bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallothionein mediates gene expression of 3.1 mRNA (PTZ17) related to epileptic seizure
Authors: Miura Nobuhiko , Naganuma Akira
Published: July 2002

Genes differentially expressed in association with disruption of the metallothionein gene were screened using two hepatic stellate cell lines isolated and established from the livers of normal 129/Sv (IMS/N cells) and transgenic mice deficient in the genes for metallothionein‐I and ‐II (IMS/MT (−) cells). We found one cDNA (tentatively named NM31) that was expressed only in IMS/N cells. Transfecting IMS/MT (−) cells with the genes for both metallothionein‐I and ‐II resulted in NM31 expression. These results suggest that metallothionein is essential for NM31 gene expression. The nucleotide sequence of NM31 (294 bp) was identical to the 3′ region of 3.1 mRNA (PTZ 17), which is abundant in the embryonic mouse brain and is related to chemically induced seizures. The present study indicates that metallothionein mediates the expression of specific genes. This is a novel explanation for some of the functions of metallothionein.
Expression levels of RGS7 and RGS4 proteins determine the mode of regulation of the G protein‐activated K+ channel and control regulation of RGS7 by Gβ5
Authors: Keren-Raifman Tal , Bera Amal K. , Zveig Dror , Peleg Sagit , Witherow D.Scott , Slepak Vladlen Z. , Dascal Nathan
Published: July 2002

Regulators of G protein signaling RGS4 and RGS7 accelerate the kinetics of K+ channels (GIRKs) in the Xenopus oocyte system. Here, via quantitative analysis of RGS expression, we reveal biphasic effects of RGSs on GIRK regulation. At low concentrations, RGS4 inhibited basal GIRK activity, but stimulated it at high concentrations. RGS7, which is associated with the G protein subunit Gβ5, is regulated by Gβ5 by two distinct mechanisms. First, Gβ5 augments RGS7 activity, and second, it increases its expression. These dual effects resolve previous controversies regarding RGS4 and RGS7 function and indicate that they modulate signaling by mechanisms supplementary to their GTPase‐activating protein activity.
Further evidence for a common mechanism for shedding of cell surface proteins
Authors: Müllberg Jürgen , Rauch Charles T , Wolfson Martin F , Castner Beverly , Fitzner Jeffrey N , Otten-Evans Carol , Mohler Kendall M , Cosman David , Black Roy A
Published: July 2002

Pro‐TNFα, Steel factor, type II IL‐1R and IL‐2Rα were expressed in COS‐7 cells and the generation of their soluble forms was examined. The release of all four proteins was strongly stimulated by the phorbol ester PMA and completely blocked by a hydroxamate‐based inhibitor of metalloproteases. COS‐7 cell membranes were found to cleave various synthetic pro‐TNFα peptides with the same specificity as a partially purified TNFα converting enzyme purified from human monocytic cells, suggesting that the same enzyme may be responsible for at least some of the COS‐7 cell shedding activity.
Tobacco cells contain a protein, immunologically related to the neutrophil small G protein Rac2 and involved in elicitor‐induced oxidative burst
Authors: Kieffer Flore , Simon-Plas Françoise , Maume Bernard F , Blein Jean-Pierre
Published: July 2002

© 1997 Federation of European Biochemical Societies.
Identification in the μ‐opioid receptor of cysteine residues responsible for inactivation of ligand binding by thiol alkylating and reducing agents
Authors: Gaibelet Gérald , Capeyrou Régine , Dietrich Gilles , Emorine Laurent J.
Published: July 2002

Inactivation by thiol reducing and alkylating agents of ligand binding to the human μ‐opioid receptor was examined. Dithiothreitol reduced the number of [3H]diprenorphine binding sites. Replacement by seryl residues of either C142 or C219 in extracellular loops 1 and 2 of the μ receptor resulted in a complete loss of opioid binding. A disulfide bound linking C142 to C219 may thus be essential to maintain a functional conformation of the receptor. We also demonstrated that inactivation of ligand binding upon alkylation by N‐ethylmaleimide occurred at two sites. Alteration of the more sensitive (IC50=20 μM) did not modify antagonists binding but decreased agonist affinity almost 10‐fold. Modification of the less reactive site (IC50=2 mM) decreased the number of both agonist and antagonist binding sites. The alkylation site of higher sensitivity to N‐ethylmaleimide was shown by mutagenesis experiments to be constituted of both C81 and C332 in transmembrane domains 1 and 7 of the μ‐opioid receptor.
Contribution of the second transmembrane helix of the secretin receptor to the positioning of secretin
Authors: Di Paolo Emmanuel , De Neef Philippe , Moguilevsky Nicole , Petry Han , Bollen Alex , Waelbroeck Magali , Robberecht Patrick
Published: July 2002

The secretin amino‐terminal residues are essential for high affinity binding to its cognate receptor and for its biological activity. Mutation of the [Asp3] residue of secretin to [Asn3] decreased the ligand's affinity for the rat wild‐type receptor 100–300‐fold. Receptor mutations in the transmembrane 2 domain and the beginning of the first extracellular loop allowed the identification of three residues involved in recognition of the [Asp3] residue: D174, K173 and R166. Mutation of K173 and D174 not only reduced the secretin and [Asn3]secretin affinities, but also changed the receptor's selectivity as judged by a decreased secretin and [Asn3]secretin potency ratio. The most striking effect was observed when R166 was mutated to Q, D or L. This led to receptors with a very low affinity for secretin but an up to 10‐fold higher affinity than the wild‐type receptor for [Asn3]secretin. This suggested that R166, highly conserved in that subgroup of receptor, is a major determinant for the recognition of the [Asp3] of the ligand.
Synthesis and characterization of a specific peptide nucleic acid that inhibits expression of inducible NO synthase
Authors: Giovine Marco , Gasparini Anna , Scarfı̀ Sonia , Damonte Gianluca , Sturla Laura , Millo Enrico , Tonetti Michela , Benatti Umberto
Published: July 2002

Inducible nitric oxide synthase (iNOS) is modulated at the transcriptional level. Overexpression of this protein may result in high levels of nitric oxide leading to tissue damage and immunosuppression. In order to reduce the pathological effects of NO overproduction many efforts have been devoted to the identification of specific inhibitors of iNOS. The discovery of peptide nucleic acids (PNA), a novel class of molecules able to selectively interact with nucleic acids, prompted us to attempt a new way for the regulation of NO production. Here we describe the synthesis, characterization and in vitro effects of a PNA molecule bearing a homopyrimidine sequence complementary to the 5′ coding region of murine iNOS mRNA. This PNA shows specific interactions with iNOS mRNA in RNase protection assays and is able to block the synthesis of iNOS protein selectively in a rabbit reticulocyte lysate system. These results strengthen the view of a possible pharmacological application of PNA as a compound able to interfere with a specific enzymatic activity even at low concentrations.
Differential effects of bacterial lipopolysaccharides upon neutrophil function
Authors: Ruchaud-Sparagano Marie-Hélène , Ruivenkamp Claudia A , Riches Philip L , Poxton Ian R , Dransfield Ian
Published: July 2002

Lipopolysaccharide (LPS) is a potent inflammatory agent which augments neutrophil sensitivity to subsequent inflammatory stimuli. In this study, the effects of structurally different LPS types upon neutrophil effector functions were examined. Rough LPS types, which have lost the O‐polysaccharide moiety, were found to act more rapidly than smooth LPS types in stimulating neutrophil β2 integrin activity and fMLP‐induced respiratory burst. These findings suggest an involvement of the O‐polysaccharide region of LPS in regulating neutrophil responsiveness to different LPS chemotypes with important implications for the mechanisms underlying regulation of the inflammatory response in conditions associated with elevation of LPS in plasma, e.g. septic shock or acute respiratory distress syndrome.
Effects of a time‐varying strong magnetic field on transient increase in cytosolic free Ca2+ induced by bradykinin in cultured bovine adrenal chromaffin cells
Authors: Ikehara Toshitaka , Park Ki Ho , Houchi Hitoshi , Yamaguchi Hisao , Hosokawa Keiko , Shono Masayuki , Minakuchi Kazuo , Tamaki Toshiaki , Kinouchi Yohsuke , Yoshizaki Kazuo , Miyamoto Hiroshi
Published: July 2002

We tested the effects of exposure to a time‐varying magnetic field changing between 0.07 and 1.7 T at an interval of 3 s on transient increase in intracellular Ca2+ stimulated by bradykinin in bovine adrenal chromaffin cells. Addition of bradykinin induced the increase in intracellular Ca2+ within a few minutes. The exposure to the magnetic field perfectly suppressed the increase in intracellular Ca2+ in Ca2+‐free medium. The inhibition occurred for 15 min when the maximum magnetic flux density was more than 1.4 T. These results suggest that the exposure inhibits Ca2+ release from intracellular Ca2+ stores.
The nuclear protein PH5P of the inter‐α‐inhibitor superfamily: a missing link between poly(ADP‐ribose)polymerase and the inter‐α‐inhibitor family and a novel actor of DNA repair?
Authors: Jean L. , Risler J.L. , Nagase T. , Coulouarn C. , Nomura N. , Salier J.P.
Published: July 2002

Poly(ADP‐ribose)polymerase is a nuclear NAD‐dependent enzyme and an essential nick sensor involved in cellular processes where nicking and rejoining of DNA strands are required. The inter‐α‐inhibitor family is comprized of several plasma proteins that all harbor one or more so‐called heavy chains designated H1–H4. The latter originate from precursor polypeptides H1P–H4P whose upper two thirds are highly homologous. We now describe a novel protein that includes (i) a so‐called BRCT domain found in many proteins involved in DNA repair, (ii) an area that is homologous to the NAD‐dependent catalytic domain of poly(ADP‐ribose)polymerase, (iii) an area that is homologous to the upper two thirds of precursor polypeptides H1P–H4P and (iv) a proline‐rich region with a potential nuclear localization signal. This protein now designated PH5P points to as yet unsuspected links between poly(ADP‐ribose)polymerase and the inter‐α‐inhibitor family and is likely to be involved in DNA repair.
Modified peptide nucleic acids are internalized in mouse macrophages RAW 264.7 and inhibit inducible nitric oxide synthase
Authors: Scarfi Sonia , Giovine Marco , Gasparini Anna , Damonte Gianluca , Millo Enrico , Pozzolini Marina , Benatti Umberto
Published: July 2002

Overexpression of inducible nitric oxide synthase causes the production of high levels of nitric oxide, which, under pathological conditions, leads to immunosuppression and tissue damage. The results recently obtained using peptide nucleic acids, rather than traditional oligonucleotides as antigen and antisense molecules, prompted us to test their efficacy in the regulation of nitric oxide production, thereby overcoming the obstacle of cellular internalization. The cellular permeability of four inducible nitric oxide synthase antisense peptide nucleic acids of different lengths was evaluated. These peptide nucleic acids were covalently linked to a hydrophobic peptide moiety to increase internalization and to a tyrosine to allow selective 125I radiolabelling. Internalization experiments showed a 3–25‐fold increase in the membrane permeability of the modified peptide nucleic acids with respect to controls. inducible nitric oxide synthase inhibition experiments on intact stimulated macrophages RAW 264.7 after passive permeation of the two antisense peptide nucleic acids 3 and 4 demonstrated a significant decrease (43–44%) in protein enzymatic activity with respect to the controls. These data offer a basis for developing a good alternative to conventional drugs directed against inducible nitric oxide synthase overexpression.
Proton nuclear magnetic resonance study of the binary complex of cytochrome P450cam and putidaredoxin: interaction and electron transfer rate analysis
Authors: Mouro C. , Bondon A. , Jung C. , Hui Bon Hoa G. , De Certaines J.D. , Spencer R.G.S. , Simonneaux G.
Published: July 2002

A 1H nuclear magnetic resonance study of the complex of cytochrome P450cam‐putidaredoxin has been performed. Isocyanide is bound to cytochrome P450cam in order to increase the stability of the protein both in the reduced and the oxidized state. Diprotein complex formation was detected through variation of the heme methyl proton resonances which have been assigned in the two redox states. The electron transfer rate at equilibrium was determinated by magnetization transfer experiments. The observed rate of oxidation of reduced cytochrome P450 by the oxidized putidaredoxin is 27 (±7) per s.
Generation of multiple transcripts from the chicken chondromodulin‐I gene and their expression during embryonic development
Authors: Shukunami Chisa , Yamamoto Saori , Tanabe Tadashi , Hiraki Yuji
Published: July 2002

Chondromodulin‐I (ChM‐I) is an angiogenesis inhibitor isolated from fetal bovine cartilage. Here, we report the nucleotide sequence of chicken ChM‐I cDNA. Chicken mature ChM‐I had a significantly larger N‐terminal hydrophilic domain than its mammalian counterparts. Chicken embryos expressed multiple transcripts (3.3, 2.0 and 1.7 kb in size) due to the alternative utilization of polyadenylation signals, whereas only the 1.7 kb transcripts were detected in mammals. Although confined to cartilage and eye at a later stage of development, whole‐mount in situ hybridization revealed the expression of ChM‐I mRNA in somites, heart, bronchial arches, roof plate, retina and limb buds. The expression pattern of the gene suggests a role for ChM‐I in the morphogenesis during embryonic development.
Mapping the cytochrome c553 interacting site using 1H and 15N NMR
Authors: Morelli Xavier , Guerlesquin Françoise
Published: July 2002

Cytochrome c
553 is the electron transfer partner of formate dehydrogenase and of [Fe]‐hydrogenase, two metalloenzymes essential in the metabolism of sulfate reducing bacteria. These two enzymes contain a ‘ferredoxin‐like’ domain which presents 30% identity with Desulfovibrio desulfuricans Norway ferredoxin I. This was chosen as a model for the ‘ferredoxin‐like’ domain involved in the electron transfer reaction with cytochrome c
553. 1D NMR titration of complex formation gave us the stoichiometry (1:1) and the dissociation constant of the complex (K
d ∼3×10−6 M). 2D heteronuclear NMR experiments were performed to analyze the 1H and 15N chemical shift variations that are induced by the protein‐protein recognition. This is the first mapping of the interaction site on a c‐type cytochrome, using heteronuclear NMR.
Pheochromocytoma in pregnancy manifesting hypertensive crisis induced by metoclopramide
Authors: Takai Y , Seki H , Kinoshita K
Published: July 2002

Pheochromocytoma is a rare disease that may occur during pregnancy. Antenatal diagnosis is essential to improve fetal and maternal mortality and morbidity, but is difficult. A hypertensive crisis was induced by metoclopramide, a widely used anti‐emetic, in a pregnant normotensive woman. Biochemical measurements of plasma and urine catecholamines and magnetic resonance imaging (MRI) established the diagnosis of pheochromocytoma. She was medically treated with prazocin and electively delivered by cesarean section simultaneously with tumor resection.
News and views on the nucleolus in 1996: Report on the ‘Colloquium on the nucleolus,’ a meeting at Paris‐Grignon, July 18–20, 1996
Authors: Mosgoeller Wilhelm , Jordan E Gwyn , Hernandez‐Verdun Danièle
Published: July 2002

Summry— The new data presented by the participants during the ‘Colloquium on the Nucleolus’ were reviewed and regrouped in different topics concerning the molecular and functional significance of nucleolar structure. The topics included: rRNA transcription and nucleolar organization, the nucleolus in relation to cell proliferation including nucleolus in pathology during the cell cycle and cell division, nucleologenesis, and nucleolar proteins.
ET‐18‐OCH3‐induced cytotoxicity and DNA damage in rat astrocytes
Authors: Renis Marcella , Cardile Venera , Palumbo Maddalena , Russo Alessandra
Published: July 2002

The ether lipid 1‐octadecyl‐2‐methyl‐rac‐glicero‐3‐phosphocholine (ET‐18‐OCH3) is known to be selectively cytotoxic toward several types of tumor cells, in which it seems to activate a process of apoptotic cell death. Moreover, the drug has been demonstrated to be active in normal cells too, particularly in rat astrocytes. In these cells at low dosage (from 1 to 6 μg/ml of medium) ET‐18‐OCH3 stimulates maturation and protective responses, whereas at increasing dosages (from 8 to 20 μg/ml) it shows cytotoxic effects. The present study demonstrates that when ET‐18‐OCH3 is added to astrocytes, it activates, in a time‐ and concentration‐dependent manner, an oxidative process by increasing both the generation of reactive oxygen species (ROS), including nitric oxide, and lipid peroxidation. When there is a high ET‐18‐OCH3 concentration or the time of treatment is prolonged, the increased oxidative condition seems to trigger DNA fragmentation (monitored by COMET assay) as well as loss in cell viability. These cytotoxic effects indicate that ROS may be considered, in our experimental model, as executioners of a program of cell death. In addition, ET‐18‐OCH3 being a promising molecule in antitumor therapy, our data, while reinforcing the importance of monitoring the therapeutic drug dosage employed, also suggest that it may be useful to associate some antioxidants with antitumor treatments.
Cloning, characterization and developmental expression of α2,8 sialyltransferase (GD3 synthase, ST8Sia I) gene in chick brain and retina
Authors: Daniotti Jose L. , Fritz Víctor Rosales , Kunda Patricia , Nishi Tatsunari , Maccioni Hugo J.F.
Published: July 2002

GD3 and GM2 synthases act on ganglioside GM3 at the branching point of the pathway of synthesis of gangliosides in which the “a”, “b” and “c” families are produced. The relative activities of these enzymes are important for regulating the ganglioside composition of a given tissue. In the present work, we report the cloning and characterization of a chick GD3 synthase cDNA. The cloned cDNA directed the synthesis of a functionally active enzyme in transiently transfected CHO‐K1 cells and was highly homologous to mammalian GD3 synthases. In Northern blot experiments the cDNA detected a single specific GD3 synthase mRNA of about 9.0 kb both in the chicken brain and retina. The abundance of the specific mRNA transcript declined steadily from E7–E9 to very low values around PN2. The levels of enzyme activities measured at the same developmental stages roughly followed the changes of specific mRNA levels in both tissues. Insitu hybridization of embryonic neural retina cells in culture showed that both glial‐ and neuron‐like cells expressed the specific GD3 synthase mRNA, although with different intensities. Results indicate that transcription and/or stability of the specific GD3 synthase mRNA constitute a level of control of the expression of GD3 synthase and indirectly of the ganglioside composition in the developing chicken central nervous system (CNS).
Postnatal development of somatostatin‐ andneuropeptide y‐immunoreactive neurons in rat cerebralcortex : a double‐labeling immunohistochemical study
Authors: Lee Eun Young , Lee Tae Soo , Baik Sang Ho , Cha Choong Ik
Published: July 2002

The postnatal development of somatostatin (SOM)‐ and neuropeptide Y(NPY)‐immunoreactive (ir) neurons was examined in rat cerebral cortex, while considering theircoexistence in cortical neurons. Using double immunohistochemical staining for SOM and NPYwith diaminobenzidine and benzidine dihydrochloride as chromogens, we subdividedimmunoreactive cells into double‐labeled SOM/NPY‐, SOM only‐, and NPY only‐ir neurons.SOM/NPY‐ and SOM only‐ir neurons were detectable even at the day of birth, in contrast toNPY only‐ir cells which first appeared in most cortices from week two. The morphologicalfeatures of double‐labeled SOM/NPY neurons differed with those of SOM only‐ and NPYonly‐ir neurons. No apparent changes in the shape and size of single‐labeled neurons occurredwith age ; throughout their postnatal life they were round and ovoid, had a thin rim ofperinuclear cytoplasm, and short processes. However, the features of SOM/NPY‐ir neurons werenot consistent according to postnatal age ; by day P7, these neurons showed immature featuresand they began to show more advanced neuronal characteristics by week P2, when they had alarger and more intensely‐stained cytoplasm. In addition, their processes were longer, thicker andmore complex than at earlier ages. At this age, SOM/NPY‐ir somata were close to their nearmaximum size. From week P4, they became smaller and were lightly labeled. SOM/NPY‐irsomata were larger than SOM only‐ and NPY only‐ir somata at and after two weeks of age. Thepresent results, showing different postnatal maturation patterns such as time of appearance andmorphological features, raise the possibilities that double‐labeled SOM/NPY and single‐labeledimmunoreactive neurons may be different populations regulated by different mechanisms in theirdevelopment, and with different functional properties during development.
Expression of the proteolytic factors, tPA and uPA, PAI‐1 and VEGF during malignant glioma progression
Authors: Sandström Maria , Johansson Mikael , Sandström Jan , Bergenheim A.Tommy , Henriksson Roger
Published: July 2002

Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue‐type plasminogen activator urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meningies, as well as scattered neurons expressed tissue‐type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co‐operation of tissue‐type plasminogen activator, urokinase‐type plasminogen activator, plasminogen activator inhibitor‐1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.
EVIDENCE‐BASED PRENATAL CARE VISITS: WHEN LESS IS MORE
Authors: Walker Deborah S. , McCully Laura , Vest Victoria
Published: July 2002

Traditionally, low‐risk pregnant women in the United States who participate in prenatal care have been scheduled for approximately 14–16 prenatal visits, which is the schedule recommended by the American College of Obstetricians and Gynecologists. In 1989, an expert panel convened by the United States Department of Health and Human Services proposed a reduced frequency prenatal visit schedule for low‐risk, healthy women based on the timing of specific tests or events that occur in pregnancy. Available evidence shows no adverse effect on maternal or neonatal outcomes for low‐risk pregnant women who follow a reduced visit schedule, making it a highly important consideration for pregnant women and their health care providers. Other important aspects of prenatal care, especially related to adequacy and content, will be explored in‐depth in a future segment of this series on evidence‐based prenatal care.
DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies
Authors: Rominiyi Ola , Collis Spencer J.
Published: May 2021

Glioblastoma is the most frequently diagnosed type of primary brain tumour in adults. These aggressive tumours are characterised by inherent treatment resistance and disease progression, contributing to ~ 190 000 brain tumour‐related deaths globally each year. Current therapeutic interventions consist of surgical resection followed by radiotherapy and temozolomide chemotherapy, but average survival is typically around 1 year, with < 10% of patients surviving more than 5 years. Recently, a fourth treatment modality of intermediate‐frequency low‐intensity electric fields [called tumour‐treating fields (TTFields)] was clinically approved for glioblastoma in some countries after it was found to increase median overall survival rates by ~ 5 months in a phase III randomised clinical trial. However, beyond these treatments, attempts to establish more effective therapies have yielded little improvement in survival for patients over the last 50 years. This is in contrast to many other types of cancer and highlights glioblastoma as a recognised tumour of unmet clinical need. Previous work has revealed that glioblastomas contain stem cell‐like subpopulations that exhibit heightened expression of DNA damage response (DDR) factors, contributing to therapy resistance and disease relapse. Given that radiotherapy, chemotherapy and TTFields‐based therapies all impact DDR mechanisms, this Review will focus on our current knowledge of the role of the DDR in glioblastoma biology and treatment. We also discuss the potential of effective multimodal targeting of the DDR combined with standard‐of‐care therapies, as well as emerging therapeutic targets, in providing much‐needed improvements in survival rates for patients.
Molecular Evolution of Reef‐Building Corals
Authors: Forsman Zac H
Published: May 2021

Reef‐building corals form complex structures foundational to one of the most biodiverse ecosystems on Earth. These ecosystems are sensitive to anthropogenic influence and are rapidly collapsing, threatening loss of biodiversity that is poorly understood yet key to understanding the past, documenting the present and predicting the future capacity to adapt. For centuries, coral taxonomy and systematics was based on morphology, but genetic studies over the past few decades have radically reshaped our view of the coral tree of life, uncovering examples of convergent and parallel evolution, potential hybridisation or recent divergence and extreme phenotypic variation and plasticity. Biotechnology is enabling a new high‐resolution view of evolutionary processes, revealing coevolution between the host and symbionts, recent speciation and potential mechanisms for adaptation across habitats. Biologists are racing against time to discover biodiversity before it is lost and to try to understand if reef‐building corals can adapt to keep pace with the changing oceans.

Reef building corals provide the foundation for one of the most biodiverse ecosystems on earth.

Reef‐building corals have a unique symbiotic partnership with highly specialised dinoflagellate algae that enables calcification and reef formation in nutrient‐poor water, but the partnership is highly vulnerable to marine heatwaves that have resulted in widespread coral bleaching and reduced coral cover.

The evolution of corals is poorly understood due to high morphological variation and early limits of molecular markers.

Corals have an excellent fossil record, but genetic data has revealed that morphology is less reliable than previously thought with surprising cases of convergent evolution and phenotypic plasticity.

Genomic data is revolutionising coral conservation by providing insights into resilience to coral bleaching, uncovering new cryptic species and surprising diversification and specialisation across habitats while identifying new rare and endemic species threatened with extinction.
Terrestrialisation (Precambrian–Devonian)
Authors: Selden Paul
Published: May 2021

The emergence of plants and animals from the sea on to land – terrestrialisation – was one of the major advances in the history of life on Earth. Evidence for early colonisation is poor, but the fossil record reveals that by mid‐Palaeozoic times complex terrestrial ecosystems had become established. The first phase of land colonisation by organisms may have started in the Precambrian, some 2.6 Ga ago, in the form of microbially bound alluvial sands. The second phase began in earnest in Ordovician times, when early land plants, in the form of bryophyte‐like spores, first appeared in the fossil record. By the Silurian, true vascular plants were present, and these green swards were inhabited by mainly detritivorous and predatory arthropods. By the late Devonian, true forests had developed, but it was not until the latest Palaeozoic that modern‐type terrestrial ecosystems, with abundant herbivores in the food chain, appeared.

Organisms need to overcome many physiological barriers when colonising the land from the sea.

Conditions on the early Earth (∼4.6–1.0 Ga) were inhospitable to terrestrial life.

Microbial crusts were likely the earliest land life.

Higher plants appeared on land in the Ordovician period; vascular plants in the Silurian.

The first land animals (Silurian) were detritivorous and predatory arthropods.

Modern‐type ecosystems, with abundant herbivory and vertebrates, came in the latest Palaeozoic.
Online dating applications and risk of youth victimization: A lifestyle exposure perspective
Authors: Kaakinen Markus , Koivula Aki , Savolainen Iina , Sirola Anu , Mikkola Marko , Zych Izabela , Paek Hye‐Jin , Oksanen Atte
Published: May 2021

Based on lifestyle exposure theory (LET), this study examined online dating application (ODA) use and victimization experiences among adolescents using large cross‐national samples of Finnish, American, Spanish, and South Korean young people between ages 15 and 18. According to logistic regression analyses in two substudies, ODA use was associated with more likely victimization to online harassment, online sexual harassment, and other cybercrimes and sexual victimization by adults and peers. According to mediation analyses, this relationship was mainly accounted for by the fact that ODA users engage in more risky activities in online communication and information sharing. Attention should be paid to the risks ODAs pose to vulnerable groups, such as young people, with insufficient skills to regulate their social relationships online.
I2‐Promoted [3+2] Cyclization of 1,3‐Diketones with Potassium Thiocyanate: a Route to Thiazol‐2(3H)‐One Derivatives
Authors: An Zhenyu , Liu Yafeng , Zhao Pengbo , Yan Rulong
Published: May 2021

An I2‐promoted strategy has been developed for the synthesis of thiazol‐2(3H)‐one derivatives from 1,3‐diketones with potassium thiocyanate. This [3+2] cyclization reaction involves C−S and C−N bond formation and exhibits good functional group tolerance. A series of thiazol‐2(3H)‐one derivatives are obtained in moderate to good yields.

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Expanding the clinical spectrum in trichohepatoenteric syndrome
Authors: Dorum Sevil , Gorukmez Ozlem
Published: May 2021

Trichohepatoenteric syndrome (THES) is a very rare autosomal recessive genetic disorder, which is characterized by intractable diarrhea during infancy, dysmorphic features, immunodeficiency, and a failure to thrive. There are still significant difficulties for patients and clinicians in terms of the management of THES, even though its molecular basis has been uncovered in the last decade. In this article, we have presented two cases relating to siblings that have been diagnosed with the condition. Concerning one of the patients, we described a novel variation (c.2114 + 5G > A) in the TTC37 gene and a mild clinical course; meanwhile, the other one was clinically diagnosed with THES at 17 years of age, but they had seizures and died suddenly. These cases expand the spectrum of clinical findings in relation to THES.
Contemporary experience of polyhydramnios: A single‐centre experience
Authors: Kyriacou Christopher , Roper Louise , Mappouridou Stephanie , Lees Christoph , Prior Tomas
Published: May 2021

Introduction

Polyhydramnios is common; the majority of cases are idiopathic, but maybe associated with fetal abnormality. Literature suggests the volume of amniotic fluid discriminates idiopathic from pathological polyhydramnios but is not unanimous. We assessed fetal anomaly incidence amongst women with polyhydramnios and the role of discriminatory variables in identifying pathological cases.

Methods

Retrospective observational cohort study at an inner‐city London fetal medicine centre. Records for patients referred and/or diagnosed with polyhydramnios were reviewed as well as maternal/fetal demographics, amongst singleton pregnancies using the Astraia™ database from January 2015–2016. Estimated fetal weight was calculated using the Hadlock model (biometry undertaken at diagnosis). Student's t‐test/one‐way ANOVA compared means; chi‐squared tests compared proportions.

Results

120 cases were identified. 36 (30%) had fetal abnormality. There was no difference in AFI between fetuses with an abnormality and without (26.7 vs 25.2 cm, P = 0.22). AFI was normalised for weight (AFI (cm)/estimated fetal weight (kg)): AFI/kg was significantly different between cases with fetal abnormality and without (24.4 vs 16.7 cm/kg, P < 0.001) – incidence of abnormality increased with increasing AFI/kg (P = 0.007). Early gestational diagnosis was associated with higher rates of anomaly (P = 0.004). Differences in AFI/kg between those with and without abnormality were not significant when adjusted for gestation. AFI was significantly higher in cases of abnormality diagnosed at later gestation (P = 0.005).

Conclusion

Excess volume of amniotic fluid alone does not denote abnormality. Earlier gestations and higher AFI/kg corresponded with significantly increased rates of anomaly. However, the latter is a result of confounding by gestation, which is closely correlated with fetal weight.
Be2(BO3)(IO3): The First Anion‐mixed Van der Waals Member in the KBe2BO3F2 Family with a Very Strong Second Harmonic Generation Response
Authors: Peng Guang , Lin Chensheng , Fan Huixin , Chen Kaichuang , Li Bingxuan , Zhang Ge , Ye Ning
Published: May 2021

To obtain new nonlinear optical (NLO) materials with a large second harmonic generation (SHG) effect has always been a great challenge. We have synthesized the first metal borate‐iodate NLO crystal, Be2(BO3)(IO3) (BBIO), by multicomponent modification of KBe2BO3F2 (KBBF), in which the structural features of KBBF were maintained and (IO3)− groups were connected to honeycomb [Be2BO3O2]∞ layers. As the first KBBF family member with mixed anionic groups, BBIO benefited from the synergistic effect of (IO3)−, (BO3)3− and (BeO4)6− groups, and exhibited a very strong SHG response of ≈7.2×KH2PO4 (KDP, @1064 nm) and a large birefringence (Δn) of 0.172 at 1064 nm. BBIO may, unexpectedly, optimize growth habits via van der Waals forces. This study presents borate‐iodate as a new NLO material and it demonstrates opportunities in KBBF structural engineering.
Platin‐vermittelte Kupplung von B=N‐Einheiten: Synthese von BNBN‐Analoga von 1,3‐Dienen und Butatrien
Authors: Brunecker Carina , Arrowsmith Merle , Fantuzzi Felipe , Braunschweig Holger
Published: May 2021

Die 1:2‐Reaktion von [μ‐(dmpm)Pt(nbe)]2 (dmpm=Bis(dimethylphosphino)methan, nbe=Norbornen) mit Cl2BNR(SiMe3) (R=tBu, SiMe3) führt durch eine B‐N‐Kupplung über eine ClSiMe3‐Eliminierung zu unsymmetrischen (N‐Aminoboryl)aminoboryl‐PtI2‐Komplexen. Eine anschließende intramolekulare ClSiMe3‐Eliminierung des tBu‐Derivats führt zu einer Cyclisierung der BNBN‐Einheit unter Bildung eines einzigartigen 1,3,2,4‐Diazadiboretidin‐2‐yl‐Liganden. Im Gegensatz hierzu steht die analoge Reaktion mit Br2BN(SiMe3)2, die über eine zweifache BrSiMe3‐Eliminierung zu einem PtII2‐A‐Frame‐Komplex führt, der von einem linearen Isoster des Butatriens verbrückt wird. Strukturelle und theoretische Daten bestätigen eine π‐Elektronen‐Delokalisierung über die gesamte BNBN‐Einheit.
The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐epi‐Leucophyllidine
Authors: Reimann Christopher E. , Ngamnithiporn Aurapat , Hayashida Kohei , Saito Daisuke , Korch Katerina M. , Stoltz Brian M.
Published: May 2021

A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium‐catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine‐derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline‐derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol‐directed hydrogenation united the two monomeric fragments to afford 16′‐epi‐leucophyllidine in 21 steps from commercial material.
Synthesis and catalytic activity of N‐heterocyclic silylene (NHSi) iron (II) hydride for hydrosilylation of aldehydes and ketones
Authors: Du Xinyu , Qi Xinghao , Li Kai , Li Xiaoyan , Sun Hongjian , Fuhr Olaf , Fenske Dieter
Published: May 2021

A novel silylene supported iron hydride [Si, C]FeH (PMe3)3 (1) was synthesized by C (sp3)‐H bond activation with zero‐valent iron complex Fe (PMe3)4. Complex 1 was fully characterized by spectroscopic methods and single crystal X‐ray diffraction analysis. To the best of our knowledge, 1 is the first example of silylene‐based hydrido chelate iron complex produced through activation of the C (sp3)−H bond. It was found that complex 1 exhibited excellent catalytic activity for hydrosilylation of aldehydes and ketones. The catalytic system showed good tolerance and catalytic activity for the substrates with different functional groups on the benzene ring. It is worth mentioning that, the experimental results showed that both ketones and aldehydes could be reduced in good to excellent yields under the same catalytic conditions. Based on the experiments and literature reports, a possible catalytic mechanism was proposed.
Prevalence of nonsensical algorithmically generated papers in the scientific literature
Authors: Cabanac Guillaume , Labbé Cyril
Published: May 2021

In 2014 leading publishers withdrew more than 120 nonsensical publications automatically generated with the SCIgen program. Casual observations suggested that similar problematic papers are still published and sold, without follow‐up retractions. No systematic screening has been performed and the prevalence of such nonsensical publications in the scientific literature is unknown. Our contribution is 2‐fold. First, we designed a detector that combs the scientific literature for grammar‐based computer‐generated papers. Applied to SCIgen, it has a 83.6% precision. Second, we performed a scientometric study of the 243 detected SCIgen‐papers from 19 publishers. We estimate the prevalence of SCIgen‐papers to be 75 per million papers in Information and Computing Sciences. Only 19% of the 243 problematic papers were dealt with: formal retraction (12) or silent removal (34). Publishers still serve and sometimes sell the remaining 197 papers without any caveat. We found evidence of citation manipulation via edited SCIgen bibliographies. This work reveals metric gaming up to the point of absurdity: fraudsters publish nonsensical algorithmically generated papers featuring genuine references. It stresses the need to screen papers for nonsense before peer‐review and chase citation manipulation in published papers. Overall, this is yet another illustration of the harmful effects of the pressure to publish or perish.
Harmonizing and publishing heterogeneous premodern manuscript metadata as Linked Open Data
Authors: Koho Mikko , Burrows Toby , Hyvönen Eero , Ikkala Esko , Page Kevin , Ransom Lynn , Tuominen Jouni , Emery Doug , Fraas Mitch , Heller Benjamin , Lewis David , Morrison Andrew , Porte Guillaume , Thomson Emma , Velios Athanasios , Wijsman Hanno
Published: May 2021

Manuscripts are a crucial form of evidence for research into all aspects of premodern European history and culture, and there are numerous databases devoted to describing them in detail. This descriptive information, however, is typically available only in separate data silos based on incompatible data models and user interfaces. As a result, it has been difficult to study manuscripts comprehensively across these various platforms. To address this challenge, a team of manuscript scholars and computer scientists worked to create “Mapping Manuscript Migrations” (MMM), a semantic portal, and a Linked Open Data service. MMM stands as a successful proof of concept for integrating distinct manuscript datasets into a shared platform for research and discovery with the potential for future expansion. This paper will discuss the major products of the MMM project: a unified data model, a repeatable data transformation pipeline, a Linked Open Data knowledge graph, and a Semantic Web portal. It will also examine the crucial importance of an iterative process of multidisciplinary collaboration embedded throughout the project, enabling humanities researchers to shape the development of a digital platform and tools, while also enabling the same researchers to ask more sophisticated and comprehensive research questions of the aggregated data.
Flocculation of Chlorella vulgaris with alum and pH adjustment
Authors: Mohseni Farnaz , Moosavi Zenooz Alireza
Published: May 2021

Microalgae, a group of photosynthetic microorganisms, are a promising feedstock for biodiesel production, but their biomass retrieval is a challenging task. Flocculation is a feasible method for dewatering and harvesting microalgae biomass. In the current study, the effect of alum flocculation on Chlorella vulgaris biomass retrieval has been studied. Alum structural changes with pH were led to a full factorial design to address the effect of this chemical structure changes at different pH values. It is observed that the best flocculation efficiency could be achieved in the natural pH value of C. vulgaris growth medium (8.2) with less than 0.5 g/L flocculant addition, which would lead to the flocculation efficiency of more than 90%. An ensemble architecture of neural networks successfully employed for flocculation modeling.
Comparative pharmacokinetics study of six effective components between two dosage forms of Qixue–Shuangbu Prescription in rats by UPLC–MS/MS
Authors: Chen Linwei , Liu Lunyuan , Wang Qin , Jiang Yong , Tian Hu
Published: May 2021

Qixue–Shuangbu Prescription (QSP) is an efficacious prescription for treating heart failure, myocardial ischemia and other diseases. It is composed of nine Chinese herbs. This study investigated and compared the pharmacokinetics of QSP in rats by UPLC–MS/MS between two dosage forms of traditional decoction (TD) and compound tincture (CT). Owing to the complexity of the chemicals in QSP, ginsenoside Rg1, ginsenoside Re, ferulic acid, astragaloside IV, rhein and calycosin were chosen for the pharmacokinetics study. The method established for detecting serum specimens was shown to have acceptable selectivity, linearity, lower limit of quantitation, precision, accuracy, recovery, matrix effect and stability. The peak concentration, AUC0–t and AUC0–∞ of ginsenoside Re, ginsenoside Rg1, ferulic acid and rhein were significantly increased after oral administration of CT (P < 0.05), the half‐life of ferulic acid in the CT group was lower than that in the TD group (P < 0.05) and the half‐life and AUC0–∞ of astragaloside IV in the CT group were significantly increased (P < 0.05), which revealed that wine‐processing could influence the bioavailability and the elimination of these compounds. For better clinical efficacy, we suggest that the CT dosage form of QSP should be selected.
Enhanced tumor cell killing by ultrasound after microtubule depolymerization
Authors: Singh Aditi , Tijore Ajay , Margadant Felix , Simpson Chloe , Chitkara Deepak , Low Boon Chuan , Sheetz Michael
Published: May 2021

Recent studies show that tumor cells are vulnerable to mechanical stresses and undergo calcium‐dependent apoptosis (mechanoptosis) with mechanical perturbation by low‐frequency ultrasound alone. To determine if tumor cells are particularly sensitive to mechanical stress in certain phases of the cell cycle, inhibitors of the cell‐cycle phases are tested for effects on mechanoptosis. Most inhibitors show no significant effect, but inhibitors of mitosis that cause microtubule depolymerization increase the mechanoptosis. Surprisingly, ultrasound treatment also disrupts microtubules independent of inhibitors in tumor cells but not in normal cells. Ultrasound causes calcium entry through mechanosensitive Piezo1 channels that disrupts microtubules via calpain protease activation. Myosin IIA contractility is required for ultrasound‐mediated mechanoptosis and microtubule disruption enhances myosin IIA contractility through activation of GEF‐H1 and RhoA pathway. Further, ultrasound promotes contractility‐dependent Piezo1 expression and localization to the peripheral adhesions where activated Piezo1 allows calcium entry to continue feedback loop. Thus, the synergistic action of ultrasound and nanomolar concentrations of microtubule depolymerizing agents can enhance tumor therapies.
Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83
Authors: Rathnakar Bethi , Sinha Kislay Kumar , Prasad Surendra Rajit , Khan Mohd. Imran , Narsaiah Chelimela , Rameshwar Nimma , Satyanarayana Mavurapu
Published: May 2021

We have developed a new series of simple biaryl piperidine derivatives (11–19) based on biaryl naphthylisoquinoline alkaloid Ealamine‐A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5′‐fluoro‐2′‐methoxyphenyl derivative 14 and 3′,5′‐difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.