Malic acid production from renewables: a review

Malic acid derived from fossil resources is currently applied in the food and beverage industries with a medium global production capacity. However, in the transition from a fossil-based to a bio-based economy, biotechnologically produced l -malic acid may become an important platform chemical with many new applications, especially in the field of biopolymers. In this review, currently used petrochemical production routes to dl -malic acid are outlined and insights into possible bio-based alternatives for microbial l -malic acid production are provided. Besides ecological reasons, the possibility to produce enantiopure l -malic acid by microbial fermentation is the biggest advantage over chemical synthesis. State-of-the-art and open challenges concerning production host engineering, substrate choice and downstream processing are addressed. With regard to production hosts, a literature overview is given covering the leading natural production strains of Aspergillus, Ustilago and Aureobasidium, as well as Escherichia coli as the most important engineered recombinant host. The utilization of renewable substrates as an alternative to glucose is emphasized in particular as a key aspect for a competitive bio-based production. Out of the alternative substrates discussed in this review, the industrial side-streams crude glycerol and molasses seem to be most promising for large-scale l -malic acid production. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts

The effects of arginine vasopressin (AVP) and oxytocin (OT) upon thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) release were studied in euthyroid rats. Intracerebroventricular (i.c.v.) infusion of AVP in doses of 0.5 ng or 5 ng led to significant increases in plasma levels of TSH as well as FT4 and FT3. The effects of OT injected i.c.v. in similar doses were not consistent (there was no parallel between the changes of respective hormones plasma levels). It may be concluded that vasopressin modulate the pituitary-thyroid system function; AVP is probably a physiological stimulator of TSH and thyroid hormones secretion.