Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift ...mutations in TREX1, which encodes a 3′-5′ exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.
•The most common patterns of epileptiform activity during follow-up were described.•Three trajectories of evolution in the epileptiform activity were identified.•A previously unreported abnormal ...background rhythm in these children was described.•Multifocal discharges over time were associated with neuroimaging findings.•Multifocal discharges over time had less focal epilepsy and more spasms.
To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics.
As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups.
Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy.
These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.
Wilms' tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of WT1 have been classically associated with ...Denys-Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between WT1 disorders has been frequently observed. New WT1 variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic WT1 variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of WT1 between exons 9 and 10. Two pathogenic missense WT1 variants were identified in two 46,XY individuals with Wilms' tumors; both patients were <1 year of age at the time of diagnosis. A novel WT1 variant, c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with WT1 variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.
Background and Research Aims
Although fundamental to tropical forest biodiversity, fungi have been largely neglected in conservation research. To examine the fungal response to increased ultraviolet ...C (UVC) radiation, we analyzed UVC radiation effects on the survival, growth, and amylase activity of Aspergillus carbonarius and Aspergillus japonicus.
Methods
A. carbonarius (strain URM 7305) and A. japonicus (URM 7270) were exposed to UVC (254 nm) for different periods, and morphological changes were compared to the control.
Results
Survival capacity and growth decreased after 10 min of exposure in A. carbonarius and after 25 min in A. japonicus. After 40 min, amylase activity decreased (A. carbonarius: 35.8%; A. japonicus: 30.3%). Amylase thermostability at 60°C was lower in UVC-exposed strains (T50 15 min) compared to controls (A. japonicus, 45 min; A. carbonarius, 30 min). However, the protein amount remained stable in all UVC-treated strains. Contamination by other fungi was observed in the UVC-exposed strains, confirming competitive strength loss in both species. This was not observed in the controls due to secondary metabolite production, which increased their competitive fitness.
Conclusion
We provide new information about UVC’s adverse effects on the survival and enzyme production of A. carbonarius and A. japonicus, which could mean a loss of species essential for proper soil functioning and biodiversity.
Implications for conservation
Experimental manipulation of biochemical and physiological reactions advances fungal conservation beyond distributional data. The experimental evidence supports previous studies, suggesting that the increased UV radiation caused by climate change may drastically affect fungal biochemistry and physiology.
RNA-seq is increasingly used for quantitative profiling of small RNAs (for example, microRNAs, piRNAs and snoRNAs) in diverse sample types, including isolated cells, tissues and cell-free biofluids. ...The accuracy and reproducibility of the currently used small RNA-seq library preparation methods have not been systematically tested. Here we report results obtained by a consortium of nine labs that independently sequenced reference, 'ground truth' samples of synthetic small RNAs and human plasma-derived RNA. We assessed three commercially available library preparation methods that use adapters of defined sequence and six methods using adapters with degenerate bases. Both protocol- and sequence-specific biases were identified, including biases that reduced the ability of small RNA-seq to accurately measure adenosine-to-inosine editing in microRNAs. We found that these biases were mitigated by library preparation methods that incorporate adapters with degenerate bases. MicroRNA relative quantification between samples using small RNA-seq was accurate and reproducible across laboratories and methods.
Purpose
Delineate retrospectively and prospectively the incidence and characteristics of transient ST-segment elevation during transseptal puncture.
Methods
The study retrospectively evaluated 307 ...patients from January 1, 2015, to December 31, 2017, and prospectively evaluated 231 patients from January 1, 2018, to July 31, 2019.
Results
The presence of ST-segment elevation was significantly higher in the prospective sample than in the retrospective sample (5.2% vs. 1.3%,
p
< 0.05). Between the two groups, there was no significant difference in age, sex, comorbidities, left atrial volume index, and the etiology of atrial fibrillation among patients with ST-segment alteration. In all patients, the ST-segment elevation was observed in the inferior wall derivations, except for one patient with ST elevation in lead I, AVL, V1-V4 during the septal puncture, associated with sinus bradycardia and reversed hypotension with intravenous fluids. Comparative analysis of the systolic and diastolic arterial pressure and the minimum heart rate during the phenomenon demonstrated more severity in the retrospectively evaluated population than in the prospective population. There was a significant association between the occurrence of ST-segment elevation > 2 mm and the presence of symptoms. In these patients, coronary angiography showed no alterations. Atropine was administered to one patient who presented with junctional bradycardia after the puncture. This medication reversed the situation.
Conclusion
ST-segment elevation is a short-term phenomenon that can occur during transseptal catheterization without clinically evident symptoms. The catheter ablation procedure can be safely concluded despite the occurrence of the phenomenon.
Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and ...pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.
•Aerococcus viridans is a human and animal invasive pathogen.•Aerococcal infections are underestimated due to bacteria misidentification.•Porcine A. viridans were identified by MALDI-TOF MS and 16S ...rRNA sequencing.•High genetic heterogeneity and alarming high MICs were detected.
Aerococcus viridans has been reported as a human and animal pathogen causing urinary tract infection, arthritis, pneumonia, meningitis and endocarditis. Routinely, A. viridans is not surveyed in clinical diagnosis laboratories and commonly is misidentified as other bacteria. There is no concrete data on the prevalence and impact of the pathogen to both human and animal health. In the present study, we report the isolation and molecular and antibiotic susceptibility characterization of A. viridans strains from porcine urinary infections. A total of 22 isolates were identified as A. viridans by MALDI-TOF MS and confirmed by 16S rRNA gene sequencing. Isolates were genotyped by single enzyme amplified fragments length polymorphism (SE-AFLP) that resulted in 19 clusters of which 81.2% were composed by single isolates. The high genetic heterogeneity corroborates previous studies and appears to be a particularity of A. viridans. The minimal inhibitory concentration (MIC) values also presented variability especially for ceftiofur, fluoroquinolones and aminoglycosides. The high MICs of aminoglycosides, tetracyclines and macrolides seen among the A. viridans corroborate previous reports and the widespread veterinary usage of these antibiotics demand attention for the implication of A. viridans infection to both human and animal health.
Purulent vulvar discharge is a clinical sign of genitourinary tract infections, which are a significant concern in swine facilities, leading to sow culling and mortality.
is one of the main agents ...involved in these diseases. This study aimed to characterize the virulence and antimicrobial resistance profiles as well as the phylotype of
strains isolated from sows with purulent vulvar discharge. The results showed that at least 2 of the 29 tested virulence genes related to extraintestinal pathogenic
were present in all strains tested. The most frequent gene was
, present in all strains, followed by the genes
,
,
, and
. Associations between iron uptake genes, genes related to adhesion, attachment, and serum resistance, as well as genes related to toxin release and bacteriocin, were frequent. The most prevalent phylotype was B1 (40.0%), followed by A (18.5%), D (11.9%), C (9.6%), B2 (7.4%), E (4.4%), F (1.5%), and Clade I (0.7%), with B2 being related to highly virulent traits. The strains presented elevated resistance to antimicrobials such as ciprofloxacin, streptomycin, cephalexin, florfenicol, and ampicillin. More than 90% of the strains were identified as multidrug-resistant, indicating the selection that is induced by the high use of antimicrobials in swine farming.
The photophysical properties of two quinolin-2-one and two coumarin derivatives, 3-amino-4-phenylquinolin-2-one (
1
),
N
-(
tert
-butyloxycarbonyl)amino-4-phenylcoumarin (
2
), and the dipeptides
3
...and
4
bearing the quinolin-2-one or the coumarin moiety, respectively, synthesized earlier by some of us, were studied in solvents of varying polarity. Compounds
1
and
2
show a moderate solvent sensitive emission, quinolinone
1
exhibited the highest fluorescence quantum yields (between 0.04 and 0.24). The dipeptide derivatives
3
and
4
present reasonable fluorescence quantum yields in several media, including water (between 0.02 and 0.08). Quinolin-2-one (
1
and
3
) and coumarin (
2
and
4
) derivatives were incorporated in lipid vesicles of egg lecithin (egg-PC), DPPC, DPPG and mixed DPPC/DPPG (1 : 1). All compounds are mainly located in the lipid bilayer, feeling the transition between the rigid gel phase and the fluid liquid-crystalline phase. Dynamic light scattering measurements indicated that the liposomes with the encapsulated compounds are generally monodisperse and with hydrodynamic diameters lower than 160 nm, suitable for biomedical applications.
The interaction with lipid bilayers of a quinolin-2-one and a coumarin including dipeptides was investigated through fluorescence and DLS measurements.
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