bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Interaction of CCR4-NOT Proteins With TATAA-Binding Protein (TBP) and Its Associated Factors in Yeast
Authors: Badarinarayana Vasudeo , Chiang Yueh-Chin , Denis Clyde L
Published: April 2021

The CCR4-NOT transcriptional regulatory complex affects expression of a number of genes both positively and negatively. We report here that components of the CCR4-NOT complex functionally and physically interact with TBP and TBP-associated factors. First, mutations in CCR4-NOT components suppressed the his4-912δ insertion in a manner similar to that observed for the defective TBP allele spt15-122. Second, using modified HIS3 promoter derivatives containing specific mutations within the TATA sequence, we found that the NOT proteins were general repressors that disrupt TBP function irrespective of the DNA sequence. Third, increasing the dosage of NOT1 specifically inhibited the ability of spt15-122 to suppress the his4-912δ insertion but did not affect the Spt− phenotype of spt3 or spt10 at this locus. Fourth, spt3, spt8, and spt15-21 alleles (all involved in affecting interaction of SPT3 with TBP) suppressed ccr4 and caf1 defects. Finally, we show that NOT2 and NOT5 can be immunoprecipitated by TBP. NOT5 was subsequently shown to associate with TBP and TAFs and this association was dependent on the integrity of TFIID. These genetic and physical interactions indicate that one role of the CCR4-NOT proteins is to inhibit functional TBP-DNA interactions, perhaps by interacting with and modulating the function of TFIID.
Genetic Analyses ofSchizosaccharomyces pombe dna2+ Reveal That Dna2 Plays an Essential Role in Okazaki Fragment Metabolism
Authors: Kang Ho-Young , Choi Eunjoo , Bae Sung-Ho , Lee Kyoung-Hwa , Gim Byung-Soo , Kim Hee-Dai , Park Chankyu , MacNeill Stuart A , Seo Yeon-Soo
Published: April 2021

In this report, we investigated the phenotypes caused by temperature-sensitive (ts) mutant alleles of dna2+ of Schizosaccharomyces pombe, a homologue of DNA2 of budding yeast, in an attempt to further define its function in vivo with respect to lagging-strand synthesis during the S-phase of the cell cycle. At the restrictive temperature, dna2 (ts) cells arrested at late S-phase but were unaffected in bulk DNA synthesis. Moreover, they exhibited aberrant mitosis when combined with checkpoint mutations, in keeping with a role for Dna2 in Okazaki fragment maturation. Similarly, spores in which dna2+ was disrupted duplicated their DNA content during germination and also arrested at late S-phase. Inactivation of dna2+ led to chromosome fragmentation strikingly similar to that seen when cdc17+, the DNA ligase I gene, is inactivated. The temperature-dependent lethality of dna2 (ts) mutants was suppressed by overexpression of genes encoding subunits of polymerase δ (cdc1+ and cdc27+), DNA ligase I (cdc17+), and Fen-1 (rad2+). Each of these gene products plays a role in the elongation or maturation of Okazaki fragments. Moreover, they all interacted with S. pombe Dna2 in a yeast two-hybrid assay, albeit to different extents. On the basis of these results, we conclude that dna2+ plays a direct role in the Okazaki fragment elongation and maturation. We propose that dna2+ acts as a central protein to form a complex with other proteins required to coordinate the multienzyme process for Okazaki fragment elongation and maturation.
Joint Effects of Natural Selection and Recombination on Gene Flow Between Drosophila ananassae Populations
Authors: Chen Ying , Marsh Brenda J , Stephan Wolfgang
Published: April 2021

We estimated DNA sequence variation in a 5.7-kb fragment of the furrowed (fw) gene region within and between four populations of Drosophila ananassae; fw is located in a chromosomal region of very low recombination. We analyzed gene flow between these four populations along a latitudinal transect on the Indian subcontinent: two populations from southern, subtropical areas (Hyderabad, India, and Sri Lanka) and two from more temperate zones in the north (Nepal and Burma). Furthermore, we compared the pattern of differentiation at fw with published data from Om(1D), a gene located in a region of normal recombination. While differentiation at Om(1D) shows an isolation-by-distance effect, at fw the pattern of differentiation is quite different such that the frequencies of single nucleotide polymorphisms are homogenized over extended geographic regions (i.e., among the two populations of the northern species range from Burma and Nepal as well as among the two southern populations from India and Sri Lanka), but strongly differentiated between the northern and southern populations. To examine these differences in the patterns of variation and differentiation between the Om(1D) and fw gene regions, we determine the critical values of our previously proposed test of the background selection hypothesis (henceforth called FST test). Using these results, we show that the pattern of differentiation at fw may be inconsistent with the background selection model. The data depart from this model in a direction that is compatible with the occurrence of recent selective sweeps in the northern as well as southern populations.
Chromosomal Position Effects Reveal Different cis-Acting Requirements for rDNA Transcription and Sex Chromosome Pairing in Drosophila melanogaster
Authors: Briscoe Albert , Tomkiel John E
Published: April 2021

In Drosophila melanogaster, the rDNA loci function in ribosome biogenesis and nucleolar formation and also as sex chromosome pairing sites in male meiosis. These activities are not dependent on the heterochromatic location of the rDNA, because euchromatic transgenes are competent to form nucleoli and restore pairing to rDNA-deficient X chromosomes. These transgene studies, however, do not address requirements for the function of the endogenous rDNA loci within the heterochromatin. Here we describe two chromosome rearrangements that disrupt rDNA functions. Both rearrangements are translocations that cause an extreme bobbed visible phenotype and XY nondisjunction and meiotic drive in males. However, neither rearrangement interacts with a specific Y chromosome, Ymal+, that induces male sterility in combination with rDNA deletions. Molecular studies show that the translocations are not associated with gross rearrangements of the rDNA repeat arrays. Rather, suppression of the bobbed phenotypes by Y heterochromatin suggests that decreased rDNA function is caused by a chromosomal position effect. While both translocations affect rDNA transcription, only one disrupts meiotic XY pairing, indicating that there are different cis-acting requirements for rDNA transcription and rDNA-mediated meiotic pairing.
Nucleotide Polymorphism at the RpII215 Gene in Drosophila subobscura: Weak Selection on Synonymous Mutations
Authors: Llopart Ana , Aguadé Montserrat
Published: April 2021

Nucleotide variation in an 8.1-kb fragment encompassing the RpII215 gene, which encodes the largest subunit of the RNA polymerase II complex, is analyzed in a sample of 11 chromosomes from a natural population of Drosophila subobscura. No amino acid polymorphism was detected among the 157 segregating sites. The observed numbers of preferred and unpreferred derived synonymous mutations can be explained by neutral mutational processes. In contrast, preferred mutations segregate at significantly higher frequency than unpreferred mutations, suggesting the action of natural selection. The polymorphism to divergence ratio is different for preferred and unpreferred changes, in agreement with their beneficial and deleterious effects on fitness, respectively. Preferred and unpreferred codons are nonrandomly distributed in the RpII215 gene, leading to a heterogeneous distribution of polymorphic to fixed synonymous differences across this coding region. This intragenic variation of the polymorphism/divergence ratio cannot be explained by different patterns of gene expression, mutation, or recombination rates, and therefore it indicates that selection coefficients for synonymous mutations can vary extensively across a coding region. The application of nucleotide composition stationarity tests in coding and flanking noncoding regions, assumed to behave neutrally, allows the detection of the action of natural selection when stationarity holds in the noncoding region.
Cellular Consequences in the Brain and Liver of Age-Specific Selection for Rate of Development in Mice
Authors: Atchley William R , Wei Rong , Crenshaw Pamela
Published: April 2021

Changes in cell number (hyperplasia) and cell size (hypertrophy) in the brain and liver are described for mice subjected to 24 generations of age-specific restricted index selection for rate of development in body weight. One selection treatment (E) altered rate of development between birth and 10 days of age, another treatment (L) involved changes in rate of development between 28 and 56 days of age, while a third control treatment (C) involved random selection. Each selection treatment was replicated three times. These age-specific selection treatments focused on intervals during ontogeny when different developmental processes (hypertrophy or hyperplasia) were more predominant in the control of growth. Significant changes in brain and liver weight occurred at both 28 and 70 days of age. Early selection (E) generated significant changes in the number of cells in the brain while later selection (L) had no effect since the brain had stopped growth before selection was initiated. For the liver, early and late selection produced significant effects on both cell number and cell size. These results describe the dynamic and multidimensional aspects of selection in terms of its ability to alter different cellular and developmental components of complex morphological traits.
Bayesian Mapping of Quantitative Trait Loci for Complex Binary Traits
Authors: Yi Nengjun , Xu Shizhong
Published: April 2021

A complex binary trait is a character that has a dichotomous expression but with a polygenic genetic background. Mapping quantitative trait loci (QTL) for such traits is difficult because of the discrete nature and the reduced variation in the phenotypic distribution. Bayesian statistics are proved to be a powerful tool for solving complicated genetic problems, such as multiple QTL with nonadditive effects, and have been successfully applied to QTL mapping for continuous traits. In this study, we show that Bayesian statistics are particularly useful for mapping QTL for complex binary traits. We model the binary trait under the classical threshold model of quantitative genetics. The Bayesian mapping statistics are developed on the basis of the idea of data augmentation. This treatment allows an easy way to generate the value of a hypothetical underlying variable (called the liability) and a threshold, which in turn allow the use of existing Bayesian statistics. The reversible jump Markov chain Monte Carlo algorithm is used to simulate the posterior samples of all unknowns, including the number of QTL, the locations and effects of identified QTL, genotypes of each individual at both the QTL and markers, and eventually the liability of each individual. The Bayesian mapping ends with an estimation of the joint posterior distribution of the number of QTL and the locations and effects of the identified QTL. Utilities of the method are demonstrated using a simulated outbred full-sib family. A computer program written in FORTRAN language is freely available on request.
Multipoint Mapping of Viability and Segregation Distorting Loci Using Molecular Markers
Authors: Vogl Claus , Xu Shizhong
Published: April 2021

In line-crossing experiments, deviations from Mendelian segregation ratios are usually observed for some markers. We hypothesize that these deviations are caused by one or more segregation-distorting loci (SDL) linked to the markers. We develop both a maximum-likelihood (ML) method and a Bayesian method to map SDL using molecular markers. The ML mapping is implemented via an EM algorithm and the Bayesian method is performed via the Markov chain Monte Carlo (MCMC). The Bayesian mapping is computationally more intensive than the ML mapping but can handle more complicated models such as multiple SDL and variable number of SDL. Both methods are applied to a set of simulated data and real data from a cross of two Scots pine trees.
Zygotic Associations and Multilocus Statistics in a Nonequilibrium Diploid Population
Authors: Yang Rong-Cai
Published: April 2021

The usual approach to characterizing and estimating multilocus associations in a diploid population assumes that the population is in Hardy-Weinberg equilibrium. The purpose of this study is to develop a set of summary statistics that can be used to characterize and estimate the multilocus associations in a nonequilibrium population. The concept of “zygotic associations” is first expanded to facilitate the development. The summary statistics are calculated using the distribution of a random variable, the number of heterozygous loci (K) found in diploid individuals in the population. In particular, the variance of K consists of single-locus and multilocus components with the latter being the sum of zygotic associations between pairs of loci. Simulation results show that the multilocus associations in the variance of K are detectable in a sample of moderate size (≥30) when the sum of all pairwise zygotic associations is greater than zero and when gene frequency is intermediate. The method presented here is a generalization of the well-known development for the Hardy-Weinberg equilibrium population and thus may be of more general use in elucidating the multilocus organizations in nonequilibrium and equilibrium populations.
A Unique Academic–Government Collaboration Yields First Report of Detailed Habitat Description for Haemaphysalis longicornis (Ixodida: Ixodidae) in Madison County, KY
Authors: Vogt J T , Allen B D , Paulsen D , Trout Fryxell R T
Published: April 2021

Haemaphysalis longicornis Neumann, Asian longhorned tick, was collected in Madison County, Kentucky, United States as part of an ongoing collaborative-tick surveillance project. This is the first collection of this invasive tick that includes ancillary data on habitat and landscape features derived from the USDA Forest Service, Forest Inventory and Analysis program.
HDAC9 exacerbates myocardial infarction via inactivating Nrf2 pathways
Authors: Liu Fan , Di Yali , Ma Wei , Kang Xiaoli , Li Xia , Ji Zheng
Published: April 2021

Objectives

Myocardial infarction (MI) is the leading cause of death worldwide. Histone deacetylases (HDACs) collectively participate in the initiation and progression of heart diseases, including MI. This study aimed to investigate the roles of histone deacetylase 9 (HDAC9) in the development of MI.

Methods

In vivo and in vitro assays were conducted to determine the effects of HDAC9 on heart function and MI. qRT-PCR was applied to determine the mRNA level. Western blot was performed for protein expression. Immunofluorescence was applied to detect the fluorescence tensity of Myog and Myod. CCK-8, flow cytometry and transwell assays were carried out for function analysis.

Key findings

HDAC9 was upregulated in MI models in vivo and in vitro. Downregulated HDAC9 modulated the changes in left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS) and left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD). Moreover, HDAC9 knockdown activated NFE2-related factor 2 (Nrf2)/Keap1/HO-1 pathways. Additionally, HDAC9/Nrf2 axis modulated the proliferation, apoptosis and myogenesis of cardiomyocytes.

Conclusions

Taken together, HDAC9 knockout induced the activation of Nrf2 and protected heart from MI injury. Thus, the HDAC9/Nrf2 axis can be a novel marker for the treatment of MI.
Slow control and monitoring system at the JSNS2
Authors: Park J S , Ajimura S , Botran M , Choi J H , Choi J W , Cheoun M K , Dodo T , Furuta H , Goh J , Harada M , Hasegawa S , Hino Y , Hiraiwa T , Jang H I , Jang J S , Jang M C , Jeon H , Jeon S , Joo K K , Jordan J R , Jung D E , Kang S K , Kasugai Y , Kawasaki T , Kim E J , Kim J Y , Kim S B , Kim W , Konno T , Lee D H , Lee S , Lim I T , Marzec E , Maruyama T , Meigo S , Monjushiro S , Moon D H , Nakano T , Niiyama M , Nishikawa K , Nomachi M , Pac M Y , Peeters S J M , Ray H , Roellinghoff G , Rott C , Sakai K , Sakamoto S , Shima T , Shin C D , Spitz J , Stancu I , Sugaya Y , Suekane F , Suzuya K , Taira M , Ujiie R , Yeh M , Yeo I S , Yoo C , Yu I , Zohaib A
Published: April 2021

The Sterile Neutrino Search at the J-PARC Spallation Neutron Source (JSNS$^2$) experiment aims to search for sterile neutrino oscillations using a neutrino beam from muon decays at rest. The JSNS$^2$ detector contains 17 tons of 0.1$\%$ gadolinium (Gd) loaded liquid scintillator (LS) as a neutrino target. Detector construction was completed in the spring of 2020. A slow control and monitoring system (SCMS) was implemented for reliable control and quick monitoring of the detector operational status and environmental conditions. It issues an alarm if any of the monitored parameters exceed a preset acceptable range. The SCMS monitors the high voltage of the photomultiplier tubes, the LS level in the detector, possible LS overflow and leakage, the temperature and air pressure in the detector, the humidity of the experimental hall, and the LS flow rate during filling and extraction. An initial 10 days of data-taking with a neutrino beam was done following a successful commissioning of the detector and SCMS in 2020 June. In this paper, we present a description of the assembly and installation of the SCMS and its performance.
Stress debriefing
Authors: Anniello Laura W. , Karl Cherry A.
Published: April 2021

The critical care work environment is a high-stakes, high-stress setting where moral distress occurs frequently among nurses.
How to deliver family-centered care amidst visitor limitations
Authors: Jones Uletha M.
Published: April 2021

Communication and support for patient family members can be challenging, especially when in-person visitation is limited or eliminated entirely.
Prevalence and Risk Factors for Intraductal Papillary Mucinous Neoplasm in Patients With Chronic Kidney Disease
Authors: Shah Rushikesh , Mulki Ramzi , Lamm Vladimir , Kapil Neil , Patel Vaishali , Chawla Saurabh , Cai Qiang , Willingham Field F. , Keilin Steven
Published: April 2021

Objectives

The exact prevalence for intraductal papillary mucinous neoplasm (IPMN) in patients with chronic kidney disease (CKD) remains unknown. In this single-center case-control study, we aimed to study the prevalence and risk factors for IPMN in patients with CKD.

Methods

We performed a retrospective case-control study comparing patients with and without CKD who had magnetic resonance imaging of the abdomen performed between January 2018 and December 2018. Patient demographic, clinical, and imaging metrics were extracted from chart review. The prevalence of IPMN was compared between the 2 groups.

Results

A total of 800 patient charts were reviewed. There were 400 patients with CKD compared with an age-matched control group of 400 patients without CKD. The total prevalence of IPMN in patients with CKD was 13.7% (55/400) compared with 7.8% (29/400; P = 0.002) in non-CKD patients. The prevalence of diabetes mellitus was significantly higher in the CKD group (41% vs 14%, P = 0.0001). The percentage of patients consuming alcohol was significantly higher in the non-CKD group (23% vs 35%, P = 0.002).

Conclusions

Patients with CKD have a significantly higher prevalence of IPMN compared with non-CKD patients. Larger population-based studies are needed to confirm these findings.
The Value of Managing Acute Pancreatitis With Standardized Order Sets to Achieve “Perfect Care”
Authors: Shah Jimmy , Nwogu Christiana , Vivian Elaina , John Elizabeth S. , Kedia Prashant , Sellers Brad , Cler Leslie , Acharya Priyanka , Tarnasky Paul
Published: April 2021

Objectives

We aimed to define perfect care index (PCI) metrics and to evaluate whether implementation of standardized order sets would improve outcomes without increasing hospital-based charges in patients with acute pancreatitis (AP).

Methods

This is a retrospective, pre-post, observational study measuring clinical quality, processes of care, and hospital-based charges at a single tertiary care center. The first data set included AP patients from August 2011 to December 2014 (n = 219) before the implementation of a standardized order set (Methodist Acute Pancreatitis Protocol [MAPP]) and AP patients after MAPP implementation from January 2015 to September 2018 (n = 417). The second data set included AP patients (n = 150 in each group) from January 2013 to September 2014 (pre-MAPP) and January 2018 to September 2019 (post-MAPP) to evaluate perfect care between the 2 cohorts after controlling for systemic inflammatory response syndrome at baseline. Length of stay, PCI, and hospital-based charges were measured.

Results

The post-MAPP cohort had a significantly shorter length of stay (median, 3 days vs 4 days; P = 0.01). In the second data set, PCI significantly increased after implementation of MAPP order sets (5.3%–35.3%, P < 0.0001).

Conclusions

The MAPP order sets increased the value of care by improving clinical outcomes without increasing hospital-based charges.
Metastatic Acinar Cell Carcinoma of the Pancreas
Authors: Busch Elena , Werft Wiebke , Bougatf Nina , Hackert Thilo , Jäger Dirk , Springfeld Christoph , Berger Anne Katrin
Published: April 2021

Objectives

Acinar cell carcinoma of the pancreas (pACC) forms a rare subgroup of pancreatic tumors. We report on our institutional experience with systemic first- and further-line therapy in patients with metastatic pACC and embed our findings in a review of the literature.

Methods

Patients with stage IV pACC who started systemic treatment between 2008 and 2019 at our institution were identified via our institutional database. Clinical data were extracted from the patients’ electronic data records. Survival times were calculated by the Kaplan-Meier method.

Results

Six patients received a fluoropyrimidine- and oxaliplatin-containing first-line treatment, and 4 patients were started on gemcitabine-based protocols. Median progression-free survival was 4.8 months [95% confidence interval (CI), 3.3 to not available (n.a.)], and median overall survival was 15.3 months (95% CI, 10.1 to n.a.). Residual survival for second-line treatment was 2.1 months (95% CI, 1.3 to n.a.), although 1 patient experienced almost complete remission under targeted therapy.

Conclusions

The most encouraging and deep responses result from poly-chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), which seems to be the appropriate choice in fit patients. Gemcitabine monotherapy seems without substantial activity in pACC. Whenever possible, patients with pACC should be screened for targetable mutations.
Pathological Features and Imaging Findings in Pancreatic Carcinoma In Situ
Authors: Hanada Keiji , Fukuhara Motomitsu , Minami Tomoyuki , Yano Shigeki , Ikemoto Juri , Shimizu Akinori , Kurihara Keisuke , Okuda Yasuhiro , Ikeda Morito , Yokode Masataka , Abe Tomoyuki , Yonehara Shuji , Yanagisawa Akio
Published: April 2021

Objectives

This study aimed to evaluate the pathological features and imaging findings of pancreatic carcinoma in situ (PCIS).

Methods

Twenty patients with PCIS were categorized as flat (F) (n = 6) and low papillary (LP) (n = 14) types.

Results

None of F type and 8 (57%) of 14 with LP type lesions showed intraductal infiltrations of the main pancreatic duct (MPD) greater than 10 mm. None of F type and 3 (21%) of 14 with LP type lesions showed skip lesions in the MPD. Magnetic resonance cholangiopancreatography showed irregular MPD stenoses in 5 (83%) of 6 with F and 13 (100%) of 13 with LP type lesions. Magnetic resonance cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 3.6 mm for F, and 11.6 mm for LP type lesions. Endoscopic retrograde cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 2.8 mm for F, and 14.3 mm for LP type lesions. Pancreatic cancer recurrences limited to the remnant pancreas occurred in 2 patients with LP type lesions.

Conclusions

In LP type PCIS, intraductal infiltration of the MPD occurs frequently. There may be multiple lesions, and lesions may recur in the remnant pancreas. Long-term strict follow-up assessments should be implemented for LP type PCIS.
Evaluation of Postoperative Quality of Life After Pancreatic Surgery and Determination of Influencing Risk Factors
Authors: Deichmann Steffen , Manschikow Sanda G. , Petrova Ekaterina , Bolm Louisa , Honselmann Kim C. , Frohneberg Laura , Keck Tobias , Wellner Ulrich F. , Bausch Dirk
Published: April 2021

Objectives

The postoperative quality of life (QoL) after pancreatic surgery is frequently impaired. The aim of this study was to evaluate the QoL after pancreatic surgery and its influencing risk factors. Furthermore, an age-adjusted comparison with the normal population of Germany was performed.

Methods

A total of 94 patients were surveyed. The Short Form-36 questionnaire was sent to all patients undergoing pancreatic surgery between 2013 and 2017. All pathologies and types of pancreatic resections were included. Statistical analyses were performed, and an analysis by the Robert Koch-Institute to determine the health-related age-adjusted QoL in Germany served as control group.

Results

Response rate was 29%. Median time of survey was 28 months. As compared with a normative population, QoL after pancreaticoduodenectomy was significantly impaired. Distal pancreatic resection showed no significant differences. Univariate and Lasso analyses showed that the following factors had a negative impact: coronary artery disease, chronic pancreatitis, and open access. Postoperative enzyme supplementation seemed to have a positive impact.

Conclusions

Pancreatic surgery leads to long-lasting negative effect on QoL. Distal pancreatic resections and laparoscopic access seemed to be the best tolerated. Complications seems to have less impact, whereas maintaining exocrine and endocrine function seems to have a positive effect.
A Novel Treatment for Metastatic Serous Cystadenocarcinoma Using a Microwave Ablation
Authors: Murtha Timothy D. , Cornman-Homonoff Joshua , Ayyagari Rajasekhara , Zhang Xuchen , Salem Ronald R.
Published: April 2021

The incidence of pancreatic cystic neoplasms has grown because of increased detection. Among these lesions, serous cystadenoma was traditionally thought to be universally benign and indolent. However, there is an exceedingly rare malignant variant of serous cystadenoma known as serous cystadenocarcinoma (SCAC) that can exhibit local invasion into adjacent structures, hepatic implants, and metastatic spread to the abdominal viscera. Diagnosis of SCAC can be challenging as it is histologically identical to serous cystadenoma. To better understand this entity, a review of all published accounts of SCAC was performed in which tumor and patient factors were characterized. In addition, we present the case of a 49-year-old woman who was found to have a solitary hepatic metastasis due to SCAC, 11 years after a distal pancreatectomy for serous cystadenoma. She was successfully treated with percutaneous microwave ablation and has no evidence of recurrence 3 years later. This report details the first published account of percutaneous ablation in such a setting. Compared with hepatectomy, hepatic ablation may offer a less invasive but equally effective treatment option in well-selected patients.
Rigid intramedullary nail fixation of traumatic femoral fractures in the skeletally immature
Authors: Del Balso Christopher , Bartley Debra , Cashin Megan , Carey Timothy , Lawendy Abdel Rahman
Published: April 2021

Objective:

To determine the rate of femoral head osteonecrosis, and other complications following rigid intramedullary (IM) nail fixation of traumatic diaphyseal femur fractures through the greater trochanter in the skeletally immature.

Design:

Retrospective review, case series.

Setting:

Level I academic trauma center.

Patients/Participants:

One hundred forty-eight traumatic pediatric diaphyseal femur fractures in 145 patients treated with rigid IM nail fixation from November 1, 2004 to December 31, 2018.

Intervention:

Rigid intramedullary nail fixation of traumatic diaphyseal femur fractures through a trochanteric start point in the skeletally immature.

Main outcome measurement:

Rate of osteonecrosis of the femoral head.

Results:

Sixty-five fractures in 64 skeletally immature patients met inclusion criteria. Motor vehicle collisions were implicated in 32 fractures. Of the 65 fractures, 5 were open. All rigid IM nails were anterograde with a trochanteric start point. Mean radiographic follow-up was 27.4 ± 8.1 months. Twenty-two patients experienced postoperative pain and/or hardware irritation, with 24 patients (36.9%) undergoing reoperation for hardware removal. No occurrences of infection, malunion, nonunion, refracture, venous thromboembolism, fat embolism, significant leg length discrepancy, or femoral head osteonecrosis were documented. Two cases of heterotopic ossification were observed, 1 requiring surgical excision, yielding a complication rate of 3.1%.

Conclusions:

No cases of femoral head osteonecrosis were observed following treatment of 65 traumatic diaphyseal femur fractures with rigid IM nailing through the greater trochanter with a mean radiographic follow-up of 27 months. Rigid IM nail fixation with a trochanteric start point is both safe and efficacious for management of diaphyseal femur fractures in the skeletally immature.
Region-specific microRNA alterations in marmosets carrying SLC6A4 polymorphisms are associated with anxiety-like behavior
Authors: Popa Natalia , Bachar Dipankar , Roberts Angela C. , Santangelo Andrea M. , Gascon Eduardo
Published: April 2021

Psychiatric diseases such as depression and anxiety are multifactorial conditions, highly prevalent in western societies. Human studies have identified a number of high-risk genetic variants for these diseases. Among them, polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) have attracted much attention. However, due to the paucity of experimental models, molecular alterations induced by these genetic variants and how they correlate to behavioral deficits have not been examined. Marmosets have emerged as a powerful model in translational neuroscience to investigate molecular underpinnings of complex behaviors. Here, we took advantage of naturally occurring genetic polymorphisms in marmosetSLC6A4gene that have been linked to anxiety-like behaviors. Using FACS-sorted cells from different brain regions, we revealed that marmosets bearing differentSLC6A4variants exhibit distinct microRNAs signatures in a region of the prefrontal cortex whose activity has been consistently altered in patients with depression/anxiety. We also identified DCC, a gene previously linked to these diseases, as a downstream target of the dysregulated microRNAs. Significantly, we showed that levels of both microRNAs and DCC in this region were highly correlated to anxiety-like behaviors as well as to the response to citalopram, a selective serotonin re-uptake inhibitor and widely prescribed anti-depressant. Our findings establish links between genetic variants, molecular modifications in specific cortical regions and complex behavioral/pharmacological responses, providing new insights into gene-behavior relationships underlying human psychopathology.
Chromosome-level genome assembly ofAcanthopagrus latususing PacBio and Hi-C technologies
Authors: Gao Dong , Fang Wenyu , Sims Ying , Collins Joanna , Torrance James , Lin Genmei , Xie Jingui , Howe Kerstin , Lu Jianguo
Published: April 2021

The yellowfin seabream,Acanthopagrus latus, is widely distributed throughout the Indo-West Pacific. This fish is an ideal model species in which to study the mechanism of sex reversal since it exhibits a specific feature: sequential hermaphrodite. Here, we report a chromosome-scale assembly of theA. latusbased on PacBio and Hi-C data. 22,485 protein-coding genes were annotated in whole genome level using transcriptome data. Taken together, this highly accurate, chromosome-level reference genome can provide a valuable resource to elucidate the mechanism of sex reversal forA. latus.

Background & Summary

Evolution of sex, especially the evolution of different sexual systems, is a fascinating subject in evolutionary biology. The Sparidae, commonly known as seabreams or progies, is a family of fishes of the order Perciformes. And this family consist about 150 species in the world, which are mainly coastal fish1. Previous researchers mentioned that Sparidae is an ideal taxon to study the evolution history and adaptive significance of sexual systems, particularly for both types of sequential hermaphroditism, given that this group contains many protogyny, protandry and genochorist species2.

The yellowfin seabream,Acanthopagrus latusis a protandry species which belongs to the Sparidae family. It is widely distributed in Indo-West Pacific area3. It has a great relevance for marine aquaculture and its biology is well focused on reproductive physiology and nutrition4. Interestingly,A. latushas a special gender feature is that it belongs to protandrous sexual system (initially as male and change later to female)5. Most of the past studies ofA. latusmainly focused on the reproductive biology, population structure, aquaculture and taxonomy3,4,6–8. Although some sex reversal related genes were found inA. latus, the lack of genomic resources still limit us to elucidate the mechanism of sex reversal for this species.9,10. In addition, this lack was also limited the studies of evolution of sexual systems for Sparidae.

In this study, long-read (PacBio SMRT) sequencing and Hi-C sequencing technologies were applied to construct a high quality reference genome for yellowfin seabream. This high-quality genome can provide a valuable resource to elucidate the mechanism of sex reversal forA. latus. Furthermore, this genome can also facilitate the studies of evolution of sexual systems for Sparidae.
Separable neural signatures of confidence during perceptual decisions
Authors: Balsdon T. , Mamassian P. , Wyart V.
Published: April 2021

Perceptual confidence is an evaluation of the validity of perceptual decisions. While there is behavioural evidence that confidence evaluation differs from perceptual decision-making, disentangling these two processes remains a challenge at the neural level. Here we examined the electrical brain activity of human participants in a protracted perceptual decision-making task where observers tend to commit to perceptual decisions early whilst continuing to monitor sensory evidence for evaluating confidence. Premature decision commitments were revealed by patterns of spectral power overlying motor cortex, followed by an attenuation of the neural representation of perceptual decision evidence. A distinct neural representation was associated with the computation of confidence, with sources localised in the superior parietal and orbitofrontal cortices. In agreement with a dissociation between perception and confidence, these neural resources were recruited even after observers committed to their perceptual decisions, and thus delineate an integral neural circuit for evaluating perceptual decision confidence.
E2F/Dp inactivation in fat body cells triggers systemic metabolic changes
Authors: Zappia Maria Paula , Guarner Ana , Kellie-Smith Nadia , Rogers Alice , Morris Robert , Nicolay Brandon , Boukhali Myriam , Haas Wilhelm , Dyson Nicholas J. , Frolov Maxim V.
Published: April 2021

The E2F transcription factors play a critical role in controlling cell fate. InDrosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently, rescued animal lethality. Collectively, our data highlight the unexpected complexity ofE2Fmutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development.
Frontal-sensory cortical projections become dispensable for attentional performance upon a reduction of task demand in mice
Authors: Norman Kevin J. , Bateh Julia , Maccario Priscilla , Cho Christina , Caro Keaven , Nishioka Tadaaki , Koike Hiroyuki , Morishita Hirofumi
Published: April 2021

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVISprojections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVISprojections are necessary when task demand is high, but once a task demand is lowered, ACAVISneuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVISprojection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.
Prefrontal coding of learned and inferred knowledge during REM & NREM sleep
Authors: Abdou Kareem , Aly Mohamed H. , Ibrahim Ahmed Z. , Choko Kiriko , Nomoto Masanori , Okubo-Suzuki Reiko , Muramatsu Shin-ichi , Inokuchi Kaoru
Published: April 2021

Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving1-4. However, it remains unclear how and when the subconscious brain can create novel ideas. Here, we show coordinated roles of non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in weaving inferential information from learned information. In a transitive inference paradigm, mice gained the inference one day, but not shortly, after complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either NREM or REM sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge.In vivoCa2+imaging showed gradual development of inference-related representation, peaking at post-training REM sleep. Neurons representing learned information co-reactivated significantly during post-training NREM sleep, while their co-reactivation with neurons representing inferential information was significantly higher during REM sleep. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialogue during only REM sleep created inferential knowledge. These findings suggest that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.
Effects of excitotoxicity in the hypothalamus in transgenic mouse models of Huntington disease
Authors: Henningsen Jo B. , Soylu-Kucharz Rana , Björkqvist Maria , Petersén Åsa
Published: April 2021

Huntington disease (HD) is a fatal neurodegenerative movement disorder caused by an expanded CAG repeat in the huntingtin gene (HTT). The mutant huntingtin protein is ubiquitously expressed, but only certain brain regions are affected. The hypothalamus has emerged as an important area of pathology with selective loss of neurons expressing the neuropeptides orexin (hypocretin), oxytocin and vasopressin in human postmortem HD tissue. Hypothalamic changes in HD may have implications for early disease manifestations affecting the regulation of sleep, emotions and metabolism. The underlying mechanisms of selective vulnerability of certain neurons in HD are not fully understood, but excitotoxicity has been proposed to play a role. Further understanding of mechanisms rendering neurons sensitive to mutant huntingtin may reveal novel targets for therapeutic interventions. In the present study, we wanted to examine whether transgenic HD mice display altered sensitivity to excitotoxicity in the hypothalamus. We first assessed effects of hypothalamic injections of the excitotoxin quinolinic acid (QA) into wild-type (WT) mice. We show that neuronal populations expressing melanin-concentrating hormone (MCH) and cocaine and amphetamine-regulated transcript (CART) display a dose-dependent sensitivity to QA. In contrast, neuronal populations expressing orexin, oxytocin, vasopressin as well as tyrosine hydroxylase in the A13 area are resistant to QA-induced toxicity. We demonstrate that the R6/2 transgenic mouse model expressing a short fragment of mutant HTT displays hypothalamic neuropathology with discrete loss of the neuronal populations expressing orexin, MCH, CART, and orexin at 12 weeks of age. The BACHD mouse model expressing full-length mutant HTT does not display any hypothalamic neuropathology at 2 months of age. There was no effect of hypothalamic injections of QA on the neuronal populations expressing orexin, MCH, CART or oxytocin in neither HD mouse model. In conclusion, we find no support for a role of excitotoxicity in the loss of hypothalamic neuronal populations in HD.
Personalized genome assembly for accurate cancer somatic mutation discovery using cancer-normal paired reference samples
Authors: Xiao Chunlin , Chen Zhong , Chen Wanqiu , Padilla Cory , Fang Li-Tai , Liu Tiantian , Schneider Valerie , Wang Charles , Xiao Wenming
Published: April 2021

The use of personalized genome assembly as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but never been systematically investigated. Here we address the critical need of assessing the accuracy of somatic mutation detection using personalized genome assembly versus the standard human reference assembly (i.e. GRCh38). We first obtained massive whole genome sequencing data using multiple sequencing technologies, and then performedde novoassembly of the first tumor-normal paired genomes, both nuclear and mitochondrial, derived from the same donor with triple negative breast cancer. Compared to standard human reference assembly, the haplotype phased chromosomal-scale personalized genome was best demonstrated with individual specific haplotypes for some complex regions and medical relevant genes. We then used this well-assembled personalized genome as a reference for read mapping and somatic variant discovery. We showed that the personalized genome assembly results in better alignments of sequencing reads and more accurate somatic mutation calls. Direct comparison of mitochondrial genomes led to discovery of unreported nonsynonymous somatic mutations. Our findings provided a unique resource and proved the necessity of personalized genome assembly as a reference in improving somatic mutation detection at personal genome level not only for breast cancer reference samples, but also potentially for other cancers.
Establishment of the family Zarkiaceae (Oscillatoriales, Cyanobacteria) and description of the new marine generaZarkia(Zarkiaceae, Oscillatoriales) andRomeriopsis(Leptolyngbyaceae, Synechococcales), from northern Portugal
Authors: Hentschke Guilherme S. , Pinheiro Ângela , Ramos Vitor , Barreiro Aldo , Costa M. Sofia , Brule Sébastien , Vasconcelos Vitor M. , Leão Pedro N.
Published: April 2021

Abstract Figure

The morphology, 16S rRNA gene phylogeny and the 16S-23S rRNA gene ITS secondary structures of three strains of marine Cyanobacteria, isolated from inter- and subtidal environments from north Portugal were studied, resulting in the description ofZarkia subtidalensisgen. et. sp. nov. (Zarkiaceae fam. nov.) andRomeriopsis marinagen. et. sp. nov (Leptolyngbyaceae). No diacritical morphological characters were found either for the new family or for the new genera. The 16S rRNA gene Maximum Likelihood and Bayesian phylogenies supported thatZarkiaand Zarkiaceae are members of the Oscillatoriales, positioned close to Microcoleaceae genera, but distant fromMicrocoleus. Romeriopsisis positioned within the Leptolyngbyaceae and is closely related toAlkalinema. The secondary structures of the D1-D1’, Box B, V2 and V3 helices corroborate with the phylogenetic results. Furthermore, our study supports previous observations of polyphyletic Oscillatoriales families and reinforces the need for their taxonomical revision.
Evaluation of endogenous miRNA reference genes across different zebrafish strains, developmental stages and kidney disease models
Authors: Siegerist Florian , Lange Tim , Iervolino Anna , Koppe Thor Magnus , Zhou Weibin , Capasso Giovambattista , Endlich Karlhans , Endlich Nicole
Published: April 2021

The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseasesin vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments.

Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences.

All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies.