bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Corneal Biomechanical Properties on Rebound Tonometry (Icare200) and Applanation Tonometry (Perkins) Readings in Patients With Primary Congenital Glaucoma
Authors: Morales-Fernandez Laura , Saenz-Frances Federico , Pérez-García Pilar , Garcia-Feijoo Julian , Garcia-Saenz Sofia , Gómez de Liaño Rosario , Martinez-de-la-Casa Jose M. 
Published: July 2021

Objective:
The aim was to assess the influence of corneal biomechanics on intraocular pressure (IOP) measurements made with the Icare200 (IC200) rebound tonometer and the Perkins handheld applanation tonometer in patients with primary congenital glaucoma (PCG).

Materials and Methods:
A total of 40 PCG patients and 40 healthy controls, age, and sex-matched, were recruited. IOP was measured with the Ocular Response Analyzer (IOPc, IOPg), IC200 and Perkins. The variables age, IOP, corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), best-corrected visual acuity, spherical equivalent, medications, and glaucoma surgeries were recorded for each subject. Univariate and multivariate analysis were used to detect effects of variables on IOP measurements.

Results:
Mean CCT was 545.65±71.88 μm in PCG versus 558.78±27.58 μm in controls (P=0.284). CH and CRF were significantly lower in PCG group than in control group: mean CH 8.11±1.69 versus 11.15±1.63 mm Hg (P<0.001), and mean CRF 9.27±2.35 versus 10.71±1.75 mm Hg (P=0.002). Mean differences between IOP IC200-Perkins were 0.79±0.53 mm Hg in PCG versus 0.80±0.23 mm Hg in controls (P<0.001) and mean differences IC200-IOPc were −0.89±5.15 mm Hg in PCG (P<0.001) versus 1.60±3.03 mm Hg in controls (all P<0.009). Through multivariate analysis, CRF showed positive association and CH negative association with IOP measured with Perkins or IC200 in both subject groups. No association was detected for CCT, age, or sex.

Conclusion:
CH and CRF were identified as the main factors interfering with IOP measurements made with both tonometers in patients with PCG and healthy controls.
Mode of Presentation and Outcomes of COVID-19 Cases in a Tertiary Hospital in Nigeria
Authors: Raji Yakubu Egigogo , Waziri Bala , Hussaini Sadiq Aliyu , Ja’agi Ahmad Idris , Alhaji Umar Isah , Aliyu Abdulmalik M. , Muhammad Abdullahi , Garba Adama Saidu 
Published: July 2021

AbstractCoronavirus disease 2019 (COVID-19) has spread across the globe with its consequent human and economic challenges. To achieve effective control of the pandemic, efforts need to be holistic and global. Understanding patients’ demographics and clinical characteristics will assist in the control of the infection. However, there is a paucity of studies on the clinical presentation of COVID-19 patients from Nigeria and indeed Africa. Thus, this retrospective case series evaluated the medical records of COVID-19 patients admitted in a tertiary hospital in Nigeria. Patients’ demographics, and other clinical variables were assessed and presented. Data of 14 patients with complete records were included in the study. Most of the patients (78.6%) were males and the mean age of the study participants is 63.5 years (SD; 11.5). The commonest presenting symptoms were fever (93%), cough (71.4%), and dyspnoea (57.1%). At presentation, 13 patients had coexisting diseases while 8 (57.0%) patients had moderate disease and the remaining 6 (43.0%) had severe cases. After management, 1 patient died, two were referred and 11 recovered and were discharged alive. Thus, this study has identified advanced age, male gender, and comorbidity as increased risk factors for hospitalisation. The patient survival outcome in this study was also good.
Indications that Stockholm has reached herd immunity, given limited restrictions, against several variants of SARS-CoV-2
Authors: Carlsson Marcus , Söderberg-Nauclér Cecilia 
Published: July 2021

Abstract“When COVID-19 cases go up, public compliance with restrictions is poor, when cases go down, public compliance is good.” In this article, we question this explanation and show that relatively low levels of sero-prevalence helps to keep cases down. In other words, the herd-immunity threshold appears to be much lower than previously thought. We construct a mathematical model taking pre-immunity, antibody waning and more infectious variants of concern into consideration, thereby providing a theoretical framework in which the cases in Stockholm county can be fully predicted without relying on neither oscillations in restrictions (and public compliance thereof) nor vaccination roll-out. We also show that it is very difficult to match the data from Stockholm without including pre-immunity, or, which turns out to be equivalent, great variations in susceptibility.
A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases
Authors: Carlsson Marcus , Wittsten Jens , Söderberg-Nauclér Cecilia 
Published: July 2021

AbstractThe unfolding of the COVID-19 pandemic has been very difficult to predict using mathematical models for infectious diseases. While it has been demonstrated that variations in susceptibility have a damping effect on key quantities such as the incidence peak, the herd-immunity threshold and the final size of the pandemic, this complex phenomenon is almost impossible to measure or quantify, and it remains unclear how to incorporate it for modeling and prediction.In this work we show that, from a modeling perspective, variability in susceptibility on an individual level is equivalent with a fraction θ of the population having an “artificial” sterilizing immunity. Given that this new parameter θ can be estimated, we also derive formulas for R0, the herd-immunity threshold and the final size of the pandemic. In the particular case of SARS-CoV-2, there is by now undoubtedly variable susceptibility due to waning immunity from both vaccines and previous infections, and our findings may be used to greatly simplify models. If such variations were also present prior to the first wave, as indicated by a number of studies, these findings can help explain why the magnitude of the initial waves of SARS-CoV-2 was relatively low, compared to what one may have expected based on standard models.
Dysregulated myogenesis and autophagy in genetically induced pulmonary emphysema
Authors: Balnis Joseph , Drake Lisa A. , Singer Diane V. , Vincent Catherine E. , Korponay Tanner C. , D’Armiento Jeanine , Lee Chun Geun , Elias Jack A. , Singer Harold A. , Jaitovich Ariel 
Published: July 2021

AbstractPatients with chronic obstructive pulmonary disease (COPD)-pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced muscle mass and force-generation capacity, which are influenced by fibers integrity. Myogenesis, which is muscle turnover driven by progenitor cells such as satellite cells, contributes to the maintenance of muscle integrity in the context of organ development and injury-repair cycles. Injurious events crucially occur in COPD patients’ skeletal muscles in the setting of exacerbations and infections which lead to acute decompensations for limited periods of time after which, patients typically fail to recover the baseline status they had before the acute event. Autophagy, which is dysregulated in muscles from COPD patients, is a key regulator of satellite cells activation and myogenesis, yet very little research has so far investigated the mechanistic role of autophagy dysregulation in COPD muscles. Using a genetically inducible murine model of COPD-driven muscle dysfunction and confirmed with a second genetic animal model, we found a significant myogenic dysfunction associated with a reduced proliferative capacity of freshly isolated satellite cells. Transplantation experiments followed by lineage tracing suggest that an intrinsic defect in satellite cells, and not in the COPD environment, plays a dominant role in the observed myogenic dysfunction. RNA sequencing analysis of freshly isolated satellite cells suggests dysregulation of transcripts associated with control of cell cycle and autophagy, which is confirmed by a direct observation of COPD mice satellite cells fluorescent-tracked autophagosome formation. Moreover, spermidine-induced autophagy stimulation leads to improved satellite cells autophagosome turnover, replication rate and myogenesis. Our data suggests that pulmonary emphysema causes a disrupted myogenesis, which could be improved with stimulation of autophagy and satellite cells activation, leading to an attenuated muscle dysfunction in this context.
De novo synthesized polyunsaturated fatty acids operate as both host immunomodulators and nutrients for Mycobacterium tuberculosis
Authors: Laval Thomas , Pedró-Cos Laura , Malaga Wladimir , Guenin-Macé Laure , Pawlik Alexandre , Mayau Véronique , Yahia-Cherbal Hanane , Frigui Wafa , Bertrand-Michel Justine , Guilhot Christophe , Demangel Caroline 
Published: July 2021

ABSTRACTSuccessful control of Mycobacterium tuberculosis (Mtb) infection by macrophages relies on immunometabolic reprogramming, where the role of fatty acids (FAs) remains poorly understood. Recent studies unraveled Mtb’s capacity to acquire saturated and monounsaturated FAs via the Mce1 importer. However, upon activation macrophages produce polyunsaturated FAs (PUFAs), mammal-specific FAs mediating the generation of key immunomodulatory eicosanoids. Here, we asked whether de novo synthesis of PUFAs is modulated in Mtb-infected macrophages and benefits host or pathogen. Quantitative lipidomics revealed that Mtb infection activates the early PUFA biosynthetic pathway for production of eicosanoids. While PUFA synthesis blockade significantly impaired the inflammatory and antimicrobial responses of infected macrophages, it had no effect on Mtb growth in vivo. Using a click-chemistry approach, we found that Mtb efficiently imports PUFAs of the ω6 subset via Mce1 in axenic culture, including the eicosanoid precursor arachidonic acid (AA). Notably, Mtb preferentially internalized AA over all other FAs within infected macrophages, but here Mtb’s import of AA was largely Mce1-independent and correlated with elevated AA uptake by host cells. Together, these findings reveal AA as a major FA substrate for intracellular Mtb. They suggest that Mtb’s hijacking of host-derived AA may counteract its stimulatory effect on anti-mycobacterial immune responses.
Thioredoxin reductase controls the capacity of peroxiredoxins to limit mitochondrial H2O2release
Authors: Hoehne Michaela Nicole , Jacobs Lianne J.H.C. , Lapacz Kim Jasmin , Murschall Lena Maria , Marker Teresa , Morgan Bruce , Fricker Mark , Belousov Vsevolod V. , Riemer Jan 
Published: July 2021

SUMMARYH2O2performs central roles in signaling at physiological levels, while at elevated levels it causes molecular damage. Mitochondria are major producers of H2O2, which has been implied in regulating diverse processes inside and outside the organelle. However, it still remains unclear whether and how mitochondria in intact cells release H2O2. Here we employed the genetically encoded high-affinity H2O2sensor HyPer7 in mammalian tissue culture cells to investigate different modes of mitochondrial H2O2release. We found substantial heterogeneity of HyPer7 dynamics between individual cells, and observed H2O2released from mitochondria directly at the surface of the organelle and in the bulk cytosol, but not in the nucleus nor on the plasma membrane, pointing to steep gradients emanating from mitochondria. These gradients are controlled by cytosolic peroxiredoxins that act redundantly and are present with a substantial reserve capacity. Furthermore, dynamic adaptation of cytosolic thioredoxin reductase levels during metabolic changes results in improved H2O2handling and explains previously observed cell-to-cell differences. Thus, our data indicate that H2O2-mediated signaling likely occurs close to mitochondria during specific metabolic conditions.HIGHLIGHTSMitochondrial H2O2can be detected in the cytosol in intact human cellsMitochondrial H2O2gradients are steep and controlled by peroxiredoxins 1 and 2Peroxiredoxins 1 and 2 complement for each otherPeroxiredoxins 1 and 2 are present with a substantial reserve capacityMetabolism-induced changes of reducing processes control peroxiredoxin activity
Myosin-driven Nucleation of Actin Filaments Drives Stereocilia Development Critical for Hearing
Authors: Moreland Zane G. , Jiang Fangfang , Aguilar Carlos , Barzik Melanie , Gong Rui , Shams Arik , Faaborg-Andersen Christian , Werth Jesse C. , Harley Randall , Sutton Daniel C. , Cole Stacey M. , Parker Andrew , Morse Susan , Wilson Elizabeth , Takagi Yasuharu , Sellers James R. , Brown Steve D.M. , Friedman Thomas B. , Alushin Gregory M. , Bowl Michael R. , Bird Jonathan E. 
Published: July 2021

SUMMARYThe assembly and maintenance of actin-based mechanosensitive stereocilia in the cochlea is critical for lifelong hearing. Myosin-15 (MYO15) is hypothesized to modulate stereocilia height by trafficking actin regulatory proteins to their tip compartments, where actin polymerization must be precisely controlled during development. We identified a mutation (p.D1647G) in the MYO15 motor-domain that initially maintained trafficking, but caused progressive hearing loss by stunting stereocilia growth, revealing an additional function for MYO15. Consistent with its maintenance of tip traffickingin vivo, purified p.D1647G MYO15 modestly reduced actin-stimulated ATPase activityin vitro. Using ensemble and single-filament fluorescencein vitroassays, we demonstrated that wild-type MYO15 directly accelerated actin filament polymerization by driving nucleation, whilst p.D1647G MYO15 blocked this activity. Collectively, our studies suggest direct actin nucleation by MYO15 at the stereocilia tip is necessary for elongationin vivo, and that this is a primary mechanism disrupted in DFNB3 hereditary human hearing loss.
Identification of general acid catalyst for the ATPase activity of Lynch syndrome-related MutL homologs
Authors: Fukui Kenji , Fujii Yuki , Yano Takato 
Published: July 2021

AbstractMutations of mismatch repair MutL homologs are causative of a hereditary cancer, Lynch syndrome. Investigation of MutL facilitates genetic diagnoses essential for cancer risk managements and therapies. We characterized MutL homologs from human and a hyperthermophile, Aquifex aeolicus, (aqMutL) to reveal the catalytic mechanism for the ATPase activity. Although existence of a general acid catalyst had not been conceived in the mechanism, analysis of the pH dependence of the aqMutL ATPase activity revealed that the reaction is accelerated by general acid-base catalysis. Analyses of mutant aqMutLs showed that Lys79 is the general acid, and the corresponding residues were confirmed to be critical for activities of human homologs, on the basis of which a catalytic mechanism for MutL ATPase is proposed. These and other results described here would contribute to evaluating the pathogenicity of Lynch syndrome-associated missense mutations.
Cation-chloride cotransporters, Na/K pump, and channels in cell water and ions regulation: in silico and experimental studies of the U937 cells under stopping the pump and during RVD
Authors: Yurinskaya Valentina E. , Vereninov Alexey A. 
Published: July 2021

ABSTRACTCation-coupled chloride cotransporters play a key role in generating the Cl‾ electrochemical gradient on the cell membrane which is important for regulation of many cellular processes. However, the cooperation of transporters and channels of the plasma membrane in holding the ionic homeostasis of the whole cell remains poorly characterized because of the lack of a suitable tool for its computation. Our software successfully predicted in real-time changes in the ion homeostasis of U937 cells after stopping the Na/K pump, but so far considered the model with only NC cotransporter. Here the model with all main types of cotransporters is used in computation of the rearrangements of ionic homeostasis due to stopping the pump and associated with the regulatory volume decrease (RVD) of cells swollen in hypoosmolar medium. The parameters obtained for the real U937 cells are used. Successful prediction of changes in ion homeostasis in real-time after stopping the pump using the model with all major cotransporters indicates that the model is reliable. Using this model for analysis RVD showed that there is a “physical” RVD, associated with the time-dependent changes in electrochemical ion gradients, but not with alteration of channels and transporters of the plasma membrane that should be considered in studies of truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the partial unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.
Longitudinal in vivo changes in radial peripapillary capillaries and optic nerve head structure in non-human primates with early experimental glaucoma
Authors: Musial Gwen , Adhikari Suman , Mirhajianmoghadam Hanieh , Queener Hope M. , Schill Alexander W. , Patel Nimesh B. , Porter Jason 
Published: July 2021

ABSTRACTPurposeThere is conflicting evidence as to whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time-course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG).MethodsSpectral domain optical coherence tomography images were acquired before and approximately every 2 weeks after inducing unilateral EG in 9 rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes.ResultsMean ALCSD and/or MRW were the first parameters to change in 8 EG eyes. RPC density changed first in the 9th. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 μm, MRW thinned by 82.3 ± 65.9 μm, RNFLT decreased by 25 ± 14 μm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in 2 EG eyes, while 2 EG eyes had simultaneous changes.ConclusionsIn most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.
Loss of muscarinic M5 receptor function manifests disparate impairments in exploratory behavior in male and female mice despite common dopamine regulation
Authors: Razidlo John A. , Fausner Skylar M.L. , Wang Liuchang C. , Mirza Salahudeen A. , Alvarez Veronica A. , Lemos Julia C. 
Published: July 2021

AbstractThere are five cloned muscarinic acetylcholine receptors (M1-M5). Of these, the muscarinic type 5 receptor (M5) is the only one localized to dopamine neurons in the ventral tegmental area and substantia nigra. Unlike M1-M4, the M5 receptor has relatively restricted expression in the brain, making it an attractive therapeutic target. Here we performed an in-depth characterization of M5-dependent potentiation of dopamine transmission in the nucleus accumbens and accompanying exploratory behaviors in male and female mice. We show that M5 receptors potentiate dopamine transmission by acting directly on the terminals within the nucleus accumbens. Using the agonist oxotremorine, we revealed a unique concentration response curve and a sensitivity to repeated stressor exposure. We found that constitutive deletion of M5 receptors reduced exploration of the center of an open field while at the same time impairing normal habituation only in male mice. In addition, M5 deletion reduced exploration of salient stimuli, especially under conditions of high novelty, yet had no effect on hedonia. We conclude that M5 receptors are critical for both engaging with the environment and updating behavioral output in responses to the environment cues, specifically in male mice. A cardinal feature of mood and anxiety disorders is a withdrawal from the environment. These data indicate that boosting M5 receptor activity may be a useful therapeutic target for ameliorating these symptoms of depression and anxiety.Significance StatementThe basic physiological and behavioral functions of the muscarinic M5 receptor remain understudied. Furthermore, its presence on dopamine neurons, relatively restricted expression in the brain, and recent crystallization make it an attractive target for therapeutic development. Yet, most preclinical studies of M5 receptor function have primarily focused on substance use disorders in male rodents. Here we characterized the role of M5 receptors in potentiating dopamine transmission in the nucleus accumbens, finding impaired functioning after stress exposure. Furthermore, we show that M5 receptors can modulate exploratory behavior in a sex-specific manner, without impacting hedonic behavior. These findings further illustrate the therapeutic potential of the M5 receptor, warranting further research in the context of treating mood disorders.
Sex Identification in Cattle, based on Amelogenin Gene
Authors: Ahmad Aftab , Israr Muhammad , Rahat Murad Ali , Wahab Adnan , Uddin Subhan , Rasool Akhtar , Akbar Fazal , Shah Muzafar 
Published: July 2021

AbstractSex identification is considered an important step in the field of forensic sciences, wildlife and livestock breeding management. In the current experiment we used Amelogenin gene as a biological marker for polymerase chain reaction test to identify the sex of cattle from blood remnants, collected at slaughter house. Due to the conserved region of the gene on both sex chromosomes (X and Y) a single primers pair was employed to amplify the gene in a single polymerase chain reaction. In case of band patterns, a 178 base pair fragment for AMELY and a 241 base pair fragment for AMELX genes were produced. The primer’s competence and exactness was initially checked on known gender cattle samples and then applied to unknown cattle samples for the validation of the experiment. PCR amplicons of unknown gender showed only one band (241-bp) for female DNA and two bands (241-bp, 178-bp) for male DNA, on the platform of agarose gel upon electrophoresis. Our findings showed that the PCR protocol based on AMELX/Y gene is a reliable technique for the identification of cattle sex.