bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity
Authors: De León Reyes N. S. , Mederos S. , Varela I. , Weiss L. A. , Perea G. , Galazo M. J. , Nieto M. 
Published: October 2019

AbstractInterhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex. According to current views, callosal and non-callosal fates are determined early after a neuron’s birth, and certain populations, such as cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel, project only ipsilaterally. Using a novel axonal-retrotracing strategy and GFP-targeted visualization of Rorb+ neurons, we instead demonstrate that L4 neurons develop transient interhemispheric axons. Locally restricted L4 connectivity emerges when exuberant contralateral axons are refined in an area- and layer-specific manner during postnatal development. Surgical and genetic interventions of sensory circuits demonstrate that refinement rates depend on distinct inputs from sensory-specific thalamic nuclei. Reductions in input-dependent refinement result in mature functional interhemispheric hyperconnectivity, demonstrating the plasticity and bona fide callosal potential of L4 neurons. Thus, L4 neurons discard alternative interhemispheric circuits as instructed by thalamic input. This may ensure optimal wiring.
Artificial intelligence reveals environmental constraints on colour diversity in insects
Authors: Wu Shipher , Chang Chun-Min , Mai Guan-Shuo , Rubenstein Dustin R. , Yang Chen-Ming , Huang Yu-Ting , Lin Hsu-Hong , Shih Li-Cheng , Chen Sheng-Wei , Shen Sheng-Feng 
Published: October 2019

AbstractExplaining colour variation among animals at broad geographic scales remains challenging. Here we demonstrate how deep learning—a form of artificial intelligence—can reveal subtle but robust patterns of colour feature variation along an ecological gradient, as well as help identify the underlying mechanisms generating this biogeographic pattern. Using over 20,000 images with precise GPS locality information belonging to nearly 2,000 moth species from Taiwan, our deep learning model generates a 2048-dimension feature vector that accurately predicts each species’ mean elevation based on colour and shape features. Using this multidimensional feature vector, we find that within-assemblage image feature variation is smaller in high elevation assemblages. Structural equation modeling suggests that this reduced image feature diversity is likely the result of colder environments selecting for darker colouration, which limits the colour diversity of assemblages at high elevations. Ultimately, with the help of deep learning, we will be able to explore the endless forms of natural morphological variation at unpreceded depths.
A large data resource of genomic copy number variation across neurodevelopmental disorders
Authors: Zarrei Mehdi , Burton Christie L. , Engchuan Worrawat , Young Edwin J. , Higginbotham Edward J. , MacDonald Jeffrey R. , Trost Brett , Chan Ada J. S. , Walker Susan , Lamoureux Sylvia , Heung Tracy , Mojarad Bahareh A. , Kellam Barbara , Paton Tara , Faheem Muhammad , Miron Karin , Lu Chao , Wang Ting , Samler Kozue , Wang Xiaolin , Costain Gregory , Hoang Ny , Pellecchia Giovanna , Wei John , Patel Rohan V. , Thiruvahindrapuram Bhooma , Roifman Maian , Merico Daniele , Goodale Tara , Drmic Irene , Speevak Marsha , Howe Jennifer L. , Yuen Ryan K. C. , Buchanan Janet A. , Vorstman Jacob A. S. , Marshall Christian R. , Wintle Richard F. , Rosenberg David R. , Hanna Gregory L. , Woodbury-Smith Marc , Cytrynbaum Cheryl , Zwaigenbaum Lonnie , Elsabbagh Mayada , Flanagan Janine , Fernandez Bridget A. , Carter Melissa T. , Szatmari Peter , Roberts Wendy , Lerch Jason , Liu Xudong , Nicolson Rob , Georgiades Stelios , Weksberg Rosanna , Arnold Paul D. , Bassett Anne S. , Crosbie Jennifer , Schachar Russell , Stavropoulos Dimitri J. , Anagnostou Evdokia , Scherer Stephen W. 
Published: October 2019

AbstractCopy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.
Pyroglutamyl leucine, a peptide in fermented foods, attenuates dysbiosis by increasing host antimicrobial peptide
Authors: Shirako Saki , Kojima Yumi , Tomari Naohiro , Nakamura Yasushi , Matsumura Yasuki , Ikeda Kaori , Inagaki Nobuya , Sato Kenji 
Published: October 2019

AbstractPyroGlu-Leu is present in certain food protein hydrolysates and traditional Japanese fermented foods. Our previous study demonstrated that the oral administration of pyroGlu-Leu (0.1 mg/kg body weight) attenuates dysbiosis in mice with experimental colitis. The objective of this study was to elucidate why such a low dose of pyroGlu-Leu attenuates dysbiosis in different animal models. High fat diet extensively increased the ratio of Firmicutes/Bacteroidetes in feces of rats compared to control diet. Oral administration of pyroGlu-Leu (1 mg/kg body weight) significantly attenuated high fat diet-induced dysbiosis. By focusing on the production of intestinal antimicrobial peptides, we found that pyroGlu-Leu significantly increased the level of 4962 Da peptides, which identified as the propeptide of rattusin or defensin alpha 9, in ileum. We also observed increased tryptic fragment peptides from rattusin in the lumen. Here, we report that orally administered pyroGlu-Leu attenuates dysbiosis by increasing in the host antimicrobial peptide, rattusin.
Complete chloroplast genome sequence and phylogenetic analysis of wasabi (Eutrema japonicum) and its relatives
Authors: Haga Natsuko , Kobayashi Masaaki , Michiki Nana , Takano Tomoyuki , Baba Fujio , Kobayashi Keiko , Ohyanagi Hajime , Ohgane Jun , Yano Kentaro , Yamane Kyoko 
Published: October 2019

AbstractIn Japan, two Eutrema species, wasabi (Eutrema japonicum, the important traditional Japanese condiment) and yuriwasabi (E. tenue), have been recognized as endemic species. We sequenced complete chloroplast (cp) genomes of seven wasabi and yuriwasabi accessions from Japan to study their phylogeny and evolution, using molecular dating of species divergence. Phylogenetic analyses of the complete cp DNA of these two Japanese species and five other Eurasian Eutrema species revealed that wasabi and yuriwasabi did not form a monophyletic group. One yuriwasabi accession (Gifu) formed a clade with E. yunnanense from China, indicating that this accession should be considered as a different species from the other yuriwasabi accessions. We reveal that Japanese Eutrema species diverged from the ‘E. yunnanense–yuriwasabi (Gifu)’ clade approximately 1.3 million years ago (Mya), suggesting that the connection between Japan and the Eurasian continent has existed more recently than the Quaternary period. The abundance of cp sequence data in this study also allowed the detection of genetic differentiation among wasabi cultivars. The two polymorphic sites detected between ‘Fujidaruma’ and ‘Shimane No.3’ were used to develop genotyping markers. The cp genome information provided here will thus inform the evolutionary histories of Japanese Eutrema species and help in genotyping wasabi cultivars.
CD138 plasma cells may predict brain metastasis recurrence following resection and stereotactic radiosurgery
Authors: Soike Michael H. , Logue Jennifer , Qasem Shadi , Hughes Ryan T. , McTyre Emory , Su Jing , Triozzi Pierre , Bendandi Maurizio , Lo Hui-Wen , Ahmed Tamjeed , O’Neill Stacey S. , Debinski Waldemar , Pasche Boris , Watabe Kounosuke , Miller Lance D. , Chan Michael D. , Ruiz Jimmy 
Published: October 2019

AbstractWe sought to identify candidate biomarkers for early brain metastasis (BM) recurrence in patients who underwent craniotomy followed by adjuvant stereotactic radiosurgery. RNA sequencing was performed on eight resected brain metastasis tissue samples and revealed B-cell related genes to be highly expressed in patients who did not experience a distant brain failure and had prolonged overall survival. To translate the findings from RNA sequencing data, we performed immunohistochemistry to stain for B and T cell markers from formalin-fixed parffin-embedded tissue blocks on 13 patients. CD138 expressing plasma cells were identified and quantitatively assessed for each tumor sample. Patients’ tumor tissues that expressed high levels of CD138 plasma cells (N = 4) had a statistically significant improvement in OS compared to low levels of CD138 (N = 9) (p = 0.01). Although these findings are preliminary, the significance of CD138 expressing plasma cells within BM specimens should be investigated in a larger cohort. Immunologic markers based on resection cavity analysis could be predictive for determining patient outcomes following cavity-directed SRS.
A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT
Authors: Tsao David S. , Silas Sukrit , Landry Brian P. , Itzep Nelda P. , Nguyen Amy B. , Greenberg Samuel , Kanne Celeste K. , Sheehan Vivien A. , Sharma Rani , Shukla Rahul , Arora Prem N. , Atay Oguzhan 
Published: October 2019

AbstractNext-generation DNA sequencing is currently limited by an inability to accurately count the number of input DNA molecules. Molecular counting is particularly needed when accurate quantification is required for diagnostic purposes, such as in single gene non-invasive prenatal testing (sgNIPT) and liquid biopsy. We developed Quantitative Counting Template (QCT) molecular counting to reconstruct the number of input DNA molecules using sequencing data. We then used QCT molecular counting to develop sgNIPTs of sickle cell disease, cystic fibrosis, spinal muscular atrophy, alpha-thalassemia, and beta-thalassemia. The analytical sensitivity and specificity of sgNIPT was >98% and >99%, respectively. Validation of sgNIPTs was further performed with maternal blood samples collected during pregnancy, and sgNIPTs were 100% concordant with newborn follow-up.
Long-term Prognostic Value of Estimated Plasma Volume in Heart Failure with Preserved Ejection Fraction
Authors: Huang Chen-Yu , Lin Ting-Tse , Wu Yi-Fan , Chiang Fu-Tien , Wu Cho-Kai 
Published: October 2019

AbstractPlasma volume, estimated by several indirect methods, has been viewed as a biological surrogate for intravascular fluid status. The clinical implication of estimated plasma volume status (ePVS) for long term outcomes in heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigate the prognostic value of ePVS calculated by Strauss formula and its association with cardiovascular events and mortality in a prospective HFpEF cohort. There were 449 individuals met the inclusion criteria of our cohort. Estimated plasma volume variation (ΔePVS) and its instantaneous derivatives were calculated by the Strauss formula. Our study endpoints were events of heart failure hospitalization and mortality. Kaplan–Meier estimates and Cox regression analysis were applied to determine the power of ΔePVS and baseline ePVS in predicting long term cardiovascular outcomes. Both baseline ePVS and ΔePVS were independent predictors of heart failure hospitalization and mortality. Kaplan-Meier estimates of these outcomes stratified by optimal cut-off value showed that HFpEF individuals with higher baseline ePVS and ΔePVS were associated with elevated risk of composite endpoint of heart failure hospitalization and mortality. This study demonstrated the prognostic value of a novel biological surrogate, instantaneous derivatives ePVS, in predicting long term cardiovascular outcomes in HFpEF population. Monitoring instantaneous plasma volume may assist in identifying patients at high risk for future cardiovascular events. Further prospective studies validating the role of ePVS in predicting long-term prognosis in patients with HFpEF are warranted.
Finding Hadamard Matrices by a Quantum Annealing Machine
Authors: Suksmono Andriyan Bayu , Minato Yuichiro 
Published: October 2019

AbstractFinding a Hadamard matrix (H-matrix) among the set of all binary matrices of corresponding order is a hard problem, which potentially can be solved by quantum computing. We propose a method to formulate the Hamiltonian of finding H-matrix problem and address its implementation limitation on existing quantum annealing machine (QAM) that allows up to quadratic terms, whereas the problem naturally introduces higher order ones. For an M-order H-matrix, such a limitation increases the number of variables from M2 to (M3 + M2 − M)/2, which makes the formulation of the Hamiltonian too exhaustive to do by hand. We use symbolic computing techniques to manage this problem. Three related cases are discussed: (1) finding N < M orthogonal binary vectors, (2) finding M-orthogonal binary vectors, which is equivalent to finding a H-matrix, and (3) finding N-deleted vectors of an M-order H-matrix. Solutions of the problems by a 2-body simulated annealing software and by an actual quantum annealing hardware are also discussed.
On Information Extraction and Decoding Mechanisms Improved by Noisy Amplification in Signaling Pathways
Authors: Vazquez-Jimenez Aaron , Rodriguez-Gonzalez Jesus 
Published: October 2019

AbstractThe cells need to process information about extracellular stimuli. They encode, transmit and decode the information to elicit an appropriate response. Studies aimed at understanding how such information is decoded in the signaling pathways to generate a specific cellular response have become essential. Eukaryotic cells decode information through two different mechanisms: the feed-forward loop and the promoter affinity. Here, we investigate how these two mechanisms improve information transmission. A detailed comparison is made between the stochastic model of the MAPK/ERK pathway and a stochastic minimal decoding model. The maximal amount of transmittable information was computed. The results suggest that the decoding mechanism of the MAPK/ERK pathway improve the channel capacity because it behaves as a noisy amplifier. We show a positive dependence between the noisy amplification and the amount of information extracted. Additionally, we show that the extrinsic noise can be tuned to improve information transmission. This investigation has revealed that the feed-forward loop and the promoter affinity motifs extract information thanks to processes of amplification and noise addition. Moreover, the channel capacity is enhanced when both decoding mechanisms are coupled. Altogether, these findings suggest novel characteristics in how decoding mechanisms improve information transmission.
A microcosm approach highlights the response of soil mineral weathering bacterial communities to an increase of K and Mg availability
Authors: Nicolitch O. , Feucherolles M. , Churin J.-L. , Fauchery L. , Turpault M.-P. , Uroz S. 
Published: October 2019

AbstractThe access and recycling of the base cations are essential processes for the long-lasting functioning of forest ecosystems. While the role of soil bacterial communities has been demonstrated in mineral weathering and tree nutrition, our understanding of the link between the availability of base cations and the functioning of these communities remains limited. To fill this gap, we developed a microcosm approach to investigate how an increase in key base cations (potassium or magnesium) impacted the taxonomic and functional structures of the bacterial communities. During a 2-month period after fertilization with available potassium or magnesium, soil properties, global functions (metabolic potentials and respiration) as well as mineral weathering bioassays and 16S rRNA amplicon pyrosequencing were monitored. Our analyses showed no or small variations in the taxonomic structure, total densities and global functions between the treatments. In contrast, a decrease in the frequency and effectiveness of mineral weathering bacteria was observed in the fertilized treatments. Notably, quantitative PCR targeting specific genera known for their mineral weathering ability (i.e., Burkholderia and Collimonas) confirmed this decrease. These new results suggest that K and Mg cation availability drives the distribution of the mineral weathering bacterial communities in forest soil.
Enhanced flow-motion complexity of skin microvascular perfusion in Sherpas and lowlanders during ascent to high altitude
Authors: Carey Deborah , Thanaj Marjola , Davies Thomas , Gilbert-Kawai Edward , Mitchell Kay , Levett Denny Z. H. , Mythen Michael G. , Martin Daniel S. , Grocott Michael P. , Chipperfield Andrew J. , Clough Geraldine F. 
Published: October 2019

AbstractAn increased and more effective microvascular perfusion is postulated to play a key role in the physiological adaptation of Sherpa highlanders to the hypobaric hypoxia encountered at high altitude. To investigate this, we used Lempel-Ziv complexity (LZC) analysis to explore the spatiotemporal dynamics of the variability of the skin microvascular blood flux (BF) signals measured at the forearm and finger, in 32 lowlanders (LL) and 46 Sherpa highlanders (SH) during the Xtreme Everest 2 expedition. Measurements were made at baseline (BL) (LL: London 35 m; SH: Kathmandu 1300 m) and at Everest base camp (LL and SH: EBC 5,300 m). We found that BF signal content increased with ascent to EBC in both SH and LL. At both altitudes, LZC of the BF signals was significantly higher in SH, and was related to local slow-wave flow-motion activity over multiple spatial and temporal scales. In SH, BF LZC was also positively associated with LZC of the simultaneously measured tissue oxygenation signals. These data provide robust mechanistic information of microvascular network functionality and flexibility during hypoxic exposure on ascent to high altitude. They demonstrate the importance of a sustained heterogeneity of network perfusion, associated with local vaso-control mechanisms, to effective tissue oxygenation during hypobaric hypoxia.
Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes
Authors: Cha Do Hyeon , Gee Heon Yung , Cachau Raul , Choi Jong Mun , Park Daeui , Jee Sun Ha , Ryu Seungho , Kim Kyeong Kyu , Won Hong-Hee , Limou Sophie , Myung Woojae , Winkler Cheryl A. , Cho Sung Kweon 
Published: October 2019

AbstractDifferentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258*, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258* and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.
Identification of somatic alterations in lipoma using whole exome sequencing
Authors: Kanojia Deepika , Dakle Pushkar , Mayakonda Anand , Parameswaran Rajeev , Puhaindran Mark E. , Min Victor Lee Kwan , Madan Vikas , Koeffler Phillip 
Published: October 2019

AbstractLipomas are benign fatty tumors with a high prevalence rate, mostly found in adults but have a good prognosis. Until now, reason for lipoma occurrence not been identified. We performed whole exome sequencing to define the mutational spectrum in ten lipoma patients along with their matching control samples. We presented genomic insight into the development of lipomas, the most common benign tumor of soft tissue. Our analysis identified 412 somatic variants including missense mutations, splice site variants, frameshift indels, and stop gain/lost. Copy number variation analysis highlighted minor aberrations in patients. Kinase genes and transcriptions factors were among the validated mutated genes critical for cell proliferation and survival. Pathway analysis revealed enrichment of calcium, Wnt and phospholipase D signaling in patients. In conclusion, whole exome sequencing in lipomas identified mutations in genes with a possible role in development and progression of lipomas.
Memory influences haptic perception of softness
Authors: Metzger Anna , Drewing Knut 
Published: October 2019

AbstractThe memory of an object’s property (e.g. its typical colour) can affect its visual perception. We investigated whether memory of the softness of every-day objects influences their haptic perception. We produced bipartite silicone rubber stimuli: one half of the stimuli was covered with a layer of an object (sponge, wood, tennis ball, foam ball); the other half was uncovered silicone. Participants were not aware of the partition. They first used their bare finger to stroke laterally over the covering layer to recognize the well-known object and then indented the other half of the stimulus with a probe to compare its softness to that of an uncovered silicone stimulus. Across four experiments with different methods we showed that silicon stimuli covered with a layer of rather hard objects (tennis ball and wood) were perceived harder than the same silicon stimuli when being covered with a layer of rather soft objects (sponge and foam ball), indicating that haptic perception of softness is affected by memory.