bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ed Zigler's developmental approach to intellectual disabilities: Past, present, and future contributions
Authors: Hodapp Robert M. 
Published: May 2021

AbstractComprising two parts, Ed Zigler's developmental approach has greatly influenced how one conceptualizes children with intellectual disabilities (ID). In part one, Zigler championed a “two-group approach” concerning the cause of children's ID. He distinguished persons with a clear, organic cause of their ID from those displaying no clear cause. Members of this “organic” group often displayed IQs below 50 and co-occurring physical–medical conditions. The second, “cultural–familial” group, mostly showed IQs of 50–70, did not possess co-occurring physical or health problems, and often came from families of lower IQs and lower socioeconomic status. While the presence of these two groups has been supported, recent advances have also further differentiated the organic group, mostly in relation to behavioral phenotypes of persons with several genetic etiologies. In part two, Zigler championed the child with ID as a “whole person.” Originally focused on the child's reactions to social deprivation and failure, recent studies directly examine parent–child, within-family, and wider system interactions throughout the life span. For decades a force within the ID field, Zigler's developmental approach to children with ID continues to influence researchers, interventionists, and policymakers.
A Statistical Study of Lower Hybrid Waves in the Earth's Magnetosphere by Van Allen Probes
Authors: Liu Xu , Chen Lunjin , Ma Qianli 
Published: May 2021

AbstractThe lower hybrid (LH) waves are electrostatic emissions near the LH resonant frequency. They propagate perpendicularly with a small wavelength comparable to Larmor radius of thermal particles and can be capable of heating both ions and electrons. In this study, we statistically study the global distribution of LH waves in the inner magnetosphere by using Van Allen Probes observation from 2012 to 2018. We find that (a) LH waves are commonly observed in the inner magnetosphere. Most LH waves are confined near the magnetic equator with typical amplitudes of 0.02–0.2 mV/m and occurrence rates up to 10%. (b) LH waves extend to inner L regions with increasing wave amplitudes as AE* increases. (c) Weak LH waves occur at the nightside inside the plasmapause. Moderate and strong LH waves occur at the nightside and noon inside the plasmapause. As AE* increases, they extend to all magnetic local times inside the plasmapause and dawnside outside the plasmapause.
Integrase-derived peptides together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells
Authors: Shapira Shiran , Finkelshtein Eynat , Kazanov Dina , Naftali Esmira , Stepansky Irena , Loyter Abraham , Elbirt Daniel , Hay-Levy Mori , Brazowski Eli , Bedny Faina , Dekel Roy , Hershkovitz Dov , Blachar Arye , Wolf Ido , Arber Nadir 
Published: May 2021

AbstractThe integration of viral DNA into the host genome is mediated by viral integrase, resulting in the accumulation of double-strand breaks. Integrase-derived peptides (INS and INR) increase the number of integration events, leading to escalated genomic instability that induces apoptosis. CD24 is a surface protein expressed mostly in cancer cells and is very rarely found in normal cells. Here, we propose a novel targeted cancer therapeutic platform based on the lentiviral integrase, stimulated by integrase-derived peptides, that are specifically delivered to cancerous cells via CD24 antigen-antibody targeting. INS and INR were synthesized and humanized and anti-CD24 antibodies were fused to the lentivirus envelope. The activity, permeability, stability, solubility, and toxicity of these components were analyzed. Cell death was measured by fluorescent microscopy and enzymatic assays and potency were tested in vitro and in vivo. Lentivirus particles, containing non-functional DNA led to massive cell death (40–70%). Raltegravir, an antiretroviral drug, inhibited the induction of apoptosis. In vivo, single and repeated administrations of INS/INR were well tolerated without any adverse effects. Tumor development in nude mice was significantly inhibited (by 50%) as compared to the vehicle arm. In summary, a novel and generic therapeutic platform for selective cancer cell eradication with excellent efficacy and safety are presented.
Infant formula containing bovine milk-derived oligosaccharides supports age-appropriate growth and improves stooling pattern
Authors: Estorninos E. , Lawenko R. B. , Palestroque E. , Lebumfacil J. , Marko M. , Cercamondi C. I. 
Published: May 2021

Abstract
Background
Adding bovine milk-derived oligosaccharides (MOS) enhances the oligosaccharide profile of infant formula. This study aimed to evaluate the safety and efficacy of a MOS-supplemented infant formula.

Methods
In this double-blind randomized controlled trial, healthy infants 21–26 days old were either assigned to bovine milk-based, alpha-lactalbumin, and sn-2 palmitate enriched infant formula (control, n = 115) or the same formula with 7.2 g MOS/L (test, n = 115) until aged 6 months. Co-primary endpoints were weight gain through 4 months and stool consistency (validated scale: 1 = watery to 5 = hard). Secondary endpoints included parent-reported GI tolerance, health-related quality of life (HRQoL), and adverse events (AEs).

Results
Weight gain was similar (p = 0.695); the difference between test and control (mean; 95% CI: 0.29; −1.15, 1.73 g/day) was above the non-inferiority margin (−3 g/day). Test had softer stools than control (mean difference in stool consistency score: −0.31; 95% CI: −0.42, −0.21; P < 0.0001); fewer parental reports of harder stools (OR = 0.32, 95% CI: 0.20, 0.49; P < 0.0001) and less difficulties in passing stool (OR = 0.25, 95% CI: 0.09, 0.65; P = 0.005). Parent-reported GI tolerance and HRQoL were similar between groups as were the overall low AEs.

Conclusions
MOS-supplemented infant formula is safe and well-tolerated while supporting normal infant growth and promotes softer stooling pattern without increasing parent-reported and physician-confirmed adverse health concerns.

Impact

This is the first study investigating the addition of bovine milk-derived oligosaccharides to an infant formula enriched with alpha-lactalbumin and elevated levels of sn-2 palmitate, providing safety and efficacy data for such a formula.

Term infant formula supplemented with 7.2 g bovine milk-derived oligosaccharides per liter supported normal infant growth, was well-tolerated and safe.

Addition of bovine milk-derived oligosaccharides to term infant formula promoted softer stooling pattern and reduced difficulties in passing stool.

The study shows that bovine milk-derived oligosaccharide supplemented infant formula is a safe and effective option for healthy term infants who are formula-fed.
MTA2 silencing attenuates the metastatic potential of cervical cancer cells by inhibiting AP1-mediated MMP12 expression via the ASK1/MEK3/p38/YB1 axis
Authors: Lin Chia-Liang , Ying Tsung-Ho , Yang Shun-Fa , Chiou Hui-Ling , Chen Yong-Syuan , Kao Shao-Hsuan , Hsieh Yi-Hsien 
Published: May 2021

AbstractMetastasis-associated protein 2 (MTA2) is a transcription factor that is highly associated with matrix metalloproteinase 12 (MMP12). Thus, we hypothesized that MTA2 may regulate MMP12 expression and is involved in cervical cancer metastasis. Results showed that MTA2 and MMP12 were highly expressed in cervical cancer cells, and MTA2 knockdown reduced MMP12 expression and inhibited the metastasis of cervical cancer cells in xenograft mice. MMP12 knockdown did not influence the viability of cervical cancer cells but clearly inhibited cell migration and invasion both in vitro and in vivo. MMP12 was highly expressed in cervical tumor tissues and correlated with the poor survival rate of patients with cervical cancer. Further investigations revealed that p38 mitogen-activated protein kinase (p38), mitogen-activated protein kinase kinase 3 (MEK3), and apoptosis signal-regulating kinase 1 (ASK1) were involved in MMP12 downregulation in response to MTA2 knockdown. Results also demonstrated that p38-mediated Y-box binding protein1 (YB1) phosphorylation disrupted the binding of AP1 (c-Fos/c-Jun) to the MMP12 promoter, thereby inhibiting MMP12 expression and the metastatic potential of cervical cancer cells. Collectively, targeting both MTA2 and MMP12 may be a promising strategy for the treatment of cervical cancer.
Comprehensive molecular dissection of TIFY Transcription factors reveal their dynamic responses to biotic and abiotic stress in wheat (Triticum aestivum L.)
Authors: Singh Poonam , Mukhopadhyay Kunal 
Published: May 2021

AbstractThe plant specific TIFY (previously known as ZIM) transcription factor (TF) family plays crucial roles in cross talk between Jasmonic Acid and other phytohormones like gibberellins, salicylic acid, abscisic acid, auxin, and ethylene signaling pathways. Wheat yield is severely affected by rust diseases and many abiotic stresses, where different phytohormone signaling pathways are involved. TIFYs have been studied in many plants yet reports describing their molecular structure and function in wheat are lacking. In the present study, we have identified 23 novel TIFY genes in wheat genome using in silico approaches. The identified proteins were characterized based on their conserved domains and phylogenetically classified into nine subfamilies. Chromosomal localization of the identified TIFY genes showed arbitrary distribution. Forty cis-acting elements including phytohormone, stress and light receptive elements were detected in the upstream regions of TIFY genes. Seventeen wheat microRNAs targeted the identified wheat TIFY genes. Gene ontological studies revealed their major contribution in defense response and phytohormone signaling. Secondary structure of TIFY proteins displayed the characteristic alpha–alpha–beta fold. Synteny analyses indicated all wheat TIFY genes had orthologous sequences in sorghum, rice, maize, barley and Brachypodium indicating presence of similar TIFY domains in monocot plants. Six TIFY genes had been cloned from wheat genomic and cDNA. Sequence characterization revealed similar characteristics as the in silico identified novel TIFY genes. Tertiary structures predicted the active sites in these proteins to play critical roles in DNA binding. Expression profiling of TIFY genes showed their contribution during incompatible and compatible leaf rust infestation. TIFY genes were also highly expressed during the initial hours of phytohormone induced stress. This study furnishes fundamental information on characterization and putative functions of TIFY genes in wheat.
Hydrological projections in the upper reaches of the Yangtze River Basin from 2020 to 2050
Authors: Huang Ya , Xiao Weihua , Hou Baodeng , Zhou Yuyan , Hou Guibing , Yi Ling , Cui Hao 
Published: May 2021

AbstractUnderstanding the impact of climate change on runoff is essential for effective water resource management and planning. In this study, the regional climate model (RCM) RegCM4.5 was used to dynamically downscale near-future climate projections from two global climate models to a 50-km horizontal resolution over the upper reaches of the Yangtze River (UYRB). Based on the bias-corrected climate projection results, the impacts of climate change on mid-twenty-first century precipitation and temperature in the UYRB were assessed. Then, through the coupling of a large-scale hydrological model with RegCM4.5, the impacts of climate change on river flows at the outlets of the UYRB were assessed. According to the projections, the eastern UYRB will tend to be warm-dry in the near-future relative to the reference period, whereas the western UYRB will tend to be warm-humid. Precipitation will decreases at a rate of 19.05–19.25 mm/10 a, and the multiyear average annual precipitation will vary between − 0.5 and 0.5 mm/day. Temperature is projected to increases significantly at a rate of 0.38–0.52 °C/10 a, and the projected multiyear average air temperature increase is approximately 1.3–1.5 ℃. The contribution of snowmelt runoff to the annual runoff in the UYBR is only approximately 4%, whereas that to the spring runoff is approximately 9.2%. Affected by climate warming, the annual average snowmelt runoff in the basin will be reduced by 36–39%, whereas the total annual runoff will be reduced by 4.1–5%, and the extreme runoff will be slightly reduced. Areas of projected decreased runoff depth are mainly concentrated in the southeast region of the basin. The decrease in precipitation is driving this decrease in the southeast, whereas the decreased runoff depth in the northwest is mainly driven by the increase in evaporation.
The paradoxical role of emotional intensity in the perception of vocal affect
Authors: Holz N. , Larrouy-Maestri P. , Poeppel D. 
Published: May 2021

AbstractVocalizations including laughter, cries, moans, or screams constitute a potent source of information about the affective states of others. It is typically conjectured that the higher the intensity of the expressed emotion, the better the classification of affective information. However, attempts to map the relation between affective intensity and inferred meaning are controversial. Based on a newly developed stimulus database of carefully validated non-speech expressions ranging across the entire intensity spectrum from low to peak, we show that the intuition is false. Based on three experiments (N = 90), we demonstrate that intensity in fact has a paradoxical role. Participants were asked to rate and classify the authenticity, intensity and emotion, as well as valence and arousal of the wide range of vocalizations. Listeners are clearly able to infer expressed intensity and arousal; in contrast, and surprisingly, emotion category and valence have a perceptual sweet spot: moderate and strong emotions are clearly categorized, but peak emotions are maximally ambiguous. This finding, which converges with related observations from visual experiments, raises interesting theoretical challenges for the emotion communication literature.
Steroid hormone bioavailability is controlled by the lymphatic system
Authors: Klossner Rahel , Groessl Michael , Schumacher Nadine , Fux Michaela , Escher Geneviève , Verouti Sophia , Jamin Heidi , Vogt Bruno , Mohaupt Markus G. , Gennari-Moser Carine 
Published: May 2021

AbstractThe steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17β-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.
Study on effects of sweating treatment and different drying methods on the quality of Gentianae macrophyllae Radix
Authors: Chen Qianliang , Shi Zhangyan , Wang Yedan , Zhang Run , Hu Hehe 
Published: May 2021

AbstractTo provide basis for improving the quality of Gentianae macrophyllae Radix and optimising the field processing method. Gentianae macrophyllae Radix samples were collected from Long County. Five main active iridoids were determined by using HPLC. The HPLC fingerprints were measured and analysed by the traditional Chinese medicine chromatographic fingerprint similarity evaluation system. Water, total ash, acid insoluble ash and ethanol extract contents were determined in accordance with Chinese Pharmacopoeia (2015). Colour of the surface and powdered samples were determined by using a colorimeter. Data were analysed by SPSS11.0. Notable differences were found among samples from different sweating and drying processes, in spite of the relatively consistent overall chemical characteristics. Sweating and drying methods influenced the contents of some active ingredients and colour very significantly; moreover, they also showed significant effects on the water, ash, and ethanol extract contents. The necessity of sweating treatment in the field processing of Gentianae macrophyllae Radix may be insufficient. Drying in the shade and oven drying are more profitable for preserving the active constituents. Gentianae macrophyllae Radix should be dried directly without sweating, and drying in the shade and oven drying should be adopted preferentially to improve the quality.
Spatiotemporal slope stability analytics for failure estimation (SSSAFE): linking radar data to the fundamental dynamics of granular failure
Authors: Tordesillas Antoinette , Kahagalage Sanath , Campbell Lachlan , Bellett Pat , Intrieri Emanuele , Batterham Robin 
Published: May 2021

AbstractImpending catastrophic failure of granular earth slopes manifests distinct kinematic patterns in space and time. While risk assessments of slope failure hazards have routinely relied on the monitoring of ground motion, such precursory failure patterns remain poorly understood. A key challenge is the multiplicity of spatiotemporal scales and dynamical regimes. In particular, there exist a precursory failure regime where two mesoscale mechanisms coevolve, namely, the preferred transmission paths for force and damage. Despite extensive studies, a formulation which can address their coevolution not just in laboratory tests but also in large, uncontrolled field environments has proved elusive. Here we address this problem by developing a slope stability analytics framework which uses network flow theory and mesoscience to model this coevolution and predict emergent kinematic clusters solely from surface ground motion data. We test this framework on four data sets: one at the laboratory scale using individual grain displacement data; three at the field scale using line-of-sight displacement of a slope surface, from ground-based radar in two mines and from space-borne radar for the 2017 Xinmo landslide. The dynamics of the kinematic clusters deliver an early prediction of the geometry, location and time of failure.
Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants
Authors: Witek Wojciech , Sliwiak Joanna , Ruszkowski Milosz 
Published: May 2021

AbstractThe second and third steps of the histidine biosynthetic pathway (HBP) in plants are catalyzed by a bifunctional enzyme–HISN2. The enzyme consists of two distinct domains, active respectively as a phosphoribosyl-AMP cyclohydrolase (PRA-CH) and phosphoribosyl-ATP pyrophosphatase (PRA-PH). The domains are analogous to single-domain enzymes encoded by bacterial hisI and hisE genes, respectively. The calculated sequence similarity networks between HISN2 analogs from prokaryotes and eukaryotes suggest that the plant enzymes are closest relatives of those in the class of Deltaproteobacteria. In this work, we obtained crystal structures of HISN2 enzyme from Medicago truncatula (MtHISN2) and described its architecture and interactions with AMP. The AMP molecule bound to the PRA-PH domain shows positioning of the N1-phosphoribosyl relevant to catalysis. AMP bound to the PRA-CH domain mimics a part of the substrate, giving insights into the reaction mechanism. The latter interaction also arises as a possible second-tier regulatory mechanism of the HBP flux, as indicated by inhibition assays and isothermal titration calorimetry.
Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
Authors: Tripaldi Romina , Lanuti Paola , Simeone Paola Giustina , Liani Rossella , Bologna Giuseppina , Ciotti Sonia , Simeone Pasquale , Di Castelnuovo Augusto , Marchisio Marco , Cipollone Francesco , Santilli Francesca 
Published: May 2021

AbstractProtease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing endothelial repair. We hypothesized that the effect of PCSK9 on vascular homeostasis may be mediated by EPCs in patients with or without type 2 diabetes mellitus (T2DM). Eighty-two patients (45 with, 37 without T2DM) at high cardiovascular risk were enrolled in this observational study. Statin treatment was associated with higher circulating levels of PCSK9 in patients with and without T2DM (p < 0.001 and p = 0.036) and with reduced CD45neg/CD34bright (total EPC compartment) (p = 0.016) and CD45neg/CD34bright/CD146neg (early EPC) (p = 0.040) only among patients with T2DM. In the whole group of patients, statin treatment was the only independent predictor of low number of CD45neg/CD34bright (β = − 0.230; p = 0.038, adjusted R2 = 0.041). Among T2DM patients, PCSK9 circulating levels were inversely related and predicted both the number of CD45neg/CD34bright (β = − 0.438; p = 0.003, adjusted R2 = 0.173), and CD45neg/CD34bright/CD146neg (β = − 0.458; p = 0.002, adjusted R2 = 0.191) independently of age, gender, BMI and statin treatment. In high-risk T2DM patients, high endogenous levels of PCSK9 may have a detrimental effect on EPCs by reducing the endothelial repair and worsening the progression of atherothrombosis.
Endothelial angiogenic activity and adipose angiogenesis is controlled by extracellular matrix protein TGFBI
Authors: Lee Seul Gi , Kim Jin Soo , Kim Ha-Jeong , Schlaepfer David D. , Kim In-San , Nam Ju-Ock 
Published: May 2021

AbstractSeveral studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM. The treatment of Ad-CM-stimulated SVEC-10 endothelial cells with TGFBI protein reduced migration and tube-forming activity. TGFBI protein suppressed the activation of the Src and extracellular signaling-related kinase signaling pathways of these SVEC-10 endothelial cells. Our findings indicated that TGFBI inhibited adipose angiogenesis by suppressing the activation of Src and ERK signaling pathways, possibly because of the stimulation of the angiogenic activity of endothelial cells.