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Abstract Purpose It is a central goal in current ecology to investigate the effects of global changes on ecosystem productivity, which includes above- and below-ground plant productivity as well as soil microbial productivity, but most studies focus on aboveground plant productivity. As plant and microbial communities have different attributes, it is intuitive to hypothesize that belowground plant root productivity will respond to global changes more similarly as aboveground stem/leaf productivity than soil microbial productivity; however, this hypothesis remains largely unexplored. Methods Here we conducted a long-term nitrogen deposition experiment in the Eurasian steppe, manipulating nine rates (0–50 g N m− 2 yr− 1) at two frequencies under two management strategies (fencing or mowing). Results Belowground plant productivity was found to respond similarly as soil microbial productivity rather than aboveground plant productivity, contrary to the hypothesis. And this pattern was more obvious under mowing than fencing, because mowing decreased soil water content and caused another pressure beyond the decreased pH induced by N addition. Conclusions Overall, our results demonstrated the importance of microhabitat (below- or above-ground) relative to community attribute (plants or microorganisms) in determining productivity response to nitrogen deposition, emphasizing the necessity to integratively study the response of both above- and below-ground productivities to global changes.

Abstract Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (f NO3-), ammonium (f NH4+), and organic N (f EON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of f NO3-, f NH4+, and f EON. The f NO3- increases with MAT, reaching 46% at 28.5 °C. The f NH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the f EON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Soil nematodes are among the most significant soil-dwelling organisms in forest ecosystems. However, the factors that shape the distribution of soil nematodes are still not well explored. Therefore, we collected soil samples from 20 forest sites along the eastern transect of China and sequenced 18S rRNA V9 region to reveal the biodiversity of soil nematodes. Our study found that soil nematode richness is higher in temperate mixed needleleaf and broadleaf forests compared with the other four vegetation regions. Soil physiochemical properties overrode climatic factors to be the primary drivers of soil nematode richness and community composition. Importantly, the soil nematode richness significantly enhanced ecosystem multifunctionality, especially bacterial biomass and enzyme activities, with a determination coefficient (r2) of 0.23, suggesting that soil nematodes played essential roles in the forest ecosystem.

Maize residue retention is an effective agricultural practice for improving soil fertility in black soil region, where suffered from long freezing-thawing periods and intense freeze-thawing (FT) cycles. However, very few studies have examined the influence of maize residue retention on soil microbial communities under FT cycles. We investigated the response of soil microbial communities and co-occurrence networks to maize residue retention at different FT intensities over 12 cycles using a microcosm experiment conditioned in a temperature incubator. Our results indicated that maize residue retention induced dramatic shifts in soil archaeal, bacterial and fungal communities towards copiotroph-dominated communities. Maize residue retention consistently reduced soil fungal richness across all cycles, but this effect was weaker for archaea and bacteria. Normalized stochastic ratio analysis revealed that maize residue retention significantly enhanced the deterministic process of archaeal, bacterial and fungal communities. Although FT intensity significantly impacted soil respiration, it did not induce profound changes in soil microbial diversity and community composition. Co-occurrence network analysis revealed that maize residue retention simplified prokaryotic network, while did not impact fungal network complexity. The network robustness index suggested that maize residue retention enhanced the fungal network stability, but reduced prokaryotic network stability. Moreover, the fungal network in severe FT treatment harbored the most abundant keystone taxa, mainly being cold-adapted fungi. By identifying modules in networks, we observed that prokaryotic Module #1 and fungal Module #3 were enhanced by maize residue retention and contributed greatly to soil quality. Together, our results showed that maize residue retention exerted stronger influence on soil microbial communities and co-occurrence network patterns than FT intensity and highlighted the potential of microbial interactions in improving soil functionality.

Summary: The cerebral cortex is widely considered part of the neural substrate of consciousness, but direct causal evidence is missing. Here, we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.

Purpose: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model. Methods: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education–accredited LGG fellowship programs at the time. The data were collected, and the responses were aggregated for each question. Results: All of the responding PDs had started training at least 1 LGG fellow. PDs noted challenges with funding, staff shortages, molecular/cytogenetics content integration, limited total training time, increased remote work, increased sendout testing, and a lack of prior cytogenetics knowledge among incoming fellows. Conclusion: This survey attempted to assess the challenges that LGG PDs have been facing in offering and integrating clinical molecular genetics and clinical cytogenetics fellowship training. Common challenges between programs were noted, and a set of 6 concluding comments are provided to facilitate future discussion.

Boreal peatlands, a crucial stock of dissolved organic matter (DOM), are susceptible to increased reactive nitrogen (N) inputs. However, the response of DOM characteristics to elevated N availability in these ecosystems is still obscure. Here, we investigated the seasonal variability of DOM quantity and characteristics in surface water and soil pore water after 5-year multi-level N addition (0, 3, 6, and 12 g N m−2 year−1) in a permafrost peatland of Northeast China. In this study, we used the excitation-emission matrix fluorescent spectroscopy combined with fluorescence regional integration, parallel factor analysis, and fluorescence parameters to decipher the effects of N addition on DOM composition, origin, and fate. Irrespective of N addition level, increased N availability reduced dissolved organic carbon concentrations in surface water and soil pore water. However, DOM characteristics are more responsive to N addition in soil pore water than in surface water. Nitrogen addition did not affect DOM composition in surface water, but altered the proportions of tyrosine-, tryptophan-, fulvic acid-, and humic-like DOM in soil pore water. Moreover, the changing trends of DOM composition were diverse during the growing season. In addition, compositional transformations of DOM did not change its biogenic signals, freshness, and humification in both surface water and soil pore water across the growing season. Our results suggest that increased N availability reduces DOM quantity and alters DOM chemical composition, which will improve our understanding of soil organic matter dynamics in boreal peatlands.

Abstract Background Nutrient resorption is an important plant nutrient conservation strategy in wetlands. However, how shrub encroachment alters plant nutrient resorption processes is unclear in temperate wetlands. Here, we collected green and senesced leaves of common sedge, grass, and shrub species in wetlands with high (50–65%) and low (20–35%) shrub covers in the Sanjiang Plain of Northeast China, and assessed the impact of shrub encroachment on leaf nitrogen (N) and phosphorus (P) resorption efficiency and proficiency at both plant growth form and community levels. Results The effects of shrub cover on leaf nutrient resorption efficiency and proficiency were identical among shrubs, grasses, and sedges. Irrespective of plant growth forms, increased shrub cover reduced leaf N resorption efficiency and proficiency, but did not alter leaf P resorption efficiency and proficiency. However, the effect of shrub cover on leaf nutrient resorption efficiency and proficiency differed between plant growth form and community levels. At the community level, leaf N and P resorption efficiency decreased with increasing shrub cover because of increased dominance of shrubs with lower leaf nutrient resorption efficiency over grasses and sedges. Accordingly, community-level senesced leaf N and P concentrations increased with elevating shrub cover, showing a decline in leaf N and P resorption proficiency. Moreover, the significant relationships between leaf nutrient resorption efficiency and proficiency indicate that shrub encroachment increased senesced leaf nutrient concentrations by decreasing nutrient resorption efficiency. Conclusions These observations suggest that shrub encroachment reduces community-level leaf nutrient resorption efficiency and proficiency and highlight that the effect of altered plant composition on leaf nutrient resorption should be assessed at the community level in temperate wetlands.

The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non–SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non–SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs). Samples positive for anti-cytokine antibodies were tested for receptor blocking activity using cell-based functional assays. Anti-cytokine antibodies were identified in > 50% of patients across all 5 acutely ill cohorts. In critically ill patients, anti-cytokine antibodies were far more common in infected versus uninfected patients. In cell-based functional assays, 11 of 39 samples positive for select anti-cytokine antibodies displayed receptor blocking activity against surface receptors for Type I IFN, GM-CSF, and IL-6. Autoantibodies against CTD-associated autoantigens were also commonly observed, including newly detected antibodies that emerged in longitudinal samples. These findings demonstrate that anti-cytokine and autoantibodies are common across different viral and nonviral infections and range in severity of illness.

Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.

Northern peatlands have undergone widespread expansion of nitrogen (N)-fixing woody plants such as alder species. However, how alder expansion alters soil microbial necromass carbon (C) is unclear in these ecosystems. We compared the differences in soil stoichiometric ratios among C, nitrogen (N), and phosphorus (P), microbial biomass C (MBC) and N (MBN), basal respiration rate, net N mineralization rate, glucosamine, muramic acid, and galactosamine at 0–10 cm, 10–20 cm, and 20–40 cm layers between Alnus sibirica patches (alder patches) and open peatlands in a permafrost peatland in the Heilongjiang Province of China, and assessed the impact of alder expansion on soil bacterial, fungal, and total necromass C in this peatland. Compared with open peatlands, alder patches have lower C:N ratio at each soil layer but have higher C:P ratio at 10–20 cm layer. Across soil layers, alder patches had higher soil MBC, MBN, basal respiration rate, and net N mineralization rate, but lower soil MBC:MBN ratio than open peatlands. Moreover, alder expansion enhanced the concentrations of glucosamine and muramic acid at 0–10 cm layer, but only increased muramic acid concentration at 20–40 cm layer. Accordingly, soil bacterial, fungal, and total necromass C were increased by alder expansion at 0–10 cm layer, whereas only soil bacterial necromass C was enhanced at 20–40 cm layer. In addition, bacterial necromass C correlated negatively with both soil C:N and MBC:MBN ratios. These results suggest that alder expansion promotes microbial necromass C accumulation in surface soils, and highlight that altered C:N stoichiometry drives alder expansion-induced shifts in soil bacterial necromass C in northern peatlands.

Abstract Background Angelman syndrome (AS) occurs due to a lack of expression or function of the maternally inherited UBE3A gene. Individuals with AS typically have significant developmental delay, severe speech impairment with absent to minimal verbal language, gait abnormalities including ataxia, and an incongruous happy demeanor. The majority of individuals with AS also have seizures and microcephaly. Some individuals with mosaic AS have been reported to have expressive language and milder levels of developmental delay. Case Report We report a male patient presenting with mild to moderate intellectual disability, hyperphagia, obesity, and the ability to communicate verbally. His phenotype was suggestive of Prader‐Willi syndrome. However, methylation testing was positive for Angelman syndrome and additional methylation specific multiplex ligation‐dependent amplification (MS‐MLPA) study revealed low‐level mosaicism for AS. Conclusion A broader phenotypic spectrum should be considered for AS as patients with atypical presentations may otherwise elude diagnosis.

Mendelian disorders are prevalent in neonatal and pediatric intensive care units and are a leading cause of morbidity and mortality in these settings. Current diagnostic pipelines that integrate phenotypic and genotypic data are expert-dependent and time-intensive. Artificial intelligence (AI) tools may help address these challenges. Dx29 is an open-source AI tool designed for use by clinicians. It analyzes the patient’s phenotype and genotype to generate a ranked differential diagnosis. We used Dx29 to retrospectively analyze 25 acutely ill infants who had been diagnosed with a Mendelian disorder, using a targeted panel of ~5000 genes. For each case, a trio (proband and both parents) file containing gene variant information was analyzed, alongside patient phenotype, which was provided to Dx29 by three approaches: (1) AI extraction from medical records, (2) AI extraction with manual review/editing, and (3) manual entry. We then identified the rank of the correct diagnosis in Dx29’s differential diagnosis. With these three approaches, Dx29 ranked the correct diagnosis in the top 10 in 92–96% of cases. These results suggest that non-expert use of Dx29’s automated phenotyping and subsequent data analysis may compare favorably to standard workflows utilized by bioinformatics experts to analyze genomic data and diagnose Mendelian diseases.

Abstract In studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we explore effective guidelines for variant (SNP and INDEL) filtering and report the expected number of candidates for de novo dominant, recessive, and autosomal dominant modes of inheritance. We derived these guidelines using two large family-based cohorts that underwent whole-genome sequencing, as well as two family cohorts with whole-exome sequencing. The filters are applied to common attributes, including genotype-quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield ~10 candidate SNP and INDEL variants per exome, and 18 per genome for recessive and de novo dominant modes of inheritance, with substantially more candidates for autosomal dominant inheritance. For family-based, whole-genome sequencing studies, this number includes an average of three de novo, ten compound heterozygous, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at https://github.com/brentp/slivar under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis.

Abstract Background Genetic disorders contribute to significant morbidity and mortality in critically ill newborns. Despite advances in genome sequencing technologies, a majority of neonatal cases remain unsolved. Complex structural variants (SVs) often elude conventional genome sequencing variant calling pipelines and will explain a portion of these unsolved cases. Methods As part of the Utah NeoSeq project, we used a research‐based, rapid whole‐genome sequencing (WGS) protocol to investigate the genomic etiology for a newborn with a left‐sided congenital diaphragmatic hernia (CDH) and cardiac malformations, whose mother also had a history of CDH and atrial septal defect. Results Using both a novel, alignment‐free and traditional alignment‐based variant callers, we identified a maternally inherited complex SV on chromosome 8, consisting of an inversion flanked by deletions. This complex inversion, further confirmed using orthogonal molecular techniques, disrupts the ZFPM2 gene, which is associated with both CDH and various congenital heart defects. Conclusions Our results demonstrate that complex structural events, which often are unidentifiable or not reported by clinically validated testing procedures, can be discovered and accurately characterized with conventional, short‐read sequencing and underscore the utility of WGS as a first‐line diagnostic tool.

Dissolved organic matter (DOM) plays an indispensable role in ecosystem services and functions in wetlands. While most wetlands have undergone increased nitrogen (N) loading due to intensive human activities, the response of DOM characteristics to long-term N addition remains unexplored. In this study, we assessed the changes in dissolved organic carbon (DOC), NH4+, NO3-, dissolved organic N (DON), dissolved total N (DTN), and dissolved total phosphorus (DTP) in surface water and soil pore water at 15 cm depth after 10 years of N addition at four levels (0, 60, 120, and 240 kg N hm−2 year−1) in a freshwater marsh of Northeast China. We also examined the effect of N addition on DOM aromaticity and humification by measuring the specific UV absorbance at 254 nm (SUVA254), the color per C unit (C/C ratio), and the fulvic acid/humic acid ratio (E4/E6 ratio). Our results showed that N addition significantly altered DOM properties, but the direction and magnitude of these changes generally did not vary with the N addition level. During the growing season, DOC, NH4+, NO3-, DON, and DTN concentrations in both surface water and soil pore water were increased by N addition. Accordingly, N addition increased the DOC/DTP and DTN/DTP ratios but decreased the DOC/DTN ratio in surface water and soil pore water. In addition, the SUVA254 value and C/C ratio increased, while the E4/E6 ratio reduced after N addition in surface water and soil pore water, indicating increases in DOM aromaticity and humification. These observations suggest that long-term N addition changes DOM characteristics by causing stoichiometric imbalances and increasing recalcitrant compounds in temperate freshwater wetlands, which may then deteriorate water quality, alter microbial-mediated ecological processes, and impact downstream aquatic ecosystem structures.

This paper investigates whether corporate social responsibility active (CSR active) firms operate dissimilarly from other firms in their financial reporting. Specifically, we examine whether the corporate social responsibility (CSR) attitude of a firm sways its reporting incentives, in respect of the extent of earning management. To test our predictions, we use a sample of 25,861 year-company observations, corresponding to 3538 Chinese listed companies, for the period 2009–2019. We find a significant positive association between CSR activity and earning management assessed by the level of discretionary accruals in Chinese listed companies. Moreover, we document that Chinese CSR active firms engage more in earnings management through discretionary accruals than CSR inactive firms. These findings are consistent with the opportunistic financial reporting hypothesis: advances in CSR used by managers to safeguard their position by evading scrutiny from stakeholder activists. This study contributes to the growing awareness among investors, stakeholders and researchers that we should distinguish between CSR active firms and socially responsible firms and that being the latter entail something more than just mechanically produce CSR reports.

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Abstract Quantifying soil organic carbon (SOC) changes is a fundamental issue in ecology and sustainable agriculture. However, the algorithm‐derived biases in comparing SOC status have not been fully addressed. Although the methods based on equivalent soil mass (ESM) and mineral‐matter mass (EMMM) reduced biases of the conventional methods based on equivalent soil volume (ESV), they face challenges in ensuring both data comparability and accuracy of SOC estimation due to unequal basis for comparison and using unconserved reference systems. We introduce the basal mineral‐matter reference systems (soils at time zero with natural porosity but no organic matter) and develop an approach based on equivalent mineral‐matter volume (EMMV). To show the temporal bias, SOC change rates were recalculated with the ESV method and modified methods that referenced to soils at time t1 (ESM, EMMM, and EMMV‐t1) or referenced to soils at time zero (EMMV‐t0) using two datasets with contrasting SOC status. To show the spatial bias, the ESV‐ and EMMV‐t0‐derived SOC stocks were compared using datasets from six sites across biomes. We found that, in the relatively C‐rich forests, SOC accumulation rates derived from the modified methods that referenced to t1 soils and from the EMMV‐t0 method were 5.7%–13.6% and 20.6% higher than that calculated by the ESV method, respectively. Nevertheless, in the C‐poor lands, no significant algorithmic biases of SOC estimation were observed. Finally, both the SOC stock discrepancies (ESV vs. EMMV‐t0) and the proportions of this unaccounted SOC were large and site‐dependent. These results suggest that although the modified methods that referenced to t1 soils could reduce the biases derived from soil volume changes, they may not properly quantify SOC changes due to using unconserved reference systems. The EMMV‐t0 method provides an approach to address the two problems and is potentially useful since it enables SOC comparability and integrating SOC datasets.

It is well-known that relative growth rate (RGR) is closely related to C:N:P stoichiometry at the whole-plant level, yet it remains a misgiving to determine whether the growth-rate hypothesis is consistent between plant organs. Here, we examined RGR, C, N, P concentrations and their ratios of N:C, P:C, and N:P for four marsh herbaceous species (two gramineous species, Deyeuxia angustifolia and Glyceria spiculosa; two sedge species, Carex pseudocuraica and Carex lasiocarpa) grown in an increasing water level gradient (−5, 0, +5, and +15 cm relative to the soil surface) in the Sanjiang Plain of Northeast China. The applicability of the growth-rate hypothesis to leaf, stem, root, and total biomass was subsequently tested. With the increase of flooding stress, RGR and root mass ratio decreased to a certain degree for all species, whereas the above-ground biomass allocation was increased. The variation of N was much greater than that of P; hence the change in N:P ratios was determined mainly by N concentration. RGR was positively correlated with N concentration, N:C, and N:P for stem and total biomass when the data were pooled for all species but was negatively correlated with those for leaf and root organs. Furthermore, the theoretical predictions regarding the relationship between RGR and nutrient ratios were not always the case for each of the marsh herbs. Therefore, our results indicated that the organ-specific and species-specific for vascular plants should be carefully considered when using the theoretical association of growth rate with C:N:P stoichiometry.

Biotinidase deficiency is an autosomal recessive disorder in which affected individuals are unable to recycle biotin. Untreated, children usually exhibit hypotonia, seizures, ataxia, developmental delay, and/or hearing loss. Individuals diagnosed by newborn screening have an excellent prognosis with life-long biotin supplementation. We report a young adult diagnosed with profound biotinidase deficiency by newborn screening who was asymptomatic while on therapy. At 18 years of age, 6 months after voluntarily discontinuation of biotin, he developed a progressive distal muscle weakness. Molecular analysis of the BTD gene showed a pathogenic homozygous duplication c.1372_1373dupT p.(Cys458LeufsTer26) (1). Despite 16 months since reintroduction of biotin, muscle strength only partially recovered. Transition to adulthood in chronic metabolic diseases is known to be associated with an increased risk for non-compliance. Neurological findings in this adult are similar to those described in others with adult-onset biotinidase deficiency. Long-term prognosis in non-compliant symptomatic adult with biotinidase deficiency likely depends on the delay and/or severity of intervening symptoms until reintroduction of biotin.

Abstract Background Exome/genome sequencing (ES/GS) have been recently used in neonatal and pediatric/cardiac intensive care units (NICU and PICU/CICU) to diagnose and care for acutely ill infants, but the effectiveness of targeted gene panels for these purposes remains unknown. Methods RapSeq, a newly developed panel targeting 4,503 disease‐causing genes, was employed on selected patients in our NICU/PICU/CICU. Twenty trios were sequenced from October 2015 to March 2017. We assessed diagnostic yield, turnaround times, and clinical consequences. Results A diagnosis was made in 10/20 neonates (50%); eight had de novo variants (ASXL1, CHD, FBN1, KMT2D, FANCB, FLNA, PAX3), one was a compound heterozygote for CHAT, and one had a maternally inherited GNAS variant. Preliminary reports were generated by 9.6 days (mean); final reports after Sanger sequencing at 16.3 days (mean). In all positive infants, the diagnosis changed management. In a case with congenital myasthenia, diagnosis and treatment occurred at 17 days versus 7 months in a historical control. Conclusions This study shows that a gene panel that includes the majority of known disease‐causing genes can rapidly identify a diagnosis in a large number of tested infants. Due to simpler deployment and interpretation and lower costs, this approach might represent an alternative to ES/GS in the NICU/PICU/CICU.

Decomposition of litter mixtures generally cannot be predicted from the component species incubated in isolation. Therefore, such non-additive effects of litter mixing on soil C and N dynamics remain poorly understood in terrestrial ecosystems. In this study, litters of Mongolian pine and three dominant understory species and soil were collected from a Mongolian pine plantation in Northeast China. In order to examine the effects of mixed-species litter on soil microbial biomass N, soil net N mineralization and soil respiration, four single litter species and their mixtures consisting of all possible 2-, 3- and 4-species combinations were added to soils, respectively. In most instances, species mixing produced synergistic non-additive effects on soil microbial biomass N and soil respiration, but antagonistic non-additive effects on net N mineralization. Species composition rather than species richness explained the non-additive effects of species mixing on soil microbial biomass N and net N mineralization, due to the interspecific differences in litter chemical composition. Both litter species composition and richness explained non-additive soil respiration responses to mixed-species litter, while litter chemical diversity and chemical composition did not. Our study indicated that litter mixtures promoted soil microbial biomass N and soil respiration, and inhibited net N mineralization. Soil N related processes rather than soil respiration were partly explained by litter chemical composition and chemical diversity, highlighting the importance of functional diversity of litter on soil N cycling.

A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.

Tubulocystic renal cell carcinoma (TRCC) is an indolent type of renal cell carcinoma with a good prognosis based on the limited number of published cases. Herein, we describe the unusual clinical, pathologic and molecular findings in a case of TRCC. Our patient with TRCC had two local recurrences and a brain metastasis following radical nephrectomy. Unusual histologic findings included focal solid growth pattern and cytologic atypia. A genome-wide molecular inversion probe assay identified copy number (CN) loss in three chromosome regions and one region with copy-neutral loss of heterozygosity (copy-neutral LOH). Copy number variations (CNVs) were observed (chromosomes 4p16.1 and 17q21.31-q21.32) in both the tumor and the normal tissue, and most likely represents benign variations. The loss of entire chromosomes 9, 18 and 15 and copy-neutral LOH involving 6p22.1 was observed only in the tumor. The presence of these clinical, pathologic and molecular findings could be related to an increased risk for tumor recurrence and poor prognosis. The novel molecular findings described in TRCC might represent new targets for novel therapies.

Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons.

This study aims to evaluate the impacts of changes in litter quantity under simulated N deposition on litter decomposition, CO2 release, and soil C loss potential in a larch plantation in Northeast China. We conducted a laboratory incubation experiment using soil and litter collected from control and N addition (100 kg ha-1 year-1 for 10 years) plots. Different quantities of litter (0, 1, 2 and 4 g) were placed on 150 g soils collected from the same plots and incubated in microcosms for 270 days. We found that increased litter input strongly stimulated litter decomposition rate and CO2 release in both control and N fertilization microcosms, though reduced soil microbial biomass C (MBC) and dissolved inorganic N (DIN) concentration. Carbon input (C loss from litter decomposition) and carbon output (the cumulative C loss due to respiration) elevated with increasing litter input in both control and N fertilization microcosms. However, soil C loss potentials (C output-C input) reduced by 62% in control microcosms and 111% in N fertilization microcosms when litter addition increased from 1 g to 4 g, respectively. Our results indicated that increased litter input had a potential to suppress soil organic C loss especially for N addition plots.

Background/Objectives. To identify copy number variants (CNVs) which are associated with body mass index (BMI). Subjects/Methods. CNVs were identified using array comparative genomic hybridization (aCGH) on members of pedigrees ascertained through severely obese (BMI ≥ 35 kg/m2) sib pairs (86 pedigrees) and thin (BMI ≤ 23 kg/m2) probands (3 pedigrees). Association was inferred through pleiotropy of BMI with CNV log⁡2 intensity ratio. Results. A 77-kilobase CNV on chromosome 20q13.3, confirmed by real-time qPCR, exhibited deletions in the obese subjects and duplications in the thin subjects (P=2.2×10-6). Further support for the presence of a deletion derived from inference by likelihood analysis of null alleles for SNPs residing in the region. Conclusions. One or more of 7 genes residing in a chromosome 20q13.3 CNV region appears to influence BMI. The strongest candidate is ARFRP1, which affects glucose metabolism in mice.

The Cognitive Avoidance Questionnaire (CAQ) is a self-reported measure relating to multidimensional cognitive avoidance. Prior research has supported its correlated five-factor model, however, the tenability of a bifactor model and its measurement invariance have not been examined. With a Chinese adolescent sample (N = 734), a bifactor model of the CAQ, comprising a general cognitive avoidance and five orthogonal urge-related domain-specific factors, was supported. Multiple-group confirmatory factor analysis showed strict measurement invariance (including configural, metric, scalar, and error invariances) across genders but only configural invariance across grades. Predominately the general factor was positively correlated with worry, depression, anxiety, and stress. This study suggests that general and distinct factors should be considered to properly contextualize cognitive avoidance in adolescents., Author(s): Shan-Shan Xie [sup.1] , Sai-Li Shen [sup.2] [sup.3] , Xia-Xin Xiong [sup.3] , Yan-Ping Chen [sup.3] , Yi-Lin Shen [sup.3] , Nan Lin [sup.3] , Rong-Mao Lin [sup.3] Author [...]