bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclopamine-Induced Holoprosencephaly and Associated Craniofacial Malformations in the Golden Hamster: Anatomic and Molecular Events
Authors: Coventry Susan , Kapur Raj P. , Siebert Joseph R.
Published: July 2002

Holoprosencephaly is a complex congenital malformation of the brain and is often associated with a spectrum of facial anomalies ranging from normocephaly or nondiagnostic changes to cleft lip/palate (premaxillary dysgenesis), cebocephaly ethmocephaly and cyclopia. The primary insult is thought to occur during gastrulation, when prechordal mesenchyme and overlying anterior neural plate undergo complex developmental interactions. Exposure to cyclopamine, a steroid isolated from the desert plant Veratrum californicum, causes holoprosencephaly in mammalian embryos. We have begun to study the pathogenesis of cyclopamine-induced holoprosencephaly and associated craniofacial anomalies in Syrian golden hamsters ( Mesocricetus auratus). Embryos were exposed to a single maternal dose of cyclopamine during gastrulation on embryonic day (E) 7.0. By E13.0, 62% of fetuses showed craniofacial malformations, including premaxillary dysgenesis, ocular hypotelorism, and cebocephaly. Facial anomalies were associated with absence of the premaxilla and abnormalities of the midline cranial base, particularly the ethmoid and sphenoid bones. Histological sections from cyclopamine-treated embryos at earlier stages showed marked deficiency of cranial mesenchyme derived from the rostral neural crest. Expression of two transcription factors, HNF-3β and Hox-b5, which have been implicated in specification of rostral and caudal neural crest cells, respectively, were examined immunohistochemically. Treatment with cyclopamine caused a transient loss of HNF-3β immunoreactivity in prechordal mesenchyme, but had no effect on Hox-b5 expression. The findings suggest that an early event in the pathogenesis of cyclopamine-induced holoprosencephaly may be altered expression of selected proteins in the prechordal mesenchyme and floor plate with secondary impaired development of the adjacent neural plate and cranial neural crest.
Medullary Ray Nodule of the Kidney
Authors: Smith N.M. , Evans M.J. , Smith V. , Kelsey A.
Published: July 2002

In this short report we describe three preterm infants who died within the first 8 months of life (corrected age). All presented similar histological features within the kidney, showing medullary ray nodules composed of tubules lined by low columnar epithelium with clear cytoplasm. The immunohistochemical profile of these lesions was identical and suggested origin from distal convoluted tubule or collecting duct. The aim of this report is to draw attention to this entity and to suggest a possible origin of these lesions.
Metabolic and Molecular Bases of Menkes Disease and Occipital Horn Syndrome
Authors: Kaler Stephen G.
Published: July 2002

Menkes disease and occipital horn syndrome (OHS) are related disorders of copper transport that involve abnormal neurodevelopment, connective tissue problems, and often premature death. Location of the gene responsible for these conditions on the X chromosome was indicated by pedigree analysis from the time of these syndromes' earliest descriptions. Characterization of an affected female with an X-autosomal translocation was used to identify the Menkes/OHS gene, which encodes a highly evolutionarily conserved, copper-transporting P-type ATPase. The gene normally is expressed in nearly all human tissues, and it localizes to the trans-Golgi network of cells. However, in over 70% of Menkes and OHS patients studied, expression of this gene has been demonstrated to be abnormal. Major gene deletions detectable by Southern blotting account for 15–20% of patients, and an interesting spectrum of other mutations is evident among 58 families whose precise molecular defects have been reported as of this writing. The center region of the gene seems particularly prone to mutation, and those that influence mRNA processing and splicing appear to be relatively common. Further advances in understanding the molecular and cell biological mechanisms involved in normal copper transport may ultimately yield new and better approaches to the management of these disorders.
Thiol reagents are substrates for the ADP‐ribosyltransferase activity of pertussis toxin
Authors: Lobban Margaret D. , van Heyningen Simon
Published: July 2002

Thiols such as cysteine and dithiothreitol are substrates for the ADP‐ribosyltransferase activity of pertussis toxin. When cysteine was incubated with NAD+ and toxin at pH 7.5, a product containing ADP‐ribose and cysteine (presumably ADP‐ribosylcysteine) was isolated by high‐performance liquid chromatography, and characterized by its composition and release of AMP with phosphodiesterase. Cysteine has a K
m of 105 mM at saturating NAD+ concentration. The ability of thiols to act as a substrate is one explanation for the very high concentrations (250 mM or greater) that have been observed to enhance the apparent NAD glycohydrolase activity of the toxin.
Detection of VAC‐β (annexin‐8) in human placenta
Authors: Pepinsky R.Blake , Hauptmann Rudolf
Published: July 2002

A36 kDa calcium/phospholipid binding protein in human placenta was identified as VAC‐β (annexin‐8) by a combination of immunological and peptide mapping analyses. The protein is a minor product in placenta, accounting for less than 1% of extracted annexins. From 150 g of tissue, only 100 μg of the protein was isolated. By anion‐exchange chromatography on diethylaminoethyl‐cellulose annexin‐8 coeluted with annexin‐3. By gel filtration, the protein chromatographed as a broad peak, where half the product eluted as a monomer and half eluted as a heterodimer that was associated with a 10 kDa subunit. The combination of annexin‐8 being a minor component in standard annexin preparations and it co‐eluting with annexin‐3 by ion exchange chromatography are likely to account for the failure of other labs to characterize the product.
Effects of amino acid substitution on the thermal stability of MS2 capsids lacking genomic RNA
Authors: Stonehouse N.J. , Stockley P.G.
Published: July 2002

The thermal stability of capsids of the bacteriophage MS2, lacking genomic RNA, has been investigated using electron microscopy. Coat protein mutants with amino acid substitutions at residues involved in making contacts at both inter‐molecular interfaces and within the coat protein subunit are also capable of forming ‘empty’ capsids of the same size and symmetry as the wild‐type protein. Mutations have been characterised which are neutral, deleterious or advantageous in terms of thermal stability. In some cases, the results can be rationalised by reference to the recently refined X‐ray crystal structure of the wild‐type particle.
A novel human tyrosine kinase gene inducible in T cells by interleukin 2
Authors: Tanaka Nobuyuki , Asao Hironobu , Ohtani Kiyoshi , Nakamura Masataka , Sugamura Kazuo
Published: July 2002

We have cloned a novel human protein tyrosine kinase gene specific to T cells by the polymerase chain reaction method. This gene encodes a 620 amino‐acid polypeptide including a catalytic domain for tyrosine kinase, an SH2 domain and an SH3 domain, seemingly belonging to the src family. However, characteristics of a long unique N‐terminal stretch and lack of a myristylation site at the N‐terminus and of a kinase regulatory tyrosine residue in the C‐terminus classify this molecule into a new subfamily comprising recently cloned mouse tec, itk/tsk and human atk/bpk genes. This gene was transcriptionally induced in normal T cells by interleukin 2 stimulation. These results suggest the crucial roles of this gene in T cell proliferation and differentiation.
Site‐specific15N‐labelling of oligonucleotides for NMR: thetrpoperator and its interaction with thetrprepressor
Authors: Ramesh Vasudevan , Xu Yao-Zhong , Roberts Gordon C.K.
Published: July 2002

A convenient and economical method is described for the site‐specific15N‐labelling of the 4‐amino group of individual cytidine residues in oligonucleotides. This is applied to a 20 base‐pair oligonucleotide corresponding to thetrpoperator; this oligonucleotide and its complex with theE. coli trprepressor are studied by NMR, using1H‐15N HMQC and15N‐edited1H‐1H NOESY experiments.
An investigation of the binding of protein proteinase inhibitors to trypsin by electrospray ionization mass spectrometry
Authors: Kraunsoe James A.E. , Aplin Robin T. , Green Brian , Lowe Gordon
Published: July 2002

The binding of BPTI and SBTI with trypsin has been investigated by ESI MS, using the mutant K15V‐BPTI and the chemically modified RcamBPTI as controls. Although high cone voltages (+80 V) produce sharp spectra of BPTI, RcamBPTI, SBTI and trypsin alone, the complexes of BPTI, RcamBPTI and SBTI with trypsin undergo partial dissociation due to collisional activation. At lower cone voltages (+40 V) these non‐covalent complexes are stable. The charge distribution on the trypsin and the inhibitors produced by gas phase dissociation of the complexes are markedly different from those of the components alone, indicating that ESI MS provides a novel probe for exploring the ionic interactions at the contact surface of proteins. Moreover, by determining the cone voltage at which the gas phase dissociation of complexes occurs it may be possible to use ESI MS to compare the binding energies of closely related complexes.
Computer based psychiatric rehabilitation: current activities in Germany
Authors: Olbrich R
Published: July 2002

The present paper deals with computer based training approaches in psychiatric rehabilitation. First an overview of programs is presented, which are currently available on the software market in Germany and appear suitable for the training of patients with information processing (including sensorimotor) deficits. Then a description follows dealing with a clinical setting which may serve to illustrate how computer based cognitive training can be organized in a group format. Finally a couple of clinical studies which have aimed to determine the efficacy of PC based training programs in schizophrenic patients are briefly reviewed.
Duplication of genes encoding non‐clathrin coat protein γ‐COP in vertebrate, insect and plant evolution
Authors: Hahn Yoonsoo , Lee Young Jae , Yun Ji Hye , Yang Seung Kyoung , Park Chang Won , Mita Kazuei , Huh Tae-Lin , Rhee Myungchull , Chung Jae Hoon
Published: July 2002

Coatomer is a major component of COPI vesicles and consists of seven subunits. The γ‐COP subunit of the coatomer is believed to mediate the binding to the cytoplasmic dilysine motifs of membrane proteins. We characterized cDNAs for Copg genes encoding γ‐COP from mouse, zebrafish, Drosophila melanogaster and Bombyx mori. Two copies of Copg genes are present in vertebrates and in B. mori. Phylogenetic analysis revealed that two paralogous genes had been derived from a single ancestral gene by duplication independently in vertebrates and in B. mori. Mouse Copg1 showed ubiquitous expression with the highest level in testis. Zebrafish copg2 was biallelically expressed in hybrid larvae in contrast to its mammalian ortholog expressed in a parent‐of‐origin‐specific manner. A phylogenetic analysis with partial plant cDNA sequences suggested that copg gene was also duplicated in the grass family (Poaceae).
Regulation of tumor necrosis factor cytotoxicity by calcineurin
Authors: Kantrow Stephen P. , Gierman Joshua L. , Jaligam Vijayendra R. , Zhang Ping , Piantadosi Claude A. , Summer Warren R. , Lancaster Jack R.
Published: July 2002

Cyclosporin (CsA) inhibits mitochondrial death signaling and opposes tumor necrosis factor (TNF)‐induced apoptosis in vitro. However, CsA is also a potent inhibitor of calcineurin, a phosphatase that may participate in cell death. Therefore, we tested the hypothesis that calcineurin regulates TNF cytotoxicity in rat hepatoma cells (FTO2B). TNF‐treated FTO2B cells appeared apoptotic by DNA fragmentation, nuclear condensation, annexin V binding, and caspase activation. We studied two calcineurin inhibitors, CsA and FK506, and found that each potently inhibited TNF cytotoxicity. Western blot demonstrated calcineurin in FTO2B homogenates. In a model of mitochondrial permeability transition (MPT), we found that CsA prevented MPT and cytochrome c release, while FK506 inhibited neither. In summary, we present evidence that calcineurin participates in an apoptotic death pathway activated by TNF. CsA may oppose programmed cell death by inhibiting calcineurin activity and/or inhibiting mitochondrial signaling.
Stoichiometry of dipalmitoylphosphatidylcholine‐DNA interaction in the presence of Ca2+: a temperature‐scanning ultrasonic study
Authors: Kharakoz D.P. , Khusainova R.S. , Gorelov A.V. , Dawson K.A.
Published: July 2002

DNA‐DPPC complexes can be prepared by means of a single step procedure of mixing DNA solution and aqueous lipid dispersion in the presence of calcium ions. Interaction between DPPC and DNA brings about a biphasic shape of melting curves corresponding to the free lipid and the strongly bound one. The amount of the strongly bound lipid is 5 molecules per nucleotide which is close to the size of the first lipid monolayer around DNA molecule.
A downstream splicing enhancer is essential for in vitro pre‐mRNA splicing
Authors: Yue Bai-Gong , Akusjärvi Göran
Published: July 2002

Splicing enhancers have previously been shown to promote processing of introns containing weak splicing signals. Here, we extend these studies by showing that also ‘strong’ constitutively active introns are absolutely dependent on a downstream splicing enhancer for activity in vitro. SR protein binding to exonic enhancer elements or U1 snRNP binding to a downstream 5′ splice site serve redundant functions as activators of splicing. We further show that a 5′ splice site is most effective as an enhancer of splicing. Thus, a 5′ splice site is functional in S100 extracts, under conditions where a SR enhancer is non‐functional. Also, splice site pairing occurs efficiently in the absence of exonic SR enhancers, emphasizing the significance of a downstream 5′ splice site as the enhancer element in vertebrate splicing.
Characterization of elicitin‐like phospholipases isolated fromPhytophthora capsiciculture filtrate
Authors: Nespoulous Claude , Gaudemer Odile , Huet Jean-Claude , Pernollet Jean-Claude
Published: July 2002

The phytopathogenic oomycetePhytophthora capsicisecretes in culture a phospholipase activity. Two enzyme isoforms exhibiting a high phospholipase B activity were isolated by chromatography and electrophoresis. They differ in their apparent molar masses (22 and 32 kDa). Both proteins are glycosylated and share the same N‐terminal amino acid sequence up to the 39th residue with a high homology with capsicein, theP. capsicielicitin. Although devoid of phospholipase activity, capsicein was shown by circular dichroism to specifically interact with negatively charged phospholipids, suggesting that the membrane lipids could be a potential target for elicitins.
Mapping of putative binding sites on the ectodomain of the type II TGF‐β receptor by scanning‐deletion mutagenesis and knowledge‐based modeling
Authors: Guimond Alain , Sulea Traian , Pepin Marie-Claude , O'Connor-McCourt Maureen D
Published: July 2002

Binding surfaces of the type II transforming growth factor (TGF)‐β receptor extracellular domain (TβRII‐ECD) are mapped by combining scanning‐deletion mutagenesis results with knowledge‐based modeling of the ectodomain structure. Of the 17 deletion mutants produced within the core binding domain of TβRII‐ECD, only three retained binding to TGF‐β. Comparative modeling based on the crystal structure of the activin type II receptor extracellular domain (ActRII‐ECD) indicates that the TβRII mutants which retain TGF‐β binding are deleted in some of the loops connecting the β‐strands in the TβRII‐ECD model. Interpretation of the mutagenesis data within the structural framework of the ectodomain model allows for the prediction of potential binding sites at the surface of TβRII‐ECD.
Family planning in Russia
Authors: Savelyeva G.M. , Gavrilova D.V. , Lobova T.A.
Published: July 2002

The data concerning the abortion rate in Russia for the past 5 years are presented. They demonstrate that abortion has been the main means of birth control. At present, the government, the Ministry of Public Health, obstetricians and gynecologists, and public organizations are making every effort to introduce medical and non‐medical means of contraception.
Confidential enquiry of stillbirths in current obstetric practice
Authors: Tham W.L , Tan K.H , Tee C.S , Yeo G.S.H
Published: July 2002

Objective: Confidential panel enquiry into sub‐optimal factors relating to stillbirths. Method: All 121 stillbirths in KK Women's and Children's Hospital in the years 1995 and 1996 were studied. Three assessors reviewed the case records of each death, and panel consensus was reached regarding sub‐optimal antenatal care and factors leading to stillbirths. Result: The incidence rate of stillbirth was 4.04 per 1000 deliveries. A total of 76 cases (62.8%) were found to have grade II and III sub‐optimal factors in their management. Patients themselves were involved in the sub‐optimal management of their own pregnancy in 52.9% of the stillbirths. Primary healthcare givers were involved in 8.3% of all stillbirths, specialist caregivers 12.4% and antenatal care system 4.1%. Conclusion: The study has identified sub‐optimal antenatal management in over 60% of cases. As patients' factors form the major contribution towards sub‐optimal care, management strategy aimed towards improving patients' education and compliance to antenatal care should be a priority.
Association of genital mycoplasma colonization with low birth weight
Authors: Paul V.K , Gupta U , Singh M , Nag V.L , Takkar D , Bhan M.K
Published: July 2002

Objective: This study was conducted to document the prevalence of maternal genital tract colonization by Ureaplasma urealyticum and Mycoplasma hominis, and to assess its association with low birth weight (LBW) and prematurity. Methods: The high vaginal swabs of pregnant women in spontaneous labor after 26 weeks of gestation were cultured for U. urealyticum and M. hominis. Clinical details and perinatal outcomes including birth weight and gestation were documented. Results: Of a total of 303 women enrolled, 148 (48.8%) had positive vaginal cultures for U. urealyticum, while only five (1.6%) grew M. hominis. The mean birth weight and the incidences of LBW and preterm neonates among ureaplasma positive and ureaplasma negative mothers were statistically comparable. Conclusions: U. urealyticum emerged as a common inhabitant of the lower genital tract of women in labor, being present in nearly half of them. Its presence was not a risk factor of LBW or prematurity. Maternal colonization with M. hominis was uncommon.
Respective roles of protein tyrosine kinases and protein kinases C in the upregulation of β‐catenin distribution, and compaction in mouse preimplantation embryos: a pharmacological approach
Authors: Goval Jean‐Jacques , Van Cauwenberge Anne , Alexandre Henri
Published: July 2002

The cellular distribution of β‐catenin was determined by western blotting and laser confocal scanning microscopy in both control and pharmacologically‐manipulated mouse preimplantation embryos. Most of the stored maternal β‐catenin is Triton X—100‐extractable and distributed throughout the cytoplasm. In 2‐cell stage embryos, the remaining molecules are concentrated in regions of cell contact and, to a lesser extent, at non apposed surfaces. Association of β‐catenin with the cortex of non apposed membranes decreases as cleavage proceeds, and is lost at compaction. In contrast to the rapid cross‐linking of cell surfaces induced by wheat germ agglutinin, the diacylglyceride‐induced compaction‐like adhesion of 2‐ and 4‐cell embryos correlates with complete restriction of β‐catenin to the apposing membranes. On the contrary, tyrphostin B46, a specific protein tyrosine kinase inhibitor, fails to induce both premature β‐catenin relocalisation and compaction. In addition, we show that orthovanadate induces a dramatic increase in the level of phosphotyrosine labelling of cell‐cell junctions in compacted 8‐cell stage embryos without inducing their decompaction. However, most of these orthovanadate tyrosine‐phosphorylated proteins are detergent‐soluble, while β‐catenin restricted to the apposing membranes is not.

In conclusion, our results confirm that diacylglycerol‐dependent kinases upregulate both β‐catenin redistribution and compaction, and indicate that neither tyrosine kinases, nor tyrosine phosphatases are critical for the proper onset of compaction which seems, in addition, not causally linked to tyrosine dephosphorylation of β‐catenin.
Length control of primary cilia: analysis of monociliate and multiciliate PtK1 cells
Authors: Wheatley Denys N. , Bowser Samuel S.
Published: July 2002

Summry— Lengths of primary cilia in cultured PtK1 cells, on both a population basis and within individual (multiciliate) cells, have been compared. The latter examines the degree of discrepancy between cilia arising within the same cell and using a common precursor pool, on the hypothesis that a better correlation would be expected between cilia issuing from the same centrosome than between those in the population in general.

To obtain accurate et plentiful measurements, a ‘flow—fixation’ technique was devised, which flattens the long primary cilia of cultured PtK1 cells (a kidney epithelial cell line from Potorous tridactylus, the kangaroo rat), prior to immunostaining with an antibody directed against detyrosinated tubulin (ID5). Comparisons of the flow‐fixed measurements with a through‐focus procedure for upright cilia in conventionally fixed cultures showed reasonable agreement, but not as closely as with measurements made on the living cells using the edge‐on method of Roth et al. (J. Cell Sci. 89 (1988) 457).

The incidence of multiciliation of confluent PtK1 cells cultures was approximately 5%, of which the majority were biciliates. Although shaft length in general varied considerably, biciliates and multiciliates showed a greater internal consistency, with discrepancies of < 25% in 70% of the cases. On both accounts, this consistency is far poorer than in, for comparison, Chlamydomonas, where its two flagella were < 5% different in length and within 10% tolerance throughout the whole population. Thus, length of primary cilia in PtK1 cell populations is considerably less stringently controlled than in PtK1 cells bearing 9 + 2 cilia, but those issuing from a single multiciliated cell tend to show better correspondence.
The capacity of connective tissue stromas to sustain myelopoiesis depends both upon the growth factors and the local intercellular environment
Authors: Carvalho Marcelo A , Arcanjo Katia , Silva Luiz Claudio F , Borojevic Radovan
Published: July 2002

Summry— In adults, haemopoiesis is located in the bone marrow, where it is tightly regulated by cytokines and by a physical association of haemopoietic progenitors with the stroma. However, in pathological situations, haemopoiesis can be partly or fully dislodged to peripheral tissues. It is not clear which are the requirements for a given peripheral stroma to sustain haemopoiesis. Using the growth factor‐dependent cell line FDC‐P1, we have compared the myelopoietic capacities of a murine bone marrow‐derived cell line S17, a liver inflammatory granuloma‐derived stroma (GR) that sustains haemopoiesis, and normal skin fibroblasts (SF) that sustain neither survival nor proliferation of myeloid cells. All three stromas expressed mRNA for major haemopoietins with the exception of IL‐3. Despite the incapacity of SF to sustain FDC‐P1 cells, the biologically active GM—CSF could be recovered from all the studied stromas by treatment with high‐salt buffers that release non‐covalently bound molecules from stroma cells. Glycosaminoglycans purified from stromas had distinct effect on the GM—CSF‐mediated proliferation of FDC‐P1 cells: those purified from S17 and GR cells were stimulatory, whereas those obtained from SF cells were slightly stimulatory at low concentration, but inhibitory at the higher ones. We conclude that the quality of the stroma pericellular glycoconjugates is determinant for the ability of a given stroma to sustain myelopoiesis, even when biologically active haemopoietins are locally produced.
Monitoring of effector and target cell stimulation during conjugation by fluorescence polarization
Authors: Fixler Dror , Tirosh Reuven , Eisenthal Avi , Marder Oleg , Irlin Yosef , Lalchuk Shlomo , Deutsch Mordechai
Published: July 2002

The aim of the present study was to trace early intracellular changes induced in effector and target cells during their conjugation. This was performed by monitoring the intracellular fluorescein fluorescence polarization (IFFP), using the Cellscan apparatus. This apparatus permits the repetitive spectroscopic measurement of individual selected live cells within a population of many cells, while the location of each cell is known and preserved during the various cell manipulations and/or their suspending medium. Both natural killer (NK) and lymphocyte activated killer (LAK) cells were used as effector cells, while NK‐sensitive K562 and NK‐resistant Daudi cell lines were used as targets. In this study kinetic IFFP measurements were carried out for a period of approximately 4 h following cell attachment. Within minutes following effector‐target conjugation, transient reduction of IFFP was observed consecutively, first in the effector and then in the target cells. A continuous reduction of IFFP occurring only in target cells was also found 50 min following conjugation. No reduction in IFFP was observed using NK‐ and LAK‐resistant target cells. Good correlation was found between early stages of conjugation, as assessed by IFFP, and cytolytic efficiency as assessed by 51chromium release assay. When NK‐resistant and LAK‐resistant target cells were used, no reduction of IFFP was observed.
Regularizing effects for multidimensional scalar conservation laws
Authors: Cheverry C
Published: July 2002

In this article, we introduce a general method for studying the smoothing effects resulting from the non linearity in a multidimensional scalar conservation law. It turns out that the regularity of physical solutions is intimately related to a number

Θ

delivered after a scattering procedure. Using this approach, we recover and unify previous information while obtaining new results.

Dans cet article, on s’intéresse à l’effet de lissage induit par la non linéarité dans une loi de conservation scalaire multidimensionnelle. Il se trouve que la régularité des solutions entropiques est liée à un nombre

Θ

obtenu à l’issue d’une procédure de scattering. Cette approche permet de retrouver, d’unifier, d’étendre et d’améliorer les résultats antérieurs. Voir Cheverry (1999) pour une présentation concise en français.
Screening For Hypoglycemia In Healthy Term Neonates: Effects On Breastfeeding
Authors: Haninger Nancy C. , Farley Cynthia L.
Published: July 2002

Transient hypoglycemia in the early neonatal period is a common adaptive phenomenon as the newborn changes from the fetal state of continuous transplacental glucose consumption to intermittent nutrient supply following cessation of maternal nutrition at birth. Research has demonstrated that in the term, healthy newborn, this dynamic process is self‐limiting and is not considered pathologic.

The American Academy of Pediatrics and the World Health Organization recommend that neonatal blood glucose screening be reserved for newborns who are at risk or symptomatic and conclude that universal hypoglycemia screening is inappropriate, unnecessary, and potentially harmful. Nevertheless, many hospital nurseries continue the clinical practice of routine early glucose screening on healthy, term newborns. This results in the misidentification of neonates captured while experiencing the normal, self‐correcting physiologic blood glucose nadir who are then diagnosed with pathologic neonatal hypoglycemia.

Subsequent to this misdiagnosis, further surveillance and unnecessary, aggressive treatment interventions will follow that are potentially harmful to the successful establishment of positive maternal‐infant interactions and the breastfeeding experience.

Research studies indicate that routine hypoglycemia screens, treatments, and interventions in the healthy infant are not evidence‐based and result in a serious disruption of the initiation process and duration patterns of lactation.

Using the perspective of the theory of technology dependency, this inquiry explores the potential adverse sequelae of inappropriate glucose screening in the healthy breastfeeding newborn and describes selected outcome variables including: 1) the consequences of early maternal‐infant separation, 2) the influence of early formula supplementation on breastfeeding discontinuance rates, 3) the effect of separation and supplementation on the onset of lactogenesis, and 4) the impact of hospital staff and provider recommendations of formula supplementation on maternal confidence to independently nurture her baby.
The Optical Constants of Solution‐Processed Semiconductors—New Challenges with Perovskites and Non‐Fullerene Acceptors
Authors: Kerremans Robin , Kaiser Christina , Li Wei , Zarrabi Nasim , Meredith Paul , Armin Ardalan
Published: May 2020

Accurate determination of the optical constants of thin film solids has been an ongoing endeavor in optoelectronics and related fields for decades. These constants, namely the refractive index and extinction (or attenuation) coefficient, are the fundamental material properties that dictate electromagnetic field propagation in any medium. They form the inputs to well‐established models that allow for design and optimization of multilayer stack structures such as thin film solar cells, light‐emitting diodes, and photodetectors. These determinations are particularly challenging for materials that are scattering and highly absorbing. In this work, a new and resource‐efficient approach for optical constant determination based upon transmission spectrophotometry in combination with an iterative, reverse transfer matrix model and the Kramers–Kronig relation is reported. The approach is validated using more conventional ellipsometry for a number of functionally important semiconductors, including the recently emergent organic non‐fullerene electron acceptors (NFAs) and perovskites for which the optical constants in the UV–vis–near IR region are provided. Notably, the NFAs are found to present anomalously high refractive indices and extinction coefficients that are predicted to have a profound influence on the cavity electro‐optics of the new record efficiency organic solar cells of which they are key components.
Selective C(sp3)−H Functionalization of Alkyl Esters with N‐/S‐/O‐Nucleophiles Using Perfluoroalkyl Iodide as Oxidant
Authors: Zhao Shi‐Wen , Cai Song‐Zhou , Wang Mao‐Lin , Rao Weidong , Xu Haiyan , Zhang Lei , Chu Xue‐Qiang , Shen Zhi‐Liang
Published: May 2020

An efficient transition metal‐free approach to achieve the selective cleavage of the α‐carbonyl C(sp3)−H bond in alkyl esters by using inexpensive, low‐toxic, and insensitive perfluoroalkyl iodide as the radical initiator has been developed. A variety of enamides, N‐heterocycles, amides, thiophenols, and phenols could be successfully incorporated into functionalized alkyl groups by intermolecular amination, thioetherification, and etherification. The distinguishing features of this CDC reaction are its broad substrate scope, synthetic simplicity, and mild reaction conditions.

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Amorphous TiO2‐Derived Large‐Capacity Lithium Ion Sieve for Lithium Recovery
Authors: Li Xiaowei , Chen Linlin , Chao Yanhong , Chen Wang , Luo Jing , Xiong Jun , Zhu Fengxia , Chu Xiaozhong , Li Huaming , Zhu Wenshuai
Published: May 2020

The lithium titanium oxide ion sieve with good structural stability and high adsorption capacity is generally considered to be a promising adsorbent for lithium recovery. Herein, the lithium ion sieve precursor Li2TiO3 was prepared based on amorphous TiO2, and then Li+ was acid‐eluted to obtain the lithium adsorbent H2TiO3, denoted as HTO‐Am. The structure and adsorption properties of HTO‐Am were investigated, and the results demonstrated that the HTO‐Am prepared at the optimum temperature had excellent adsorption properties for Li+. The adsorption process follows pseudo‐second‐order kinetic and Langmuir isotherm equations, indicating that lithium is adsorbed chemically and monolayer on HTO‐Am. HTO‐Am ion sieves were prepared successfully for the first time and exhibited high selectivity, favorable adsorption rate, and cycle performance for Li+.
Plasma Treatment: a Novel Approach to Improve the Photoelectroactivity of Sb2S3 Thin Films to Water Splitting
Authors: de Araújo Moisés A. , Mascaro Lucia H.
Published: May 2020

The present study reports a novel and fast nitrogen plasma treatment approach to boost hydrogen evolution on antimony(III) sulphide (Sb2S3) thin films via light‐driven water splitting. The Sb2S3 films were synthesised by electrodepositing antimony followed by sulphurisation, and then using different treatment times under nitrogen plasma. The plasma treatment time did not result in significant changes in the microstructural and optical properties, compared to the non‐plasma films. However, the wettability drastically changed from superhydrophobic for the non‐plasma film to hydrophilic once treated. Photoelectrochemical analysis showed a substantial photocurrent density increase (24‐fold) for the film treated for 10 s in comparison with the non‐plasma film. Further characterisation by X‐ray photoelectron spectroscopy and scanning electron microscopy revealed chemical and morphological modifications for the films treated, which explain the enhancement of photoelectroactivity and wettability.
FuSTM: ProM plugin for fuzzy similar tasks mining based on entropy measure
Authors: Amrou M'hand Mouna , Boulmakoul Azedine , Badir Hassan
Published: May 2020

Organizational perspectives of process mining consist of organizing and classifying the organization in terms of missions, roles as well as the interactions between the performers. Social mining is a branch of process mining that centralizes on construction social graphs based on the information held in the process. However, standard clustering approaches are not always proper to business processes as they are known for their complex, flexible, and intrinsic nature. Therefore, fuzzy clustering is capable of identifying indeterminate frontiers that hard clustering omits to identify. In this article, we propose a plugin that applies entropy‐based fuzzy clustering for mining similar tasks using event data. The plugin is intended to be integrated into ProM6 framework as a package. It is the first plugin that uses fuzzy clustering for mining social networks and adopts data‐driven documents library to visualize graphs. The results of the plugins' applicability are illustrated using a case study of a Dutch financial institute.
Intestinal P‐gp and Putative Hepatic OATP1B Induction: International Transporter Consortium Perspective on Drug Development Implications
Authors: Zamek‐Gliszczynski Maciej J. , Patel Mitesh , Yang Xinning , Lutz Justin D. , Chu Xiaoyan , Brouwer Kim L. R. , Lai Yurong , Lee Caroline A. , Neuhoff Sibylle , Paine Mary F. , Sugiyama Yuichi , Taskar Kunal S. , Galetin Aleksandra
Published: May 2020

There is an increasing interest in transporter induction (i.e., decreased systemic drug exposure due to increased efflux‐limited absorption or transporter‐mediated clearance) as a mechanism of drug–drug interactions (DDIs), although evidence of clinical relevance is still evolving. Intestinal P‐glycoprotein (P‐gp) and hepatic organic anion transporting polypeptides 1B (OATP1B) can be important determinants of drug absorption and disposition, as well as targets for DDIs. Current data indicate that intestinal P‐gp protein levels can be induced up to threefold to fourfold in humans primarily with pregnane X receptor (PXR) activators, and that this induction can decrease the systemic exposure of drugs with P‐gp efflux‐limited absorption (e.g., ≤ 67% decrease in the exposure of total dabigatran following rifampin multiple oral dosing). Evaluation of the clinical relevance of P‐gp induction as a DDI mechanism must consider the induction potential of the perpetrator drug for P‐gp and attenuation of exposure of the victim drug in the context of its therapeutic window. Practical drug development recommendations are provided herein. Reports are contradictory on OATP1B induction by PXR activators in human hepatocytes and liver biopsies. Some clinical investigations demonstrated that rifampin pretreatment decreased exposure of OATP1B substrates, while other studies found no differences, and the potential involvement of other mechanisms in these observed DDIs cannot be definitively ruled out. Thus, further studies are needed to understand hepatic OATP1B induction and potential involvement of other mechanisms contributing to reduced exposure of OATP1B substrates. This review critically summarizes the state‐of‐the‐art on intestinal P‐gp and hepatic OATP1B induction, and highlights implications for drug development.
Intermittent moisture supply induces drought priming responses in some heat‐tolerant chickpea genotypes
Authors: Makonya Givemore M. , Ogola John B.O. , Muasya A. Muthama , Crespo Olivier , Maseko Sipho , Valentine Alex J. , Ottosen Carl‐Otto , Rosenqvist Eva , Chimphango Samson B.M.
Published: May 2020

Heat and drought stresses are two abiotic factors that often occur simultaneously and are predicted to increase, consequently hampering plant growth. Response of different species to either stresses is well documented but information on the response of the same genotypes to both stresses in chickpea (Cicer arietinumL.) is limited. We aimed to determine whether previously noted heat‐stress‐tolerant genotype (Acc#7) is drought tolerant, that heat‐sensitive genotype (Acc#8) is drought sensitive, and whether intermittent moisture supply at vegetative stage would induce priming effect to later drought at flowering. At vegetative stage, plants were divided into three groups, nonstressed (watered to 75% field capacity [FC], severe water stress (moisture withholding for 14 d), and treated to 40% FC throughout the experiment (mild stress), with recovery for the severely stressed plants after which they were stressed (double stress) at flowering. Drought treatments at vegetative and flowering growth stages decreased physiological parameters and biomass accumulation in both genotypes except low water supply at 40% FC that decreased biomass in Acc#7 but not Acc#8. Double‐drought stress resulted in priming effect in Acc#7, having higher biomass, chlorophyll fluorescence, stomatal conductance (gs), net photosynthesis, and relative water content (RWC) vs. the introduction of stress only at flowering growth stage as well as in comparison with Acc#8. These results showed that both Acc#7 and Acc#8 are sensitive to drought, whereas after priming, Acc#7 is better acclimated to drought than Acc#8 associated with osmotic adjustment on leaf RWC and higher capacity to protect photosynthetic activity, making Acc#7 potentially ideal for areas associated with intermittent drought spells.
Improved Flow Cytometric Light Scatter Detection of Submicron‐Sized Particles by Reduction of Optical Background Signals
Authors: Arkesteijn Ger J. A. , Lozano‐Andrés Estefanía , Libregts Sten F. W. M. , Wauben Marca H. M.
Published: May 2020

Flow cytometry allows multiparameter analysis on a single‐cell basis and is currently the method of choice to rapidly assess heterogeneity of cell populations in suspension. With the research field of extracellular vesicles (EV) rapidly expanding, there is an increased demand to address heterogeneity of EV populations in biological samples. Although flow cytometry would be the ideal technique to do so, the available instruments are in general not equipped to optimally detect the dim light scatter signals generated by submicron‐sized particles like EV. Although sideward scatter light and fluorescence are currently used as a threshold signal to identify EV within samples, the forward scatter light (FSC) parameter is often neglected due to the lack of resolution to distinguish EV‐related signals from noise. However, after optimization of FSC detection by adjusting the size of the obscuration bar, we recently showed that certain EV‐subsets could only be identified based on FSC. This observation made us to further study the possibilities to enhance FSC‐detection of submicron‐sized particles. By testing differently sized obscuration bars and differently sized pinholes in the focal plane behind the FSC detection lens, we generated a matrix that allowed us to determine which combination resulted in the lowest optical background in terms of numbers of events regarding FSC detection of submicron‐sized particles. We found that a combination of an 8‐mm obscuration bar and a 200‐μm pinhole reduced optical background in a reproducible manner to such extent that it allowed a robust separation of 100‐nm polystyrene beads from background signals within the FSC channel, and even allowed thresholding on FSC without the interference of massive background signals when both beads and EV were measured. These technical adaptations thus significantly improved FSC detection of submicron‐sized particles and provide an important lead for the further development and design of flow cytometers that aid in detection of submicron‐sized particles. © 2020 The Authors.Cytometry Part Apublished by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Itch attenuates CD4 T‐cell proliferation in mice by limiting WBP2 protein stability
Authors: Field Natania S. , Elbulok Omar A. , Dybas Joseph M. , Moser Emily K. , Dar Asif A. , Spruce Lynn A. , Fazelinia Hossein , Seeholzer Steven H. , Oliver Paula M.
Published: May 2020

To mount an antipathogen response, CD4 T cells must undergo rapid cell proliferation; however, poorly controlled expansion can result in diseases such as autoimmunity. One important regulator of T‐cell activity is the E3 ubiquitin ligase Itch. Itch deficient patients suffer from extensive autoinflammation. Similarly, Itch deficient mice exhibit inflammation characterized by high numbers of activated CD4 T cells. While the role of Itch in limiting CD4 T‐cell cytokine production has been extensively studied, it is less clear whether and how Itch regulates proliferation of these cells. We determined that Itch deficient CD4 T cells are hyperproliferative in vitro and in vivo, due to increased S phase entry. Whole cell proteomics analysis of Itch deficient primary mouse CD4 T cells revealed increased abundance of the β‐catenin coactivator WW domain‐binding protein 2 (WBP2). Furthermore, Itch deficient cells demonstrate increased WBP2 protein stability, and Itch and WBP2 interact in CD4 T cells. Knockdown of WBP2 in CD4 T cells caused reduced proliferation. Together, our data support that Itch attenuates CD4 T cell proliferation by promoting WBP2 degradation. This study identifies novel roles for Itch and WBP2 in regulating CD4 T cell proliferation, providing insight into how Itch may prevent inflammation.
Evaluations of Automated Scoring Systems in Practice
Authors: Rotou Ourania , Rupp André A.
Published: May 2020

This research report provides a description of the processes of evaluating the “deployability” of automated scoring (AS) systems from the perspective of large‐scale educational assessments in operational settings. It discusses a comprehensive psychometric evaluation that entails analyses that take into consideration the specific purpose of AS, the test design, the quality of human scores, the data collection design needed to train and evaluate the AS model, and the application of statistics and evaluation criteria. Finally, it notes that an effective evaluation of an AS system requires professional judgment coupled with statistical and psychometric knowledge and understanding of the risk assessment and business metrics.
Layering‐Triggered Delayering with Exfoliated High‐Aspect Ratio Layered Silicate for Enhanced Gas Barrier, Mechanical Properties, and Degradability of Biodegradable Polymers
Authors: Zhu Jian , Kumar Anil , Hu Pin , Habel Christoph , Breu Josef , Agarwal Seema
Published: May 2020

Research on biodegradable polymers with the intention of fast, complete degradation in industrial compost (i‐compost) for organic recyclability is paramount to identifying solutions to the problem of excessive plastic waste originating specifically from packaging. Conventional biodegradable polymers, such as polylactide (PLA), are far from optimum for this application due to the poor gas barrier properties and slow degradation. In the paper, a new concept (triggered degradation by delayering) is shown in which exfoliated, self‐assembled sodium‐hectorite (Hec) arranged in a layer‐by‐layer manner alternating with electrospun hot‐pressed PLA provides strong gas barrier properties at high humidity and simultaneously accelerates the degradation of PLA, as tested in an enzymatic solution and i‐compost. A thin composite film (thickness 56 µm) shows a tensile strength and modulus 58 and 2000 MPa, respectively, whereas oxygen permeability is as low as 0.0064 cm3 cm m−2 day−1 bar−1. Furthermore, the delayering of the composite film by swelling of Hec layer led to accelerated degradation of PLA, as shown in detail by enzymatic and compost degradation. Since such concepts for enhanced degradability are urgently needed for sustainable utilization of biodegradable polymers in plastic waste management, the present work is an important step ahead.
Activation of astrocytic sigma‐1 receptor exerts antidepressant‐like effect via facilitating CD38‐driven mitochondria transfer
Authors: Wang Yun , Ni Jing , Gao Tianyu , Gao Ce , Guo Lin , Yin Xiaoxing
Published: May 2020

Despite sigma‐1 receptor (Sig‐1R) is a promising therapeutic target in depression, little is known regarding the cellular mechanisms underlying its antidepressant responses. Here, we demonstrated that astrocyte can be a direct cellular target of Sig‐1R exerting antidepressant‐like effect. In multiple behavioral models including forced swimming test (FST), tail suspension test (TST), open field test (OFT), and chronic unpredictable mild stress (CUMS), inhibition of astrocyte function blocked pharmacological Sig‐1R activation‐induced antidepressant‐like effect, while specific activation of astrocytc Sig‐1R by adeno‐associated virus (AAV) was sufficient to produce antidepressant‐like effect. In depression‐related cellular tests, Sig‐1R agonist or lentivirus‐stimulated astrocyte conditioned medium (ACM) promoted neuronal neurite outgrowth, dendritic branch, and survival. Mechanismly, stimulation of Sig‐1R enhanced the expression of CD38 via activation of extracellular regulated protein kinases 1/2 (ERK1/2), resulting in facilitating mitochondrial transfer from astrocyte. Furthermore, blockage of CD38‐driven astrocyte transferring mitochondria in vivo and in vitro reversed the antidepressant‐like effect of pharmacological Sig‐1R activation. Thus, this study sheds light on the cellular mechanism of Sig‐1R activation producing antidepressant‐like effect. These data present the first evidence that enhancement of Sig‐1R action on astrocytes entirely exerts antidepressant‐like effect, indicating that specific activation of astrocytic Sig‐1R may provide a new approach for antidepressant drug development.