bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of the Initial Cost Associated With Resection Versus Laparoscopic Radiofrequency Ablation of Small Solitary Colorectal Liver Metastasis
Authors: Takahashi Hideo , Akyuz Muhammet , Kahramangil Bora , Kose Emin , Aucejo Federico , Fung John , Berber Eren
Published: September 2018

Introduction:

The aim of this report was to perform a cost-comparison between liver resection (LR) and radiofrequency ablation (RFA).

Method:

Patients with colorectal liver metastasis (CRLM)≤3 cm, who underwent LR or laparoscopic RFA between 2006 and 2015 were included in the study. Using a prospectively maintained CRLM database, clinical, oncologic, and financial parameters were compared.

Results:

Sixty-three patients underwent open or laparoscopic LR, and 25 patients underwent laparoscopic RFA. No significant difference was noted in postoperative complications, readmission rate, and local recurrence rate. With a median follow-up of 40 months for RFA, and 36 months for LR (P=0.61), mean cancer-specific overall survival was 51 months for RFA and 63 months for LR (P=0.64). The median disease-free survival was 14 months for RFA, and 21 months for LR (P=0.59). The mean operating room and hospital costs were 51% and 55% higher in the LR (P<0.001, each).

Conclusions:

The results of the study suggest that in selected patients with small solitary CRLM, laparoscopic tumor ablation might offer opportunities for cost-savings compared with resection as the primary treatment. This model may suggest possible equivalent oncologic outcomes between the 2 modalities.
Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats
Authors: McKinley Todd O. , Lei Zhigang , Kalbas Yannik , White Fletcher A. , Shi Zhongshan , Wu Fan , Xu Zao C. , Rodgers Richard B.
Published: September 2018

BACKGROUND

Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS.

METHODS

Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact to their brain and pressure-controlled HS. Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96 hours postinjury.

RESULTS

Hemoadsorption improved survival from 47% in sham-treated rats to 86% in HA-treated rats. There were no treatment-related changes in histologic appearance. Hemoadsorption affected biomarker concentrations both during the treatment and over the ensuing 4 days after injury. Distinct changes in biomarker concentrations were also measured in survivor and nonsurvivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury.

CONCLUSION

Blood purification by nonselective HA is an effective intervention to prevent death in a combined TBI/HS rat model. Hemoadsorption changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. Hemoadsorption has been safely implemented in human patients with sepsis and may be a treatment option after injury.
Aortic branch vessel flow during resuscitative endovascular balloon occlusion of the aorta
Authors: Hoehn Melanie R. , Teeter William A. , Morrison Jonathan J. , Gamble William B. , Hu Peter , Stein Deborah M. , Brenner Megan L. , Scalea Thomas M.
Published: September 2018

BACKGROUND

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a torso hemorrhage control adjunct. Aortic branch vessel flow (BVF) during REBOA is poorly characterized and has implications for ischemia-reperfusion injury. The aim of this study is to quantify BVF in hypovolemic shock with and without REBOA.

METHODS

Female swine (79–90 kg) underwent anesthesia, 40% controlled hemorrhage and sonographic flow monitoring of the carotid, hepatic, superior mesenteric, renal, and femoral arteries. Animals were randomized to REBOA (n = 5) or no-REBOA (n = 5) for 4 hours, followed by full resuscitation and balloon deflation for 1 hour.

RESULTS

All animals were successfully induced into hemorrhagic shock with a mean decrease of flow in all vessels of 50% from baseline (p < 0.001). Deployment of REBOA resulted in a 200% to 400% increase in carotid flow, but near complete abolition of BVF distal to the balloon. The no-REBOA group saw recovery of BVF to 100% of baseline in all measured vessels, except the hepatic at 50% to 75%. two-way analysis of variance confirmed a significant difference between the groups throughout the protocol (p < 0.001). During resuscitation, the REBOA group saw BVF restore to between 25% and 50%, but never achieving baseline values. The lactate at 4 hours was significantly higher in the REBOA versus no-REBOA group (17.2 ± 0.1 vs. 4.9 ± 1.4; p < 0.001).

CONCLUSION

REBOA not only abolishing BVF during occlusion, but appears to have a post-REBOA effect, reducing visceral perfusion. This may be a source of REBOA associated ischemia-reperfusion injury and warrants further investigation in order to mitigate this effect.
Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation From Maastricht Category-III Donors After Circulatory Death
Authors: Favi Evaldo , Puliatti Carmelo , Iesari Samuele , Monaco Andrea , Ferraresso Mariano , Cacciola Roberto
Published: September 2018

Background

Standard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use.

Methods

In this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor <60 years, 72 recipients) or old DCD (donor ≥60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor ≥60 years, 40 recipients).

Results

After 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 45.0, 33.0-58.0 mL/min per 1.73 m2; P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 41, 40.0-42.0 mL/min per 1.73 m2; P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti–IL2-receptor-α monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss.

Conclusions

Overall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation.
Retinal Nerve Fiber Layer and Peripapillary Capillary Density Reduction Detected Using Optical Coherence Tomography Enface Images and Angiography in Optic Tract Syndrome
Authors: Goto Katsutoshi , Miki Atsushi , Yamashita Tsutomu , Araki Syunsuke , Takizawa Go , Ieki Yoshiaki , Kiryu Junichi
Published: September 2018

In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.
Double-Shock Stimulation of the Superficial Radial Nerve Compared With Standard Medial Plantar Nerve Conduction in the Early Detection of Asymptomatic Diabetic Neuropathy: A Pilot Study
Authors: Thabit Mohamed N. , Sedky Alaaeldin , Sayed Mohamed A. , Baddary Hemed M. , Mohamed Menatollah
Published: September 2018

Purpose:

Diabetes mellitus is a major public health problem. Diabetic polyneuropathy (DP) is one of the most common complications of diabetes mellitus. The early detection of DP is very important for timely treatment of symptoms and preventative foot care.

Methods:

Participants were sorted into 3 age- and sex-matched groups: 20 “healthy” individuals; 21 diabetic patients without DP symptoms, “asymptomatic”; and 24 diabetic patients suffering from symptoms consistent with DP, “symptomatic.” All study participants had normal results on conventional nerve conduction studies. All groups underwent both medial plantar mixed nerve conduction (as a single-shock stimulation technique) and superficial radial nerve conduction (double-shock stimulation) measurements. Interstimulus intervals of 2 to 8 ms were used to record sensory nerve action potentials (SNAP) 1 and SNAP 2 for both stimuli.

Results:

We found statistically significant decreases in medial plantar NAPs' amplitude and conduction velocity, and SNAP1/SNAP2 ratios between the three groups, especially at smaller interstimulus intervals.

Conclusions:

Both medial plantar mixed nerve conduction and double-shock superficial radial nerve stimulation are reliable methods for the early detection of asymptomatic DP. However, the medial plantar mixed nerve technique is easier and less time-consuming.
Intraoperative Neuromonitoring of Motor-Evoked Potentials in Infants Undergoing Surgery of the Spine and Spinal Cord
Authors: Aydinlar Elif Ilgaz , Dikmen Pinar Yalinay , Kocak Muge , Baykan Nigar , Seymen Nogayhan , Ozek Memet Metin
Published: September 2018

Purpose:

The aim of this single-center prospective cohort study is to record reliable transcranial motor-evoked potentials (TcMEPs) and to determine their thresholds under inhalational anesthesia in infants undergoing spine and spinal cord surgery.

Methods:

A total of 15 infants (age <12 months) with mean (SD) months: 5.82 ± 3.45 were included. The entry criteria were that the child should be no older than 1 year of age and undergoing a surgical procedure at the conus-cauda region. The patients were monitored with motor-evoked potentials (TcMEPs) and bulbocavernosus reflex.

Results:

Transcranial motor-evoked potentials were recorded in all the patients in both upper and lower extremities in one muscle at least. All patients were monitored with a mean TcMEP threshold of 488.46 ± 99.76 V (range 310–740 V). The lowest threshold of TcMEPs was used to record the musculus abductor pollicis brevis mean of 315.15 ± 126.95 V (range 140–690 V) and the highest for musculus sphincter ani mean of 444.17 ± 138.54 V (range 206–700 V).

Conclusions:

Intraoperative neuromonitoring for spine and spinal cord procedures of the infant population requires higher TcMEP thresholds and train count. Most patients aged older than 6 months require significantly lower TcMEPs.
Calciphylaxis
Authors: Masoetsa Richard , A'Groof Ala , Kapoor Madan , Messenger Grace , Hussain Imtiaz
Published: September 2018

BACKGROUND:

Calciphylaxis is a potentially life-threatening condition involving painful necrotic skin ulcerations, especially of the lower extremities. It is generally associated with chronic kidney failure but may be seen in nonuremic cases.

CASE REPORT:

We report a case of calciphylaxis in a 60-year-old man with diabetes on dialysis for end-stage renal disease and known to have other typical combination of risk factors associated with calciphylaxis syndrome. On examination, he presented with multiple intensely painful calciphylaxis wounds on his legs and ankles. Despite regular wound management of his condition in our ambulatory care setting, his ulcers deteriorated. The patient's pain also increased and he was referred for hospital admission.

CONCLUSION:

This case presentation emphasizes the importance of an interdisciplinary team in the treatment of the complex, life-threatening cutaneous manifestations of calciphylaxis. When indicated, prompt referral to a hospital setting is necessary for appropriate care.
Intermittent Catheterization and Urinary Tract Infection
Authors: Faleiros Fabiana , de Oliveira Käppler Christoph , Rosa Talita , Gimenes Fernanda Raphael Escobar
Published: September 2018

PURPOSE:

The purpose of this study was to describe and compare factors that affect urinary tract infection (UTI) rates in people with spina bifida (SB) and neurogenic bladder dysfunction before and following initiation of intermittent catheterization (IC).

DESIGN:

A quantitative, descriptive, correlational study.

SUBJECTS AND SETTING:

The study included people who were from Germany, a high-income nation, and Brazil, a middle-income nation. Brazilian participants were recruited from a public rehabilitation hospital in the state of Minas Gerais. German participants were drawn from different regions of the country. The study sample included 200 participants; participants were either individuals diagnosed with SB and neurogenic bladder dysfunction and using IC, or caregivers of persons using IC for bladder management.

METHODS:

Data were collected through a survey questionnaire developed for urological follow-up of SB patients. A translated and validated version of the form was used to collect data in Germany. To evaluate annual episodes of UTI, we considered the number of symptomatic UTI before and after IC.

RESULTS:

Participants from Brazil were significantly younger than German patients (median age 9 vs 20 years, P < .001). Brazilians predominately used assisted catheterization (63.0%), whereas most Germans performed self-catheterization (61.0%). Use of IC greatly reduced the incidence of UTI in both groups (mean 2.8 episodes per year before IC vs mean 1.1 episodes after starting IC, P < .001). Women had a higher number of UTI, both before and after IC, but enjoyed greater reduction in UTI after initiating IC than men. Self-catheterization also promoted a greater reduction of UTI than assisted IC (P = .022).

CONCLUSIONS:

Intermittent catheterization reduced annual episodes of UTI in both samples despite differences in catheterization technique. Patients practicing and performing self-catheterization achieved a greater reduction than those who relied on assisted IC. Comparative studies among additional countries with varying median income levels are needed to better understand the needs of individuals with SB and their families, and to plan and implement safe nursing interventions.
All common bipedal gaits emerge from a single passive model
Authors: Gan Zhenyu , Yesilevskiy Yevgeniy , Zaytsev Petr , Remy C. David
Published: September 2018

In this paper, we systematically investigate passive gaits that emerge from the natural mechanical dynamics of a bipedal system. We use an energetically conservative model of a simple spring-leg biped that exhibits well-defined swing leg dynamics. Through a targeted continuation of periodic motions of this model, we systematically identify different gaits that emerge from simple bouncing in place. We show that these gaits arise along one-dimensional manifolds that bifurcate into different branches with distinctly different motions. The branching is associated with repeated breaks in symmetry of the motion. Among others, the resulting passive dynamic gaits include walking, running, hopping, skipping and galloping. Our work establishes that the most common bipedal gaits can be obtained as different oscillatory motions (or nonlinear modes) of a single mechanical system with a single set of parameter values. For each of these gaits, the timing of swing leg motion and vertical motion is matched. This work thus supports the notion that different gaits are primarily a manifestation of the underlying natural mechanical dynamics of a legged system. Our results might explain the prevalence of certain gaits in nature, and may provide a blueprint for the design and control of energetically economical legged robots.
The global geography of human subsistence
Authors: Gavin Michael C. , Kavanagh Patrick H. , Haynie Hannah J. , Bowern Claire , Ember Carol R. , Gray Russell D. , Jordan Fiona M. , Kirby Kathryn R. , Kushnick Geoff , Low Bobbi S. , Vilela Bruno , Botero Carlos A.
Published: September 2018

How humans obtain food has dramatically reshaped ecosystems and altered both the trajectory of human history and the characteristics of human societies. Our species' subsistence varies widely, from predominantly foraging strategies, to plant-based agriculture and animal husbandry. The extent to which environmental, social and historical factors have driven such variation is currently unclear. Prior attempts to resolve long-standing debates on this topic have been hampered by an over-reliance on narrative arguments, small and geographically narrow samples, and by contradictory findings. Here we overcome these methodological limitations by applying multi-model inference tools developed in biogeography to a global dataset (818 societies). Although some have argued that unique conditions and events determine each society's particular subsistence strategy, we find strong support for a general global pattern in which a limited set of environmental, social and historical factors predicts an essential characteristic of all human groups: how we obtain our food.
Removal of Cr
6+
ions from water by electrosorption on modified activated carbon fibre felt
Authors: Zhao Xinkun , Jia Bingxin , Sun Qianqian , Jiao Gaojie , Liu Lili , She Diao
Published: September 2018

Electrosorption is a novel desalination technique that has many advantages in the treatment of sewage. However, commercially available activated carbon electrodes for electrosorption commonly have low microporosity, poor moulding performance, and low adsorption and regeneration efficiency. Here, we evaluated a novel adsorbent material, activated carbon fibre felt (ACFF), for electrosorption of chromium ions (Cr
6+
) in sewage treatment. The ACFF was modified with 20% nitric acid and its modified structure was characterized. The modified ACFF was used as an adsorbing electrode to investigate its desalination effect by electrosorption. Results showed that compared with those of unmodified ACFF, the modified ACFF had more carbonyl and carboxyl groups and the specific surface area, average pore size and micropore volume of the modified ACFF also improved by 32.2%, 2.5% and 23.1%, respectively. The kinetics of Cr
6+
adsorption conformed to the pseudo-second-order kinetic equation, and the adsorption isotherm conformed to the Langmuir model. In addition, the regeneration rate of the modified ACFF electrode was more than 94%. In conclusion, the modified ACFF exhibits excellent electrosorption and regeneration performance for Cr
6+
removal from water and thus is of great value for promotion in sewage treatment.
Composition, mineralization potential and release risk of nitrogen in the sediments of Keluke Lake, a Tibetan Plateau freshwater lake in China
Authors: Wang W. W. , Jiang X. , Zheng B. H. , Chen J. Y. , Zhao L. , Zhang B. , Wang S. H.
Published: September 2018

The lakes distributed in the Tibetan Plateau constitute a lake group with the highest altitude, largest lakes and largest area in the world and are important in global climate and environmental effects. Freshwater lakes in the Tibetan Plateau possess high ecological values and high vulnerability. The migration and transformation of nitrogen in sediments are critical to lake ecosystems, but information on sedimentary nitrogen in the freshwater lakes in the Tibetan Plateau is limited. A case study was conducted in Keluke Lake, China, to reveal the effects of sedimentary nitrogen on water quality in plateau freshwater lakes. Nitrogen speciation, mineralization potential and release flux were analysed through a sequential extraction method, waterlogged incubation experiment and Fick's first diffusion law, respectively. The content of total nitrogen (TN) was 1295.75–6151.69 mg kg
−1
, and 94.2% of TN was organic nitrogen (ON). The contents of three nitrogen fractions were in the order of hydrolysable nitrogen > residual nitrogen > exchangeable nitrogen. Ammonia nitrogen

(
N

H
4
+

−
N
)

was the main mineralization product, and hydrolysable ON was the most significant contributor. The sediments showed a great mineralization potential, with a potentially mineralizable nitrogen value of 408.76 mg N kg
−1
of sediment, that was mainly affected by hydrolysable ammonium nitrogen. The

N

H
4
+

−
N

diffusion flux ranged from 24.14 to 148.75 mg m
−2
d
−1
, and the sediments served as an internal nitrogen source. Nitrogen release from sediments was considerably influenced by exchangeable ammonia nitrogen. The sediments in Keluke Lake pose a potential nitrogen release risk and threaten the water quality of the lake. The total content, speciation, mineralization of ON and the release flux at sediment–water interface should be considered comprehensively to evaluate the effects of nitrogen in sediments to water quality.
The catalytic effect of calcium and potassium on CO
2
gasification of Shengli lignite: the role of carboxyl
Authors: Ban Yanpeng , Wang Yan , Li Na , He Runxia , Zhi Keduan , Liu Quansheng
Published: September 2018

The CO
2
gasification of Chinese Shengli lignite (SL) catalysed by K
+
and Ca
2+
was studied. The results showed that calcium could greatly decrease the gasification reaction temperature of SL, and the gasification reaction rates of acid-treated SL catalysed by calcium were significantly higher than that catalysed by potassium. Kinetic analysis showed that the activation energy of the reaction catalysed by calcium was much lower than that catalysed by potassium, which was the reason for the higher catalytic activity of calcium. Fourier transform infrared characterization showed that, compared with acid-treated SL, the addition of K
+
/Ca
2+
resulted in the significant weakening of C=O bond, and new peaks attributed to carboxylate species appeared. X-ray photoelectron spectroscopy results indicated that the numbers of C=O decreased after the metal ions were added, indicating the formation of metal–carboxylate complexes. Raman characterization showed that the
I
D1
/
I
G
values increased, suggesting more structural defects, which indicated that the reactivity of coal samples had a close relation with amorphous carbon structures. Ca
2+
could interact with the carboxyl structure in lignite by both ionic forces and polycarboxylic coordination, while K
+
interacted with carboxyl structure mainly via ionic forces.
Synthesis of cyclic ethers by cyclodehydration of 1,
n
-diols using heteropoly acids as catalysts
Authors: Sun Yufeng , Huang Yatao , Li Minmin , Lu Jia , Jin Nuo , Fan Bei
Published: September 2018

Heteropoly acids were used as catalysts for cyclodehydration of various 1,
n
-diols. Cyclodehydration of butane-1,4-diol, pentane-1,5-diol and hexane-1,6-diol catalysed by H
3
PW
12
O
40
gave tetrahydrofuran, tetrahydropyran and oxepane, respectively. Cyclodehydration of diethylene glycol, triethylene glycol, diethylene glycol monomethyl ether and polyethylene glycol 200 catalysed by H
3
PW
12
O
40
gave 1,4-dioxane. In particular, cyclodehydration of hexane-1,6-diol gave an excellent yield of oxepane (80%). The selectivity exhibited by the H
3
PW
12
O
40
catalyst was even better than that exhibited by other reported catalyst systems for similar cyclodehydration reactions.
Synthesis of transition metal sulfide and reduced graphene oxide hybrids as efficient electrocatalysts for oxygen evolution reactions
Authors: Hong Yu-Rim , Mhin Sungwook , Kwon Jiseok , Han Won-Sik , Song Taeseup , Han HyukSu
Published: September 2018

The development of electrochemical devices for renewable energy depends to a large extent on fundamental improvements in catalysts for oxygen evolution reactions (OERs). OER activity of transition metal sulfides (TMSs) can be improved by compositing with highly conductive supports possessing a high surface-to-volume ratio, such as reduced graphene oxide (rGO). Herein we report on the relationship between synthetic conditions and the OER catalytic properties of TMSs and rGO (TMS–rGO) hybrids. Starting materials, reaction temperature and reaction time were controlled to synergistically boost the OER catalytic activity of TMS–rGO hybrids. Our results showed that (i) compared with sulfides, hydroxides are favourable as starting materials to produce the desired TMS–rGO hybrid nanostructure and (ii) high reaction temperatures and longer reaction times can increase physico-chemical interaction between TMSs and rGO supports, resulting in highly efficient OER catalytic activity.
Effect of the second chromophore energy gap on photo-induced electron injection in di-chromophoric porphyrin-sensitized solar cells
Authors: Zhao Long
Published: September 2018

This work investigates the effect of the second chromophore energy gap on charge generation in porphyrin-based di-chromophoric dye-sensitized solar cells (DSSCs). Three di-chromophoric porphyrin dyes (PorY, PorO and PorR) containing three organic chromophores with decreasing frontier orbital energy offsets, including a carbazole-triphenylamine chromophore (yellow, Y), a carbazole fused-thiophene chromophore (orange, O) or a carbazole-thiophene benzothiadiazole thiophene chromophore (red, R), were investigated using optical and electrochemical methods, steady-state photoluminescence and photovoltaic device characterization. Energy transfer from the organic chromophore to the porphyrin was suggested in PorY and PorO as the main charge generation mechanism in DSSCs using these di-chromophoric dyes. On the other hand, electron transfer from the photo-excited porphyrin to the organic chromophore as a competing pathway leading to the loss of photocurrent is suggested for PorR-sensitized solar cells. The latter pathway leading to a loss of photocurrent is due to the lower lying lowest unoccupied molecular orbital of the additional organic chromophore (R) and suggests the limitation of the current di-chromophoric approach to increase the overall efficiency of DSSCs.
Unexpected diversity within the extinct elephant birds (Aves: Aepyornithidae) and a new identity for the world's largest bird
Authors: Hansford James P. , Turvey Samuel T.
Published: September 2018

Madagascar's now-extinct radiation of large-bodied ratites, the elephant birds (Aepyornithidae), has been subject to little modern research compared to the island's mammalian megafauna and other Late Quaternary giant birds. The family's convoluted and conflicting taxonomic history has hindered accurate interpretation of morphological diversity and has restricted modern research into their evolutionary history, biogeography and ecology. We present a new quantitative analysis of patterns of morphological diversity of aepyornithid skeletal elements, including material from all major global collections of aepyornithid skeletal remains, and constituting the first taxonomic reassessment of the family for over 50 years. Linear morphometric data collected from appendicular limb elements, and including nearly all type specimens, were examined using multivariate cluster analysis and the Bayesian information criterion, and with estimation of missing data using multiple imputation and expectation maximization algorithms. These analyses recover three distinct skeletal morphotypes within the Aepyornithidae. Two of these morphotypes are associated with the type specimens of the existing generaMullerornisandAepyornis, and represent small-bodied and medium-bodied aepyornithids, respectively.Aepyorniscontains two distinct morphometric subgroups, which are identified as the largely allopatric speciesA. hildebrandtiandA. maximus.The third morphotype, which has not previously been recognized as a distinct genus, is described as the novel taxonVorombe titan.Voromberepresents the largest-bodied aepyornithid and is the world's largest bird, with a mean body mass of almost 650 kg. This new taxonomic framework for the Aepyornithidae provides an important new baseline for future studies of avian evolution and the Quaternary ecology of Madagascar.
An ordinary state-based peridynamic model for the fracture of zigzag graphene sheets
Authors: Liu Xuefeng , He Xiaoqiao , Wang Jinbao , Sun Ligang , Oterkus Erkan
Published: September 2018

This study develops an ordinary state-based peridynamic coarse-graining (OSPD-CG) model for the investigation of fracture in single-layer graphene sheets (SLGS), in which the peridynamic (PD) parameters are derived through combining the PD model and molecular dynamics (MD) simulations from the fully atomistic system via energy conservation. The fracture failure of pre-cracked SLGS under uniaxial tension is studied using the proposed PD model. And the PD simulation results agree well with those from MD simulations, including the stress–strain relations, the crack propagation patterns and the average crack propagation velocities. The interaction effect between cracks located at the centre and the edge on the crack propagation of the pre-cracked SLGS is discussed in detail. This work shows that the proposed PD model is much more efficient than the MD simulations and, thus, indicates that the PD-based method is applicable to study larger nanoscale systems.
Influence of early-life nutritional stress on songbird memory formation
Authors: Bell B. A. , Phan M. L. , Meillère A. , Evans J. K. , Leitner S. , Vicario D. S. , Buchanan K. L.
Published: September 2018

In birds, vocal learning enables the production of sexually selected complex songs, dialects and song copy matching. But stressful conditions during development have been shown to affect song production and complexity, mediated by changes in neural development. However, to date, no studies have tested whether early-life stress affects the neural processes underlying vocal learning, in contrast to song production. Here, we hypothesized that developmental stress alters auditory memory formation and neural processing of song stimuli. We experimentally stressed male nestling zebra finches and, in two separate experiments, tested their neural responses to song playbacks as adults, using either immediate early gene (IEG) expression or electrophysiological response. Once adult, nutritionally stressed males exhibited a reduced response to tutor song playback, as demonstrated by reduced expressions of two IEGs (
Arc
and
ZENK
) and reduced neuronal response, in both the caudomedial nidopallium (NCM) and mesopallium (CMM). Furthermore, nutritionally stressed males also showed impaired neuronal memory for novel songs heard in adulthood. These findings demonstrate, for the first time, that developmental conditions affect auditory memories that subserve vocal learning. Although the fitness consequences of such memory impairments remain to be determined, this study highlights the lasting impact early-life experiences can have on cognitive abilities.
Royalactin induces copious longevity via increased translation and proteasome activity in C. elegans
Authors: Detienne Giel , Van de Walle Pieter , De Haes Wouter , Cockx Bram , Braeckman Bart P. , Schoofs Liliane , Temmerman Liesbet
Published: September 2018

As demonstrated in various animal models, organismal longevity can be achieved via interventions that at the mechanistic level could be considered to entail ‘defensive’ responses: most long-lived mutants focus on somatic maintenance, while reducing growth pathway signalling and protein translation and turnover. We here provide evidence that the opposite mechanism can also lead to longevity and improved health.

We report on the mode of action of royalactin, a glycoprotein activator of epidermal growth factor signalling, capable of extending lifespan in several animals. We show that in Caenorhabditis elegans, royalactin-induced longevity depends on increased protein translation and entails increased proteasome activity. We propose the term ‘copious longevity’ to describe this newly-elucidated mechanism. In contrast to what is true for many other lifespan-extending interventions, we observed no obvious trade-offs between royalactin-induced longevity and several life history traits. Our data point towards increased protein turnover to support healthy ageing, and provide a means for future comparative studies of defensive vs. copious mechanisms.
BrainNet: A Multi-Person Brain-to-Brain Interface for Direct Collaboration Between Brains
Authors: Jiang Linxing , Stocco Andrea , Losey Darby M. , Abernethy Justin A. , Prat Chantel S. , Rao Rajesh P. N.
Published: September 2018

We present BrainNet which, to our knowledge, is the first multi-human non-invasive direct brain-to-brain interface for collaborative problem solving. The interface combines electroencephalography (EEG) to record brain signals and transcranial magnetic stimulation (TMS) to deliver information noninvasively to the brain. The interface allows three human subjects to collaborate and solve a task using direct brain-to-brain communication. Two of the three subjects are designated as “Senders” whose brain signals are decoded using real-time EEG data analysis. The decoding process extracts each Sender’s decision about whether to rotate a block in a Tetris-like game before it is dropped to fill a line. The Senders’ decisions are transmitted via the Internet to the brain of a third subject, the “Receiver,” who cannot see the game screen. The Senders’ decisions are delivered to the Receiver’s brain via magnetic stimulation of the occipital cortex. The Receiver integrates the information received from the two Senders and uses an EEG interface to make a decision about either turning the block or keeping it in the same orientation. A second round of the game provides an additional chance for the Senders to evaluate the Receiver’s decision and send feedback to the Receiver’s brain, and for the Receiver to rectify a possible incorrect decision made in the first round. We evaluated the performance of BrainNet in terms of (1) Group-level performance during the game, (2) True/False positive rates of subjects’ decisions, and (3) Mutual information between subjects. Five groups, each with three human subjects, successfully used BrainNet to perform the Tetris task, with an average accuracy of 81.25%. Furthermore, by varying the information reliability of the Senders by artificially injecting noise into one Sender’s signal, we investigated how the Receiver learns to integrate noisy signals in order to make a correct decision. We found that like conventional social networks, BrainNet allows Receivers to learn to trust the Sender who is more reliable, in this case, based solely on the information transmitted directly to their brains. Our results point the way to future brain-to-brain interfaces that enable cooperative problem solving by humans using a “social network” of connected brains.
Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites
Authors: Guo Yukuang , Crnkovic Camila Manoel , Won Kyoung-Jae , Yang Xiaotong , Lee John Richard , Orjala Jimmy , Lee Hyunwoo , Jeong Hyunyoung
Published: September 2018

Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance ofFaecalibacterium prausnitziiand oral tacrolimus dose in kidney transplant patients, we tested whetherF. prausnitziiand other gut abundant bacteria are capable of metabolizing tacrolimus. Incubation ofF. prausnitziiwith tacrolimus led to production of two compounds (the major one named M1), which was not observed upon tacrolimus incubation with hepatic microsomes. Isolation, purification, and structure elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy indicated that M1 is a C-9 keto-reduction product of tacrolimus. Pharmacological activity testing using human peripheral blood mononuclear cells demonstrated that M1 is 15-fold less potent than tacrolimus as an immunosuppressant. Screening of 22 gut bacteria species revealed that mostClostridialesbacteria are extensive tacrolimus metabolizers. Tacrolimus conversion to M1 was verified in fresh stool samples from two healthy adults. M1 was also detected in the stool samples from kidney transplant recipients who had been taking tacrolimus orally. Together, this study presents gut bacteria metabolism as a previously unrecognized elimination route of tacrolimus, potentially contributing to the low and variable tacrolimus exposure after oral dosing.
SWI/SNF coordinates transcriptional activation through Rpd3-mediated histone hypoacetylation during quiescence entry
Authors: Spain Marla M. , Braceros Keean C.A. , Tsukiyama Toshio ,   Fred Hutchinson Cancer Research Center, Division of Basic Sciences
Published: September 2018

Whether or not a cell chooses to divide is a tightly regulated and extremely important decision. Cells from yeast to human are able to reversibly exit the cell cycle in response to environmental changes such as nutritional changes or removal of growth cues to become quiescent. An inappropriate response to environmental cues can result in overproliferation which can lead to cancer, or a failure to proliferate which can result in developmental defects, premature aging and defects in wound healing. While many of the cell signaling pathways involved in regulating cellular quiescence have been identified, how these pathways translate their messages into transcriptional outputs is not well characterized. We previously showed that the histone deacetylase Rpd3 mediates global histone deacetylation and transcription repression upon quiescence entry. How the activation of quiescence-specific genes occurs in the midst of this transcriptionally repressive environment is not well understood. We show that the SWI/SNF chromatin remodeling complex activates quiescence specific genes to promote entry into quiescence. We additionally show that SWI/SNF binding early during quiescence entry is important for facilitating localization of the transcriptional activator Gis1, as well as histone H4 hypoacetylation in coding regions later on. The increase in H4 acetylation that we observe at Snf2-regulated genes upon Snf2 depletion corresponds to a decrease in promoter-bound Rpd3, suggesting that Snf2 remodels chromatin not only to facilitate activator binding, but also the binding of Rpd3. These observations provide mechanistic insight as to how quiescence-specific genes can be activated in the face of global deacetylation and transcription repression.
Slow transcriptional elongation causes embryonic lethality and perturbs kinetic coupling of long neural genes
Authors: Maslon Magdalena M. , Braunschweig Ulrich , Aitken Stuart , Mann Abigail R. , Kilanowski Fiona , Hunter Chris J. , Blencowe Benjamin J. , Kornblihtt Alberto R. , Adams Ian R. , Cáceres Javier F.
Published: September 2018

The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of Alternative splicing (AS); however, thein vivoconsequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice and impairs the differentiation of ESCs into the neural lineage. This is accompanied by changes in splicing and in gene expression in ESCs and along the pathway of neuronal differentiation. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is more predominant in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.
Human chaperones untangle fibrils of the Alzheimer protein Tau
Authors: Ferrari Luca , Geerts Willie J.C. , van Wezel Marloes , Kos Renate , Konstantoulea Aikaterini , van Bezouwen Laura S. , Förster Friedrich G. , Rüdiger Stefan G.D.
Published: September 2018

Alzheimer’s Disease is the most common neurodegenerative disorder. A hallmark of this disease is aggregation of the protein Tau into fibrillar tangles, which is ultimately linked to neuronal death 1,2. Oligomeric precursors of Tau fibrils are suspected to be the neurotoxic agent while fibrils themselves may be less harmful end products of the aggregation process 3,4. Evolutionary conserved families of molecular chaperones maintain protein homeostasis in healthy cells, preventing aggregation 5,6. Here, we investigate whether such chaperones could possibly reverse the aggregation reaction and dissolve Tau fibrils. Indeed we find that the human Hsp70 chaperone system disaggregates Tau fibrils. Both the bacterial and human Hsp70 chaperone systems disassemble fibril superstructures assembled of several fibril strands into single fibrils, indicating that this is an evolutionary conserved capacity of the Hsp70 system. However, further disaggregation of Tau fibrils into oligomers and even monomers is reserved to the human homologue. Thus, although bacteria possess an effective machinery to dissolve amorphous aggregates 7-9, we see that they do not have the means to disaggregate fibrils. Fibrillar aggregates, therefore, require different chaperone systems than amorphous aggregates, and this is a property acquired by Hsp70 during evolution. This makes the Hsp70 system an interesting target for novel drug strategies in Alzheimer.
Leveraging mouse chromatin data for heritability enrichment informs common disease architecture and reveals cortical layer contributions to schizophrenia
Authors: Hook Paul W. , McCallion Andrew S.
Published: September 2018

Genome-wide association studies have implicated thousands of non-coding variants across human phenotypes. However, they cannot directly inform the cellular context in which disease-associated variants act. Here, we use open chromatin profiles from discrete mouse cell populations to address this challenge. We applied stratified linkage disequilibrium score regression and evaluated heritability enrichment in 64 genome-wide association studies, emphasizing schizophrenia. We provide evidence that mouse-derived human open chromatin profiles can serve as powerful proxies for difficult to obtain human cell populations, facilitating the illumination of common disease heritability enrichment across an array of human phenotypes. We demonstrate signatures from discrete subpopulations of cortical excitatory and inhibitory neurons are significantly enriched for schizophrenia heritability with maximal enrichment in discrete cortical layer V excitatory neurons. We also show differences between schizophrenia and bipolar disorder are concentrated in excitatory neurons in layers II-III, IV, V as well as the dentate gyrus. Finally, we use these data to fine-map variants in 177 schizophrenia loci, nominating variants in 104/177 loci, and place them in the cellular context where they may modulate risk.
Whole-Mount Immunofluorescence for Visualizing Endogenous Protein and Injected RNA in Xenopus Oocytes
Authors: Jeschonek Samantha P. , Mowry Kimberly L.
Published: September 2018

Asymmetric distribution of mRNA and protein is a hallmark of cell polarity in many systems. The Xenopus laevis oocyte provides many technical advantages to studying such polarity. Thousands of oocytes at different stages of maturity can be harvested from a single ovary and, owing to their relatively large size, even the youngest oocytes can be manually microinjected. Microinjection of fluorescently labeled RNA combined with immunofluorescence of endogenous proteins can provide insight into the cytoplasmic interactions contributing to polarity. Here, we present an updated method to image endogenous protein and microinjected RNA in X. laevis oocytes.
Spemann–Mangold Grafts
Authors: Cousin Hélène
Published: September 2018

In 1924, Hans Spemann and Hilde Mangold (née Pröscholdt) published their famous work describing the transplantation of dorsal blastopore lip of one newt gastrula embryo onto the ventral side of a host embryo at the same stage. They performed these grafts using two newt species with different pigmentation (Triturus taeniatus and Triturus cristatus) to follow the fate of the grafted tissue. These experiments resulted in the development of conjoined twins attached through their belly. Because of the difference in embryo pigmentation between the two Triturus species, they determined that the bulk of the secondary embryo arose from the host embryo while the grafted tissue per se gave increase to the notochord and a few somitic cells. This meant that the dorsal blastopore lip was able to organize an almost complete embryo out of ventral tissue. The dorsal blastopore lip is now called the Spemann–Mangold organizer. Here, we describe a simple yet efficient protocol to perform these grafts using the anuran Xenopus laevis.
Adoptive Transfer of Fluorescently Labeled Immune Cells in Xenopus
Authors: Rhoo Kun Hyoe , Robert Jacques
Published: September 2018

Adoptive cell transfer from inbred adult Xenopus to inbred tadpoles is a useful way to study the dissemination of immune cells or pathogen-infected immune cells in tadpoles. For example, Xenopus peritoneal leukocytes (PLs) can be readily infected by pathogens such as Frog virus 3 (FV3) and Mycobacterium marinum (M. marinum). By transferring fluorescently labeled, FV3-infected PLs into tadpoles, we observed infiltration of these cells into the tadpole's brain, which indicates that FV3-infected PLs can cross blood brain barrier. Taking advantage of tadpoles’ transparency, fluorescently labeled immune cells can be tracked in real time using fluorescence microscopy.
Lymphocyte Deficiency Induced by Sublethal Irradiation in Xenopus
Authors: Rollins-Smith Louise A. , Robert Jacques
Published: September 2018

In many studies of diseases affecting amphibians, it is important to determine to what extent lymphocyte-mediated defenses are involved. For example, in studies of the nature of the immune response of Xenopus laevis to the amphibian chytrid fungus, Batrachochytrium dendrobatidis, it was essential to determine if mucosal antimicrobial peptides or lymphocyte-mediated immunity was most important for resistance to this skin pathogen. In this protocol, we describe a method for sublethal irradiation to reduce lymphocyte numbers. Briefly, X. laevis adults or tadpoles are exposed to 9 Gy (900 rads) of irradiation applied by exposure to a cesium source or gamma irradiator to reduce lymphocyte populations in the spleen.