bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infundibular sperm storage and uterine muscular twisting in the Amazonian lancehead, Bothrops atrox
Authors: Silva Karina M. P. , Barros Verônica A. , Rojas Claudio A. , Almeida‐Santos Selma M. 
Published: November 2019

AbstractAlthough knowledge about the reproduction of snakes of the genus Bothrops has increased recently, many questions remain regarding sperm storage by these neotropical pitvipers. The relationship between two known sperm storage sites—the nonglandular uterus and the infundibulum—has yet to be detailed for Bothrops. In addition, the formation of uterine muscular twisting (UMT) and its function in sperm storage in the nonglandular uterus have been questioned. This article presents data on both sperm storage sites (posterior infundibulum and nonglandular uterus) in the Amazonian lancehead, Bothrops atrox, aiming to address the role of UMT in bothropoid reproduction considering female reproductive stages, timing of sperm storage, and morphology and histochemistry of sperm receptacles. The oviduct of B. atrox is composed of the infundibulum (anterior and posterior), the glandular uterus, the nonglandular uterus and the pouch. Sperm storage occurs in the posterior infundibulum and nonglandular uterus in vitellogenic females. In the posterior infundibulum sperm is stored in receptacles, while in the nonglandular uterus it is stored in crypts in the UMT of vitellogenic females. Both sperm storage sites possess granules testing positive for neutral mucopolysaccharides in the presence of spermatozoa, possibly favoring the conditions for spermatozoa surveillance during sperm storage in the reproductive tract.
The use of Thiel embalmed human cadavers for retrograde injection and visualization of the lymphatic system
Authors: Stouthandel Michael E. J. , Veldeman Liv , Achten Eric , Van Hoof Tom 
Published: November 2019

AbstractIn order to provide an alternative for fresh frozen specimens to map the lymphatic system, the possibility of using Thiel embalmed specimens for this purpose was explored. The thoracic duct was used to investigate if retrograde injection of contrast agent was possible in Thiel embalmed specimens and to verify up to which diameter lymphatic vessels could be reconstructed and rendered in 3D, after CT scanning. 3D renderings were used for digital diameter measurement, to determine the smallest lymphatic diameter that could still be visualized on CT. Finally, the contrast agent concentration was adapted based on the findings during image reconstruction and 3D rendering. All Thiel embalmed specimens proved suitable for retrograde injection of contrast agent into the thoracic duct and all 3D renderings perfectly overlapped with the dissection pictures. The smallest diameter of contrast filled lymphatics that could be reconstructed and rendered in 3D was 0.23 mm. Increasing the concentration of barium sulfate from 10 to 50% reduced the postprocessing time needed to render a “clean” 3D structure, following automatic segmentation based on grey values, by 95%. The authors would recommend the use of Thiel embalmed specimens for mapping the lymphatic system, as these specimens do not show the rapid putrefaction that occurs in fresh frozen specimens, thus greatly facilitating experimental planning.
Proton‐Conducting Hydrogen‐Bonded 3D Frameworks of Imidazo‐Pyridine‐Based Coordination Complexes Containing Naphthalene Disulfonates in Rhomboid Channels
Authors: Garai Abhijit , Kumar Anaparthi Ganesh , Banerjee Susanta , Biradha Kumar 
Published: November 2019

AbstractCoordination complexes of an olefinic molecule (PIP) containing pyridine and imidazopyridine moieties with ZnII/NiII metal salts were shown to exhibit appreciable proton conductivity. These complexes form 3D‐hydrogen bonded frameworks containing rhomboidal channels that are occupied by uncoordinated 1,5‐naphthalenedisulfonate (NDS). The extensive hydrogen bonding between the frameworks and NDS resulted in thermally stable and water‐insoluble materials. Irrespective of the metal atom present, both complexes exhibited moderate to high proton conduction in the range of 10−5 to 0.5×10−3 S cm−1 depending on the temperature and humidity levels.
Hypoxia‐induced HIF‐1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF‐β‐dependent EMT
Authors: Yoshimoto Shohei , Tanaka Fumie , Morita Hiromitsu , Hiraki Akimitsu , Hashimoto Shuichi 
Published: November 2019

AbstractAmeloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia‐inducible factor 1 alpha subunit (HIF1A) and zinc finger E‐box‐binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial‐mesenchymal transition (EMT). In addition, expressions of HIF‐1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM‐1, hypoxia condition upregulated the expression of transforming growth factor‐β (TGF‐β) and induced EMT. Furthermore, the hypoxia‐induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia‐induced HIF‐1α and ZEB1 were critical for the malignant transformation of AB via TGF‐β‐dependent EMT. Then, both HIF‐1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.
Nanoweb Surface‐Mounted Metal–Organic Framework Films with Tunable Amounts of Acid Sites as Tailored Catalysts
Authors: Mandemaker Laurens D. B. , Rivera‐Torrente Miguel , Delen Guusje , Hofmann Jan P. , Lorenz Matthias , Belianinov Alex , Weckhuysen Bert M. 
Published: November 2019

AbstractMetal–organic frameworks (MOFs) are a promising class of materials for many applications, due to their high chemical tunability and superb porosity. By growing MOFs as (thin‐)films, additional properties and potential applications become available. Here, copper (II) 1,3,5‐benzenetricarboxylate (Cu‐BTC) metal–organic framework (MOF) thin‐films are reported, which were synthesized by spin‐coating, resulting in “nanowebs”, that is, fiber‐like structures. These surface‐mounted MOFs (SURMOFs) were studied by using photoinduced force microscopy (PiFM) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). The optimal concentration of precursors (10 mm) was determined that resulted in chemically homogeneous, pure nanowebs. Furthermore, the morphology and (un)coordinated Cu sites in the web were tuned by varying the rotation speed of the spin‐coating process. X‐ray diffraction (XRD) analysis showed that rotation speeds ≥2000 rpm (with precursors in a water/ethanol solution) generate the catena‐triaqua‐μ‐(1,3,5‐benzenetricarboxylate)‐copper(II), or Cu(BTC)(H2O)3 coordination polymer. X‐ray photoelectron spectroscopy (XPS) highlighted the strong decrease in number of (defective) Cu+ sites, as the nanowebs mainly consist of coordinated Cu2+ Lewis acid sites (LAS) and organic linker–linker, for example, hydrogen‐bonding, interactions. Finally, the Lewis‐acidic character of the Cu sites is illustrated by testing the films as catalysts in the isomerization of α‐pinene oxide. The higher number of LAS (≥3000 rpm), result in higher campholenic aldehyde selectivity reaching up to 87.7 %. Furthermore, the strength of a combined micro‐ and spectroscopic approach in understanding the nature of MOF thin‐films in a spatially resolved manner is highlighted.
Shortcuts for Electron‐Transfer through the Secondary Structure of Helical Oligo‐1,2‐Naphthylenes
Authors: Castrogiovanni Alessandro , Herr Patrick , Larsen Christopher B. , Guo Xingwei , Sparr Christof , Wenger Oliver S. 
Published: November 2019

AbstractAtropisomeric 1,2‐naphthylene scaffolds provide access to donor–acceptor compounds with helical oligomer‐based bridges, and transient absorption studies revealed a highly unusual dependence of the electron‐transfer rate on oligomer length, which is due to their well‐defined secondary structure. Close noncovalent intramolecular contacts enable shortcuts for electron transfer that would otherwise have to occur over longer distances along covalent pathways, reminiscent of the behavior seen for certain proteins. The simplistic picture of tube‐like electron transfer can describe this superposition of different pathways including both the covalent helical backbone, as well as noncovalent contacts, contrasting the wire‐like behavior reported many times before for more conventional molecular bridges. The exquisite control over the molecular architecture, achievable with the configurationally stable and topologically defined 1,2‐naphthylene‐based scaffolds, is of key importance for the tube‐like electron transfer behavior. Our insights are relevant for the emerging field of multidimensional electron transfer and for possible future applications in molecular electronics.
Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
Authors: Gozzi Marta , Murganic Blagoje , Drača Dijana , Popp John , Coburger Peter , Maksimović‐Ivanić Danijela , Mijatović Sanja , Hey‐Hawkins Evamarie 
Published: November 2019

AbstractThe role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐(η6‐p‐cymene)‐1‐(quinolin‐8‐yl‐acetate)‐3,1,2‐RuC2B9H10] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor‐promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy‐prone glioblastomas.
Cell‐Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit
Authors: Stubba Daniel , Bensinger Dennis , Steinbacher Janika , Proskurjakov Lilia , Salcedo Gómez Álvaro , Schmidt Uwe , Roth Stefan , Schmitz Katja , Schmidt Boris 
Published: November 2019

AbstractThe ubiquitin‐proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly‐reversibly binding boronates, optimization of novel covalent‐reversibly binding warheads remains largely unattended. We previously reported α‐ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy‐substituted α‐ketoamides combining the structure‐activity relationships from the primed and the non‐primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3‐phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time‐dependent inhibition of cellular substrate conversion. Furthermore, the α‐ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.
Synthesis and Structure‐Activity Relationships of N‐(4‐Benzamidino)‐Oxazolidinones: Potent and Selective Inhibitors of Kallikrein‐Related Peptidase 6
Authors: De Vita Elena , Smits Niels , van den Hurk Helma , Beck Elizabeth M. , Hewitt Joanne , Baillie Gemma , Russell Emily , Pannifer Andrew , Hamon Véronique , Morrison Angus , McElroy Stuart P. , Jones Philip , Ignatenko Natalia A. , Gunkel Nikolas , Miller Aubry K. 
Published: November 2019

AbstractKallikrein‐related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high‐throughput screen within the European Lead Factory program. Structure‐guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)‐3‐(4‐carbamimidoylphenyl)‐N‐((S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) and 34 ((5R)‐3‐(6‐carbamimidoylpyridin‐3‐yl)‐N‐((1S)‐1‐(naphthalen‐1‐yl)propyl)‐2‐oxooxazolidine‐5‐carboxamide) have single‐digit nanomolar potency against KLK6, with over 25‐fold and 100‐fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32, effectively reduces KLK6‐dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.
Distribution of tyrosine‐hydroxylase‐immunoreactive neurons in the hypothalamus of tree shrews
Authors: Huang Zhao‐Huan , Ni Rong‐Jun , Luo Peng‐Hao , Zhou Jiang‐Ning 
Published: November 2019

AbstractThe tree shrew (Tupaia belangeri chinensis) is the closest living relative of primates. Yet, little is known about the anatomical distribution of tyrosine hydroxylase (TH)‐immunoreactive (ir) structures in the hypothalamus of the tree shrew. Here, we provide the first detailed description of the distribution of TH‐ir neurons in the hypothalamus of tree shrews via immunohistochemical techniques. TH‐ir neurons were widely distributed throughout the hypothalamus of tree shrew. The majority of hypothalamic TH‐ir neurons were found in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), as was also observed in the human hypothalamus. In contrast, rare TH‐ir neurons were localized in the PVN and SON of rats. Vasopressin (AVP) colocalized with TH‐ir neurons in the PVN and SON in a large number of neurons, but oxytocin and corticotropin‐releasing hormone did not colocalize with TH. In addition, colocalization of TH with AVP was also observed in the other hypothalamic regions. Moreover, TH‐ir neurons in the PVN and SON of tree shrews expressed other dopaminergic markers (aromatic l‐amino acid decarboxylase and vesicular monoamine transporter, Type 2), further supporting that TH‐ir neurons in the PVN and SON were catecholaminergic. These findings provide a detailed description of TH‐ir neurons in the hypothalamus of tree shrews and demonstrate species differences in the distribution of this enzyme, providing a neurobiological basis for the participation of TH‐ir neurons in the regulation of various hypothalamic functions.
Self‐Supported, Sulfate‐Functionalized Nickel Hydroxide Nanoplates with Enhanced Wettability and Conductivity for Use in High‐Performance Supercapacitors
Authors: Gao Miao , Guo Zhi‐Yan , Wang Xing‐Yi , Li Wen‐Wei 
Published: November 2019

AbstractNickel hydroxide is promising for use in supercapacitor applications because of its low cost and tunable electrochemical properties, but its performance is usually restricted by insufficient conductivity and surface reactivity. In this work, sulfate‐functionalized Ni(OH)2 (SNO) nanoplates were grown in situ on nickel foam (NF) by a green and facile one‐step hydrothermal treatment of NF without the need for an external Ni source or surfactant addition. The resulting material showed a 9.3 times higher areal capacity and 1.8 times higher rate capability than the sulfate‐free control and retained 81.3 % capacity after 5000 cycles. If used as the positive electrode in a hybrid supercapacitor, the SNO/NF//activated carbon system achieved >95 % Coulombic efficiency, a maximum energy density of 3.59 Wh m−2, and a maximum power density of 44.63 Wm−2, which surpass those achievable by most known Ni‐based supercapacitors. Detailed material characterization and DFT calculations revealed that the introduction of sulfate expanded the layer spacing of Ni(OH)2 and improved the electrical conductivity and wettability to favor more efficient electrolyte diffusion, charge transfer, and reactant adsorption. The high loading of reactive components and inherited porous structure also contributed to the superior capacitive performance of the SNO/NF electrodes. Therefore, SNO/NF holds great potential for commercialized supercapacitor applications.
Leukocyte telomere length is reduced in patients with major depressive disorder
Authors: Pisanu Claudia , Tsermpini Evangelia Eirini , Skokou Maria , Kordou Zoe , Gourzis Philippos , Assimakopoulos Konstantinos , Congiu Donatella , Meloni Anna , Balasopoulos Dimitrios , Patrinos George P. , Squassina Alessio 
Published: November 2019

AbstractMajor depressive disorder (MDD) is a chronic, severe psychiatric illness with an incidence of 3% worldwide. MDD patients have a significantly impaired quality of life and reduced life expectancy compared to unaffected individuals, the latter being largely accounted for by an increased incidence of suicide and cardiovascular disorders. The premature mortality observed in MDD has been considered a signature of accelerated aging, a hypothesis supported by data showing altered functioning and morphology of several brain regions that are typically present in the aging population. Telomere shortening is a hallmark of cellular aging, and as such several studies explored the involvement of disrupted telomere dynamics in MDD, reporting contrasting findings. In the current study, we measured leukocyte telomere length (LTL) in a sample of 54 MDD patients and 47 non‐psychiatric controls characterized for response to antidepressant treatment. After correcting for age, sex, and body mass index, we showed significantly reduced LTL in affected individuals compared to controls (beta = −.22, p = .02). There was no difference in LTL between treatment resistant or responsive MDD patients. Moreover, we observed no correlation between lifetime exposure to antidepressants and LTL. Our study showed that MDD patients have shorter telomeres compared to controls, supporting the hypothesis of accelerated aging in this disorder. However, LTL seemed not to be influenced by antidepressant treatment or to correlate with clinical response to these antidepressants. Further investigations in larger samples and possibly with longitudinal design are warranted to elucidate the role of altered telomere dynamics in MDD.
Potential for post‐fire recovery of Greater Sage‐grouse habitat
Authors: Riginos Corinna , Monaco Thomas A. , Veblen Kari E. , Gunnell Kevin , Thacker Eric , Dahlgren David , Messmer Terry 
Published: November 2019

AbstractIn the western United States, fire has become a significant concern in the management of big sagebrush (Artemisia tridentata Nutt.) ecosystems. This is due to large‐scale increases in cover of the fire‐prone invasive annual cheatgrass (Bromus tectorum L.) and, concurrently, concerns about declining quantity and quality of habitat for Greater Sage‐grouse (Centrocercus urophasianus). The prevailing paradigm is that fire results in a loss of sage‐grouse habitat on timescales relevant to conservation planning (i.e., 1–20 yr), since sagebrush cover can take many more years to recover post‐fire. However, fire can have effects that improve sage‐grouse habitat, including stimulating perennial grass and forb production. The conditions under which fire results in the permanent loss or enhancement of sage‐grouse habitat are not well understood. We used long‐term data from the Utah Division of Wildlife Resources Range Trend Project to assess short‐term (1–4 yr post‐treatment) and long‐term (6–10 yr post‐treatment) effects of fire on vegetation cover at 16 sites relative to sage‐grouse habitat vegetation guidelines. Sagebrush cover remained low post‐fire at sites considered historically unsuitable for sage‐grouse (<10% initial sagebrush cover). In contrast, at sites that had higher (>10%) pre‐fire sagebrush cover, sagebrush cover decreased to <10% in the short‐term post‐fire, but by 6–10 yr after fire, most of these sites exhibited a recovering trajectory and two sites had recovered to >10% cover. Post‐fire sagebrush cover was positively related to elevation. Across all sites, perennial grasses and forbs increased in cover to approximately meet the habitat vegetation guidelines for sage‐grouse. Cheatgrass cover did not change in response to fire, and increased perennial grass cover appears to have played an important role in suppressing cheatgrass. Our results indicate that, while fire poses a potential risk for sage‐grouse habitat loss and degradation, burned sites do not necessarily need to be considered permanently altered, especially if they are located at higher elevation, have high sagebrush cover pre‐fire, and are reseeded with perennial grasses and forbs post‐fire. However, our results confirm that fire at more degraded sites, for example, those with <10% sagebrush cover, can result in cheatgrass‐dominated landscapes and sagebrush loss at these sites should be avoided.