bluuebunny/crossref_metadata_2025 huggingface dataset:
Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice
Authors: Han Qi , Ordaz Josue D. , Liu Nai-Kui , Richardson Zoe , Wu Wei , Xia Yongzhi , Qu Wenrui , Wang Ying , Dai Heqiao , Zhang Yi Ping , Shields Christopher B. , Smith George M. , Xu Xiao-Ming
Published: December 2019

Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.
Attribute driven inverse materials design using deep learning Bayesian framework
Authors: Tagade Piyush M. , Adiga Shashishekar P. , Pandian Shanthi , Park Min Sik , Hariharan Krishnan S. , Kolake Subramanya Mayya
Published: December 2019

Much of computational materials science has focused on fast and accurate forward predictions of materials properties, for example, given a molecular structure predict its electronic properties. This is achieved with first principles calculations and more recently through machine learning approaches, since the former is computation-intensive and not practical for high-throughput screening. Searching for the right material for any given application, though follows an inverse path—the desired properties are given and the task is to find the right materials. Here we present a deep learning inverse prediction framework, Structure Learning for Attribute-driven Materials Design Using Novel Conditional Sampling (SLAMDUNCS), for efficient and accurate prediction of molecules exhibiting target properties. We apply this framework to the computational design of organic molecules for three applications, organic semiconductors for thin-film transistors, small organic acceptors for solar cells and electrolyte additives with high redox stability. Our method is general enough to be extended to inorganic compounds and represents an important step in deep learning based completely automated materials discovery.
Neural correlates of tactile simultaneity judgement: a functional magnetic resonance imaging study
Authors: Kimura Takahiro , Kadota Hiroshi , Kuroda Tsuyoshi , Funai Tomomi D. , Iwata Makoto , Kochiyama Takanori , Miyazaki Makoto
Published: December 2019

Simultaneity judgement (SJ) is a temporal discrimination task in which the targets span an ultimately short time range (zero or not). Psychophysical studies suggest that SJ is adequate to probe the perceptual components of human time processing in pure form. Thus far, time-relevant neural correlates for tactile SJ are unclear. We performed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of tactile SJ using tactile number judgement as a time-irrelevant control task. As our main result, we demonstrated that the right inferior parietal lobule (IPL) is an SJ-specific region. The right IPL was detected by both parametric and non-parametric statistical analyses, and its activation intensity fulfilled a strict statistical criterion. In addition, we observed that some left-dominant regions (e.g., the striatum) were specifically activated by successive stimuli during SJ. Meanwhile, no region was specifically activated by simultaneous stimuli during SJ. Accordingly, we infer that the neural process for tactile SJ is as follows: the striatum estimates the time interval between tactile stimuli; based on this interval, the right IPL discriminates the successiveness or simultaneity of the stimuli. Moreover, taking detailed behavioural results into account, we further discuss possible concurrent or alternative mechanisms that can explain the fMRI results.
Optimized Measurement Parameters of Sensory Evoked Cortical Potentials to Assess Human Bladder Afferents - A Randomized Study
Authors: van der Lely Stéphanie , Liechti Martina D. , Schmidhalter Melanie R. , Schubert Martin , Bachmann Lucas M. , Kessler Thomas M. , Mehnert Ulrich
Published: December 2019

Overactive bladder and voiding dysfunction are highly prevalent and often associated with malfunction of the bladder afferent pathways. Appropriate diagnostic tools for an objective assessment of afferent nerve function of the human bladder are currently missing. One promising possibility is the assessment of sensory evoked potentials (SEP) during repetitive electrical bladder stimulation, which proved feasible in healthy subjects. For an implementation into clinical practice, however, further refinements for efficient and reliable data acquisition are crucial. The aim of this randomized study was to find the optimal measurement settings regarding stimulation frequency, repetition number, and data acquisition. Forty healthy subjects underwent two visits of SEP (Cz-Fz) assessments using repetitive (500 stimuli) electrical stimulation of 0.5 Hz, 1.1 Hz, and 1.6 Hz and pulse width of 1 ms at the bladder dome or trigone. SEP analyses revealed higher amplitudes and better signal-to-noise ratio (SNR) with lower stimulation frequencies, while latencies remained unchanged. Decreasing amplitudes and SNR were observed with continuing stimulation accompanied by decreasing responder rate (RR). When applying stimuli at a frequency of 0.5 Hz, averaging across 200 stimuli revealed optimal reliability with best SNR, RR and sufficiently high amplitudes. This constitutes an optimal compromise between the duration of the assessment and SEP peak-to-peak amplitudes.
Long-term effectiveness and safety of varenicline and nicotine replacement therapy in people with neurodevelopmental disorders: A prospective cohort study
Authors: Itani Taha , Rai Dheeraj , Jones Tim , Taylor Gemma M. J. , Thomas Kyla H. , Martin Richard M. , Munafò Marcus R. , Davies Neil M. , Taylor Amy E.
Published: December 2019

This study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.
A prospective compound screening contest identified broader inhibitors for Sirtuin 1
Authors: Chiba Shuntaro , Ohue Masahito , Gryniukova Anastasiia , Borysko Petro , Zozulya Sergey , Yasuo Nobuaki , Yoshino Ryunosuke , Ikeda Kazuyoshi , Shin Woong-Hee , Kihara Daisuke , Iwadate Mitsuo , Umeyama Hideaki , Ichikawa Takaaki , Teramoto Reiji , Hsin Kun-Yi , Gupta Vipul , Kitano Hiroaki , Sakamoto Mika , Higuchi Akiko , Miura Nobuaki , Yura Kei , Mochizuki Masahiro , Ramakrishnan Chandrasekaran , Thangakani A. Mary , Velmurugan D. , Gromiha M. Michael , Nakane Itsuo , Uchida Nanako , Hakariya Hayase , Tan Modong , Nakamura Hironori K. , Suzuki Shogo D. , Ito Tomoki , Kawatani Masahiro , Kudoh Kentaroh , Takashina Sakurako , Yamamoto Kazuki Z. , Moriwaki Yoshitaka , Oda Keita , Kobayashi Daisuke , Okuno Tatsuya , Minami Shintaro , Chikenji George , Prathipati Philip , Nagao Chioko , Mohsen Attayeb , Ito Mari , Mizuguchi Kenji , Honma Teruki , Ishida Takashi , Hirokawa Takatsugu , Akiyama Yutaka , Sekijima Masakazu
Published: December 2019

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds usingin silicomethods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.
Publisher Correction: A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation
Authors: Hatakeyama Masahiro , Kanazawa Masato , Ninomiya Itaru , Omae Kaoru , Kimura Yasuko , Takahashi Tetsuya , Onodera Osamu , Fukushima Masanori , Shimohata Takayoshi
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Inferring pathogen-host interactions between Leptospira interrogans and Homo sapiens using network theory
Authors: Kumar Swapnil , Lata Kumari Snehkant , Sharma Priyanka , Bhairappanavar Shivarudrappa B. , Soni Subhash , Das Jayashankar
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preventive Pharmacotherapy for Cardiovascular Disease: A Modelling Study Considering Health Gain, Costs, and Cost-Effectiveness when Stratifying by Absolute Risk
Authors: Nghiem Nhung , Knight Josh , Mizdrak Anja , Blakely Tony , Wilson Nick
Published: December 2019

Cardiovascular disease (CVD) is the leading cause of death internationally. We aimed to model the impact of CVD preventive double therapy (a statin and anti-hypertensive) by clinician-assessed absolute risk level. An established and validated multi-state life-table model for the national New Zealand (NZ) population was adapted. The new version of the model specifically considered the 60–64-year-old male population which was stratified by risk using a published NZ-specific CVD risk equation. The intervention period of treatment was for five years, but a lifetime horizon was used for measuring benefits and costs (a five-year horizon was also implemented). We found that for this group offering double therapy was highly cost-effective in all absolute risk categories (eg, NZ$1580 per QALY gained in the >20% in 5 years risk stratum; 95%UI: Dominant to NZ$3990). Even in the lowest risk stratum (≤5% risk in 5 years), the cost per QALY was only NZ$25,500 (NZ$28,200 and US$19,100 in 2018). At an individual level, the gain for those who responded to the screening offer and commenced preventive treatment ranged from 0.6 to 4.9 months of quality-adjusted life gained (or less than a month gain with a five-year horizon). Nevertheless, at the individual level, patient considerations are critical as some people may decide that this amount of average health gain does not justify taking daily medication.
Resistance to Haemonchus contortus in Corriedale sheep is associated to high parasite-specific IgA titer and a systemic Th2 immune response
Authors: Escribano Cecilia , Saravia Anderson , Costa Monique , Castells Daniel , Ciappesoni Gabriel , Riet-Correa Franklin , Freire Teresa
Published: December 2019

Gastrointestinal nematode infections, including Haemonchus contortus, are one of the main causes of economic losses to ovine farmers worldwide. In order to contribute to the control of nematode infections and avoid parasite spreading we generated divergent resistant and susceptible sheep breeds and evaluated the adaptive immunity of these animals developed upon experimental infection against H. contortus. The selection of resistant or susceptible animals from the Corriedale Breed has been based on Expected Progeny Differences for faecal egg counts per gram. Furthermore, animals from the resistant Corriedale line were inseminated with imported semen from Australian Rylington Merino rams. Thus, the objective of this work was to analyze the adaptive immune response in both susceptible and resistant obtained lambs. Our results indicate that there is a potent parasite-specific local and systemic immune response in resistant animals and that although susceptible lambs can produce high levels of IgA antibodies during the infection, their antibody response is delayed which, together with an impaired specific-Th2 response, does not contribute to initial parasite elimination. Our results shed light into the immune mechanisms that mediate resistance to H. contortus and could constitute important assets to sheep farmers, not only as a means to detect resistance, but also to enhance the efficiency of selection in stud flocks.
A predation assay using amoebae to screen for virulence factors unearthed the first W. chondrophila inclusion membrane protein
Authors: Kebbi-Beghdadi C. , Pilloux L. , Croxatto A. , Tosetti N. , Pillonel T. , Greub G.
Published: December 2019

Waddlia chondrophila is an intracellular bacterium phylogenetically related to the well-studied human and animal pathogens of the Chlamydiaceae family. In the last decade, W. chondrophila was convincingly demonstrated to be associated with adverse pregnancy outcomes in humans and abortions in animals. All members of the phylum Chlamydiae possess a Type Three Secretion System that they use for delivering virulence proteins into the host cell cytosol to modulate their environment and create optimal conditions to complete their life cycle. To identify W. chondrophila virulence proteins, we used an original screening approach that combines a cosmid library with an assay monitoring resistance to predation by phagocytic amoebae. This technique combined with bioinformatic data allowed the identification of 28 candidate virulence proteins, including Wimp1, the first identified inclusion membrane protein of W. chondrophila.
Allergen-induced anxiety-like behavior is associated with disruption of medial prefrontal cortex - amygdala circuit
Authors: Dehdar Kolsoum , Mahdidoust Shirin , Salimi Morteza , Gholami-Mahtaj Leila , Nazari Milad , Mohammadi Sadeq , Dehghan Samaneh , Jamaati Hamidreza , Khosrowabadi Reza , Nasiraei-Moghaddam Abbas , Barkley Victoria , Javan Mohammad , Mirnajafi-Zadeh Javad , Sumiyoshi Akira , Raoufy Mohammad Reza
Published: December 2019

Anxiety is prevalent in asthma, and is associated with disease severity and poor quality of life. However, no study to date provides direct experimental evidence for the effect of allergic inflammation on the structure and function of medial prefrontal cortex (mPFC) and amygdala, which are essential regions for modulating anxiety and its behavioral expression. We assessed the impact of ovalbumin (OVA)-induced allergic inflammation on the appearance of anxiety-like behavior, mPFC and amygdala volumes using MRI, and the mPFC-amygdala circuit activity in sensitized rats. Our findings exhibited that the OVA challenge in sensitized rats induced anxiety-like behavior, and led to more activated microglia and astrocytes in the mPFC and amygdala. We also found a negative correlation between anxiety-like behavior and amygdala volume. Moreover, OVA challenge in sensitized rats was associated with increases in mPFC and amygdala activity, elevation of amygdala delta-gamma coupling, and the enhancement of functional connectivity within mPFC-amygdala circuit – accompanied by an inverted direction of information transferred from the amygdala to the mPFC. We indicated that disrupting the dynamic interactions of the mPFC-amygdala circuit may contribute to the induction of anxiety-related behaviors with asthma. These findings could provide new insight to clarify the underlying mechanisms of allergic inflammation-induced psychiatric disorders related to asthma.
A novel murine model for assessing fetal and birth outcomes following transgestational maternal malaria infection
Authors: Morffy Smith Catherine D. , Russ Brittany N. , Andrew Alicer K. , Cooper Caitlin A. , Moore Julie M.
Published: December 2019

Plasmodium falciparum infection during pregnancy is a major cause of severe maternal illness and neonatal mortality. Mouse models are important for the study of gestational malaria pathogenesis. When infected with Plasmodium chabaudi chabaudi AS in early gestation, several inbred mouse strains abort at midgestation. We report here that outbred Swiss Webster mice infected with P. chabaudi chabaudi AS in early gestation carry their pregnancies to term despite high parasite burden and malarial hemozoin accumulation in the placenta at midgestation, with the latter associated with induction of heme oxygenase 1 expression. Infection yields reduced fetal weight and viability at term and a reduction in pup number at weaning, but does not influence postnatal growth prior to weaning. This novel model allows for the exploration of malaria infection throughout pregnancy, modeling chronic infections observed in pregnant women prior to the birth of underweight infants and enabling the production of progeny exposed to malaria in utero, which is critical for understanding the postnatal repercussions of gestational malaria. The use of outbred mice allows for the exploration of gestational malaria in a genetically diverse model system, better recapitulating the diversity of infection responses observed in human populations.
The CXCL12 SNPs and their haplotypes are associated with serum lipid traits
Authors: Qiu Ling , Yin Rui-Xing , Nie Rong-Jun , Hu Xi-Jiang , Khounphinith Eksavang , Zhang Fen-Han
Published: December 2019

The relationship among the single nucleotide polymorphisms (SNPs) of the C-X-C motif chemokine ligand 12 gene (CXCL12) and the serum lipid profiles in the Chinese population has rarely been described, especially in somewhat old-fashioned and isolated Maonan minority. The goal of the current study was to elucidate the connection among the CXCL12 rs501120 and rs1746048 SNPs, haplotypes, several environmental factors and serum lipid traits in the Maonan as well as Han populations. Genotyping of the two SNPs, gel electrophoresis and direct sequencing were accomplished in 1,494 distinct subjects (Maonan, 750 and Han, 744) using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of genotypes as well as alleles of the two SNPs were not similar between the two ethnic groups. The rs501120 SNP was related with serum total cholesterol levels, while the rs1746048 SNP was related with serum apolipoprotein (Apo) B levels. Four haplotypes were identified, of which the rs501120A-rs1746048C haplotype was the most common. The haplotypes of rs501120A-rs1746048T increased and rs501120G-rs1746048C decreased the risk of hyperlipidemia (P < 0.001 for each), showing consistent association with the levels of serum triglyceride, ApoA1 and ApoB. These outcomes specify that the CXCL12 SNPs as well as their haplotypes are related to serum lipid levels. Different serum lipid levels between both populations may partially be related to the CXCL12 SNPs, their haplotypes along with several environmental factors.
Assimilating Satellite Land Surface States Data from Fengyun-4A
Authors: Meng Chunlei , Li Huoqing
Published: December 2019

Fengyun-4A is the new generation of Chinese geostationary meteorological satellites. Land surface albedo, land surface emissivity and land surface temperature are key states for land surface modelling. In this paper, the land surface albedo, land surface emissivity and land surface temperature data from Fengyun-4A were assimilated into the Integrated Urban land Model. The Fengyun-4A data are one of the data sources for the land data assimilation system which devoted to produce the high spatial and temporal resolution, multiple parameters near real-time land data sets. The Moderate-Resolution Imaging Spectroradiometer (MODIS) LSA and LSE data, the Institute of Atmospheric Physics, China Academy of Sciences (IAP) 325 m tower observation data and the observed 5 cm and 10 cm soil temperature data in more than 100 sites are used for validation. The results indicate the MODIS land surface albedo is much smaller than the Fengyun-4A and is superior to the Fengyun-4A for the Institute of Atmospheric Physics, China Academy of Sciences 325 m tower site. The Moderate-Resolution Imaging Spectroradiometer land surface emissivity is smaller than the Fengyun-4A in barren land surface and the differences is relatively small for other land use and land cover categories. In most regions of the research area, the Fengyun-4A land surface albedo and land surface emissivity are larger than those of the simulations. After the land surface albedo assimilation, in most regions the simulated net radiation was decreased. After the land surface emissivity assimilation, in most regions the simulated net radiation was increased. After the land surface temperature assimilation, the biases of the land surface temperature were decreased apparently; the biases of the daily average 5 cm and 10 cm soil temperature were decreased.
High-temperature martensitic transformation of CuNiHfTiZr high- entropy alloys
Authors: Chang Shan-Hsiu , Lin Po-Ting , Tsai Che-Wei
Published: December 2019

One of the major challenges of near-equiatomic NiTi shape memory alloys is their limitation for high-temperature applications. To overcome this barrier, researchers have tried to enhance the transformation temperatures by addition of alloying elements or even by introducing the concept of high-entropy alloys (HEAs). In this study, the CuNiHfTiZr HEAs were developed for high-temperature shape memory effect. Based on their solubility and electron configurations, the alloying elements are divided into two groups, (CuNi)50 and (HfTiZr)50. The content of Cu in (CuNi)50 is modulated to investigate the influences of Cu on martensitic transformation of the HEAs by studying structural evolution and transformation behavior. The results of x-ray diffraction and thermal expansion tests revealed that Cu15Ni35Hf16.67Ti16.67Zr16.67 possesses high transformation temperature, narrow hysteresis temperature loops, and good dimensional stability within this HEA system.
Survival of a long-lived single island endemic, the Raso lark Alauda razae, in relation to age, fluctuating population and rainfall
Authors: Dierickx E. G. , Robinson R. A. , Brooke M. de L.
Published: December 2019

Estimating and understanding variation in survival rates is crucial for the management of threatened species, especially those with limited population sizes and/or restricted ranges. Using a capture-resighting dataset covering 2004–2017, we estimate adult survival in the Raso larkAlauda razae, a Critically Endangered single-island Cape Verdean endemic, whose population varied 25-fold during the study. Average annual adult survival was similar for males (0.813 ± 0.011) and females (0.826 ± 0.011) over the period. These values are high for a temperate passerine but not unusual for an insular tropical species like the lark. The oldest bird was recorded 13 years after first ringing. There was strong evidence that survival varied among years (between 0.57 and 0.95), being generally higher in wetter years. Survival, especially of males, was lower when the population was large, but only in drier years. Survival declined with age but there was no evidence that this decline was other than linear. High survival, even in the face of dry conditions, at least when the population is depressed, has probably contributed to the persistence of the species on its 7 km2island home over several centuries.
Neutronic investigation of alternative & composite burnable poisons for the soluble-boron-free and long life civil marine small modular reactor cores
Authors: Alam Syed Bahauddin , Almutairi Bader , Ridwan Tuhfatur , Kumar Dinesh , Goodwin Cameron S. , Atkinson Kirk D. , Parks Geoffrey T.
Published: December 2019

Concerns about the effects of global warming provide a strong case to consider how best nuclear power could be applied to marine propulsion. Currently, there are persistent efforts worldwide to combat global warming, and that also includes the commercial freight shipping sector. In an effort to decarbonize the marine sector, there are growing interests in replacing the contemporary, traditional propulsion systems with nuclear propulsion systems. The latter system allows freight ships to have longer intervals before refueling; subsequently, lower fuel costs, and minimal carbon emissions. Nonetheless, nuclear propulsion systems have remained largely confined to military vessels. It is highly desirable that a civil marine core not use soluble boron for reactivity control, but it is then a challenge to achieve an adequate shutdown margin throughout the core life while maintaining reactivity control and acceptable power distributions in the core. High-thickness ZrB2 150 μm Integral Fuel Burnable Absorber (IFBA) is an excellent burnable poison (BP) candidate for long life soluble-boron-free core. However, in this study, we want to minimize the use of 150 μm IFBA since B-10 undergoes an (n, α) capture reaction, and the resulting helium raises the pressure within the plenum and in the cladding. Therefore, we have considered several alternative and novel burnable BP design strategies to minimize the use of IFBA for reactivity control in this study: (Case 1) a composite BP: gadolinia (Gd2O3) or erbia (Er2O3) with 150 μm thickness ZrB2 IFBA; (Case 2) Pu-240 or Am-241 mixed homogeneously with the fuel; and (Case 3) another composite BP: Pu-240 or Am-241 with 150 μm thickness ZrB2 IFBA. The results are compared against those for a high-thickness 150 μm 25 IFBA pins design from a previous study. The high-thickness 150 μm 25 IFBA pins design is termed the “IFBA-only” BP design throughout this study. We arrive at a design using 15% U-235 fuel loaded into 13 × 13 assemblies with Case 3 BPs (IFBA+Pu-240 or IFBA+Am-241) for reactivity control while reducing 20% IFBA use. This design exhibits lower assembly reactivity swing and minimal burnup penalty due to the self-shielding effect. Case 3 provides ~10% more initial (beginning-of-life) reactivity suppression with ~70% less reactivity swing compared to the IFBA-only design for UO2 fuel while achieving almost the same core lifetime. Finally, optimized Case 3 assemblies were loaded in 3D nodal diffusion and reactor model code. The results obtained from the 3D reactor model confirmed that the designed core with the proposed Case 3 BPs can achieve the target lifetime of 15 years while contributing to ~10% higher BOL reactivity suppression, ~70% lower reactivity swings, ~30% lower radial form factor and ~28% lower total peaking factor compared to the IFBA-only core.
Clinical characteristics, risk factors, and surgical outcomes of secondary macular hole after vitrectomy
Authors: Kang Hyun Goo , Han Jae Yong , Choi Eun Young , Byeon Suk Ho , Kim Sung Soo , Koh Hyoung Jun , Lee Sung Chul , Kim Min
Published: December 2019

Secondary macular hole(MH) formation after vitrectomy is rare and its risk factors and pathogenesis are not clearly understood. This retrospective study was conducted to identify the risk factors of this complication and assess outcomes at 2 tertiary centres. The primary outcomes were the clinical characteristics associated with development of secondary MH, which included the primary diagnosis for initial vitrectomy, features on optical coherence tomography, and adjuvant surgical techniques used during the initial surgery. Secondary outcomes included the change in best-corrected visual acuity(BCVA), clinical factors associated with the need for re-operations for MH closure and prognostic factors for the visual outcomes. Thirty-eight eyes out of 6,354 cases (incidence 0.60%) developed secondary MH after undergoing vitrectomy for various vitreoretinal disorders over an 11-year period, most frequently after initial surgery for retinal detachment(RD) (9 eyes) and secondary epiretinal membrane (6 eyes). The mean age was 57.1 years (range: 17.8–76.7), and the mean follow-up was 51.1 months (range: 6.8 to 137.6). Prior to secondary MH formation, development of ERM was the most common OCT feature (19 eyes, 50%), and no cases of cystoid macular oedema (CME) were observed. A greater proportion of eyes with secondary MH had long axial lengths (32% ≥26 mm vs 5% of eyes ≤22 mm). MH closure surgery was performed in 36 eyes and closure was achieved in 34 (success rate 94%, final BCVA 20/86), with ≥3-line visual gain in 18 cases. BCVA at MH onset (OR = 0.056, P = 0.036), BCVA at post-MH surgery month 3 (OR = 52.671, P = 0.011), and axial length ≥28 mm (OR = 28.487, P = 0.030) were associated with ≥3-line visual loss; a history of macula-off RD (OR = 27.158, P = 0.025) was associated with the need for multiple surgeries for MH closure. In conclusion, secondary MH occurs rarely but most commonly after vitrectomy for RD. Patients with axial length ≥28 mm and poor BCVA at 3 months post-operation may have limited visual prognosis; those with a history of macula-off RD may require multiple surgeries for hole closure.
Release of Porcine Sperm from Oviduct Cells is Stimulated by Progesterone and Requires CatSper
Authors: Machado Sergio A. , Sharif Momal , Wang Huijing , Bovin Nicolai , Miller David J.
Published: December 2019

Sperm storage in the female reproductive tract after mating and before ovulation is a reproductive strategy used by many species. When insemination and ovulation are poorly synchronized, the formation and maintenance of a functional sperm reservoir improves the possibility of fertilization. In mammals, the oviduct regulates sperm functions, such as Ca2+influx and processes associated with sperm maturation, collectively known as capacitation. A fraction of the stored sperm is released by unknown mechanisms and moves to the site of fertilization. There is an empirical association between the hormonal milieu in the oviduct and sperm detachment; therefore, we tested directly the ability of progesterone to induce sperm release from oviduct cell aggregates. Sperm were allowed to bind to oviduct cells or an immobilized oviduct glycan and then challenged with progesterone, which stimulated the release of 48% of sperm from oviduct cells or 68% of sperm from an immobilized oviduct glycan. The effect of progesterone on sperm release was specific; pregnenolone and 17α-OH-progesterone did not affect sperm release. Ca2+influx into sperm is associated with capacitation and development of hyperactivated motility. Progesterone increased sperm intracellular Ca2+, which was abrogated by blocking the sperm–specific Ca2+channel CatSper with NNC 055-0396. NNC 055-0396 also blocked the progesterone-induced sperm release from oviduct cells or immobilized glycan. An inhibitor of the non-genomic progesterone receptor that activates CatSper similarly blocked sperm release. This is the first report indicating that release of sperm from the sperm reservoir is induced by progesterone action through CatSper channels.
Phenotypic alterations in liver cancer cells induced by mechanochemical disruption
Authors: Murad Hakm Y. , Bortz Emma P. , Yu Heng , Luo Daishen , Halliburton Gray M. , Sholl Andrew B. , Khismatullin Damir B.
Published: December 2019

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis worldwide. Currently, no curative treatment is available for early-to-intermediate stage HCC, characterized by large and/or multifocal tumors. If left untreated, HCC rapidly progresses to a lethal stage due to favorable conditions for metastatic spread. Mechanochemical disruption of cellular structures can potentially induce phenotypic alterations in surviving tumor cells that prevent HCC progression. In this paper, HCC response to mechanical vibration via high-intensity focused ultrasound and a chemical disruptive agent (ethanol) was examined in vitro and in vivo. Our analysis revealed that mechanochemical disruption caused a significant overproduction of reactive oxygen species (ROS) in multiple HCC cell lines (HepG2, PLC/PRF/5, and Hep3B). This led to a decrease in cell viability and long-term proliferation due to increased expression and activity of death receptors TNFR1 and Fas. The cells that survived mechanochemical disruption had a reduced expression of cancer stem cell markers (CD133, CD90, CD49f) and a diminished colony-forming ability. Mechanochemical disruption also impeded HCC migration and their adhesion to vascular endothelium, two critical processes in hematogenous metastasis. The HCC transformation to a non-tumorigenic phenotype post mechanochemical disruption was confirmed by a lack of tumor spheroid formation in vitro and complete tumor regression in vivo. These results show that mechanochemical disruption inhibits uncontrolled proliferation and reduces tumorigenicity and aggressiveness of HCC cells through ROS overproduction and associated activation of TNF- and Fas-mediated cell death signaling. Our study identifies a novel curative therapeutic approach that can prevent the development of aggressive HCC phenotypes.
An experiment-informed signal transduction model for the role of the Staphylococcus aureus MecR1 protein in β-lactam resistance
Authors: Belluzo Bruno S. , Abriata Luciano A. , Giannini Estefanía , Mihovilcevic Damila , Dal Peraro Matteo , Llarrull Leticia I.
Published: December 2019

The treatment of hospital- and community-associated infections by methicillin-resistant Staphylococcus aureus (MRSA) is a perpetual challenge. This Gram-positive bacterium is resistant specifically to β-lactam antibiotics, and generally to many other antibacterial agents. Its resistance mechanisms to β-lactam antibiotics are activated only when the bacterium encounters a β-lactam. This activation is regulated by the transmembrane sensor/signal transducer proteins BlaR1 and MecR1. Neither the transmembrane/metalloprotease domain, nor the complete MecR1 and BlaR1 proteins, are isolatable for mechanistic study. Here we propose a model for full-length MecR1 based on homology modeling, residue coevolution data, a new extensive experimental mapping of transmembrane topology, partial structures, molecular simulations, and available NMR data. Our model defines the metalloprotease domain as a hydrophilic transmembrane chamber effectively sealed by the apo-sensor domain. It proposes that the amphipathic helices inserted into the gluzincin domain constitute the route for transmission of the β-lactam-binding event in the extracellular sensor domain, to the intracellular and membrane-embedded zinc-containing active site. From here, we discuss possible routes for subsequent activation of proteolytic action. This study provides the first coherent model of the structure of MecR1, opening routes for future functional investigations on how β-lactam binding culminates in the proteolytic degradation of MecI.
Predicting cognitive performance from physical activity and fitness in adolescents and young adults in Botswana relative to HIV status
Authors: Malete Leapetswe , Etnier Jennifer L. , Tladi Dawn M. , Vance Jarod C. , Anabwani Gabriel M.
Published: December 2019

Little is known about whether physical activity and fitness could enhance cognition in adolescents and young adults living with HIV. The purpose of this study was to examine this relationship in a group of 250 HIV+ (n = 88) and HIV negative (n = 162) participants from Botswana, aged 12–23 years (Mean = 17.87, SD = 2.24). Fitness was operationalized as muscular strength (push-ups) and aerobic endurance (PACER). PA was assessed using items from the Youth Risk Behavior Surveillance Survey. Cognition was measured using the Corsi Test, Berg Card Sorting Task (BCST), and Stroop Color Word Task (Stroop). Multiple regression analyses indicated that the HIV x push-ups interaction was a significant predictor of Corsi performance, and HIV status was a significant predictor of BCST performance (p < 0.05). For the Stroop portions, HIV status and HIV x push-ups were significant predictors (p < 0.01). HIV status is predictive of cognition and interacts with muscular fitness to predict cognition.
Self-reported insomnia as a marker for anxiety and depression among migraineurs: a population-based cross-sectional study
Authors: Kim Kyung Min , Lee Dong Hyun , Lee Eun Ju , Roh Yun Ho , Kim Won-Joo , Cho Soo-Jin , Yang Kwang Ik , Yun Chang-Ho , Chu Min Kyung
Published: December 2019

Anxiety, depression, and insomnia are highly prevalent among migraineurs and are associated with negative health consequences. Anxiety and depression, however, unlike insomnia, are usually underdiagnosed, due to less self-reporting of these two conditions. The aim of the present study was to evaluate the risk of anxiety and depression in migraineurs with self-reported insomnia, using a general population-based sample. We used data from a nationwide population-based survey on headache and sleep, the Korean Headache-Sleep Study. Of all 2,695 participants, 143 (5.3%), 268 (10.0%), 116 (4.3%), and 290 (10.8%) were classified as having migraine, anxiety, depression, and self-reported insomnia, respectively. The risk of anxiety (odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.0–16.7) and depression (OR = 3.3, 95% CI = 1.3–8.5) was significantly increased in migraineurs with self-reported insomnia. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for anxiety in migraineurs with self-reported insomnia were 46.5%, 89.0%, 64.5%, and 79.5%, respectively. For depression, the sensitivity, specificity, PPV, and NPV were 41.7%, 82.4%, 32.3%, and 87.5%, respectively. Self-reported insomnia is likely to be comorbid with anxiety and depression in migraineurs and could thus be a useful predictor of anxiety and depression in migraine.
Shoulder tenderness was associated with the inflammatory changes on magnetic resonance imaging in patients with rheumatoid arthritis
Authors: Shinagawa Satoshi , Okamura Koichi , Yonemoto Yukio , Shitara Hitoshi , Suto Takahito , Sakane Hideo , Dam Trang Thuy , Tajika Tsuyoshi , Tsushima Yoshito , Takagishi Kenji , Chikuda Hirotaka
Published: December 2019

The aim of this study was to assess the association between the shoulder tenderness and the inflammatory changes on magnetic resonance imaging (MRI) in the rheumatoid shoulder. Forty-one shoulders of 41 patients with rheumatoid arthritis (RA) were examined. We evaluated synovitis, erosion and bone marrow edema, by counting the numbers of each positive site, and rotator cuff tears on shoulder MRI. The association between the shoulder tenderness and the MRI findings were statistically analyzed. Twenty-three of 41 patients had tenderness in the shoulder joints. There were 20 shoulders (48.8%) with rotator cuff tear, and no significant difference was observed in the prevalence of rotator cuff tear between the tenderness group and non-tenderness group (p = 0.080). There were no significant differences in the demographic data between these two groups. In MRI findings, we found significant difference for the synovitis (p = 0.001) and bone marrow edema (p = 0.021). Synovitis was strongly associated with the shoulder tenderness (OR: 3.996, 95% CI: 1.651–9.671). Synovitis was the factor most associated with shoulder tenderness.
Subducting serpentinites release reduced, not oxidized, aqueous fluids
Authors: Piccoli F. , Hermann J. , Pettke T. , Connolly J. A. D. , Kempf E. D. , Vieira Duarte J. F.
Published: December 2019

The observation that primitive arc magmas are more oxidized than mid-ocean-ridge basalts has led to the paradigm that slab-derived fluids carry SO2 and CO2 that metasomatize and oxidize the sub-arc mantle wedge. We combine petrography and thermodynamic modelling to quantify the oxygen fugacity (fO2) and speciation of the fluids generated by serpentinite dehydration during subduction. Silicate-magnetite assemblages maintain fO2 conditions similar to the quartz-fayalite-magnetite (QFM) buffer at fore-arc conditions. Sulphides are stable under such conditions and aqueous fluids contain minor S. At sub-arc depth, dehydration occurs under more reducing conditions producing aqueous fluids carrying H2S. This finding brings into question current models in which serpentinite-derived fluids are the cause of oxidized arc magmatism and has major implications for the global volatile cycle, as well as for redox processes controlling subduction zone geodynamics.
The Otranto Channel (South Adriatic Sea), a hot-spot area of plankton biodiversity: pelagic polychaetes
Authors: Guglielmo Rosanna , Bergamasco Alessandro , Minutoli Roberta , Patti Francesco P. , Belmonte Genuario , Spanò Nunziacarla , Zagami Giacomo , Bonanzinga Vincenzo , Guglielmo Letterio , Granata Antonia
Published: December 2019

Composition, density and specimen sizes of pelagic polychaete assemblages were analyzed in the Southern Adriatic Sea. The study was based on finely stratified vertical (0–1100 m) and spatial sampling (17 stations) representing spring conditions. Holoplanktonic polychaetes were distributed in both neritic and pelagic waters, although the highest densities were observed along the Otranto Channel. Analysis of the size frequency distribution revealed a trend with depth only for some species. Spatial distribution of holoplanktonic polychaete density was not related to bottom depth, being the organisms mainly concentrated in the epipelagic layer (0–100 m). The most abundant species showed maximum values below or within the thermocline and within the Deep Chlorophyll Maximum or just above it. Relations between polychaete presence and the underlying oceanographic mechanisms regulating the circulation in the Otranto Channel were discussed. The presence of several non-determined polychaete larvae (e.g. Syllidae) in the pelagic waters at 800–1100 m depths suggests the importance of the role of Levantine waters as main actual and potential carrier of species in the area, though a relevant contribution comes also from North Adriatic dense waters through deep spilling and cascading in the Southern Adriatic pit. These findings increase the knowledge on holoplanktonic polychaetes ecology within the South Adriatic Sea, and represent significant data in the monitoring of changes in biodiversity.
Determining the duration of an ultra-intense laser pulse directly in its focus
Authors: Mackenroth Felix , Holkundkar Amol R.
Published: December 2019

Ultra-intense lasers facilitate studies of matter and particle dynamics at unprecedented electromagnetic field strengths. In order to quantify these studies, precise knowledge of the laser’s spatiotemporal shape is required. Due to material damage, however, conventional metrology devices are inapplicable at highest intensities, limiting laser metrology there to indirect schemes at attenuated intensities. Direct metrology, capable of benchmarking these methods, thus far only provides static properties of short-pulsed lasers with no scheme suggested to extract dynamical laser properties. Most notably, this leaves an ultra-intense laser pulse’s duration in its focus unknown at full intensity. Here we demonstrate how the electromagnetic radiation pattern emitted by an electron bunch with a temporal energy chirp colliding with the laser pulse depends on the laser’s pulse duration. This could eventually facilitate to determine the pulse’s temporal duration directly in its focus at full intensity, in an example case to an accuracy of order 10% for fs-pulses, indicating the possibility of an order-of magnitude estimation of this previously inaccessible parameter.
Lipid accumulation and oxidation in glioblastoma multiforme
Authors: Taïb Bouchra , Aboussalah Amine M. , Moniruzzaman Mohammed , Chen Suming , Haughey Norman J. , Kim Sangwon F. , Ahima Rexford S.
Published: December 2019

Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.
Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice
Authors: Lang Philipp , Hasselwander Solveig , Li Huige , Xia Ning
Published: December 2019

The aim of the present study was to compare different diets used to induce obesity in a head-to-head manner with a focus on insulin resistance and vascular dysfunction. Male C57BL/6J mice were put on standard chow diet (SCD), normal-fat diet (NFD), cafeteria diet (CAF) or high-fat diet (HFD) for 12 weeks starting at the age of 6 weeks. Both CAF and HFD led to obesity (weight gain of 179% and 194%, respectively), glucose intolerance and insulin resistance to a comparable extent. In aortas containing perivascular adipose tissue (PVAT), acetylcholine-induced vasodilation was best in the NFD group and worst in the CAF group. Reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 was observed in both CAF and HFD groups. Plasma coagulation activity was highest in the HFD group and lowest in the SCD group. Even the NFD group had significantly higher coagulation activity than the SCD group. In conclusions, CAF and HFD are both reliable mouse diets in inducing visceral obesity, glucose intolerance and insulin resistance. CAF is more effective than HFD in causing PVAT dysfunction and vascular dysfunction, whereas hypercoagulability was mostly evident in the HFD group. Coagulation activity was higher in NFD than NCD group.