The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

T cell receptor repertoires after adoptive transfer of expanded allogeneic regulatory T cells.

Regulatory T cell (Treg ) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GVHD). However, our knowledge on the in-vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCR-α-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer. We applied TCR-α-NGS to samples from two patients with chronic GVHD who received comparable doses of stem cell donor derived expanded Treg . We found that in-vitro polyclonal expansion led to notable repertoire changes in vitro and that Treg cell therapy altered the peripheral Treg repertoire considerably towards that of the infused cell product, to different degrees, in each patient. Clonal changes in the peripheral blood were transient and correlated well with the clinical parameters. We suggest that T cell clonotype analyses using TCR sequencing should be considered as a means to monitor longevity and fate of adoptively transferred T cells.

Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation.

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αß sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.

The effect of episodic anxiety on an in vitro fertilization and intracytoplasmic sperm injection treatment outcome: a pilot study.

This study examines whether the inconsistent and contradictory findings from prospective studies on the effect of psychosocial factors on treatment outcome of in vitro fertilization (IVF) can be explained by the fact that no clear distinction has been made between acute and chronic emotional stress responses. Because chronicity is difficult to measure within the context of an IVF-procedure, the focus of the present study was on episodic anxiety. We compared its predictive value on treatment outcome after the second IVF and intracytoplasmic sperm injection (ICSI) with the predictive value of trait anxiety and acute anxiety. In a prospective study with 47 women who failed to conceive after the first IVF, state anxiety was measured both before and after the first IVF treatment. Episodic anxiety was operationalized as high state anxiety both before and after the first IVF treatment Student's t-test and logistic regression analysis were used to determine the predictive value of episodic anxiety compared with acute or trait anxiety. Women with episodic anxiety, but not those with high levels of trait or acute anxiety, were less likely to become pregnant after the second IVF/ICSI. The results suggest that future studies should differentiate between acute and chronic stress, when examining the effects of psychosocial factors on treatment outcome after a fertility treatment

Prevalence of leptospiral infection in Texas cattle: implications for transmission to humans.

Of 1193 Texas slaughterhouse cattle serum samples assayed for anti-leptospiral antibodies by microscopic agglutination testing, 262 (22%) reacted with serovar pomona and 179 (15%) with serovar hardjo. Of 300 urine samples tested for leptospiral DNA by a polymerase chain reaction assay, 106 (35%) were positive. The high prevalence of leptospiral infection of cattle represents potential threats to human health and agricultural economics.

Stress and marital satisfaction among women before and after their first cycle of in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To determine differences in emotional status (anxiety and depression) and marital satisfaction in pregnant and nonpregnant women before and after their first cycle of IVF and intracytoplasmic sperm injection (ICSI). DESIGN: Repeated measurement. SETTING: Fertility department at a university and a regional hospital. PATIENT(S): Women entering their first treatment cycle of IVF or ICSI. INTERVENTION(S): Questionnaires on psychological factors were administered 3 to 12 days before the start of their first treatment cycle and repeated 3 weeks after the pregnancy test. MAIN OUTCOME MEASURE(S): State anxiety, depression, mood, and marital satisfaction. RESULT(S): At pretreatment, the women who became pregnant showed lower levels of depression than those who did not. Higher levels of depression in the pregnant women after the first cycle were due to higher scores on vital aspects of depression, related to signs of early pregnancy. Higher levels of depression in the nonpregnant women were due to a higher score on cognitive aspects of depression. CONCLUSION(S): Differences in emotional status between pregnant and nonpregnant women were present before treatment and became more apparent after the first IVF and ICSI cycle. There were no differences in emotional status between the women who underwent IVF and those who underwent ICSI.

The effect of anxiety and depression on the outcome of in-vitro fertilization.

BACKGROUND: The study aim was to clarify the role of anxiety and depression on the outcome in assisted reproductive treatment. Previous studies on this topic have shown contradicting results, which may have been caused by population characteristics, the design of the study, or small sample sizes. METHODS: In a multicentre prospective study, 291 out of 359 (81%) consecutively invited women agreed to participate. Before down-regulation by means of gonadotrophin-releasing hormone (GnRH) analogues in a long IVF protocol, patients were asked to complete the Dutch version of the State and Trait Anxiety Inventory to measure anxiety, and the Dutch version of the Beck Depression Inventory (BDI) to measure depression. Multiple logistic regression analysis was used to analyse known predictors of pregnancy and psychological factors and their relationship with treatment outcome. RESULTS: A significant relationship was shown between baseline psychological factors and the probability to become pregnant after IVF/intracytoplasmic sperm injection (ICSI) treatment, controlling for other factors. State anxiety had a slightly stronger correlation (P = 0.01) with treatment outcome than depression (P = 0.03). CONCLUSIONS: Pre-existing psychological factors are independently related to treatment outcome in IVF/ICSI, and should therefore be taken into account in patient counselling. Psychological factors may be improved by intervention, whereas demographic and gynaecological factors cannot. Future studies should be directed towards underlying mechanisms involved and the role of evidence-based distress reduction in order to improve treatment results.

COP I domains required for coatomer integrity, and novel interactions with ARF and ARF-GAP.

We performed a systematic mapping of interaction domains on COP I subunits to gain novel insights into the architecture of coatomer. Using the two-hybrid system, we characterize the domain structure of the alpha-, beta'-, epsilon-COP and beta-, gamma-, delta-, zeta-COP coatomer subcomplexes and identify links between them that contribute to coatomer integrity. Our results demonstrate that the domain organization of the beta-, gamma-, delta-, zeta-COP subcomplex and AP adaptor complexes is related. Through in vivo analysis of alpha-COP truncation mutants, we characterize distinct functional domains on alpha-COP. Its N-terminal WD40 domain is dispensable for yeast cell viability and overall coatomer function, but is required for KKXX-dependent trafficking. The last approximately 170 amino acids of alpha-COP are also non-essential for cell viability, but required for epsilon-COP incorporation into coatomer and maintainance of normal epsilon-COP levels. Further, we demonstrate novel direct interactions of coatomer subunits with regulatory proteins: beta'- and gamma-COP interact with the ARF-GTP-activating protein (GAP) Glo3p, but not Gcs1p, and beta- and epsilon-COP interact with ARF-GTP. Glo3p also interacts with intact coatomer in vitro.

Psychological aspects of in vitro fertilization: a review.

This paper reviews psychological research within the context of in vitro fertilization (IVF). The focus will be on psychological reactions before entering an IVF-procedure, during an IVF-treatment, and after both unsuccessful and successful IVF. The effects of psychosocial factors on the treatment outcome after IVF and interventions on conception rates will also be discussed. Undergoing an IVF-treatment is an emotional and physical burden, for both the woman and her partner. Research results suggest that couples entering an IVF-treatment program are, in general, psychologically well adjusted. Concerning reactions during the treatment, both women and men experience waiting for the outcome of the IVF-treatment and an unsuccessful IVF. as most stressful. Common reactions during IVF are anxiety and depression, while after an unsuccessful IVF, feelings of sadness, depression and anger prevail. After a successful IVF-treatment, IVF-parents experience more stress during pregnancy than 'normal fertile' parents. Mothers with children conceived by IVF express a higher quality of parent child relationship than mothers with a naturally conceived child. Research further suggests that psychosocial factors, like ineffective coping strategies, anxiety and/or depression are associated with a lower pregnancy rate following IVF-procedures. In addition, support has been found suggesting that stress reduction through relaxation training or behavioral treatment improves conception rates.

[Infantile myofibromatosis--a case report]. / Die infantile Myofibromatose--Fallbericht.

A four months old child was referred for a rapidly growing recurrency of a tumor of the left eyebrow. The tumor was excised completely. The pathologic examination revealed an infantile myofibromatosis, most probably of the solitary type. The term "infantile myofibromatosis" summarizes a heterogenous group of rare fibromatoses in childhood, characterized by the proliferation of myofibroblasts. Isolated tumors have a fair prognosis after complete excision.

Knowledge-based patient screening for rare and emerging infectious/parasitic diseases: a case study of brucellosis and murine typhus.

Many infectious and parasitic diseases, especially those newly emerging or reemerging, present a difficult diagnostic challenge because of their obscurity and low incidence. Important clues that could lead to an initial diagnosis are often overlooked, misinterpreted, not linked to a disease, or disregarded. We constructed a computer-based decision support system containing 223 infectious and parasitic diseases and used it to conduct a historical intervention study based on field investigation records of 200 cases of human brucellosis and 96 cases of murine typhus that occurred in Texas from 1980 through 1989. Knowledge-based screening showed that the average number of days from the initial patient visit to the time of correct diagnosis was significantly reduced (brucellosis-from 17.9 to 4.5 days, p = 0.0001, murine typhus-from 11.5 to 8.6 days, p = 0.001). This study demonstrates the potential value of knowledge-based patient screening for rare infectious and parasitic diseases.

Protozoal abortion in a herd of cattle concurrently infected with Hammondia pardalis.

Protozoal infection was diagnosed as the cause of abortion in a large drylot dairy herd located in northeastern Mexico. Diagnosis was made on the basis of finding encephalitis, myocarditis, protozoal cysts, and protozoal tachyzoites in aborted fetuses. The blended ration fed to the cows had been contaminated by the feces of a large resident population of feral domestic cats that used components of the blended ration for den sites (stored hay) or as a latrine (grain). The cows that aborted contained tissue phases of a protozoan infective for domestic cats. The morphologic features of the oocyst and biologic features of the protozoan were identical to those of Hammondia pardalis.

Clinical and epizootiologic characteristics of dogs seropositive for Borrelia burgdorferi in Texas: 110 cases (1988).

Of 2,409 canine serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Jan 1, 1988 and Dec 31, 1988 and tested by immunofluorescent antibody technique for antibody to Borrelia borgdorferi, 132 (5.5%) had positive results. Clinical and epizootiologic characteristics of seropositive dogs from Texas (n = 110) were examined. Male dogs were more likely than female dogs to be seropositive for B burgdorferi. The most frequent clinical sign of disease described in seropositive dogs was lameness; neurologic, ophthalmologic, dermatologic, renal, and hepatic signs also were reported by referring veterinarians.

Epizootiologic association between feline immunodeficiency virus infection and feline leukemia virus seropositivity.

Five hundred twenty-one feline serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Nov 1, 1988, and Jan 31, 1989 were tested for antibody to feline immunodeficiency virus (FIV) by use of an ELISA. The prevalence of FIV infection in this population was 11.3% (95% confidence interval: 8.6 to 14.0%). Serologic test results for FeLV were available for 156 of the 521 cats. A significant (P = 0.008) association between FIV infection and FeLV seropositivity was observed; FeLV-positive cats were nearly 4 times more likely to be seropositive for FIV than were FeLV-negative cats. The association remained statistically significant (P = 0.021) after adjusting for age and gender, using multiple-logistic regression analysis.

15N-labeled P22 c2 repressor for nuclear magnetic resonance studies of protein-DNA interactions.

The salmonella phage P22 c2 repressor was produced with 90% 15N isotope labeling of all leucines, using the expression system E. coli W3110 lac IQ¿P 125. The N-terminal DNA-binding domain 1-76 was obtained by chymotrypsin cleavage. Its characterization by biochemical techniques, mass spectrometry, and one- and two-dimensional nuclear magnetic resonance (NMR) showed that highly residue-selective isotope labeling was achieved with the minimal growth medium used. The ability to obtain such isotope labeling opens new avenues for NMR studies of protein-DNA interactions in the P22 operator system.

Treatment of giardiasis in adult Greyhounds, using ipronidazole-medicated water.

Two of 3 adult Greyhounds with clinical signs of giardiasis were treated by the addition of ipronidazole hydrochloride to their water supply (126 mg/L) for 7 days. Within 15 hours, the dogs had improved clinically, and large numbers of degenerating Giardia cysts were passed. After 54 hours, cyst shedding had ceased. The nontreated control dog continued to shed Giardia cysts. During an additional 7 days, the dogs were treated with ipronidazole-medicated water (378 mg/L) and remained clinically normal.

Catastrophic death losses in a dairy herd attributed to type D botulism.

Clostridium botulinum type D intoxication was diagnosed as the cause of death of 42 of 67 lactating cows in a southeast Texas dairy herd over an 11-day period. By necessity, the diagnosis was based on clinicopathologic findings, as the toxin could not, by standard laboratory tests, be demonstrated in affected cattle. The predominant clinical findings were hindlimb weakness/ataxia rapidly progressing to persistent recumbency. Affected cattle were alert until just before death, which occurred without notable agonal movements or respirations after 6 to 72 hours' recumbency. Abnormal laboratory findings included neutrophilic leukocytosis (all affected cattle), proteinuria (most affected cattle), slight elevations of serum aspartate transaminase and low serum inorganic phosphorus (some affected cattle), and patchy areas of hyperemia/congestion of the mucosa in the small intestine (postmortem examination of 3 affected cattle). This report confirms the findings of others with regard to the difficulty of demonstrating the causative toxin in C botulinum type D-intoxicated cattle and presents available information on the clinicopathologic features of this intoxication that may aid in the differentiation of this condition from other causes of down cows.

Determination of the coordination geometry at the heme iron in three cytochromes c from Saccharomyces cerevisiae and from Candida krusei based on individual 1H-NMR assignments for heme c and the axially coordinated amino acids.

The 1H-NMR lines of heme c and the axial ligands in reduced and oxidized Iso-1 and Iso-2 cytochromes c from Saccharomyces cerevisiae and in cytochrome c from Candida krusei were individually assigned and the conformation of the coordination sphere of the heme iron was investigated with the use of proton-proton Overhauser enhancement measurements and circular dichroism spectroscopy. The coordination geometry of the axial methionine and the axial histidine and the electronic structure of the heme were found to be closely similar in these yeast cytochromes c and in mammalian cytochromes c. In particular, R chirality at the sulfur atom of the iron-bound methionine was observed in both groups of proteins. Additional nuclear Overhauser enhancement studies of the spatial arrangement relative to the heme group of amino acid side-chains in the heme crevice of yeast ferrocytochromes c showed that the conformational homologies extend beyond the immediate coordination sphere of the heme iron. These data provide a conformational basis for observations on the functional properties of cytochromes c from yeast and mammalian species, which were reported previously by other groups.

Studies on canine parvovirus infections: development of an inactivated vaccine.

parvoviruses isolated from the intestines of dogs that died of an enteric infection were propagated in various parasynchronized canine and feline cell cultures. Viral antigen could be visualized in infected cell cultures with the aid of fluorescein-labeled feline, as well as porcine, parvovirus antisera, and in an indirect test with sera from dogs that had recovered from a parvovirus infection. The virus hemagglutinated porcine RBC at 4 C and 25 C but not at 37 C. An inactivated canine parvovirus vaccine elicited an immune response, but no adverse reactions, when inoculated into dogs. Vaccinated dogs were immune and did not show any clinical signs when challenge exposed with virulent virus, whereas nonvaccinated, nonimmune dogs became clinically ill when inoculated with the same virus. Humoral hemagglutination-inhibiting parvovirus antibody values corresponded well with susceptibility and resistance to experimental inoculation of dogs with canine parvoviruses.