Six Steps towards a Spatial Design for Large-Scale Pollinator Surveillance Monitoring.

Despite the importance of pollinators to ecosystem functioning and human food production, comprehensive pollinator monitoring data are still lacking across most regions of the world. Policy-makers have recently prioritised the development of large-scale monitoring programmes for pollinators to better understand how populations respond to land use, environmental change and restoration measures in the long term. Designing such a monitoring programme is challenging, partly because it requires both ecological knowledge and advanced knowledge in sampling design. This study aims to develop a conceptual framework to facilitate the spatial sampling design of large-scale surveillance monitoring. The system is designed to detect changes in pollinator species abundances and richness, focusing on temperate agroecosystems. The sampling design needs to be scientifically robust to address questions of agri-environmental policy at the scales of interest. To this end, we followed a six-step procedure as follows: (1) defining the spatial sampling units, (2) defining and delimiting the monitoring area, (3) deciding on the general sampling strategy, (4) determining the sample size, (5) specifying the sampling units per sampling interval, and (6) specifying the pollinator survey plots within each sampling unit. As a case study, we apply this framework to the "Wild bee monitoring in agricultural landscapes of Germany" programme. We suggest this six-step procedure as a conceptual guideline for the spatial sampling design of future large-scale pollinator monitoring initiatives.

Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.

All paths lead to hubs in the spectroscopic networks of water isotopologues H216O and H218O.

Network theory has fundamentally transformed our comprehension of complex systems, catalyzing significant advances across various domains of science and technology. In spectroscopic networks, hubs are the quantum states involved in the largest number of transitions. Here, utilizing network paths probed via precision metrology, absolute energies have been deduced, with at least 10-digit accuracy, for almost 200 hubs in the experimental spectroscopic networks of H216O and H218O. These hubs, lying on the ground vibrational states of both species and the bending fundamental of H216O, are involved in tens of thousands of observed transitions. Relying on the same hubs and other states, benchmark-quality line lists have been assembled, which supersede and improve, by three orders of magnitude, the accuracy of the massive amount of data reported in hundreds of papers dealing with Doppler-limited spectroscopy. Due to the omnipresence of water, these ultraprecise line lists could be applied to calibrate high-resolution spectra and serve ongoing and upcoming space missions.

Structural Evolution of Gene Promoters Driven by Primate-Specific KRAB Zinc Finger Proteins.

Krüppel-associated box (KRAB) zinc finger proteins (KZNFs) recognize and repress transposable elements (TEs); TEs are DNA elements that are capable of replicating themselves throughout our genomes with potentially harmful consequences. However, genes from this family of transcription factors have a much wider potential for genomic regulation. KZNFs have become integrated into gene-regulatory networks through the control of TEs that function as enhancers and gene promoters; some KZNFs also bind directly to gene promoters, suggesting an additional, more direct layer of KZNF co-option into gene-regulatory networks. Binding site analysis of ZNF519, ZNF441, and ZNF468 suggests the structural evolution of KZNFs to recognize TEs can result in coincidental binding to gene promoters independent of TE sequences. We show a higher rate of sequence turnover in gene promoter KZNF binding sites than neighboring regions, implying a selective pressure is being applied by the binding of a KZNF. Through CRISPR/Cas9 mediated genetic deletion of ZNF519, ZNF441, and ZNF468, we provide further evidence for genome-wide co-option of the KZNF-mediated gene-regulatory functions; KZNF knockout leads to changes in expression of KZNF-bound genes in neuronal lineages. Finally, we show that the opposite can be established upon KZNF overexpression, further strengthening the support for the role of KZNFs as bona-fide gene regulators. With no eminent role for ZNF519 in controlling its TE target, our study may provide a snapshot into the early stages of the completed co-option of a KZNF, showing the lasting, multilayered impact that retrovirus invasions and host response mechanisms can have upon the evolution of our genomes.

A computational neuroimaging study of reinforcement learning and goal-directed exploration in schizophrenia spectrum disorders.

BACKGROUND: Prior evidence indicates that negative symptom severity and cognitive deficits, in people with schizophrenia (PSZ), relate to measures of reward-seeking and loss-avoidance behavior (implicating the ventral striatum/VS), as well as uncertainty-driven exploration (reliant on rostrolateral prefrontal cortex/rlPFC). While neural correlates of reward-seeking and loss-avoidance have been examined in PSZ, neural correlates of uncertainty-driven exploration have not. Understanding neural correlates of uncertainty-driven exploration is an important next step that could reveal insights to how this mechanism of cognitive and negative symptoms manifest at a neural level. METHODS: We acquired fMRI data from 29 PSZ and 36 controls performing the Temporal Utility Integration decision-making task. Computational analyses estimated parameters corresponding to learning rates for both positive and negative reward prediction errors (RPEs) and the degree to which participates relied on representations of relative uncertainty. Trial-wise estimates of expected value, certainty, and RPEs were generated to model fMRI data. RESULTS: Behaviorally, PSZ demonstrated reduced reward-seeking behavior compared to controls, and negative symptoms were positively correlated with loss-avoidance behavior. This finding of a bias toward loss avoidance learning in PSZ is consistent with previous work. Surprisingly, neither behavioral measures of exploration nor neural correlates of uncertainty in the rlPFC differed significantly between groups. However, we showed that trial-wise estimates of relative uncertainty in the rlPFC distinguished participants who engaged in exploratory behavior from those who did not. rlPFC activation was positively associated with intellectual function. CONCLUSIONS: These results further elucidate the nature of reinforcement learning and decision-making in PSZ and healthy volunteers.

Parity-pair-mixing effects in nonlinear spectroscopy of HDO.

A non-linear spectroscopic study of the HDO molecule is performed in the wavelength range of 1.36-1.42 µm using noise-immune cavity-enhanced optical-heterodyne molecular spectroscopy (NICE-OHMS). More than 100 rovibrational Lamb dips are recorded, with an experimental precision of 2-20 kHz, related to the first overtone of the O-H stretch fundamental of HD16O and HD18O. Significant perturbations, including distortions, shifts, and splittings, have been observed for a number of Lamb dips. These spectral perturbations are traced back to an AC-Stark effect, arising due to the strong laser field applied in all saturation-spectroscopy experiments. The AC-Stark effect mixes parity pairs, that is pairs of rovibrational states whose assignment differs solely in the Kc quantum number, where Kc is part of the standard J K a,K c asymmetric-top rotational label. Parity-pair mixing seems to be especially large for parity pairs with Ka ≥ 3, whereby their energy splittings become as small as a few MHz, resulting in multi-component asymmetric Lamb-dip profiles of gradually increasing complexity. These complex profiles often include crossover resonances. This effect is well known in saturation spectroscopy, but has not been reported in combination with parity-pair mixing. Parity-pair mixing is not seen in H2 16O and H2 18O, because their parity pairs correspond to ortho and para nuclear-spin isomers, whose interaction is prohibited. Despite the frequency shifts observed for HD16O and HD18O, the absolute accuracy of the detected transitions still exceeds that achievable by Doppler-limited techniques.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies.

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci.

Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SINE-VNTR-Alu (SVA) elements, a class of great ape-specific transposable elements with gene-regulatory roles, which represents a major source of structural variability in the human population. We highlight the presence of structurally variable SVAs (SV-SVAs) in neurological disease-associated loci, and we further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1 and CD2AP Alzheimer's disease-associated risk loci and in the BCKDK Parkinson's disease-associated risk locus and assessed multiple aspects of their gene-regulatory influence in a human neuronal context. Together, this study reveals a novel layer of genetic variation in transposable elements that may contribute to identification of the structural variants that are the actual drivers of disease associations of GWAS loci.

Serum and Prostatic Tissue Concentrations of Cefazolin, Ciprofloxacin and Fosfomycin after Prophylactic Use for Transurethral Resection of the Prostate.

The optimal drug of choice, its time of administration and duration of antibiotic prophylaxis in patient undergoing a TURP procedure are still matters of debate. In this study, we evaluated the concentrations of cefazolin, ciprofloxacin and fosfomycin in the human prostate in a cohort of men undergoing TURP. We compared prostate tissue concentrations to the serum concentrations and MICs of common uropathogens, to determine the appropriateness of the current presurgical prophylactic antibiotics and to gain supportive data about the suitability of fosfomycin for antibiotic prophylaxis in men undergoing urological procedures of the prostate. After a single intravenous dose of cefazoline or an oral dose of ciprofloxacin prior to TURP, concentrations in serum and prostate tissue of well above the MIC (EUCAST breakpoint) of common uropathogens (Enterobacterales) were reached, and both antibiotics seem potentially effective in preventing postsurgical infections. A single dose of oral and intravenous administration of fosfomycin both led to serum concentrations above the MIC for uncomplicated urinary tract infections (8 µg/mL). The MIC for other infections (32 µg/mL) was only reached after a single dose of intravenous fosfomycin. We were unable to detect fosfomycin concentrations in prostate tissue.

Hyperfine-Resolved Near-Infrared Spectra of H217O.

Huge efforts have recently been taken in the derivation of accurate compilations of rovibrational energies of water, one of the most important reference systems in spectroscopy. Such precision is desirable for all water isotopologues, although their investigation is challenged by hyperfine effects in their spectra. Frequency-comb locked noise-immune cavity-enhanced optical-heterodyne molecular spectroscopy (NICE-OHMS) allows for achieving high sensitivity, resolution, and accuracy. This technique has been employed to resolve the subtle hyperfine splittings of rovibrational transitions of H217O in the near-infrared region. Simulation and interpretation of the H217O saturation spectra have been supported by coupled-cluster calculations performed with large basis sets and accounting for high-level corrections. Experimental 17O hyperfine parameters are found in excellent agreement with the corresponding computed values. The need of including small hyperfine effects in the analysis of H217O spectra has been demonstrated together with the ability of the computational strategy employed for providing quantitative predictions of the corresponding parameters.

Urodynamic Effects of Prostatic Urethral Lift Procedure for Male Voiding Lower Urinary Tract Symptoms.

Aims: Primary objective is to investigate whether prostatic urethral lift (PUL) results in an improvement of urodynamic parameters that define bladder outlet obstruction (urethral resistance algorithm [urethral resistance factor (URA)], Schäfer grade, detrusor pressure at maximum flow [PdetQmax], and detrusor pressure at bladder opening [PdetOpen]). Materials and Methods: Twenty patients (main inclusion criteria: ≥50 years of age, benign prostatic obstruction (BPO), international prostate symptom score (IPSS) ≥13, prostate volume ≤60 mL, and no middle prostate lobe) were enrolled in the study and a PUL was performed. Patients underwent urodynamic investigation and filled out the IPSS and quality of life (QoL) before and after PUL. A paired t-test was used to analyze the results. Results: The mean age was 68 years (range 55-79), mean prostate volume (TRUS) was 45 mL (range 20-59), and mean prostate-specific antigen was 2.0 µg/L (0.2-4.4). IPSS of the 16 patients reduced significantly (from 22.20 to 14.47, p = 0.000). Qmax during pressure flow study improved significantly (from 4.5 to 7.2 mL/s, p = 0.001), no significant difference was found in Qmax during free uroflowmetry. There was no significant difference found in postvoiding residual. URA decreased significantly post-treatment (from 52 to 37 cmH2O, p = 0.000). The Schäfer obstruction plot decreased significantly (from 3.5 to 2.6, p = 0.022). Seven patients underwent Greenlight Laser Vaporization of the prostate after the PUL attributable to unsatisfactory results. Conclusions: PUL has desobstructive effects, but they seem clinically modest. The procedure improves urodynamic parameters as well as QoL in males with lower urinary tract symptoms based on BPO. However, the mechanism how PUL leads to a remarkable symptom relief remains unclear and cannot be explained by the desobstructive mechanisms we observed.

ZNF91 deletion in human embryonic stem cells leads to ectopic activation of SVA retrotransposons and up-regulation of KRAB zinc finger gene clusters.

Transposable element (TE) invasions have shaped vertebrate genomes over the course of evolution. They have contributed an extra layer of species-specific gene regulation by providing novel transcription factor binding sites. In humans, SINE-VNTR-Alu (SVA) elements are one of three still active TE families; approximately 2800 SVA insertions exist in the human genome, half of which are human-specific. TEs are often silenced by KRAB zinc finger (KZNF) proteins recruiting corepressor proteins that establish a repressive chromatin state. A number of KZNFs have been reported to bind SVAs, but their individual contribution to repressing SVAs and their roles in suppressing SVA-mediated gene-regulatory effects remains elusive. We analyzed the genome-wide binding profile for ZNF91 in human cells and found that ZNF91 interacts with the VNTR region of SVAs. Through CRISPR-Cas9-mediated deletion of ZNF91 in human embryonic stem cells, we established that loss of ZNF91 results in increased transcriptional activity of SVAs. In contrast, SVA activation was not observed upon genetic deletion of the ZNF611 gene encoding another strong SVA interactor. Epigenetic profiling confirmed the loss of SVA repression in the absence of ZNF91 and revealed that mainly evolutionary young SVAs gain gene activation-associated epigenetic modifications. Genes close to activated SVAs showed a mild up-regulation, indicating SVAs adopt properties of cis-regulatory elements in the absence of repression. Notably, genome-wide derepression of SVAs elicited the communal up-regulation of KZNFs that reside in KZNF clusters. This phenomenon may provide new insights into the potential mechanisms used by the host genome to sense and counteract TE invasions.

Pain after midurethral sling; the underestimated role of mesh removal.

INTRODUCTION: The primary aim of this study was to evaluate the results of midurethral sling (MUS) removal in women who have pain as their single complication of MUS. MATERIAL AND METHODS: We performed a retrospective chart study supplemented with a cross sectional questionnaire. Women who underwent MUS removal for pain as the solitary reason for removal between 2004 and 2018 were included. Primary outcome was change in pain levels assessed by the visual analogue scale (VAS) pain score (range 0-10). Secondary outcome was the recurrence of stress urinary incontinence (SUI). RESULTS: Twenty-six of 31 patients returned the questionnaire. Median medical file follow-up was 12 months (range 2-66) and 25 months (range 5-104) regarding questionnaires. VAS pain score dropped from 7.8 (SD 1.9) at baseline to 4.5 (SD 3.2) at follow-up (p <.00). Seven (23%) patients were pain-free. Patients undergoing partial vaginal resection (n = 6) had a VAS pain score decrease of 4.7 (p = .02) versus 2.7 (p = .02) for complete vaginal removal (n = 14). Twenty-three (89%) patients experienced SUI at follow-up, whereof 10 (45%) reported (almost) no incidents of SUI. CONCLUSIONS: MUS removal is a viable and safe option with a significant drop in VAS pain score in patients with chronic pain after MUS placement. A post-operative increase of SUI and a possible renewed wish for SUI treatment have to be considered. This should not be a reason to refrain from information and/or referral for surgical removal.

Association between levator ani avulsion and urinary incontinence in women: A systematic review and meta-analysis.

BACKGROUND: Urinary incontinence is a bothersome symptom. Although the relationship between stress urinary incontinence (SUI) and vaginal delivery is established, the pathology underlying SUI after vaginal birth remains to be elucidated. OBJECTIVES: To determine whether levator ani muscle avulsion predisposes for SUI in women. SEARCH STRATEGY: Pubmed and Embase were searched for terms and their variations "levator ani muscle avulsion" and "urinary incontinence", from inception until 5 November 2019. SELECTION CRITERIA: Inclusion criterion: studies describing the relationship between urinary incontinence and levator ani muscle avulsion in women at least 1 year after delivery. Exclusion criterion: studies only analyzing the urethral sphincter or hiatus dimensions. DATA COLLECTION AND ANALYSIS: Odds ratios were used and if not available, were calculated as means of data synthesis, adjusted odds ratios if presented by the study, random-effects model to compute a pooled estimate. RESULTS: Seven studies were included, accounting for 2388 women. Comparing women with and without levator ani muscle avulsion, the overall odds ratio for SUI is 0.87 (95% confidence interval 0.56-1.34), and after adjustment for possible confounders was 0.72 (95% confidence interval 0.40-1.30). CONCLUSION: There is no relationship between levator ani muscle avulsion and SUI in women.

Spectroscopic-network-assisted precision spectroscopy and its application to water.

Frequency combs and cavity-enhanced optical techniques have revolutionized molecular spectroscopy: their combination allows recording saturated Doppler-free lines with ultrahigh precision. Network theory, based on the generalized Ritz principle, offers a powerful tool for the intelligent design and validation of such precision-spectroscopy experiments and the subsequent derivation of accurate energy differences. As a proof of concept, 156 carefully-selected near-infrared transitions are detected for H216O, a benchmark system of molecular spectroscopy, at kHz accuracy. These measurements, augmented with 28 extremely-accurate literature lines to ensure overall connectivity, allow the precise determination of the lowest ortho-H216O energy, now set at 23.794 361 22(25) cm-1, and 160 energy levels with similarly high accuracy. Based on the limited number of observed transitions, 1219 calibration-quality lines are obtained in a wide wavenumber interval, which can be used to improve spectroscopic databases and applied to frequency metrology, astrophysics, atmospheric sensing, and combustion chemistry.

Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.

Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.

Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work.

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits versus costs of cognitive effort by modulating striatal dopamine signaling.

Widespread correlation of KRAB zinc finger protein binding with brain-developmental gene expression patterns.

The large family of KRAB zinc finger (KZNF) genes are transcription factors implicated in recognizing and repressing repetitive sequences such as transposable elements (TEs) in our genome. Through successive waves of retrotransposition-mediated insertions, various classes of TEs have invaded mammalian genomes at multiple timepoints throughout evolution. Even though most of the TE classes in our genome lost the capability to retrotranspose millions of years ago, it remains elusive why the KZNFs that evolved to repress them are still retained in our genome. One hypothesis is that KZNFs become repurposed for other regulatory roles. Here, we find evidence that evolutionary changes in KZNFs provide them not only with the ability to repress TEs, but also to bind to gene promoters independent of TEs. Using KZNF binding site data in conjunction with gene expression values from the Allen Brain Atlas, we show that KZNFs have the ability to regulate gene expression in the human brain in a region-specific manner. Our analysis shows that the expression of KZNFs shows correlation with the expression of their target genes, suggesting that KZNFs have a direct influence on gene expression in the developing human brain. The extent of this regulation and the impact it has on primate brain evolution are still to be determined, but our results imply that KZNFs have become widely integrated into neuronal gene regulatory networks. Our analysis predicts that gene expression networks have been repeatedly innovated throughout primate evolution, continuously gaining new layers of gene regulation mediated by both TEs and KZNFs in our genome. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'.

Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells.

Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention.

Structurally Conserved Primate LncRNAs Are Transiently Expressed during Human Cortical Differentiation and Influence Cell-Type-Specific Genes.

The cerebral cortex has expanded in size and complexity in primates, yet the molecular innovations that enabled primate-specific brain attributes remain obscure. We generated cerebral cortex organoids from human, chimpanzee, orangutan, and rhesus pluripotent stem cells and sequenced their transcriptomes at weekly time points for comparative analysis. We used transcript structure and expression conservation to discover gene regulatory long non-coding RNAs (lncRNAs). Of 2,975 human, multi-exonic lncRNAs, 2,472 were structurally conserved in at least one other species and 920 were conserved in all. Three hundred eighty-six human lncRNAs were transiently expressed (TrEx) and many were also TrEx in great apes (46%) and rhesus (31%). Many TrEx lncRNAs are expressed in specific cell types by single-cell RNA sequencing. Four TrEx lncRNAs selected based on cell-type specificity, gene structure, and expression pattern conservation were ectopically expressed in HEK293 cells by CRISPRa. All induced trans gene expression changes were consistent with neural gene regulatory activity.