bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive Brain Stimulation in Epilepsy
Authors: VanHaerents Stephen , Chang Bernard S. , Rotenberg Alexander , Pascual-Leone Alvaro , Shafi Mouhsin M.
Published: March 2020

Neurostimulation in epilepsy is a long standing established concept, and through experimental and clinical uses, our understanding of neurostimulation and neuromodulation has grown substantially. Noninvasive brain stimulation techniques use electromagnetic principles to noninvasively modulate brain activity in a spatiotemporally targeted manner. This review focused on the two predominant forms of noninvasive neurostimulation: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, and their current applications in the diagnosis and management of epilepsy. A number of small randomized sham-controlled studies suggest that both TMS and transcranial direct current stimulation may have a beneficial effect in decreasing seizure frequency in patients with medically refractory epilepsy, without significant side effects. Small pilot studies also suggest that TMS in combination with EEG may be used to develop quantitative biomarkers of cortical hyperexcitability in patients with epilepsy. Furthermore, TMS is already Food and Drug Administration-cleared for presurgical mapping of eloquent cortex, and preliminary studies suggest that navigated TMS represents a highly valuable clinical supplement for preoperative functional planning. Transcranial magnetic stimulation and transcranial direct current stimulation have shown great potential benefit for patients with epilepsy; however, further large multicenter randomized sham-controlled studies are needed to better optimize stimulation settings and protocols, define mechanisms of action, assess long-term effects, and clearly define roles and determine efficacy.
Transcranial Magnetic Stimulation–Induced Motor Evoked Potentials in Hirayama Disease: Systematic Review of the Literature
Authors: Bembenek Jan P. , Kłysz Bożena , Kurkowska-Jastrzębska Iwona
Published: March 2020

Purpose:

Hirayama disease (HD) is a rare motor disorder mainly affecting young men, characterized by atrophy and unilateral weakness of forearm and hand muscles corresponding to a C7-T1 myotome distribution. The progression is self-limited. The etiology of HD is unclear. The usefulness of motor evoked potentials (MEPs) in pyramidal tracts damage evaluation still appears to be somehow equivocal.

Methods:

We searched PubMed for original articles, evaluating the use of transcranial magnetic stimulation elicited MEPs in HD using keywords “motor evoked potentials Hirayama” and “transcranial magnetic stimulation Hirayama.”

Results:

We found seven articles using the above keywords that met inclusion criteria. The number of participants was small, and diagnostic procedures varied. There were also differences in methodology. Abnormal central motor conduction time was found in 17.1% of patients in one study, whereas it was normal in two other studies. Peripheral motor latency was evaluated in one study, which found abnormally increased peripheral motor latencies in at least one tested muscle in 16 of 41 HD patients (39.0%). Abnormal MEP parameters were found in three studies in 14.3% to 100% patients. In one study they were not evaluated, in three other studies they were normal, and in one they were normal also in standard and flexed neck position In one study, inconsistent results were found in MEP size after neck flexion in patients after treatment with neck collar.

Conclusions:

Although MEP parameters may be abnormal in some HD patients, these have not been thoroughly assessed. Further studies are indispensable to evaluate their usefulness in assessing pyramidal tract damage in HD.
Quantitative EEG Changes Correlate With Post-Clamp Ischemia During Carotid Endarterectomy
Authors: Kamitaki Brad K. , Tu Bin , Wong Stephen , Mendiratta Anil , Choi Hyunmi
Published: March 2020

Introduction:

EEG monitoring is a critical tool for identifying cerebral ischemia during carotid endarterectomy (CEA). Quantitative EEG can be used to supplement visual EEG review, but which measures best predict post-clamp ischemia is unclear.

Purpose:

To determine which quantitative EEG parameters reliably detect intraoperative ischemia during CEA.

Methods:

The authors identified patients who underwent carotid endarterectomy at Columbia University Medical Center from 2007 to 2014 with intraoperative EEG monitoring. Two masked physicians reviewed these EEGs retrospectively and determined whether there was post-clamp ischemia, categorizing patients into (1) ischemic-change and (2) no-ischemic-change groups. The authors then studied the performance of a battery of quantitative EEG measures (alpha, beta, theta, and delta power bands, alpha–delta ratio, beta–delta ratio, amplitude-integrated EEG, and 90% spectral edge frequency) against physician review as the gold standard.

Results:

Of 118 patients, 15 were included in the ischemic-change group and 103 in the no-ischemic-change group. Ipsilateral post-clamp trough values of all the quantitative EEG measures assessed were significantly decreased for patients in the ischemic-change group. Decreases in alpha, beta, and theta power of 52.1%, 41.6%, and 36.4% or greater, respectively, were most predictive of post-clamp ischemia.

Conclusions:

Quantitative EEG monitoring during carotid endarterectomy, in addition to visual EEG monitoring, may improve the detection of cerebral ischemia and thus result in fewer perioperative strokes.
Predictors of Nonconvulsive Seizure and Their Effect on Short-term Outcome
Authors: Singh Jaysingh , Thakur Gaurav , Alexander Jonathan , Rayi Appaji , Peng Juan , Bell William , Britton Jeffrey
Published: March 2020

Introduction:

Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs.

Methods:

We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled.

Results:

Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197–2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027–2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1).

Conclusions:

Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.
Nocardioides euryhalodurans sp. nov., Nocardioides seonyuensis sp. nov. and Nocardioides eburneiflavus sp. nov., isolated from soil
Authors: Roh Su Gwon , Lee Chan , Kim Min-Kyeong , Kang Hye-Jeong , Kim Yeong Seok , Kim Min Ji , Malik Adeel , Kim Seung Bum
Published: March 2020

Three aerobic, rod-shaped actinobacterial strains, designated MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T, were isolated from soil and their taxonomic positions were analysed using a polyphasic approach. The isolates showed best growth at 30 °C, pH 7 and 0–1 % (w/v) NaCl. On the basis of 16S rRNA gene sequence similarity, the isolates were affiliated to the genus

Nocardioides

, and the closest species to MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T were

Nocardioides aestuarii

JC2056T (97.76%),

Nocardioides currus

IB-3T (97.41%) and

Nocardioides exalbidus

RC825T (98.71%), respectively. Each isolate formed a distinct cluster within the

Nocardioides

clade in the phylogenetic tree. The orthologous average nucleotide identity and digital DNA–DNA hybridization values were in the range of 74.4–85.7 % and 16.6–39.2 %, respectively, with the type strains of related species. The major polar lipids in all three strains were phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol. The predominant fatty acids were iso-C16 : 0 and C17 : 1 ω8c. MK-8(H4) was the major isoprenoid quinone and ll-DAP was the major diamino acid. Galactose, glucose and rhamnose were present in the whole-cell hydrolysate, and MMS17-SY213T also contained mannose and ribose. The DNA G+C contents of MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T were 72.2, 70.4 and 71.5 mol%, respectively. The phylogenetic, phenotypic and chemotaxonomic data supported the classification of each strain as representing a new species of

Nocardioides

, for which the names Nocardioides euryhalodurans sp. nov. (MMS17-SY117T=KCTC 49175T=JCM 32831T), Nocardioides seonyuensis sp. nov. (MMS17-SY207-3T=KCTC 49176T=JCM 32832T) and Nocardioides eburneiflavus sp. nov. (MMS17-SY213T=KCTC 49177T=JCM 32833T) are proposed accordingly.
Mycoparasitism illuminated by genome and transcriptome sequencing of Coniothyrium minitans, an important biocontrol fungus of the plant pathogen Sclerotinia sclerotiorum
Authors: Zhao Huizhang , Zhou Ting , Xie Jiatao , Cheng Jiasen , Chen Tao , Jiang Daohong , Fu Yanping
Published: March 2020

Coniothyrium minitans is a mycoparasite of the notorious plant pathogen Sclerotinia sclerotiorum. To further understand the parasitism of C. minitans, we assembled and analysed its genome and performed transcriptome analyses. The genome of C. minitans strain ZS-1 was assembled into 350 scaffolds and had a size of 39.8 Mb. A total of 11 437 predicted genes and proteins were annotated, and 30.8 % of the blast hits matched proteins encoded by another member of the Pleosporales, Paraphaeosphaeria sporulosa, a worldwide soilborne fungus with biocontrol ability. The transcriptome of strain ZS-1 during the early interaction with S. sclerotiorum at 0, 4 and 12 h was analysed. The detected expressed genes were involved in responses to host defenses, including cell-wall-degrading enzymes, transporters, secretory proteins and secondary metabolite productions. Seventeen differentially expressed genes (DEGs) of fungal cell-wall-degrading enzymes (FCWDs) were up-regulated during parasitism, with only one down-regulated. Most of the monocarboxylate transporter genes of the major facilitator superfamily and all the detected ABC transporters, especially the heavy metal transporters, were significantly up-regulated. Approximately 8 % of the 11 437 proteins in C. minitans were predicted to be secretory proteins with catalytic activity. In the molecular function category, hydrolase activity, peptidase activity and serine hydrolase activity were enriched. Most genes involved in serine hydrolase activity were significantly up-regulated. This genomic analysis and genome-wide expression study demonstrates that the mycoparasitism process of C. minitans is complex and a broad range of proteins are deployed by C. minitans to successfully invade its host. Our study provides insights into the mechanisms of the mycoparasitism between C. minitans and S. sclerotiorum and identifies potential secondary metabolites from C. minitans for application as a biocontrol agent.
Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China
Authors: Zhao Zonghao , Xie Jiajia , Yin Ming , Yang Yun , He Hongliang , Jin Tengchuan , Li Wenting , Zhu Xiaowu , Xu Jing , Zhao Changcheng , Li Lei , Li Yi , Mengist Hylemariam Mihiretie , Zahid Ayesha , Yao Ziqin , Ding Chengchao , Qi Yingjie , Gao Yong , Ma Xiaoling
Published: March 2020

The outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.
Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data
Authors: Henry Brandon Michael , de Oliveira Maria Helena Santos
Published: March 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19

Methods

In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms.

Results

A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%).

Conclusions

The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.
Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome
Authors: Yang Yang , Shen Chenguang , Li Jinxiu , Yuan Jing , Yang Minghui , Wang Fuxiang , Li Guobao , Li Yanjie , Xing Li , Peng Ling , Wei Jinli , Cao Mengli , Zheng Haixia , Wu Weibo , Zou Rongrong , Li Delin , Xu Zhixiang , Wang Haiyan , Zhang Mingxia , Zhang Zheng , Liu Lei , Liu Yingxia
Published: March 2020

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.
Estimation of COVID-19 outbreak size in Italy based on international case exportations
Authors: Tuite Ashleigh R. , Ng Victoria , Rees Erin , Fisman David
Published: March 2020

Italy is currently experiencing an epidemic of COVID-19 which emerged in the Lombardy region 1. During the interval between February 25-29, 2020, we identified 46 cases of COVID-19 reported in 21 countries in Europe, Africa, North America, and South America which were either in individuals with recent travel from Italy, or who had presumed infection by a traveler from Italy 2. In six cases, in four of the affected countries (Switzerland, France, Austria, Croatia), land travel was a likely route of introduction, or was documented to have been the route of introduction2.
Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea from 31 January to 1 March 2020
Authors: Zhuang Zian , Zhao Shi , Lin Qianying , Cao Peihua , Lou Yijun , Yang Lin , Yang Shu , He Daihai
Published: March 2020

The novel coronavirus disease 2019 (COVID-19) outbreak in Republic of Korea has caused 3736 cases and 18 deaths by 1 March 2020. We modeled the transmission process in Republic of Korea with a stochastic model and estimated the basic reproduction numberR0as 2.6 (95%CI: 2.3-2.9) and 3.2 (95%CI: 2.9-3.5), under the assumption that the exponential growth starting 31 January and 5 February, 2020, respectively. Estimates of dispersion term (k) were larger than 10 significantly, which implies few super-spreading events..
Preliminary estimation of the novel coronavirus disease (COVID-19) cases in Iran: a modelling analysis based on overseas cases and air travel data
Authors: Zhuang Zian , Zhao Shi , Lin Qianying , Cao Peihua , Lou Yijun , Yang Lin , He Daihai
Published: March 2020

As of 1 March 2020, Iran has reported 987 COVID-19 cases and including 54 associated deaths. At least six neighboring countries (Bahrain, Iraq, Kuwait, Oman, Afghanistan and Pakistan) have reported imported COVID-19 cases from Iran. We used air travel data and the cases from Iran to other Middle East countries and estimated 16533 (95% CI: 5925, 35538) COVID-19 cases in Iran by 25 February, before UAE and other Gulf Cooperation Council countries suspended inbound and outbound flights from Iran.
A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19
Authors: Zhou Hong , Chen Xing , Hu Tao , Li Juan , Song Hao , Liu Yanran , Wang Peihan , Liu Di , Yang Jing , Holmes Edward C. , Hughes Alice C. , Bi Yuhai , Shi Weifeng
Published: March 2020

The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.
Creating a Survey Instrument for Self-Assessed Menstrual Cycle Characteristics and Androgen Excess
Authors: Mahalingaiah Shruthi , Cosenza Carol , Cheng J. Jojo , Rodriguez Erika , Aschengrau Ann
Published: March 2020

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, but tools for self-reported ascertainment are currently lacking. We created and evaluated an online survey instrument for identification of PCOS by incorporating clinically derived reproductive health questions and a novel pictorial tool for androgen excess. The survey was cognitively tested for question comprehension and usability. Comprehension problems included simplifying the PCOS definition and questions on bleeding duration. Recall and answer formation problems included beverage consumption and questions using symbols. Evaluation of this survey instrument via cognitive testing may help to accurately ascertain the prevalence of PCOS in general population settings.
Caution: The clinical characteristics of COVID-19 patients at admission are changing
Authors: Chen Zhaowei , Hu Jijia , Zhang Zongwei , Jiang Shan , Wang Tao , Shi Zhengli , Zhang Zhan
Published: March 2020

Background

With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19.

Methods

Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness.

Results

Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24).

Conclusions

The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.

Compared with the cases admitted earlier, more hidden initial symptoms and improved immune system disorders appeared in COVID-19 patients infected recently.
CoalQC - Quality control while inferring demographic histories from genomic data: Application to forest tree genomes
Authors: Patil Ajinkya Bharatraj , Shinde Sagar Sharad , Raghavendra S , Satish B.N , Kushalappa C.G , Vijay Nagarjun
Published: March 2020

Estimating demographic histories using genomic datasets has proven to be useful in addressing diverse evolutionary questions. Despite improvements in inference methods and availability of large genomic datasets, quality control steps to be performed prior to the use of sequentially Markovian coalescent (SMC) based methods remains understudied. While various filtering and masking steps have been used by previous studies, the rationale for such filtering and its consequences have not been assessed systematically. In this study, we have developed a reusable pipeline called “CoalQC”, to investigate potential sources of bias (such as repeat regions, heterogeneous coverage, and callability). First, we demonstrate that genome assembly quality can affect the estimation of demographic history using the genomes of several species. We then use the CoalQC pipeline to evaluate how different repeat classes affect the inference of demographic history in the plant speciesPopulus trichocarpa.Next, we assemble a draft genome by generating whole-genome sequencing data forMesua ferrea(sampled from Western Ghats, India), a multipurpose forest plant distributed across tropical south-east Asia and use it as an example to evaluate several technical (sequencing technology, PSMC parameter settings) and biological aspects that need to be considered while comparing demographic histories. Finally, we collate the genomic datasets of 14 additional forest tree species to compare the temporal dynamics of Ne and find evidence of a strong bottleneck in all tropical forest plants during Mid-Pleistocene glaciations. Our findings suggest that quality control prior to the use of SMC based methods is important and needs to be standardised.
In vivox-ray diffraction and simultaneous EMG reveal the time course of myofilament lattice dilation and filament stretch
Authors: Malingen SA , Asencio AM , Cass JA , Ma W , Irving TC , Daniel TL
Published: March 2020

Muscle’s function within an organism depends on the feedback between molecular to meter-scale processes. While the motions of muscle’s contractile machinery are well described in isolated preparations, only a handful of experiments have documented the kinematics of the lattice occurring when multi-scale interactions are fully intact. We used time-resolved x-ray diffraction to record the kinematics of the myofilament lattice within a normal operating context: the tethered flight ofManduca sexta. Since the primary flight muscles ofManduca sextaare synchronous, we used these results to reveal the timing ofin vivocross-bridge recruitment, which occurred 24 (s.d. 26) ms following activation. In addition, the thick filaments stretched an average of 0.75 (s.d. 0.32)% and thin filaments stretched 1.11 (s.d. 0.65)%. In contrast to otherin vivopreparations, lattice spacing changed an average of 2.72 (s.d. 1.47)%. Lattice dilation of this magnitude significantly impacts shortening velocity and force generation, and filament stretching tunes force generation. While kinematics were consistent within individual trials, there was extensive variation between trials. Using a mechanism-free machine learning model we searched for patterns within and across trials. While lattice kinematics were predictable within trials, the model could not create predictions across trials. This indicates that the variability we see across trials may be explained by latent variables occurring in this naturally functioning system. The diverse kinematic combinations we documented mirror muscle’s adaptability and may facilitate its robust function in unpredictable conditions.
Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As Candidate Therapeutic Target
Authors: Johnson Katherine J. , Kumar Vikas , Kurimchak Alison M. , Srivastava Nishi , Peri Suraj , Cai Kathy Q. , Mantia-Smaldone Gina M. , Duncan James S.
Published: March 2020

Protein kinases (collectively, termed the kinome) represent one of the most tractable drug targets in the pursuit of new and effective cancer treatments. However, less than 20% of the kinome is currently being explored as primary targets for cancer therapy, leaving the majority of the kinome untargeted for drug therapy. Chemical proteomics approaches such as Multiplexed Inhibitor Beads and Mass Spectrometry (MIB-MS) have been developed that measure the abundance of a significant portion of the kinome, providing a strategy to interrogate kinome landscapes and dynamics. Kinome profiling of cancer cell lines using MIB-MS has been extensively characterized, however, application of this method to measure tissue kinome(s) has not been thoroughly explored. Here, we present a quantitative proteomics workflow specifically designed for kinome profiling of tissues that pairs MIB-MS with a newly designed super-SILAC kinome standard. Using this workflow, we mapped the kinome landscape of endometrial carcinoma (EC) tumors and normal endometrial (NE) tissues and identified several kinases overexpressed in EC tumors, including Serine/Arginine-Rich Splicing Factor kinase, (SRPK1). Immunohistochemical (IHC) analysis of EC tumor TMAs confirmed MIB-MS findings and showed SRPK1 protein levels were highly expressed in endometrioid and uterine serous cancer (USC) histological subtypes. Querying large-scale genomics studies of EC tumors revealed high expression of SRPK1 correlated with poor survival. Inhibition of SRPK1 in USC cells altered mRNA splicing, downregulating several oncogenes including MYC and Survivin resulting in apoptosis. Taken together, we present a SILAC-based MIB-MS kinome profiling platform for measuring kinase abundance in tumor tissues, and demonstrate its application to identify SRPK1 as a plausible kinase drug target for the treatment of EC.
Biodiversity mediates the effects of stressors but not nutrients on litter decomposition
Authors: Beaumelle Léa , Laender Frederik De , Eisenhauer Nico
Published: March 2020

Understanding the consequences of ongoing biodiversity changes for ecosystems is a pressing challenge. Controlled biodiversity-ecosystem function experiments with random biodiversity loss scenarios have demonstrated that more diverse communities usually provide higher levels of ecosystem functioning. However, it is not clear if these results predict the ecosystem consequences of environmental changes that cause non-random alterations in biodiversity and community composition. We synthesized 69 independent studies reporting 660 observations of the impacts of two pervasive drivers of global change (chemical stressors and nutrient enrichment) on animal and microbial decomposer diversity and litter decomposition. Using meta-analysis and structural equation modelling, we show that declines in decomposer diversity and abundance explain reduced litter decomposition in response to stressors but not to nutrients. While chemical stressors generally reduced biodiversity and ecosystem functioning, detrimental effects of nutrients occurred only at high levels of nutrient inputs. Thus, more intense environmental change does not always result in stronger responses, illustrating the complexity of ecosystem consequences of biodiversity change. Overall, these findings provide strong empirical evidence for significant real-world biodiversity-ecosystem functioning relationships when human activities decrease biodiversity. This highlights that the consequences of biodiversity change for ecosystems are nontrivial and depend on the kind of environmental change.
Population Stratification at the Phenotypic Variance level and Implication for the Analysis of Whole Genome Sequencing Data from Multiple Studies
Authors: Sofer Tamar , Zheng Xiuwen , Laurie Cecelia A. , Gogarten Stephanie M. , Brody Jennifer A. , Conomos Matthew P. , Bis Joshua C. , Thornton Timothy A. , Szpiro Adam , O’Connell Jeffrey R. , Lange Ethan M. , Gao Yan , Cupples L. Adrienne , Psaty Bruce M. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Rice Kenneth M.
Published: March 2020

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term ‘variance stratification’. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We also illustrate the variance stratification problem, its solutions, and a corresponding diagnostic procedure in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.
The physical form of microbial ligands bypasses the need for dendritic cell migration to stimulate adaptive immunity
Authors: Borriello Francesco , Spreafico Roberto , Poli Valentina , Chou Janet , Barrett Nora A. , Lacanfora Lucrezia , Franco Marcella E , Marongiu Laura , Iwakura Yoichiro , Pucci Ferdinando , Kruppa Michael D , Ma Zuchao , Wiliams David L , Zanoni Ivan
Published: March 2020

A central paradigm of immunology is that the innate immune system first detects infectious agents in peripheral tissues, shortly after a pathogen has breached an epithelial barrier. This detection event is mediated by pattern recognition receptors in phagocytes, which then migrate to draining lymph nodes (dLNs), where information of a microbial encounter is conveyed to T and B lymphocytes to generate adaptive immunity. Through the study of fungal moieties, we present data that challenge this model. We found that soluble fungal polysaccharides are immunosilent in the periphery, but become potent immunogens in the dLN. These ligands completely bypass the need of phagocyte migration and, instead, directly activate an immune response that is most similar to those that typify viral infections. These data establish a class of microbial products that violate a central tenet of the immunological lexicon and illustrate that the physical form (not just the chemical structure) impacts innate and adaptive immunity.
Plagues of Desert Locust: No invasion risk to China
Authors: Wang Yun-Ping , Wu Ming-Fei , Lin Pei-Jiong , Wang Yao , Chen Ai-Dong , Jiang Yu-Ying , Zhai Bao-Ping , Chapman Jason W. , Hu Gao
Published: March 2020

Recently, the most serious upsurge of desert locust (Schistocerca gregaria) in the last 25 years is spreading across eastern Africa and southwestern Asia. Parts of the desert locust ‘invasion area’, namely the northern border areas of Pakistan and India are very close to China, and whether locust swarms will invade China is of wide concern. To answer this question, we identified areas of potentially suitable habitat for the desert locust within China based on historical precipitation and temperature data, and found that parts of Xinjiang and Inner Mongolia provinces could provide ephemeral habitat in summer, but these places are remote from any other desert locust breeding area. Presently, the desert locust populations in Pakistan and India are mature and have laid eggs, and are less likely to spread long distances. The next generation of adults will appear in April and May, and so we examined twenty years’ historical wind data (2000–2019) for this period. Our results showed that winds at the height of locust swarm flight blew eastward during April and May, but the wind speeds were quite slow and would not facilitate desert locust eastward migration over large distances. Furthermore, simulated trajectories of desert locust swarms with 10 days’ migration mostly ended within India. The most easterly point of these trajectories just reached eastern India, close to the border between India and Myanmar, and this is very close to the eastern border of the invasion area of desert locust described in previous studies. In conclusion, the risk that the desert locust will invade China is very low.
Direction-selective motion discrimination by traveling waves in visual cortex
Authors: Heitmann Stewart , Ermentrout G. Bard
Published: March 2020

The majority of neurons in primary visual cortex respond selectively to bars of light that have a specific orientation and move in a specific direction. The spatial and temporal responses of such neurons are non-separable. How neurons accomplish that computational feat without resort to explicit time delays is unknown. We propose a novel neural mechanism whereby visual cortex computes non-separable responses by generating endogenous traveling waves of neural activity that resonate with the space-time signature of the visual stimulus. The spatiotemporal characteristics of the response are defined by the local topology of excitatory and inhibitory lateral connections in the cortex. We simulated the interaction between endogenous traveling waves and the visual stimulus using spatially distributed populations of excitatory and inhibitory neurons with Wilson-Cowan dynamics and inhibitory-surround coupling. Our model reliably detected visual gratings that moved with a given speed and direction provided that we incorporated neural competition to suppress false motion signals in the opposite direction. The findings suggest that endogenous traveling waves in visual cortex can impart direction-selectivity on neural responses without resort to explicit time delays. They also suggest a functional role for motion opponency in eliminating false motion signals.

Author summary

It is well established that the so-called ‘simple cells’ of the primary visual cortex respond preferentially to oriented bars of light that move across the visual field with a particular speed and direction. The spatiotemporal responses of such neurons are said to be non-separable because they cannot be constructed from independent spatial and temporal neural mechanisms. Contemporary theories of how neurons compute non-separable responses typically rely on finely tuned transmission delays between signals from disparate regions of the visual field. However the existence of such delays is controversial. We propose an alternative neural mechanism for computing non-separable responses that does not require transmission delays. It instead relies on the predisposition of the cortical tissue to spontaneously generate spatiotemporal waves of neural activity that travel with a particular speed and direction. We propose that the endogenous wave activity resonates with the visual stimulus to elicit direction-selective neural responses to visual motion. We demonstrate the principle in computer models and show that competition between opposing neurons robustly enhances their ability to discriminate between visual gratings that move in opposite directions.
Noise Invariance in Inferior Colliculus Neurons is Dependant on the Input Noisy Conditions
Authors: Hosseini Maryam , Rodriguez Gerardo , Guo Hongsun , Lim Hubert H. , Plourde Éric
Published: March 2020

The auditory system is extremely efficient to extract audio information in the presence of background noise. However, the neural mechanisms related to this efficiency is still greatly misunderstood, especially in the inferior colliculus (IC). In fact, while noise processing under different conditions has been investigated at the auditory cortex level, studies in the IC have been much limited. One interesting observation has been that there seems to be some degree of noise invariance in the IC in the presence of white noise. We wish to broaden this knowledge by investigating if there is a difference in the activity of neurons in the IC, when presenting noisy vocalisations with different types of noises, input signal-to-noise ratios (SNR) and signal levels. We do so using a generalized linear model (GLM), which gives us the ability to study the neural activity under these different conditions at a per neuron level. We found that non-stationary noise is the only noise type that clearly contributes to the neural activity in the IC, regardless of the SNR, input level or vocalisation type. However, when presenting white or natural stationary noises, a great diversity of responses was observed for the different conditions, where the activity of some neurons was affected by the presence of noise and the activity of others was not. Therefore, there seems to be some level of background noise invariance as early as the IC level, as reported before, however, this invariance seems to be highly dependent on the noisy conditions.

New & Noteworthy

The neural mechanisms of auditory perception in the presence of background noise are still not well understood, especially in the IC. We studied neural activity in the IC when presenting noisy vocalisations using different background noise types, SNRs and input sound levels. We observed that only the non-stationary noise type clearly contributes to the neural activity in the IC. The noise invariance previously observed in the IC thus seems dependent on the noisy conditions.
OGP: A Repository of Experimentally Characterized O-Glycoproteins to Facilitate Studies on O-Glycosylation
Authors: Huang Jiang-Ming , Wu Meng-Xi , Zhang Yang , Kong Si-Yuan , Liu Ming-Qi , Jiang Bi-Yun , Yang Peng-Yuan , Cao Wei-Qian
Published: March 2020

Numerous studies on cancer, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation. However, the lack of updated and convenient databases deters the storage and utilization of emerging O-glycoprotein data. To resolve this issue, an O-glycoprotein repository named OGP was established in this work. It was constructed with a collection of O-glycoprotein data from different sources. OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far. Based on the recorded O-glycosites, an O-glycosylation site prediction tool was developed. Moreover, an OGP-backed website is already available (http://www.oglyp.org/). The website comprises four specially designed and user-friendly modules: Statistic Analysis, Database Search, Site Prediction, and Data Submit. The first version of OGP repository and the website allow users to obtain vast O-glycoprotein related information, such as protein accession numbers, glycopeptides, site-specific glycan structures, experimental methods, and potential glycosylation sites. O-glycosylation data mining can be performed efficiently on this website, which can greatly facilitates O-glycosylation studies.
Coral accurately bridges paired-end RNA-seq reads alignment
Authors: Shi Qian , Shao Mingfu
Published: March 2020

Motivation

The established high-throughput RNA-seq technologies usually produce paired-end reads. A challenging problem is therefore to computationally infer the alignment of entire fragments given the alignment of the two mate ends. Solving this problem essentially provide longer RNA-seq reads, and hence benefits downstream RNA-seq analysis.

Results

We introduce Coral, a new tool that can accurately bridge paired-end RNA-seq reads. The core of Coral is a novel optimization formulation that can capture the most reliable bridging path while also filter out false paths. An efficient dynamic programming algorithm is designed to calculate the topNoptimum. Coral implements a consensus approach to select the best solution among theNcandidates by taking into account the distribution of fragment length. Coral is modular, can be easily incorporated into existing RNA-seq analysis pipeline. We show that Coral can improve transcript assembly by a large margin: on average over 2377 RNA-seq samples from GTEx, the improvement (measured with adjusted precision) is 7.5% and 11.2% when Coral is incorporated with StringTie and Scallop, respectively.

Availability

Coral is open-source, freely available at GitHub (https://github.com/Shao-Group/coral) and Bioconda. Scripts, datasets and documentations that can reproduce all experimental results in this paper are available athttps://github.com/Shao-Group/coraltest.
Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type1 diabetes therapeutic reversal in preclinical models
Authors: Pham Vinh , Ramirez David G. , Benninger Richard K.P.
Published: March 2020

In type 1 diabetes (T1D) immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes presents. Non-invasively detecting insulitis and β-cell decline would allow diagnosis of eventual diabetes and provide a means to monitor the efficacy of therapeutic intervention. However, there is a lack of validated clinical approaches for non-invasively imaging disease progression leading to T1D. Islets have a dense microvasculature that reorganizes during diabetes. We previously demonstrated contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics could predict disease progression in T1D pre-clinical models. Here we test whether these measurements can predict successful therapeutic prevention of T1D. We performed destruction-reperfusion measurements using a small-animal ultrasound machine and size-isolated microbubbles, in NOD-scid mice receiving an adoptive transfer of diabetogenic splenocytes (AT mice). Mice received vehicle control or either of the following treatments: 1) antiCD4 to deplete CD4+T cells; 2) antiCD3 to block T cell activation, 3) Verapamil to reduce β-cell apoptosis and 4) TUDCA to reduce ER stress. We compared measurements of pancreas blood-flow dynamics with subsequent progression to diabetes. In AT mice blood-flow dynamics were altered >2 weeks after splenocyte transfer. AntiCD4, antiCD3 and verapamil provided a significant delay in diabetes development. Treated AT mice with delayed or absent diabetes development showed significantly altered blood flow dynamics compared to untreated AT mice. Conversely, treated AT mice that developed diabetes, despite therapy, showed similar blood-flow dynamics to untreated AT mice. Thus, contrast-enhanced ultrasound measurement of pancreas blood-flow dynamics can predict the successful or unsuccessful delay or prevention of diabetes upon therapeutic treatments that target both immune activity or β-cell protection. This strategy may provide a clinically deployable predictive marker for disease progression and therapeutic reversal in asymptomatic T1D.