bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducibility and repeatability of optical coherence tomography imaging of the optic nerve head in normal beagle eyes
Authors: Bemis Alexandra M. , Pirie Christopher G. , LoPinto Alexander J. , Maranda Louise
Published: February 2017

Objective

To assess the reproducibility and repeatability of an optical coherence tomography (OCT) device for imaging the optic nerve region of normal canines.

Animals studied

Twelve clinically healthy beagles.

Procedures

All animals were anesthetized, and an OCT device was used to image the optic disk region. Total disk area and retinal nerve fiber layer (NFL) thickness in eight segments were obtained from each image. Images were collected by two operators in succession and each operator took five scans, repositioning the device between measurements. B‐scan segmentations and disk outlines were subsequently redrawn to obtain manual measurements, allowing for comparisons between automated measurements.

Results

Operator 1 had a mean (±SD) NFL thickness (automatic) and disk area of 73.38 ± 7.41 μm and 3.69 ± 0.52 mm², while operator 2 had 74.27 ± 7.33 μm and 3.67 ± 0.51 mm², respectively. With manual corrections, operator 1 had a NFL thickness and disk area of 86.19 ± 8.26 μm and 3.74 ± 0.68 mm², while operator 2 had 86.85 ± 6.91 μm and 3.81 ± 0.56 mm², respectively. Operators did not obtain significantly different values for any region. Intraclass correlation ranged from 0.33 to 0.97 (average 0.78). Coefficient of variation ranged from 8.8 to 36.2%.

Conclusion

The OCT device demonstrated high inter‐rater reliability. Intrarater reliability was strong for disk area and total NFL; however, the segmental regions demonstrated a higher degree of variability. Manual and automated measurements were significantly different for total NFL and some segmental regions; therefore, users should consistently use one method for longitudinal studies.
Canine acute cervical myelopathy: Hydrated nucleus pulposus extrusion or intraspinal discal cysts?
Authors: Falzone Cristian
Published: February 2017

Objective

To differentiate between hydrated nucleus pulposus extrusion and ventral intraspinal discal cysts in dogs.

Study design

Prospective case series.

Animals

Twenty dogs with acute onset of cervical myelopathy due to hydrated nucleus pulposus extrusion or ventral intraspinal discal cysts.

Methods

Clinical and magnetic resonance (MR) imaging findings, outcome after surgical treatment, cytologic and histologic findings of compressive material were taken into account. Comparisons and considerations were done between findings reported herein and what was previously described as suspected hydrated nucleus pulposus extrusion and intraspinal cysts.

Results

All dogs were presented with acute onset of cervical myelopathy. MR imaging showed compressive cervical myelopathy at C2‐C3 (n = 1), C3‐C4 (n = 6), C4‐C5 (n = 8), and C5‐C6 (n = 5) intervertebral disc spaces, due to extradural material suggestive of either partially hydrated nucleus pulposus extrusion or intraspinal discal cyst, with T2 hyperintense and T1 iso‐hypointense signal and variable contrast enhancement after gadolinium injection. All dogs were treated surgically by ventral slot (n = 15) or dorsolateral hemilaminectomy (n = 5). All dogs had a favorable outcome and regained a normal gait. The extradural material collected at surgery varied from liquid to more obvious gelatinous material. Cytologic or histologic examination of the material revealed similar findings for all dogs, compatible with partially degenerated nucleus pulposus.

Conclusions

Dogs with acute onset of compressive cervical myelopathy due to extradural material resembling human intraspinal cysts on MR images are most likely to have extrusion of partially degenerated nucleus pulposus and should be treated accordingly.
A Comparison of the Roughness Regimes in Hydrodynamic Lubrication
Authors: Fabricius John , Tsandzana Afonso , Perez-Rafols Francesc , Wall Peter
Published: February 2017

This work relates to previous studies concerning the asymptotic behavior of Stokes flow in a narrow gap between two surfaces in relative motion. It is assumed that one of the surfaces is rough, with small roughness wavelength μ, so that the film thickness h becomes rapidly oscillating. Depending on the limit of the ratio h/μ, denoted as λ, three different lubrication regimes exist: Reynolds roughness (λ = 0), Stokes roughness (0 < λ < ∞), and high-frequency roughness (λ = ∞). In each regime, the pressure field is governed by a generalized Reynolds equation, whose coefficients (so-called flow factors) depend on λ. To investigate the accuracy and applicability of the limit regimes, we compute the Stokes flow factors for various roughness patterns by varying the parameter λ. The results show that there are realistic surface textures for which the Reynolds roughness is not accurate and the Stokes roughness must be used instead.
Hepatitis B Virus-Encoded MicroRNA Controls Viral Replication
Authors: Yang Xi , Li Hongfeng , Sun Huahui , Fan Hongxia , Hu Yaqi , Liu Min , Li Xin , Tang Hua
Published: February 2017

MicroRNAs (miRNAs) are a class of small, single-stranded, noncoding, functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA virus with virions and subviral forms of particles that lack a core. It was not known whether HBV encodes miRNAs. Here, we identified an HBV-encoded miRNA (called HBV-miR-3) by deep sequencing and Northern blotting. HBV-miR-3 is located at nucleotides (nt) 373 to 393 of the HBV genome and was generated from 3.5-kb, 2.4-kb, and 2.1-kb HBV in a classic miRNA biogenesis (Drosha-Dicer-dependent) manner. HBV-miR-3 was highly expressed in hepatoma cell lines with an integrated HBV genome and HBV
+
hepatoma tumors. In patients with HBV infection, HBV-miR-3 was released into the circulation by exosomes and HBV virions, and HBV-miR-3 expression had a positive correlation with HBV titers in the sera of patients in the acute phase of HBV infection. More interestingly, we found that HBV-miR-3 represses HBsAg, HBeAg, and replication of HBV. HBV-miR-3 targets the unique site of the HBV 3.5-kb transcript to specifically reduce HBc protein expression, levels of pregenomic RNA (pgRNA), and HBV replication intermediate (HBV-RI) generation but does not affect the HBV DNA polymerase level, thus suppressing HBV virion production (replication). This may explain the low levels of HBV virion generation with abundant subviral particles lacking core during HBV replication, which may contribute to the development of persistent infection in patients. Taken together, our findings shed light on novel mechanisms by which HBV-encoded miRNA controls the process of self-replication by regulating HBV transcript during infection.

IMPORTANCE
Hepatitis B is a liver infection caused by the hepatitis B virus (HBV) that can become a long-term, chronic infection and lead to cirrhosis or liver cancer. HBV is a small DNA virus that belongs to the hepadnavirus family, with virions and subviral forms of particles that lack a core. MicroRNA (miRNA), a small (∼22-nt) noncoding RNA, was recently found to be an important regulator of gene expression. We found that HBV encodes miRNA (HBV-miR-3). More importantly, we revealed that HBV-miR-3 targets its transcripts to attenuate HBV replication. This may contribute to explaining how HBV infection leads to mild damage in liver cells and the subsequent establishment/maintenance of persistent infection. Our findings highlight a mechanism by which HBV-encoded miRNA controls the process of self-replication by regulating the virus itself during infection and might provide new biomarkers for diagnosis and treatment of hepatitis B.
Computational Prediction of the Heterodimeric and Higher-Order Structure of gpE1/gpE2 Envelope Glycoproteins Encoded by Hepatitis C Virus
Authors: Freedman Holly , Logan Michael R. , Hockman Darren , Koehler Leman Julia , Law John Lok Man , Houghton Michael
Published: February 2017

Despite the recent success of newly developed direct-acting antivirals against hepatitis C, the disease continues to be a global health threat due to the lack of diagnosis of most carriers and the high cost of treatment. The heterodimer formed by glycoproteins E1 and E2 within the hepatitis C virus (HCV) lipid envelope is a potential vaccine candidate and antiviral target. While the structure of E1/E2 has not yet been resolved, partial crystal structures of the E1 and E2 ectodomains have been determined. The unresolved parts of the structure are within the realm of what can be modeled with current computational modeling tools. Furthermore, a variety of additional experimental data is available to support computational predictions of E1/E2 structure, such as data from antibody binding studies, cryo-electron microscopy (cryo-EM), mutational analyses, peptide binding analysis, linker-scanning mutagenesis, and nuclear magnetic resonance (NMR) studies. In accordance with these rich experimental data, we have built an
in silico
model of the full-length E1/E2 heterodimer. Our model supports that E1/E2 assembles into a trimer, which was previously suggested from a study by Falson and coworkers (P. Falson, B. Bartosch, K. Alsaleh, B. A. Tews, A. Loquet, Y. Ciczora, L. Riva, C. Montigny, C. Montpellier, G. Duverlie, E. I. Pecheur, M. le Maire, F. L. Cosset, J. Dubuisson, and F. Penin, J. Virol. 89:10333–10346, 2015,
https://doi.org/10.1128/JVI.00991-15
). Size exclusion chromatography and Western blotting data obtained by using purified recombinant E1/E2 support our hypothesis. Our model suggests that during virus assembly, the trimer of E1/E2 may be further assembled into a pentamer, with 12 pentamers comprising a single HCV virion. We anticipate that this new model will provide a useful framework for HCV envelope structure and the development of antiviral strategies.

IMPORTANCE
One hundred fifty million people have been estimated to be infected with hepatitis C virus, and many more are at risk for infection. A better understanding of the structure of the HCV envelope, which is responsible for attachment and fusion, could aid in the development of a vaccine and/or new treatments for this disease. We draw upon computational techniques to predict a full-length model of the E1/E2 heterodimer based on the partial crystal structures of the envelope glycoproteins E1 and E2. E1/E2 has been widely studied experimentally, and this provides valuable data, which has assisted us in our modeling. Our proposed structure is used to suggest the organization of the HCV envelope. We also present new experimental data from size exclusion chromatography that support our computational prediction of a trimeric oligomeric state of E1/E2.
Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats
Authors: Rizo-Roca David , Ríos-Kristjánsson Juan Gabriel , Núñez-Espinosa Cristian , Santos-Alves Estela , Magalhães José , Ascensão António , Pagès Teresa , Viscor Ginés , Torrella Joan Ramon
Published: February 2017

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption, and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD) in trained rats using 2 recovery protocols based on: (i) intermittent hypobaric hypoxia (IHH) and (ii) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress, and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7, and 14 days after an EEIMD protocol. The following treatments were applied 1 day after the EEIMD: passive normobaric recovery (PNR), 4 h daily exposure to passive IHH at 4000 m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity was reduced at 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1α and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1, and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser36)/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.
Strong decays of 2+ charm and charm-strange mesons
Authors: Zhang Si-Cheng , Wang Tianhong , Jiang Yue , Li Qiang , Wang Guo-Li
Published: February 2017

In this paper, we calculate the strong decays of [Formula: see text] heavy-light states, namely, the charmed [Formula: see text] meson and the charm-strange [Formula: see text] meson. The method we adopt is the reduction formula, PCAC relation and low energy theorem, following which, the transition amplitudes are calculated. The wave functions of the heavy mesons involved are achieved by solving the instantaneous Bethe–Salpeter equation. As the OZI-allowed two-body strong decays give the dominant contribution, they can be used to estimate the total widths of mesons. Our results are: [Formula: see text] and [Formula: see text]. The ratios of branching ratios of two main channels are [Formula: see text] and [Formula: see text], respectively.
A charged anisotropic well-behaved Adler–Finch–Skea solution satisfying Karmarkar condition
Authors: Bhar Piyali , Singh Ksh. Newton , Rahaman Farook , Pant Neeraj , Banerjee Sumita
Published: February 2017

In the present paper, we discover a new well-behaved charged anisotropic solution of Einstein–Maxwell’s field equations. We ansatz the metric potential [Formula: see text] of the form given by Maurya et al. (Eur. Phys. J. C 76(12) (2016) 693) with [Formula: see text]. In their paper, it is mentioned that for [Formula: see text], the solution is not well-behaved for neutral configuration as the speed of sound is nondecreasing radially outward. However, the solution can represent a physically possible configuration with the inclusion of some net electric charge, i.e. the solution can become a well-behaved solution with decreasing sound speed radially outward for a charged configuration. Due to the inclusion of electric charge, the solution leads to a very stiff equation-of-state (EoS) with the velocity of sound at the center [Formula: see text] [Formula: see text] and the compactness parameter [Formula: see text] is close to the Buchdahl limit 0.889. This stiff EoS support a compact star configuration of mass [Formula: see text] and radius of 10.1[Formula: see text]km.
Exact saturation in simple and NIP theories
Authors: Kaplan Itay , Shelah Saharon , Simon Pierre
Published: February 2017

A theory [Formula: see text] is said to have exact saturation at a singular cardinal [Formula: see text] if it has a [Formula: see text]-saturated model which is not [Formula: see text]-saturated. We show, under some set-theoretic assumptions, that any simple theory has exact saturation. Also, an NIP theory has exact saturation if and only if it is not distal. This gives a new characterization of distality.
Reductive nitrosylation of ferric carboxymethylated-cytochromec
Authors: Ascenzi Paolo , Ciaccio Chiara , De Simone Giovanna , Santucci Roberto , Coletta Massimo
Published: February 2017

Horse heart carboxymethylated-cyt[Formula: see text] (CM-cyt[Formula: see text] displays myoglobin-like properties due to the cleavage of the heme-Fe-Met80 axial bond. Here, reductive nitrosylation of CM-cyt[Formula: see text](III) between pH 8.5 and 9.5, at [Formula: see text] 20.0 C, is reported. Under anaerobic conditions, the addition of NO to CM-cyt[Formula: see text](III) leads to the transient formation of CM-cyt[Formula: see text](III)-NO in equilibrium with CM-cyt[Formula: see text](II)-NO[Formula: see text]. In turn, CM-cyt[Formula: see text](II)-NO[Formula: see text] is converted to CM-cyt[Formula: see text](II) by OH[Formula: see text]-based catalysis. Then, CM-cyt[Formula: see text](II) binds NO very rapidly leading to CM-cyt[Formula: see text](II)-NO. Kinetics of NO binding to CM-cyt[Formula: see text](III) is independent of the ligand concentration, [Formula: see text] values ranging between 3.6 ± 0.4 s[Formula: see text] and 7.1 ± 0.7 s[Formula: see text]. This indicates that the formation of the CM-cytc(III)-NO complex is rate-limited by the cleavage of the weak heme-Fe(III) distal bond (likely Lys79). The conversion of CM-cyt[Formula: see text](III)-NO to CM-cyt[Formula: see text](II)-NO is rate-limited by the OH[Formula: see text]-mediated reduction of CM-cyt[Formula: see text](II)-NO[Formula: see text] ([Formula: see text] (1.2 ± 0.1) × 103M[Formula: see text].s[Formula: see text]. Lastly, the very fast nitrosylation of CM-cyt[Formula: see text](II) takes place, values of [Formula: see text] ranging between[Formula: see text]5.3 × 106M[Formula: see text].s[Formula: see text] and 1.4 × 107M[Formula: see text].s[Formula: see text]. These results indicate that CM-cyt[Formula: see text] behaves as the cardiolipin-cyt[Formula: see text] complex highlighting the role of the sixth axial ligand of the heme-Fe atom in the modulation of the metal-based reactivity.
Chapter 12 Inner-arc volcanism: Barren and Narcondam islands
Authors: Bandopadhyay P. C.
Published: February 2017

Barren and Narcondam are active and now extinct, respectively, volcanic islands that belong to the inner-arc volcanic belt that extends from Java in the east to Burma in the north. Modern eruptions on Barren Island have been exclusively scoria cone-forming Strombolian-type activity in contrast to historic (1787–32) eruptions that witnessed a switch from scoria cone activity to abundant basaltic lava flows. Prehistoric (late Pleistocene) eruptions were alternating effusive and explosive events. The prehistoric events formed a mafic stratovolcano (island) and the associated large eruptions produced a
c.
2.0 km diameter crater at the centre of the stratocone. Barren Island lavas are mainly basalts and basaltic andesites, whereas Narcondam rocks are dacite-andesite-rhyolite and contain evidence of magma mixing of both mantle and crustal material. The types of volcanoes and volcanism associated with Barren and Narcondam have been attributed to differences in tectonic setting and the nature of the basement below the volcanoes. It is likely that continental or transitional crust exists below Narcondam, in contrast to oceanic lithosphere below Barren Island.
Chapter 16 Natural resources
Authors: Bandopadhyay P. C. , Ghosh Biswajit , Carter A.
Published: February 2017

The natural resources of the Andaman–Nicobar Islands and surrounding seas are discussed. Rocks and minerals found on the Andaman Islands include magnetite, pyrite-chalcopyrite, chromite, gold, nickel, sulphur, coal and limestone, but in most cases their concentrations are sub-economic. Lensoid bodies of algal-biohermal limestones of Palaeogene age on Middle Andaman Island are abundant, accessible and of good grade for cement or foundry work. The Neogene limestones are also suitable for this purpose. Basalts and strongly indurated sedimentary rocks, without any overburden, are quarried for construction work. Limited offshore exploration for oil and natural gas shows great promise, but has yet to be developed.
Chapter 4 Cenozoic rifting, passive margin development and strike-slip faulting in the Andaman Sea: a discussion of established v. new tectonic models
Authors: Morley C. K.
Published: February 2017

The Andaman Sea evolved from near-pure extension (WNW–ESE) during the Late Palaeogene, to highly oblique extension (NNW–SSE) during the Neogene, to strike-slip-dominated deformation (Late Miocene–Recent). These changes in extension direction and deformation style probably reflect the switch from slab rollback-driven extension to India coupling with Myanmar and driving oblique extension/dextral strike-slip. The East Andaman, Mergui–North Sumatra and Martaban Shelf basins, along with the Alcock and Sewell rises and Central Andaman Basin (CAB), were all involved with this deformation which became increasingly focused on the CAB and the rises with time. Possible revisions to traditional models for the Andaman Sea include: (1) the Alcock and Sewell rises are hyper-extended continental or island arc crust, not Miocene oceanic crust; (2) the East Andaman Basin is predominantly underlain by strongly necked to hyper-extended continental crust, not oceanic crust; or (3) CAB oceanic crust is of Miocene, not Pliocene–Recent age. At present a number of major issues can be addressed but not fully resolved, including: (1) the distribution, timing, volume and origin of magmatism in the basins; (2) the causes and significance of strong crustal reflections imaged on 2D and 3D seismic data; (3) implications for crustal thinning geometries, upper crustal extensional patterns and distribution of igneous intrusions for current models of passive margin development (i.e. volcanic v. non-volcanic margins), and how the back-arc setting modifies these models. Elements of both volcanic and non-volcanic margins are present in the East Andaman Sea, with well-developed necking of continental crust (perhaps due to dry mafic, granulite facies lower crust) and extensive igneous intrusions in the lower and middle crust.
Chapter 6 Geological framework of the Andaman–Nicobar Islands
Authors: Bandopadhyay P. C. , Carter A.
Published: February 2017

The Andaman–Nicobar archipelago that forms the western margin of the Andaman Sea is a sediment-dominated accretionary wedge (outer-arc island) associated with a convergent margin tectonic setting. The Andaman accretionary ridge consists of two stratigraphically and structurally distinct terranes, juxtaposed and telescoped into a north–south-trending high-relief fold-thrust belt formed along the obliquely subducting eastern margin of the Indo-Australian oceanic lithospheric plate. The geology and structure of the ridge reflect the complexity of the evolving tectonics and stratigraphy of an accretionary wedge. Pre-Cretaceous meta-sedimentary rocks, Upper Cretaceous ophiolites and Palaeogene–Neogene sedimentary formations indicate rapid, spatial and temporal changes in lithology, sedimentology, sedimentary and tectonic environments, and palaeogeographic setting. This chapter outlines the current geodynamic setting, evidence for the history of accretion and regional geology and introduces the regional stratigraphic framework.
Chapter 9 Submarine fan deposits: petrography and geochemistry of the Andaman Flysch
Authors: Bandopadhyay P. C. , Carter A.
Published: February 2017

The Andaman Flysch of Oligocene age comprises basinal-scale deposits of marine turbidites from an axially fed submarine fan. It is intermittently exposed across the entire chain of the Andaman–Nicobar Islands from the northernmost tip of North Andaman to the southernmost part of Great Nicobar. This chapter reviews the field and petrographic attributes, heavy mineral assemblages, major and trace elements, and isotope geochemistry of the most accessible outcrops on the main Andaman islands.
Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor Ly-GDI in platelet function: a spatial systems approach
Authors: Ngo Anh T. P. , Thierheimer Marisa L. D. , Babur Özgün , Rocheleau Anne D. , Huang Tao , Pang Jiaqing , Rigg Rachel A. , Mitrugno Annachiara , Theodorescu Dan , Burchard Julja , Nan Xiaolin , Demir Emek , McCarty Owen J. T. , Aslan Joseph E.
Published: February 2017

On activation at sites of vascular injury, platelets undergo morphological alterations essential to hemostasis via cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42, and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in platelet function. We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. Whereas RhoGDI localizes throughout platelets in a granule-like manner, Ly-GDI shows an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adherent to fibrinogen. Antibody interference and platelet spreading experiments suggest a specific role for Ly-GDI in platelet function. Intracellular signaling studies based on interactome and pathways analyses also support a regulatory role for Ly-GDI, which is phosphorylated at PKC substrate motifs in a PKC-dependent manner in response to the platelet collagen receptor glycoprotein (GP) VI–specific agonist collagen-related peptide. Additionally, PKC inhibition diffuses the polarized organization of Ly-GDI in spread platelets relative to its colocalization with Rac1 and Cdc42. Together, our results suggest a role for Ly-GDI in the localized regulation of Rho GTPases in platelets and hypothesize a link between the PKC and Rho GTPase signaling systems in platelet function.
Primary proximal tubule hyperreabsorption and impaired tubular transport counterregulation determine glomerular hyperfiltration in diabetes: a modeling analysis
Authors: Hallow K. Melissa , Gebremichael Yeshitila , Helmlinger Gabriel , Vallon Volker
Published: February 2017

Glomerular hypertension and hyperfiltration in early diabetes are associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (PBow). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response. The model implicates that the primary hyperreabsorption of Na in the PT produces a Na imbalance that is only partially restored by the hyperfiltration induced by TGF and changes in PBow. Thus secondary adaptations are needed to restore Na balance. This may include neurohumoral transport regulation and/or pressure-natriuresis (i.e., the decrease in Na reabsorption in response to increased renal perfusion pressure). We explored the role of each tubular segment in contributing to this compensation and the consequences of impairment in tubular compensation. The simulations indicate that impaired secondary downregulation of transport potentiated the rise in glomerular hypertension and hyperfiltration needed to restore Na balance at a given level of primary PT hyperreabsorption. Therefore, we propose for the first time that both the extent of primary PT hyperreabsorption and the degree of impairment of the distal tubular responsiveness to regulatory signals determine the level of glomerular hypertension and hyperfiltration in the diabetic kidney, thereby extending the tubule-centric concept of diabetic hyperfiltration and potential therapeutic approaches beyond the proximal tubule.
Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes
Authors: Malas Tareq B. , Formica Chiara , Leonhard Wouter N. , Rao Pooja , Granchi Zoraide , Roos Marco , Peters Dorien J. M. , 't Hoen Peter A. C.
Published: February 2017

Polycystic kidney disease (PKD) is a major cause of end-stage renal disease. The disease mechanisms are not well understood and the pathogenesis toward renal failure remains elusive. In this study, we present the first RNASeq analysis of a Pkd1-mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD Signature, a set of 1,515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions. Moreover, genes with a role in injury repair, as evidenced by expression data and/or automated literature analysis, were significantly enriched in the PKD Signature, with 35% of the PKD Signature genes being directly implicated in injury repair. NF-κB signaling, epithelial-mesenchymal transition, inflammatory response, hypoxia, and metabolism were among the most prominent injury or repair-related biological processes with a role in the PKD etiology. Novel PKD genes with a role in PKD and in injury were confirmed in another Pkd1-mutant mouse model as well as in animals treated with a nephrotoxic agent. We propose that compounds that can modulate the injury-repair response could be valuable drug candidates for PKD treatment.
Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats
Authors: Yang Shuai , Abbott Geoffrey W. , Gao Wei Dong , Liu Jin , Luo Chaozhi , Hu Zhaoyang
Published: February 2017

Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway.

NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury. However, it is unclear whether ischemic conditioning of visceral organs such as the liver, the largest metabolic organ in the body, can produce cardioprotection. This is the first study to show the cardioprotective effect of remote liver ischemic conditioning in a rat model of myocardial I/R injury. We also, for the first time, demonstrated these protective properties are associated with glycogen synthase kinase-3β-dependent cell-survival signaling pathway.
Effects of Gait Speed of Femoroacetabular Joint Forces
Authors: Weinhandl Joshua T. , Irmischer Bobbie S. , Sievert Zachary A.
Published: February 2017

Alterations in hip joint loading have been associated with diseases such as arthritis and osteoporosis. Understanding the relationship between gait speed and hip joint loading in healthy hips may illuminate changes in gait mechanics as walking speed deviates from preferred. The purpose of this study was to quantify hip joint loading during the gait cycle and identify differences with varying speed using musculoskeletal modeling. Ten, healthy, physically active individuals performed walking trials at their preferred speed, 10% faster, and 10% slower. Kinematic, kinetic, and electromyographic data were collected and used to estimate hip joint force via a musculoskeletal model. Vertical ground reaction forces, hip joint force planar components, and the resultant hip joint force were compared between speeds. There were significant increases in vertical ground reaction forces and hip joint forces as walking speed increased. Furthermore, the musculoskeletal modeling approach employed yielded hip joint forces that were comparable to previous simulation studies and in vivo measurements and was able to detect changes in hip loading due to small deviations in gait speed. Applying this approach to pathological and aging populations could identify specific areas within the gait cycle where force discrepancies may occur which could help focus management of care.
Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model
Authors: Songia Paola , Porro Benedetta , Chiesa Mattia , Myasoedova Veronika , Alamanni Francesco , Tremoli Elena , Poggio Paolo
Published: February 2017

Background. Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. Besides echocardiography, up to now there are no reliable biomarkers available for the identification of this pathology. We aim to generate a predictive model, based on circulating biomarkers, able to identify MVP patients with the highest accuracy. Methods. We analysed 43 patients who underwent mitral valve repair due to MVP and compared to 29 matched controls. We assessed the oxidative stress status measuring the oxidized and the reduced form of glutathione by liquid chromatography‐tandem mass spectrometry method. Osteoprotegerin (OPG) plasma levels were measured by an enzyme‐linked immunosorbent assay. The combination of these biochemical variables was used to implement several logistic regression models. Results. Oxidative stress levels and OPG concentrations were significantly higher in patients compared to control subjects (0.116 ± 0.007 versus 0.053 ± 0.013 and 1748 ± 100.2 versus 1109 ± 45.3 pg/mL, respectively; p < 0.0001). The best regression model was able to correctly classify 62 samples out of 72 with accuracy in terms of area under the curve of 0.92. Conclusions. To the best of our knowledge, this is the first study to show a strong association between OPG and oxidative stress status in patients affected by MVP with severe regurgitation.
Effects of Beeswax Coating on the Oxidative Stability of Long-Ripened Italian Salami
Authors: Trevisani Marcello , Cecchini Matilde , Siconolfi Daniela , Mancusi Rocco , Rosmini Roberto
Published: February 2017

Beeswax coating of foods put a barrier to oxygen, light, and vapour that can help to prevent oxidation of fat and pigments and water loss. The amounts of 2-thiobarbituric acid reactive substances (TBARS) and water activity (Aw) were assessed in Italian salami coated with beeswax at 55 days of ripening and compared with controls at 5, 6, and 7 months of shelf life. The results were correlated with sensory quality. TBARS levels were below 0.8 mg kg−1 in the beeswax-coated salami until 6 months of aging (median 0.697, max 0.795) and significantly higher in the uncoated salami (median 1.176, max 1.227). A slight correlation between the amount of TBARS and Aw was observed in beeswax-coated salamis, whereas this effect was masked in controls by the large Aw variability observed at 7 months. Beeswax coating prevents case hardening and facilitated the peeling.
A Global Path Planning Algorithm Based on Bidirectional SVGA
Authors: Lv Taizhi , Zhao Chunxia , Bao Jiancheng
Published: February 2017

For path planning algorithms based on visibility graph, constructing a visibility graph is very time-consuming. To reduce the computing time of visibility graph construction, this paper proposes a novel global path planning algorithm, bidirectional SVGA (simultaneous visibility graph construction and path optimization by A⁎). This algorithm does not construct a visibility graph before the path optimization. However it constructs a visibility graph and searches for an optimal path at the same time. At each step, a node with the lowest estimation cost is selected to be expanded. According to the status of this node, different through lines are drawn. If this line is free-collision, it is added to the visibility graph. If not, some vertices of obstacles which are passed through by this line are added to the OPEN list for expansion. In the SVGA process, only a few visible edges which are in relation to the optimal path are drawn and the most visible edges are ignored. For taking advantage of multicore processors, this algorithm performs SVGA in parallel from both directions. By SVGA and parallel performance, this algorithm reduces the computing time and space. Simulation experiment results in different environments show that the proposed algorithm improves the time and space efficiency of path planning.
A Prodrug of Two Approved Drugs, Cisplatin and Chlorambucil, for Chemo War Against Cancer
Authors: Pathak Rakesh K. , Wen Ru , Kolishetti Nagesh , Dhar Shanta
Published: February 2017

Cancer cells maintain normal mitochondrial glutathione as one of the defense mechanisms to inhibit mitochondrial membrane polarization and hence apoptosis. A combinational therapeutic modality Platin-Cbl, a prodrug of FDA-approved chemotherapeutic agents, cisplatin and chlorambucil (Cbl), was synthesized and characterized to explore the potential of this compound to initiate chemo war on cancer cells using the active drugs, cisplatin and Cbl, when delivered to the cellular power house mitochondrion using a targeted nanoparticle designed to get associated with this organelle. Platin-Cbl demonstrated significantly high cytotoxic activity across a number of tumor cell lines as well as in a cisplatin-resistant cancer cell line compared with cisplatin or its mixture with Cbl suggesting its unique potency in cisplatin-resistant tumors. A mitochondria-targeted nanoparticle formulation of Platin-Cbl allowed for its efficacious mitochondrial delivery. In vitro studies documented high potency of Platin-Cbl nanoparticle formulations. Cisplatin-resistant cells upon treatment with Platin-Cbl were still able to manage energy production to a certain extent via fatty acid pathway; the advantage of using T-Platin-Cbl-NP is that this nanoparticle treatment causes impairment of all metabolic pathways in cisplatin-resistant cells forcing the cells to undergo efficient apoptosis. This study highlights a combination of several beneficial effects for a cascade of events to overcome resistance associated with single drug therapy. Mol Cancer Ther; 16(4); 625–36. ©2017 AACR.
Fibrin clot structure - pro-fibrinolytic effect of oral contraceptives in apparently healthy women
Authors: Kluft Cornelis , Krug Andrea , Winkler Ulrich , Jespersen Jørgen , Gram Jørgen , Sidelmann Johannes J.
Published: February 2017

Fibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism. The study included 70 women treated with seven different OC-formulations. Blood was collected at baseline and after six months of OCs. The plasma concentration of fibrinogen, thrombin-antithrombin complex (TAT), plasminogen, plasmin-antiplasmin complex (PAP), D-Dimer and thrombin generation measures were determined. Fibrin structure measures and fibrin clot lysis not affected by the plasma concentration of plasminogen activators and inhibitors were determined. OCs increased the concentration of fibrinogen, TAT, plasminogen, PAP and D-dimer significantly and affected measures of thrombin generation (p<0.001). The maximal optical density of fibrin (p<0.001), the fibrin fibre density (p=0.03), fibrin fibre diameter (p=0.003), fibrin mass-length ratio (p<0.001) and lysis per hour (p<0.001) increased significantly upon OC-treatment. Lysis per hour was not correlated to the concentration of plasminogen. We conclude that the effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC. These alterations may counterbalance the OC-induced increased thrombin generation and reduced coagulation inhibitory potential, contributing to maintenance of the haemostatic balance in women receiving OCs.
Vascular Cognitive Impairment
Authors: Dichgans Martin , Leys Didier
Published: February 2017

Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer’s disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.
Stroke Caused by Atherosclerosis of the Major Intracranial Arteries
Authors: Banerjee Chirantan , Chimowitz Marc I.
Published: February 2017

Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and intracranial atherosclerosis. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics, and Asians compared with whites. Diabetes mellitus, hypertension, metabolic syndrome, smoking, hyperlipidemia, and a sedentary lifestyle are the major modifiable risk factors associated with intracranial atherosclerotic disease. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with intracranial atherosclerotic disease. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serological, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients.
Sex-Based Differences in Cardiometabolic Biomarkers
Authors: Lew Jeanney , Sanghavi Monika , Ayers Colby R. , McGuire Darren K. , Omland Torbjørn , Atzler Dorothee , Gore Maria O. , Neeland Ian , Berry Jarett D. , Khera Amit , Rohatgi Anand , de Lemos James A.
Published: February 2017

Background:

Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology.

Methods:

A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass.

Results:

After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin,
d
-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C.

Conclusions:

Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD.