bluuebunny/crossref_metadata_2025 huggingface dataset:
Infertility management in women with polycystic ovary syndrome: a review
Authors: Cunha Anita , Póvoa Ana Margarida
Published: January 2021

Polycystic ovary syndrome is the most common endocrine disorder in women and a major cause of anovulatory infertility. Various medical options are used, alone or in combination, to treat subfertility associated with polycystic ovary syndrome. This narrative review was conducted to provide an update and summarize the available evidence on the management of polycystic ovary syndrome related infertility. A wide literature search was performed and preferably randomized controlled trials and systematic reviews were included. Management is often centered on lifestyle changes. Pharmacological ovulation induction is the next step, with recommended use of letrozole, clomiphene citrate or gonadotropins. When it fails, assisted reproductive technologies or laparoscopic ovarian drilling are frequently advised. Combination treatment with metformin is often recommended. More recent alternative and adjunctive treatments have been suggested, like inositol, vitamin D, bariatric surgery and acupuncture, but further research is needed for recommendation.
Reducing Food Waste and Saving Money
Authors: Conrad Zach , Reinhardt Sarah L. , McDowell Acree , Nance Julie
Published: January 2021

The COVID-19 pandemic has heightened the importance of affordable nutrition. Fruits and vegetables are among the most commonly wasted food items, representing waste of key nutrients that are needed to maintain health and support the immune system. Food waste also represents substantial environmental burden and more than one-quarter of consumer food spending. Practical strategies are urgently needed to help nutritionists support their clients in reducing food waste, which can help improve diet quality, reduce environmental impacts, and increase financial flexibility during this critical time. Fortunately, recent research has demonstrated that efforts to reduce waste of fruits and vegetables at home, as well as meat and seafood away from home, will be particularly impactful. A number of strategies exist to help consumers reduce their food waste while making affordable food choices, and nutritionists are well poised to communicate these strategies to their clients and communities of practice.
A Personal Perspective on Alzheimer's Disease
Authors: Achterberg Cheryl
Published: January 2021

This article describes the experience of a nutritionist in coping with Alzheimer's disease in her family. The disease and its stages as well as the challenges for patients and caregivers are described.
Special feature: measuring components of ecological resilience in long-term ecological datasets
Authors: Seddon Alistair W. R.
Published: January 2021

Ecological resilience has become a focal concept in ecosystem management. Palaeoecological records (i.e. the sub-fossil remains preserved in sediments) are useful archives to address ecological resilience since they can be used to reconstruct long-term temporal variations in ecosystem properties. The special feature presented here includes nine new papers from members and associates of the PAGES EcoRe3 community. The papers build on previous work in palaeoecology to investigate, identify and compare components of ecosystem resilience on centennial to millennial timescales. There are four key messages that can be summarized from the findings of papers within the special feature: (i) multi-proxy studies reveal insights into the presence and mechanisms of alternative states; (ii) transitions between alternative states may not necessarily be abrupt; (iii) components of ecological resilience can be identified in long-term ecological data and (iv) the palaeoecological record can also provide insights into factors influencing the resilience of ecosystem functioning. Overall, these papers demonstrate the importance of using long-term ecological records for addressing questions related to the theoretical framework provided by ecological resilience.
Optimal experimental design for mathematical models of haematopoiesis
Authors: Lomeli Luis Martinez , Iniguez Abdon , Tata Prasanthi , Jena Nilamani , Liu Zhong-Ying , Van Etten Richard , Lander Arthur D. , Shahbaba Babak , Lowengrub John S. , Minin Vladimir N.
Published: January 2021

The haematopoietic system has a highly regulated and complex structure in which cells are organized to successfully create and maintain new blood cells. It is known that feedback regulation is crucial to tightly control this system, but the specific mechanisms by which control is exerted are not completely understood. In this work, we aim to uncover the underlying mechanisms in haematopoiesis by conducting perturbation experiments, where animal subjects are exposed to an external agent in order to observe the system response and evolution. We have developed a novel Bayesian hierarchical framework for optimal design of perturbation experiments and proper analysis of the data collected. We use a deterministic model that accounts for feedback and feedforward regulation on cell division rates and self-renewal probabilities. A significant obstacle is that the experimental data are not longitudinal, rather each data point corresponds to a different animal. We overcome this difficulty by modelling the unobserved cellular levels as latent variables. We then use principles of Bayesian experimental design to optimally distribute time points at which the haematopoietic cells are quantified. We evaluate our approach using synthetic and real experimental data and show that an optimal design can lead to better estimates of model parameters.
The limits of egg recognition: testing acceptance thresholds of American robins in response to decreasingly egg-shaped objects in the nest
Authors: Hauber Mark E. , Winnicki Sarah K. , Hoover Jeffrey P. , Hanley Daniel , Hays Ian R.
Published: January 2021

Some hosts of avian brood parasites reduce or eliminate the costs of parasitism by removing foreign eggs from the nest (rejecter hosts). In turn, even acceptor hosts typically remove most non-egg-shaped objects from the nest, including broken shells, fallen leaves and other detritus. In search for the evolutionary origins and sensory mechanisms of egg rejection, we assessed where the potential threshold between egg recognition and nest hygiene may lie when it comes to stimulus shape. Most previous studies applied comparisons of egg-sized objects with non-continuous variation in shape. Here, instead, we used two series of three-dimensional-printed objects, designed
a priori
to increasingly diverge from natural eggs along two axes (width or angularity) of shape variation. As predicted, we detected transitions from mostly acceptance to mostly rejection in the nests of American robins
Turdus migratorius
along each of the two axes. Our methods parallel previous innovations in egg-rejection studies through the use of continuous variation in egg coloration and maculation contrast, to better understand the sensory limits and thresholds of variation in egg recognition and rejection in diverse hosts of avian brood parasites.
Superinfection and the evolution of an initial asymptomatic stage
Authors: Saad-Roy Chadi M. , Grenfell Bryan T. , Levin Simon A. , Pellis Lorenzo , Stage Helena B. , van den Driessche P. , Wingreen Ned S.
Published: January 2021

Pathogens have evolved a variety of life-history strategies. An important strategy consists of successful transmission by an infected host before the appearance of symptoms, that is, while the host is still partially or fully asymptomatic. During this initial stage of infection, it is possible for another pathogen to superinfect an already infected host and replace the previously infecting pathogen. Here, we study the effect of superinfection during the first stage of an infection on the evolutionary dynamics of the degree to which the host is asymptomatic (host latency) in that same stage. We find that superinfection can lead to major differences in evolutionary behaviour. Most strikingly, the duration of immunity following infection can significantly influence pathogen evolutionary dynamics, whereas without superinfection the outcomes are independent of host immunity. For example, changes in host immunity can drive evolutionary transitions from a fully symptomatic to a fully asymptomatic first infection stage. Additionally, if superinfection relative to susceptible infection is strong enough, evolution can lead to a unique strategy of latency that corresponds to a local fitness minimum, and is therefore invasible by nearby mutants. Thus, this strategy is a branching point, and can lead to coexistence of pathogens with different latencies. Furthermore, in this new framework with superinfection, we also find that there can exist two interior singular strategies. Overall, new evolutionary outcomes can cascade from superinfection.
Contact lines on stretched soft solids: modelling anisotropic surface stresses
Authors: Heyden Stefanie , Bain Nicolas , Xu Qin , Style Robert W. , Dufresne Eric R.
Published: January 2021

We present fully analytical solutions for the deformation of a stretched soft substrate due to the static wetting of a large liquid droplet, and compare our solutions to recently published experiments (Xu
et al.
2018
Soft Matter
14, 916–920 (doi:10.1039/C7SM02431B)). Following a Green’s function approach, we extend the surface-stress regularized Flamant–Cerruti problem to account for uniaxial pre-strains of the substrate. Surface profiles, including the heights and opening angles of wetting ridges, are provided for linearized and finite kinematics. We fit experimental wetting ridge shapes as a function of applied strain using two free parameters, the surface Lamé coefficients. In comparison with experiments, we find that observed opening angles are more accurately captured using finite kinematics, especially with increasing levels of applied pre-strain. These fits qualitatively agree with the results of Xu
et al
., but revise values of the surface elastic constants.
Touch inhibits touch: sanshool-induced paradoxical tingling reveals perceptual interaction between somatosensory submodalities
Authors: Cataldo Antonio , Hagura Nobuhiro , Hyder Yousef , Haggard Patrick
Published: January 2021

Human perception of touch is mediated by inputs from multiple channels. Classical theories postulate independent contributions of each channel to each tactile feature, with little or no interaction between channels. In contrast to this view, we show that inputs from two sub-modalities of mechanical input channels interact to determine tactile perception. The flutter-range vibration channel was activated anomalously using
hydroxy-α-sanshool
, a bioactive compound of Szechuan pepper, which chemically induces vibration-like tingling sensations. We tested whether this tingling sensation on the lips was modulated by sustained mechanical pressure. Across four experiments, we show that sustained touch inhibits sanshool tingling sensations in a location-specific, pressure-level and time-dependent manner. Additional experiments ruled out the mediation of this interaction by nociceptive or affective (C-tactile) channels. These results reveal novel inhibitory influence from steady pressure onto flutter-range tactile perceptual channels, consistent with early-stage interactions between mechanoreceptor inputs within the somatosensory pathway.
Corynebacterium phoceense – a rare Corynebacterium species isolated from a urine sample
Authors: Barberis Claudia M. , Traglia Germán M. , Almuzara Marisa N. , Rocha Danilo J. P. G. , Santos Carolina S. , Aguiar Eric R. G. R. , Pacheco Luis G. C. , Vay Carlos A.
Published: January 2021

Corynebacterium

spp. are Gram-positive rods that are recognized to cause opportunistic diseases under certain predisposing clinical conditions. Some species have been described in urinary tract infections. In this report we document a new episode of urinary tract infection caused by Corynebacterium phoceense and describe the whole-genome sequencing, phenotypic characteristics and mass spectra obtained by matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on genome identification and DNA-to-DNA hybridization, we can assume that our strain is the second isolate of C. phoceense to be described in a urine sample. No other infectious diseases have been reported to be associated with this species.
Greenland and Svalbard glaciers host unknown basidiomycetes: the yeast Camptobasidium arcticum sp. nov. and the dimorphic Psychromyces glacialis gen. and sp. nov.
Authors: Perini Laura , Andrejašič Kristina , Gostinčar Cene , Gunde-Cimerman Nina , Zalar Polona
Published: January 2021

Sampling campaigns in Greenland and Svalbard were executed to explore fungal diversity in cold habitats. Three very abundant groups of strains were discovered, consisting either of recently described or of yet-undescribed psychrophilic and oligotrophic yeasts and dimorphic fungi, accounting for around 50 % of the total cultivable diversity of basidiomycetes in our studies. The occurrence of these taxa has also been demonstrated by culture-independent methods. Based on phylogenetic analyses of ribosomal gene cluster sequences (D1/D2 domains of 28S (LSU), 18S (SSU), ITS with 5.8S rDNA) and sequences of protein-coding genes for elongation factor one alpha (TEF), cytochrome b (CYTB) and two subunits of the RNA polymerase II (RPB1 and RPB2) obtained from pure cultures, the isolated taxa presented in this study belong to Basidiomycota, subphylum Pucciniomycotina, class Microbotryomycetes, family Camptobasidiaceae. The dataset of the sequences supported the recognition of three species: Camptobasidium gelus, Camptobasidium arcticum sp. nov. (ex-type strain EXF-12713) and Psychromyces glacialis gen. and sp. nov. (ex-type strain EXF-13111). Camptobasidium gelus was found in the Svalbard and Greenland samples, while representatives of the here proposed new species, C. arcticum, were found only in the Greenland Ice Sheet. Psychromyces gen. nov. was erected for the dimorphic/filamentous isolates found in Svalbard and Greenland glacial environments. The taxon, for which the invalid name ‘Rhodotorula svalbardensis’ has been used, belongs to this genus. Based on ribosomal genes, Camptobasidium arcticum and Psychromyces glacialis are related, phylogenetically most closely related to the genera Glaciozyma and Cryolevonia. Seven genes phylogeny restricted to taxa with available sequences, supported the placement of Psychromyces to Camptobasidiaceae.
Companilactobacillus pabuli sp. nov., a lactic acid bacterium isolated from animal feed
Authors: Jung Ji Young , Kang Hye Kyeong , Jin Hyun Mi , Han Sang-Soo , Kwon Young Chul , Eun Jong Jun , Kim Sang Cheol , Seo Min Jeong , Ryu Byung-Gon , Chung Eu Jin
Published: January 2021

A Gram-positive, facultative anaerobic, catalase-negative, non-motile, non-spore-forming and rod-shaped lactic acid bacterium strain, denoted as NFFJ11T and isolated from total mixed fermentation feed in the Republic of Korea, was characterized through polyphasic approaches, including sequence analyses of the 16S rRNA gene and housekeeping genes (rpoA and pheS), determination of average nucleotide identity and in silico DNA–DNA hybridization, fatty acid methyl ester analysis, and phenotypic characterization. Phylogenetic analyses based on 16S rRNA, rpoA and pheS gene sequences revealed that strain NFFJ11T belonged to the genus

Companilactobacillus

. The 16S rRNA gene sequence of strain NFFJ11T exhibited high similarity to

Companilactobacillus formosensis

S215T (99.66 %),

Companilactobacillus farciminis

Rv4 naT (99.53 %),

Companilactobacillus crustorum

LMG 23699T (99.19 %),

Companilactobacillus futsaii

YM 0097T (99.06 %),

Companilactobacillus zhachilii

HBUAS52074T (98.86 %) and Companilactobacillus heilongiiangensis S4-3T (98.66 %). However, average nucleotide identity and in silico DNA–DNA hybridization values for these type strains were in the range of 79.90–92.93 % and 23.80–49.30 %, respectively, which offer evidence that strain NFFJ11T belongs to a novel species of the genus

Companilactobacillus

. The cell-wall peptidoglycan type was A4α (l-Lys–d-Asp) and the G+C content of the genomic DNA was 35.7 mol%. The main fatty acids of strain NFFJ11T were C18 : 1
 ω9c (43.3 %), C16 : 0 (20.1 %) and summed feature 7 (18.3 %; comprising any combination of C19 : 1
 ω7c, C19 : 1
 ω6c and C19 : 0 cyclo ω10c). Through polyphasic taxonomic analysis, it was observed that strain NFFJ11T represents a novel species belonging to the genus

Companilactobacillus

, for which the name Companilactobacillus pabuli sp. nov. is proposed. The type strain is NFFJ11T (= KACC 21771T= JCM 34088T).
Ligilactobacillus agilis BKN88 possesses thermo-/acid-stable heteropolymeric flagellar filaments
Authors: Eguchi Naoto , Suzuki Shunya , Yokota Kenji , Igimi Shizunobu , Kajikawa Akinobu
Published: January 2021

Many flagellated bacteria possess multiple flagellins, but the roles and the compositions of each flagellin are diverse and poorly understood. In

Ligilactobacillus agilis

BKN88, there are two active flagellin gene paralogues but their function and composition in its flagellar filaments have not been described. The aim of this study is to find the function and composition of the flagellins by employing mutant strains each of which expresses a single flagellin or a modified flagellin. Two single flagellin-expressing strains were both flagellated while the number of flagella per cell in the single flagellin-expressing derivatives was lower than that in the wild type. Nonetheless, these derivative strains were apparently equally motile as the wild type. This indicates that either flagellin is sufficient for cell motility. The immunological activity via Toll-like receptor 5 of the single flagellin-expressing strains or purified single flagellins was readily detectable but mostly variably weaker than that of the wild type. The flagellar filaments of wild type

L. agilis

BKN88 were more acid-/thermo-stable than those of single flagellin-expressing derivatives. Using a combination of immunoprecipitation and flagellin-specific staining, wild type BKN88 appeared to possess heteropolymeric flagellar filaments consisting of both flagellins and each flagellin appeared to be equally distributed throughout the filaments. The results of this study suggest that the two flagellins together form a more robust filament than either alone and are thus functionally complementary.
Embryonic development in the acoelHofstenia miamia
Authors: Kimura Julian O. , Ricci Lorenzo , Srivastava Mansi
Published: January 2021

Acoels are marine worms that belong to the phylum Xenacoelomorpha. The phylogenetic placement of this group as a deep-diverging lineage makes acoel embryos an attractive system to study the evolution of major bilaterian traits. Thus far, acoel development has not been described in detail at the morphological and transcriptomic levels in a species where functional genetic studies are possible. Here, we present a set of developmental landmarks for embryogenesis in the highly regenerative acoelHofstenia miamia. We generated a developmental staging atlas from zygote to hatched worm based on gross morphology, with accompanying bulk transcriptome data for each of the stages.Hofsteniaembryos undergo a stereotyped cleavage program known as duet cleavage, which results in two large ‘macromeres’ at the vegetal pole and numerous small ‘micromeres’ at the animal pole. The macromeres become internalized as micromere progeny proliferate and move vegetally, enveloping the larger blastomeres. We also noted a second, previously undescribed cell internalization event at the animal pole, following which we detected tissues corresponding to all three germ layers. Our work onHofsteniaembryos provides a resource for future investigations of acoel development, which will yield insights into the evolution of development and regeneration.

Summary Statement

Comprehensive characterization of embryonic development in the acoel wormHofstenia miamiawith accompanying transcriptome data.
Nickel-Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long Range Electron Transfer
Authors: Patwardhan Anjali , Sarangi Ritimukta , Ginovska Bojana , Raugei Simone , Ragsdale Stephen W.
Published: January 2021

Methyl-coenzyme M reductase (MCR) catalyzes both synthesis and anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of Cofactor F430. The Ni ion, in its low-valent Ni(I) state lights the fuse leading to homolysis of the C-S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from Coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. Based on crystal structures, which reveal a Ni-thiol interaction between Ni(II)-MCR and inhibitor CoMSH, a Ni(I)-thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)-disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)-sulfur interaction poses a conundrum for the proposed hydrogen atom abstraction reaction because the >6 Å distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears too long for such a reaction. Spectroscopic, kinetic, structural and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)-N/O complex, not Ni(I)-S. These studies rule out direct Ni(I)-sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both forward and reverse MCR reactions emanate through long-range electron transfer from Ni(I)-sulfonate complexes with methyl-SCoM or CoMSSCoB, respectively.
Structural and immunological identification and antiviral infection experiment of the dominant cytotoxic T lymphocyte epitopes of the oncogenic Marek’s disease virus
Authors: Sun Beibei , Wang Yawen , Wang Zhenbao , Lu Shuangshuang , Xia Chun
Published: January 2021

Marek’s disease (MD) is a serious cancer caused by MDV in chickens, and it is also the first tumor disease that could be controlled by an attenuated vaccine in the world. However, the attenuated vaccine is able to inhibit only the formation of tumors but cannot prevent the infection of oncogenic viruses; instead, it leads to mutations and the emergence of a number of virulent strains. In this paper, the crystal structures of chicken MHC class I (pBF2*1501) molecules bound with 8-mer and 9-mer MDV peptides were solved. The results showed that the conformations of the 8-mer and 9-mer peptides in the antigen-binding groove (ABG) of pBF2*1501 are different; the ABG-8-mer is flat, and the ABG-9-mer has the “featured” M-type epitope morphology. Based on these results, multiple MDV epitopes were confirmed using the tetramer technique, and the immunoprotective effect of dominant epitope was confirmed using the protein adjuvant HSP108-N333 in BF2*1501-expressing chickens. The results showed that the two epitopes have obvious protective effects after a standard immunization program. After challenge, the mortality rate was only 20%, and the protective index (PI) reached 33% in the epitope group. The results verified that a single epitope could induce extremely strong specific antitumor T lymphocyte immunity. The results show that three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant cytotoxic T lymphocyte (CTL) epitopes, efficient protein adjuvant and MHC matching. Meanwhile, the results also provided obvious advantages for the development of multiple epitope vaccines for tumor diseases.

Importance

Marek’s disease (MD) is the first tumor disease that can be controlled by an attenuated vaccine. However, the attenuated vaccine cannot prevent the infection of the oncogenic virus and instead leads to the emergence of a number of mutated virulent strains. First, the mechanism of the chicken BF2*1501 preferentially presents 9-mer peptide was clarified. Based on this result, multiple MDV epitopes were confirmed, and the dominant epitopes were identified. Subsequently, two epitope groups showed obvious protective effects after a standard immunization program, and the protective index (PI) of one of the epitope groups reached over 30%. The results showed that a single epitope could induce strong and efficient antitumor CTL immunity. Overall, three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant epitopes, efficient protein adjuvant and MHC matching. Our results provide an obvious strategy for the development of multiple epitope vaccines in tumor diseases.
PERIPHERAL INOTROPES IN CRITICALLY ILL CHILDREN - IS IT SAFE?
Authors: Mooli Ravi K , Sadasivam K
Published: January 2021

Many children needing paediatric intensive care units care require inotropes, which are started peripherally prior to securing a central venous access. However, many hospitals in low- and middle-income countries may not have access to central lines and the vasoactive medications are frequently given through a peripheral venous access.

Aim

The aim of our study was to estimate the safety of peripheral vasoactive inotropes in children.

Methods

Children requiring peripheral vasoactive medications were included in this study. We retrospectively collected data at two time points on use and complications of peripheral vasoactive medications.

Results

Eighty-four children (51 pre-COVID era and 33 COVID pandemic) received peripheral vasoactive medications. Only 3% of children (3/84) developed extravasation injury, all of whom recovered completely.

Conclusions

Results from our study suggest that extravasation injury due to peripheral inotrope infusion is very low (3%) and it can be safely administered in children at a diluted concentration.
Impact of COVID-19 on education, health and lifestyle behaviour of Brazilian urology residents
Authors: Prezotti Jose Antonio , Henriques João Victor T. , Favorito Luciano A. , Canalini Alfredo F. , Machado Marcos G. , Brandão Thulio B. V. , Barbosa Akemi M. V. , Moromizato Julyana K.M. , Anzolch Karin M. J. , de C. Fernandes Roni , Rodrigues Fransber R. A. , Bellucci Carlos H. S. , Silva Caroline S. , Pompeo Antonio Carlos L. , de Bessa Jose , Gomes Cristiano M.
Published: January 2021

Objectives

To evaluate the impact of COVID-19 on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents.

Materials and Methods

A web-based survey was sent to 468 Brazilian urology residents from postgraduate years (PGY) 3 to 5 to collect data on clinical practice and training after 4 months of COVID-19. We also assessed health-related and behavior changes, rate of infection by SARS-CoV-2, deployment to the front line of COVID-19, residents’ concerns, and access to personal protective equipment (PPE).

Results

Massive reductions in elective and emergency patient consultations, diagnostic procedures and surgeries were reported across the country, affecting PGY 3 to 5 alike. Most in-person educational activities were abolished. The median damage to the urological training expected for 2020 was 6.0 [3.4 -7.7], on a scale from 0 to 10, with senior residents estimating a greater damage (P< 0.001). Educational interventions developed included online case-based discussions, subspeciality conferences and lectures, and grand rounds. Most senior residents favored extending residency to compensate for training loss and most younger residents favored no additional training (p< 0.001). Modifications in health and lifestyle included weight gain (43.8%), reduced physical activity (68.6%), increased alcoholic intake (44.9%) and cigarette consumption (53.6%), worsening of sexual life (25.2%) and feelings of sadness or depression (48,2%). Almost half were summoned to work on the COVID-19 front-line and 24.4% had COVID-19. Most residents had inadequate training to deal with COVID-19 patients and most reported a shortage of PPE. Residents’ concerns included the risk of contaminating family members, being away from residency program, developing severe COVID-19 and overloading colleagues.

Conclusions

COVID-19 had a massive impact in Brazilian urology residents’ training, health and lifestyle behavior, which may reflect what happened in other medical specialties. Studies should confirm these findings to help developing strategies to mitigate residents’ losses.
Role of tonsillar chronic inflammation and commensal bacteria in the pathogenesis of pediatric OSA
Authors: Varón Lindybeth Sarmiento , De Rosa Javier , Rodriguez Raquel , Fernández Pablo M. , Billordo L. Ariel , Baz Plácida , Beccaglia Gladys , Spada Nicolás , Mendoza F. Tatiana , Barberis Claudia M. , Vay Carlos , Arabolaza M. Elena , Paoli Bibiana , Arana Eloísa I.
Published: January 2021

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We uncovered a crucial role of pro-inflammatory tonsillar B and T cells in sustaining hypertrophy and hyperplasia by producing TNF and IL17, respectively. We detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. By combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work shed light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization.
Local adaptation and archaic introgression shape global diversity at human structural variant loci
Authors: Yan Stephanie M. , Sherman Rachel M. , Taylor Dylan J. , Nair Divya R. , Bortvin Andrew N. , Schatz Michael C. , McCoy Rajiv C.
Published: January 2021

Large genomic insertions, deletions, and inversions are a potent source of functional and fitness-altering variation, but are challenging to resolve with short-read DNA sequencing alone. While recent long-read sequencing technologies have greatly expanded the catalog of structural variants (SVs), their costs have so far precluded their application at population scales. Given these limitations, the role of SVs in human adaptation remains poorly characterized. Here, we used a graph-based approach to genotype 107,866 long-read-discovered SVs in short-read sequencing data from diverse human populations. We then applied an admixture-aware method to scan these SVs for patterns of population-specific frequency differentiation—a signature of local adaptation. We identified 220 SVs exhibiting extreme frequency differentiation, including several SVs that were among the lead variants at their corresponding loci. The top two signatures traced to separate insertion and deletion polymorphisms at the immunoglobulin heavy chain locus, together tagging a 325 Kbp haplotype that swept to high frequency and was subsequently fragmented by recombination. Alleles defining this haplotype are nearly fixed (60-95%) in certain Southeast Asian populations, but are rare or absent from other global populations composing the 1000 Genomes Project. Further investigation revealed that the haplotype closely matches with sequences observed in two of three high-coverage Neanderthal genomes, providing strong evidence of a Neanderthal-introgressed origin. This extraordinary episode of positive selection, which we infer to have occurred between 1700 and 8400 years ago, corroborates the role of immune-related genes as prominent targets of adaptive archaic introgression. Our study demonstrates how combining recent advances in genome sequencing, genotyping algorithms, and population genetic methods can reveal signatures of key evolutionary events that remained hidden within poorly resolved regions of the genome.
Fine-tuned control of stress priming and thermotolerance
Authors: Pfeuty Benjamin , Courtade Emmanuel , Thommen Quentin
Published: January 2021

A common signature of cell adaptation to stress is the improved resistance upon priming by prior stress exposure. In the context of hyperthermia, priming or preconditioning with sublethal heat shock can be a useful tool to confer thermotolerance and competitive advantage to cells. In the present study, we develop a data-driven modeling framework that is simple and generic enough to capture a broad set of adaptation behaviors to heat stress at both molecular and cellular levels. The model recovers the main features of thermotolerance and clarifies the tradeoff principles which maximize the thermotolerance effect. It therefore provides an effective predictive tool to design preconditioning and fractionation hyperthermia protocols for therapeutic purpose.
Structural characterization and theoretical calculations of the monohydrate of the 1:2 cocrystal salt formed from acriflavine and 3,5-dinitrobenzoic acid
Authors: Marczak Maria , Biereg Kinga , Zadykowicz Beata , Sikorski Artur
Published: January 2021

The synthesis and structural characterization of the monohydrated 1:2 cocrystal salt of acriflavine with 3,5-dinitrobenzoic acid [systematic name: 3,6-diamino-10-methylacridin-10-ium 3,5-dinitrobenzoate–3,5-dinitrobenzoic acid–water (1/1/1), C14H14N3
+·C7H3N2O6
−·C7H4N2O6·H2O] are reported. Single-crystal X-ray diffraction measurements show that the title solvated monohydrate salt crystalizes in the monoclinic space group P21 with one acriflavine cation, a 3,5-dinitrobenzoate anion, a 3,5-dinitrobenzoic acid molecule and a water molecule in the asymmetric unit. The neutral and anionic forms of 3,5-dinitrobenzoic acid are linked via O—H...O hydrogen bonds to form a monoanionic dimer. Neighbouring monoanionic dimers of 3,5-dinitrobenzoic acid are linked by nitro–nitro N—O...N and nitro–acid N—O...π intermolecular interactions to produce a porous organic framework. The acriflavine cations are linked with carboxylic acid molecules directly via amine–carboxy N—H...O, amine–nitro N—H...O and acriflavine–carboxy C—H...O hydrogen bonds, and carboxy–acriflavine C—O...π, nitro–acriflavine N—O...π and acriflavine–nitro π–π interactions, or through the water molecule by amino–water N—H...O and water–carboxy O—H...O hydrogen bonds, and are located in the voids of the porous organic framework. The intermolecular interactions were studied using the CrystalExplorer program to provide information about the interaction energies and the dispersion, electrostatic, polarization and repulsion contributions to the lattice energy.
Phenological shift along an elevational gradient and dispersal of pollen and seeds maintain a hybrid zone between two cherry tree species
Authors: Tochigi Kahoko , Shuri Kato , Kikuchi Satoshi , Naoe Shoji , Koike Shinsuke , Nagamitsu Teruyoshi
Published: January 2021

Hybrid zones between species with staggered reproductive phenology sometimes occur along elevational gradients. The maintenance of such hybrid zones may depend on elevational shift in phenology and vertical dispersal of pollen and seeds. In a hybrid zone ofCerasus leveilleana(Cl) andC. sargentii(Cs), 111 adults, 372 embryos of 65 mothers, and 133 juveniles were sampled across elevations of 900–1,400 m in central Japan. Using the hybrid index estimated from nuclear microsatellites, the samples were assigned toCl,Csor their hybrid taxon.Cswas in higher elevations thanClwith an overlapping range, and their hybrids were in intermediary elevations. Flowering periods were earlier inCsthan inClwith little overlap at the same elevation and were intermediate in their hybrids. Flowering periods were delayed in higher elevations and overlapped betweenClandCsin different elevations. Fruiting periods were slightly earlier inCsthan inClbut were largely overlapped. Effective pollinators and seed dispersers were common among the taxa. Changes in the hybrid index from mothers to their embryos were larger in hybrid mothers than inClorCsmothers, indicating mating of hybrids with diverse taxa. InCs, juveniles were more abundant in lower elevations than embryos, indicating downhill seed dispersal. Proportions of hybrids were 19% in embryos, 17% in juveniles and 12% in adults. The findings suggest that the hybrid zone is maintained by interspecific pollination between different elevations, backcrossing with hybrids at similar elevations, vertical seed dispersal and mild selection against hybrids.
Synchronous digital couple and family psychotherapy: a meta‐narrative review
Authors: Helps Sarah , Le Coyte Grinney Marianne
Published: January 2021

Objective

Our objective was to identify, review and synthesise the findings of articles regarding the practice of synchronous digital couple and family psychotherapy over the past three decades.

Methods

A meta‐narrative approach was adopted.

Results

Thirty‐one papers were identified for inclusion in the review, including nine descriptions of practice and 22 empirical studies.

Conclusions

Findings show that practitioners have used synchronous digital technologies in their work over decades. Psychoeducative and cognitive‐behaviourally oriented hybrid, self‐directed synchronous family and couple psychotherapeutic interventions have been found to be feasible, effective with diverse populations, are associated with good user satisfaction, and are found to have similar clinical outcomes to in‐person psychotherapy. Further research is required.

Practitioner points

Over the past 30 years there has been increasing interest in utilising new technologies in couple and family psychotherapeutic interventions to improve access to services and to help with a variety of presenting problems

For families and couples, interventions involving web‐based psychoeducative material combined with ‐ often minimal ‐ synchronous therapeutic or coaching input seem feasible, acceptable and effective

More quantitative and qualitative research into digitally mediated couple, family and systemic psychotherapy is required to determine what works, with whom and how it works in practice.
Delivering Group Lifestyle Triple P through digital practice: A case study with Portuguese parents
Authors: Canário Catarina , Abreu‐Lima Isabel , Santos Susana , Silva‐Martins Marco , Campos Joana , Enes Rodrigues Catarina , Tavares Mónica , Mansilha Helena , Torres Sandra , Serra Lemos Marina , Cruz Orlanda
Published: January 2021

The purpose of the current study was to explore the delivery of the Group Lifestyle Triple P (GLTP) parent group programme through digital practice. Eight mothers of obese children aged 6–11 were recruited from a university hospital. Using a mixed‐methods approach, the study sought to characterise the perceived changes throughout the intervention and explore the outcome measures on children’s BMI z‐score, weight‐related behaviour problems, parents’ self‐efficacy, interparental conflict and parenting styles assessed pre‐ and post‐intervention. Participants identified changes in themselves, in positive parenting, and in their ability to manage children’s nutrition and physical activity, contributing to improve children’s lifestyle behaviours. The clinical results were similar to the findings of studies in which GLTP was delivered in‐person. Delivering GLTP through digital practice seems to be a possible way of implementing the intervention, particularly during the COVID‐19 pandemic.

Practitioner points

GLTP sessions’ contents and activities were adapted for digital delivery without compromising the programme’s implementation fidelity.

Parents perceived an increase in positive parenting behaviours and their ability to manage children’s nutrition and physical activity.

The clinical results of the GLTP delivered through digital practice were similar to those of studies in which the programme was delivered in‐person.
Chromosome‐level assembly of southern catfish (silurus meridionalis) provides insights into visual adaptation to nocturnal and benthic lifestyles
Authors: Zheng Shuqing , Shao Feng , Tao Wenjing , Liu Zhilong , Long Juan , Wang Xiaoshuang , Zhang Shuai , Zhao Qingyuan , Carleton Karen L. , Kocher Thomas D. , Jin Li , Wang Zhijian , Peng Zuogang , Wang Deshou , Zhang Yaoguang
Published: January 2021

The Southern catfish (Silurus meridionalis) is a nocturnal and benthic freshwater fish endemic to the Yangtze River and its tributaries. In this study, we constructed a chromosome‐level draft genome of S. meridionalis using 69.7‐Gb Nanopore long reads and 49.5‐Gb Illumina short reads. The genome assembly was 741.2 Mb in size with a contig N50 of 13.19 Mb. An additional 116.4 Gb of Bionano and 77.4 Gb of Hi‐C data were applied to assemble contigs into scaffolds and further into 29 chromosomes, resulting in a 738.9‐Mb genome with a scaffold N50 of 28.04 Mb. A total of 22,965 protein‐coding genes were predicted from the genome with 22,519 (98.06%) genes functionally annotated. Comparative genomic and transcriptomic analyses revealed a rod‐dominated visual system which was responsible for scotopic vision. The absence of cone opsins SWS1 and SWS2 resulted in the lack of ultraviolet and blue violet sensitivity. Mutations at key amino acid sites of RH1.1, RH1.2 and RH2 resulted in spectral tuning good for dim light vision and narrow colour vision. A higher expression level of rod phototransduction genes than that of cone genes and higher rod‐to‐cone ratio led to higher optical sensitivity under dim light conditions. In addition, analysis of the genes involved in eye morphogenesis and development revealed the loss of some conserved noncoding elements, which might be associated with the small eyes in catfish. Together, our study provides important clues for the adaptation of the catfish visual system to the nocturnal and benthic lifestyles. The draft genome of S. meridionalis represents a valuable resource for studies of the molecular mechanisms of ecological adaptation.
A plant‐derived TRPV3 inhibitor suppresses pain and itch
Authors: Han Yalan , Luo Anna , Kamau Peter Muiruri , Takomthong Pitchayakarn , Hu Jingmei , Boonyarat Chantana , Luo Lei , Lai Ren
Published: January 2021

Background and Purpose

Itching is the most frequent pathology in dermatology that has significant impacts on people's mental health and social life. Transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. However, few selecetive and potent antagonists have been reported. This study was designed to identify selective TRPV3 antagonist and elucidate its anti‐pruritus pharmacology.

Experimental Approach

FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole‐cell patch clamp was used to record itch‐related ion channel currents. Homologous recombination and site‐directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations for exploring pharmacological mechanism. Mouse models were used for in vivo anti‐pruritus assay.

Key Results

An acridone alkaloid (citrusinine‐II) was purified and characterized from Atalantia monophylla. It directly interacts with Y564 within S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC50) of 12.43 μM. Citrusinine‐II showed potential efficacy to attenuate both chronic and acute itch. Intradermal administration of citrusinine‐II (143 ng/skin site) nearly completely inhibited itch behaviours. It also shows significant analgesic effects. Little side effects of the compound are observed.

Conclusion and Implications

By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine‐II shows valuable therapeutic effects in pruritus animal models and is a promising candidate drug and/or lead molecule for the development of anti‐pruritus drugs.
Oxysterols and retinal degeneration
Authors: Zhang Xun , Alhasani Reem Hasaballah , Zhou Xinzhi , Reilly James , Zeng Zhihong , Strang Niall , Shu Xinhua
Published: January 2021

Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol‐producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol‐producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol‐associated pathophysiology will help in the development of effective retinal degeneration therapies.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
Beneficial effects of atorvastatin on sex‐specific cognitive impairment induced by a cerebral microhaemorrhage in mice
Authors: Bergeron Sandrine , Barus Romain , Leboullenger Clémence , Auger Florent , Bongiovanni Antonino , Tardivel Meryem , Jonneaux Aurélie , Laloux Charlotte , Potey Camille , Bordet Régis , Chen Yaohua , Gautier Sophie
Published: January 2021

Background and Purposes

Cerebral microhaemorrhages (CMHs) are associated with cognitive decline in humans. In rodents, CMHs induces cognitive impairment in male mice along with sex‐specific cortical and hippocampal changes affecting neural, glial and vascular functions. Statins, have been proposed to prevent cognitive decline. We tested here the action of atorvastatin on CMH‐induced cognitive impairment in a murine model of CMH.

Experimental Approach

Using a multimodal approach combining behavioural tests, in vivo imaging, biochemistry and molecular biology, the effects of oral administration of atorvastatin on the sex‐specific changes induced by a cortical CMH were studied in male and female mice (C57BL/6J) at 6‐week post‐induction using a collagenase‐induced model.

Key Results

Atorvastatin caused specific effects according to the sex‐specific CMH‐induced changes. In males, atorvastatin improved the visuospatial memory, induced a local modulation of microglial response and enhanced brain‐derived neurotrophic factor (BDNF)‐tropomyosin receptor kinase B (trkB) and vascular endothelial growth factor (VEGF) expression in the cortex. In the hippocampus, atorvastatin increased glucose metabolism and modulated astrocytes morphology. In females, atorvastatin did not modulate visuospatial memory despite the increased expression of cortical BDNF and the decrease in the number of hippocampal astrocytes. Atorvastatin also induced a decrease in the expression of cortical oestrogen receptors but did not modify body weight nor serum cholesterol levels in both sexes.

Conclusion and Implications

Atorvastatin modulated the sex‐specific cognitive impairment induced by the CMH with a pathophysiological impact mainly within the cortical area. It could represent a promising candidate for future sex‐stratified clinical trials in patients with CMH.