated services

This paper presents an enhancement of the flow control mechanism of traditional TCP, which is called the differentiated service Fast-TCP policy. The basic idea of this policy is delaying ACK from the destination towards the source to inform the source that the network will be congested, and to direct the TCP source to slowdown its output rates. Considering various performance requirement of services and users, the ACK delay time is set at several levels to slowdown the output rate of services in a different extent to satisfy their delay and throughput requirement. Simulation and results comparison show the effect of this proposed policy in a simple network.
Ultrafast time-resolved carotenoid to-bacteriochlorophyll energy transfer in LH2 complexes from photosynthetic bacteria.

Steady-state and ultrafast time-resolved optical spectroscopic investigations have been carried out at 293 and 10 K on LH2 pigment-protein complexes isolated from three different strains of photosynthetic bacteria: Rhodobacter (Rb.) sphaeroides G1C, Rb. sphaeroides 2.4. 1 (anaerobically and aerobically grown), and Rps. acidophila 10050. The LH2 complexes obtained from these strains contain the carotenoids, neurosporene, spheroidene, spheroidenone, and rhodopin glucoside, respectively. These molecules have a systematically increasing number of pi-electron conjugated carbon-carbon double bonds. Steady-state absorption and fluorescence excitation experiments have revealed that the total efficiency of energy transfer from the carotenoids to bacteriochlorophyll is independent of temperature and nearly constant at approximately 90% for the LH2 complexes containing neurosporene, spheroidene, spheroidenone, but drops to approximately 53% for the complex containing rhodopin glucoside. Ultrafast transient absorption spectra in the near-infrared (NIR) region of the purified carotenoids in solution have revealed the energies of the S1 (2(1)Ag-)-->S2 (1(1)Bu+) excited-state transitions which, when subtracted from the energies of the S0 (1(1)Ag-)-->S2 (1(1)Bu+) transitions determined by steady-state absorption measurements, give precise values for the positions of the S1 (2(1)Ag-) states of the carotenoids. Global fitting of the ultrafast spectral and temporal data sets have revealed the dynamics of the pathways of de-excitation of the carotenoid excited states. The pathways include energy transfer to bacteriochlorophyll, population of the so-called S* state of the carotenoids, and formation of carotenoid radical cations (Car*+). The investigation has found that excitation energy transfer to bacteriochlorophyll is partitioned through the S1 (1(1)Ag-), S2 (1(1)Bu+), and S* states of the different carotenoids to varying degrees. This is understood through a consideration of the energies of the states and the spectral profiles of the molecules. A significant finding is that, due to the low S1 (2(1)Ag-) energy of rhodopin glucoside, energy transfer from this state to the bacteriochlorophylls is significantly less probable compared to the other complexes. This work resolves a long-standing question regarding the cause of the precipitous drop in energy transfer efficiency when the extent of pi-electron conjugation of the carotenoid is extended from ten to eleven conjugated carbon-carbon double bonds in LH2 complexes from purple photosynthetic bacteria.
The evolution of mammal body sizes: responses to Cenozoic climate change in North American mammals

Explanations for the evolution of body size in mammals have remained surprisingly elusive despite the central importance of body size in evolutionary biology. Here, we present a model which argues that the body sizes of Nearctic mammals were moulded by Cenozoic climate and vegetation changes. Following the early Eocene Climate Optimum, forests retreated and gave way to open woodland and savannah landscapes, followed later by grasslands. Many herbivores that radiated in these new landscapes underwent a switch from browsing to grazing associated with increased unguligrade cursoriality and body size, the latter driven by the energetics and constraints of cellulose digestion (fermentation). Carnivores also increased in size and digitigrade, cursorial capacity to occupy a size distribution allowing the capture of prey of the widest range of body sizes. With the emergence of larger, faster carnivores, plantigrade mammals were constrained from evolving to large body sizes and most remained smaller than 1 kg throughout the middle Cenozoic. We find no consistent support for either Cope's Rule or Bergmann's Rule in plantigrade mammals, the largest locomotor guild (n = 1186, 59% of species in the database). Some cold‐specialist plantigrade mammals, such as beavers and marmots, showed dramatic increases in body mass following the Miocene Climate Optimum which may, however, be partially explained by Bergmann's rule. This study reemphasizes the necessity of considering the evolutionary history and resultant form and function of mammalian morphotypes when attempting to understand contemporary mammalian body size distributions.