bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized Inhibitors of MDM2 via an Attempted Protein‐Templated Reductive Amination
Authors: van der Vlag Ramon , Yagiz Unver M. , Felicetti Tommaso , Twarda‐Clapa Aleksandra , Kassim Fatima , Ermis Cagdas , Neochoritis Constantinos G. , Musielak Bogdan , Labuzek Beata , Dömling Alexander , Holak Tad A. , Hirsch Anna K. H. 
Published: November 2019

AbstractInnovative and efficient hit‐identification techniques are required to accelerate drug discovery. Protein‐templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein‐templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein‐templated reductive amination to target protein‐protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure‐based drug design. After careful analysis we did not find one of the possible products in the kinetic target‐guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm) identified is almost as active as Nutlin‐3, a potent inhibitor of the p53‐MDM2 PPI.
Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells
Authors: Wullimann Mario F. , Umeasalugo Kosisochukwu E. 
Published: November 2019

AbstractVentralization, a major patterning process in the developing vertebrate neural tube (central nervous system, CNS), depends on Sonic hedgehog (SHH) as a main signaling morphogen. We studied the CNS of late larval and young adult zebrafish in a transgenic shh‐GFP line revealing increased neuroanatomical detail due to the progressed differentiation state compared to earlier stages. Some major findings emerge from the present study. (a) shh –GFP is still expressed along the adult zebrafish CNS neuraxis in most locations seen in larvae. (b) We newly identify a ventroposterior shh pallidal domain representing the basal telencephalic signaling center important for basal ganglia development known in other vertebrates (i.e., the anterior entopeduncular area—basal medial ganglionic eminence of mammals). (c) We further show late‐emerging shh‐GFP positive radial glia cells in the medial zone of the dorsal telencephalon (i.e., the teleostan pallial amygdala). (d) Immunostains for tyrosine hydroxylase demonstrate that there is selective colocalization in adult dopamine cells with shh‐GFP in the posterior tuberculum, including in projection cells to striatum, which represents a striking parallel to amniote mesodiencephalic dopamine cell origin from shh expressing floor plate cells. (e) There is no colocalization of shh and islet1 as shown by respective shh‐GFP and islet1‐GFP lines. (f) The only radially far migrated shh‐GFP cells are located in the preglomerular area. (g) There are no adult cerebellar and tectal shh‐GFP cells confirming their exclusive role during early development as previously reported by our laboratory.
Drosophila pericentrin‐like protein promotes the formation of primordial germ cells
Authors: Fang Junnan , Lerit Dorothy A. 
Published: November 2019

SummaryPrimordial germ cells (PGCs) are the precursors to the adult germline stem cells that are set aside early during embryogenesis and specified through the inheritance of the germ plasm, which contains the mRNAs and proteins that function as the germline fate determinants. In Drosophila melanogaster, formation of the PGCs requires the microtubule and actin cytoskeletal networks to actively segregate the germ plasm from the soma and physically construct the pole buds (PBs) that protrude from the posterior cortex. Of emerging importance is the central role of centrosomes in the coordination of microtubule dynamics and actin organization to promote PGC development. We previously identified a requirement for the centrosome protein Centrosomin (Cnn) in PGC formation. Cnn interacts directly with Pericentrin‐like protein (PLP) to form a centrosome scaffold structure required for pericentriolar material recruitment and organization. In this study, we identify a role for PLP at several discrete steps during PGC development. We find PLP functions in segregating the germ plasm from the soma by regulating microtubule organization and centrosome separation. These activities further contribute to promoting PB protrusion and facilitating the distribution of germ plasm in proliferating PGCs.
Water availability drives aboveground biomass and bird richness in forest restoration plantings to achieve carbon and biodiversity cobenefits
Authors: Hagger Valerie , Wilson Kerrie , England Jacqueline R. , Dwyer John M. 
Published: November 2019

AbstractTo combat global warming and biodiversity loss, we require effective forest restoration that encourages recovery of species diversity and ecosystem function to deliver essential ecosystem services, such as biomass accumulation. Further, understanding how and where to undertake restoration to achieve carbon sequestration and biodiversity conservation would provide an opportunity to finance ecosystem restoration under carbon markets. We surveyed 30 native mixed‐species plantings in subtropical forests and woodlands in Australia and used structural equation modeling to determine vegetation, soil, and climate variables most likely driving aboveground biomass accrual and bird richness and investigate the relationships between plant diversity, aboveground biomass accrual, and bird diversity. We focussed on woodland and forest‐dependent birds, and functional groups at risk of decline (insectivorous, understorey‐nesting, and small‐bodied birds). We found that mean moisture availability strongly limits aboveground biomass accrual and bird richness in restoration plantings, indicating potential synergies in choosing sites for carbon and biodiversity purposes. Counter to theory, woody plant richness was a poor direct predictor of aboveground biomass accrual, but was indirectly related via significant, positive effects of stand density. We also found no direct relationship between aboveground biomass accrual and bird richness, likely because of the strong effects of moisture availability on both variables. Instead, moisture availability and patch size strongly and positively influenced the richness of woodland and forest‐dependent birds. For understorey‐nesting birds, however, shrub cover and patch size predicted richness. Stand age or area of native vegetation surrounding the patch did not influence bird richness. Our results suggest that in subtropical biomes, planting larger patches to higher densities, ideally using a diversity of trees and shrubs (characteristics of ecological plantings) in more mesic locations will enhance the provision of carbon and biodiversity cobenefits. Further, ecological plantings will aid the rapid recovery of woodland and forest bird richness, with comparable aboveground biomass accrual to less diverse forestry plantations.
The von Willebrand Factor Facilitates Model for End‐Stage Liver Disease–Independent Risk Stratification on the Waiting List for Liver Transplantation
Authors: Györi Georg P. , Pereyra David , Rumpf Benedikt , Hackl Hubert , Köditz Christoph , Ortmayr Gregor , Reiberger Thomas , Trauner Michael , Berlakovich Gabriela A. , Starlinger Patrick 
Published: November 2019

Background and Aims
The Model for End‐Stage Liver Disease (MELD) is used for clinical decision‐making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD‐Na). However, MELD‐Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF‐Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF‐Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT.

Approach and Results
Hence, WF‐Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting‐list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF‐Ag (P < 0.001). MELD‐Na and vWF‐Ag were comparable and independent in their predictive potential for 3‐month mortality on the waiting list (area under the curve [AUC], vWF‐Ag = 0.739; MELD‐Na = 0.764). Importantly, a vWF‐Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD‐Na of 20 points (vWF‐Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD‐Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF‐Ag into the MELD‐Na equation significantly improved prediction of 3‐month waiting‐list mortality (AUC, MELD‐Na–vWF = 0.804).

Conclusions
A single measurement of vWF‐Ag at listing for OLT predicts early mortality. Combining vWF‐Ag levels with MELD‐Na improves risk stratification and may help to prioritize organ allocation to decrease waiting‐list mortality.
Experimental investigation of thermal performance of the graphene oxide–coated plates
Authors: Ghasemiasl Ramin , Taheri Mohammad Ali , Molana Maysam , Raoufi Nahid 
Published: November 2019

AbstractThis paper experimentally investigates the conductive heat transfer of samples with different materials and coatings. A range of graphene oxide nanoparticle concentration has been employed. Results demonstrate that utilizing nanoparticles leads to enhancement of conductive heat transfer by 10.07% and 8.01% for EK2 and ST14 samples, respectively. The aforementioned nanoparticles also reduce coating thickness and yield an enhanced quality of the surface, in terms of mechanical properties. The convective and radiative methods of heat transfer have been ignored in this study.
Role of miR‐106‐mediated mitogen‐activated protein kinase signaling pathway in oxidative stress injury and inflammatory infiltration in the liver of the mouse with gestational hypertension
Authors: Wang Zhihui , Bao Xiufang , Song Limeng , Tian Yuying , Sun Ping 
Published: November 2019

AbstractWe aim to investigate the role of miR‐106‐mediated mitogen‐activated protein kinase (MAPK) signaling pathway in oxidative stress (OS) injury and inflammatory infiltration in the liver of the mouse with gestational hypertension (GH). Ninety specific pathogen‐free mice (Kunming species) during middle to late gestation were selected for the study. Fifteen mice were used as control, while the rest were used for establishing the GH model. The mice were assigned to six groups: normal group (normal gestation), model group (GH model), negative control group (GH model, intravenously injected with negative control vector), miR‐106a‐mimic group (GH model, intravenously injected with vector overexpressing miR‐106a, which mimics the overexpression of endogenous mature miR‐106a), SB203580 group (GH model, intravenously injected with MAPK pathway inhibitor SB203580), and miR‐106a‐mimic+SB203580 group (GH model, intravenously injected with SB203580 and vector overexpressing miR‐106a). Fourteen days after electrical stimulation, all the groups except for the normal group had elevated blood pressure vs those on day 0 and 7. Compared with the normal group, the other groups had lower levels of miR‐106a expression, nitric oxide, nitric oxide synthase, catalase, superoxide dismutase, S cell ratio, and interleukin‐4 (IL‐4) and IL‐10 in the serum and liver as opposed to increased levels of blood pressure, p38MAPK mRNA expression, p‐p38MAPK positive expression rate, protein expressions of p‐p38MAPK, p‐ERK, and p‐JNK, H2O2 and malondialdehyde in liver, G0/G1 cell ratio, apoptosis rate, and IL‐6, interferon‐γ (IFN‐γ), and IFN‐α in the serum and liver (all P < .05). The miR‐106 overexpression or inhibiting MAPK signaling pathway can attenuate OS injury and inflammatory response in the liver of the mouse with GH, and the effect can be even better if both miR‐106a overexpression and inhibiting MAPK pathway are applied. In conclusion, miR‐106a overexpression can inhibit OS injury and inflammatory infiltration in the liver of the mouse with GH by mediating MAPK signaling pathway.
Ganglion cysts developed from the flexor tendon sheaths in the fingers: Clinical and sonographic features
Authors: Jang Yeonjung , Kang Byeong S. , Bang Minseo , Lim Soyeoun , Park Gyeong M. , Lee Tae Y. , Kwon Woon J. 
Published: November 2019

AbstractPurposeThe purpose of this study was to assess the clinical and sonographic features of flexor tendon sheath ganglion cysts in the fingers.MethodsWe retrospectively reviewed the clinical and sonographic features of 35 cases of flexor tendon sheath ganglion cysts in the fingers in 34 patients that were pathologically confirmed between 2003 and 2018.ResultsThe mean age of the patients was 44.2 years (range, 11‐73 years). Lesions were located at the level of the metacarpophalangeal joint (n = 22 [63%]) and proximal phalanx (n = 11 [31%]), and involvement of the third finger was common (n = 19 [54%]). The mean lesion size was 6 mm and the mean volume was 90 mm3. None of the lesions had a pedicle. Lesions were homogeneous (n = 24 [69%]) and anechoic (n = 23 [66%]). A septum was noted in 12 cases (34%).ConclusionsFlexor tendon sheath ganglion cysts are most commonly located in the third finger and at the level of the metacarpophalangeal joint and proximal phalanx. It usually presents as a simple cyst without a pedicle, but occasionally exhibits a mixed echogenicity and contains a septum.
Transcranial Doppler waveform changes due to increased cerebrovascular resistance and raised intracranial pressure in a patient with cirrhosis: A difference in shapes, not in numbers
Authors: Khan Khurram S. , Wiersema Ubbo F. 
Published: November 2019

AbstractWe report and discuss a case that illustrate the clinical utility of transcranial Doppler (TCD) ultrasound in a patient with cirrhosis. A 43‐year‐old female presented with acute decompensation of cirrhosis with hepatic encephalopathy, requiring mechanical ventilation. TCD showed low diastolic flow velocities and high pulsatility index (PI) consistent with increased cerebrovascular resistance (CVR). The flow velocities and PI normalized over a period of few days and correlated well with neurological improvement after treatment. Subsequently, the patient developed a large intracerebral hemorrhage with mass effect. The TCD measurements in intracranial hypertension were similar to those with cirrhosis and hepatic encephalopathy. However, the windkessel notch in the systolic phase of TCD waveform, related to the distensibility of arterial wall, was absent during raised intracranial pressure (ICP). The absence of a windkessel notch may help to differentiate a high downstream resistance due to raised ICP from increased CVR.
Climate change projections in the Awash River Basin of Ethiopia using Global and Regional Climate Models
Authors: Tadese Mahtsente T. , Kumar Lalit , Koech Richard 
Published: November 2019

AbstractUnderstanding the long‐term variability and change in climate variables is critical for the sustainable management of water resources. This research aimed to project and analyse climate change in the Awash River Basin (ARB) using bias‐corrected Global and Regional Climate Model simulations. The analysis included a baseline period from 1986 to 2005 and two future scenarios (2050s and 2070s) under two representative concentration pathways (RCP4.5 and RCP8.5). Following the evaluation of bias correction methods, the distribution mapping and power transformation were used for temperature and precipitation projection, respectively. The 2050s and 2070s RCP4 simulations showed an increase in precipitation during half of the months with 32 and 10%, respectively. Moreover, the 2050s and 2070s RCP8.5 simulation indicated a decrease in precipitation with 18 and 26%, respectively. The 2050s and 2070s RCP8.5 simulation indicated a significant decrease in precipitation in four of the months (February/March to May) with the highest decreasing rate of 34.7%. The 2050s and 2070s RCP4.5 simulation showed an increase of 0.48–2.6°C in maximum temperature. In the case of RCP8.5, the simulated maximum temperature increase reached 3.4 and 4.1°C in the 2050s and 2070s, respectively. The future precipitation and temperature change projected in ARB might worsen the water stress and incidence of dry spells in the basin, and hence mitigation strategies and management options to reduce this negative impact should be developed.
Is the personalized approach the key to improve clinical diagnosis of peri‐implant conditions? The role of bone markers
Authors: Rakic Mia , Monje Alberto , Radovanovic Sandro , Petkovic‐Curcin Aleksandra , Vojvodic Danilo , Tatic Zoran 
Published: November 2019

AbstractBackgroundStudy objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa‐B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri‐implant condition (HI), peri‐implant mucositis (PIM) and peri‐implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring.MethodsSplit‐mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri‐implant crevicular fluid using enzyme‐linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees.ResultsBleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri‐implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site.ConclusionsBTMs demonstrated capacity to substantially improve clinical diagnosis of peri‐implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri‐implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.
Evaluation of the Umbrella Species Concept at Fine Spatial Scales
Authors: Barlow Natasha L. , Kirol Christopher P. , Doherty Kevin E. , Fedy Bradley C. 
Published: November 2019

ABSTRACTDeclines in the spatial extent of the sagebrush ecosystem have prompted the consideration of conservation efforts that view the greater sage‐grouse (Centrocercus urophasianus; sage‐grouse) as an umbrella species at landscape scales. Conservation strategies that focus on an umbrella species, however, may have unintended negative consequences for co‐occurring species at finer scales. In North America, grassland and shrubland songbird populations are declining faster than other avian groups. Conservation of sage‐grouse habitats may protect songbird habitats where distributions overlap. To assess the umbrella species concept at fine scales, we quantified nest‐site selection for a sagebrush‐obligate songbird, the Brewer's sparrow (Spizella breweri). We then compared the fine‐scale habitat variables that influenced Brewer's sparrow nest‐site selection with fine‐scale nest‐site selection for sage‐grouse in the Powder River Basin region of northeastern Wyoming, USA. We modeled nest‐site selection using conditional logistic regression for Brewer's sparrow (2016–2017) and logistic regression for sage‐grouse (2004–2007). Both species selected nest sites with higher visual obstruction, shrub height, and branching density, although the selection for higher shrub height was stronger for sage‐grouse. Brewer's sparrows selected nest shrubs with higher percentage of living foliage (vigor), and the opposite was shown for sage‐grouse. At the nest site, based on the variables we measured, our results suggest that Brewer's sparrows and sage‐grouse select for similar habitat attributes, with the exception of shrub vigor of the nest shrub. The stronger selection for more vigorous shrubs in Brewer's sparrows may be because they nest in shrubs, rather than on the ground under shrubs (as in sage‐grouse). Most of the conservation objectives for protection of sage‐grouse habitats appear to be beneficial or inconsequential for Brewer's sparrow. Local habitat management for sage‐grouse as a proxy for conservation of other species may be justified if the microhabitat preferences of the species under the umbrella are understood to avoid unintentional negative effects. © 2019 The Wildlife Society.