bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA
Authors: Richardson Peter T. , Westby Michael , Roberts Lynne M. , Gould Jane H. , Colman Alan , Lord J.Michael
Published: July 2002

Preproricin transcripts microinjected into Xenopus oocytes were expressed and the product was segregated by the oocyte endoplasmic reticulum and core glycosylated. Recombinant proricin was soluble, stabilised by intramolecular disulfide bonds and biologically active in that it could bind to immobilized lactose (selectin 2) or immobilized asialofetuin. Affinity‐purified proricin did not catalyse the depurination of 28 S ribosomal RNA unless it was reduced, when slight but significant activity was observed. Gel filtration of the reduced proricin fraction showed that this depurination activity was not associated with proricin. The activity was apparently due to ricin A chain released by reduction from mature ricin which was, in turn, generated from proricin, presumably via endogenous oocyte endoprotease activity.
Two lipoyl domains in the dihydrolipoamide acetyltransferase chain of the pyruvate dehydrogenase multienzyme complex of Streptococcus faecalis
Authors: Allen Andrew G. , Perham Richard N.
Published: July 2002

A fragment of DNA incorporating the gene, pdhC. that encodes the dihydrolipoamide acetyltransferase (E2) chain of the pyruvate dehydrogenase multienzyme complex of Streptococcus faecalis was cloned and a DNA sequence of 2360 bp was determined. The pdhC gene (1620 bp) corresponds to an E2 chain of 539 amino acid residues. M
r 56 466, comprising two lipoyl domains, a peripheral subunit‐binding domain and an acetyltransferase domain, linked together by regions of polypeptide chain rich in alanine, proline and charged amino acids. The S. faecalis E2 chain differs in the number of its lipoyl domains from the E2 chains of all bacterial pyruvate dehydrogenase complexes hitherto described.
Reactions of the α‐tocopheroxyl radical in micellar solutions studied by nanosecond laser flash photolysis
Authors: Bisby Roger H. , Parker Anthony W.
Published: July 2002

Laser flash photolysis of α‐tocopherol in methanol and in aqueous micellar solutions has been shown to produce the α‐tocopheroxyl radical. The reaction between the α‐tocopheroxyl radical and ascorbate in positively charged hexadecyltrimethylammonium chloride (HTAC) micelles occurred with a second order rate constant of 7.2 × 107 M−1·s−1, whereas in negatively charged sodium dodecyl sulphate (SDS) micelles the rats constant was only 3.8 × 104 M−1·s−1. The α‐tocopheroxyl radical was found to be relatively long‐lived in HTAC micelles (t½ ⩾ 5 min), allowing the slow disappearance of the α‐tocopheroxyl radical by reaction with glutathione to be observed.
The sodium ion pumping oxaloacetate decarboxylase of Klebsiella pneumoniae Metal ion content, inhibitors and proteolytic degradation studies
Authors: Dimroth Peter , Thomer Anna
Published: July 2002

Oxaloacetate decarboxylase of Klebsiella pneumoniae was shown to contain between 0.6 and 1.0 mol zinc per mol enzyme in different preparations. The decarboxylase activity was completely abolished after 15 min incubation with 1 mM Hg(NO3)2 in phosphate buffer, while the activity decreased only 20% if the incubation was performed in MES/Trix buffer. Treatment of the isolated subunits with Hg(NO3)2 indicated that the binding site for Hg2+ ions is on the α subunit. Other inhibitors of the decarboxylase are KSCN and diethylstilbestrol. Inactivation of the enzyme with 2% 1‐butanol was significantly reduced by 100 mM NaCl. Sodium ions also protected the isolated β+γ subunits from a digestion with trypsin.
Reversal of oxidative phosphorylation in submitochondrial particles using glucose 6‐phosphate and hexokinase as an ATP regenerating system
Authors: de Meis Leopoldo , Grieco Maria Angela B. , Galina Antonio
Published: July 2002

The different reaction measured with the use of glucose‐6‐phosphate and hexokinase were inhibited by glucose concentrations varying from 0.2 to 2 mM. Glucose shifts be equilibrium of the reaction towards glucose‐6‐phosphate formation thus leading to a decrease of the ATP concentration in the medium.
Purification of two active fusion proteins of the Na+‐dependent citrate carrier of Klebsiella pneumoniae
Authors: Pos Klaas M. , Bott Michael , Dimroth Peter
Published: July 2002

The sodium‐ion‐dependent citrate carrier of Klebsiella pneumoniae (CitS) was purified by means of bioengineerical methods. By fusing the biotin acceptor domain of the α‐subunit of the oxaloacetate decarboxylase of K pneumoniae to the C‐terminus of CitS, purification of the carrier was achieved by use of a monomeric avidin‐Sepharose column. Additionally, we were able to purify a CitS‐protein with an N‐terminal histidine‐tag by immobilized metal chelate affinity chromatography (with Ni2+‐nitrilotriacetic acid‐(NTA‐) resin). Both purified fusion proteins showed citrate transport activity after reconstitution into liposomes by the freeze/thaw/sonication procedure.
Sarcoidosis in a uterine leiomyoma
Authors: Menzin A.W. , You T.T. , Deger R.B. , Brooks J.S.J. , King S.A.
Published: July 2002

Sarcoidosis is a granulomatous condition of unknown etiology. Though the lung and lymph nodes are most commonly involved, other organs may also be affected. Involvement of the female reproductive system is very uncommon and usually has been found in the endometrium or myometrium. A case is described of a 43‐year‐old nulligravida who presented for evaluation of a dry cough and who was found to have a pelvic mass. Preoperative evaluation revealed the presence of pulmonary sarcoidosis. At the time of exploratory laparotomy, a large, pedunculated fibroid was resected along with an inflammatory cyst. Histopathologic examination revealed the presence of sarcoid lesions within the fibroid. This is the first report of such a finding, and the implications are discussed.
The high affinity ATP binding site modulates the SecA–precursor interaction
Authors: van Voorst Frank , Vereyken Ingrid J , de Kruijff Ben
Published: July 2002

SecA is the central component of the protein‐translocation machinery of Escherichia coli. It is able to interact with the precursor protein, the chaperone SecB, the integral membrane protein complex SecYEG, acidic phospholipids and its own mRNA. We studied the interaction between prePhoE and SecA by using a site‐specific photocrosslinking strategy. We found that SecA is able to interact with both the signal sequence and the mature domain of prePhoE. Furthermore, this interaction was dependent on the type of nucleotide bound. SecA in the ADP‐bound conformation was unable to crosslink with the precursor, whereas the ATP‐bound conformation was active in precursor crosslinking. The SecA–precursor interaction was maintained in the presence of E. coli phospholipids but was loosened by the presence of phosphatidylglycerol bilayers. Examining SecA ATP binding site mutants demonstrated that ATP hydrolysis at the N‐terminal high affinity binding site is responsible for the changed interaction with the preprotein.
The biochemical profile of rat testicular tissue as measured by magic angle spinning 1H NMR spectroscopy
Authors: Griffin J.L. , Troke J. , Walker L.A. , Shore R.F. , Lindon J.C. , Nicholson J.K.
Published: July 2002

The testis is the principal organ of male fertility, responsible for the production of spermatozoa and their maturation into sperm. However, the underlying biochemistry of the testis is relatively understudied. The fluidic and homogeneous nature of the testis makes it an ideal organ for high resolution magic angle spinning (MAS) 1H NMR spectroscopy. In this study we have catalogued the low molecular weight metabolites. The testis contains large amounts of creatine, of which a substantial proportion was shown to be extracellular using bipolar gradients to measure apparent diffusion coefficients. The tissue also contained relatively high amounts of uridine.
New genotypes of TT virus (TTV) and a genotyping assay based on restriction fragment length polymorphism1
Authors: Tanaka Yasuhito , Mizokami Masashi , Orito Etsuro , Ohno Tomoyoshi , Nakano Tatsunori , Kato Takanobu , Kato Hideaki , Mukaide Motokazu , Park Young-Min , Kim Boo-Sung , Ueda Ryuzo
Published: July 2002

A phylogenetic analysis, using the open reading frame 1 sequence of 93 TT viruses (TTV) obtained from various geographical areas, indicated that the virus could be classified into six different genotypes including three hitherto unreported genotypes. The high reliability of the six clusters was confirmed by bootstrap analysis. On the basis of these sequence data, a new simple genotyping assay based on a restriction fragment length polymorphism of TTV was developed. Using the enzymes NdeI and PstI, followed by cleavage with NlaIII or MseI, it was possible to distinguish between the six TTV genotypes. This system will provide the framework for future detailed epidemiological and clinical investigations.
Chemical modification of lysine side chains of cyclodextrin glycosyltransferase from Thermoanaerobacter causes a shift from cyclodextrin glycosyltransferase to α‐amylase specificity
Authors: Alcalde Miguel , Plou Francisco J , Andersen Carsten , Martı́n M.Teresa , Pedersen Sven , Ballesteros Antonio
Published: July 2002

cyclodextrin glycosyltransferases and α‐amylases are two groups of enzymes with related secondary structures. However, cyclodextrin glycosyltransferases display transferase activities not present in α‐amylases, probably derived from the existence of two more domains and different amino acid sequences. The hydrolytic activity of cyclodextrin glycosyltransferases is generally quite low, except for two cyclodextrin glycosyltransferases from termophiles. In this work, we have carried out the chemical modification (with acetic anhydride) of the amino groups of cyclodextrin glycosyltransferase from Thermoanaerobacter to assess their contributions to protein function. The acetylated cyclodextrin glycosyltransferase showed a significant reduction of its cyclization, coupling and disproportionation activities. Surprisingly, the hydrolytic (saccharifying) activity was slightly enhanced. These results suggest the participation of one or more lysine side chains in the interactions contributing to the transferase activity, either in any of the Sn subsites or in the acceptor binding site.
The broad spectrum of comorbid depression: implications for treatment
Authors: Mendlewicz J
Published: July 2002

There is a high rate of depression in patients with medical or other psychiatric disorders. This comorbid depression is associated with an increased morbidity and mortality from medical illness, poor compliance with treatment, a worsening of somatic symptoms, and often a decrease in functional status. Several recent studies have demonstrated that comorbid depression is highly treatable and that effective treatment often enhances patients' adaptive coping with medical illness. However, when choosing antidepressant therapy, care must be taken to evaluate the patient's illness fully and to avoid potential drug-drug interactions and drug-related illness. This review investigates the use of antidepressants in depressed patients with medical and psychiatric disorders and their effect on prognosis and morbidity, and suggests that there is a place for the use of antidepressant medications in the treatment of comorbid conditions. Generally, the greater safety and tolerability of the selective serotonin reuptake inhibitors provides improved options for the treatment of depression in the medically and psychiatrically ill.
Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C
Authors: Chong Shi Min Sherilyn , Kamariah Neelagandan , Grüber Gerhard
Published: June 2020

The ability of Mycobacteria to overcome oxidative stress is of paramount importance for its survival within the host. One of the key enzymes that are involved in protecting the bacterium from reactive oxygen species is the catalase‐peroxidase (KatG). However, in strains resistant to the antibiotic isoniazid, KatG is rendered ineffective, which is associated with an increased expression of alkylhydroperoxide reductase subunit C (AhpC). Mycobacterial AhpC possesses a unique helical displacement when compared to its bacterial counterparts. Here, via mutagenesis studies, we demonstrate the importance of this helix for redox modulation of the catalytic activity of AhpC. Along with structural insights from crystallographic data, the impact of critical residues on the structure and flexibility of the helix and on AhpC oligomerization is described.
Algimonas
Authors: Fukui Youhei
Published: June 2020

Al.gi.mo'nas. L. fem. n.
alga
seaweed; L. fem. n.
monas
a monad, a unit; N.L. fem. n.
Algimonas
a monad isolated from seaweed.

Proteobacteria / Alphaproteobacteria / Rhodobacterales / Hyphomonadaceae / Algimonas

The genus
Algimonas
comprises three species,
Algimonas porphyrae
(the type species),
Algimonas ampicilliniresistens
, and
Algimonas arctica
. Cells exhibit rod‐shaped morphology. One cell possesses a single polar flagellum and the other, a prosthecum. Cell division occurs by binary fission. Colonies are round, convex, and orange or pale orange. Cells are Gram‐negative, motile, aerobic, and produce carotenoid pigments but not bacteriochlorophyll
a
. Growth occurs at 10–30°C (optimum, 20–25°C), pH 6.0–9.0 (optimum, 7.0–8.0), and 1.0–5.0% NaCl (optimum, 2.0–3.0%). Cells are positive for catalase, nitrate reduction, and hydrolysis of esculin and negative for methyl red and Voges–Proskauer reactions, indole and H
2
S production, and hydrolysis of starch and gelatin. Analysis of 16S rRNA gene sequences revealed that the genus
Algimonas
belongs to the family
Hyphomonadaceae
and is related to the genera
Litorimonas
,
Fretibacter
,
Hellea
, and
Robiginitomaculum
. The predominant respiratory quinone is ubiquinone‐10. The major polar lipids are phosphatidylglycerol, glucuronopyranosyl diglyceride, monoglycosyl diglyceride, and three unidentified phospholipids. The major fatty acids (>10%) are C
18:1
ω7
c
and C
18:1
2‐OH. Members of the genus have been isolated from marine red alga or intertidal sand.

DNA G
 + 
C content (mol%)
: 54.3–60.6 (HPLC or
T
m
).

Type species
:
Algimonas porphyrae
Fukui et al. 2013a
VP
.
LarC Cyclometallase
Authors: Desguin Benoit
Published: June 2020

Bacterial lactate racemase is a nickel‐dependent enzyme that contains the nickel‐pincer nucleotide (NPN) cofactor. The LarC enzyme participates in NPN biosynthesis by inserting nickel ion into the cofactor precursor, forming the mature NPN. This reaction, known in organometallic chemistry as a cyclometalation, is characterized by the formation of new NiC and NiS σ bonds. LarC is therefore the first cyclometallase identified in nature. LarC behaves as a single turnover enzyme
in vitro
and its reaction requires Mn
2+
‐dependent CTP hydrolysis. The crystal structure of the C‐terminal domain of LarC (LarC2) revealed the CTP binding pocket. LarC1 domain, on the other hand, is responsible for the cyclometalation reaction. Its structure has not been solved but a model has been constructed using evolutionary information. LarC1 catalysis requires acidic residues, which are probably involved in proton abstraction from the NPN precursor and nickel transfer, but the mechanism remains elusive.
Membrane‐Bound Superoxide Oxidase
Authors: Sjöstrand Dan , Högbom Martin , von Ballmoos Christoph
Published: June 2020

Reactive oxygen species (ROS) are formed as natural byproducts of aerobic metabolism. Their reactivity toward lipids, proteins, and DNA causes extensive cellular damage, and most cells have dedicated enzymes for their scavenging, such as superoxide dismutase (SOD) and catalase. Superoxide oxidase (SOO) is a 20‐kDa integral membrane enzyme/protein that directly oxidizes superoxide, reducing ubiquinone in the process. The enzymatic reaction of SOO is diffusion limited, similar to the soluble SOD enzymes. The X‐ray structure shows a bundle of four transmembrane (TM) helices with two internal hemes. One heme is partially exposed to the bulk of the periplasm, sitting at the bottom of a positively charged funnel‐shaped pocket, presumably representing the entry point of superoxide. The other heme is positioned next to a membrane‐exposed cavity, which is likely binding and orienting the ubiquinone head group for the reduction step of the reaction. The structural architecture of SOO resembles the core four‐helix, two‐heme motif of a group of other diheme enzymes catalyzing a variety of redox reactions. This article includes a detailed description of the structural features of SOO, as well as a discussion on the currently available evidence for its function.
Dimeric P‐loop ATPase CFD1 and Related Proteins
Authors: Freibert Sven A , Jeoung Jae‐Hun , Stehling Oliver , Dobbek Holger , Lill Roland
Published: June 2020

The assembly of iron–sulfur (Fe/S) proteins in living cells requires complex machineries. The initial synthesis of a Fe/S cluster occurs on specialized scaffold proteins rather than on target apoproteins. The scaffold needs to support both facile assembly and ready transfer of clusters to Fe/S trafficking proteins that assist cluster delivery to final recipients. In the cytosolic iron–sulfur protein assembly (CIA) machinery of eukaryotes, the hetero‐oligomeric CFD1‐NBP35 complex is performing a scaffold function. Both proteins belong to the metal binding P‐loop NTPase family whose members typically are involved in metal center assembly.
In vivo
, Fe/S cluster assembly on CFD1‐NBP35 depends on functional nucleotide binding sites in both proteins, a sulfur compound exported from mitochondria, and the CIA electron transfer chain TAH18‐DRE2.
In vitro
, CFD1‐NBP35 bind a bridging [4Fe–4S] cluster at two conserved cysteine residues of each protein. The crystal structure of homodimeric CFD1, as a model of the heterodimer, locates these clustercoordinating cysteine residues on exposed loops. The bridging cluster coordination appears to be ideal for both facile cluster assembly and rapid transfer to downstream CIA trafficking proteins. The crucial cellular function of CFD1‐NBP35 is indicated by their essential
in vivo
requirement for assembly of most cytosolic and nuclear Fe/S proteins.
Microstructural Optimization of Fe‐Rich Intermetallic in Al–12 wt% Si–2 wt% Fe alloys by Adding Travelling Magnetic Fields
Authors: Luo Lei , Xia Hongying , Luo Liangshun , Su Yanqing , Wang Liang , Guo Jingjie , Fu Hengzhi
Published: June 2020

Iron can cause negative effects on the recycling and mechanical performance of Al–Si alloys, because it is difficult to remove, and easy to form Fe‐rich intermetallic with large size. In this regard, travelling magnetic fields are performed to optimize Fe‐rich intermetallic in Al–12 wt% Si–2 wt% Fe alloys; and experiments and simulations are conducted to study the related evolutions induced by different Fe content from 0.1 to 2 wt% and by travelling magnetic fields. Current findings conclude that the increase of Fe content changes the precipitation sequence, causing Fe‐rich intermetallic to preferentially form and convert from α‐Al8Fe2Si to β‐Al9Fe2Si2; accompanied by the increase of aspect ratio and max‐length from 1.81 and 15.0 μm ( wt% Fe) to 50.2 and 578.2 μm (2 wt% Fe) respectively, as well as the decrease of curvature from 0.079 μm−1 (0.1 wt% Fe) to 0.001 μm−1 (2 wt% Fe). Moreover, precipitates containing Cu shift from adhering to the (Al, Si) phases to Fe‐rich intermetallic. In additionally, primary Si particles and Al–Si eutectic phases decrease. Noteworthily, travelling magnetic fields can reduce nucleate radius and generate intense long‐range directional melt flows, further to distribute temperature and solute uniformly and break up Fe‐rich intermetallic, so as to optimize them. Consequently, max‐length and aspect ratio decrease by 43.7% and 44.6%, whereas curvature increases by 2.7 times.
Wearable Triboelectric/Aluminum Nitride Nano‐Energy‐Nano‐System with Self‐Sustainable Photonic Modulation and Continuous Force Sensing
Authors: Dong Bowei , Shi Qiongfeng , He Tianyiyi , Zhu Shiyang , Zhang Zixuan , Sun Zhongda , Ma Yiming , Kwong Dim‐Lee , Lee Chengkuo
Published: June 2020

Wearable photonics offer a promising platform to complement the thriving complex wearable electronics system by providing high‐speed data transmission channels and robust optical sensing paths. Regarding the realization of photonic computation and tunable (de)multiplexing functions based on system‐level integration of abundant photonic modulators, it is challenging to reduce the overwhelming power consumption in traditional current‐based silicon photonic modulators. This issue is addressed by integrating voltage‐based aluminum nitride (AlN) modulator and textile triboelectric nanogenerator (T‐TENG) on a wearable platform to form a nano‐energy‐nano‐system (NENS). The T‐TENG transduces the mechanical stimulations into electrical signals based on the coupling of triboelectrification and electrostatic induction. The self‐generated high‐voltage from the T‐TENG is applied to the AlN modulator and boosts its modulation efficiency regardless of AlN's moderate Pockels effect. Complementarily, the AlN modulator's capacitive nature enables the open‐circuit operation mode of T‐TENG, providing the integrated NENS with continuous force sensing capability which is notably uninfluenced by operation speeds. Furthermore, a physical model is proposed to describe the coupled AlN modulator/T‐TENG system. With the enhanced photonic modulation and the open‐circuit operation mode enabled by synergies between the AlN modulator and the T‐TENG, optical Morse code transmission and continuous human motion monitoring are demonstrated for practical wearable applications.
Joint Evaluation of the System ofUSDA's Farm Income Forecasts
Authors: Isengildina‐Massa Olga , Karali Berna , Kuethe Todd H. , Katchova Ani L.
Published: June 2020

This study evaluates a system of USDA's Net Cash Income forecasts, released as part of the farm sector's income statement, which includes crop receipts, livestock receipts, government payments, farm‐related income, and expenses from 1986 to 2017. We examine these forecasts jointly for bias, accuracy, efficiency, and compositional consistency. Our findings demonstrate that underestimation in early Net Cash Income forecasts stems from underestimation in crop and livestock receipts as well as expenses forecasts. While most components except government payments contribute to the improvement in 12‐month‐ahead forecasts, improvements in 9‐month‐out forecasts are mostly due to crop receipts and expenses forecasts, and government payment forecasts were a main source of improvement in 6‐month‐ahead forecasts. Despite the observed biases and inefficiencies, these forecasts are compositionally consistent with the actual outcomes and represent realistic projections of the farm sector accounts.
Emergency Medicine/Internal Medicine Combined Residency Graduates Have High Career Satisfaction and Commonly Practice in Both Specialties
Authors: Scott Nathaniel , Rodos Adam , Dwyer Ryan , Tyo Carissa , Martin Daniel
Published: June 2020

Objectives

The first combined emergency medicine/internal medicine (EM/IM) residency was established in 1991. As the 30th anniversary of this unique dual‐training opportunity approaches, multiple changes to the practice and educational landscape have occurred. Previous surveys examining this topic are now more than 10 years old and occurred prior to the establishment of the EM/IM/critical care medicine (EM/IM/CCM) pathway. We conducted a survey to investigate career trajectories, satisfaction, and opportunities available to EM/IM graduates.

Methods

Survey questions were developed to both allow for comparison with previously published data and examine new topics not previously investigated. A group of EM/IM and EM/IM/CCM program directors validated the survey questions. Eligible respondents were identified and contacted through their previous residency program leadership.

Results

Fifty‐two percent (152/290) of graduates completed the survey. Thirty‐seven percent of respondents practice both EM and IM, 51% practice EM only, and the remainder practice IM only. Thirty‐one percent of total respondents completed a fellowship, with critical care being the most popular choice. Seventy‐one percent of graduates practice in an academic center, and many hold leadership positions within education, research, and hospital administration. Eighty‐seven percent of graduates were “extremely satisfied” with their choice to pursue EM/IM or EM/IM/CCM and 95% reported that they would choose this path again.

Conclusions

Most respondents are satisfied with their residency choice and would choose to pursue this training again, despite the additional years of training. The proportion of graduates pursuing fellowship is higher than previously published data. Most continue to work in academics, and many are leaders within their institutions. The changing health care landscape offers multiple opportunities to dually trained graduates.
Bleeding phenotype and diagnostic characterization of patients with congenital platelet defects
Authors: Blaauwgeers Maaike W. , Kruip Marieke J.H.A. , Beckers Erik A.M. , Coppens Michiel , Eikenboom Jeroen , van Galen Karin P.M. , Tamminga Rienk Y.J. , Urbanus Rolf T. , Schutgens Roger E.G.
Published: June 2020

Phenotypic characterization of congenital platelet defects (CPDs) could help physicians recognize CPD subtypes and can inform on prognostic implications. We report the analyses of the bleeding phenotype and diagnostic characteristics of a large cohort of adult patients with a confirmed CPD. A total of 96 patients were analyzed and they were classified as Glanzmann thrombasthenia, Bernard‐Soulier syndrome, dense granule deficiency, defects in the ADP or thromboxane A2 (TxA2) pathway, isolated thrombocytopenia or complex abnormalities. The median ISTH‐BAT bleeding score was nine (IQR 5‐13). Heavy menstrual bleeding (HMB) (80%), post‐partum hemorrhage (74%), post‐operative bleeds (64%) and post‐dental extraction bleeds (57%) occurred most frequently. Rare bleeding symptoms were bleeds from the urinary tract (4%) and central nervous system (CNS) bleeds (2%). Domains with a large proportion of severe bleeds were CNS bleeding, HMB and post‐dental extraction bleeding. Glanzmann thrombasthenia and female sex were associated with a more severe bleeding phenotype.
Assessing the reliability of virtual reconstruction of mandibles
Authors: Godinho Ricardo Miguel , O'Higgins Paul , Gonçalves Célia
Published: June 2020

Objectives

Mandibular morphological variation is often used to examine various aspects of human palaeobiology. However, fossil and archeological skeletal remains are often fragmented/distorted and so are frequently excluded from studies. This leads to decreased sample sizes and, potentially, to biased results. Thus, it is of interest to restore the original anatomy of incomplete/distorted specimens. Thin plate splines (TPS), commonly used in Geometric Morphometrics (GM), offer the prospect of reconstruction of missing parts and particularly of interest here, missing landmarks.

Materials and methods

Here, the reliability of TPS based mandibular reconstruction is tested. To that end missing landmarks were simulated in originally complete hemimandibles. TPS was then used to restore the location of simulated missing data and the predicted landmarks were compared to the original ones.

Results

Results show that error varies according to the number and location of estimated landmarks. Notwithstanding, estimation error is usually considerably smaller than the morphological differences between individuals from the same species.

Discussion

TPS based reconstruction allows fragmentary mandibles to be used in studies of whole mandibular variation, provided the above mentioned caveats are considered.
Cognitive tests aid in clinical differentiation of Alzheimer's disease versus Alzheimer's disease with Lewy body disease: Evidence from a pathological study
Authors: Azar Martina , Chapman Silvia , Gu Yian , Leverenz James B. , Stern Yaakov , Cosentino Stephanie
Published: June 2020

Introduction

Clinical differentiation between Alzheimer's disease (AD) and AD with Lewy body disease (LBD) is relatively imprecise. The current study examined pathologically confirmed group differences in neuropsychological functioning, and the classification ability of specific tests.

Methods

Fifty‐one participants with postmortem diagnoses of AD (n = 34) and AD plus LBD (n = 17) were drawn from the Predictors Study. One‐way analyses of variance (ANOVAs) and χ2 analyses examined group differences in neuropsychological performance. Binary logistic regressions examined predictive utility of specific tests for pathological diagnosis.

Results

Individuals with AD had better visuoconstruction (P = .006), phonemic fluency (P = .08), and processing speed than AD plus LBD (P = .013). No differences were found in memory, naming, semantic fluency, or set‐switching. Processing speed and visuoconstruction predicted pathologic group (P = .03).

Discussion

Processing speed and visuoconstruction predicted postmortem diagnosis of AD versus AD plus LBD. Current results offer guidance in the selection and interpretation of neuropsychological tests to be used in the differential diagnosis of early dementia.
Proving and Probing the Presence of the Elusive C−H⋅⋅⋅O Hydrogen Bond in Liquid Solutions at Room Temperature
Authors: Galle Kankanamge Susith R. , Ma Jianbo , Mackin Robert T. , Leonik Fedra M. , Taylor Carol M. , Rubtsov Igor V. , Kuroda Daniel G.
Published: June 2020

Hydrogen bonds (H bonds) play a major role in defining the structure and properties of many substances, as well as phenomena and processes. Traditional H bonds are ubiquitous in nature, yet the demonstration of weak H bonds that occur between a highly polarized C−H group and an electron‐rich oxygen atom, has proven elusive. Detailed here are linear and nonlinear IR spectroscopy experiments that reveal the presence of H bonds between the chloroform C−H group and an amide carbonyl oxygen atom in solution at room temperature. Evidence is provided for an amide solvation shell featuring two clearly distinguishable chloroform arrangements that undergo chemical exchange with a time scale of about 2 ps. Furthermore, the enthalpy of breaking the hydrogen bond is found to be 6–20 kJ mol−1. Ab‐initio computations support the findings of two distinct solvation shells formed by three chloroform molecules, where one thermally undergoes hydrogen‐bond making and breaking.
Novel heteronuclear Pt (II)‐L‐Zn (II) complexes: synthesis, interactions with biomolecules, cytotoxic properties. Two metals give promising antitumor activity?
Authors: Soldatović Tanja V. , Selimović Enisa , Milivojević Nevena , Jovanović Milena , Šmit Biljana
Published: June 2020

The novel heteronuclear complexes [{cis‐PtCl (NH3)(μ‐pyrazine)ZnCl (terpy)}](ClO4)2 (Pt‐L1‐Zn) and [{cis‐PtCl (NH3)(μ‐4,4′‐bipyridyl)ZnCl (terpy)}](ClO4)2 (Pt‐L2‐Zn) (where terpy = 2,2′:6′,2′′‐terpyridine, L1 = pyrazine, L2 = 4,4′‐bipyridyl) were synthesized and characterized. The pKa values were determined, and based on them it was established that the π‐acceptor ability of the pyrazine bridging ligand is more affective on lower pKa values. The kinetic measurements of the substitution reactions with biologically relevant ligands, such as guanosine‐5′‐monophosphate (5′‐GMP), inosine‐5′‐monophosphate (5′‐IMP) and glutathione (GSH), were studied at pH 7.4. The reactions were followed under pseudo‐first‐order conditions by UV–Vis spectrophotometry. The order of reactivity of the investigated biomolecules for the first reaction is 5′‐GMP > 5′‐IMP > GSH, while for the second is 5′‐IMP > GSH. Pt‐L1‐Zn complex is more reactive than Pt‐L2‐Zn. The cytotoxic activity of heteronuclear Pt‐L1‐Zn and Pt‐L2‐Zn complexes was determined on human colorectal cancer cell line (HCT‐116) and human breast cancer cell line (MDA‐MB‐231). Both complexes significantly reduced cell viability on tested cell lines and exerted significant cytotoxic effects, with better effect on HCT‐116 cells than cisplatin, especially after 72 hr (IC50 < 0.52 μM). The Pt‐L2‐Zn complex showed higher activity against human breast cancer cells (MDA‐MB‐231) than cisplatin after 72 hr. The higher reactivity toward DNA constituent and significant cytotoxic activity may be attributed to the different geometry, Lewis acidity of different metal centers, as well as, to choice of bridging ligands.
Isothermal Crystallization of Palm Oil‐Based Fats with and without the Addition of Essential Oils
Authors: Chikhoune Anis , Shashkov Mikhail , Piligaev Aleksandr Vasilyevich , Lee Juhee , Boudjellal Abdelghani , Martini Silvana
Published: June 2020

The objective of study was to evaluate the crystallization behavior of palm oil‐based fats processed with and without the addition of essential oils (5% w/w) obtained from the flowers (EsOF) and stems (EsOS) of Pituranthos scoparius. Palm oil (PO) and a mixture of PO, soybean oil, and sunflower oil (Mix) were tested. The addition of the essential oils did not change the melting points of the fats but affected their crystallization behavior. A delay in crystallization was observed, evidenced by lower crystallization rates, and lower solid fat contents. This delay was comparable in the samples crystallized with EsOF and EsOS for the PO samples but EsOF was more efficient at delaying crystallization in the Mix sample. EsOF generated a less organized crystalline network in both samples (lower enthalpy values) while EsOS generated a more organized crystalline network (high enthalpy values) when used in the Mix sample. The addition of EsO also affected the crystal microstructure in some cases. While a slight increase in crystal size was observed for some PO samples crystallized with EsOF, no change or a decrease in crystal size was observed for the samples crystallized with EsOS. A slight decrease in crystal size was observed for Mix samples crystallized with EsOF while no effect was observed for these samples crystallized with EsOS. Results from this study show that these essential oils can be used as natural additives to modify the crystallization of fats for food applications and therefore widen their functional properties.
PBAT/hybrid nanofillers composites—Part 1: Oxygen and water vapor permeabilities, UV barrier and mechanical properties
Authors: Calderaro Mayara Pollyane , de Luca Sarantopóulos Claire Isabel Grígoli , Sanchez Elisabete Maria Saraiva , Morales Ana Rita
Published: June 2020

This work evaluated the effect of the combination of nanofillers: organically modified montmorillonite (MMT), sepiolite (SEP) and nano titanium dioxide (TiO2) on the oxygen and water vapor permeability coefficients, light transmission and mechanical properties of poly(butylene adipate‐co‐terephthalate) (PBAT) aiming at packaging application. The clays concentrations were chosen considering percolation threshold from the clays aspect ratio by TEM analyses. Comparing to neat PBAT, oxygen and vapor permeability coefficients showed reduction with the increase of MMT while SEP and nano‐TiO2 did not show significant influence. However, nano‐TiO2 was the only filler able to reduce UV and visible light transmission. Nanofillers and their combinations showed to be statistically significant for the increase in Young's modulus, although the tensile strength and elongation showed no influence. The results were discussed in terms of the fillers' morphology and dispersion. Nielsen's model was applied to estimate the aspect ratio of the MMT in nanocomposites.
Effect of hybrid polysphosphazene coating treatment on carbon fibers on the interfacial properties of CF/PA6 composites
Authors: Chen Xiang , Xu Haibing , Liu Dong , Yan Chun , Yao Youqiang , Zhu Yingdan
Published: June 2020

Carbon fiber (CF) reinforced polyamide 6 (PA6) composite has an extensive application. However, the performances of CF/PA6 composite are constrained by the poor interfacial adhesion between CF and PA6 matrix. In this article, in order to strengthen the interfacial adhesion of CF/PA6 composite, a layer of poly(cyclotriphosphazene‐co‐4,4′‐sulfonyldiphonel) (PZS) hybrid coating with plenty of PZS microspheres (PZSMS) was successfully introduced onto CF surface through facile in situ polymerization. After surface modification, the surface morphologies and the surface chemical structures of fibers changed distinctly. On one hand, the PZSMS provided more contact points and increased mechanical interlocking between CF and PA6 matrix. On the other hand, numerous hydrogen bonds between CF and PA6 were formed due to a great amount of unique polar groups on modified CF surface. Consequently, in comparison with untreated CF, the interfacial shear strength of CF‐PZSMS/PA6 composites was improved from 37.68 ± 3.16 to 53.79 ± 3.38 MPa, by 42.75 ± 3.02%. The results indicated that PZS hybrid coating on fiber surface effectively improved the interfacial adhesion of CF/PA6 composites, and the stronger hydrogen bonding and the enhanced mechanical interlocking synergistically played a major role in such significant improvements.
Expert Perspectives On Clinical Challenges: Expert Perspectives: Challenges in Scleroderma
Authors: Simms Robert W.
Published: June 2020

You are consulted to evaluate a 56‐year‐old woman with known Raynaud's phenomenon, finger swelling of several; months’ duration, and new hypertension with a blood pressure of 160/100 mm/Hg. She also reports progressive shortness of breath. Physical examination reveals telangiectasias, sclerodactyly, and proximal skin sclerosis (thick shiny skin on the chest and upper arms), and bibasilar crackles are found on chest examination. Laboratory tests reveal evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevation of the serum creatinine level (previously normal), and chest computed tomography shows evidence of ground‐glass opacification in both lower lung fields.
Effects of gut microbiota on in vivo metabolism and tissue accumulation of cytochrome P450 3A metabolized drug: Midazolam
Authors: Togao Masao , Kawakami Koji , Otsuka Jun , Wagai Gaku , Ohta‐Takada Yuki , Kado Shoichi
Published: June 2020

The link between drug‐metabolizing enzymes and gut microbiota is well established. In particular, hepatic cytochrome P450 (CYP) 3A activities are presumed to be affected by gut microbiota. However, there is no direct evidence that the gut microbiota affects CYP3A metabolism or the clearance of clinically relevant drugs in vivo. Our purpose was to evaluate the effects of gut microbiota on in vitro and in vivo drug metabolism and on the clearance of midazolam, which is a standard CYP3A metabolized drug. Hepatic Cyp3a activity and in vitro midazolam hydroxylase activity were compared using specific pathogen‐free (SPF) and germ‐free (GF) mice. In a pharmacokinetics (PK) study, SPF and GF mice were intraperitoneally injected with 60 mg/kg of midazolam, and plasma and tissue concentrations were measured. Hepatic Cyp3a activity and midazolam hydroxylase activity were significantly lower in GF mice than in SPF mice. Notably, in the PK study, the area under the plasma concentration–time curve from time zero to infinity and the elimination half‐life were approximately four‐fold higher in GF mice compared with SPF mice. Furthermore, the concentration of midazolam in the brain 180 min after administration was about 14‐fold higher in GF mice compared with SPF mice. Together, our results demonstrated that the gut microbiota altered the metabolic ability of Cyp3a and the tissue accumulation of midazolam.
Rh(III)‐Catalyzed [4+1] Cyclization of Sulfoxonium Ylides and Anthranils for Accessing N‐Arylisatins
Authors: Zhou Peng , Yang Wei‐Tao , Li Guigen , Hao Wen‐Juan , Jiang Bo
Published: June 2020

A rhodium(III)‐catalyzed [4+1] cyclization between aroyl sulfoxonium ylides and anthranils has been developed, offering a wide range of new aldehyde‐containing N‐arylisatins in good to excellent yields. The highlight of this reaction shows the construction of two C−N and one C=O bonds through [4+1] annulation consisted of C−H activation, ring opening of anthranils and oxygen insertion.
Diastereo‐ and Enantioselective Cross‐Couplings of Secondary Alkylcopper Reagents with 3‐Halogeno‐Unsaturated Carbonyl Derivatives
Authors: Kremsmair Alexander , Skotnitzki Juri , Knochel Paul
Published: June 2020

Chiral secondary alkylcopper reagents were prepared from the corresponding alkyl iodides with retention of configuration by an I/Li‐exchange using tBuLi (−100 °C, 1 min) followed by a transmetalation with CuBr⋅P(OEt)3 (−100 °C, 20 s). These stereodefined secondary alkylcoppers underwent stereoretentive cross‐couplings with several 3‐iodo or 3‐bromo unsaturated carbonyl derivatives leading to the corresponding γ‐methylated Michael acceptors in good yields and with high diastereoselectivities (dr up to 96:4). The method was extended to enantiomerically enriched alkylcoppers, providing optically enriched advanced natural product intermediates with up to 90 % ee.
Highly Selective Nucleophilic 4‐Aryl‐2,3‐allenylation of Malonates†
Authors: Song Shihua , Ma Shengming
Published: June 2020

Summary of main observation and conclusion

Allenes are a class of very important compounds and the development of straightforward, efficient, and highly enantioselective synthetic strategies for allenes have attracted extensive interests. Along this line, it is well known that aryl‐substituted allenes may be readily racemized, thus, difficult to prepare in high ee. Herein, an efficient palladium‐catalyzed nucleophilic allenylation of malonates with racemic 4‐aryl‐2,3‐butadienyl carbonates has been developed. The selectivity issue of mono‐ vs. bis‐allenylation with 2‐non‐substituted malonates has been addressed. By utilizing (R)‐(–)‐DTBM‐SEGPHOS (5,5'‐bis[di(3,5‐di‐t‐butyl‐4‐methoxyphenyl)phosphino]‐4,4'‐bi‐1,3‐benzodioxole) as a chiral ligand, various aryl‐substituted allenes and bisallenes have been prepared with good to excellent yields with high chemoselectivity and enantioselectivity under mild reaction conditions. Au‐catalyzed cycloisomerization and APK (allenic Pauson–Khand) reactions affording optically active mono‐ and bicyclic products have been demonstrated.
From Femtosecond to Nanosecond Laser Microstructuring of Conical Aluminum Surfaces by Reactive Gas Assisted Laser Ablation
Authors: Rauh Simon , Wöbbeking Karl , Li Mingji , Schade Wolfgang , Hübner Eike G.
Published: June 2020

A conical microstructure is one of the most versatile surface textures obtained by ultrashort laser micromachining. Besides an increased surface area, unique surface properties such as superhydrophilicity, increased absorptivity; and thermal emissivity can be tailored. On metals, usually ultrashort laser pulses in the femtosecond to low picosecond range are used to obtain these surface structures, whereas nanosecond laser pulses favor melting processes. Herein, we report on an investigation of reactive gas atmospheres such as oxygen, steam, and halogens during laser micromachining of aluminum with 6 ns laser pulses. At a reduced pressure of 20 hPa (air) with additional iodine vapor as reactive species, we found a perfectly microconical structured surface to be formed with nanosecond laser pulses. The resulting surface structures were proven to be free of residual halogens. The application of nanosecond instead of femtosecond laser pulses for the surface structuring process allows to apply significantly less complex laser sources.
Can a Multistakeholder Prioritization Structure Support Regulatory Decision Making? A Review of Pediatric Oncology Strategy Forums Reflecting on Challenges and Opportunities of this Concept
Authors: Karres Dominik , Lesa Giovanni , Ligas Franca , Annunen Pia , van Dartel Maaike , Demolis Pierre , Galluzzo Sara , Herold Ralf , van Criekingen Olga Kholmanskikh , Stoyanova‐Beninska Violeta , Norga Koen
Published: June 2020

Timely and successful drug development for rare cancer populations, such as pediatric oncology, requires consolidated efforts in the spirit of shared responsibility. In order to advance tailored development efforts, the concept of multistakeholder Strategy Forum involving industry, academia, patient organizations, and regulators has been developed. In this study, we review the first five pediatric oncology Strategy Forums co‐organized by the European Medicines Agency between 2017 and 2020, reflecting on the outcomes and the evolution of the concept over time and providing an outline of how a “safe space” for multistakeholder engagement facilitated by regulators could be of potential value beyond pediatric oncology drug development.
Genomewide Meta‐Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent‐Induced Sensory Peripheral Neuropathy
Authors: Chua Katherina C. , Xiong Chenling , Ho Carol , Mushiroda Taisei , Jiang Chen , Mulkey Flora , Lai Dongbing , Schneider Bryan P. , Rashkin Sara R. , Witte John S. , Friedman Paula N. , Ratain Mark J. , McLeod Howard L. , Rugo Hope S. , Shulman Lawrence N. , Kubo Michiaki , Owzar Kouros , Kroetz Deanna L.
Published: June 2020

Microtubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose‐limiting toxicity for MTAs and can limit clinical efficacy. The current pharmacogenomic study aimed to identify genetic variations that explain patient susceptibility and drive mechanisms underlying development of MTA‐induced PN. A meta‐analysis of genomewide association studies (GWAS) from two clinical cohorts treated with MTAs (Cancer and Leukemia Group B (CALGB) 40502 and CALGB 40101) was conducted using a Cox regression model with cumulative dose to first instance of grade 2 or higher PN. Summary statistics from a GWAS of European subjects (n = 469) in CALGB 40502 that estimated cause‐specific risk of PN were meta‐analyzed with those from a previously published GWAS of European ancestry (n = 855) from CALGB 40101 that estimated the risk of PN. Novel single nucleotide polymorphisms in an enhancer region downstream of sphingosine‐1‐phosphate receptor 1 (S1PR1 encoding S1PR1; e.g., rs74497159, βCALGB 40101 per allele log hazard ratio (95% confidence interval (CI)) = 0.591 (0.254–0.928), βCALGB 40502 per allele log hazard ratio (95% CI) = 0.693 (0.334–1.053); PMETA = 3.62 × 10−7) were the most highly ranked associations based on P values with risk of developing grade 2 and higher PN. In silico functional analysis identified multiple regulatory elements and potential enhancer activity for S1PR1 within this genomic region. Inhibition of S1PR1 function in induced pluripotent stem cell‐derived human sensory neurons shows partial protection against paclitaxel‐induced neurite damage. These pharmacogenetic findings further support ongoing clinical evaluations to target S1PR1 as a therapeutic strategy for prevention and/or treatment of MTA‐induced neuropathy.