bluuebunny/crossref_metadata_2025 huggingface dataset:
Casein-Coated Iron Oxide Nanoparticles for in vitro Hyperthermia for Cancer Therapy
Authors: Bani Milad Salimi , Hatamie Shadie , Haghpanahi Mohammad , Bahreinizad Hossein , Alavijeh Mohammad Hossein Shahsavari , Eivazzadeh-Keihan Reza , Wei Zhung Hang
Published: January 2019

Iron oxide nanoparticles (NPs) have been a very appealing choice in magnetic-mediated hyperthermia for cancer therapy. The responses of NPs to hyperthermia as a cancer treatment method are complex and variable. Herein, the heating properties of the casein-coated magnetic NPs (MNPs) under an alternating magnetic field were investigated. The casein-coated MNPs were synthesized via one-pot chemical method. The casein-coated MNPs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDAX), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), zeta potential, dynamic light scattering (DLS), and vibrating sample magnetometer (VSM) analysis. TEM images of casein-coated MNPs show that their shapes are spherical and their core sizes are between 20[Formula: see text]nm and 25[Formula: see text]nm. The FTIR and EDAX results confirmed the presence of casein on the surface of MNPs. The VSM shows the superparamagnetic nature of iron oxide and casein-coated iron oxide NPs with the magnetic saturation of 60[Formula: see text]emu/g and 44.86[Formula: see text]emu/g, respectively, at room temperature. Furthermore, hyperthermia tests for casein-coated MNPs with various concentrations and frequencies are performed. Hyperthermia results show that lower concentrations of casein-coated MNPs dispatch higher heating into their surrounding medium, whereas maximum specific absorption rate occurs at the concentration of 1[Formula: see text]mg/mL for the frequency of 150[Formula: see text]kHz. Findings of this study suggest that casein-coated MNPs have great potential as an anticancer agent in hyperthermia cancer therapy.
The Tcf21 lineage constitutes the lung lipofibroblast population
Authors: Park Juwon , Ivey Malina J. , Deana Yanik , Riggsbee Kara L. , Sörensen Emelie , Schwabl Veronika , Sjöberg Caroline , Hjertberg Tilda , Park Ga Young , Swonger Jessica M. , Rosengreen Taylor , Morty Rory E. , Ahlbrecht Katrin , Tallquist Michelle D.
Published: January 2019

Transcription factor 21 (Tcf21) is a basic helix-loop-helix transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. To explore the Tcf21 mesenchymal lineage, we traced Tcf21-expressing cells during embryogenesis and in the adult. Our results showed that Tcf21 progenitor cells at embryonic day (E)11.5 generated a subpopulation of fibroblasts and lipofibroblasts and a limited number of smooth muscle cells. After E15.5, Tcf21 progenitor cells exclusively become lipofibroblasts and interstitial fibroblasts. Lipid metabolism genes were highly expressed in perinatal and adult Tcf21 lineage cells. Overexpression of Tcf21 in primary neonatal lung fibroblasts led to increases in intracellular neutral lipids, suggesting a regulatory role for Tcf21 in lipofibroblast function. Collectively, our results reveal that Tcf21 expression after E15.5 delineates the lipofibroblast and a population of interstitial fibroblasts. The Tcf21 inducible Cre mouse line provides a novel method for identifying and manipulating the lipofibroblast.
Modulation of cardiac vascular endothelial growth factor and PGC-1α with regular postexercise cold-water immersion of rats
Authors: Al-horani Ramzi A. , Al-Trad Bahaa , Haifawi Saja
Published: January 2019

Myocardial mitochondrial biogenesis and vascular angiogenesis biomarker responses to postexercise cold-water immersion (CWI) have not been reported. Therefore, to determine those cardiac adaptations, adult male Sprague-Dawley rats were divided into three groups: postexercise CWI (CWI; n = 13), exercise only (Ex; n = 12), and untreated control (CON; n = 10). CWI and Ex were trained for 10 wk, 5 sessions/wk, 30–60 min/session. CWI rats were immersed after each session in cold water (15 min at ~12°C). CON remained sedentary. Left ventricle tissue was obtained 48 h after the last exercise session and analyzed for peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), vascular endothelial growth factor (VEGF), and heat shock protein 70 kDa (Hsp70) protein content and mRNA expression levels. In addition, superoxide dismutase activity and mRNA and malondialdehyde levels were evaluated. Ex and CWI induced higher PGC-1α protein content compared with CON (1.8 ± 0.6-fold, P < 0.001), which was significantly higher in CWI than Ex rats ( P = 0.01). VEGF protein (4.3 ± 3.7-fold) and mRNA (10.1 ± 1.1-fold) were markedly increased only in CWI ( P < 0.001) relative to CON. CWI and Ex augmented cardiac Hsp70 protein to a similar level relative to CON ( P < 0.05); however, Hsp70 mRNA increased only in Ex ( P = 0.002). No further differences were observed between groups. These results suggest that postexercise CWI may further enhance cardiac oxidative capacity by increasing the angiogenic and mitochondrial biogenic factors. In addition, CWI does not seem to worsen exercise-induced cardioprotection and oxidative stress.

NEW & NOTEWORTHY A regular postexercise cold-water immersion for 10 wk of endurance training augmented the myocardial mitochondrial biogenesis and vascular angiogenesis coactivators peroxisome proliferator-activated receptor γ coactivator-1α and vascular endothelial growth factor, respectively. In addition, postexercise cold-water immersion did not attenuate the exercise-induced increase in the cardioprotective biomarker heat shock protein 70 kDa or increase exercise-induced oxidative stress.
Impact of Control and Trust on Megaproject Success: The Mediating Role of Social Exchange Norms
Authors: Wang Dedong , Fang Shaoze , Fu Hongwei
Published: January 2019

Trust and control are the two main governance mechanisms in megaprojects. However, the role of social exchange norms in trust and control governance remains unclear. Based on social exchange theory, we explored the impact of control and trust on megaproject success by considering the mediating effect of social exchange norms, which include reciprocity, negotiation, and information sharing. Partial least squares structural equation modeling was used to test the hypotheses based on data collected from 155 respondents. Results show that control and trust have positive effects on megaproject success. Trust can promote social exchange norms. That is, the higher the level of trust is, the greater the likelihood that reciprocity, negotiation, and information sharing will increase. Control does not have a significant impact on social exchange norms. Social exchange norms have a mediating effect on the relationship between trust and megaproject success but not on the link between control and megaproject success. Our findings fill in the gaps in the literature on megaproject governance and contribute to the development of megaproject management theory, which can help project managers understand the motivation orientations of all parties to make decisions wisely and rationally under complex environments.
Pleiotropic Effects of PPARD Accelerate Colorectal Tumorigenesis, Progression, and Invasion
Authors: Liu Yi , Deguchi Yasunori , Tian Rui , Wei Daoyan , Wu Ling , Chen Weidong , Xu Weiguo , Xu Min , Liu Fuyao , Gao Shen , Jaoude Jonathan C. , Chrieki Sarah P. , Moussalli Micheline J. , Gagea Mihai , Morris Jeffrey , Broaddus Russell R. , Zuo Xiangsheng , Shureiqi Imad
Published: January 2019

APC mutations activate aberrant β-catenin signaling to drive initiation of colorectal cancer; however, colorectal cancer progression requires additional molecular mechanisms. PPAR-delta (PPARD), a downstream target of β-catenin, is upregulated in colorectal cancer. However, promotion of intestinal tumorigenesis following deletion of PPARD in Apcmin mice has raised questions about the effects of PPARD on aberrant β-catenin activation and colorectal cancer. In this study, we used mouse models of PPARD overexpression or deletion combined with APC mutation (ApcΔ580) in intestinal epithelial cells (IEC) to elucidate the contributions of PPARD in colorectal cancer. Overexpression or deletion of PPARD in IEC augmented or suppressed β-catenin activation via up- or downregulation of BMP7/TAK1 signaling and strongly promoted or suppressed colorectal cancer, respectively. Depletion of PPARD in human colorectal cancer organoid cells inhibited BMP7/β-catenin signaling and suppressed organoid self-renewal. Treatment with PPARD agonist GW501516 enhanced colorectal cancer tumorigenesis in ApcΔ580 mice, whereas treatment with PPARD antagonist GSK3787 suppressed tumorigenesis. PPARD expression was significantly higher in human colorectal cancer–invasive fronts versus their paired tumor centers and adenomas. Reverse-phase protein microarray and validation studies identified PPARD-mediated upregulation of other proinvasive pathways: connexin 43, PDGFRβ, AKT1, EIF4G1, and CDK1. Our data demonstrate that PPARD strongly potentiates multiple tumorigenic pathways to promote colorectal cancer progression and invasiveness.

Significance:

These findings address long-standing, important, and unresolved questions related to the potential role of PPARD in APC mutation-dependent colorectal tumorigenesis by showing PPARD activation enhances APC mutation-dependent tumorigenesis.
The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C
Authors: D'Arcy Brandon M. , Swingle Mark R. , Papke Cinta M. , Abney Kevin A. , Bouska Erin S. , Prakash Aishwarya , Honkanen Richard E.
Published: January 2019

LB-100 is an experimental cancer therapeutic with cytotoxic activity against cancer cells in culture and antitumor activity in animals. The first phase I trial (NCT01837667) evaluating LB-100 recently concluded that safety and efficacy parameters are favorable for further clinical testing. Although LB-100 is widely reported as a specific inhibitor of serine/threonine phosphatase 2A (PP2AC/PPP2CA:PPP2CB), we could find no experimental evidence in the published literature demonstrating the specific engagement of LB-100 with PP2A in vitro, in cultured cells, or in animals. Rather, the premise for LB-100 targeting PP2AC is derived from studies that measure phosphate released from a phosphopeptide (K-R-pT-I-R-R) or inferred from the ability of LB-100 to mimic activity previously reported to result from the inhibition of PP2AC by other means. PP2AC and PPP5C share a common catalytic mechanism. Here, we demonstrate that the phosphopeptide used to ascribe LB-100 specificity for PP2A is also a substrate for PPP5C. Inhibition assays using purified enzymes demonstrate that LB-100 is a catalytic inhibitor of both PP2AC and PPP5C. The structure of PPP5C cocrystallized with LB-100 was solved to a resolution of 1.65Å, revealing that the 7-oxabicyclo[2.2.1]heptane-2,3-dicarbonyl moiety coordinates with the metal ions and key residues that are conserved in both PP2AC and PPP5C. Cell-based studies revealed some known actions of LB-100 are mimicked by the genetic disruption of PPP5C. These data demonstrate that LB-100 is a catalytic inhibitor of both PP2AC and PPP5C and suggest that the observed antitumor activity might be due to an additive effect achieved by suppressing both PP2A and PPP5C.
A Kinase Inhibitor with Anti-Pim Kinase Activity is a Potent and Selective Cytotoxic Agent Toward Acute Myeloid Leukemia
Authors: Bjørnstad Ronja , Aesoy Reidun , Bruserud Øystein , Brenner Annette K. , Giraud Francis , Dowling Tara Helen , Gausdal Gro , Moreau Pascale , Døskeland Stein Ove , Anizon Fabrice , Herfindal Lars
Published: January 2019

More than 40 years ago, the present standard induction therapy for acute myeloid leukemia (AML) was developed. This consists of the metabolic inhibitor cytarabine (AraC) and the cytostatic topoisomerase 2 inhibitor daunorubucin (DNR). In light of the high chance for relapse, as well as the large heterogeneity, novel therapies are needed to improve patient outcome. We have tested the anti-AML activity of 15 novel compounds based on the scaffolds pyrrolo[2,3-a]carbazole-3-carbaldehyde, pyrazolo[3,4-c]carbazole, pyrazolo[4,3-a]phenanthridine, or pyrrolo[2,3-g]indazole. The compounds were inhibitors of Pim kinases, but could also have inhibitory activity against other protein kinases. Ser/Thr kinases like the Pim kinases have been identified as potential drug targets for AML therapy. The compound VS-II-173 induced AML cell death with EC50 below 5 μmol/L, and was 10 times less potent against nonmalignant cells. It perturbed Pim-kinase–mediated AML cell signaling, such as attenuation of Stat5 or MDM2 phosphorylation, and synergized with DNR to induce AML cell death. VS-II-173 induced cell death also in patients with AML blasts, including blast carrying high-risk FLT3-ITD mutations. Mutation of nucleophosmin-1 was associated with good response to VS-II-173. In conclusion new scaffolds for potential AML drugs have been explored. The selective activity toward patient AML blasts and AML cell lines of the pyrazolo-analogue VS-II-173 make it a promising drug candidate to be further tested in preclinical animal models for AML.
Combined MEK and BCL-2/XL Inhibition Is Effective in High-Grade Serous Ovarian Cancer Patient–Derived Xenograft Models and BIM Levels Are Predictive of Responsiveness
Authors: Iavarone Claudia , Zervantonakis Ioannis K. , Selfors Laura M. , Palakurthi Sangeetha , Liu Joyce F. , Drapkin Ronny , Matulonis Ursula A. , Hallberg Dorothy , Velculescu Victor E. , Leverson Joel D. , Sampath Deepak , Mills Gordon B. , Brugge Joan S.
Published: January 2019

Most patients with late-stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient–derived xenograft models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition. Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the proapoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death, and displayed synergy in vitro in most models. In vivo, GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models—those with high BIM at baseline that was increased with MEK inhibition and those with low basal BIM and high pERK levels. Models with low BIM and low pERK were nonresponsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for the clinical evaluation of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.
Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis
Authors: Ramchandani Divya , Lee Seung Koo , Yomtoubian Shira , Han Myung Shin , Tung Ching-Hsuan , Mittal Vivek
Published: January 2019

Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherry+ miR-708low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.
Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the MPZ Gene
Authors: Nadol Jr. Joseph B. , Hedley-Whyte E. Tessa , Amr Sami Samir , O'Malley Jennifer T. , Kamakura Takefumi
Published: January 2019

Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Molecular genetic testing of DNA obtained at autopsy revealed a missense variant in the MPZ gene (p.Thr65Ala), pathogenic for an autosomal-dominant form of CMT1B. The temporal bones were also prepared for light microscopy by hematoxylin and eosin and Gömöri trichome stains, and immunostaining for anti-myelin protein zero. Pathology was consistent with a myelinopathy of the auditory, vestibular, and facial nerves bilaterally. The pathophysiology of cranial nerve dysfunction in CMT is unknown. Findings in the current case suggested, at least in cranial nerves 7 and 8, that a myelinopathy may be causative.
Pediatric IgA Nephropathy in Europe
Authors: Coppo Rosanna
Published: January 2019

Background: In Europe IgA nephropathy (IgAN) is detected in 20% of children with glomerular diseases diagnosed by renal biopsy. The outcome during childhood is generally good, but progression in the long-term follow-up may occur in about 20% of children after 20 years. Summary: In Europe, urine screening programs are not active, and there is variability in the policy to perform renal biopsies in oligo-symptomatic children. Hence, a suitable observational approach to pediatric IgAN is offered by the VALIGA study which included 174 children aged < 18 years from 13 European countries followed over a median of 4.4 (2.5–7.5) years. Renal pathology lesions were centrally scored according to the Oxford Classification of IgAN (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C [MEST-C]). Children had renal biopsy mostly with normal estimated glomerular filtration rate (eGFR) and moderate proteinuria of a median of 0.84 g/day/1.73 m2 (< 0.30 g/day/1.73 m2 in 30% of the cases). Children showed M1 in 21.8%, E1 in 13.8%, S1 in 42.5%, T1–2 in 6.3%, and C1 in 14.9%. The survival at the combined endpoint of 50% eGFR decrease or end-stage renal disease at 15 years was 94%. The slow progression rate and the limited number of cases progressing to the combined endpoint (6.4%) did not allow the detection of a predictive value of the MEST-C score. Moreover, the predictive value of clinical and pathological features was likely blunted by the use of corticosteroid/immunosuppressive treatment (CS/IS) in 50% of the cases. The survival tree analysis also proved that children < 16 years old with IgAN without mesangial hypercellularity (M0) and well preserved eGFR (> 90 mL/min/1.73 m2) had a high probability of proteinuria remission during follow-up. Moreover, in this subgroup of children, the benefits of CS/IS therapy reached statistical significance. In Europe, the use of CS/IS treatment in IgAN is still a debated issue, but most children tend to be treated more commonly than adults with CS/IS. A recent uncontrolled study reports a favorable outcome in European children with IgAN and very active acute forms of IgAN with improvement in eGFR and reduction in proteinuria. Key Messages: In Europe, children with IgAN have a favorable prognosis in the short term, and this may be due also to the frequently adopted CS/IS therapy, particularly with acute and active pathological features. The risk of progression over decades of follow-up remains an unsolved problem which needs to be addressed by controlling subtle chronic pathogenetic factors which work in children as well as in adult cases of IgAN.
Vascular Risk Factors and Findings on Brain MRI of Elderly Adult American Indians: The Strong Heart Study
Authors: Shibata Dean  , Suchy-Dicey Astrid , Carty Cara L. , Madhyastha Tara  , Ali Tauqeer , Best Lyle  , Grabowski Jr. Thomas J. , Longstreth Jr. W.T. , Buchwald Dedra
Published: January 2019

Background: Clinical stroke is prevalent in American Indians, but the risk factors for cerebrovascular pathology have not been well-studied in this population. The purpose of this study was to correlate abnormalities on brain magnetic resonance imaging (MRI) with clinical risk factors in a cohort of elderly American Indians. Methods: Brain MRI scans from 789 participants of the Strong Heart Study were analyzed for infarcts, hemorrhage, white matter disease, and measures of cerebral atrophy including ventricular and sulcal grade and total brain volume. Clinical risk factors included measures of hypertension, diabetes, and high levels of low-density lipoprotein (LDL) cholesterol. Regression models adjusted for potential confounders were used to estimate associations between risk factors and brain MRI outcomes. Results: ­Hypertension was associated with the presence of infarcts (p = 0.001), ventricle enlargement (p = 0.01), and increased white matter hyperintensity volume (p = 0.01). Diabetes was associated with increased prevalence of cerebral atrophy (p < 0.001), ventricular enlargement (p = 0.001), and sulcal widening (p = 0.001). High LDL was not significantly associated with any of the measured cranial imaging outcomes. Conclusions: This study found risk factors for cerebrovascular disease in American Indians similar to those seen in other populations and provides additional evidence for the important roles of hypertension and diabetes in promoting cerebral infarcts and brain atrophy, respectively.
HETEROGENEITY OF PROTEINS IN BIRDSâ€™ EGG-WHITES
Authors: Hashim Hayder Obayes , Al-Shuhaib Mohammed Baqur Sahib , Ewadh Mufeed Jaleel
Published: January 2019

Little is known about the comparative heterogeneity of protein compounds among a wide variety of birdsâ€™ egg white, particularly, an analysis of their detailed, in-parallel protein composition. Hence this research is conducted mainly to evaluate the extent of variability among 42 types of birdsâ€™ egg white. To improve the perception of these biological fluids, the main phenotypic variations of egg whites were evaluated using the discontinuous denaturing polyacrylamide gel electrophoresis (SDS-PAGE), Gradient SDS-PAGE, Native-PAGE, cellulose acetate electrophoresis, and the reverse-phase high-performance liquid chromatography (RP-HPLC). The results showed that the Native-PAGE and SDS-PAGE produced better screening results than other methods in identifying protein. Although Â Native-PAGE and SDS-PAGE did not show remarkable variability in terms of hydrophobicity, several electrophoretic differences of egg-white proteins were observed. Several unknown proteins in the egg white samples of different bird species were also identified through the electrophoretic experiments. Hence, it might be possible, as in the case of egg white samples, to provide a characterized assessment among birds by using only the available gel electrophoresis techniques. This study also provided a rapid snapshot of the initial identification of several unknown components of egg white proteins. Accordingly, this study constituted the first large-scale comparative proteomics investigation performed among the largely varying types of egg whites from commercial stores and bird keepers in the middle Euphrates areas in Iraq.
CD73 (Cluster of Differentiation 73) and the Differences Between Mice and Humans
Authors: Joolharzadeh Pouya , St. Hilaire Cynthia
Published: January 2019

As vascular disease is complex and the various manifestations are influenced by differences in vascular bed architecture, exposure to shear and mechanical forces, cell types involved, and inflammatory responses, in vivo models are necessary to recapitulate the complex physiology and dynamic cellular interactions during pathogenesis. Murine knockout models are commonly used tools for investigators to study the role of a specific gene or pathway in multifaceted disease traits. Although valuable, these models are not perfect, and this is particularly true in regard to CD73 (cluster of differentiation 73), the extracellular enzyme that generates adenosine from AMP. At baseline, CD73-deficient mice do not present with an overt phenotype, whereas CD73-deficient humans present with the complex phenotype of vascular calcification, arteriomegaly and tortuosity, and calcification in small joints. In this review, we highlight the differences between the mouse and human systems and discuss the potential to leverage findings in mice to inform us on the human conditions.
Moving Targets
Authors: Larsen Lars E. , Stoekenbroek Robert M. , Kastelein John J.P. , Holleboom Adriaan G.
Published: January 2019

Statin therapy has delivered tremendous value to society by improving the burden of atherosclerotic cardiovascular disease. Nonetheless, atherosclerotic cardiovascular disease remains the leading cause of death globally. Technological advances such as in the field of genomics have revolutionized drug discovery and development and have revealed novel therapeutic targets to lower low-density lipoprotein cholesterol (LDL-C), as well as other detrimental lipids and lipoproteins. Therapeutic LDL-C lowering prevents atherosclerotic cardiovascular disease with an effect size proportional to absolute LDL-C reductions and time of exposure. This understanding supports the notion that reducing cumulative LDL-C exposure should be a key therapeutic target. PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibiting monoclonal antibodies provides the possibility of reducing LDL-C to very low levels. Novel therapeutic platforms such as RNA inhibition present opportunities to combine robust lipid lowering with infrequent dosing regimens, introducing therapies with vaccine-like properties. The position of lipid-lowering therapies with targets other than LDL-C, such as Lp(a) [lipoprotein(a)], TRL (triglyceride-rich lipoproteins), and remnant cholesterol, will likely be determined by the results of ongoing clinical trials. Current evidence suggests that reducing Lp(a) or TRLs could attenuate atherosclerotic cardiovascular disease risk in specific categories of patients. This review provides an overview of the latest therapeutic developments, focusing on their mechanisms, efficacy, and safety.
Ricotia candiriana (Brassicaceae), a new species from southern Anatolia, Turkey
Authors: ÖZÇANDIR AYŞEN , AYKURT CANDAN , ÖZÜDOĞRU BARIŞ
Published: January 2019

Ricotia candiriana, from Alakır Valley (Kumluca, Antalya) in southern Anatolia (Turkey), is described as a new species and compared with its related species (R. davisiana). Its phylogenetic relationships within the genus are provided based on the nuclear-encoded ribosomal internal transcribed spacer (ITS) region. The International Union for Conservation of Nature (IUCN) threat category and observations on the ecology of the population are noted. The seed micromorphology of R. candiriana was examined using a scanning electron microscope and compared with R. davisiana.
On the formation of family-group names and gender of genera based on the stem—butis (Teleostei: Perciformes: Gobioidei)
Authors: GILL ANTHONY C. , HOESE DOUGLAS F.
Published: January 2019

The familial classification of gobioid fishes is in a state of flux, reflecting incomplete understanding of phylogenetic relationships within the suborder. However, there has been rapid progress over the past decade or so, which is likely to continue, undoubtedly leading to the erection of new family-group names. One such family, Odontobutidae, was erected by Hoese and Gill (1993) for several Asiatic freshwater genera. Recently, the spelling of this taxon has been challenged (Kottelat, 2001; Chen et al., 2002). According to Chen et al. (2002: 233): “Although commonly spelled Odontobutidae, a family-group name based on the genus group name Odontobutis should be spelled Odontobutididae as the stem of the genus group name is odontobutid- (ICZN art. 29). The spelling Odontobutidae can be retained under ICZN art. 29.3.1.1 only if it is the “prevailing usage”, but ICZN is logically flawed on this point as it does not provide a tool to objectively decide what is the “prevailing usage”. Both spellings are in use, and it seems thus logical to stick to the letter of the ICZN.”
Gustav Heinrich Kirchenpauer (1808–1887) of the City of Hamburg, and his research on hydroids and bryozoans
Authors: CALDER DALE R. , BRINCKMANN-VOSS ANITA
Published: January 2019

Gustav Heinrich Kirchenpauer was born 2 February 1808 in Hamburg, and he died in that city on 3 March 1887. In 1810 he was taken with his family to St. Petersburg, Russia, to escape economic hardships during the occupation of Hamburg and continental blockade of the United Kingdom by Napoleon. He attended secondary school and university in Dorpat (Tartu), Estonia, and earned a doctorate in law from Universtät Heidelberg in 1831. Kirchenpauer returned to Hamburg in 1832 as a lawyer and journalist, gaining recognition as a specialist in international trade. He later served as senator, federal council representative, and seven-time Bürgermeister (mayor) of the city. One of his avocations was natural history, especially taxonomy of hydroids and bryozoans. While he published only six papers with information on Hydrozoa, Kirchenpauer described and named eight genera and 77 species and subspecies of hydroids. Three familiar genera (Abietinaria, Lytocarpia, Macrorhynchia) and nearly half of the species he founded are still recognized as valid. In four papers dealing at least in part with Bryozoa, he named and described one new genus and 26 new species-group taxa in that group. Hydroids and bryozoans studied and described by Kirchenpauer came from many parts of the world, especially Australia, the western Pacific and mid-Pacific islands, South Africa, Europe, the Russian Far East, and the eastern South Atlantic. Kirchenpauer was awarded an honorary doctorate from Universtät Kiel in 1876 for his scientific contributions. One family, one genus, and four species have been named in his honour.
Taxonomy and the DNA Barcoding Enterprise
Authors: EBACH MALTE C.
Published: January 2019

DNA Barcoding is elusive to many taxonomists. Like the numbers in a barcode, barcoding attempts to link a type specimen with a part of its DNA, most commonly from the mitochondrial Cytochrome c Oxidase subunit I (COI) gene.
Phylogenetic relationships within the genus Staurois (Anura, Ranidae) based on 16S rRNA sequences
Authors: ARIFIN UMILAELA , ISKANDAR DJOKO T. , BICKFORD DAVID P. , BROWN RAFE M. , MEIER RUDOLF , KUTTY SUJATHA NARAYANAN
Published: January 2019

We estimate the phylogenetic relationships among all six recognized species of the genus Staurois based on 16S rRNA sequences (~522 bp) for 92 specimens from Borneo and the Philippines. Our preferred phylogenetic tree inferred from Maximum Parsimony and Bayesian methods reveal six major clades within the genus leading to recognition of S. natator, S. nubilus, S. guttatus, S. tuberilinguis, S. parvus, and S. latopalmatus. For species where multiple populations were assessed, we found high genetic variation that may eventually support the recognition of new species.
Redescription of Callianassa jousseaumei Nobili, 1904, a junior subjective synonym of Callianassa indica de Man, 1905 with description of a new species of Neocallichirus (Decapoda: Axiidea: Callianassidae)
Authors: DWORSCHAK PETER C.
Published: January 2019

Investigation of newly collected material from the Philippines during the Panglao Marine Biodiversity Project 2004, together with re-examination of the type material of Callianassa jousseaumei Nobili, 1904 and numerous specimens identified as Neocallichirus indicus (de Man, 1905), revealed that the latter is identical with the former and has to be considered a junior synonym of Callianassa jousseaumei. A redescription of this species is presented together with notes on its morphological variability and its ecology. A new species of Neocallichirus, N. vaugelasi, is described for specimens from Aqaba, previously attributed erroneously to C. (or N.) jousseaumei, and N. natalensis Barnard, 1947 is removed from the synonymy of the latter. This is the first record of this species for the Philippines and Thailand.
Securicauda hermani and Carinacauda stormi, two new genera and species of slug from the Pacific Northwest of the United States (Gastropoda: Stylommatophora: Arionidae), with notes on Gliabates oregonius Webb 1959
Authors: LEONARD WILLIAM P. , CHICHESTER LYLE , RICHART CASEY H. , YOUNG TIFFANY A.
Published: January 2019

Two new genera and species of arionid slug, Securicauda hermani n. gen. et n. sp. and Carinacauda stormi n. gen. et n. sp., are described from the United States in northern Idaho and western Oregon, respectively. This taxonomic decision is based on anatomical comparisons to the ten genera of Arionidae native to northwestern North America. Securicauda lacks an atrium and atrial accessory structures and the epiphallus is almost entirely buried in the penis; Carinacauda has an atrium, a pair of atrial accessory structures, and a long epiphallus that is not embedded in the penis.
New species of Klinckowstroemia Baker & Wharton, 1952 (Acari: Klinckowstroemiidae), associated with passalid beetles from Mexico and Panama
Authors: VILLEGAS-GUZMÁN GABRIEL A. , REYES-CASTILLO PEDRO , PÉREZ TILA M.
Published: January 2019

Four new species of the genus Klinckowstroemia are described, all obtained from passalid beetles collected in Mexico and Panama. The species are: Klinckowstroemia pennula, sp. nov., K. melissae sp. nov., K. stilla sp. nov., and K. oconnori sp. nov. We found two instances where different mite species inhabited the same host, K. pennula, and K. melissae on Pseudacanthus sp., and K. pennula and K. candidoi on Oileus bifidus. This is the first record of the genus Klinckowstroemia from Panama. An updated key for the 24 species of Klinckowstroemia is presented.
A review of the boneti-group of the genus Coecobrya (Collembola: Entomobryidae)
Authors: ZHANG FENG , MAN LE CONG , DEHARVENG LOUIS
Published: January 2019

The genus Coecobrya is divided here into tenebricosa- and boneti-groups, blind and with a large outer tooth on the unguiculus in the former, and eyed and with the outer edge of unguiculus smooth or serrate in the latter. All five species of boneti-group are reviewed here and their diagnostic characters compared in a table. Coecobrya. boneti (Denis) and C. tetrophthalma (Denis) from Vietnam, are redescribed based on examination of their types and of newly collected topotypes. A key to the species of boneti-group is provided.
New semionotiform (Neopterygii) from the Tlayúa Quarry (Early Cretaceous, Albian), Mexico
Authors: LÓPEZ-ARBARELLO ADRIANA , ALVARADO-ORTEGA JESÚS
Published: January 2019

We describe a new semionotiform fish, Tlayuamichin itztli gen. et sp. nov. from the Early Cretaceous (Albian) of Mexico, which constitutes one of the youngest semionotid articulated remains. The new taxon is represented by five well-preserved specimens from the Tlayúa Quarry near Tepexi de Rodríguez in Puebla State, central Mexico. A series of paraethmoid bones anterior to the supraorbital series, supraorbital bones extending beyond the anterior rim of the orbit, the presence of a large pentagonal supraorbital closing the anterior rim of the orbit, seven anterior infraorbitals, dorsally expanded infraorbitals at the ventral border of the orbit, and the most dorsal suborbital separating the preoperculum from the dermopterotic are potential autapomorphic features of the new taxon. The very long frontals, a dermopterotic that does not contact the anterodorsal corner of the operculum and the presence of a modified pectoral scale are additional features that help to diagnose the taxon. Tlayuamichin itztli gen. et sp. nov. resembles most closely “Lepidotes” minor from the Middle Purbeck Beds (early Berriasian), England. These two taxa share similarity with other species of Semionotus from the Early Jurassic of North America and the Triassic of Europe, suggesting interesting biogeographic relationships.
New species and records for the mayfly families Caenidae, Leptohyphidae and Coryphoridae (Ephemeroptera, Pannota) from Venezuelan Guayana’s Uplands
Authors: MOLINERI CARLOS , GRILLET MARIA-EUGENIA , NIETO CAROLINA , DOMINGUEZ EDUARDO , GUERRERO EDMUNDO
Published: January 2019

We give new geographical and morphological data for the Pannota mayflies of Venezuelan Guayanan uplands. Coryphorus aquilus (Coryphoridae), Amanahyphes saguassu and Tricorythopsis yucupe (Leptohyphidae) are newly recorded for Venezuela, the adults of the last species are described for the first time. Macunahyphes pemonensis sp. nov. and Macunahyphes incognitus sp. nov. (Leptohyphidae) are described from adults from Venezuela and Brazil, respectively. Both new species of Macunahyphes are very nearly related, and are characterized among other features, by the absence of forceps, and the great development of large paired projections on the styliger plate. Caenis teipunensis sp. nov. (Caenidae) is also described from adults, its diagnostic characters include: forceps apically sharp and sclerotized, and very large apophyses of the styliger sclerite. We give new locality records for Tricorythopsis volsellus, previously known from other localities in Venezuela.
A new species of Pristapenesia Brues (Hymenoptera, Scolebythidae) from Asia
Authors: AZEVEDO CELSO O. , XU ZAIFU , BEAVER ROGER A.
Published: January 2019

Pristapenesia asiatica sp. nov. is described and illustrated from two female specimens collected in China and Thailand. This species is readily recognized by the absence of a tubular radial vein in the fore wings. A key to world fossil and living species of Pristapenesia is provided.
Two new species of Rhogadopsis Brèthes (Braconidae: Opiinae) as solitary
parasitoids of Merochlorops species complex (Diptera: Chloropidae) from India
Authors: GUPTA ANKITA , VAN ACHTERBERG CORNELIS , BALLAL CHANDISH R. , MACZEY NORBERT , DJEDDOUR DJAMI , BHUTIA SANGAY GYAMPO , RAJESHWARI S. K.
Published: January 2019

During surveys for the potential biocontrol agents Merochlorops species complex (Diptera: Chloropidae), to control the invasive weed Hedychium gardnerianum Sheppard ex Ker Gawl. (Zingiberaceae), two new species of Rhogadopsis Brèthes (Braconidae: Opiinae) viz., R. gratia Gupta & van Achterberg, sp. n. and R. macrusa Gupta & van Achterberg, sp. n. were reared as solitary larval-pupal parasitoids of Merochlorops in the stems of H. gardnerianum. Interestingly, both wasp species have very different ovipositor lengths, in addition to other characters for species delimitation. Perhaps parasitism by the respective wasp species depends on the thickness of the stem harbouring the chloropid larvae. In the present study, both these new species of wasps are described and illustrated, together with notes on their biology. For the first time the genus Rhogadopsis has been found associated with Chloropidae; earlier records concern Agromyzidae.
A new testate amoebae species Planhoogenraadia wuchanica sp. nov. from subtropical forest soils in Wuhan, central China
Authors: BOBROV ANATOLY , QIN YANGMIN , PAYNE RICHARD J.
Published: January 2019

Here we describe a new testate amoeba species Planhoogenraadia wuchanica sp. nov. identified in subtropical forest soils in Wuhan, central China. The smaller shell length, narrower aperture and distinctive ‘cap’ structure make P. wuchanica morphologically distinct from similar taxa in the genus. While this new species is morphologically distinctive, phylogenetic analyses would be beneficial to clarify taxonomic relationships within the genus Planhoogenraadia.
Seawater Icicles of the Adriatic Sea
Authors: Malačič Vlado , Žagar Nedjeljka
Published: January 2019

The marine icicles that form on coastal constructions (e.g., piers and railings) are very common in polar and subpolar areas. The occasional formation of icicles in the coastal zones of the Mediterranean Sea occurs in relation to cold-air outbreaks from the polar region, such as the one presented in this paper in February 2018. The air temperatures over the northern Adriatic Sea, the northernmost part of the Mediterranean, dropped below –2.1°C, a necessary condition for seawater to freeze, with salinity between 38.0 and 38.5 PSU. The formation of icicles on the coastal structures was further enabled by the bora wind and related high seas along the coast. Measurements presented in this paper confirm that the icicles in the Bay of Piran in the Gulf of Trieste (45.55°N) were formed from the seawater. The measured salinity level of the melted icicles, around 9 PSU, is a typical value reported for marine icicles in polar regions.
The Impact of the QBO on MJO Convection in Cloud-Resolving Simulations
Authors: Martin Zane , Wang Shuguang , Nie Ji , Sobel Adam
Published: January 2019

This study examines the relationship between the Madden–Julian oscillation (MJO) and the stratospheric quasi-biennial oscillation (QBO) in a limited-area cloud-resolving model with parameterized large-scale dynamics. The model is used to simulate two consecutive MJO events that occurred during the late fall and early winter of 2011. To test the influence of the QBO on the simulated MJO events, various QBO states are imposed via the addition of characteristic wind and temperature anomalies. In experiments with only QBO temperature anomalies imposed (without corresponding zonal wind anomalies) the strength of convection during MJO active phases is amplified for the QBO easterly phase [an anomalously cold tropical tropopause layer (TTL)] compared to the westerly QBO phase (a warm TTL), as measured by outgoing longwave radiation, cloud fraction, and large-scale ascent. This response is qualitatively consistent with the observed MJO–QBO relationship. The response of precipitation is weaker, and is less consistent across variations in the simulation configuration. Experiments with only imposed QBO wind anomalies (without corresponding temperature anomalies) show much weaker effects altogether than those with imposed temperature anomalies, suggesting that TTL temperature anomalies are a key pathway through which the QBO can modulate the MJO. Sensitivity tests indicate that the QBO influence on MJO convection depends on both the amplitude and the height of the QBO temperature anomaly: lower-altitude and larger-amplitude temperature anomalies have more pronounced effects on MJO convection.
Power-Law Scaling in the Internal Variability of Cumulus Cloud Size Distributions due to Subsampling and Spatial Organization
Authors: Neggers R. A. J. , Griewank P. J. , Heus T.
Published: January 2019

In this study, the spatial structure of cumulus cloud populations is investigated using three-dimensional snapshots from large-domain LES experiments. The aim is to understand and quantify the internal variability in cloud size distributions due to subsampling effects and spatial organization. A set of idealized shallow cumulus cases is selected with varying degrees of spatial organization, including a slowly organizing marine precipitating case and five more quickly organizing diurnal cases over land. A subdomain analysis is applied, yielding cloud number distributions at sample sizes ranging from severely undersampled to nearly complete. A strong power-law scaling is found in the relation between cloud number variability and subdomain size, reflecting an inverse linear relation. Scaling subdomain size by cloud size yields a data collapse across time points and cases, highlighting the role played by cloud spacing in controlling the stochastic variability. Spatial organization acts on top of this baseline model by increasing the maximum cloud size and by enhancing the variability in the number of smallest clouds. This reflects that the smaller clouds start to live on top of larger-scale thermodynamic structures, such as cold pools, which favor or inhibit their formation. Compositing all continental cumulus cases suggests the existence of a prototype diurnal time dependence in the spatial organization. A simple stochastic expression for cloud number variability is proposed that is formulated in terms of two dimensionless groups, which allows objective estimation of the degree of spatial organization in simulated and observed cumulus cloud populations.
The Annual Cycle of Northern Hemisphere Storm Tracks. Part I: Seasons
Authors: Hoskins B. J. , Hodges K. I.
Published: January 2019

In this paper and Part II a comprehensive picture of the annual cycle of the Northern Hemisphere storm tracks is presented and discussed for the first time. It is based on both feature tracking and Eulerian-based diagnostics, applied to vorticity and meridional wind in the upper and lower troposphere. Here, the storm tracks, as diagnosed using both variables and both diagnostic techniques, are presented for the four seasons for each of the two levels. The oceanic storm tracks retain much of their winter mean intensity in spring with only a small change in their latitude. In the summer they are much weaker, particularly in the Pacific and are generally farther poleward. In autumn the intensities are larger again, comparable with those in spring, but the latitude is still nearer to that of summer. However, in the lower troposphere in the eastern ocean basins the tracking metrics show northern and southern tracks that change little with latitude through the year. The Pacific midwinter minimum is seen in upper-troposphere standard deviation diagnostics, but a richer picture is obtained using tracking. In winter there are high intensities over a wide range of latitudes in the central and eastern Pacific, and the western Pacific has high track density but weak intensity. In the lower troposphere all the diagnostics show that the strength of the Pacific and Atlantic storm tracks are generally quite uniform over the autumn–winter–spring period. There is a close relationship between the upper-tropospheric storm track, particularly that based on vorticity, and tropopause-level winds and temperature gradients. In the lower troposphere, in winter the oceanic storm tracks are in the region of the strong meridional SST gradients, but in summer they are located in regions of small or even reversed SST gradients. However, over North America the lower-tropospheric baroclinicity and the upstream portion of the Atlantic storm track stay together throughout the year.