The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases.

The rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high stability is due to the presence of characteristic (methyl-) lanthionine rings, which makes them promising candidates as bacteriocides. However, innate resistance against lantibiotics exists in nature, emphasizing the need for artificial or tailor-made lantibiotics. Obviously, such an approach requires an in-depth mechanistic understanding of the modification enzymes, which catalyze the formation of (methyl-)lanthionine rings. Here, we determined the structure of a class I cyclase (MadC), involved in the modification of maddinglicin (MadA) via X-ray crystallography at a resolution of 1.7 Å, revealing new insights about the structural composition of the catalytical site. These structural features and substrate binding were analyzed by mutational analyses of the leader peptide as well as of the cyclase, shedding light into the mode of action of MadC.

A Structural View on the Maturation of Lanthipeptides.

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, which display diverse bioactivities (e.g., antifungal, antimicrobial, and antiviral). One characteristic of these lanthipeptides is the presence of thioether bonds, which are termed (methyl-) lanthionine rings. These modifications are installed by corresponding modification enzymes in a two-step modality. First, serine and threonine residues are dehydrated followed by a subsequent catalyzed cyclization reaction, in which the dehydrated serine and threonine residues are undergoing a Michael-type addition with cysteine residues. The dedicated enzymes are encoded by one or two genes and the classification of lanthipeptides is pending on this. The modification steps form the basis of distinguishing the different classes of lanthipeptides and furthermore reflect also important mechanistic differences. Here, we will summarize recent insights into the mechanisms and the structures of the participating enzymes, focusing on the two core modification steps - dehydration and cyclization.

Is there a two-humped stage in the embryonic development of the dromedary?

It has been postulated that the one-humped (Arabian) dromedary and the two-humped (Bactrian) camel originated from a single ancestor. Consequently, the dromedary was considered a breed of the two-humped camel, based on an anatomical study by Lombardini L, 1879: Ann. Del. Universita Toscane, 259, 147, who described a reduced second hump like structure in foetal and adult dromedaries. To resolve this lingering issue, we analysed dromedary foetuses and calves. In contrast to the situation in two-humped camels, we never observed any rudimentary second hump in the dromedary foetuses or calves.

[The average lifespan of a veterinary anatomist in a German speaking veterinary educational institution]. / Die Mittlere Lebensdauer Der Veterinäranatomen an Deutschsprachigen, Tierärztlichen Bildungsstätten.

The average lifespan of veterinary anatomists was statistically analysed. All teachers who ever taught veterinary anatomy (formerly 'zootomy') and histology/embryology separately or in combination with other subjects in Germany, Austria and Switzerland were included in that circle. The observation period was from the foundation of the veterinary schools up to the present. We find that the average lifespan of this specific group is not different from that of the general population. Comparable previous opinions on the lifespan of anatomists, estimated as shorter than that of the general population by Hyrtl, and longer by Voss, are incorrect. This opportunity is also used to mention our time-honored; especially the early completed and aged colleagues.

On the nomenclature of coelom-derived body cavities.

A rationalization of terms about the body cavities is urgently needed. Students and practitioners have difficulty in understanding the contradictory terms prevalent at present. For many years, the International Committee on Veterinary Gross Anatomical Nomenclature has failed to bring it off; therefore some proposals for the anatomical instruction until the next edition of the Nomina Anatomica Veterinaria are made.

[Max Flesch (1852-1943): veterinary anatomist, physician and Nazi victim]. / Max Flesch (1852-1943): Veterinäranatom, Arzt und NS-Opfer.

The Jewish physician Dr. med. Max Flesch, a student of the Würzburger anatomist Albert von Kölliker (1817-1905), was professor of anatomy, histology and embryology at the School of Veterinary Medicine in Bern from 1882-1887. He was the first at that school who unified the three anatomical fields in one hand. From his Institute came Oskar Rubeli (1861-1952) who was also his successor. From 1888 on Max Flesch was engaged as practitioner and later as gynaecologist. During the First World War he proved his worth as a hospital physician. After the war he most likely was working for another decade in his practice in Frankfurt before retiring in Hochwaldhausen at the Hessian Vogelsberg. During his retirement Flesch published his experiences as 1 nurse and hospital physician, respectively during the wars 1870/71 and 1914-1918. With the assumption of power by the National Socialists the living conditions for Jews in Germany radically changed; also Max Flesch became victim of the Nazi racism. Although very old he was carried off 1942 into the concentration camp Theresienstadt where he lost his life in May 1943. We owe Max Flesch honourable remembrance.

[Phylogeny, form and function of canine teeth in the horse]. / [Zur Phylogenie, Form und Funktion der Dentes canini des Pferdes]

The canine teeth of the horse developed phylogenically from the simple, pointed, short-rooted tooth form of the leaf eating, in pairs living, Eocene horse Hyracotherium and served up to the Oligocene as a means of defense (self preservation). In the Miocene the living conditions of the Merychippus changed and they took to eating grass and adopted as a new behavior the life in a herd. The canine teeth possibly played an important role in fights for social ranking; they changed from a crown form to knife-like shape. In the Pliohippus the canine tooth usually remained in male horses and since the Pliocene, it contributed to the fights between stallions, to ensure that the offspring only came from the strongest animals (preservation of the species). Form and construction of the canine tooth are described and discussed in detail under the above mentioned phylogenic and ethologic aspects.

Periods and stages of the prenatal development of the domestic cat.

Twenty-two stages of the prenatal development of the domestic cat are described for intraspecies comparison in embryological studies. These are assigned to the 15 embryonal periods based on the Nomina Embryologica Veterinaria to make the interspecies comparison possible.

[The origin and function of the enamel cup, infundibulum dentis, on the incisors of the horse]. / Zur Entstehung und Funktion der Kunde, Infundibulum dentis, an den Schneidezähnen der Pferde.

The enamel cups of equids originated phylogenetically through several phases in Oligocene and Miocene horses, which readjusted from hard to soft leaf food and from double nutrition (leaves and grass) to a pure grass intake. This has been proved experimentally. The resulting construction of the incisor is continually changed on its occlusal surface by erosion according to the pattern of the enamel crests. Referring to the whole incisor tooth, this results in an equid life cycle in which the good grip of the occlusal surface and the efficiency of ingestion favours the young, sexually mature horses, which are at the best age for food intake.

[The phylogenesis of equine teeth]. / Zur Phylogenie des Equidengebisses.

Phylogenetic research on the teeth of equidae beginning with dagger Hyracotherium ('Eohippus') will be summarized, subdivided into its components, analysed in a new way and finally interpreted according to several theories of evolution. In this context, specific cells (ameloblasts, odontoblasts, cementoblasts) are discussed and valued according to Preuss (1987) as active carriers of the evolution of teeth.

[Evolution and Darwinian theory]. / Evolution und die Darwinsche Theorie.

The Darwinian theory today is broadly accepted as one cornerstone of science. However, isn't biology as a life science both, material- and art subject?

[The development of the horse testis]. / Zur Entwicklund des Pferdehodens.

The aim of the study was to answer the open questions concerning the development of the horse's testis. This study revealed that the seminiferous tubules originate from the sex cords of the coelomic epithelium and Leydig cells from the proximal part of mesonephric nephrons, whereas the rete and the ductuli efferentes derive from intermediate and distal parts of the mesonephric tubules. During the development the Leydig cells undergo an enormous proliferation due to the PMSG secretion in the mare. The proliferation of these cells prevent the deep penetration of the rete into the medulla and is therefore the reason for the reduced extension of the rete and mediastinum testis in the stallion, although 80% of these cells degenerate in the last third of pregnancy. The growth of the seminiferous tubules during sexual maturity reduces the rete to the extremitas capitata of the testis.

Histochemical demonstration of lipase activity in the gastric mucosa of the cat.

The aim of the present study was to determine, histochemically, the onset and location of production of preduodenal lipase in fetal, suckling, weaned and adult cats. Strong enzymatic activity was localized in the surface mucous cells of the gastric mucosa in animals at postpartal day 1 after ingestion of milk. Activity of gastric lipase persisted as long as animals were nursed. No gastric lipase could be demonstrated in weaned and adult cats. Lingual lipase was not found at any developmental stage examined. Thus, in the newborn cat, lipase of the gastric mucosa is responsible for milk fat lipolysis.

[Observations on epidural anesthesia in cats from the anatomical viewpoint]. / Bemerkungen zur Epiduralanästhesie bei der Katze aus anatomischer Sicht.

The topographic-anatomical situation of the conus medullaris and the cauda equina in cats is shown: in about two thirds of the cases the conus medullaris at least reaches the level of the first sacral vertebra. As far as the site of the epidural injection is concerned the sacrococcygeal space or the first intercoccygeal space are proposed in order to avoid damage to the spinal cord. When seeking the site of injection it is advantageous to orientate oneself by following the sacral processus spinosi in caudal direction beginning with the lumbosacral space. In case of adipose animals the first intercoccygeal space can be palpated by moving the tail up and down. Both sites are equivalent. The volume to be injected varies between 0.3 and 0.9 ml solution per cat depending on the needs.

[On the costal articulations XI, XII, XIII of the domestic cat (Felis catus)]. / Uber die Rippengelenke XI, XII, XIII der Hauskatze (Felis catus).

The costal articulations XI, XII, XIII of the cat are simple, synovial joints. This dot-shaped suspension of the last ribs from the spinal column and the existence of a costo-vertebral ligament are coordinated functionally.

[Development of the gastric glands of cats (Felis silvestris catus)]. / Die Entwicklung der Magendrüsen der Katze (Felis silvestris catus).

There are five stages in the development of the cat's gastric glands: 1. During the stage of the indifferent epithelium from day 19 to day 24, the anlage of the stomach develops with all layers; 2. The stage of gland formation from day 24 to day 41 is the beginning of the gland buds. They develop in connection with endocrine cells on day 34 into primitive oxyntic and primitive mucous cells. The latter form the basis for all other cells, including the surface mucous cells; 3. During the stage of gland evagination from day 42 to 55, the anlagen are separated into primitive pits and tubules, while the cells continue to differentiate and the first intermediate cells are seen; 4. The stage of gland branching from day 56 to birth is characterized by the formation of additional glands at the bottom of the pits which change the ordinary anlagen into branched glands. During this stage, the cardiac glands are formed; 5. In the stage of gland maturation from birth to the 9th week, the peptic cells are formed and the glands start functioning. The oxyntic cells show carbonic-anhydrase activity and signs of acid secretion, and, between the weeks 4 and 8, the peptic cells contain pepsinogen, producing a negative reaction to PAS and a positive reaction to HID. Mucous cells and mucous neck cells produce PAS- and AB-positive mucin.

[Prenatal development of the mandibular gland and parotid gland in cats]. / Zur pränatalen Entwicklung der Glandula mandibularis und Glandula parotis der Katze.

The prenatal development of the cat's mandibular and parotid gland was examined by means of serial section of 36 cat embryos at 14-62 days of development. Both glands were excised from the epithelium of the primitive oral cavity and branched up to day 36 of the branching phase into a specific connective tissue. This tissue contained besides fine collagenous fibres, a high amount of proteoglycans. In the subsequent separation phase, ducts and acini differentiated themselves in primitive lobules which were separated by connective tissue. In the prenatal differentiation phase, from about day 50 up to birth, intercalated ducts and striated ducts were formed. In the acini, mucous and serous cells contained different amounts of complex carbohydrates. This secretory component changed shortly before birth.

[The temporomandibular joint of the domestic cat (Felis silvestris catus)]. / Zur Articulatio temporomandibularis der Hauskatze (Felis silvestris catus).

The mandibular joint of the cat is an incongruent cylindrical joint, which works as a hinge or screw joint. The course of motion is unilateral in the plane of the cutting edge of the molar/premolar border [symbol: see text]. The articular disc is a connective tissue membrane; its new function is decreasing the friction.

Development of spatial relations of shoulder and brachium in embryonal chick wing.

The linear marking method was employed to study morphogenetic movements of tissues involved in the development of the definitive position and shaping of the shoulder and arm. Chick embryos in the range of embryonal day 3.5 to 4.5 were used with the following results: -Asymmetrical growth of the early wing bud and the oblique position of humerus anlage in the early wing bud as proposed by Saunders (1948) and Seichert (1965) were confirmed. -It was found that the cranial ascend of the shoulder (Seichert and Knospe 1992) is accompanied by the slight ventromedial rotation of the complex consisting of the scapula and coracoid. -Torsion along the longitudinal axis of the stylopodium was observed: the proximal part of the stylopodium (both the humerus anlage and related soft tissues) moves in the sense of supination, the distal part moves in the sense of pronation.

[Prenatal development of the horse ovary]. / Zur praenatalen Entwicklung des Pferdeovars.

To answer the many open questions concerning the development of the horse's ovary, first the prenatal development was investigated. It resulted that follicles derive from the germinal epithelium and its cords, whereas the Leydig cells and the rete blastema originate from the mesonephros. In the second third of pregnancy the Leydig cells undergo an enormous proliferation, in the last third they degenerate. However this degeneration is not connected with the postnatal development of the ovulation groove.