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Comparison between apexcardiographic and angiographic indexes of left ventricular performance in patients with aortic incompetence.

Left ventricular (LV) apexcardiogram (ACG) and its first derivative (dA/dt) was obtained in 104 normal subjects and 34 patients with chronic aortic incompetence (AI). In the patients with AI the ACG was recorded simultaneously with LV pressure (tipmanometer). The systolic upstroke time (SUT), the time to peak dA/dt (t-dA/dt) and the a wave percentage amplitude (a/H) of the ACG was measured. In normal subjects SUT averaged 99 +/- 17 (SD) msec. In 17 patients with AI and normal ejection fraction (EF) (group 1) SUT was within normal limits; in 17 patients with AI and decreased EF (group 2) it was prolonged (142 +/- 19 msec) (P less than 0.001). The SUT was closely correlated with EF (r = 0.85) and less with contractile indexes derived from pressure curves. The indexes t-dA/dt and a/H were not significantly different in groups 1 and 2; they were weakly correlated only with the time to peak rate of LV pressure rise (r = +0.56) and the LV end-diastolic pressure (r = +0.59), respectively. These results demonstrate the superiority of SUT over the other apexcardiographic parameters. The measure provides another means of noninvasive assessment of the LV performance in patients with AI.

Adolescent

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Serologic, structural, and genetic analyses have shown that the constant (C) region of human kappa light chains is encoded by a single gene, whereas that of lambda chains is encoded by multiple genes. We have determined the complete C region amino acid sequence of two monoclonal lambda VI light chains, Bence Jones proteins Sut and Mor. The C region of lambda chains Sut and Mor consists of 105 residues, as is characteristic for human lambda light chains, of which 102 are identical in sequence. Protein Sut has the C region sequence associated with the C lambda isotype Mcg-, Kern-, Oz+ and represents a product of the C lambda 3 (Kern-, Oz+) gene. Protein Mor has a C region sequence associated with Mcg-, Kern-, and Oz- proteins but differs from protein Sut by the presence of three amino acid interchanges at positions 168, 176, and 194. These substitutions distinguish protein Mor from lambda chains encoded by the C lambda 1 (Mcg+), C lambda 2 (Kern-, Oz-), and C lambda 3 (Kern-, Oz+) genes and provide further evidence for polymorphism of the human C lambda genome. The gene encoding the C region sequence of lambda chain Mor is designated CMor lambda.

Amino Acid Sequence

Association of human lambda light chain V/J/C segments: serologic analysis and primary structure of the lambda VI Bence Jones protein THO.

The complete amino acid sequence of the human monoclonal lambda VI light chain Bence Jones protein THO was determined. We have found it to have remarkable similarities to the previously sequenced lambda VI Bence Jones protein SUT. Immunochemical analyses demonstrated that both lambda VI chains belong to a V lambda VI sub-subgroup. The 98-residue V gene-encoded segments of proteins THO and SUT are closely homologous and are distinguished from other lambda VI chains by a one-residue deletion at the V-J recombination site. Proteins THO and SUT have identical 13-residue J segments and therefore are encoded by the same J lambda gene. Further, both proteins have identical 105-residue C regions that by sequence represent products of the C lambda 3 (Kern-, Oz+) gene. The primary structure and serologic properties of proteins THO and SUT imply at the protein level of association between certain types of V lambda, J lambda, and C lambda segments.

Amino Acid Sequence

Relationship between duration of systolic upstroke of apexcardiogram and internal indexes of myocardial function in man.

In 11 patients with nonobstructive cardiomyopathy and coronary heart disease and decreased myocardial function of the left ventricle, as well as in nine patients without left heart valvular or myocardial disease, left apexcardiograms were recorded during diagnostic heart catheterization, wherein micromanometers were used; ACG's were registered additionally in 54 healthy volunteers in order to establish the normal range of apexcardiographic parameters. In all cases the apex tracings were recorded by means of a pulse transducer with infinite time constant. The most important finding of this study was the close correlation between the duration of the systolic upstroke (SUT) of the apex tracing and some accepted isovolumic indexes of left heart function (isovolumic contraction time, time interval from the onset to peak of the first derivative of left ventricular pressure, maximal value of the first derivative of left ventricular pressure, and the peak measured velocity of shortening of the contractile elements). Further, the mean value of SUT in patients with impaired left myocardial function was significantly prolonged, compared to the control subjects; an overlap was apparent due to the fact that some of these patients showed a normal left myocardial performance at rest, having an abnormal response only to exercise tests. The apexcardiographic SUT can practically always be measured when the first derivative of apex tracing is simultaneously recorded. It showed itself to be only slightly influenced by the resting heart rate. The mentioned relationship of the systolic upstroke time of the ACG to internal isovolumic indexes of myocardial function makes this noninvasive measurable parameter an additional excellent tool for the evaluation of the left myocardial state, thus supporting a new aspect of the value of quantitative apexcardiography.

Adult

Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3).

The human interleukin-3 receptor (IL-3R) is composed of an IL-3 specific alpha subunit (IL-3R alpha) and a common beta subunit (beta c) that is shared by IL-3, granulocyte/macrophage colony stimulating factor (GM-CSF) and IL-5 receptors. In contrast to the human, the mouse has two distinct but related genes, AIC2A and AIC2B, both of which are homologous to the human beta c gene. AIC2B has proved to encode a common beta subunit between mouse GM-CSF and IL-5 receptors. AIC2A is unique to the mouse and encodes a low affinity IL-3 binding protein. Based on the observation that the AIC2A protein is a component of a high affinity IL-3R, we searched for a cDNA encoding a protein which conferred high affinity IL-3 binding when coexpressed with the AIC2A protein in COS7 cells. We obtained such a cDNA (SUT-1) encoding a mature protein of 70 kDa that has weak homology to the human IL-3R alpha. The SUT-1 protein bound IL-3 with low affinity and formed high affinity receptors not only with the AIC2A protein but also with the AIC2B protein. Both high affinity IL-3Rs expressed on a mouse T cell line, CTLL-2, showed similar IL-3 binding properties and transmitted a growth signal in response to IL-3. Thus, the mouse has two distinct functional high affinity IL-3Rs, providing a molecular explanation for the differences observed between mouse and human IL-3Rs.

Amino Acid Sequence

Genomic and functional characterization of sugar transporters reveals potential roles in sugar accumulation in a modern sugarcane cultivar.

Sugarcane (Saccharum spp.) is a globally important sugar crop whose productivity depends on efficient sugar transport from source to sink organs. However, systematic identification and functional characterization of sugar transporters (STs) in sugarcane cultivars remain limited. Here, we identified 190 non-redundant ST genes in sugarcane cultivar Guitang 42 (GT42) and phylogenetically classified them into nine groups within the Monosaccharide Transporter (MST), Sucrose Transporter (SUT), and Sugars Will Eventually be Exported Transporters (SWEET) families. Comparative evolutionary analysis revealed significant lineage-specific expansions in the PMT, STP subfamilies, and SWEET families compared to diploid and wild relatives, likely driven by polyploidization and intensive selection for sugar yield. Transcriptomic profiling across tissues and internode elongation stages demonstrated marked tissue-specific and developmental expression patterns. Yeast complementation assays confirmed the transport activity of candidate MSTs, SUTs and SWEETs, with confocal microscopy verifying their distinct subcellular localization at the plasma membrane, tonoplast, or endoplasmic reticulum. Furthermore, transient overexpression of several candidate transporters (ScSWEET4-T2, ScSWEET15, and ScTST4-T1) in Nicotiana benthamiana modulated soluble sugar accumulation, and their expression in sugarcane protoplasts activated key sugar-responsive marker genes (ScGPT2 and ScWIP4). Together, our study establishes a systematic genomic framework and identifies candidate functional transporters that govern sugar partitioning and storage, providing valuable genetic targets for molecular breeding and quality enhancement in sugarcane.

Functional characterization

Local tumor recurrence after curative resection for rectal cancer. A ten-hospital review.

Local tumor recurrence rates after curative rectal cancer surgery with the end-to-end anastomosis stapler (EEA) are reportedly high. Therefore, a retrospective review in ten Yale-affiliated hospitals was undertaken to establish the outcome of surgical resection for rectal cancer in this patient population. Of those 373 patients who had had curative resections, 192 (52 percent) were abdominoperineal resections (APR); 105 patients (28 percent) had restorative resections with sutured anastomoses, and the EEA stapler was used in 76 patients (20 percent). There was an equal distribution of tumors in the various Dukes' stages in all three procedures. Local tumor recurrence was: APR 19 percent, SUT 17 percent, and EEA 24 percent, but local tumor recurrence was more frequent after EEA than APR for tumors 7 to 10 cm from the anal verge (32 vs. 13 percent, respectively, P less than 0.05), and the time to recurrence was least in EEA patients. It is concluded that local tumor recurrence is higher than expected for all three procedures and that the EEA stapler was associated with a greater risk of local tumor recurrence. These findings are attributed to surgeon-related technical operative factors rather than to the nature of the tumors themselves.

Adult

Multipotential hemopoietic cell lines isolated from stem cell cultures infected with Friend virus complex (MuLV + F-SFFV) show presence of MuLV but not F-SFFV.

The only factor-dependent or factor-independent hemopoietic murine stem cell lines which can be permanently maintained in vitro are cell lines which originate from bone marrow cultures of congenic mice differing in the Fv-2 locus infected with Friend spleen focus forming virus (F-SFFV) in conjunction with either Rauscher or Friend helper virus (R-MuLV or F-MuLV). We determined the viral state of these cells by restriction enzyme analysis, measurement of SFFV and MuLV related RNA, immunoprecipitation analysis of viral related proteins and biological activity to test whether integration and expression of R-MuLV or F-SFFV are obligatory. All stem cell lines (SUT, JUT, 416B) showed expression of MuLV coded proteins or virus but SFFV was not found in these cell lines. A two-fold difference of RNA hybridizing with SFFV-specific cDNAs observed in stem cells of Fv-2rr and of Fv-2ss genotype is in agreement with data published earlier.

Animals

Selection of dieldrin-resistant strains of Lucilia cuprina (Diptera: Calliphoridae) after ethyl methanesulfonate mutagenesis of a susceptible strain.

After ethyl methanesulfonate (EMS) mutagenesis of a susceptible strain (SWT), selective screening of Lucilia cuprina (Wiedemann) resulted in four strains that were resistant to the insecticide dieldrin. Concentrations used for selection were greater than LC99 of susceptible phenotypes. No resistant variants were screened from the standard laboratory strain (SWT) not treated with EMS. The resistance phenotypes of the four resistant strains were similar to each other and to that of a field-selected resistant strain. The genetic basis of resistance is monogenic in all strains and the data are consistent with the same locus, Rdl, determining resistance status in each strain. The Rdl locus maps to chromosome V, approximately 3.5 map units distal to the Sut locus. Dieldrin resistance may be caused by less effective blocking of insect neuronal GABA receptors by the chemical in resistant strains. The data indicate that the evolution of resistance to an insecticide in the field may be constrained by a limited number of genetical and biochemical options if a monogenic response is selected for and that the spontaneous mutation rate to the Rdl allele is less than 1 in 10(6) in the laboratory.

Animals

Amino acid sequence of a lambda VI primary (AL) amyloid protein (WLT).

It has been observed that monoclonal immunoglobulin proteins of the lambda VI subgroup have a high propensity to form amyloid deposits. To ascertain whether lambda VI proteins have unique structure determinants that would account for self association and resultant fibril formation, we have determined the complete amino acid sequence of the AL amyloid protein WLT. This protein, isolated from the spleen of a patient with AL amyloid, has 134 amino acid residues and contains the entire variable region, the joining segment, and the first tryptic peptide of the constant region. Comparison of the structure of this protein with the 3 completely sequenced lambda VI proteins reveals that they are highly homologous and contain a 2-residue insertion at positions 68 and 69. Phylogenetic comparisons of the variable domain of all lambda VI proteins reveal that the 3 amyloid proteins WLT, SUT, and AR are all more closely related to each other than to the myeloma protein NIG48. Separating the variable domains into framework (FR) and complementarity-determining regions (CD) and recalculating the phylogenetic comparisons, we identify major substitutions in the FR regions of NIG48 in relation to the amyloid proteins. This supports the hypothesis that the formation of AL amyloid is a result of the secondary structure of the FR regions of the precursor molecules.

Adult

Toxic effect of endocytobionts from Dermacentor reticulatus ticks in three tick species after in vivo application.

The endocytobionts from ovaries of partially engorged female Dermacentor reticulatus ticks, inoculated introcoelomally into females of three tick species, D. reticulatus, Ixodes ricinus and Haemaphysalis inermis, caused considerable morphological alterations in the examined cells and tissues of the synganglion, fat body, tracheal complex and ovary of these recipients.

Animals

Mycobacteria glycolipids as potential pathogenicity effectors: alteration of model and natural membranes.

Four mycobacterial wall glycolipids were tested for their effects on phospholipidic liposome organization and passive permeability and on oxidative phosphorylation of isolated mitochondria. From fluorescence polarization of diphenylhexatriene performed on liposomes it was concluded that the two trehalose derivatives (dimycoloyltrehalose and polyphthienoyltrehalose) rigidified the fluid state of liposomes, the triglycosyl phenolphthiocerol slightly fluidized the gel state, while the peptidoglycolipid ("apolar" mycoside C) just shifted the phase transition temperature upward. Dimycoloyltrehalose was without effect on liposome passive permeability, as estimated from dicarboxyfluorescein leak rates, and polyphthienoyltrehalose and triglycosyl phenolphthiocerol slightly decreased leaks, while mycoside C dramatically increased leaks. Activity of these lipids on mitochondrial oxidative phosphorylation was examined. The two trehalose derivatives have been tested previously: both had the same type of inhibitory activity, dimycoloyltrehalose being the most active. Triglycosyl phenolphthiocerol was inactive. Mycoside C was very active, with effects resembling those of classical uncouplers: this suggested that its activity on mitochondria was related to its effect on permeability. All these membrane alterations were called nonspecific because it is likely that they result from nonspecific lipid-lipid interactions, and not from recognition between specific molecular structures. Such nonspecific interactions could be at the origin of some of the effects of mycobacteria glycolipids on cells of the immune system observed in the last few years.

Animals

Tonoplast sucrose transporter SUT4-dependent sugar partitioning modulates phenological transitions and reproductive success in poplar.

Climate uncertainty is intensifying the need for greater plasticity in carbohydrate reserve utilization to support winter survival and spring growth in woody perennials. In poplar, the single-copy SUT4, which encodes a tonoplast-localized sucrose transporter, and the SUT5/SUT6 genome duplicates, which encode plasma membrane-localized transporters, are expressed year-round, with SUT4 showing the highest expression during cool seasons. Given its role in vacuolar sucrose efflux and winter-predominant expression, SUT4 may play a key role in modulating seasonal carbohydrate dynamics. While SUT4-knockdown and knockout effects have been studied under greenhouse conditions, their impact under field conditions remains unexplored. Here, we report a field-based study comparing CRISPR knockout mutants of winter-expressed SUT4 and SUT5/SUT6 in Populus tremula × alba. We show that sut4, but not sut5/6, mutants exhibited earlier autumn leaf senescence, delayed spring bud flush, reduced stem growth, and altered sugar partitioning in winter xylem and bark relative to controls. After 2 years in the field, all genotypes flowered before leaf flush in early spring; however, sut4 mutants produced sterile ovules despite developing normal-looking catkins. Metabolic profiling revealed disrupted sucrose and raffinose dynamics in elongating sut4 catkins. This was accompanied by transcriptomic signatures of elevated stress and downregulation of proanthocyanidin biosynthesis and circadian clock genes. These findings highlight the critical role of SUT4 in coordinating sugar allocation, stress responses, and seasonal development in poplar.

Populus

Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio-adipose-muscle axis.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood. METHODS: We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction. RESULTS: Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty. CONCLUSIONS: Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress-muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio-adipose-muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.

Humans