bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulfonyl thiourea derivatives from 2‐aminodiarylpyrimidines: In vitro and in silico evaluation as potential carbonic anhydrase I, II, IX, and XII inhibitors
Authors: Thanh Nguyen Dinh , Giang Nguyen Thi Kim , Hai Do Son , Toan Vu Ngoc , Van Hoang Thi Kim , Tri Nguyen Minh
Published: March 2024

A series of synthesized sulfonyl thiourea derivatives (7a–o) of substituted 2‐amino‐4,6‐diarylpyrimidines (4a–o) exhibited the remarkable inhibitory activity against some the human carbonic anhydrases (hCAs), including hCA I, II, IX, and XII isoforms. The inhibitory efficacy of synthesized sulfonyl thiourea derivatives were experimentally validated by in vitro enzymatic assays. 7a (KI = 46.14 nM), 7j (KI = 48.92 nM), and 7m (KI = 62.59 nM) (for isoform hCA I); 7f (KI = 42.72 nM), 7i (KI = 40.98 nM), and 7j (KI = 33.40 nM) (for isoform hCA II); 7j (KI = 228.5 nM), 7m (KI = 195.4 nM), and 7n (KI = 210.1 nM) (for isoform hCA IX); 7l (KI = 116.9 nM), 7m (KI = 118.8 nM), and 7n (KI = 147.2 nM) (for isoform hCA XII) in comparison with KI values of 452.1, 327.3, 437.2, and 338.9 nM, respectively, of the standard drug AAZ. These compounds also had significantly more potent inhibitory action against cytosolic isoform hCA I and tumor‐associated isoforms hCA IX and hCA XII. Furthermore, the potential inhibitory compounds were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7a, 7j, and 7m were the most promising derivatives in this series due to their significant effects on studied hCA I, II, IX, and XII isoforms, respectively. The results showed that the sulfonyl thiourea moiety was accommodated deeply in the active site and interacted with the zinc ion in the receptors.
Understanding gut microbiome‐based machine learning platforms: A review on therapeutic approaches using deep learning
Authors: Malakar Shilpa , Sutaoney Priya , Madhyastha Harishkumar , Shah Kamal , Chauhan Nagendra Singh , Banerjee Paromita
Published: March 2024

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture‐independent techniques such as high‐throughput and meta‐omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole‐genome shotgun metagenomic sequencing of site‐specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis‐associated diseases permits investigation of pharmacokinetic‐pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through “omics‐based” methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.
Supporting Latinx immigrant children and families in the transition to elementary school
Authors: Palacios Natalia , Paulick Judy
Published: March 2024

Current approaches to supporting students in the transition to elementary school fail to meet the needs of Latinx immigrant children and their families in the United States. Typical approaches place the responsibility on families to help their children adapt to the expectations of their teacher, classroom, and school without recognizing the specific barriers to participation faced by Latinx immigrant parents. In this article, we describe these barriers and consider the ways community‐based practice can support and prioritize co‐constructed partnerships among teachers, schools, parents, and communities.
Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia
Authors: Cao Fuyang , Guo Yongxin , Guo Shuting , Hao Xinyu , Yang Lujia , Cao Jiangbei , Zhou Zhikang , Mi Weidong , Tong Li
Published: March 2024

Aims

General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr) and its projections to VTA (PrLPyr‐VTA) are involved in anesthesia‐arousal regulation.

Methods

We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr‐VTA pathway. Electroencephalography spectra and burst‐suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr‐VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK‐801) or AMPA receptor antagonists (NBQX) into the VTA.

Results

Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr‐VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr‐VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr‐VTA projections.

Conclusion

This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr‐VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.
Investigating the role of an immediate early gene FOS as a potential regulator of autophagic response to hypoglycemia in embryonic hypothalamic neurons
Authors: Ramakrishnan Rakhee K. , Srivastava Ankita , Rajan Reeja , Abusnana Salah , Mussa Bashair M.
Published: March 2024

Hypoglycemia‐associated autonomic failure (HAAF) is a well‐established complication of diabetes. Although HAAF has serious outcomes such as recurrent morbidity, coma, and death, the mechanisms of HAAF and its pathological components are largely unknown. Our previous studies have revealed that hypoglycemia is associated with the upregulation of an immediate early gene – FOS. In addition, it is documented that glucose deprivation activates neuronal autophagic activities. Therefore, the present study aimed to identify the role of FOS and one of the core components of the autophagy pathway, Beclin‐1 (encoded by the BECN1 gene), in the regulation of autophagic mechanisms in embryonic hypothalamic neurons in response to hypoglycemic conditions. Embryonic Mouse Hypothalamic Cell Line N39 (mHypoE‐N39 or N39) was cultured in reduced concentrations of glucose (2000, 900, 500, and 200 mg/L). Gene and protein expression, as well as immunofluorescence studies on autophagy were conducted under different reduced glucose concentrations in N39 hypothalamic neurons with and without FOS and BECN1 gene knockdowns (KD). The outcomes of the present study have demonstrated a significant increase in autophagosome formation and subsequent lysosomal degradation in the hypothalamic neurons in response to reduced glucose concentrations. This hypoglycemic response appears to be lowered to a similar extent in the FOS KD and BECN1 KD cells, albeit insignificantly from the negative control, is indicative of the involvement of FOS in the autophagic response of hypothalamic neurons to hypoglycemia. Moreover, the KD cells exhibited a change in morphology and reduced cell viability compared with the control cells. Our findings suggest that reduced FOS expression could potentially be associated with impaired autophagic activities that are dependent on BECN1, which could lead to decreased or blunted hypothalamic activation in response to hypoglycemia, and this, in turn, may contribute to the development of HAAF.
Bioavailability of three novel oral, sustained‐release pellets, relative to an immediate‐release tablet containing 500 mg flucytosine: A randomized, open‐label, crossover study in healthy volunteers
Authors: Goyal Vishal , Krantz Edrich , Simon Francois , Neven Anouk , Eriksson Johanna , Saayman Amaria , Ibnou Zekri Lassout Nabila , Louis Mathieu , Robinson Stephen , Deshmukh Abhijit , Antarkar Amit , Ruffell Carol , Victor Sarika , Chenel Marylore , Celebic Aljosa , Caplain Henri , Gillon Jean‐Yves , Ribeiro Isabela
Published: March 2024

The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub‐Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four‐period crossover phase I trial of three sustained‐release (SR) oral pellet formulations of 5‐flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5‐flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty‐two healthy participants were included. All treatments were well‐tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax) and area under the concentration‐time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically‐based PK modeling indicated a twice‐daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady‐state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).
FAK mediates hypoxia‐induced pulmonary artery smooth muscle cell proliferation by modulating mitochondrial transcription termination factor 1/cyclin D1
Authors: Lin Chunlong , Yang Hui , Luo Qiong , Liu Qi
Published: March 2024

This study aimed to investigate the mechanism of FAK‐dependent hypoxia‐induced proliferation on human pulmonary artery smooth muscle cells (HPASMCs). Primary HPASMCs were isolated and cultured in vitro under normal and hypoxia conditions to assess cell proliferation with cell counting kit‐8. FAK and mitochondrial transcription termination factor 1 (mTERF1) were silenced with siRNA, mRNA, and protein levels of FAK, mTERF1, and cyclin D1 were determined. HPASMC proliferation increased under hypoxia compared to normal conditions. Knocking down FAK or mTERF1 with siRNA led to decreased cell proliferation under both normal and hypoxia conditions. FAK knockdown led to the reduction of both mTERF1 and cyclin D1 expressions under the hypoxia conditions, whereas mTERF1 knockdown led to the downregulation of cyclin D1 expression but not FAK expression under the same condition. However, under normal conditions, knocking down either FAK or mTERF1 had no impact on cyclin D1 expression. These results suggested that FAK may regulate the mTERF1/cyclin D1 signaling pathway to modulate cell proliferation in hypoxia.
Heterogeneity and Labour Agency in Artisanal and Small‐scale Gold Mining in the Democratic Republic of Congo
Authors: Geenen Sara , Bikubanya Divin‐Luc
Published: March 2024

This article considers the broad question of how to improve the conditions of workers in artisanal and small‐scale gold mining (ASGM), which relies on predominantly informal activities. While acknowledging that formalization can provide ASGM miners with tenure security and protection of labour rights, it is important to highlight that not all workers are likely to benefit from formalization in the same way, and that decent work ambitions should extend to all workers, regardless of whether or not they are formalized. It is therefore crucial to understand the heterogeneity in the ASGM workforce. This article describes working conditions for different categories of workers based on a survey carried out in the Watsa and Shabunda territories in Eastern Democratic Republic of Congo. It analyses labour agency and shows that workers are diversely integrated in the labour process and may use power resources in various ways. The discussion reflects on ways to consider the heterogeneity in ASGM labour and to push the ASGM agenda beyond formalization.
Efficacy of 1‐hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes‐related complications: A post hoc analysis of the 30‐year follow‐up of the Da Qing IGT and Diabetes Study
Authors: Peng Minying , He Siyao , Wang Jinping , An Yali , Qian Xin , Zhang Bo , Zhang Lihong , Chen Bo , Yang Zhiwei , Li Guangwei , Gong Qiuhong ,   for the Da Qing Diabetes Prevention Outcome Study Group
Published: March 2024

Aim

To evaluate whether 1‐hour plasma glucose (1hPG) can be a comparable measurement to 2‐hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes.

Methods

A total of 1026 non‐diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6‐, 20‐ and 30year follow‐up for outcomes including diabetes, all‐cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a ‘1hPG‐normal’ group (1hPG <8.6 mmol/L) and a ‘1hPG‐high’ group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time‐dependent receiver‐operating characteristic (ROC) curve.

Results

Compared with the 1hPG‐normal group, the 1hPG‐high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43–5.79), all‐cause mortality (HR 1.46, 95% CI 1.07–2.01), CVD mortality (HR 1.84, 95% CI 1.16–2.95), CVD events (HR 1.39, 95% CI 1.03–1.86) and microvascular disease (HR 1.70, 95% CI: 1.03–2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long‐term follow‐up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009).

Conclusions

Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long‐term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.
The efficacy of spatio‐temporal predictors in forecasting the risk of Cydia nigricana infestation
Authors: Riemer Natalia , Schieler Manuela , Saucke Helmut
Published: March 2024

The ability to estimate the risk of pest infestation can help farmers to reduce pesticide application and provide guidance that would result in better management decisions. This study tested whether different combinations of spatial and temporal risk factors may be used to predict the damage potential of pea moth, Cydia nigricana Fabricius (Lepidoptera: Tortricidae), a major pest in field pea (Pisum sativum L., Fabaceae). Over four consecutive years, the abundance of pea moth was monitored by placing pheromone traps at various field pea‐cultivation sites. We also assessed the phenological development stages and the percentage of damaged seeds per 100 pods collected from each growing pea field in a region of approximately 30 km in diameter. The study found the significant infestation risk indicators to be the time of flowering, the date on which male pea moths are first detected in the monitoring traps and the minimum distance to pea fields that were planted and harvested in the previous growing season. The combination of all three factors using a general additive model approach yielded the best results. The model proposed by this study accurately discriminated between low‐infestation and high‐infestation fields in 95% of cases.
Phenotypic plasticity of a Baetid mayfly larvae (Baetis rhodani) at sites with high levels of deposited fine sediment
Authors: McKenzie Morwenna , Scott Jennifer , Wood Paul J. , Mathers Kate L.
Published: March 2024

Excess fine sediment (particles <2 mm) delivery and deposition in freshwater systems is a significant factor in structuring aquatic communities and populations.

Invertebrate gill surfaces can become covered with fine sediment, potentially compromising osmoregulatory function.

Ionocytes are specialised structures for osmoregulation found on the tracheal gills of mayflies. The number of cells has been shown to change in order to maintain osmoregulatory demands under environmentally variable conditions.

To investigate whether ionocytes vary in response to fine sediment pressure, individuals of Baetis rhodani were collected from two high and low fine sediment cover sites, respectively, in the UK. Tracheal gills were subsequently examined for the number of ionocytes present on the upper and lower gill surfaces, standardised by gill size.

Results indicated that the number of ionocytes was significantly higher for mayflies collected from areas with high fine sediment cover. High fine sediment sites were also characterised by lower altitude and dissolved oxygen concentrations. Mayfly gills collected from high sediment cover sites were also significantly larger than those collected from low sediment sites.

The results illustrate the potential for mayfly larvae to demonstrate phenotypic plasticity to the pressures associated with fine sediment but that these responses are likely dependent on the composition of fine sediment deposits (organic or mineral) and associated oxygen concentrations.
Re‐evaluating patient communication and care in angiographically negative subarachnoid hemorrhage: Balancing realism and optimism
Authors: Khosdelazad Sara , Spikman Jacoba M. , Solvang Sofie , Wermer Marieke J. H. , Pender Niall , Jorna Lieke S. , Rakers Sandra E. , van der Hoorn Anouk , Javadpour Mohsen , Groen Rob J. M. , Buunk Anne M.
Published: March 2024

Angiographically negative subarachnoid hemorrhage (anSAH) has traditionally been considered a benign condition, mainly because of favorable outcomes in the acute stage in comparison to the often negative acute outcomes of aneurysmal subarachnoid hemorrhage. However, a growing body of research in recent years shows that anSAH often leads to cognitive impairments, emotional distress, and difficulties in resuming work or other daily life activities. Therefore, in this position paper, we call for a change in neurological care and a shift in patient communication, emphasizing the importance of addressing patient needs and fostering realistic expectations rather than solely focusing on the benign nature of the condition.
Clinical and molecular characterization of patients with YWHAG‐related epilepsy
Authors: Cetica Valentina , Pisano Tiziana , Lesca Gaetan , Marafi Dana , Licchetta Laura , Riccardi Florence , Mei Davide , Chung Hon‐yin B. , Bayat Allan , Balasubramanian Meena , Lowenstein Daniel H. , Endzinienė Milda , Alotaibi Maha , Villeneuve Nathalie , Jacobs Julia , Isidor Bertrand , Solazzi Roberta , den Hollander Nicolette S. , Marjanovic Dragan , Rougeot‐Jung Christelle , Jung Julien , Lesieur‐Sebellin Marion , Accogli Andrea , Salpietro Vincenzo , Saadi Nebal W. , Panagiotakaki Eleni , Foiadelli Thomas , Redon Sylvia , Tsai Meng‐Han , Bisulli Francesca , Hammer Trine B. , Lupski James R. , Parrini Elena , Guerrini Renzo ,   the YWHAG Study Group
Published: March 2024

Objective

YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG‐related epilepsy.

Methods

We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients.

Results

The phenotypic spectrum of YWHAG‐related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype–phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand‐binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p < .001).

Significance

This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype–phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.
Investigating structural variant, indel and single nucleotide polymorphism differentiation between locally adapted Atlantic salmon populations
Authors: Lecomte Laurie , Árnyasi Mariann , Ferchaud Anne‐Laure , Kent Matthew , Lien Sigbjørn , Stenløkk Kristina , Sylvestre Florent , Bernatchez Louis , Mérot Claire
Published: March 2024

Genomic structural variants (SVs) are now recognized as an integral component of intraspecific polymorphism and are known to contribute to evolutionary processes in various organisms. However, they are inherently difficult to detect and genotype from readily available short‐read sequencing data, and therefore remain poorly documented in wild populations. Salmonid species displaying strong interpopulation variability in both life history traits and habitat characteristics, such as Atlantic salmon (Salmo salar), offer a prime context for studying adaptive polymorphism, but the contribution of SVs to fine‐scale local adaptation has yet to be explored. Here, we performed a comparative analysis of SVs, single nucleotide polymorphisms (SNPs) and small indels (<50 bp) segregating in the Romaine and Puyjalon salmon, two putatively locally adapted populations inhabiting neighboring rivers (Québec, Canada) and showing pronounced variation in life history traits, namely growth, fecundity, and age at maturity and smoltification. We first catalogued polymorphism using a hybrid SV characterization approach pairing both short‐ (16X) and long‐read sequencing (20X) for variant discovery with graph‐based genotyping of SVs across 60 salmon genomes, along with characterization of SNPs and small indels from short reads. We thus identified 115,907 SVs, 8,777,832 SNPs and 1,089,321 short indels, with SVs covering 4.8 times more base pairs than SNPs. All three variant types revealed a highly congruent population structure and similar patterns of FST and density variation along the genome. Finally, we performed outlier detection and redundancy analysis (RDA) to identify variants of interest in the putative local adaptation of Romaine and Puyjalon salmon. Genes located near these variants were enriched for biological processes related to nervous system function, suggesting that observed variation in traits such as age at smoltification could arise from differences in neural development. This study therefore demonstrates the feasibility of large‐scale SV characterization and highlights its relevance for salmonid population genomics.
Adaptation to seasonal reproduction and environment‐associated factors drive temporal and spatial differentiation in northwest Atlantic herring despite gene flow
Authors: Fuentes‐Pardo Angela P. , Stanley Ryan , Bourne Christina , Singh Rabindra , Emond Kim , Pinkham Lisa , McDermid Jenni L. , Andersson Leif , Ruzzante Daniel E.
Published: March 2024

Understanding how marine organisms adapt to local environments is crucial for predicting how populations will respond to global climate change. The genomic basis, environmental factors and evolutionary processes involved in local adaptation are however not well understood. Here we use Atlantic herring, an abundant, migratory and widely distributed marine fish with substantial genomic resources, as a model organism to evaluate local adaptation. We examined genomic variation and its correlation with environmental variables across a broad environmental gradient, for 15 spawning aggregations in Atlantic Canada and the United States. We then compared our results with available genomic data of northeast Atlantic populations. We confirmed that population structure lies in a fraction of the genome including likely adaptive genetic variants of functional importance. We discovered 10 highly differentiated genomic regions distributed across four chromosomes. Nine regions show strong association with seasonal reproduction. One region, corresponding to a known inversion on chromosome 12, underlies a latitudinal pattern discriminating populations north and south of a biogeographic transition zone on the Scotian Shelf. Genome–environment associations indicate that winter seawater temperature best correlates with the latitudinal pattern of this inversion. The variation at two so‐called ‘islands of divergence’ related to seasonal reproduction appear to be private to the northwest Atlantic. Populations in the northwest and northeast Atlantic share variation at four of these divergent regions, simultaneously displaying significant diversity in haplotype composition at another four regions, which includes an undescribed structural variant approximately 7.7 Mb long on chromosome 8. Our results suggest that the timing and geographic location of spawning and early development may be under diverse selective pressures related to allelic fitness across environments. Our study highlights the role of genomic architecture, ancestral haplotypes and selection in maintaining adaptive divergence in species with large population sizes and presumably high gene flow.
Resource level modifies heatwave responses in the freshwater snail Lymnaea stagnalis
Authors: Seppälä Otto , Katsianis Georgios , Stabauer Veronika , Seppälä Katri , Salo Tiina
Published: March 2024

Predicting climate change‐mediated environmental effects on organisms is difficult because their direction and strength may depend on multiple ecological factors that vary in nature. This is because the effects of environmental factors often interact. One potentially important factor modifying organisms' thermal performance is their resource level.

We experimentally examined the dependence of phenotypic responses to heatwaves on resource/food availability in the freshwater snail, Lymnaea stagnalis. We maintained snails at different food levels (unlimited, reduced [50% of expected consumption], no food), and exposed them to either a heatwave temperature (27°C) or a benign temperature (17°C) for 1 week, followed by a post‐heatwave week (17°C). To estimate snail performance, we quantified their metabolic activity (respiration rate), growth rate, fecundity, and immune activity.

All examined traits responded to temperature, and changes in fitness‐related traits (growth rate, fecundity) depended on snail resource level. During the heatwave phase, the benefits of the elevated temperature (enhanced growth rate and fecundity) were higher with unlimited than with limited resources. Additionally, during the post‐heatwave phase, the performance of previously heat‐challenged snails reduced most strongly in resource‐limited snails. The high‐temperature treatment negatively affected snail immune activity even under the high food supply, but immune traits recovered after the heatwave. Interestingly, the phenotypic effects of the high temperature were mainly direct rather than driven by increased metabolic activity.

Our results indicate that heatwave responses of L. stagnalis snails are sensitive to their resource level. Such condition dependence may have important ecological and evolutionary implications by: (1) making natural populations in low‐quality habitats the most susceptible to heatwaves; and (2) altering climate change‐mediated evolution by modifying the expression of phenotypic variation in thermal performance. By demonstrating condition‐dependent heatwave responses, our study highlights the importance of examining the interactive effects of climate change‐mediated environmental alterations and ecological factors that vary in nature.
Depth‐dependent responses of soil organic carbon under nitrogen deposition
Authors: Hu Yuanliu , Deng Qi , Kätterer Thomas , Olesen Jørgen Eivind , Ying Samantha C. , Ochoa‐Hueso Raúl , Mueller Carsten W. , Weintraub Michael N. , Chen Ji
Published: March 2024

Emerging evidence points out that the responses of soil organic carbon (SOC) to nitrogen (N) addition differ along the soil profile, highlighting the importance of synthesizing results from different soil layers. Here, using a global meta‐analysis, we found that N addition significantly enhanced topsoil (0–30 cm) SOC by 3.7% (±1.4%) in forests and grasslands. In contrast, SOC in the subsoil (30–100 cm) initially increased with N addition but decreased over time. The model selection analysis revealed that experimental duration and vegetation type are among the most important predictors across a wide range of climatic, environmental, and edaphic variables. The contrasting responses of SOC to N addition indicate the importance of considering deep soil layers, particularly for long‐term continuous N deposition. Finally, the lack of depth‐dependent SOC responses to N addition in experimental and modeling frameworks has likely resulted in the overestimation of changes in SOC storage under enhanced N deposition.
Rethinking ‘causality’ in quantitative human geography
Authors: Zhang Jing , Wolf Levi John
Published: March 2024

Causality is at the core of much contemporary discussion in social sciences, philosophy, and computer science—from the establishment of basic definitions of causality to developing methods for causal inference, this discussion is increasingly finding voice within geographical literature. However, geographers have long discussed (and differed) about the role “causality” plays in our work. We present a history of contemporary definitions of causality arising from philosophy and examine how these intellectual currents interact with past and present geographical thinking about causal relations. In particular, we focus on how new thinking about counterfactual causality can help re‐route inquiry around a well‐known impasse: law‐based causality in geography. In other words, while different perspectives around “laws” of geography exist, we argue that it is more productive to put aside these differences and find common ground in counterfactual causal thinking. To demonstrate, we outline new kinds of scholarship enabled by counterfactual causality and contemporary challenges that counterfactual causality faces in spatial analysis. Throughout, we refer interested readers to contemporary work on spatial causal inference and methods useful for scholars interested in analysing causal relationships in geographical systems.
Integrated crop‐livestock versus conventional systems: Effects on the chemical and physical characteristics of an Oxisol
Authors: Augusto Jeferson Garcia , de Paz Claudia Cristina Paro , Mendonça Gabriela Geraldi , Moitinho Mara Regina , Menegatto Leonardo Sartori , Bolonhezi Denizart , Salles Márcia Saladini Vieira , Simili Flávia Fernanda
Published: March 2024

Studies have reported improvements in soil quality in integrated crop‐livestock systems (ICLS) when compared to conventional systems. The hypothesis of this study was that ICLS improve Oxisol quality due to the use of intercropping, adding pasture and cattle to the systems. The aim of the study was to evaluate the chemical and physical characteristics of an Oxisol and pasture production in the integrated system versus conventional system. We compared two conventional systems: crop system (maize grain production) and livestock system (beef cattle on single pasture) and, four ICLS: maize plus Marandu palisade grass sown simultaneously without herbicide (ICLS‐1); maize plus Marandu palisade grass sown simultaneously with herbicide (ICLS‐2); maize plus Marandu palisade grass in lagged sowing (ICLS‐3); and maize plus Marandu palisade grass sown simultaneously in maize rows and inter‐rows with herbicide (ICLS‐4). A randomized block design with six treatments and three replicates was used. The results suggest improvements in soil quality, including soil organic carbon (ICLS‐4), total nitrogen, and nitrogen stocks (ICLS‐1, ICLS‐2, and ICLS‐4). The intercropping technique influenced pasture production and soil quality during the implementation of integrated systems. The lowest soil strength was obtained for the crop system compared to systems with grazing animals but there were no changes in the soil physical characteristics that could compromise the production system.
Dandruff lesional scalp skin exhibits epidermal T cell infiltration and a weakened hair follicle immune privilege
Authors: Limbu Susan L. , Purba Talveen S. , Harries Matthew , Kundu Rhia , Bhogal Ranjit K. , Paus Ralf
Published: March 2024

Objective

Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff‐affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff‐affected scalp skin.

Methods

We assessed relevant key parameters in healthy versus dandruff‐affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing.

Results

The number of epidermal CD4+ and CD8+ T cells was increased in lesional dandruff scalp skin, while the number of MHC class II+/CD1a+ Langerhans cells was decreased in the infundibulum. The number of intrafollicular and perifollicular CD4+ T cells and CD8+ T cells, perifollicular CD68+ macrophages, and tryptase+ mast cells remained unchanged. Interestingly, MHC class Ia and ß2‐microglobulin protein expression were significantly increased specifically in the suprabulbar outer root sheath (ORS) compartment of dandruff‐associated HFs. RNAseq analysis of laser capture micro‐dissected suprabulbar ORS compartment revealed antigen presentation pathway as the top regulated canonical pathway, along with the upregulation of HF‐IP genes such as HLA‐C, HLA‐DP, and TAP1, which are normally down‐regulated in healthy HFs. Intrafollicular protein expression of known HF IP guardians (CD200 and α‐MSH) and ‘danger signals’ (MICA and CXCL10) remained unaltered at the IP sites of dandruff lesional HFs compared to non‐lesional and healthy HFs. Instead, the expression of macrophage migration inhibiting factor (MIF), another HF IP guardian, was reduced.

Conclusion

Together, this work shows that dandruff is associated with epidermal T‐cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp.
Consumer embarrassment: A systematic literature review and research agenda
Authors: Sangwan Vaishali , Maity Moutusy
Published: March 2024

Embarrassment plays a crucial role in shaping the consumer landscape by influencing perceptions, choices, and experiences. In a marketplace, customers get embarrassed when personally implicated in transgressions, and also vicariously, while observing the predicament of others. Vicarious embarrassment, though ubiquitous and detrimental for firms, has received limited attention in marketing scholarship. This article offers a comprehensive review of consumers' personal and vicarious embarrassment by incorporating content and bibliometric analysis methodologies. The bibliometric study comprises a review of 203 articles published from 1900 to 2022. Techniques of citation analysis and co‐citation analysis reveal the prominent authors, journals, and articles and trace the intellectual structures of thoughts contributing to the domain. Additionally, social network analysis delineates the centrality features of the leading studies in the consumer embarrassment domain. Further, the article provides a comprehensive content analysis of 109 studies relevant to the purchase and consumption contexts. A review of the extant findings on major theoretical perspectives, triggers, coping strategies, moderators, and desirable and adverse outcomes of personal and vicarious embarrassment is presented. The article offers actionable future research directions for theoretical advancement of the phenomenon of consumer embarrassment. This research will assist firms and marketers in understanding and mitigating the aversive outcomes of embarrassment.
Dual envy influences online shoppers' intention to purchase luxury counterfeits
Authors: Gupta Tanvi , Lyndem Preeti Krishnan
Published: March 2024

Envy fuels luxury consumption—both real and fake. Through three studies, we show that benign envy motivates online shoppers to purchase authentic luxury products, whereas malicious envy encourages counterfeiting. By triggering envy through its antecedents of deservingness and pride, we show that benign (malicious) envy motivates a general tendency towards moral (immoral) behavior, which has distinct downstream effects on consumer attitude towards luxury. Benign envy increases belief in the moral virtue of hard work, thereby inspiring consumers to aspire and strive for original luxury products. Whereas malicious envy triggers moral disengagement—dissolving the moral dilemma associated with counterfeiting. Malicious envy also makes consumers appraise luxury corporations as immoral—fueling the desire to punish the brand through counterfeiting. The effects hold for both brand‐generated envy and incidental envy. The findings have important implications for luxury branding to help control consumer demand for counterfeits.
Polygenic adaptation of a cosmopolitan pest to a novel thermal environment
Authors: Lei Gaoke , Huang Jieling , Zhou Huiling , Chen Yanting , Song Jun , Xie Xuefeng , Vasseur Liette , You Minsheng , You Shijun
Published: March 2024

The fluctuation in temperature poses a significant challenge for poikilothermic organisms, notably insects, particularly in the context of changing climatic conditions. In insects, temperature adaptation has been driven by polygenes. In addition to genes that directly affect traits (core genes), other genes (peripheral genes) may also play a role in insect temperature adaptation. This study focuses on two peripheral genes, the GRIP and coiled‐coil domain containing 2 (GCC2) and karyopherin subunit beta 1 (KPNB1). These genes are differentially expressed at different temperatures in the cosmopolitan pest, Plutella xylostella. GCC2 and KPNB1 in P. xylostella were cloned, and their relative expression patterns were identified. Reduced capacity for thermal adaptation (development, reproduction and response to temperature extremes) in the GCC2‐deficient and KPNB1‐deficient P. xylostella strains, which were constructed by CRISPR/Cas9 technique. Deletion of the PxGCC2 or PxKPNB1 genes in P. xylostella also had a differential effect on gene expression for many traits including stress resistance, resistance to pesticides, involved in immunity, trehalose metabolism, fatty acid metabolism and so forth. The ability of the moth to adapt to temperature via different pathways is likely to be key to its ability to remain an important pest species under predicted climate change conditions.
Chronic hepatitis B care in regional Australia: implications for clinical practice and public health policy
Authors: Han Chaw , Karamatic Rozemary , Hanson Josh
Published: March 2024

Background

Australia is struggling to meet its National Hepatitis B Strategy care targets, particularly in nonmetropolitan settings. It is vital to engage priority populations and improve their access to recommended care to reach these targets.

Aims

This retrospective study examined people living with chronic hepatitis B (CHB) in regional North Queensland, Australia, and determined whether their care adhered to current national CHB management guidelines. The analysis aimed to identify gaps in care that might be addressed to improve future outcomes.

Methods

All individuals referred to the gastroenterology clinic at the Townsville University Hospital in regional North Queensland, Australia, for CHB care between January 2015 and December 2020 were identified. Their linkage to care, engagement in care and receipt of guideline‐recommended CHB care were determined.

Results

Of 255 individuals, 245 (96%) were linked to care; 108 (42%) remained engaged in care and 86 (38%) were receiving guideline‐recommended care in 2021. There were 91/255 (36%) who identified as Indigenous Australians. Indigenous status was the only independent predictor of not being linked to care (odds ratio (OR): 0.13 (95% confidence interval (CI): 0.03–0.60), P = 0.01), not being engaged in care (OR: 0.19 (95% CI: 0.10–0.36), P < 0.0001), not receiving guideline‐recommended CHB care (OR: 0.16 (95% CI: 0.08–0.31), P < 0.0001) or not being engaged in a hepatocellular carcinoma surveillance programme (OR: 0.08 (95% CI: 0.02–0.27), P < 0.0001).

Conclusion

Current approaches are failing to deliver optimal CHB care to Indigenous Australians in regional North Queensland. Targeted strategies to ensure that Indigenous Australians in the region receive equitable care are urgently needed.
Epigenetic control of microglial immune responses
Authors: Scholz Rebekka , Brösamle Desirée , Yuan Xidi , Beyer Marc , Neher Jonas J.
Published: March 2024

Microglia, the major population of brain‐resident macrophages, are now recognized as a heterogeneous population comprising several cell subtypes with different (so far mostly supposed) functions in health and disease. A number of studies have performed molecular characterization of these different microglial activation states over the last years making use of “omics” technologies, that is transcriptomics, proteomics and, less frequently, epigenomics profiling. These approaches offer the possibility to identify disease mechanisms, discover novel diagnostic biomarkers, and develop new therapeutic strategies. Here, we focus on epigenetic profiling as a means to understand microglial immune responses beyond what other omics methods can offer, that is, revealing past and present molecular responses, gene regulatory networks and potential future response trajectories, and defining cell subtype‐specific disease relevance through mapping non‐coding genetic variants. We review the current knowledge in the field regarding epigenetic regulation of microglial identity and function, provide an exemplary analysis that demonstrates the advantages of performing joint transcriptomic and epigenomic profiling of single microglial cells and discuss how comprehensive epigenetic analyses may enhance our understanding of microglial pathophysiology.
Group 3 innate lymphoid cells: A trained Gutkeeper
Authors: Serafini Nicolas , Di Santo James P.
Published: March 2024

Group 3 innate lymphoid cells (ILC3s) are tissue‐resident immune lymphocytes that critically regulate intestinal homeostasis, organogenesis, and immunity. ILC3s possess the capacity to “sense” the inflammatory environment within tissues, especially in the context of pathogen challenges that imprints durable non‐antigen‐specific changes in ILC3 function. As such, ILC3s become a new actor in the emerging field of trained innate immunity. Here, we summarize recent discoveries regarding ILC3 responses to bacterial challenges and the role these encounters play in triggering trained innate immunity. We further discuss how signaling events throughout ILC3 ontogeny potentially control the development and function of trained ILC3s. Finally, we highlight the open questions surrounding ILC3 “training” the answers to which may reveal new insights into innate immunity. Understanding the fundamental concepts behind trained innate immunity could potentially lead to the development of new strategies for improving immunity‐based modulation therapies for inflammation, infectious diseases, and cancer.
Spawn and development of the olivid gastropod Olivancillaria carcellesi from north Patagonia, Argentina
Authors: Zabala Soledad , Teso Valeria , Penchaszadeh Pablo E. , Averbuj Andrés
Published: March 2024

Olivancillaria carcellesi occurs in shallow sandy shores from north Patagonia, in intertidal and subtidal sandy bottoms. Females of O. carcellesi exhibited a remarkable specificity for spawning on the shells of living males and females, indiscriminately, of the buccinanopsid Buccinastrum deforme, measuring 26.9 ± 4.7 mm in shell length. The egg capsule was semispherical and attached to B. deforme shells by a small elliptical and wide base. The capsule was translucid when spawned, with a thick and semirigid wall and a hatching aperture of 1.8 ± 0.1 mm (n = 111) in diameter. Each egg capsule contained a single egg that measured 1367 ± 34 μm (n = 5) in diameter before cleavage. The embryo developed a small bilobed velum and an operculum, which were both lost before hatching as a crawling juvenile of 1762 ± 47 μm (n = 28) in shell length. As in other species in the genus, the eggs of O. carcellesi are among the largest in the caenogastropods with direct development. The time from oviposition to hatching is estimated to be approximately 6 months.
Factors influencing the oral health behaviour of Dutch adolescents with mild to borderline intellectual disabilities living in residential care: A qualitative study
Authors: Kalf‐Scholte Sonja M. , van Zoonen Renate , Sijperda‐Abdul Dina , Algra Henk , Valkenburg Cees
Published: March 2024

Background

Toothbrushing, limiting intake frequency, and scheduled visits to an oral healthcare professional (OHP) are key for good oral health. We aimed to explore factors influencing these oral health behaviours in Dutch adolescents with mild to borderline intellectual disabilities (MBID) in residential care.

Method

Using a qualitative, descriptive approach, we conducted focus groups and interviews with 12 adolescents, 9 counsellors, and 6 OHPs. Thematic analysis mapped factors influencing adolescents' knowledge, attitude, planning, and execution of oral health behaviours to oral care stakeholders.

Results

Of nine identified influencing factors, three were pivotal: Structure (influencing toothbrushing and intake frequency), Anxiety (impeding dental visits), and Support (provided by counsellors).

Conclusions

Counsellors should provide structured daily guidance on oral hygiene and diet for adolescents with MBID, while respecting the adolescents' autonomy. As intermediaries between adolescents and OHPs, counsellors are key in reducing dental anxiety. Counsellors need clear oral health policies within care facilities to address competing priorities.