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A structural equation model for describing relationships between somatic cell score and milk yield in first-lactation dairy cows.

Relationships between production and diseases may involve recursive or simultaneous effects between traits. Four structural equation models (SEqM) for somatic cell score and milk yield, with varying specifications for the effects relating the 2 traits, were compared. Data consisted of repeated records of milk yield and somatic cell score of 33,453 first-lactation daughters of 245 Norwegian Red sires that had their first progeny test in 1991 and 1992. All models included random effects of the sire and of the cow and were fitted using the LISREL software. The Bayesian information criterion clearly favored a model with a recursive effect from somatic cell score on milk yield over the 3 other models fitted (absence of recursive effects; an effect from milk yield on somatic cell score; simultaneity of effects between the 2 traits). This provides evidence that the negative association between milk yield and somatic cell score is more likely due to an effect of infection (measured indirectly by the somatic cell score) on production than to a dilution effect. Estimates indicated that a mastitis event would reduce milk yield in the following 15 d by about 900 g/d. The estimated genetic (co)variances did not change sizably when the specification of recursive or simultaneous effects was varied. However, estimates of the phenotypic covariance were altered when a recursive effect from somatic cell score on milk yield was included in the model.

Age Factors↗

Variability of test-day milk production and composition and relations of somatic cell counts with yield and compositional changes of bovine milk.

Between November 1979 and November 1981, 41,783 test-day observations were obtained from 63 Holstein herds in the province of Quebec. Measured were milk yield, percentages of fat, protein, casein, and serum protein, and somatic cell counts that had unadjusted means with standard errors 20.44 +/- .04 kg, 3.684 +/- .003%, 3.314 +/- 002%, 2.694 +/- .001, .669 +/- .001%, and 313625 +/- 3238/ml of milk. Casein as a percentage of total protein (casein number) was 79.35 +/- .015. Least squares analyses showed significant effects of herd, calendar month of test, age of sample at laboratory testing, stage of lactation, age of cow, and somatic cell counts on milk yield and composition. Milk yield was higher whereas percentages of fat and protein and somatic cell counts were lower in summer than in winter months. Somatic cells, fat, protein, and casein contents were high during early stages of lactation, reached a minimum at 2 mo in lactation, and rose gradually throughout the rest of the lactation. A comparison of younger cows (less than or equal to 2 yrs) with older one (greater than or equal to 6 yr) revealed that somatic cell counts increased from 166,000 to 507,000/ml of milk and casein number decreased from 80.14 to 78.88. Increase of somatic cell counts in milk was associated with increased protein content, which was mainly from the serum protein fraction as the casein fraction was not related with somatic cells.

Age Factors↗

Effective use of dairy herd improvement somatic cell counts in mastitis control.

The single most important factor affecting somatic cell count in milk is mammary gland infection status. In comparison, all other factors are minor. Consideration needs to be given to diurnal effects on Dairy Herd Improvement a.m.-p.m. sampling schemes. Somatic cell count linear score of 5 (283,000) appears to be a good choice of threshold for mastitis control applications. A greater understanding of the nonbacteriological factors affecting somatic cell count is needed so that relative thresholds could be used to improve the clarity of somatic cell count interpretation. Linear score loss estimates are effective educational tools providing motivation for mastitis control implementation. Infection status or milk loss estimates based on single somatic cell count tests on individual cows are weak. A lactational average linear score on individual cows or linear score compilations across a herd provide credible estimates. Treatment of subclinical mastitis based on somatic cell count levels is not economically beneficial and is not recommended. Usefulness of Dairy Herd Improvement somatic cell count data as a mastitis management tool requires measures of mastitis level, new infection rate, and mastitis pattern within the herd over time.

Animals↗

Variability in true protein, casein, nonprotein nitrogen, and proteolysis in high and low somatic cell milks.

Monthly variation in milk protein (total nitrogen X 6.38) and milk fat was determined for 115 farms over 2 yr. Yearly average milk protein and fat tests in each year were 3.16 and 3.62%, respectively. The mean regression coefficient for milk protein with respect to milk fat was .47 for the entire period. Twenty-four farms were selected and grouped high or low based on their previous 2-yr somatic cell history. Monthly milk samples for each farm were tested for direct microscopic somatic cell count, total nitrogen, noncasein nitrogen, and nonprotein nitrogen. No differences in monthly nonprotein nitrogen, true protein, and casein were found between groups. Casein as a percent of total nitrogen was significantly higher for the low somatic group for seven of the 12 mo studied but was significantly higher for 9 mo when expressed as a percent of true protein. The average increase in tyrosine value for incubated preserved milk was significantly higher for the high somatic cell milk, indicating higher proteolytic activity in high somatic cell milk. Electrophoretic analysis of high and low somatic cell milk indicated that there was substantial proteolytic breakdown of alpha S-casein and beta-casein by proteases associated with elevated somatic cell counts.

Animals↗

Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects.

The negative affective aspects of nicotine withdrawal have been hypothesized to contribute to tobacco dependence. In the present studies in rats, brain stimulation reward thresholds, conditioned place aversions, and somatic signs of withdrawal were used to investigate the role of central and peripheral nicotinic acetylcholine and opioid receptors in nicotine withdrawal. Rats prepared with s.c. osmotic mini-pumps delivering 9.0 mg/kg/day nicotine hydrogen tartrate or saline were administered various doses of the nicotinic antagonists mecamylamine (s.c.), chlorisondamine (s. c. or i.c.v.), dihydro-beta-erythroidine (s.c.), or the opiate antagonist naloxone (s.c.). Nicotine-treated rats receiving mecamylamine or i.c.v. chlorisondamine exhibited elevated thresholds and more somatic signs than saline-treated rats. Nicotine-treated rats receiving s.c. chlorisondamine, at doses that do not readily cross the blood-brain barrier, exhibited more somatic signs than saline-treated rats with no threshold elevations. Naloxone administration produced threshold elevations and somatic signs only at high doses that induced similar magnitude effects in both nicotine- and saline-treated subjects. Mecamylamine or dihydro-beta-erythroidine administration induced conditioned place aversions in nicotine-treated rats but required higher doses than those needed to precipitate threshold elevations. In contrast, naloxone administration induced conditioned place aversions at lower doses than those required to precipitate threshold elevations and somatic signs. These data provide evidence for a dissociation between centrally mediated elevations in reward thresholds and somatic signs that are both centrally and peripherally mediated. Furthermore, threshold elevations and somatic signs of withdrawal appear to be mediated by cholinergic neurotransmission, whereas conditioned place aversions appear to be primarily mediated by the opioid system.

Animals↗

[The effects of Ag+ on the absorption of trace metal ion during the somatic embryogenesis of Lycium barbarum. L].

We used callus of medical plant, Ningxia Lycium barbarum. L as material to induce somatic embryo genesis, and used multitracer technique and gamma-ray energy spectrum analytical method to study different concentration of AgNO3 on some absorption of trace metal ions during the somatic embryogenesis of Lycium barbarum. L. The results show that (1) when the concentration of AgNO3 is less then 50 mg/L, with the increase of AgNO3 concentration, the absorption rate of some metal ions is increasing, but when the concentration is excess of such concentration, the effects on the absorption rate are different. Ag+ has the effect of coordination, resistance or competition on the absorption of metal ions. (2) AgNO3 in suitable concentration will promote cell differentiation and somatic embryogenesis. When the concentration of AgNO3 is less then 50 mg/L, along with the increase of the concentration, the frequency of somatic embryogenesis is increased, and Ag+ has the promotion on the somatic embryogenesis of Lycium barbarum. L. While the concentration is up to 50 mg/L, it will mostly raise somatic embryogenesis in calli, the amount of callus is about 3 times as much as that of contrast group (in which AgNO3 is not added). When excess of this concentration point, Ag+ has toxic effect, and the somatic embryogenesis is inhibited remarkably.

Absorption↗

[Culture of soybean somatic embryo line and stability of microsatellite DNA].

We cultured soybean immature cotyledons to induce somatic embryos and set up soybean somatic embryo lines by culturing the induced somatic embryos in liquid medium on shaker. Regenerated plants of normal fertility were easily obtained with the cultures of various ages by culturing the somatic embryos on differentiation media. DNAs were isolated from the embryogenic cultures after 5, 9, 15 or 17 months' suspension and from 42 plants regenerated from somatic embryos of various culturing ages. 102 SSR markers covering soybean genome almost evenly were chosen to check variation of microsatellite DNA during suspension culture and differentiation. Among the eight DNA samples of soybean somatic embryos of various ages and 42 DNA samples of regenerated plants, there was no any variation of the major bands of the 102 SSR markers during one year's subculturing and differentiation. There were only six weaker subsidiary bands of five SSR markers among the 102 SSR markers added in four of the fifty DNA samples. Two of them happened to the same regenerated plant differentiated from the 9-month embryogenic cultures. Three happened to the two DNA samples from somatic embryos irregular in morphology of the 5-month embryogenic cultures. The last subsidiary band variation happened to a DNA sample of the 17-month embryogenic cultures. The results show that stable microsatellites were maintained during the suspension culture and differentiation while we made the cultures highly embryogenic potential and easy to regenerate.

Cotyledon↗

[Somatic investigation of psychiatric patients newly admitted to Flemish general psychiatric hospitals].

BACKGROUND: In Flanders there is as yet very little consensus concerning the extent and content of somatic investigations available to and conducted on patients newly admitted to psychiatric hospitals. AIM: To obtain an overview of the numbers and specialisms of medical-somatic staff at Flemish general psychiatric hospitals, the equipment available and the somatic routine examinations regularly requested. METHOD: We compiled a questionnaire about current hospital policy concerning the diagnosis of physical illnesses in newly admitted patients and the availability of diagnostic facilities. We submitted the questionnaires to 20 Flemish psychiatrist hospitals. RESULTS: The commonest type of medical equipment available at these psychiatric hospitals consisted of ECG, X-ray and ultrasonic devices. The routine examinations that were requested most frequently were blood and urine tests, ECG'S, clinical examinations, and X-rays of the thorax. The numbers and specialisms of somatic doctors at these hospitals vary from one hospital to the next. Sometimes a hospital does not have any somatic doctors at all. CONCLUSION: The general psychiatric hospitals in Flanders do not have a uniform policy concerning somatic examinations on newly admitted patients. The equipment and the numbers and specialisms of the medical-somatic staff vary from one hospital to another. It seems reasonable that extra investigations such as blood tests, ECG's and thorax X-rays should be conducted when case histories and clinical examinations indicate that such testing may be useful.

Belgium↗

Metabolic syndrome, somatic and psychiatric comorbidity in war veterans with post-traumatic stress disorder: Preliminary findings.

BACKGROUND: There has been a growing interest in the effect that co-morbid mental and somatic disorders may have on each other. Post-traumatic stress disorders (PTSD) have been associated with comorbidity of many major somatic and mental disorders as well as with premature mortality. OBJECTIVE: The objective of this study was to examine the relationship between combat-related PTSD, metabolic syndrome and comorbid psychiatric and somatic diagnoses. METHOD: Metabolic syndrome and its components as well as comorbid somatic and mental disorders were analysed in 47 male war veterans with combat PTSD. RESULTS: Only 4.25% of our patients were without any comorbid somatic and mental disorders, metabolic syndrome or any of its components. Other psychiatric or medical condition was diagnosed in 76.6 % of the PTSD patients. Metabolic syndrome according NCEP: ATP III was found in 31.9% of our PTSD patients. CONCLUSIONS: PTSD is multisystemic mental and somatic disorder. The treatment of war veterans with PTSD should address comorbid other mental and somatic disorders including metabolic syndrome as well as the clinical features of PTSD.

Adult↗

Differential transcription of Xenopus oocyte and somatic-type 5 S genes in a Xenopus oocyte extract.

We have measured the transcription of Xenopus laevis oocyte and somatic-type 5 S RNA genes in S-150 extracts prepared from ovaries of mature X. laevis females (Glikin, G. C., Ruberti, I., and Worcel, A. (1984) Cell 37, 33-41). We find that somatic-type 5 S genes are transcribed at least 40-fold more efficiently than oocyte-type 5 S genes. Since adenovirus VA, Xenopus OAX, and Xenopus tRNAMet genes are all transcribed at levels similar to that of the somatic-type 5 S gene, this difference reflects a low level of oocyte-type 5 S gene transcription. Somatic-type 5 S transcription is a linear function of somatic-type 5 S DNA concentration and this, together with the efficient transcription of other class III genes, suggests that RNA polymerase III and the general class III transcription factors are not limiting under the conditions used here. Moreover, the 5 S gene-specific transcription factor TFIIIA does not limit transcription under these conditions as preincubation with purified TFIIIA does not alter transcription of either gene, and both genes exhibit characteristic TFIIIA footprints under transcription conditions in the S-150. Somatic-type 5 S DNA incubated in the S-150 and then injected into oocyte nuclei is actively transcribed whereas oocyte-type 5 S DNA treated in the same manner is inactive. We conclude that factors in the S-150 distinguish between somatic and oocyte-type 5 S genes, assembling active complexes preferentially on the former and inactive complexes preferentially on the latter. This process is not explained by binding properties of transcription factors for these genes as currently understood and represents a previously unrecognized mechanism of transcriptional regulation of the Xenopus 5 S genes.

Animals↗

Potential of differential somatic cell counts as indicators of mastitis in quarter milk samples from dairy cows.

Bacteriological status, somatic cell counts and proportions of lymphocytes, granulocytes and monocytes were determined in 1,659 quarter milk samples from 39 dairy cows. Discriminant analysis was performed in order to assess the ability of total and differential somatic cell counts and combinations of total somatic cell count and each of the differential cell counts, to discriminate between infected and pathogen-free quarters, as well as between quarters infected with minor pathogens and quarters infected with major pathogens. Total somatic cell count classified 82.9% of all quarters correctly with respect to bacteriological status. Differential somatic cell count was less effective than total somatic cell count in discriminating between infected and pathogen-free quarters, as well as between quarters infected with minor vs. major pathogens. Combination of total and differential somatic cell counts did not improve the rate of correctly classified quarters. Inclusion of demographic data into the discriminant function increased the number of quarters correctly classified, mainly through an increase in the proportion of correctly classified infected quarters.

Animals↗

Somatic symptoms and depression.

Patients with psychiatric illness frequently visit their medical physicians with somatic complaints or amplification of complaints about chronic medical illness, yet few of these patients meet Diagnostic and Statistical Manual of Mental Disorders-Third Edition (DSM-III) criteria for a somatoform disorder. In a sample of 197 medical patients interviewed with the Diagnostic Interview Schedule, only 7.1% met DSM-III criteria for somatization disorder, but nearly one third of these patients met criteria for an abridged notion of somatization. Patients with current and lifetime major depression had significantly higher mean totals of positive somatic symptoms compared with controls who had no psychiatric disorder. Nearly one half of these patients with one or more depressive episodes in the course of their lifetime met the abridged criteria for somatization. This association of major depression with somatization is quite similar to findings from the Epidemiologic Catchment Area study suggesting that major depression, not the somatoform disorders, may be associated with most of the somatization seen in medical clinics.

Adult↗

Structure and expression of rodent genes encoding the testis-specific cytochrome c. Differences in gene structure and evolution between somatic and testicular variants.

Mammalian testis contains two forms of cytochrome c, one identical to the form found in somatic tissues and a second that is expressed in a stage-specific manner during spermatogenic differentiation. We have isolated both rat and mouse cDNA clones and the rat gene encoding the testis-specific cytochrome c and determined their DNA sequences. The testicular variant displays a number of notable differences with its somatic counterpart. 1) In contrast to the multipseudogene family derived from mammalian somatic cytochrome c genes, the testis gene is single-copy in genomic DNA with no detectable pseudogenes. 2) The rat testis gene is approximately 7 kilobases (kb) long with three introns totaling nearly 6.5 kb whereas the two introns dividing the 2.1-kb somatic gene occupy only 0.9 kb. Introns differ in position as well as size. 3) The testicular variant has a longer 5'-untranslated leader (230 versus 70 base pairs for the somatic gene) with an upstream open reading frame of 129 base pairs beginning with an AUG in a favorable translational context. 4) A single polyadenylation site in the testicular mRNA (approximately 900 nucleotides) contrasts with the three functionally equivalent sites observed in rat somatic messages. 5) Finally, rat and mouse testis cytochromes c differ at 4 amino acid residues as opposed to the complete sequence identity found in the somatic proteins suggesting a shorter unit evolutionary period for these molecules. These observations are consistent with a duplication of an ancestral cytochrome c gene leading to the emergence of novel structural features and regulatory properties likely associated with the striking tissue specificity of the testicular cytochrome c.

Amino Acid Sequence↗

A clinical approach to the somatizing patient.

Patients with chronic, unexplained physical complaints are evaluated diagnostically in two steps in primary care: (1) brief consideration of three specific, but rare, disorders (somatic delusion, conversion, and malingering); and (2) extensive consideration of the remaining three common but overlapping disorders (somatization disorder, hypochondriasis, and psychogenic pain). Because of frequent confusion in differentiating among the common somatizing disorders and because the treatment is similar for all, the family physician can be content with the general designation of "common somatization syndrome" when unable to distinguish among them. This diagnosis can be easily established by a good history and physical examination. Psychiatric referral is required for the rare somatizing disorders. The primary physician can manage the majority of the common somatizing patients by observing the following principles: develop a good physician-patient relationship, apply techniques of behavior modification, engage the patient at the somatic level but extend it to include associated life stresses, strategically use symptomatic measures, treat depression with full doses of antidepressants, and accept the importance of ongoing contact with the patient irrespective of symptoms. When these therapeutic principles are employed, decreased morbidity, medical utilization, and cost can be expected to follow.

Appointments and Schedules↗

Reactogenicity, immunogenicity and efficacy studies of Escherichia coli type 1 somatic pili parenteral vaccine in man.

Purified type 1 somatic pili from enterotoxigenic Escherichia coli (ETEC) strain H10407 (O78:H11) was evaluated as a parenteral immunizing agent in the hope that this antigen might enhance a contemplated polyvalent pilus vaccine. Intramuscular inoculation with 45, 90, 900 or 1 800 mcg of pili vaccine was tolerated without incident in 82 volunteers. Six of 15 persons who received a 28 day booster of 1 800 mcg developed local reactions while none of 52 persons receiving 180 or 450 mcg boosters evinced such reactions. Pili vaccine did not significantly alter intestinal transit time, absorptive capacity or the prevalence of colonic E. coli bearing type 1 somatic pili of the H10407 antigenic variety. All vaccinees developed significant rises in circulating IgG antibody to type 1 somatic pili, the magnitude of the response being directly proportioned to the vaccine dose. None of the vaccinees had significant rises to CFA I or II pili nor to heat-labile enterotoxin. However, many had rises in O antibody, particularly among those inoculated with 1 800 mcg. Three challenge studies were carried out with E. coli H10407 to assess vaccine efficacy. In the initial study the vaccinees were either protected against diarrhea (2 of 6 vaccinees versus 7/7 of controls) or had milder disease than the controls. In two subsequent challenges with H10407 significant protection was not seen. It was not clear whether protection exhibited by the vaccinee group in the first challenge was due to O antibody, pili antibody, or both acting synergistically. To clarify this, a group of the immunized volunteers were challenged with ETEC strain B7A which is a different serotype (O148:H28) lacks CFA/I or II pili, but possesses type 1 somatic pili antigenically distantly related to those of H10407. Attack rates and severity of illness were similar in both vaccinee and control groups. While most volunteers challenged with E. coli H10407 developed significant rises in circulating antibody to CFA/I, LT and O antigen, none had rises to type 1 somatic pili. It is unclear if this is due to immune tolerance to this antigen when encountered enterally or whether these pili are not present in vivo in ETEC initiating diarrhea in the proximal small intestine. In summary, parenterally inoculated type 1 somatic pili were safe and highly immunogenic in man but did not consistently induce protection. Further studies are planned to clarify the role of antibody to type 1 somatic pili in mediating protection.

Adult↗

Somatic gene therapy. Present situation and future perspective.

The ultimate goal in the management of inherited as well as acquired diseases is a rational therapy with the aim to eliminate the underlying biochemical defects, rather than a symptomatic treatment. Among other approaches somatic gene therapy is a promising candidate to meet these objectives and appears to have the potential to revolutionize modern medicine. Gene therapy is characterized by the transfer of genetic information to a patient through the use of recombinant DNA technology. Several strategies for the treatment of monogenetic disorders as well as chronical diseases like cancer and AIDS have been used in various somatic gene therapy projects. So far, 329 clinical studies (phases I, I/II and II) with over 2500 patients have been initiated worldwide since 1989. No significant toxicity and adverse side effects have been observed. To allow efficient transfer of the therapeutic genes, a variety of gene delivery techniques have been developed based on viral and non-viral vector systems. For the success of this technology it is vital to achieve regulated and sustained expression of foreign genes in specific target tissues. This will be crucial for the widespread application of somatic gene therapy. So far none for the gene delivery systems is able to meet the requirements of safety, efficiency and specificity demonstrating that vector research will be an important focus in the development of optimized transfer methods. From a regulatory point of view pharmaceutical DNA-products can be regarded as drugs and are therefore subject to the same regulations. Human gene therapy must, however, be limited to manipulations affecting somatic, differentiated cells to prevent the transferred gene from being transmitted to the individual's descendants. Applications for the purpose of 'enhancement' and not for the treatment of diseases are also not acceptable. Under these prerequisites, somatic gene therapy does not raise any new ethical concerns and can be interpreted as a special form of an organ transplantation. A comparison of the different regulatory situations of gene therapy in Europe and the United States demonstrates that for the European countries a uniform regulation is desired. Today somatic gene therapy is still in its infancy. It will continue to be scientifically and technically challenging until simple and effective procedures will have been developed. Demonstration of its clinical efficacy especially in the long term will have to be the next step. Looking at the history of biotechnology and the success of the biotechnology industry that is now providing safe and efficient products from recombinant DNA-technology there is little doubt that gene therapy will become a successful treatment for various indications in the next decade. The purpose of this article is to review the current status of the development in somatic gene therapy.

Acquired Immunodeficiency Syndrome↗

Shared inheritance reveals landscape of somatic and germline cancer risk in TP53.

Pathogenic variants in TP53, the key tumor suppressor gene underlying Li-Fraumeni syndrome (LFS), are among the best-established causes of inherited cancer predisposition. However, large-scale sequencing has revealed that many apparently pathogenic TP53 variants detected in blood are the result of somatic clonal expansions, complicating risk interpretation. Using blood-derived whole-exome data from 469,391 UK Biobank participants, we combined the variant allele fraction (VAF) with haplotype-sharing analysis to distinguish germline and somatic TP53 variants. Germline variants were concentrated at sites linked to partial loss of p53 function and lower disease penetrance, whereas classic LFS alleles appeared to be predominantly somatically acquired. Classic LFS alleles at high VAF conferred markedly increased risk of hematological malignancy but not solid tumors, indicating an important contribution from large TP53-mutant clonal expansions. The prevalence of somatic clonal expansion also correlated with missense variant pathogenicity, suggesting that somatic activity provides an informative in vivo proxy for functional impact. These results provide new insights into TP53-associated cancer risk at the population level, demonstrate that somatic rather than germline risk predominates in middle-aged healthy adults, and provide a scalable framework for variant classification in large-scale population genomics.

Humans↗

A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex.

Somatic mutations in individual cells create genomic mosaicism, influencing genetic disorders and cancers. While clonal mutations in cancers are well-studied, rarer somatic variants in normal tissues remain poorly characterized. This study systematically evaluates detection methods using a personalized donor-specific assembly (DSA) from a neurotypical individual's dorsolateral prefrontal cortex assessed with Oxford Nanopore, NovaSeq, linked-read sequencing, Cas9-targeted long-read sequencing (TEnCATS), and single-neuron MALBAC amplification. The haplotype-resolved DSA improved cross-platform analysis, dramatically increasing phasing rates. Germline SNVs, structural variations (SVs), and transposable elements (TEs) were recalled with 99.4%-99.7% accuracy in bulk tissue, and phased haplotype analysis reduced false positives by 15.4%-75.1% for putative somatic candidates. Long-read single-neuron sequencing detected nine somatic SV candidates, demonstrating enhanced sensitivity for rare variants, while TEnCATS identified eight low-frequency somatic TE candidates. These findings highlight advanced methodologies for precise somatic variant detection, critical for understanding mosaicism's role in health and disease.

Multi-platform Sequencing↗