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At least 19 recordsLinked to original sources
PubMed2026

The SPL-family transcription factor MpSPL3 orchestrates the proper regulation of vegetative and reproductive programs in Marchantia polymorpha.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes encode plant-specific transcription factors that are widely distributed across the plant kingdom. In angiosperms, the multimember SPL family regulates various biological processes, including vegetative-to-reproductive phase transition, inflorescence architecture, and lateral organ development. In contrast, the liverwort Marchantia polymorpha genome encodes only four SPL genes, with functional studies available only for microRNA-targeted members, MpSPL1 and MpSPL2. MpSPL1 was shown to control the meristem dormancy to modulate the thallus architecture, whereas MpSPL2 was found to promote the transition from vegetative-to-reproductive phase. Here, we investigate the impact of the MpSPL3 gene on M. polymorpha development. We demonstrate that MpSPL3 influences coordination of the vegetative growth and the reproductive phase transition. Knockout of MpSPL3 leads to strong growth retardation with disordered thallus morphology, reduced gemma cup number, and, most strikingly, complete loss of gametangiophore formation. Interestingly, overexpression of MpSPL3.2, the shorter isoform, has no detectable morphological effect, whereas the overexpression of MpSPL3.1, the longer isoform encoding a protein with an additional 61-aa long fragment, results in a delay in timing and reduced efficiency of gametangiophore production. Moreover, all the observed developmental abnormalities might be a consequence of the altered expression of genes essential for proper vegetative development and responsible for germ cell specification in MpSPL3 knockout and overexpression plants. Altogether, our findings demonstrate that MpSPL3 is important in regulating gametophyte development and ensuring reproductive success in M. polymorpha.

Marchantia↗
PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (&#x3c7;2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗
PubMed1979

Biofeedback control of skin potential level.

This study explored the possibility of using biofeedback to arrest spontaneous declines in tonic electrodermal levels. For 3 days, 10 subjects (S) received 20 minutes of training in increasing skin potential level (SPL) negativity (arrested declines), followed by 20 minutes of training in decreasing SPL negativity (facilitating declines), with reverse order for half of the Ss. Simultaneous analogue and binary feedback of SPL were used. Training in the direction of SPL increases resulted in arrest of spontaneous declines in SPL negativity but did not result in large-magnitude increases above baseline. Training in the direction of SPL decreases facilitated declines in SPL. The absolute mean difference between the increase condition and the decrease condition on the 3rd day was 8.28 mV. Correlations suggested that considerable intraindividual variability may have been independently related to the Locus of Control personality dimension and to a Law of Initial Values limitation on SPL change. It was concluded that SPL was controllable to the extent of facilitating or arresting spontaneous declines.

Action Potentials↗
PubMed2026

Alternative transcription of the mouse Gh gene identifies an immune-associated transcript with species-specific structural divergence.

Growth hormone (GH) in mice is primarily expressed in the anterior pituitary, although Gh expression has been reported in extrapituitary tissues, including immune organs. However, the structure of immune-associated Gh transcripts remains poorly characterized. To determine whether splenic Gh transcripts differ from pituitary Gh mRNA, 5'- and 3'-rapid amplification of cDNA ends (RACE) analyses were performed. While 3' RACE showed a shared polyadenylation site, 5' RACE identified a novel exon located approximately 2&#xa0;kb upstream of the conventional exon 1, generating a transcript (spl-Gh mRNA) with a distinct first exon but shared downstream exons with pituitary Gh mRNA (pit-Gh mRNA). RT-PCR analysis revealed that spl-Gh mRNA is predominantly expressed in immune tissues such as spleen and bone marrow, and its distribution did not correlate with Pit-1 mRNA expression. Quantitative RT-PCR further demonstrated that spl-Gh mRNA was expressed at levels comparable to those of pit-Gh mRNA in the mouse spleen, indicating that spl-Gh is one of the major Gh transcript forms in this tissue. Sequence analysis indicated that spl-Gh mRNA is predicted to retain coding potential for a GH protein. Comparative genomic analyses further demonstrated that genomic features associated with the spl-Gh transcriptional unit are conserved only in a subset of closely related Mus species. In contrast, although a spl-Gh-related transcript was detected in rat spleen, no properly spliced mouse-like transcript was identified under the present experimental conditions. The detected transcript exhibited intron retention and an in-frame stop codon, suggesting that it is unlikely to produce a functional GH protein. These findings identify a distinct immune-associated Gh transcript generated through alternative transcription of the mouse Gh gene and suggest that immune-associated Gh transcriptional mechanisms have undergone species-specific divergence among rodents. Together, these findings reveal previously unrecognized complexity in Gh gene regulation and highlight species-specific differences in immune-associated Gh transcripts.

Animals↗
PubMed1977

Mechanism of target cell lysis of cytolytic T lymphocytes. I. Characterization of specific lymphocyte-target cell conjugates separated by velocity sedimentation.

Differential velocity sedimentation was applied for separating alloimmune T lymphocytes bound to target cells (TC) from free lymphocytes. Maximal size differences between lymphocytes and TC were achieved a) by isolating the fraction of small peritoneal lymphocytes (SPL) from an alloimmune peritoneal cell population, and b) by selecting large tumor cells as TC. Under the conditions used, most of the conjugates formed at room temperature consisted of one SPL bound to one TC, and adequate separation of bound from free SPL could be achieved within less than 5 min. Functional studies of the conjugate-enriched fractions showed that a minimum of 60% of TC-bound SPL were indeed cytolytic. Conjugate-depleted fractions, however, were still lytic, suggesting that not all effector cells formed stable conjugates at room temperature. Transmission and scanning electron microscopy studies revealed that binding between SPL and TC was achieved through interpenetrating membrane projections and was characterized by point and broad zone contacts. When lysis was allowed to proceed, prominent changes of the TC membrane morphology, including loss of microvillous projections, appearance of localized blebs, pseudopod-like projections, and membrane defects were documented.

Animals↗
PubMed2026

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p&#x2009;<&#x2009;0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p&#x2009;<&#x2009;0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p&#x2009;=&#x2009;0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans↗
PubMed1977

Host defenses in experimental scrub typhus: role of spleen and peritoneal exudate lymphocytes in cellular immunity.

Lymphocytes obtained from spleens or peritoneal exudates of immune donor mice were evaluated for their ability to passively confer protection on recipients subsequently challenged with virulent scrub typhus rickettsiae. Peritoneal exudate lymphocytes (PELs) injected intraperitoneally were able to transfer complete protection against rickettsial challenge by 5 days after immunization, whereas splenic lymphocytes (SpL's) required 15 days to exhibit similar resistance. When immune lymphocytes were transferred intravenously, cells from both anatomical compartments required 15 days after immunization before they were able to completely protect recipients. PELs maintained this protective capacity for 2 weeks, but the passive immunity induced by intravenously transferred SpL's rapidly diminished to insignificant levels. It was particularly interesting that the protective effect of SpL's could be dramatically reduced by the concomitant presence of a mineral oil-induced peritoneal exudate. Almost total abrogation of resistance was observed when SpL's obtained from exudate-bearing mice were transferred intravenously. The protective capacity of both PELs and SpL's was resistant to 1,200 rads of gamma radiation at 7 to 10 days after immunization, but resistance was transient and by 3 weeks was undetectable. It was not possible to determine from this study whether the transferred lymphocytes were proximate mediators of protection in scrub typhus infection of mice or whether they served to recruit the host's own defenses, or both. However, it was possible to conclude that PEL's and SpLs exhibited functional heterogeneity and that PELs were more efficient mediators of protection.

Animals↗
PubMed1975

In vitro human reactivity to staphylococcal phage lysate.

The cell-mediated reactivity of normal individuals to staphylococcal phage lysate (SPL) were tested in vitro in the lymphocyte stimulation (LS) and leukocyte migration inhibition (LMI) assays. There were 95% positive responses in LS (stimulation ratio larger than or equal to 3 with p less than 0.01) and 67% positive responses in LMI (migration index less than or equal to 0.80). Enriched subpopulations of T and B lymphocytes were prepared with rosette formation and density gradient centrifugation. SPL stimulated lymphoproliferative responses in both T and B cell subpopulations whereas phytohemagglutinin (PHA) stimulated only the T cell subpopulation. Cord blood leukocytes were tested in the LS assay and 41% gave positive responses to SPL, 81% to PHA, and 17% with SLO. SPL appears to be a useful reagent for the in vitro study of cell-mediated reactivity, and may provide somewhat different information from that obtained with other mitogens or antigens.

Antigens, Bacterial↗
PubMed1977

[Effect of single impulses on cochlear microphone potentials of the guinea-pig cochlea].

The influence of highly intensive single impulses on the cochlea of guinea pig was studied in an acute experiment. Very short impulses of less than or equal to 0.1 ms duration were produced by a sparknoise generator. The cochlear microphonics (CM) to a test stimulus (sinus tone, 3150 Hz) were recorded from the round window and measured prior to, during, and following impulse treatment. During the impulse treatment, the greatest amplitude reduction of CM occurred after the first impulse, while the further impulses caused a decreasing reduction. At first the number of impulses was varied: 1, 3, and 5 impulses were applied at intervals of 15 s each, at an impulse sound level of 164 dB sound pressure level re. 0.002 mubar (SPL). After these impulse treatments, in all cases a continual decrease of CM amplitudes up to a constant end value without recovery was found within a 2-hrs period of observation. The height of the end value depends on the number of impulses applied. Subsequently, at an exposure to 5 impluses the impulse sound level was stepwise reduced (164, 153, 144, 139 and 133 dB SPL). Again, a characteristic decrease of CM amplitudes was observed during the 2-hrs period of observation. The height of the end value is now dependent on the impluse sound level. Impulses of 164, 153 and 144 dB SPL cause a strong decrease of CM while the effect of impulses of 139 and 133 dB SPL is distinctly lower.

Acoustic Stimulation↗
PubMed2026

Spatial isoform sequencing at single-cell resolution reveals cell-type-specific spatial isoform variability in multiple brain cell types.

Spatial long-read technologies are increasingly common but usually lack single-cell resolution. This leaves unanswered whether spatially variable isoforms reflect variability within one cell type or differences in region-specific cell-type composition. Here, we developed Spl-ISO-Seq2 (500-nm resolution) and accompanying software, Spl-IsoQuant-2 and Spl-IsoFind, enabling long-read sequencing of >450 million barcodes versus 80,000 previously. Applying this to the adult mouse brain, we compared differential isoform abundance between known regions and spatial isoform patterns independent of predefined regions. Both identified overlapping hits, for example, Rps24 in oligodendrocytes. For known Snap25 spatial isoform variation, we show that it occurs in excitatory neurons. The region-agnostic approach also uncovered patterns missed by region-based comparisons, for example, for Ighm. Notably, many spatial isoform signals are not driven by cell-type composition alone. Finally, our software is applicable to many spatial and single-cell protocols, demonstrating reproducibility between platforms (for example, Visium HD/Stereo-seq). Overall, our experimental/analytical methods enable a submicron-resolution-isoform view and open avenues for spatial isoform disease research.

Animals↗
PubMed1979

Acoustic-reflex growth and loudness.

Acoustic-reflex growth functions and loudness-balance judgments were obtained for three normal-hearing subjects with normal middle-ear function. The hypothesis that acoustic reflex-activating signals producing proportionately equal acoustic-impedance changes are judged equal in loudness was evaluated. The mean acoustic impedance and associated standard deviations were computed for the baseline (static) and activator (reflex) portions of each reflex event. An acoustic-impedance change exceeding two standard deviations of baseline was defined as the criterion acoustic-reflex response. Acoustic impedance was measured as a function of activator SPL for broadband noise and a 1000-Hz tone from criterion magnitude to the maximum acoustic impedance (or 120-dB SPL). This was defined as the dynamic range of reflex growth. Loudness-balance measurements were made for the 1000-Hz tone and broadband noise at SPL's representing 30, 50, and 70% of the individual dynamic range. The data supported the hypothesis.

Acoustic Impedance Tests↗
PubMed1977

Phytohemagglutinin-induced differentiation and blastogenesis of precursor T cells from mouse bone marrow.

The cells in mouse bone marrow (BM) capable of responding to phytohemagglutinin (PHA) were shown to be precursor T cells in experiments employing athymic mice, immunofluorescence, and specific lysis of T or B cells with cytotoxic antisera + complement. In contrast, the responses of lymph node (LN) and spleen (Spl) cells to this mitogen were shown by the same techniques to rely upon resident populations of mature T lymphocytes in these peripheral lymphoid organs. Cytolysis of T cells with anti-theta (anti-Thy 1), anti-thymocyte, or anti-brain antisera abolished the PHA responses of LN and Spl, but had no appreciable effect on the BM PHA response. Lysis of B cells with anti-mouse gamma globulin or anti-mouse IgM antisera had no significant effect on either Spl or BM blastogenesis in response to this lectin. Immunofluorescent studies with fluoresceinated anti-brain sera demonstrated acquisition of T-cell surface antigens by BM null lymphocytes during the blastogenic response of this tissue to PHA. The results of these immunofluorescence experiments were reproducible even when marrow obtained from nude mice and pretreated with anti-brain serum plus complement was employed. The implications of these findings with regard to prophylaxis against graft versus host disease in BM transplant recipients are discussed.

Animals↗
PubMed2025

Privacy-Enhancing Sequential Learning under Heterogeneous Selection Bias in Multi-Site EHR Data.

OBJECTIVE: To develop privacy-enhancing statistical methods for estimation of binary disease risk model association parameters across multiple electronic health record (EHR) sites with heterogeneous selection mechanisms, without sharing raw individual-level data. We illustrate their utility through a cross-biobank analysis of smoking and 97 cancer subtypes using data from the NIH All of Us (AOU) and the Michigan Genomics Initiative (MGI). MATERIALS AND METHODS: Large-scale biobanks often follow heterogeneous recruitment strategies and store data in separate cloud-based platforms, making centralized algorithms infeasible. To address this, we propose two decentralized sequential estimators namely, Sequential Pseudo-likelihood (SPL) and Sequential Augmented Inverse Probability Weighting (SAIPW) that leverage external population-level information to adjust for selection bias, with valid variance estimation. SAIPW additionally protects against misspecification of the selection model using flexible machine learning based auxiliary outcome models. We compare SPL and SAIPW with the existing Sequential Unweighted (SUW) estimator and with centralized and meta learning extensions of IPW and AIPW in simulations under both correctly specified and misspecified selection mechanisms. We apply the methods to harmonized data from MGI ( n = 50,935) and AOU ( n = 241,563) to estimate smoking-cancer associations. RESULTS: In simulations, SUW exhibited substantial bias and poor coverage. SPL and SAIPW yielded unbiased estimates with valid coverage probabilities under correct model specification, with SAIPW remaining robust under selection model misspecification. Both approaches showed no notable efficiency loss relative to centralized methods. Meta-learning methods were efficient for large sites but failed in settings with small cohort sizes and rare outcome prevalence. In real-data analysis, strong associations were consistently identified between smoking and cancers of the lung, bladder, and larynx, aligning with established epidemiological evidence. CONCLUSION: Our framework enables valid, privacy-enhancing inference across EHR cohorts with heterogeneous selection, supporting scalable, decentralized research using real-world data.

Journal Article↗
PubMed1979

Level dependence of critical bandwidth: notched-noise masking paradigm.

The effect of increased stimulus level on critical bandwidth was investigated. Noise-masked, pulsed-tone thresholds were obtained by a Bekesy tracking procedure from 4 practiced normal-hearing adults at .5, 1, 2, and 4 kc/s. Tones were placed symmetrically within a band-reject region. Critical bandwidth was taken as the frequency separation between noise bands at which masked tonal threshold began to change and was found to increase fairly regularly as the spectrum level of the noise increased from 30-60 db SPL. However, the data at 60 db SPL may have been influenced a 2 and 4 kc/s by the detection of aural distortion products. The suggestion was made that when signal frequency is outside the spectral limits of the masker, critical bandwidth widens as masker level is raised; however, when signal frequency is within the spectral limits of the masker (as with a continuous noise wit no notches), critical bandwidth remains unchanged up to 80 bd SPL.

Adult↗
PubMed1979

Suppressor cells for in vivo cytotoxic responses--regulation of the in vivo activation of cytotoxic T-lymphocytes by suppressive cells.

A significant in vivo activation of cytotoxic T-lymphocytes (CTL) against trinitrophenyl (TNP)-modified autologous cells and of a DNA-synthesis response in the peripheral lymphnodes is observed in cyclophosphamide (CyP) treated mice after skinpainting with trinitrochlorbenzene (TNCB) or after injection of TNP-coupled spleen cells (TNP-Spl) into the footpads. The activation of these responses can be suppressed by the transfer of spleen cells or lymphnode cells from skinpainted normal mice, but not from skinpainted mice that had been pretreated with CyP. Suppressive activity is also induced by injections of TNP-Spl i.p. or trinitrobenzosulfonate (TNBS) i.v. Optimal activation of suppression occurs with 3--4 days. The suppressive activity is antigen-specific at least in respect to its activation. Suppressor cells of this kind also suppress the induction of delayed hypersensitivity (DH) responses and the priming for in vitro secondary responses. However, these two responses are less sensitive to the suppression, and their in vivo activation is accordingly much less restricted with the in vivo activation of DNA-synthesis and primary CTL responses. DH and CMC memory can be activated ty TNCB skinpainting without pretreatment with CyP.

Animals↗
PubMed1978

Hearing loss and cochlear pathology in the monkey (Macaca) following exposure to high levels of noise.

Eight Old World monkeys were exposed 8 h daily for 20 days to octave-band noise having center frequencies from 0.5--8 kHz at levels of 117--120 dB SPL. Two additional animals received exposures to wide-band, 120-dB SPL noise on the same schedule, and one animal was exposed to the 2-kHz octave band for 40 h continuously. Behavioral audiograms were measured throughout exposure and during a 1-month recovery period. Following recovery, the animals were sacrificed and their ears examined histologically. Monaural audiograms are presented showing initial and final TTS and PTS measured at the end of the recovery period. These are compared with complete cytocochleograms for each ear. Hair cell loss was generally restricted to the outer rows, and was reasonably well correlated with pattern of hearing loss. Some cell loss, including inner hair cells, was found in the extreme basal turn, usually without associated high-frequency hearing loss. The relationships between exposure frequency, hearing loss, and locus of cochlear pathology are discussed, as are changes in TTS during exposure.

Animals↗
PubMed1979

Conditioning auditory stimuli and the cutaneous eyeblink reflex in humans: differential effects according to oligosynaptic or polysynaptic central pathways.

Electromyographic activity of orbicularis oculi muscles in humans was elicited by percutaneous electrical stimulation of the supraorbital brahcn of the trigeminal nerve. The reflex consists of an early brief ipsilateral R1 and a later prolonged consensual R2. The threshold for R1 was considerably elevated compared to that of R2. In one experiment brief acoustic stimuli, at 70 dB SPL, were presented at various intervals, from 5 to 800 msec, prior to the eliciting stimulus. In a second experiment similar stimuli, with intensities varying from 30 to 70 dB SPL, were given at the fixed lead time of 100 msec. In each experiment the preliminary acoustic stimulus enhanced R1 and depressed R2. Potentiation of R1 developed more rapidly than did depression of R2 and exhibited an early and a late peak, whereas depression had a single intermediate trough. Both effects linearly increased with increases in the intensity of the acoustic prepulse. These restuls are discussed in relation to the neuronal circuits responsible for the expression of the two reflex components.

Acoustic Stimulation↗