bluuebunny/crossref_metadata_2025 huggingface dataset:
An examination of climate‐driven flowering‐time shifts at large spatial scales over 153 years in a common weedy annual
Authors: Berg Colette S. , Brown Jason L. , Weber Jennifer J.
Published: November 2019

Premise

Understanding species’ responses to climate change is a critical challenge facing biologists today. Though many species are widespread, few studies of climate‐driven shifts in flowering time have examined large continuous spatial scales for individual species. And even fewer studies have examined these shifts at time scales greater than a few decades.

Methods

We used digitized herbarium specimens and PRISM climate data to produce the spatially and temporally broadest‐scale study of flowering time in a single species to date, spanning the contiguous United States and 153 years (1863–2016) for a widespread weedy annual, Triodanis perfoliata (Campanulaceae). We examined factors driving phenological shifts as well as the roles of geographic and temporal scale in understanding these trends.

Results

Year was a significant factor in both geospatial and climatic analyses, revealing that flowering time has advanced by ~9 days over the past ~150 years. We found that temperature as well as vapor pressure deficit, an understudied climatic parameter associated with evapotranspiration and water stress, were strongly associated with peak flowering. We also examined how sampling at different spatiotemporal scales influences the power to detect flowering‐time shifts, finding that relatively large spatial and temporal scales are ideal for detecting flowering‐time shifts in this widespread species.

Conclusions

Our results emphasize the importance of understanding the interplay of geospatial factors at different scales to examine how species respond to climate change.
No sex differences in the economy of load‐carriage
Authors: Prado‐Nóvoa Olalla , Rodríguez Jesús , Vidal‐Cordasco Marco , Zorrilla‐Revilla Guillermo , Mateos Ana
Published: November 2019

Objectives

Load transport activities are of vital importance to current foragers for daily subsistence tasks; thus, it has been suggested that these practices have transformed physical and behavioral characteristics through human evolution. Together with the procurement targets and strategies, the transportation of resources acquired while foraging is strongly influenced by the sex of the foragers. In hunter‐gatherer societies, women, despite their smaller body size, usually carry heavier burdens than males. In this study, whether those behavioral differences can be explained by a different economy of load‐carriage by sex, irrespective of the body mass of the individuals, is investigated.

Material and methods

The energy expenditure of a sample of 48 volunteers (21 females, 27 males) during a set of locomotion and burden transport trials was monitored. Two indexes were computed to compare the increment in the cost of locomotion relative to the load carried by sex.

Results

The results demonstrate that both males and females, carrying the same relative loads, experience the same increment over the cost of their unloaded locomotion. Therefore, apart from obvious differences in body mass, there is no evidence of a dissimilar economy favoring one sex over the other that would explain the differences in load‐carriage activities observed among current foraging populations.

Conclusions

These outcomes provide new conclusions about the constraints of the behavioral ecology of burden transport activities, and highlight the necessity to reevaluate, from an evolutionary perspective, the ideas about the sexual division of subsistence labor in hunter‐gatherer and agriculturalist populations.
Genetic variability of serotonin pathway associated with schizophrenia onset, progression, and treatment
Authors: Hrovatin Karin , Kunej Tanja , Dolžan Vita
Published: November 2019

Schizophrenia (SZ) onset and treatment outcome have important genetic components, however individual genes do not have strong effects on SZ phenotype. Therefore, it is important to use the pathway‐based approach and study metabolic and signaling pathways, such as dopaminergic and serotonergic. Serotonin pathway has an important role in brain signaling, nevertheless, its role in SZ is not as thoroughly examined as that of dopamine pathway. In this study, we reviewed serotonin pathway genes and genetic variations associated with SZ, including variations at DNA, RNA, and epigenetic level. We obtained 30 serotonin pathway genes from Kyoto encyclopedia of genes and genomes and used these genes for the literature review. We extracted 20 protein coding serotonin pathway genes with genetic variations associated with SZ onset, development, and treatment from 31 research papers. Genes associated with SZ are present on all levels of serotonin pathway: serotonin synthesis, transport, receptor binding, intracellular signaling, and reuptake; however, regulatory genes are poorly researched. We summarized common challenges of genetic association studies and presented some solutions. The analysis of reported serotonin pathway‐SZ associations revealed lack of information about certain serotonin pathway genes potentially associated with SZ. Furthermore, it is becoming clear that interactions among serotonin pathway genes and their regulators may bring further knowledge about their involvement in SZ.
Enhancement of poly(vinyl alcohol) using delaminated layered double hydroxide for the formulation of mechanically strong nanocomposite hydrogel
Authors: Sebri Nor Jannah Mohd , Abdul Latip Ahmad Faiz , Adnan Rohana , Hussin Mohd Hazwan , Kobayashi Takaomi
Published: November 2019

In this work, a new type of nanocomposite hydrogel (NCH) has been prepared by crosslinking poly(vinyl alcohol) (PVA) with delaminated layered double hydroxides (LDHs). The LDH was first intercalated with sodium dodecyl sulfate to facilitate delamination. The intercalated LDH was synthesized via coprecipitation followed by subsequent hydrothermal treatment and delamination in dimethyl sulfoxide. The mechanical properties of PVA–NCH with 0.1 wt % LDH were significantly enhanced. The tensile strength of PVA–NCH containing 0.1 wt % LDH was remarkably increased by threefold, while the value of Young's modulus was recorded to be the highest compared to other ratios. The morphologies and microstructures of the PVA–NCH were further investigated by scanning electron microscopy, transmission electron microscopy (TEM), Fourier transform infrared, and X‐ray diffraction. TEM image showed the LDH was delaminated into single nanosheets. It was demonstrated that the delaminated LDH played an important role in increasing physical crosslinking with PVA macromolecules to form strong hydrogel through hydrogen bonding network.

RESEARCH HIGHLIGHTS

A fast and simple intercalation process of layered double hydroxides (LDHs) with dimethyl sulfoxide to delaminate the organically modified LDH at room temperature.

Delaminated Mg2Al–LDH was used as a nanocrosslinker to produce mechanically strong poly(vinyl alcohol) nanocomposite hydrogel.

Enhanced mechanical properties in terms of tensile strength and modulus of elasticity (Young's modulus) were observed with the addition of 0.1% sodium dodecyl sulfate–LDH. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2020,137, 48637.
Preparation of melamine–formaldehyde resin grafted by (3‐aminopropyl) triethoxysilane for high‐performance hydrophobic materials
Authors: Gao Yuyang , Liu Shaoying , Wang Qingyin , Wang Gongying
Published: November 2019

Aiming at meeting the specific market demands and expanding the downstream application of melamine–formaldehyde (MF) resins, a series of (3‐aminopropyl) triethoxysilane (APTES) grafted MF (MF‐Si) resins were synthesized via an effective method that minimized the hydrolysis of APTES and overcame the polarity discrepancy of APTES with MF resin matrix. The structure of MF‐Si resins was characterized by FTIR spectroscopy, Raman spectroscopy, 1H nuclear magnetic resonance (NMR), and solid state 13C NMR. It was found that APTES moieties in MF‐Si materials afforded increased hydrophobicity, water resistance, and the thermal stability was not affected. With the increasing amount of APTES, the water contact angle of MF‐Si films increased from 70.56 to 105.92°and the surface free energy decreased from 46.8 to 23.5 mN/m. The temperature of maximum weight loss rate (Tdmax) of MF‐Si materials decreased slightly from 371.15 to 353.70 °C and the ultimate residual weight of MF‐Si materials increased from 12.51 to 30.04% at 800 °C under N2. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48664.
RETRACTED: MiR‐93 blocks cell cycle progression and promotes apoptosis in uterine leiomyoma cells by targeting CCND1
Authors: Zhang Donghong , Liu Enling , Tian Wei , Zhang Zhiyong , Wang Liqun , Li Jun
Published: November 2019

Uterine leiomyoma (UL) is the most common type of benign tumor in the women's reproductive system. A number of genes has been found to play an important role in the initiation and progression of UL, including miRNAs. In this study, our results exhibited that miR‐93, a member of mir‐106b‐25 cluster, significantly reduced the cell viability, promoted cell cycle arrest, caused apoptosis, and inhibited migration in UL cells (p < .01). Moreover, our results have provided experimental evidence that miR‐93 regulated the biological functions of UL cells by targeting CCND1.
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

Although 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

In 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

Coordination 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

Ameloblastic 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

Metal–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

Atropisomeric 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

The 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

The 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

Kallikrein‐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

The 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

Nickel 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

Major 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

In 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.
Variability in nomadism: environmental gradients modulate the movement behaviors of dryland ungulates
Authors: Nandintsetseg Dejid , Bracis Chloe , Leimgruber Peter , Kaczensky Petra , Buuveibaatar Bayarbaatar , Lkhagvasuren Badamjav , Chimeddorj Buyanaa , Enkhtuvshin Shiilegdamba , Horning Ned , Ito Takehiko Y. , Olson Kirk , Payne John , Walzer Chris , Shinoda Masato , Stabach Jared , Songer Melissa , Mueller Thomas
Published: November 2019

Studying nomadic animal movement across species and ecosystems is essential for better understanding variability in nomadism. In arid environments, unpredictable changes in water and forage resources are known drivers of nomadic movements. Water resources vary temporally but are often spatially stationary, whereas foraging resources are often both temporally and spatially variable. These differences may lead to different types of nomadic movements: forage‐ vs. water‐driven nomadism. Our study investigates these two different types of nomadism in relation to resource gradients from mesic steppe to xeric desert environments in Mongolia's Gobi‐Steppe Ecosystem. We hypothesized that in the desert, where water is a key resource, animals are more water‐dependent and may show water‐driven nomadism with frequent revisits to spatially fixed resources, while in the steppe, animals are less water‐dependent and may show forage‐driven nomadism, tracking high‐quality foraging patches with infrequent revisits to previously used resources. We utilized GPS movement data from 40 individuals of four ungulate species (Mongolian gazelle, goitered gazelle, saiga antelope, and Asiatic wild ass) in the Gobi‐Steppe Ecosystem. We calculated displacement distances and recursion metrics and subsequently performed a principal component analysis to quantify the variation in movement patterns. The satellite‐derived vegetation greenness served as a proxy for the resource gradient and was associated with variation in movement behaviors described by the first principal component, demonstrating that the variability in movements was closely related to the resource gradient from mesic to xeric habitats. We showed that ungulates in the resource‐rich steppe tended to move long distances with few revisits (forage‐driven nomadism), while ungulates in the resource‐poor desert tended to move shorter distances with more revisits (water‐driven nomadism). Our results suggest that xeric and mesic habitats promote different types of nomadic strategies. These results have important implications for conservation strategies: Forage‐driven nomads primarily require a high degree of landscape‐level permeability, and water‐driven nomads additionally require the protection of ephemeral water bodies and actions to maintain the functional connectivity between them.
The demographic pattern of infection with chronic wasting disease in reindeer at an early epidemic stage
Authors: Mysterud Atle , Madslien Knut , Viljugrein Hildegunn , Vikøren Turid , Andersen Roy , Güere Mariella Evelyn , Benestad Sylvie L. , Hopp Petter , Strand Olav , Ytrehus Bjørnar , Røed Knut H. , Rolandsen Christer M. , Våge Jørn
Published: November 2019

Infection patterns linked to age and sex are crucial to predict the population dynamic effects of diseases in long‐lived species. How such demographic patterns of infection arise is often multifactorial, although the cause is commonly seen as a combination of immune status as well as variation in pathogen exposure. Prion diseases are particularly interesting, as they do not trigger an adaptive immune response; hence, differences in pathogen exposure linked to behavior could be the prime determinant of the pattern of infection. In cervids, the fatal prion disease, chronic wasting disease (CWD), is spreading geographically, with economic and cultural consequences in affected areas in North America, and all infected individuals eventually die from disease‐associated sequelae if they live long enough. Understanding the causes of the demographic pattern of infection with CWD is therefore urgent but is limited by the fact that reported data primarily come from related deer species in North America. The recent (detected 2016) emergence of CWD among wild alpine reindeer (Rangifer tarandus) in Norway with a different social organization, that is, no home range behavior and no matrilineal female groups, offers an opportunity to advance our understanding of how behavior influences the infection patterns. Testing of 1081 males and 1278 females detected 19 animals positive for abnormal prion protein in brain and/or lymphatic tissues. No calves and only one male yearling were infected, with the remaining positives being adults (representing 1.5% of adult males and 0.5% of adult females). We found a strong sex‐biased infection pattern in reindeer (with infection 2.7 times more likely in adult males), which is similar to the results reported in mule deer and white‐tailed deer. The hazard of being detected as positive increased with age in males. There was no close genetic relatedness among positive animals. The results were consistent with the within‐group contact of males being a possible major route of transmission. We discuss the demographic pattern of infection with CWD in view of the lack of stable home range behavior and other key behavioral traits of reindeer relevant to understanding pathogen exposure in general.
Automated frequency and quality‐factor matching method for frequency modulated / rate integrating gyroscope
Authors: Tsukamoto Takashiro , Tanaka Shuji
Published: November 2019

This paper reports an automated tuning method for a frequency modulated / rate integrating gyroscope (FM/RIG). The frequency and quality factor mismatches in a MEMS resonator cause the mode‐coupling, thus degrade the accuracy of the gyroscope. The X‐Y phase difference and amplitude ratio of driving signals are used as the tuning parameters for the mismatch compensation. An automated tuning method based on the relationship between those tuning parameters and mode‐coupling terms were developed. Using the proposed method, the mode‐coupling effect, which comes from the frequency and quality factor mismatch, could be 3 orders of magnitude smaller than the noncompensated one.
Ion pair assisted micro matrix solid phase dispersion extraction of alkaloids from medical plant
Authors: Dong Xin , Yang Juan , Zheng Xiao‐Ting , Chen Yan , Ye Li‐Hong , Wang Bin , Zheng Hui , Cao Jun , Wang Qiu‐Yan , Hu Yu‐Han
Published: November 2019

A novel micro matrix solid phase dispersion method was successfully used for the extraction of quaternary alkaloids in Phellodendri chinensis cortex. The elution of target compounds was accomplished with sodium hexanesulfonate as the eluent solvent. A neutral ion pair was formed between ion‐pairing reagent and positively charged alkaloids in this process, which was beneficial for selectively extraction of polar alkaloids. Several parameters were optimized and the optimal conditions were listed as follows: silica gel as the sorbent, silica to sample mass ratio of 1:1, the grinding time of 1 min. The exhaustive elution of targets was achieved by 200 µL methanol/water (9:1) containing 150 mM sodium hexane sulfonate at pH 4.5. The method validation covered linearity, recovery, precision of intraday and interday, limits of detection, limits of quantitation, and repeatability. This established method was rapid, simple, environmentally friendly, and highly sensitive.
American College of Surgeons National Surgical Quality Improvement Program assessment of risk factors for 30‐day unplanned readmission in patients undergoing head and neck surgery requiring free tissue reconstruction
Authors: Coblens Orly M. , Brant Jason A. , Thomas William W. , Fischer John P. , Newman Jason G. , Cannady Steven B.
Published: November 2019

Background

Unplanned readmissions have become a metric for measuring quality of care. We analyzed the factors associated with 30‐day unplanned readmission (30dUR) following head and neck cancer resections that included free tissue reconstruction (FTR).

Methods

The 2012‐2014 ACS‐National Surgical Quality Improvement Program (NSQIP) data set was queried. Univariate and multivariate logistic regression analyses were performed.

Results

Out of 1114 cases, 121 had a 30dUR. The most common reasons were wound complications, including incisional infections, hematoma, and hemorrhage. A significant independent risk factor for 30dUR included a clean/contaminated wound class (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.20‐4.76). Patients receiving an osseous FTR had lower readmission rates (OR, 0.51; CI, 0.27‐0.91). Discharge destination had no statistical significance.

Conclusions

Based on the NSQIP data set, 10.9% of patients receiving an FTR for head and neck malignancy had a 30dUR. Although large, population‐based data sets have limitations, these results elucidate that these patients are at an increased risk for unplanned readmissions, which can guide patient expectations and discharge planning.
Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease
Authors: Kanwal Fasiha , Kramer Jennifer R. , Li Liang , Dai Jianliang , Natarajan Yamini , Yu Xian , Asch Steven M. , El‐Serag Hashem B.
Published: November 2019

BACKGROUND AND AIMS

Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.

APPROACH AND RESULTS

We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow‐up through December 31, 2015. We performed competing risk‐adjusted cause‐specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow‐up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8‐fold higher risk of progression to cirrhosis/HCC (hazard ratio [HR] = 1.8, 95% confidence interval [CI] = 1.59‐2.06); the risk was 2.6‐fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3‐2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.

CONCLUSIONS

Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.
Hippocampal spike‐time correlations and place field overlaps during open field foraging
Authors: Monsalve‐Mercado Mauro M. , Roudi Yasser
Published: November 2019

Phase precessing place cells encode spatial information on fine timescales via the timing of their spikes. This phase code has been extensively studied on linear tracks and for short runs in the open field. However, less is known about the phase code on unconstrained trajectories lasting tens of minutes, typical of open field foraging. In previous work (Monsalve‐Mercado and Leibold, Physical Review Letters, 119, 38101 (2017)), an analytic expression was derived for the spike‐time cross‐correlation between phase precessing place cells during natural foraging in the open field. This expression makes two predictions on how this phase code differs from the linear track case: cross‐correlations are symmetric with respect to time, and they represent the distance between pairs of place fields in that the theta‐filtered cross‐correlations around zero time lag are positive for cells with nearby fields while they are negative for those with fields further apart. Here we analyze several available open field recordings and show that these predictions hold for pairs of CA1 place cells. We also show that the relationship remains during remapping in CA1, and it is also present in place cells in area CA3. For CA1 place cells of Fmr1‐null mice, which exhibit normal place fields but somewhat weaker temporal coordination with respect to theta compared to wild type, the cross‐correlations still remain symmetric but the relationship to place field overlap is largely lost. The relationship discussed here describes how spatial information is communicated by place cells to downstream areas in a finer theta‐timescale, relevant for learning and memory formation in behavioral tasks lasting tens of minutes in the open field.
Disease characteristics of diffuse large B‐cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience
Authors: Gaut Daria , Romero Tahmineh , Oveisi David , Howell Grant , Schiller Gary
Published: November 2019

While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk‐stratification of diffuse large B‐cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high‐dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010‐2015. After a median follow‐up time of 4.6 years (interquartile range [IQR] 2.2‐8.1), the likelihood of 5‐year progression‐free survival (PFS) was 62.2% (95% CI, 53.4%‐72.4%) and the likelihood of 5‐year overall survival (OS) was 68.9% (95% CI, 60.7%‐78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age‐adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post‐ASCT (P = .207 for PFS, P = .073 for OS).
Romidepsin treatment for relapsed or refractory peripheral and cutaneous T‐cell lymphoma: Real‐life data from a national multicenter observational study
Authors: Shimony Shai , Horowitz Netanel , Ribakovsky Elena , Rozovski Uri , Avigdor Abraham , Zloto Keren , Berger Tamar , Avivi Irit , Perry Chava , Abadi Uri , Raanani Pia , Gafter‐Gvili Anat , Gurion Ronit
Published: November 2019

Romidepsin is a class I selective histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for relapsed/refractory (R/R) cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphoma (PTCL), treated with at least one prior systemic therapy. Currently, there is paucity of real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. This national, multicenter study presents real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. Patients diagnosed and treated with romidepsin for R/R CTCL or PTCL between 2013 and 2018 were retrospectively reviewed. Outcomes included overall survival (OS), event‐free survival (EFS), overall response rate (ORR), complete response (CR), and adverse events. Fifty‐three patients with R/R PTCL (n = 42) or CTCL (n = 11) were included. Among CTCL patients, median OS was not reached, ORR was 25%, and none achieved CR. Among PTCL patients, median OS was 7.1 months, EFS was 1.9 months, ORR rate was 33%, and 12.5% achieved CR. In a univariate analysis, predictors for longer EFS include any response to therapy, number of previous lines, and PTCL subclass (with better results for angioimmunobalstic T‐cell lymphoma). In a univariate and multivariate analysis for OS, treatment response was the only factor predicting OS (OR 4.48; CI 95%, 1.57‐12.79; P = .005). Most grade 3 and 4 adverse events were hematological (35%). Infections were reported in 34% of patients. This real‐life experience with romidepsin confirms the results of the pivotal phase II trials. PTCL subtype and the number of previous lines of therapy have an impact on EFS. In addition, patients who had good response to romidepsin benefited most in terms of both EFS and OS. Efforts should be done to identify those patients.