The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core: An update.

Introduction: Biomarkers for Alzheimer's disease neuropathologic change (ADNC) have been instrumental in developing effective disease-modifying therapeutics. However, to prevent/treat dementia effectively, we require biomarkers for non-AD neuropathologies; for this, neuropathologic examinations and annotated tissue samples are essential.

Methods: We conducted clinicopathologic correlation for the first 100 Alzheimer's Disease Neuroimaging Initiative (ADNI) Neuropathology Core (NPC) cases.

A New Perspective on the Maillard Reaction and the Origin of Life.

The Maillard reaction, a spontaneous 'one pot' reaction between amino acids and reducing sugars that occurs at low reactant concentrations and low temperatures, is a good candidate for having played a role in the origin of life on the Earth. In view of the probability that RNA and DNA were preceded by an evolutionary forerunner with a more straightforward prebiotic synthesis, it is a testament to the prescience of Oró and colleagues that, in 1975, they drew attention to the Maillard reaction, in particular evidence that melanoidin polymers (the end-product of the reaction) contain '…heterocyclic nitrogen compounds similar to the nitrogenous bases' (Nissenbaum in J Mol Evol 6:253-270, 1975). Indeed, reports of the Maillard reaction product, 2-Acetyl-6-(Hydroxymethyl)-5,6-Dihydro-4H-Pyridinone (AHDP), with a structure reminiscent of the pyrimidine nucleobase uracil, suggest the Maillard reaction might have played a key role in the synthesis of components of a proto-RNA polymer, with AHDP and two structurally related products predicted to be similar to uracil in the latter's ability to form non-standard base pair interactions.

Making Molecules with Clay: Layered Double Hydroxides, Pentopyranose Nucleic Acids and the Origin of Life.

A mixture of sugar diphosphates is produced in reactions between small aldehyde phosphates catalysed by layered double hydroxide (LDH) clays under plausibly prebiotic conditions. A subset of these, pentose diphosphates, constitute the backbone subunits of nucleic acids capable of base pairing, which is not the case for the other products of these LDH-catalysed reactions. Not only that, but to date no other polymer found capable of base pairing-and therefore information transfer-has a backbone for which its monomer subunits have a plausible prebiotic synthesis, including the ribose-5-phosphate backbone subunit of RNA.

Physiological and Behavioral Responses of Dairy Cattle to the Introduction of Robot Scrapers.

Autonomous mobile robot scrapers are increasingly used in order to clean the floors on dairy farms. Given the complexity of robot scraper operation, stress may occur in cows due to unpredictability of the situation. Experiencing stress can impair animal welfare and, in the long term, the health and milk production of the cows.

Clues to tRNA Evolution from the Distribution of Class II tRNAs and Serine Codons in the Genetic Code.

We have previously proposed that tRNA(Gly) was the first tRNA and glycine was the first amino acid incorporated into the genetic code. The next two amino acids incorporated would have been the other two small hydrophilic amino acids serine and aspartic acid, which occurred through the duplication of the tRNA(Gly) sequence, followed by mutation of its anticodon by single C to U transition mutations, possibly through spontaneous deamination. Interestingly, however, tRNA(Ser) has a different structure than most other tRNAs, possessing a long variable arm; because of this tRNA(Ser) is classified as a class II tRNA.

Perinatal influences on the uptake of newborn Vitamin K prophylaxis--a retrospective cohort study.

Objectives: To describe rates of newborn vitamin K prophylaxis uptake according to method of administration (intramuscular [IM], oral, refused) and identify predictors for the choice of oral administration and for refusal of vitamin K prophylaxis.

Methods: A retrospective cohort study examined the relationship between method of vitamin K administration and various exposure factors (infant, maternal, socio-demographic and healthcare professional). Written and electronic data for births from a single tertiary birthing unit in New Zealand (NZ) were examined over a four-year period from January 2009 to December 2012.

Declining newborn intramuscular vitamin K prophylaxis predicts subsequent immunisation refusal: A retrospective cohort study.

Aim: Low rates of childhood immunisation are linked to outbreaks of infectious disease. Identifying and addressing barriers to immunisation may lead to improved immunisation rates. Immunisation and newborn vitamin K prophylaxis have many similarities.

The juxtaposition of ribose hydroxyl groups: the root of biological catalysis and the RNA world?

We normally think of enzymes as being proteins; however, the RNA world hypothesis suggests that the earliest biological catalysts may have been composed of RNA. One of the oldest surviving RNA enzymes we are aware of is the peptidyl transferase centre (PTC) of the large ribosomal RNA, which joins amino acids together to form proteins. Recent evidence indicates that the enzymatic activity of the PTC is principally due to ribose 2'-OHs.

Purine biosynthetic intermediate-containing ribose-phosphate polymers as evolutionary precursors to RNA.

The RNA world hypothesis proposes that RNA once functioned as the principal genetic material and biological catalyst. However, RNA is a complex molecule made up of phosphate, ribose, and nucleobase moieties, and its evolution is unclear. Yakhnin has proposed a period of prebiotic chemical evolution prior to the advent of replication and Darwinian evolution, in which macromolecules containing polyols joined by phosphodiester linkages underwent spontaneous transesterification reactions with selection for stability.

Genetic code evolution started with the incorporation of glycine, followed by other small hydrophilic amino acids.

We propose that glycine was the first amino acid to be incorporated into the genetic code, followed by serine, aspartic and/or glutamic acid-small hydrophilic amino acids that all have codons in the bottom right-hand corner of the standard genetic code table. Because primordial ribosomal synthesis is presumed to have been rudimentary, this stage would have been characterized by the synthesis of short, water-soluble peptides, the first of which would have comprised polyglycine. Evolution of the code is proposed to have occurred by the duplication and mutation of tRNA sequences, which produced a radiation of codon assignment outwards from the bottom right-hand corner.

The effect of dry cow antibiotic with and without an internal teat sealant on udder health during the first 100 d of lactation: a field study with matched pairs.

The objective of this field study was to compare the udder health status as well as the clinical mastitis rate during the first 100 d of lactation in cows that received long-acting dry cow antibiotic alone (group AB) or in combination with an internal teat sealant (group AB + OS). The study was conducted during a 9-month period and included 136 Holstein cows from 12 dairy farms in Hessia, Germany. Between days 1 and 5 after calving a California mastitis test (CMT) was performed.

The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)(a).

The problems associated with the RNA world hypothesis are well known. In the following I discuss some of these difficulties, some of the alternative hypotheses that have been proposed, and some of the problems with these alternative models. From a biosynthetic - as well as, arguably, evolutionary - perspective, DNA is a modified RNA, and so the chicken-and-egg dilemma of "which came first?" boils down to a choice between RNA and protein.

Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?

Background: The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.

Evaluation of neutron sources for ISAGE-in-situ-NAA for a future lunar mission.

For a future Moon landing, a concept for an in-situ NAA involving age determination using the (40)Ar-(39)Ar method is developed. A neutron source (252)Cf is chosen for sample irradiation on the Moon. A special sample-in-source irradiation geometry is designed to provide a homogeneous distribution of neutron flux at the irradiation position.

Efficacy of anidulafungin against biofilms of different Candida species in long-term trials of continuous flow cultivation.

Long-term continuous flow culture allows the investigation of dynamic biofilms under microaerophilic or aerobic conditions. We studied the biofilm formation and changes of susceptibility in 30 blood culture isolates (48 experiments) of different Candida species exposed to anidulafungin in 0.16 ml or 7.

[Johann Jaroslaw Marcinowski (1868-1935) and his sanatorium "Haus Sielbeck" at lake Uklei. Psychoanalysis in an in-patient setting].

Marcinowski came from an aristocratic family. He first joined the army as a lieutenant and later worked as a medical doctor. From 1908 to 1920, Marcinowski was a follower of Freud, additionally influenced by Oskar Vogt.

["A magical atmosphere was our vision when we founded the institution". The sanatorium "Schloss Tegel" in statu nascendi (1904-1907)].

This contribution addresses the early years of the sanatorium, founded by the medical doctor and later psychoanalyst Johann Jaroslaw Marcinowski. His approach to therapy, his ideas about interior design as well as landscape gardening were of significant influence on the sanatorium in which Ernst Simmel opened his psychoanalytical clinic in 1927.

A chemically defined production process for highly attenuated poxviruses.

Highly attenuated poxviruses are promising vectors for protective and therapeutic vaccines. These vectors do not replicate in human cells and can therefore be safely given even to immunocompromised recipients. They can accommodate very large inserts and provide strong stimulation of the immune system against the vectored antigen.

[Pathological diagnosis--costs and benefit].

The autopsy rate in Germany has drastically diminished in the last decades and is below 10% nowadays. Possible reasons for this development are discussed. Pressure of cost is a quoted cause, although it is not so high.

The transition from noncoded to coded protein synthesis: did coding mRNAs arise from stability-enhancing binding partners to tRNA?

Background: Understanding the origin of protein synthesis has been notoriously difficult. We have taken as a starting premise Wolf and Koonin's view that "evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e.

Evidence from glycine transfer RNA of a frozen accident at the dawn of the genetic code.

Background: Transfer RNA (tRNA) is the means by which the cell translates DNA sequence into protein according to the rules of the genetic code. A credible proposition is that tRNA was formed from the duplication of an RNA hairpin half the length of the contemporary tRNA molecule, with the point at which the hairpins were joined marked by the canonical intron insertion position found today within tRNA genes. If these hairpins possessed a 3'-CCA terminus with different combinations of stem nucleotides (the ancestral operational RNA code), specific aminoacylation and perhaps participation in some form of noncoded protein synthesis might have occurred.

Is there a need for autopsies in the management of fungal disease?

The autopsy rates in Germany became low like in other European, American and Asian countries. Main reasons for this development are the lack of acceptance of autopsy in the society as well as in the medical profession, the introduction of a requirement for consent, unclear legal position, the public health system, pressure of costs and a change in the field of activity in pathology with much more diagnostics of surgical and biopsy material. The autopsy is missing with respect to the reliability of causes of death and morbidity statistics and other epidemiological studies.

[What distinctions do Candida biofilms have to offer?].

In a miniature continuous flow cell system we investigated the influence of voriconazole (VCZ) (27 trials) or anidulafungin (ANID) (five trials) on the antimycotic resistance of C. albicans (type strain SC5314 and three strains from blood cultures). The duration of the trials was up to 10 d.

The first description of an oesophageal candidosis by Bernhard von Langenbeck in 1839.

In November 1839 the young university lecturer Bernhard (von) Langenbeck (1810-1887) published the first description of a fungus as aetiological agent of an oro-pharyngeal and oesophageal candidosis. We present his in English translated paper entitled 'Finding of fungi on the mucous membrane of the gullet of a typhoid fever corpse' (Germ.) in 'Neue Notizen aus dem Gebiete der Natur- und Heilkunde' (Froriep).