bluuebunny/crossref_metadata_2025 huggingface dataset:
Feedback regulation of Arid5a and Ppar-γ2 maintains adipose tissue homeostasis
Authors: Chalise Jaya Prakash , Hashimoto Shigeru , Parajuli Gyanu , Kang Sujin , Singh Shailendra Kumar , Gemechu Yohannes , Metwally Hozaifa , Nyati Kishan Kumar , Dubey Praveen Kumar , Zaman Mohammad Mahabub-Uz , Nagahama Yasuharu , Hamza Hanieh , Masuda Kazuya , Kishimoto Tadamitsu
Published: July 2019

Significance

Obesity is now considered an epidemic problem worldwide. To develop effective interventions against obesity, we need to understand precisely the regulatory mechanism of adipogenesis, a process of forming adipocytes from fibroblast cells. In this study, we revealed that the Arid5a protein regulates the adipogenesis and the development of obesity in mice. Arid5a inhibits adipogenesis by suppressing the transcription of peroxisome proliferator activated receptor gamma 2 (Ppar-γ2), which is the main facilitator of adipogenesis. Further, we showed adipose tissue homeostasis is maintained by the coordinated activity of Arid5a and Ppar-γ2. Our study provides important insights into the novel mechanism of adipose tissue homeostasis.
Review on the quantum emitters in two-dimensional materials
Authors: Ren Shuliang , Tan Qinghai , Zhang Jun
Published: July 2019

The solid state single photon source is fundamental key device for application of quantum communication, quantum computing, quantum information and quantum precious metrology. After years of searching, researchers have found the single photon emitters in zero-dimensional quantum dots (QDs), one-dimensional nanowires, three-dimensional wide bandgap materials, as well as two-dimensional (2D) materials developed recently. Here we will give a brief review on the single photon emitters in 2D van der Waals materials. We will firstly introduce the quantum emitters from various 2D materials and their characteristics. Then we will introduce the electrically driven quantum light in the transition metal dichalcogenides (TMDs)-based light emitting diode (LED). In addition, we will introduce how to tailor the quantum emitters by nanopillars and strain engineering, the entanglement between chiral phonons (CPs) and single photon in monolayer TMDs. Finally, we will give a perspective on the opportunities and challenges of 2D materials-based quantum light sources.
A Tough and Efficient Self-Healing Supramolecular Materials modulated with WCNT-NH2
Authors: Ma H R , Li Y X , Jiang C , Yao Y W , Yao C
Published: July 2019

Self-healing polymers crosslinked by solely reversible bonds are intrinsically weaker than common covalently crosslinked networks. In this work, a self-healing materials with excellent mechanical properties was synthesized by a new design strategy, wich is to introduce covalent into reversible networks to improve its mechanical properties. First, polyamidoamine dendrimer oligomers (PAMAM-Oligomers) was synthesized. Then amine functionalized carbon nanotubes (WCNT-NH2) reacted with PAMAM-Oligomers to form a polyamidoamine carbon nanotubes composite materials (PAMAM-WCNT-NH2). The synthesized materials behave as rubber and exhibit spontaneous self-healing behaviour at room temperature without external stimuli. The mechanical and self-healing properties are closely related to the content of WCNT-NH2. For 0.5wt% WCNT-NH2in the materials, the strain of the material is 330% and tensile strength is 0.6 MPa. Importantly it can improve the self-healing efficiency to 98% of its original tensile strength in 2h.
Study on the influence of reflecting channel position on flow velocity characteristics of ultrasonic heat meter
Authors: Liu Yonghui , Yi Fengyan , Zhou Changfeng , Tao Lili
Published: July 2019

In this paper, LES (Large eddy simulation) method is used to study the influence of different channel positions on the flow velocity of the ultrasonic heat meter, and the variation of the average linear velocity of different channel with time is researched. Through the calculation results, the velocity characteristics of 11 channels of the U-shaped reflecting device ultrasonic heat meter are analysed. The results show that the vortex behind the reflecting cylinder affects the velocity distribution in the channel. Statistical analysis shows that the linear average velocity in different positions of the channel fluctuates with time, but the fluctuation amplitude is basically the same. The average linear velocity asymmetry of reflecting channel far from the vortex zone is smaller, and the deviation of the average velocity is less than that of the average velocity, therefore, the distribution of the velocity is more reasonable.
Pruning Neural Networks Using Multi-Armed Bandits
Authors: Ameen Salem , Vadera Sunil
Published: July 2019

The successful application of deep learning has led to increasing expectations of their use in embedded systems. This, in turn, has created the need to find ways of reducing the size of neural networks. Decreasing the size of a neural network requires deciding which weights should be removed without compromising accuracy, which is analogous to the kind of problems addressed by multi-armed bandits (MABs). Hence, this paper explores the use of MABs for reducing the number of parameters of a neural network. Different MAB algorithms, namely $\epsilon $-greedy, win-stay, lose-shift, UCB1, KL-UCB, BayesUCB, UGapEb, successive rejects and Thompson sampling are evaluated and their performance compared to existing approaches. The results show that MAB pruning methods, especially those based on UCB, outperform other pruning methods.
Outcomes after tricuspid valve surgery concomitant with left ventricular assist device implantation in the EUROMACS registry: a propensity score matched analysis
Authors: Veen Kevin M , Caliskan Kadir , de By Theo M M H , Mokhles Mostafa M , Soliman Osama I , Mohacsi Paul , Schoenrath Felix , Gummert Jan , Paluszkiewicz Lech , Netuka Ivan , Loforte Antonio , Pya Yuriy , Takkenberg Johanna J M , Bogers Ad J J C
Published: July 2019

OBJECTIVES

Tricuspid regurgitation (TR) is common in patients receiving a left ventricular assist device (LVAD). Controversy exists as to whether concomitant tricuspid valve surgery (TVS) is beneficial in currently treated patients. Therefore, our goal was to investigate the effect of TVS concomitant with a LVAD implant.

METHODS

The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients. Matched patients with and without concomitant TVS were compared using a propensity score matching strategy.

RESULTS

In total, 3323 patients underwent LVAD implantation of which 299 (9%) had TVS. After matching, 258 patients without TVS were matched to 258 patients with TVS. In the matched population, hospital deaths, days on inotropic support, temporary right ventricular assist device implants and hospital stay were comparable, whereas stay in the intensive care unit was higher in the TVS cohort (11 vs 15 days; P = 0.026). Late deaths (P = 0.17), cumulative incidence of unexpected hospital readmission (P = 0.15) and right heart failure (P = 0.55) were comparable between patients with and without concomitant TVS. In the matched population, probability of moderate-to-severe TR immediately after surgery was lower in patients with concomitant TVS compared to patients without TVS (33% vs 70%; P = 0.001). Nevertheless, the probability of moderate-to-severe TR decreased more quickly in patients without TVS (P = 0.030), resulting in comparable probabilities of moderate-to-severe TR within 1.5 years of follow-up.

CONCLUSIONS

In matched patients, TVS concomitant with LVAD implant does not seem to be associated with better clinical outcomes. Concomitant TVS reduced TR significantly early after LVAD implant; however, differences in probability of TR disappeared during the follow-up period.
Extra-phosphoric effects of super dosing phytase on growth performance of pigs is not solely due to release of myo-inositol
Authors: Lu Hang , Cowieson Aaron J , Wilson Jonathan W , Ajuwon Kolapo M , Adeola Olayiwola
Published: July 2019

Two experiments were conducted to determine the effects of myo-inositol and phytase on growth performance, plasma metabolites, and nutrient digestibility of growing pigs. In experiment 1, 96 growing pigs with average initial body weight (BW) of 26.2 kg were used in a 25-d growth performance study. Pigs were assigned to four dietary treatments with three pigs per pen and eight replicate pens per treatment in a randomized complete block design. The four treatments were control diet (CD); CD + 2 g/kg inositol; CD + 1,000 FYT/kg phytase and CD + 3,000 FYT/kg phytase. Pigs were weighed individually every week. On day 25, blood sample was collected from one pig per pen to measure plasma metabolites concentrations. In experiment 2, 16 barrows (initial BW 34.8 ± 8.2 kg) were surgically fitted with T-cannulas. Pigs were allotted to four blocks based on BW and assigned to a quadruplicate 4 × 2 incomplete Latin square design with same four dietary treatments and two periods. Ileal digesta samples were collected from each pig on days 6 and 7 of each period to determine apparent ileal digestibility (AID) of nutrients. Phytase supplementation increased final BW and average daily gain (ADG) compared with CD (P < 0.05) with no effects on average daily feed intake (ADFI) and gain to feed (G:F) was higher in 3,000 FYT/kg phytase (P < 0.05). Inositol supplementation had no effects on growth performance. Plasma myo-inositol concentration was increased by inositol supplementation, and 3,000 FYT/kg phytase increased myo-inositol in the plasma by 97.2% (P < 0.05). Plasma P concentration was increased by 1,000 or 3,000 FYT/kg phytase with no effects on alkaline phosphatase (ALP), glucose, triglycerides (TAG), calcium (Ca), and urea concentrations. Phytase supplementation reduced (P < 0.05) the phytate-P concentration in the ileal digesta and increased the digestibility of phytate-P and total P with no effects on the AID of dry matter (DM), gross energy (GE), nitrogen (N), and Ca. In conclusion, the beneficial effects of 3,000 FYT/kg phytase on feed efficiency may due to the increased release of both myo-inositol and phosphorus (P), and may not be solely due to myo-inositol release by this level of phytase.
On Attitudes to Choice: Some Experimental Evidence on Choice Aversion
Authors: Le Lec Fabrice , Tarroux Benoît
Published: July 2019

This paper investigates experimentally how people value choice. Our experiments elicit subjects’ valuations of various choice sets (or menus) that differ in size and composition. The comparison of these valuations allows us to assess subjects’ preferences between sets and test a number of the theories of preferences over menus proposed in the literature. The results suggest that subjects are choice-averse: the value of a choice set is significantly and robustly lower than that of its preferred element, and adding a suboptimal option reduces the value of a set. The data also reveal that the quality of suboptimal elements has a positive effect on set preferences. Taken together, these results suggest two possible explanations. The first is that individuals fear making bad decisions in the final choice; the second is that people value choice sets heuristically as a whole, and not on the basis of their final consequences. Other explanations of choice aversion that appear in the literature are not fully consistent with the behavior we observe.
A rare cause of small bowel diaphragm disease presenting with palpated abdominal mass
Authors: Danial Aghyad K , Al-Mouakeh Ahmad , Danial Yaman K , Nawlo Ahmad A , Khalil Ahmad , Al-Haj Ahmad
Published: July 2019

Small bowel diaphragm disease is a rare complication related to non-steroidal anti-inflammatory drug (NSAID) use. It presents with non-specific symptoms such as vomiting, abdominal pain, subacute bowel obstruction and occasionally as an acute abdominal condition. We report a case of diaphragm disease in a 33-year-old female who presented with vomiting, constipation and abdominal pain started 5 days earlier. Physical examination revealed palpated abdominal mass. The patient’s past medical history was remarkable for NSAID use. The patient was managed by surgical resection of involved intestine and diagnosis was confirmed by histological examination. Although there are few published cases of diaphragm disease in the medical literature, we recommend that this disease should be considered as one of the differential diagnoses when assessing patients presenting with non-specific abdominal symptoms with remarkable past medical history of NSAID use.
Development and Trial Implementation of a 30-Day Outpatient Program for Subthreshold PTSD
Authors: Mallonee Sybil , Tate Larissa , De Oliveira Fernanda , Ruiz Augusto
Published: July 2019

Introduction

Posttraumatic stress disorder (PTSD) negatively impacts service members at high rates, causing considerable physical and psychological consequences. Additionally, many service members experience subthreshold PTSD (i.e., experiencing PTSD symptoms that do not meet full diagnostic criteria), which has also been shown to cause significant functional impairment and can be a precursor to the development of full PTSD. Typically, treatment for PTSD at Walter Reed National Military Center facility includes weekly outpatient individual therapy over a three-month period or referral to an intensive outpatient program (IOP), which emphasizes group treatment. Inclusion in these programs is dependent on the severity of symptoms. Service members with subthreshold symptoms do not typically qualify for an IOP, and weekly outpatient therapy does not meet the needs of some service members or their commands.

Methods

As a result, we developed an alternative program with the intention of allowing service members with subthreshold PTSD to receive treatment and return to full-duty status more rapidly. The program emphasized bi-weekly evidenced-based PTSD therapies treatment adjusted to meet the needs of each service member along with the option of adjunct individual and group treatments.

Results

While this program is ongoing and we have not yet conducted outcome data analyses, the structure and pace of this program have the potential to produce quicker functional improvements, prevent the development of full PTSD symptoms, and reduce long-term or recurring healthcare utilization.

Conclusion

Although more research is needed, there exists preliminary empirical evidence of efficacy for an accelerated protocol of biweekly evidence-based therapy for service members with subthreshold PTSD.

Disclaimer

The opinions expressed in this abstract are those of the authors and do not necessarily represent the opinions of the Uniformed Services University of the Health Sciences, the Department of Defense, or the United States Government. Additionally, the authors have no conflicts of interests to report.
Responses of Bacterial and Fungal Community Structure to Different Rates of 1,3-Dichloropropene Fumigation
Authors: Zeng Yuan , Abdo Zaid , Charkowski Amy , Stewart Jane E. , Frost Kenneth
Published: July 2019

1,3-Dichloropropene (1,3-D) is a well-known nematicidal soil fumigant on many crop species. Currently, little is known about its impact on soil microbial communities using culture-free methods. In this study, we investigated changes in soil bacterial and fungal diversity and composition at two depths (30.5 and 61 cm) in response to management practices of applying 1,3-D at four different rates (103, 122, 140, and 187 liters/ha) relative to an untreated control in potato production fields using 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing. A total of 12,783 operational taxonomic units (OTUs) for 16S and 1,706 OTUs for ITS were obtained. Sequencing revealed that Proteobacteria, Firmicutes, Actinobacteria, and Ascomycota were dominant phyla in soils. Comparing alpha diversity of microbial communities at the different chemical rates with untreated plots showed that bacterial communities in plots treated with 1,3-D fumigation at 140 liters/ha were richer, which was supported by higher richness indices. Other diversity indices and overall soil microbial community structure were not significantly influenced by any rates of 1,3-D fumigation, although higher bacterial and fungal richness and diversity were observed in posttreatment soils and/or at 30.5 cm. Of the identified microbial families, the differential abundance of 45 bacterial and 24 fungal families was affected by sample depth, 1,3-D rate, or the interaction of sample depth and 1,3-D. The bacterial family Enterobacteriaceae, which includes species that specialize in decay of complex carbohydrates, increased in abundance post-1,3-D fumigation, and the fungal family Ophiocordycipitaceae, which includes nematode and insect pathogens, decreased, suggesting that the nematode and soil insect death caused by fumigation may selectively impact specific fungal and bacterial families.
Dissecting Resistance to Phytophthora cinnamomi in Interspecific Hybrid Chestnut Crosses Using Sequence-Based Genotyping and QTL Mapping
Authors: Zhebentyayeva Tetyana N. , Sisco Paul H. , Georgi Laura L. , Jeffers Steven N. , Perkins M. Taylor , James Joseph B. , Hebard Frederick V. , Saski Christopher , Nelson C. Dana , Abbott Albert G.
Published: July 2019

The soilborne oomycete Phytophthora cinnamomi—which causes root rot, trunk cankers, and stem lesions on an estimated 5,000 plant species worldwide—is a lethal pathogen of American chestnut (Castanea dentata) as well as many other woody plant species. P. cinnamomi is particularly damaging to chestnut and chinquapin trees (Castanea spp.) in the southern portion of its native range in the United States due to relatively mild climatic conditions that are conductive to disease development. Introduction of resistant genotypes is the most practical solution for disease management in forests because treatment with fungicides and eradication of the pathogen are neither practical nor economically feasible in natural ecosystems. Using backcross families derived from crosses of American chestnuts with two resistant Chinese chestnut cultivars Mahogany and Nanking, we constructed linkage maps and identified quantitative trait loci (QTLs) for resistance to P. cinnamomi that had been introgressed from these Chinese chestnut cultivars. In total, 957 plants representing five cohorts of three hybrid crosses were genotyped by sequencing and phenotyped by standardized inoculation and visual examination over a 6-year period from 2011 to 2016. Eight parental linkage maps comprising 7,715 markers were constructed, and 17 QTLs were identified on four linkage groups (LGs): LG_A, LG_C, LG_E, and LG_K. The most consistent QTLs were detected on LG_E in seedlings from crosses with both ‘Mahogany’ and ‘Nanking’ and LG_K in seedlings from ‘Mahogany’ crosses. Two consistent large and medium effect QTLs located ∼10 cM apart were present in the middle and at the lower end of LG_E; other QTLs were considered to have small effects. These results imply that the genetic architecture of resistance to P. cinnamomi in Chinese chestnut × American chestnut hybrid progeny may resemble the P. sojae–soybean pathosystem, with a few dominant QTLs along with quantitatively inherited partial resistance conferred by multiple small-effect QTLs.
Strategic Planning in Health Professions Education: Scholarship or Management?
Authors: Byrne Niall , Cole Donald C. , Woods Nicole , Kulasegaram Kulamakan , Martimianakis Maria Athina , Richardson Lisa , Whitehead Cynthia R.
Published: July 2019

Strategic planning, in its various forms, is an evaluation practice that is ubiquitous in academic medicine. However, published reports of strategic planning at academic health centers usually ignore theory. In a 2017 strategic planning exercise at the Wilson Centre, a scholarly model evolved using a theoretical framework and a research approach rather than a conventional management model, which typically identifies outcomes and how to achieve them. After completing this exercise, the authors considered the larger questions of the assumptions underpinning different models of strategic planning and strategic planning’s value to academic medicine. To elaborate on these questions, the authors examine relevant literature and set out the Wilson Centre’s emergent scholarly model. They describe the main features of the scholarly model, including ways it differs from a management approach and from the typical approach to strategic planning in the authors’ experience and in the field of health professions education research. The authors also share lessons learned as a means to encourage consideration by other academic organizations.
Prosthetic Rehabilitation and Vascularized Composite Allotransplantation following Upper Limb Loss
Authors: Kubiak Carrie A. , Etra Joanna W. , Brandacher Gerald , Kemp Stephen W. P. , Kung Theodore A. , Lee W. P. Andrew , Cederna Paul S.
Published: July 2019

Background:

Upper limb loss is a devastating condition with dramatic physical, psychological, financial, and social consequences. Improvements in the fields of prosthetics and vascularized composite allotransplantation have opened exciting new frontiers for treatment and rehabilitation following upper limb loss. Each modality offers a unique set of advantages and limitations with regard to the restoration of hand function following amputation.

Methods:

Presented in this article is a discussion outlining the complex considerations and decisions encountered when determining patient appropriateness for either prosthetic rehabilitation or vascularized composite allotransplantation following upper limb loss. In this review, the authors examine how psychosocial factors, nature of injury, rehabilitation course, functional outcomes, and risks and benefits may affect overall patient selection for either rehabilitative approach.

Results:

This review summarizes the current state of the literature. Advancements in both prosthetic and biological strategies demonstrate promise with regard to facilitating rehabilitation following upper limb loss. However, there remains a dearth of research directly comparing outcomes in prosthetic rehabilitation to that following upper extremity transplantation.

Conclusions:

Few studies have performed a direct comparison between patients undergoing vascularized composite allotransplantation and those undergoing prosthetic rehabilitation. Upper extremity transplantation and prosthetic reconstruction should not be viewed as competing options, but rather as two treatment modalities with different risk-to-benefit profiles and indications.
Evolution of Bandeau Shape, Orbital Morphology, and Craniofacial Twist after Fronto-Orbital Advancement for Isolated Unilateral Coronal Synostosis: A Case-Control Study of 2-Year Outcomes
Authors: Liu Mengyuan T. , Khechoyan David Y. , Susarla Srinivas M. , Skladman Rachel , Birgfeld Craig B. , Gruss Joseph S. , Lee Amy , Ellenbogen Richard G. , Pet Mitchell A. , Hopper Richard A.
Published: July 2019

Background:

The authors’ purpose was to quantify the change in unicoronal synostosis symmetry between presentation (time 0), after fronto-orbital advancement (time 1), and 2 years later (time 2).

Methods:

Bandeau/orbital symmetry ratios and skull base/midface twists were measured on computed tomographic scans of consecutive isolated unicoronal synostosis patients. Comparisons were made across three time points and against normal controls.

Results:

Forty-three unicoronal synostosis patients and 36 controls were included. The mean bandeau ratio (symmetry = 1) changed from 0.76 (time 0), to 1.13 (time 1), and then to 1.01 (time 2). The median bandeau ratio change from time 1 to time 2 was −9.1 percent and was impacted by the degree of time 1 asymmetry. The odds of a desired symmetric or overcorrected result (bandeau ratio > 1.0) at time 2 were increased in patients with less severe preoperative asymmetry (OR, 4.2; p = 0.04) and in those who obtained symmetry or overcorrection at surgery (OR, 4.9; p = 0.02). Craniofacial twist did not significantly change after surgery but decreased at time 2. Orbital height ratios were 1.08, 1.00, and then 1.02 at time 2, respectively. The orbital width ratio was not significantly impacted by surgery, remaining at 0.89 at time 2.

Conclusions:

Overcorrection of the unicoronal synostosis bandeau resulted in these patients being five times more likely to have a desired result at time 2. Patients with a more severe brow presentation were four times more likely to be asymmetric at time 2. Orbital height was improved, but attention should be directed at addressing orbital width.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Facial Recognition Technology: A Primer for Plastic Surgeons
Authors: Zuo Kevin J. , Saun Tomas J. , Forrest Christopher R.
Published: July 2019

The face is arguably the most unique and defining feature of the human body. From birth, humans are conditioned to perceive, interpret, and react to information conveyed by faces both familiar and unfamiliar. Although face recognition is routine for humans, only recently has it become possible for a computer to accurately recognize a human face in an image or video. With advances in artificial intelligence, image capture technology, and Internet connectivity, facial recognition technology has entered the forefront of personal and commercial technology. Plastic surgeons should be prepared to answer questions from patients about the fundamentals of facial recognition technology, and the potential effects of plastic surgery on facial recognition technology performance. This article provides an overview of facial recognition technology, describes its present applications, discusses its relevance within the field of plastic surgery, and provides recommendations for plastic surgeons to consider during preoperative discussions with patients.
Eye pupil signals information gain
Authors: Zénon Alexandre
Published: July 2019

In conditions of constant illumination, the eye pupil diameter indexes the modulation of arousal state and responds to a large breadth of cognitive processes, including mental effort, attention, surprise, decision processes, decision biases, value beliefs, uncertainty, volatility, exploitation/exploration trade-off or learning rate. Here, I propose an information theoretic framework that has the potential to explain the ensemble of these findings as reflecting pupillary response to information processing. In short, updates of brain internal model, quantified formally as the Kullback-Leibler (KL) divergence between prior and posterior beliefs, are the common denominator to all these instances of pupillary dilation to cognition. I show that stimulus presentation leads to pupillary response that is proportional to the amount of information the stimulus carries about itself and to the quantity of information it provides about other task variables. In the context of decision making, pupil dilation in relation to uncertainty is explained by the wandering of the evidence accumulation process, leading to large summed KL divergences. Finally, pupillary response to mental effort and variations in tonic pupil size are also formalized in terms of information theory. On the basis of this framework, I compare pupillary data from past studies to simple information theoretic simulations of task designs and show good correspondance with data across studies. The present framework has the potential to unify the large set of results reported on pupillary dilation to cognition and to provide a theory to guide future research.
A Pro-Diabetogenic mtDNA Polymorphism in the Mitochondrial-Derived Peptide, MOTS-c
Authors: Zempo Hirofumi , Kim Su-Jeong , Fuku Noriyuki , Nishida Yuichiro , Higaki Yasuki , Wan Junxiang , Yen Kelvin , Miller Brendan , Vicinanza Roberto , Miyamoto-Mikami Eri , Kumagai Hiroshi , Naito Hisashi , Xiao Jialin , Mehta Hemal H. , Lee Changhan , Hara Megumi , Patel Yesha M. , Setiawan Veronica W. , Moore Timothy M. , Hevener Andrea L. , Sutoh Yoichi , Shimizu Atsushi , Kojima Kaname , Kinoshita Kengo , Tanaka Keitaro , Cohen Pinchas
Published: July 2019

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. An Asian mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n=27,527, J-MICC, MEC, and TMM) showed that males but not females with the C-allele exhibit a higher prevalence of T2D. Furthermore, in J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitizationin vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.
Evaluation of direct grafting strategies in Expansion Microscopy
Authors: Wen Gang , Vanheusden Marisa , Acke Aline , Vali Donato , Mayer Simon Finn , Neely Robert K. , Leen Volker , Hofkens Johan
Published: July 2019

High resolution fluorescence microscopy is a key tool in the elucidation of biological fine-structure, providing insights into the distribution and interactions of biomolecular systems down to the nanometer scale. Expansion microscopy is a recently developed approach to achieving nanoscale resolution in optical imaging. In the experiment, biological samples are embedded in a hydrogel, which is isotropicaly swollen. This physically pulls labels apart, allowing more of them to be resolved. However, in the gelation and swelling process, two factors combine to reduce the signal in the final image; signal dilution and the polymerization reaction, which can damage some fluorophores. Here, we show a chemical linking approach that allows covalent grafting of biomolecular target and reporter in expansion microscopy. Through the combination of a targeting ligand, a reporter moiety and a polymerizable group in a single linker, complex constructs can be prepared in a single, labelling step. We show application of this new series of molecules in the targeting of the cell cytoskeleton, a first example of lipid membranes in expansion microscopy; direct immunostaining with primary and secondary antibodies, and direct grafting of ISH probes and signal amplification initiators (HCR and RollFISH). Our probes allow direct, multiplexed targeting of the cellular blueprint and enable a range of novel imaging approaches in combination with expansion microscopy.
Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection
Authors: Armstrong Ellie E. , Khan Anubhab , Taylor Ryan W , Gouy Alexandre , Greenbaum Gili , Thiéry Alexandre , Kang Jonathan TL , Redondo Sergio A. , Prost Stefan , Barsh Gregory , Kaelin Christopher , Phalke Sameer , Chugani Anup , Gilbert Martin , Miquelle Dale , Zachariah Arun , Borthakur Udayan , Reddy Anuradha , Louis Edward , Ryder Oliver A. , Jhala Y V , Petrov Dmitri , Excoffier Laurent , Hadly Elizabeth , Ramakrishnan Uma
Published: July 2019

Formulating strategies for species conservation requires knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, the evolutionary history and genomic variation of tigers remain poorly known. With 70% of the worlds wild tigers living in India, such knowledge is critical for tiger conservation. We re-sequenced 65 individual tiger genomes across their extant geographic range, representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding, possibly because of small and fragmented protected areas. Surprisingly, demographic models suggest recent divergence (within the last 10,000 years) between populations, and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection mainly related to metabolic adaptation to cold, while Sumatran tigers show evidence of evolving under weak selection for genes involved in body size regulation. Depending on conservation objectives, our results support the isolation of Amur and Sumatran tigers, while geneflow between Malayan and South Asian tigers may be considered. Further, the impacts of ongoing connectivity loss on the health and persistence of tigers in India should be closely monitored.
Speaking in the brain: The interaction between words and syntax in producing sentences
Authors: Takashima Atsuko , Konopka Agnieszka , Meyer Antje , Hagoort Peter , Weber Kirsten
Published: July 2019

This neuroimaging study investigated the neural infrastructure of sentence-level language production. We compared brain activation patterns, as measured with BOLD-fMRI, during production of sentences which differed in verb argument structures (intransitives, transitives, ditransitives) and the lexical status of the verb (known verbs or pseudo-verbs). An example for the type of sentence to be produced started a mini-block of six sentences with the same structure. For each trial, participants were first given the (pseudo-)verb followed by three geometric shapes to serve as verb arguments in the sentences. Production of sentences with known verbs yielded greater activation compared to those with pseudo-verbs in the core language network of left inferior frontal gyrus, the left posterior middle temporal gyrus, and a more posterior middle temporal region extending into the angular gyrus (LpMTG/AG), analogous to effects observed in language comprehension. Increasing the number of verb arguments led to greater activation in an overlapping left pMTG/AG area, particularly for known verbs, as well as in the bilateral precuneus. Thus, producing sentences with more complex structures using existing verbs lead to increased activation in the language network, suggesting some reliance on memory retrieval of stored lexical-syntactic information during sentence production. This study thus provides evidence from sentence-level language production in line with functional models of the language network that have so far been mainly based on single word production, comprehension and processing in aphasia.
Beta-driven closed-loop deep brain stimulation can compromise human motor behavior in Parkinson’s Disease
Authors: Iturrate Iñaki , Martin Stephanie , Chavarriaga Ricardo , Orset Bastien , Leeb Robert , Sobolewski Aleksander , Pralong Etienne , Castro-Jiménez Mayte , Benninger David , Bloch Jocelyne , Millán José del R.
Published: July 2019

Closed-loop or adaptive deep brain stimulation (DBS) for Parkinson’s Disease (PD) has shown comparable clinical improvements to continuous stimulation, yet with less stimulation times and side effects. In this form of control, stimulation is driven by pathological beta oscillations recorded from the subthalamic nucleus, which have been shown to correlate with PD motor symptoms. An important consideration is that beta activity is itself modulated during volitional movements, yet it is unknown the impact that these volitional modulations may have on the efficacy of closed-loop systems. Here, three PD patients performed a functional reaching task during closed-loop stimulation while we measured their motor behavior. Our results show that closed-loop stimulation can alter motor performance at distinct movement intervals. Of particular relevance, closed-loop DBS compromised behavior during the returning period by increasing the amount of submovements executed, and in turn delayed movement termination. Following these findings, we hypothesize that the use of machine learning decoding different movement intervals to fully switch off the stimulator may be beneficial, and present here an exemplary approach decoding the initiation of the movement returning interval above chance level. These findings highlight the importance of evaluating these systems during functional tasks, and the need of extracting more robust biomarkers encoding ongoing symptoms or tasks execution intervals.
How sensitive is functional connectivity to electrode resampling on intracranial EEG? Implications for personalized network models in drug-resistant epilepsy
Authors: Conrad Erin C. , Bernabei John M. , Kini Lohith G. , Shah Preya , Mikhail Fadi , Kheder Ammar , Shinohara Russell T. , Davis Kathryn A. , Bassett Danielle S. , Litt Brian
Published: July 2019

Focal epilepsy is a clinical condition arising from disordered brain networks. Network models hold promise to map these networks, localize seizure generators, and inform targeted interventions to control seizures. However, incomplete sampling of epileptic brain due to sparse placement of intracranial electrodes may profoundly affect model results. In this study, we evaluate the robustness of several published network measures applied to intracranial electrode recordings and propose an algorithm, using network resampling, to determine confidence in model results. We retrospectively subsampled intracranial EEG data from 28 patients who were implanted with grid, strip, and depth electrodes during evaluation for epilepsy surgery. We recalculated global and local network metrics after both randomly and systematically resampling subsets of intracranial EEG electrode contacts. We found that sensitivity to incomplete sampling varied significantly across network metrics, and that this sensitivity was independent of the distance of removed contacts from the seizure onset zone. We present an algorithm, using random resampling, to compute patient-specific confidence intervals for network localizations on both global and nodal network statistics. Our findings highlight the difference in robustness between commonly used network metrics and provide tools to assess confidence in intracranial network localization. We present these techniques as an important step toward assessing the accuracy of intracranial electrode implants and translating personalized network models of seizures into rigorous, quantitative approaches to invasive therapy.
A computational framework for a Lyapunov-enabled analysis of biochemical reaction networks
Authors: Ali Al-Radhawi M. , Angeli David , Sontag Eduardo D.
Published: July 2019

Complex molecular biological processes such as transcription and translation, signal transduction, post-translational modification cascades, and metabolic pathways can be described in principle by biochemical reactions that explicitly take into account the sophisticated network of chemical interactions regulating cell life. The ability to deduce the possible qualitative behaviors of such networks from a set of reactions is a central objective and an ongoing challenge in the field of systems biology. Unfortunately, the construction of complete mathematical models is often hindered by a pervasive problem: despite the wealth of qualitative graphical knowledge about network interactions, the form of the governing nonlinearities and/or the values of kinetic constants are hard to uncover experimentally. The kinetics can also change with environmental variations.

This work addresses the following question: given a set of reactions and without assuming a particular form for the kinetics, what can we say about the asymptotic behavior of the network? Specifically, it introduces a class of networks that are “structurally (mono) attractive” meaning that they are incapable of exhibiting multiple steady states, oscillation, or chaos by virtue of their reaction graphs. These networks are characterized by the existence of a universal energy-like function called aRobust Lyapunov function(RLF). To find such functions, a finite set of rank-one linear systems is introduced, which form the extremals of a linear convex cone. The problem is then reduced to that of finding a common Lyapunov function for this set of extremals. Based on this characterization, a computational package, Lyapunov-Enabled Analysis of Reaction Networks (LEARN), is provided that constructs such functions or rules out their existence.

An extensive study of biochemical networks demonstrates thatLEARNoffers a new unified framework. Basic motifs, three-body binding, and genetic networks are studied first. The work then focuses on cellular signalling networks including various post-translational modification cascades, phosphotransfer and phosphorelay networks, T-cell kinetic proofreading, and ERK signalling. The Ribosome Flow Model is also studied.

Author summary

A theoretical and computational framework is developed for the identification of biochemical networks that are “structurally attractive”. This means that they only allow global point attractors and they cannot exhibit any other asymptotic behavior such as multi-stability, oscillations, or chaos for any choice of the kinetics. They are characterized by the existence of energy-like functions. A computational package is made available for usage by a wider community. Many relevant networks in molecular biology satisfy the assumptions, and some are analyzed for the first time.
Mapping Transcriptomic Vector Fields of Single Cells
Authors: Qiu Xiaojie , Zhang Yan , Hosseinzadeh Shayan , Yang Dian , Pogson Angela N. , Wang Li , Shurtleff Matt , Yuan Ruoshi , Xu Song , Ma Yian , Replogle Joseph M. , Darmanis Spyros , Bahar Ivet , Xing Jianhua , Weissman Jonathan S
Published: July 2019

Single-cell RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires dynamical models capable of predicting cell fate and unveiling the governing regulatory mechanisms. Here, we introducedynamo, an analytical framework that reconciles intrinsic splicing and labeling kinetics to estimate absolute RNA velocities, reconstructs velocity vector fields that predict future cell fates, and finally employs differential geometry analyses to elucidate the underlying regulatory networks. We applieddynamoto a wide range of disparate biological processes including prediction of future states of differentiating hematopoietic stem cell lineages, deconvolution of glucocorticoid responses from orthogonal cell-cycle progression, characterization of regulatory networks driving zebrafish pigmentation, and identification of possible routes of resistance to SARS-CoV-2 infection. Our work thus represents an important step in going from qualitative, metaphorical conceptualizations of differentiation, as exemplified by Waddington’s epigenetic landscape, to quantitative and predictive theories.
Multicomponent solid forms of the uric acid reabsorption inhibitor lesinurad and cocrystal polymorphs with urea: DFT simulation and solubility study
Authors: Palanisamy Vasanthi , Sanphui Palash , Prakash Muthuramalingam , Chernyshev Vladimir
Published: July 2019

Lesinurad (systematic name: 2-{[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid, C17H14BrN3O2S) is a selective uric acid reabsorption inhibitor related to gout, which exhibits poor aqueous solubility. High-throughput solid-form screening was performed to screen for new solid forms with improved pharmaceutically relevant properties. During polymorph screening, we obtained two solvates with methanol (CH3OH) and ethanol (C2H5OH). Binary systems with caffeine (systematic name: 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione, C8H10N4O2) and nicotinamide (C6H6N2O), polymorphs with urea (CH4N2O) and eutectics with similar drugs, like allopurinol and febuxostat, were prepared using the crystal engineering approach. All these novel solid forms were confirmed by XRD, DSC and FT–IR. The crystal structures were solved by single-crystal and powder X-ray diffraction. The crystal structures indicate that the lesinurad molecule is highly flexible and the triazole moiety, along with the rotatable thioacetic acid (side chain) and cyclopropane ring, is almost perpendicular to the planar naphthalene moiety. The carboxylic acid–triazole heterosynthon in the drug is interrupted by the presence of methanol and ethanol molecules in their crystal structures and forms intermolecular macrocyclic rings. The caffeine cocrystal maintains the consistency of the acid–triazole heterosynthons as in the drug and, in addition, they are bound by several auxiliary interactions. In the binary system of nicotinamide and urea, the acid–triazole heterosynthon is replaced by an acid–amide synthon. Among the urea cocrystal polymorphs, Form I (P\overline{1}, 1:1) consists of an acid–amide (urea) heterodimer, whereas in Form II (P21/c, 2:2), both acid–amide heterosynthons and urea–urea dimers co-exist. Density functional theory (DFT) calculations further support the experimentally observed synthon hierarchies in the cocrystals. Aqueous solubility experiments of lesinurad and its binary solids in pH 5 acetate buffer medium indicate the apparent solubility order lesinurad–urea Form I (43-fold) > lesinurad–caffeine (20-fold) > lesinurad–allopurinol (12-fold) ≃ lesinurad–nicotinamide (11-fold) > lesinurad, and this order is correlated with the crystal structures.
Crystal structure and Hirshfeld surface analysis of tris(2,2′-bipyridine)nickel(II) bis(1,1,3,3-tetracyano-2-ethoxypropenide) dihydrate
Authors: Chi-Duran Ignacio , Setifi Zouaoui , Setifi Fatima , Jelsch Christian , Morgenstern Bernd , Vega Andres , Herrera Felipe , Pratap Singh Dinesh , Hegetschweiler Kaspar , Boyaala Rabab
Published: July 2019

The title compound, [Ni(C10H8N2)3](C9H5N4O)2·2H2O, crystallizes as a racemic mixture in the monoclinic space group C2/c. In the crystal, the 1,1,3,3-tetracyano-2-ethoxypropenide anions and the water molecules are linked by O—H...N hydrogen bonds, forming chains running along the [010] direction. The bpy ligands of the cation are linked to the chain via C—H...π(cation) interactions involving the CH3 group. The intermolecular interactions were investigated by Hirshfeld surface analysis and two-dimensional fingerprint plots.
Two isomers of [1-benzyl-4-(pyridin-2-yl-κN)-1H-1,2,3-triazole-κN
3]dichloridobis(dimethyl sulfoxide-κS)ruthenium(II)
Authors: Khamespanah Fatemeh , Maverick Andrew W.
Published: July 2019

The structures of two isomers of the title compound, [RuCl2(C14H12N4)(C2H6OS)2], 2 and 3, are reported. Isomers 2 and 3 are produced by reaction of the pyridyltriazole ligand 1-benzyl-4-(pyridin-2-yl)-1H-1,2,3-triazole (bpt) (1) with fac-[RuCl2(DMSO-S)3(DMSO-O)]. Reaction in acetone produces ca 95% 2, which is the OC-6-14 isomer, with cis DMSO and trans chlorido ligands, and 5% 3 (the OC-6-32 isomer, with cis DMSO and cis chlorido ligands, and the pyridyl moiety of bpt trans to DMSO). Reaction in refluxing toluene initially forms 2, which slowly isomerizes to 3.
Iodo(triphenyl)silane
Authors: Schödel Frauke , Lerner Hans-Wolfram , Trageser Timo , Bolte Michael
Published: July 2019

The molecular structure of the title compound, C18H15ISi, which crystallizes in the space group C2/c, does not exhibit any unusual features. Two weak C—H...π interactions may help to consolidate the packing. The present structure is not isostructural with the known Ph3SiX (X = F, Cl or Br) compounds.