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Inhibition of cuneate neurones: its afferent source and influence on dynamically sensitive "tactile" neurones.

1. Responses were recorded in decereberate, unanaesthetized cats from individual cuneate neurones in order to determine firstly, the afferent sources of inhibition on cuneate neurones and secondly, the influence of afferent-induced inhibition on those response features of dynamically sensitive tactile neurones which determine their capacity to code information about parameters of tactile stimuli.2. For all cuneate neurones which displayed afferent-induced inhibition from areas surrounding or within their excitatory receptive field (71% of the sample) it was consistently found that 300 Hz vibration at low amplitudes (< 25-50 mum) which selectively engages Pacinian corpuscles was an effective source of inhibition. In contrast, steady indentation which activates slowly adapting tactile afferents was quite ineffective, as was low frequency vibration (30 Hz) at amplitudes of < 50-100 mum. The latter stimulus can be used to engage rapidly adapting receptors either within glabrous skin (presumed to be Meissners corpuscles) or in association with hair follicles. It is concluded that afferents from Pacinian corpuscles are the dominant or exclusive source of afferent-induced inhibition of cuneate neurones.3. For dynamically sensitive neurones responsive to low frequency cutaneous vibration (30 Hz) there was a reduction in the slope of stimulus-response relations with afferent-induced inhibition, but no expansion of the range of stimulus amplitudes over which the neurone responded.4. The influence of afferent-induced inhibition on the phase-locking of impulse activity to a cutaneous vibratory wave form was examined by constructing post-stimulus time histograms and cycle histograms. Measures of dispersion of impulse activity around the preferred point of firing in the vibratory waveform indicated that the capacity of individual cuneate neurones to code information about the frequency of the cutaneous vibration was not systematically changed in the presence of afferent-induced inhibition.

Adaptation, Physiological

Quaternary Glaciation Accelerates Speciation in Aquatic Snakes Through Recent Bottlenecks.

Climatic fluctuations during glacial periods have profoundly shaped the demographic history and gene flow dynamics of many taxa. This study integrated high-throughput sequencing of 67 individuals with comprehensive genomic analyses to investigate biogeographic patterns, genetic divergence and demographic trajectories in the Opisthotropis latouchii species complex, a group of mountain stream snakes distributed across Central China. Our analyses revealed substantial genetic divergence, identifying four distinct lineages, each confined to one of the four major mountain ranges in Central China, including one previously unrecognised species. These lineages exhibited distinct demographic signatures, with population bottlenecks occurring during Quaternary glaciations. Initial isolation in the glacial refugia of the southern regions of these mountains during the Late Pliocene was followed by postglacial expansions along a northward trajectory, with further divergence along a latitudinal gradient associated with mountain distribution. Notably, the mountain ranges of Central China acted as critical refugia during glacial periods, promoting rapid speciation, and as dispersal corridors during interglacial periods, facilitating range expansion and enabling recent gene flow. These findings highlight the profound impact of Quaternary climatic oscillations on genetic structure, demographic history and gene flow patterns of these endemic taxa.

Animals

Effects of aprotinin on renal function and urinary prostaglandin excretion in conscious rats after acute salt loading.

1. Aprotinin, a potent kallikrein inhibitor, was given to conscious rats with and without expansion of the extracellular fluid volume with isotonic saline. 2. In non-expanded rats aprotinin had no effect on arterial pressure, glomerular filtration rate (GFR), hippuran clearance, urinary flow rate, absolute sodium and potassium excretion or free-water clearance. 3. In volume-expanded rats aprotinin significantly reduced GFR, hippuran clearance, urine volume (V) UNaV, UKV and Cwater/GFR without effect on systemic arterial pressure. 4. Urinary immunoreactive prostaglandin E2 excretion significantly increased during the expansion phase but returned to below the control range during stable extracellular fluid volume expansion. 5. Aprotinin significantly suppressed urinary immunoreactive prostaglandin E2 excretion in non-expanded rats and in volume-expand rats during the expansion phase, but not during stable expansion. 6. The results suggest that the kallikrein-kinin system may contribute to changes in renal function during extracellular volume expansion. This action may not necessarily be associated with changes in renal prostaglandin E2 activity.

Animals

Technical note: an improved McCutchen miniviscometer for connective tissue fluids.

McCutchen's miniviscometer is a Couette-type instrument that requires only 0.2 ml of synovial or other test fluid. The modification described here adds to the capabilities of the original: control of temperature good to +/- 0.2 degrees C; increase of the maximum measureable viscosity at low shear rates (20 sec-1) to 3000 centipoise; and expansion of the usable range of shear rates to (20--1500 sec-1. The device is rugged and data are reproducible to +/- 1.2% (S.D.) of the mean over the full range of shear rates.

Body Fluids

Differential diagnosis of hypoechoic and anechoic masses with gray scale sonography: new observations.

With the technological advances in gray scale sonography that have permitted the use of higher-frequency transducers and expansion of the acoustic dynamic range, increasing problems in differentiating solid masses and fluid-filled masses have become apparent. These difficulties can be overcome by strict adherence to proper scanning techniques, which involve transducer selection, tissue attenuation compensation, and alterations in patient position. The availability of variable-dynamic-range signal processing and the use of real-time scanning can further increase one's confidence in the correct interpretation of these masses. The primary criteria for determining that a mass is fluid-filled have been expanded to include the presence of reverberation echoes, the "lateral shades" sign, and the presence of septations. In the past, hypoechoic masses with low-level internal echoes were termed "complex". Both fluid-filled masses and solid masses may fall into this category. By use of the sonographic criteria, an attempt should be made to determine whether a mass is primarily fluid-filled or solid. Specific anatomic locations and pathologic conditions in which differential diagnosis may be difficult are illustrated; these include abdominal masses, hepatic and renal masses, and pelvic masses.

Abdominal Neoplasms

A General Framework for Branch Length Estimation in Ancestral Recombination Graphs.

Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here we introduce, POLEGON, a novel approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and lead to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the HLA region, and show that they exceed 30 million years in multiple segments.

Ancestral Recombination Graph

Reversibility of alcoholic cardiomyopathy with abstention from alcohol.

A 46-year-old chronic alcoholic patient with typical and severe congestive cardiomyopathy was studied hemodynamically on two separate occasions. The second study followed after a 1 1/2-year period of virtually complete abstention from alcohol and revealed that the left ventricular dysfunction had disappeared. Depsite persisting atrial fibrillation, the response to moderate exercise and to plasma volume expansion was within the normal range. When last seen, 29 months after initial hospitalization, the patient was symptom-free and was not given any treatment.

Cardiomyopathy, Alcoholic

Linear dimensional change of copper-rich dental amalgam.

Copper-rich amalgams made from alloy mixtures have large expansions in air at 105 +/- 2 weeks that range from 100 to 194 micrometers/cm at 60 C, from 36 to 101 micrometers/cm at 37 C, and from 14 to 44 micrometers/cm at 23 C on unrestricted 8- x 4-mm cylinders (Dispersalloy, Micro II, and Optaloy II). Other copper-rich amalgams made from one alloy usually had a slight shrinkages at the three temperatures with an exception, a slight expansion of 12 micrometers/cm at 60 C (Aristaloy CR, Indilogy non-zinc, Sybraloy, and Tytin). Dimensional changes during hardening ranged,on the average, from -3 to +19 micrometers/cm when measured by ADA Specification methods and from -2 to +25 micrometers/cm when measured by an indirect method. The clinical significance of the foregoing findings is unknown; nor is a relationship known among dimensional change of unrestricted specimens, dimensional change of restricted specimens, creep value, and clinical behavior of amalgams generally. In specific instances, however, a relationship is sometimes shown.

Chemical Phenomena

Thermal expansion of composite resins and sealants.

Linear thermal coefficients of expansion (alpha) of seven commercial composite resins and four pit and fissure sealants were determined between 0 and 60 degrees C on a thermomechanical analyzer. The thermal expansion curves obtained were nonlinear. Values of alpha ranged from 26.5 to 39.6 x 10(-6) degrees C for the composite and from 70.9 to 93.7 x 10(-6)/degrees C for the sealants.

Composite Resins

Comparative analysis of chloroplast genomes in ten holly (Ilex) species: insights into phylogenetics and genome evolution.

In order to clarify the chloroplast genomes and structural features of ten Ilex species and provide insights into the phylogeny and genome evolution of the genus Ilex, we conducted a comparative analysis of chloroplast genomes using bioinformatics methods. The chloroplast genomes of ten Ilex species were obtained, and their structural features and variations were compared. The results indicated that all chloroplast genomes in the genus Ilex exhibit a double-stranded circular structure, with sizes ranging from 157,356 to 158,018&#xa0;bp, showing minimal differences in size. The chloroplast genomes of the ten Ilex species have a relatively conservative gene count, with a total of 134 to 135 genes, including 88 or 89 protein-coding genes, and a conserved number of 8 rRNA genes. Each chloroplast genome contains 3 to 123 SSR (Simple Sequence Repeat) sites, predominantly composed of mononucleotide and trinucleotide repeats, with no detection of pentanucleotide or hexanucleotide repeats. The variation in dispersed repeat sequences among Ilex species is minimal, with a total repeat sequence number ranging from 1 to 14, concentrated in the length range of 30 to 42 base pairs. The expansion and contraction of chloroplast genome boundaries among Ilex species are relatively stable, with only minor variations observed in individual species. Variations in non-coding regions are more pronounced than those in coding regions, with the variability in the Large Single Copy region (LSC) being the highest, while the variability in the Inverted Repeat region A (IRa) is the lowest. The divergence time among Ilex species was estimated using the MCMC-tree module, revealing the evolutionary relationships among these species, their common ancestors, and their differentiation throughout the evolutionary process. The research findings provide a valuable reference for the systematic study and molecular marker development of Ilex plants.

Genome, Chloroplast

Locus coeruleus activation transforms cortical taste representations.

Noradrenergic neurons in the locus coeruleus (LC) shape sensory processing, yet how LC activity influences population taste coding remains unclear. Using optogenetic LC activation with miniscope imaging in the gustatory cortex (GC), we examined LC modulation of multiple taste attributes. Phasic LC activation strengthens correlations between neuronal responses and palatability and expands the dynamic range of stimulus representations along a palatability axis. This expansion is driven by an aversive shift in the representations of all tastants except sucrose, the most palatable stimulus. For mixture ratio and concentration, phasic activation expands and rotates attribute axes, potentially reflecting dependencies between these attributes and palatability. These transformations likely arise from multiplicative gain modulation and more flexible tuning changes. Tonic LC activation affects fewer neurons and does not expand attribute axes. Together, the findings show that LC activation reorganizes GC population geometry in a pattern-dependent manner, linking neuromodulation with feeding behavior and affective processing.

CP: neuroscience

Temporal shifts in K-locus composition and expansion of dual-carbapenemase-producing ST11-KL62 Klebsiella pneumoniae: a retrospective genomic surveillance study.

OBJECTIVES: To characterize longitudinal changes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the recent increase in dual-carbapenemase-producing ST11-KL62 isolates. METHODS: We retrospectively analysed 1,239 non-duplicate CRKP isolates recovered at a tertiary hospital in China during 2018-2025. Antimicrobial susceptibility testing, whole-genome sequencing, K-locus and resistance/virulence gene profiling, core-genome single-nucleotide polymorphism analysis, reference-guided plasmid comparison, conjugation and stability assays, and a murine lethality model were used. RESULTS: ST11 accounted for 936/1,239 isolates (75.5%). KL47 declined from 39/151 (25.8%) in 2018-2019 to 45/755 (6.0%) in 2024-2025, whereas KL62 increased from 3/151 (2.0%) to 147/755 (19.5%). Among 148 ST11-KL62 isolates, 13/148 (8.8%) co-harboured blaKPC-2 and blaNDM-1, of which 12/13 (92.3%) met the study's molecular definition of hypervirulent CRKP. Pairwise single-nucleotide polymorphism distances among local ST11-KL62 isolates ranged from 0 to 43 (median, 14), suggesting that clonal expansion may have contributed to their increase. Complete genome analysis of ZD872 located blaKPC-2, blaNDM-1, and major virulence-associated genes on distinct plasmids; related plasmid backbones were predicted in other isolates using short-read comparisons. ZD872 exhibited a hypervirulent phenotype in the murine model. CONCLUSIONS: The ST11 CRKP population underwent temporal shifts in K-locus composition, including expansion of a closely related ST11-KL62 subset carrying dual carbapenemases and hypervirulence-associated markers. These findings support integrating longitudinal genomic surveillance with local transmission analysis.

Carbapenem-resistant Klebsiella pneumoniae

Effect of Corynebacterium parvum on hemopoietic stem-cell kinetics.

The intravenous administration of 548 microgram of killed Corynebacterium parvum (C. parvum) into C57BL mice leads to a significant decrease in the number of bone-marrow colony-forming-units in spleen (CFUs) as early as 12 h after the injection of the bacterium. This decrease persisted in varying degrees for 3 weeks. After an initial fall at 24 h, the splenic CFUs exhibited a rapid expansion and reached values 10 times higher than the control range on the ninth day. A significant rise in the number of circulating CFUs, reaching a first peak at 2 h and a second one on the fifth day, was also observed. The proliferative status of femoral CFUs was increased at 48 and 72 h, while that of splenic CFUs presented a significant increase only 48 h after the injection of C. parvum. The sequence of events which were observed in these experiments indicates that an accelerated migration of hemopoietic stem cells from bone marrow to spleen via the blood circulation has to take place.

Animals

Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications.

Long-read sequencing (LRS) technologies, namely, Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio), have emerged as promising solutions to overcome the limitations of short-read sequencing (SRS). Nevertheless, the still higher sequencing error rates compared with SRS, need for customized pipelines, rapidly updating software, and incipient scalability continue to present challenges for adopting ONT in standard clinical practice. Here we assess the performance of ONT (R9 and R10 chemistries) in comparison to Illumina and MGI across 17 well-characterized reference samples with 11 clinical variants representing nine different genetic diseases. To enable this, we have implemented a production-ready pipeline including SNV, indel, STR, SV, and CNV detection, alongside reporting key summary metrics to ensure high-quality data at the production sequencing level. Our results show high accuracy of ONT across SNVs (F-score 0.978-0.983) and SVs (F-score = 0.75) but still weaknesses across indels (F-score 0.659-0.758). However, we highlight that ONT accurately detected all four pathogenic indels as well as the performance improvement in exons and with the newer R10 chemistry. We further demonstrated the importance of long reads to detect clinically impactful variants such as a FMR1 pathogenic expansion, often misclassified by SRS as being in the premutation range. Our multiplatform analysis and Sanger validation uncovered a 1 bp error in the Coriell annotation for a cystic fibrosis-causing indel in GM07829. This work underscores the growing readiness of ONT for clinical applications, highlighting both its advancements and its potential for broader adoption in clinical genomics and large-scale operations.

Humans

[Effects of minoxidil on blood pressure and plasma volume in refractory hypertension (author's transl)].

We substituted minoxidil for dihydralazine in the treatment of 10 patients with refractory hypertension. Supine diastolic blood pressure decreased from 114 +/- 15 mmHg ou dihydralazine to 90 +/- 10 mmHg after one week on minoxidil (mean +/- ISD, p less than 0.01), the concomitant therapy being unchanged (sodium depletion and betablockade in all patients, methyl dopa or clonidine in seven). Simultaneously themean plasma volume increased by 395 ml (p less than 0.02) with no correlation to the decrease in blood pressure, and with no change in plasma renin activity and plasma aldosterone. Further expansion of plasma volume was prevented by furosemide, individual dosage requirement ranging from 40 to 500 mg/day, irrespective of the renal function. fter three to six months of ambulatory treatment a satisfactory blood pressure control was maintained. Hirsuties appeared in all our patients, but no subjective side effects was reported.

Adolescent

HSA fosters hospitals' voluntary cooperation in areawide planning.

An HSA convinced the 31 hospitals in its health service area to participate in a voluntary moratorium on expansion and a voluntary planning process through which their long-range institutional plans are reviewed for incorporation into the HSA's areawide plans.

Community Participation

Effect of renal vein ligation with or without suprarenal inferior vena cava ligation on sodium and phosphate excretions during acute extracellular volume expansion in the rat.

Right nephrectomy with or without inferior vena cava (IVC) ligation was performed in rats 1 week after left renal vein ligation. Left kidney function and sodium and phosphate excretions by volume expansion were investigated. Inulin (CIN) and para-aminohippuric acid (CPAH) clearances and fractional excretions of sodium (FENa) and phosphate (FEP) were examined before and after volume expansion was induced by normal saline. Kidney functions were well preserved with development of collateral venous channels; biochemical parameters returned to the normal ranges. However, CIN and CPAH were reduced to 33 to 25 per cent of control values and the filtration fraction was elevated. After volume expansion, a marked increment of FENa was observed in cases of IVC ligation but the increment in animals without IVC ligation was less than in the control group. FEP was also increased in experimental groups but the magnitude of phosphaturia was not so prominent compared to the control group. The increment of FEP was not comparable to that of FENa. Thus, from the aspect of kidney function, this experiment showed the rationality of left renal vein ligation with contralateral nephrectomy. From the pathophysiologic aspect, the magnitude of natriuresis and phosphaturia by volume expansion was not prominent and a reduced reabsorptive capacity for sodium and phosphate may exist in a solitary kidney with a ligated renal vein. When suprarenal IVC ligation was also done, prominent natriuresis was observed with saline infusion.

Animals