cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4818358
title: Dataset for: YOUR MITOCHONDRIA ARE WHAT YOU EAT: A HIGH-FAT OR A HIGH-SUCROSE DIET ELIMINATES METABOLIC FLEXIBILITY IN ISOLATED MITOCHONDRIA FROM RAT SKELETAL MUSCLE

description: ABSTRACT Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate- and fatty acid oxidation at the level of the mitochondria. Here we report that rat muscle mitochondria does show the normal Randle-type fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/β-oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate-fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for12 weeks to a HF- or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria.
DOI: 10.6084/m9.figshare.4818343
title: Dataset for: Chemogenetic enhancement of functional recovery after a sciatic nerve injury

description: Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools used to modulate neuronal excitability. We hypothesized that activation of excitatory (Gq) DREADD by its designer ligand, clozapine-N-oxide (CNO), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (LG) muscle of adult female Lewis rats was injected unilaterally with AAV9- hsyn- hM3Dq-mCherry (7.6x109 viral genomes/μl) to transduce Gq-DREADD expression in LG neurons. The contralateral LG muscle served as an uninjected control. No significant changes in either spontaneous EMG activity or electrically evoked direct muscle (M) responses were found in either muscle after injection of CNO (1mg/kg, i.p.). The amplitude of monosynaptic H-reflexes in LG was increased after CNO treatment exclusively in muscles previously injected with virus, suggesting that Gq-DREADD activation increased neuronal excitability. After bilateral sciatic nerve transection and repair, additional rats were treated similarly with CNO for up to three days after injury. Electrophysiological data were collected at 2, 4 and 6 weeks after injury. Evoked EMG responses were observed as early as 2 weeks after injury only in Gq-DREADD expressing virus injected LG muscle. By 4 weeks after injury, both M-response and H-reflex amplitudes were significantly greater in muscles previously injected with viral vector than contralateral, uninjected muscles. Increases in the excitability of injured neurons produced by this novel use of Gq-DREADD were sufficient to promote an enhancement in functional recovery after a sciatic nerve injury.
DOI: 10.6084/m9.figshare.4818349.v1
title: Dataset for: Statistical Consequences of a Successful Lung Allocation System - Recovering Information and Reducing Bias in Models for Urgency

description: The lung allocation system has reduced the number of waitlist deaths by ranking transplant candidates based on a lung allocation score (LAS) that requires estimation of the current 1-year restricted mean waitlist survival (urgency). Fewer waitlist deaths and the systematic removal of candidates from the waitlist for transplantation present statistical challenges that must be addressed when using recent waitlist data. Multiple overlapping 1-year follow-up windows are used in a restricted mean model that estimates patient urgency based on updated risk factors at the start of the window. In simulation studies, our proposed multiple imputation procedure was able to produce unbiased parameter estimates with similar efficiency to those obtained if censoring had never occurred. The analysis of 10,740 lung transplant candidates revealed that for most risk factors incorporating additional follow-up windows produced more efficient estimates.
DOI: 10.6084/m9.figshare.4818352.v1
title: Dataset for: Estimating marginal causal effects in a secondary analysis of case-control data

description: When an initial case-control study is performed data can be used in a secondary analysis to evaluate the effect of the case-defining event on later outcomes. In this paper, we study the example in which the role of the event is changed from a response variable to a treatment of interest. If the aim is to estimate marginal effects, such as average effects in the population, the sampling scheme needs to be adjusted for. We study estimators of the average effect of the treatment in a secondary analysis of matched and unmatched case-control data where the probability of being a case is known. For a general class of estimators, we show the components of the bias resulting from ignoring the sampling scheme and demonstrate a design-weighted matching estimator of the average causal effect. In simulations, the finite sample properties of the design-weighted matching estimator are studied. Using a Swedish diabetes incidence register with a matched case-control design we study the effect of childhood onset diabetes on the use of anti-depressant medication as an adult.
DOI: 10.6084/m9.figshare.4818346.v1
title: Dataset for: Validation of a routine two-sample iohexol plasma clearance assessment of GFR and an evaluation of common endogenous markers in a rat model of CKD

description: Endogenous markers of kidney function are insensitive to early declines in GFR and in rodent models, validated, practical alternatives are unavailable. In this study we determined GFR by modelling the plasma clearance of two compounds, iohexol and inulin, and compared the findings to common endogenous markers. All plasma clearance methods of both iohexol and inulin detected a decline in renal function weeks prior to any increase in endogenous marker. Iohexol plasma clearance and inulin plasma clearance had very high agreement and minimal bias when using 12-sample models. However, only iohexol could be accurately simplified to a two-sample, 1-compartment estimation strategy. Following an IV injection of low-dose iohexol and two timed blood samples at 30 and 90 minutes, one can accurately approximate a complex 12-sample strategy of plasma clearance. This method is simple enough to use in routine, longitudinal analysis of larger cohort animal studies.
DOI: 10.6084/m9.figshare.4818340
title: Dataset for: Novel lncRNA regulated by HIF-1 inhibits apoptotic cell death in the renal tubular epithelial cells under hypoxia.

description: Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney. Two different types of tubular cells were exposed to 1% hypoxia for 24-72 hrs. We performed RNA-seq to clarify the expression of mRNA and long non-coding RNA (lncRNA). We also examined ChIP-seq to identify HIF-1 binding sites under hypoxia. RNA-seq identified 44 lncRNAs which are up-regulated under hypoxic condition in both cells. ChIP-seq analysis demonstrated that HIF-1 also binds to the lncRNAs under hypoxia. The expression of novel lncRNA, DARS-AS1 (aspartyl-tRNA synthetase anti-sense 1), is up-regulated only under hypoxia and HIF-1 binds to its promoter region, which includes two hypoxia responsive elements. Its expression is also up-regulated with cobalt chloride exposure, while it is not under hypoxia when HIF-1 is knocked down by siRNA. To clarify the biological roles of DARS-AS1, we measured the activity of caspase 3/7 using anti-sense oligo of DARS-AS1. Knockdown of DARS-AS1 deteriorated apoptotic cell death. In conclusion, we identified the novel lncRNAs regulated by HIF-1 under hypoxia and clarified that DARS-AS1 plays an important role in inhibiting apoptotic cell death in renal tubular cells.
DOI: 10.6084/m9.figshare.4818343.v1
title: Dataset for: Chemogenetic enhancement of functional recovery after a sciatic nerve injury

description: Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools used to modulate neuronal excitability. We hypothesized that activation of excitatory (Gq) DREADD by its designer ligand, clozapine-N-oxide (CNO), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (LG) muscle of adult female Lewis rats was injected unilaterally with AAV9- hsyn- hM3Dq-mCherry (7.6x109 viral genomes/μl) to transduce Gq-DREADD expression in LG neurons. The contralateral LG muscle served as an uninjected control. No significant changes in either spontaneous EMG activity or electrically evoked direct muscle (M) responses were found in either muscle after injection of CNO (1mg/kg, i.p.). The amplitude of monosynaptic H-reflexes in LG was increased after CNO treatment exclusively in muscles previously injected with virus, suggesting that Gq-DREADD activation increased neuronal excitability. After bilateral sciatic nerve transection and repair, additional rats were treated similarly with CNO for up to three days after injury. Electrophysiological data were collected at 2, 4 and 6 weeks after injury. Evoked EMG responses were observed as early as 2 weeks after injury only in Gq-DREADD expressing virus injected LG muscle. By 4 weeks after injury, both M-response and H-reflex amplitudes were significantly greater in muscles previously injected with viral vector than contralateral, uninjected muscles. Increases in the excitability of injured neurons produced by this novel use of Gq-DREADD were sufficient to promote an enhancement in functional recovery after a sciatic nerve injury.
DOI: 10.6084/m9.figshare.4818358.v1
title: Dataset for: YOUR MITOCHONDRIA ARE WHAT YOU EAT: A HIGH-FAT OR A HIGH-SUCROSE DIET ELIMINATES METABOLIC FLEXIBILITY IN ISOLATED MITOCHONDRIA FROM RAT SKELETAL MUSCLE

description: ABSTRACT Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate- and fatty acid oxidation at the level of the mitochondria. Here we report that rat muscle mitochondria does show the normal Randle-type fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/β-oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate-fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for12 weeks to a HF- or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria.
DOI: 10.6084/m9.figshare.4818337
title: Dataset for: Musculotendon adaptations but preservation of spinal reflex pathways following agonist-to-antagonist tendon transfer

description: Tendon transfer surgeries are performed to restore lost motor function, but outcomes are variable, particularly those involving agonist-to-antagonist muscles. Here, we evaluated the possibility that lack of proprioceptive feedback reorganization and musculotendon adaptations could influence outcomes. Plantaris to tibialis anterior tendon transfer along with resection of the distal third of the tibialis anterior muscle belly was performed in 8 cats. Four cats had concurrent transection of the deep peroneal nerve. After 15-20 weeks, intermuscular length and force dependent sensory feedback were examined between hindlimb muscles, and the integrity of the tendon-to-tendon connection and musculotendon adaptations were evaluated. Three of the transferred tendons tore. A common finding was the formation of new tendinous connections, which often inserted near the original location of insertion on the skeleton (e.g. connections from plantaris toward calcaneus and from tibialis anterior toward first metatarsal). The newly formed tissue connections are expected to compromise the mechanical action of the transferred muscle. We found no evidence of changes in intermuscular reflexes between transferred plantaris muscle and synergists/antagonists whether the tendon-to-tendon connection remained intact or tore, indicating no spinal reflex reorganization. We propose the lack of spinal reflex reorganization could contribute to altered task dependent temporal activation of the transferred muscle. Taken together, these findings suggest musculotendon plasticity and lack of spinal reflex circuitry reorganization could limit functional outcomes after tendon transfer surgery. Surgical planning and outcomes assessments after tendon transfer surgery should consider potential consequences of the transferred muscle’s intermuscular spinal circuit actions.
DOI: 10.6084/m9.figshare.4818340.v1
title: Dataset for: Novel lncRNA regulated by HIF-1 inhibits apoptotic cell death in the renal tubular epithelial cells under hypoxia.

description: Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney. Two different types of tubular cells were exposed to 1% hypoxia for 24-72 hrs. We performed RNA-seq to clarify the expression of mRNA and long non-coding RNA (lncRNA). We also examined ChIP-seq to identify HIF-1 binding sites under hypoxia. RNA-seq identified 44 lncRNAs which are up-regulated under hypoxic condition in both cells. ChIP-seq analysis demonstrated that HIF-1 also binds to the lncRNAs under hypoxia. The expression of novel lncRNA, DARS-AS1 (aspartyl-tRNA synthetase anti-sense 1), is up-regulated only under hypoxia and HIF-1 binds to its promoter region, which includes two hypoxia responsive elements. Its expression is also up-regulated with cobalt chloride exposure, while it is not under hypoxia when HIF-1 is knocked down by siRNA. To clarify the biological roles of DARS-AS1, we measured the activity of caspase 3/7 using anti-sense oligo of DARS-AS1. Knockdown of DARS-AS1 deteriorated apoptotic cell death. In conclusion, we identified the novel lncRNAs regulated by HIF-1 under hypoxia and clarified that DARS-AS1 plays an important role in inhibiting apoptotic cell death in renal tubular cells.
DOI: 10.6084/m9.figshare.4818319
title: Supplementary Material for: Risk Factors for Severe Reactions during Double-Blind Placebo-Controlled Food Challenges

description: <b><i>Background:</i></b> Severe anaphylactic symptoms can occur during oral food challenges (OFCs). Thus, high-risk patients (e.g., patients with a history of anaphylaxis or high antigen-specific immunoglobulin E [IgE] levels) must carefully undergo OFCs in hospitals. We attempted to identify the risk factors for severe symptoms during OFC testing among high-risk patients. <b><i>Methods:</i></b> We retrospectively evaluated patients' characteristics and severe symptoms that were experienced during a double-blind placebo-controlled food challenge test performed before the patients underwent oral immunotherapy between June 2008 and June 2012. Patients were ≥5 years old and had an anaphylactic history or antigen-specific IgE (&gt;30 kUA/L). Severe symptoms were defined using the grading of the Japanese Anaphylaxis Guidelines, which are modified from the European Academy of Allergology and Clinical Immunology Guidelines. <b><i>Results:</i></b> We evaluated 393 cases with positive test results, including 98 cases with severe symptoms. The most frequent severe symptoms were respiratory (77%), gastrointestinal (28%), cardiovascular (27%), and neurological (13%) symptoms. Multivariate analysis revealed that the significant factors for a severe reaction were a history of anaphylaxis to the causative food (adjusted odds ratio [OR]: 2.147, <i>p</i> = 0.003), older age (per 1 year increase, adjusted OR: 1.102, <i>p</i> = 0.044), and an egg OFC (adjusted OR: 0.433, <i>p = </i>0.003). <b><i>Conclusions:</i></b> The risk factors for a severe reaction to OFCs were a history of an anaphylactic reaction and older age. An egg OFC was associated with low risk of severe symptoms during OFC. Therefore, OFCs for patients with these risk factors should only be performed under specialist supervision with access to rapid treatment and full resuscitation equipment.
DOI: 10.6084/m9.figshare.4818328
title: Petrography and provenance of Upper Cretaceous – Palaeogene sandstones in the foreland basin system of Central Nepal

description: Sedimentary deposits of the Cretaceous to Miocene Tansen Group of Lesser Himalayan association in central Nepal record passive-margin sedimentation of the Indian Continent with direct deposition onto eroded Precambrian rocks (Sisne Formation onto Kaligandaki Supergroup rocks), succeeded by the appearance of orogenic detritus as the Indian continent collided with Asia on a N-dipping subduction zone. Rock samples from two field traverses were examined petrographically and through detrital zircon U–Pb dating, one traverse being across the Tansen Group and another across the Higher and Tethyan Himalaya (TH). The Tansen Group depositional ages are well known through fossil assemblages. We examined samples from three units of the Tansen Group (Amile, Bhainskati, and Dumri Formations). The Sedimentary petrographic data and Qt F L and Qm F Lt plots indicate their ‘Quartzose recycled’ nature and classify Tansen sedimentary rocks as ‘recycled orogenic’, suggesting Indian cratonic and Lower Lesser Himalayan (LLH) sediments as the likely source of sediments for the Amile Formation (Am), the TH and the Upper Lesser Himalaya (ULH) as the source for the Bhainskati Formation (Bk), and both the Tethyan and Higher Himalaya (HH) as the major sources for the Dumri Formation (Dm). The Cretaceous–Palaeocene pre-collisional Am is dominated by a broad detrital zircon U–Pb ~1830 Ma age peak with neither Palaeozoic nor Neoproterozoic zircons grains, but hosts a significant proportion (23%) of syndepositional Cretaceous zircons (121–105 Ma) would be contributions from the LLH volcanosedimentary arc, Gangdese batholith (including the Xigaze forearc). The other formations of the Tansen Group are more similar to Tethyan units than to Higher Himalaya Crystalline (HHC). From the analysed samples, there is a lack of distinctive evidence or HH detritus in the Tansen basin. Furthermore, the presence of ~23±1 Ma zircons from the HH unit suggests that they could not have been exposed until the earliest Miocene time.
DOI: 10.6084/m9.figshare.4818328.v1
title: Petrography and provenance of Upper Cretaceous – Palaeogene sandstones in the foreland basin system of Central Nepal

description: Sedimentary deposits of the Cretaceous to Miocene Tansen Group of Lesser Himalayan association in central Nepal record passive-margin sedimentation of the Indian Continent with direct deposition onto eroded Precambrian rocks (Sisne Formation onto Kaligandaki Supergroup rocks), succeeded by the appearance of orogenic detritus as the Indian continent collided with Asia on a N-dipping subduction zone. Rock samples from two field traverses were examined petrographically and through detrital zircon U–Pb dating, one traverse being across the Tansen Group and another across the Higher and Tethyan Himalaya (TH). The Tansen Group depositional ages are well known through fossil assemblages. We examined samples from three units of the Tansen Group (Amile, Bhainskati, and Dumri Formations). The Sedimentary petrographic data and Qt F L and Qm F Lt plots indicate their ‘Quartzose recycled’ nature and classify Tansen sedimentary rocks as ‘recycled orogenic’, suggesting Indian cratonic and Lower Lesser Himalayan (LLH) sediments as the likely source of sediments for the Amile Formation (Am), the TH and the Upper Lesser Himalaya (ULH) as the source for the Bhainskati Formation (Bk), and both the Tethyan and Higher Himalaya (HH) as the major sources for the Dumri Formation (Dm). The Cretaceous–Palaeocene pre-collisional Am is dominated by a broad detrital zircon U–Pb ~1830 Ma age peak with neither Palaeozoic nor Neoproterozoic zircons grains, but hosts a significant proportion (23%) of syndepositional Cretaceous zircons (121–105 Ma) would be contributions from the LLH volcanosedimentary arc, Gangdese batholith (including the Xigaze forearc). The other formations of the Tansen Group are more similar to Tethyan units than to Higher Himalaya Crystalline (HHC). From the analysed samples, there is a lack of distinctive evidence or HH detritus in the Tansen basin. Furthermore, the presence of ~23±1 Ma zircons from the HH unit suggests that they could not have been exposed until the earliest Miocene time.