bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare codon-based translational program of cell proliferation
Authors: Guimaraes Joao C. , Mittal Nitish , Gnann Alexandra , Jedlinski Dominik , Riba Andrea , Buczak Katarzyna , Schmidt Alexander , Zavolan Mihaela 
Published: February 2020

Abstract
Background
The speed of translation elongation is primarily determined by the abundance of tRNAs. Thus, the codon usage influences the rate with which individual mRNAs are translated. As the nature of tRNA pools and modifications can vary across biological conditions, codon elongation rates may also vary, leading to fluctuations in the protein production from individual mRNAs. Although it has been observed that functionally related mRNAs exhibit similar codon usage, presumably to provide an effective way to coordinate expression of multiple proteins, experimental evidence for codon-mediated translation efficiency modulation of functionally related mRNAs in specific conditions is scarce and the associated mechanisms are still debated.

Results
Here, we reveal that mRNAs whose expression increases during cell proliferation are enriched in rare codons, poorly adapted to tRNA pools. Ribosome occupancy profiling and proteomics measurements show that upon increased cell proliferation, transcripts enriched in rare codons undergo a higher translation boost than transcripts with common codons. Re-coding of a fluorescent reporter with rare codons increased protein output by ~ 30% relative to a reporter re-coded with common codons. Although the translation capacity of proliferating cells was higher compared to resting cells, we did not find evidence for the regulation of individual tRNAs. Among the models that were proposed so far to account for codon-mediated translational regulation upon changing conditions, the one that seems most consistent with our data involves a global upregulation of ready-to-translate tRNAs, which we show can lead to a higher increase in the elongation velocity at rare codons compared to common codons.

Conclusions
We propose that the alleviation of translation bottlenecks in rapidly dividing cells enables preferential upregulation of pro-proliferation proteins, encoded by mRNAs that are enriched in rare codons.
Borrelia miyamotoi and Borrelia burgdorferi (sensu lato) identification and survey of tick-borne encephalitis virus in ticks from north-eastern Germany
Authors: Răileanu Cristian , Tauchmann Oliver , Vasić Ana , Wöhnke Elisabeth , Silaghi Cornelia 
Published: February 2020

AbstractBackgroundIxodes ricinusis the most common tick species in Europe and the main vector forBorrelia burgdorferi(sensu lato) and tick-borne encephalitis virus (TBEV). It is involved also in the transmission ofBorrelia miyamotoi, a relapsing fever spirochete that causes health disorders in humans. Little is known regarding the circulation ofBorreliaspecies and the natural foci of TBEV in north-eastern Germany. The goal of this study was to investigate the infection rates ofBorreliaspp. and of TBEV inI. ricinusticks from north-eastern Germany.MethodsTicks were collected by flagging from 14 forest sites in Mecklenburg-Western Pomerania between April and October 2018. RNA and DNA extraction was performed from individual adult ticks and from pools of 2–10 nymphs. Real time reverse transcription PCR (RT-qPCR) targeted the 3′ non-coding region of TBEV, while DNA ofBorreliaspp. was tested by nested PCR for the amplification of 16S-23S intergenic spacer. Multilocus sequence typing (MLST) was performed onB. miyamotoiisolates.ResultsIn total, 2407 ticks were collected (239 females, 232 males and 1936 nymphs). Female and maleI. ricinusticks had identical infection rates (both 12.1%) forBorreliaspp., while nymphal pools showed a minimum infection rate (MIR) of 3.3%. Sequencing revealed fourBorreliaspecies:B. afzelii,B. garinii,B. valaisianaandB. miyamotoi.Borrelia afzeliihad the highest prevalence in adult ticks (5.5%) and nymphs (MIR of 1.8%).Borrelia miyamotoiwas identified in 3.0% of adults and registered the MIR of 0.8% in nymphs.Borrelia valaisianawas confirmed in 2.5% adult ticks and nymphs had the MIR of 0.7%, whileB. gariniiwas present in 1.1% of adults and showed a MIR of 0.1% in nymphs. The MLST ofB. miyamotoiisolates showed that they belong to sequence type 635. No tick sample was positive after RT-qPCR for TBEV RNA.ConclusionsThe prevalence ofB. miyamotoiinI. ricinusticks registered similar levels to other reports from Europe suggesting that this agent might be well established in the local tick population. The detection ofB. burgdorferi(s.l.) indicates a constant circulation in tick populations from this region.
Genotypic and phenotypic analysis of biofilm formation Staphylococcus epidermidis isolates from clinical specimens
Authors: Mirzaei Bahman , Faridifar Peyman , Shahmoradi Mostafa , Shapouri Reza , Iranpour Fatemeh , Haghi Fakhri , Ezzedin Mahnaz , Babaei Reyhaneh , Mousavi Seyed Fazlollah 
Published: February 2020

Abstract
Objectives
Staphylococcus epidermidis is the primary causative agent of infections associated with indwelling biomaterials. Antibiotic susceptibility patterns, Biofilm formation capability, and screening of responsible genes in biofilm formation procedure in clinical isolates (icaA, icaB, icaC, icaD, sdrG, and atlE) were assigned as the main objectives in this study. The clinical samples were analyzed via standard biochemical assays for identifying different bacteria which were confirmed using the multiplex colony PCR method. Subsequently, biofilm-formation capability, antibiotic susceptibility testing, and the frequency of genes responsible for biofilm formation in the confirmed strains were checked.

Results
Out of 183 clinical specimens 54 S. epidermidis isolates were detected by targeting a housekeeping gene (sesc) taking advantage of the PCR procedure. All of the strains were Biofilm forming producers. The in vitro biofilm formation assays determined that 45 (83.33%), 5 (9.26%), 4 (7.41%) were strong, moderate, and weak biofilm former strains respectively. Among the isolated strains, the specific frequencies of the biofilm-forming genes were specified to be (98%) for sdrG, (84%) for atlE, (80%) for icaC, and (70%) for icaD. Cefamandole and Amikacin are the most effective antibiotics in isolated strains. All strains were ascertained to be methicillin and amoxicillin/clavulanic acid resistant.
Giant cell tumor of bone following denosumab treatment: assessment of tumor response using various imaging modalities
Authors: Alothman Maram , Althobaity Waleed , Asiri Yasser , Alreshoodi Saleh , Alismail Khalid , Alshaalan Meshal 
Published: February 2020

Abstract
Background
Giant cell tumor (GCT) is a nonmalignant neoplasm composed of multinucleated giant and mononuclear stromal cells.
This study aimed to compare imaging findings of GCT pre- and post-denosumab treatment, including lesion size, percentage of signal intensity/density change, and time of initial objective tumor response. This will have a great impact on selection of most appropriate imaging technique to accurately measure therapy response and its related complications, which would influence the physicians to tailor the treatment regimen to suit each patient.

Results
As per inverse Choi density/size (ICDS), 16 patients (84.2%) had an objective tumor response and 15 (78.9%) had an increase in density or decrease in signal intensity, and the mean of signal intensity decrease in the treated lesions was 32.4% (95% CI, 18–46.7). Only seven patients (36.8%) had tumors demonstrating ≥ 10% decrease in size, all of which showed a positive change in signal/density except for one. Moreover, 17 patients (89.4%) showed a clear demarcation/low signal intensity margin surrounding ≥ two third of the lesion periphery. The median time to first objective tumor response was approximately 23 weeks.

Conclusion
Based on the ICDS criteria, most patients with giant cell tumor of bone show objective tumor response to denosumab. Modification of ICDS to include marginal sclerosis or clear demarcation of the lesions might be considered as a separate response criterion to accurately assess the treatment response in patients with GCT.
Porcine circovirus type 2 exploits JNK-mediated disruption of tight junctions to facilitate Streptococcus suis translocation across the tracheal epithelium
Authors: Wang Qing , Zhou Hong , Lin Huixing , Ma Zhe , Fan Hongjie 
Published: February 2020

AbstractPorcine circovirus type 2 (PCV2) is considered as the primary pathogen of porcine circovirus-associated disease (PCVAD), which results in significant economic losses worldwide. Clinically, PCV2 often causes disease through coinfection with other bacterial pathogens, including Streptococcus suis (S. suis), and especially the highly prevalent S. suis serotype 2 (SS2). The present study determined that continuous PCV2 infection in piglets down-regulates tight junction proteins (TJ) ZO-1 and occludin in the lungs. Swine tracheal epithelial cells (STEC) were used to explore the mechanisms and consequences of disruption of TJ, and an in vitro tracheal epithelial barrier model was established. Our results show that PCV2 infection in STEC decreases the expression levels of ZO-1 and occludin and increases the permeability of the tracheal epithelial barrier, resulting in easier translocation of SS2. Moreover, Western blot analysis indicates that PCV2 infection activates the JNK/MAPK pathway. The disruption of TJ in SETC and increased permeability of the epithelial barrier induced by PCV2 could be alleviated by inhibition of JNK phosphorylation, which indicates that the JNK/MAPK pathway regulates the expression of ZO-1 and occludin during PCV2 infection. This study allows us to better understand the mechanisms of PCV2 coinfection with bacterial pathogens and provides new insight into controlling the occurrence of PCVAD.
Isolated Horner’s Syndrome Secondary To Rhinosinusitis: A Case Report And Literature Review
Authors: Rissardo Jamir Pitton , Caprara Ana Letícia Fornari , Silveira Juliana Oliveira Freitas , Jauris Paulo Gilberto Medeiros 
Published: February 2020

AbstractBackgroundHorner’s syndrome (HS) is characterized by unilateral ptosis, ipsilateral miosis with normally reactive pupil, and in some cases, ipsilateral facial anhidrosis.Case presentationWe report an adult male presenting with ptosis. Neurological examination revealed ptosis and miosis in the right eye. Anhidrosis was not observed, and the patient did not complain about it. Laboratory tests were within normal limits. He had searched a general practitioner because of purulent nasal discharge, nasal obstruction, and anosmia. He was diagnosed with acute rhinosinusitis. Symptomatic treatment was started. The subject had full recovery of the nasal symptoms, but his right upper eyelid was drooping progressively. In the follow-up, after the third month, the patient was recovering from ptosis and miosis. In 1 year, the ptosis was minor with less than 1 mm and miosis was no more observed.DiscussionA few cases of HS secondary to a sinus infection have been reported in the literature. To the authors’ knowledge, there are only two case reports of individuals who developed sinusitis and Horner’s syndrome. The present case is the first to present isolated HS features. Our report suggests that sinusitis should be listed as a probable cause of isolated Horner’s syndrome. Moreover, patients presenting with this presentation probably have a good prognosis.
Human motion component and envelope characterization via wireless wearable sensors
Authors: Ammann Kaitlyn R. , Ahamed Touhid , Sweedo Alice L. , Ghaffari Roozbeh , Weiner Yonatan E. , Slepian Rebecca C. , Jo Hongki , Slepian Marvin J. 
Published: February 2020

Abstract
Background
The characterization of limb biomechanics has broad implications for analyzing and managing motion in aging, sports, and disease. Motion capture videography and on-body wearable sensors are powerful tools for characterizing linear and angular motions of the body, though are often cumbersome, limited in detection, and largely non-portable. Here we examine the feasibility of utilizing an advanced wearable sensor, fabricated with stretchable electronics, to characterize linear and angular movements of the human arm for clinical feedback. A wearable skin-adhesive patch with embedded accelerometer and gyroscope (BioStampRC, MC10 Inc.) was applied to the volar surface of the forearm of healthy volunteers. Arms were extended/flexed for the range of motion of three different regimes: 1) horizontal adduction/abduction 2) flexion/extension 3) vertical abduction. Data were streamed and recorded revealing the signal “pattern” of movement in three separate axes. Additional signal processing and filtering afforded the ability to visualize these motions in each plane of the body; and the 3-dimensional motion envelope of the arm.

Results
Each of the three motion regimes studied had a distinct pattern – with identifiable qualitative and quantitative differences. Integration of all three movement regimes allowed construction of a “motion envelope,” defining and quantifying motion (range and shape – including the outer perimeter of the extreme of motion – i.e. the envelope) of the upper extremity. The linear and rotational motion results from multiple arm motions match measurements taken with videography and benchtop goniometer.

Conclusions
A conformal, stretchable electronic motion sensor effectively captures limb motion in multiple degrees of freedom, allowing generation of characteristic signatures which may be readily recorded, stored, and analyzed. Wearable conformal skin adherent sensor patchs allow on-body, mobile, personalized determination of motion and flexibility parameters. These sensors allow motion assessment while mobile, free of a fixed laboratory environment, with utility in the field, home, or hospital. These sensors and mode of analysis hold promise for providing digital “motion biomarkers” of health and disease.
Impact of Exogenous Testosterone on Reproduction in Transgender Men
Authors: Moravek Molly B , Kinnear Hadrian M , George Jenny , Batchelor Jourdin , Shikanov Ariella , Padmanabhan Vasantha , Randolph John F 
Published: February 2020

Abstract
Studies show that a subset of transgender men desire children; however, there is a paucity of literature on the effect of gender-affirming testosterone therapy on reproductive function. In this manuscript, we will review the process of gender-affirming hormone therapy for transgender men and what is known about ovarian and uterine consequences of testosterone exposure in transgender men; draw parallels with existing animal models of androgen exposure; summarize the existing literature on parenting experiences and desires in transgender people; discuss considerations for assisted reproductive technologies and fertility preservation; and identify gaps in the literature and opportunities for further research.
The Endothelial Barrier Is not Rate-limiting to Insulin Action in the Myocardium of Male Mice
Authors: Sanwal Rajiv , Khosraviani Negar , Advani Suzanne L , Advani Andrew , Lee Warren L 
Published: February 2020

Abstract
To act on tissues, circulating insulin must perfuse the relevant organ and then leave the bloodstream by crossing the endothelium—a process known as insulin delivery. It has been postulated that the continuous endothelium is a rate-limiting barrier to insulin delivery but existing data are contradictory. This conflict is in part due to the limitations of current models, including the inability to maintain a constant blood pressure in animals and the absence of shear stress in cultured cells. We developed a murine cardiac ex vivo perfusion model that delivers insulin to the heart in situ at a constant flow. We hypothesized that if the endothelial barrier were rate-limiting to insulin delivery, increasing endothelial permeability would accelerate insulin action. The kinetics of myocardial insulin action were determined in the presence or absence of agents that increased endothelial permeability. Permeability was measured using Evans Blue, which binds with high affinity to albumin. During our experiments, the myocardium remained sensitive to insulin and the vasculature retained barrier integrity. Perfusion with insulin induced Akt phosphorylation in myocytes but not in the endothelium. Infusion of platelet-activating factor or vascular endothelial growth factor significantly increased permeability to albumin without altering insulin action. Amiloride, an inhibitor of fluid-phase uptake, also did not alter insulin action. These data suggest that the endothelial barrier is not rate limiting to insulin’s action in the heart; its passage out of the coronary circulation is consistent with diffusion or convection. Modulation of transendothelial transport to overcome insulin resistance is unlikely to be a viable therapeutic strategy.
Canonical Wnt/β-catenin activity and differential epigenetic marks direct sexually dimorphic regulation of Irx3 and Irx5 in developing mouse gonads
Authors: Koth Megan L. , Garcia-Moreno S. Alexandra , Novak Annie , Holthusen Kirsten A. , Kothandapani Anbarasi , Jiang Keer , Taketo Makoto Mark , Nicol Barbara , Yao Humphrey H.-C. , Futtner Christopher R. , Maatouk Danielle M. , Jorgensen Joan S. 
Published: February 2020

ABSTRACT
Members of the Iroquois B (IrxB) homeodomain cluster genes, specifically Irx3 and Irx5, are crucial for heart, limb and bone development. Recently, we reported their importance for oocyte and follicle survival within the developing ovary. Irx3 and Irx5 expression begins after sex determination in the ovary but remains absent in the fetal testis. Mutually antagonistic molecular signals ensure ovary versus testis differentiation with canonical Wnt/β-catenin signals paramount for promoting the ovary pathway. Notably, few direct downstream targets have been identified. We report that Wnt/β-catenin signaling directly stimulates Irx3 and Irx5 transcription in the developing ovary. Using in silico analysis of ATAC- and ChIP-Seq databases in conjunction with mouse gonad explant transfection assays, we identified TCF/LEF-binding sequences within two distal enhancers of the IrxB locus that promote β-catenin-responsive ovary expression. Meanwhile, Irx3 and Irx5 transcription is suppressed within the developing testis by the presence of H3K27me3 on these same sites. Thus, we resolved sexually dimorphic regulation of Irx3 and Irx5 via epigenetic and β-catenin transcriptional control where their ovarian presence promotes oocyte and follicle survival vital for future ovarian health.
c-Src controls stability of sprouting blood vessels in the developing retina independently of cell-cell adhesion through focal adhesion assembly
Authors: Schimmel Lilian , Fukuhara Daisuke , Richards Mark , Jin Yi , Essebier Patricia , Frampton Emmanuelle , Hedlund Marie , Dejana Elisabetta , Claesson-Welsh Lena , Gordon Emma 
Published: February 2020

ABSTRACT
Endothelial cell adhesion is implicated in blood vessel sprout formation, yet how adhesion controls angiogenesis, and whether it occurs via rapid remodeling of adherens junctions or focal adhesion assembly, or both, remains poorly understood. Furthermore, how endothelial cell adhesion is controlled in particular tissues and under different conditions remains unexplored. Here, we have identified an unexpected role for spatiotemporal c-Src activity in sprouting angiogenesis in the retina, which is in contrast to the dominant focus on the role of c-Src in the maintenance of vascular integrity. Thus, mice specifically deficient in endothelial c-Src displayed significantly reduced blood vessel sprouting and loss in actin-rich filopodial protrusions at the vascular front of the developing retina. In contrast to what has been observed during vascular leakage, endothelial cell-cell adhesion was unaffected by loss of c-Src. Instead, decreased angiogenic sprouting was due to loss of focal adhesion assembly and cell-matrix adhesion, resulting in loss of sprout stability. These results demonstrate that c-Src signaling at specified endothelial cell membrane compartments (adherens junctions or focal adhesions) control vascular processes in a tissue- and context-dependent manner.
Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration
Authors: Liu Yi , Kim Jaeyoun , Philip Reuben , Sridhar Vaishali , Chandrashekhar Megha , Moffat Jason , van Breugel Mark , Pelletier Laurence 
Published: February 2020

ABSTRACT
PLK4 has emerged as a prime target for cancer therapeutics, and its overexpression is frequently observed in various types of human cancer. Recent studies have further revealed an unexpected oncogenic activity of PLK4 in regulating cancer cell migration and invasion. However, the molecular basis behind the role of PLK4 in these processes still remains only partly understood. Our previous work has demonstrated that an intact CEP85–STIL binding interface is necessary for robust PLK4 activation and centriole duplication. Here, we show that CEP85 and STIL are also required for directional cancer cell migration. Mutational and functional analyses reveal that the interactions between CEP85, STIL and PLK4 are essential for effective directional cell motility. Mechanistically, we show that PLK4 can drive the recruitment of CEP85 and STIL to the leading edge of cells to promote protrusive activity, and that downregulation of CEP85 and STIL leads to a reduction in ARP2 (also known as ACTR2) phosphorylation and reorganization of the actin cytoskeleton, which in turn impairs cell migration. Collectively, our studies provide molecular insight into the important role of the CEP85–STIL complex in modulating PLK4-driven cancer cell migration.
This article has an associated First Person interview with the first author of the paper.
FAK regulates actin polymerization during sperm capacitation via the ERK2/GEF-H1/RhoA signaling pathway
Authors: Salgado-Lucio Monica L. , Ramírez-Ramírez Danelia , Jorge-Cruz Coral Y. , Roa-Espitia Ana L. , Hernández-González Enrique O. 
Published: February 2020

ABSTRACT
Actin polymerization is a crucial process during sperm capacitation. We have recently described the participation of FAK during actin polymerization in guinea pig spermatozoa. However, the mechanism by which FAK mediates these processes is unknown. Our previous data have shown that MAPK1 (hereafter referred to as ERK2) is activated during the first minutes of capacitation, and inhibition of ERK2 blocked actin polymerization and the acrosome reaction. In this current study, we found that FAK is involved in ERK2 activation – as FAK was phosphorylated at tyrosine residue 925 and bound to Grb2 – and that inhibition of FAK results in a significant decrease of ERK2 activation. We also confirmed the presence of Rho guanine nucleotide exchange factor 2 (ARHGEF2, hereafter referred to as GEF-H1), which is able to associate with RhoA during capacitation. RhoA activation and its participation in actin polymerization were also analyzed. Inhibition of FAK or ERK1/2 impeded GEF-H1 phosphorylation, RhoA activation, and the association between GEF-H1 and RhoA. Finally, we observed the presence of fibronectin on the sperm surface, its role in sperm–sperm interaction as well as participation of β-integrin in the activation of ERK2. Our results show that the signaling pathway downstream of fibronectin, via integrin, FAK, Grb2, MEK1/2, ERK2, GEF-H1 and RhoA regulates the actin polymerization associated with spermatozoa capacitation.