Long tail kinetics in biophysics?

Long tail kinetics describe a variety of data from complex, disordered materials that cannot be described by conventional kinetics. It is suggested that the kinetics of diffusive motion in complex biological media, such as cytoplasm or biomembranes, might also have long tails. The effects of long tail kinetics are investigated for two standard biophysical measurements, fluorescence recovery after photobleaching (FRAP), and dynamic light scattering (DLS). It is shown that long tail kinetic data would yield significantly distorted and misleading results when analyzed assuming conventional kinetics.     

The C-terminal unique region of desmoglein 2 inhibits its internalization via tail–tail interactions

Desmosomal cadherins, desmogleins (Dsgs) and desmocollins, make up the adhesive core of intercellular junctions called desmosomes. A critical determinant of epithelial adhesive strength is the level and organization of desmosomal cadherins on the cell surface. The Dsg subclass of desmosomal cadherins contains a C-terminal unique region (Dsg unique region [DUR]) with unknown function. In this paper, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by inhibiting its internalization and promoted strong intercellular adhesion. DUR also facilitated Dsg tail–tail interactions. Forced dimerization of a Dsg2 tail lacking the DUR led to decreased internalization, supporting the conclusion that these two functions of the DUR are mechanistically linked. We also show that a Dsg2 mutant, V977fsX1006, identified in arrhythmogenic right ventricular cardiomyopathy patients, led to a loss of Dsg2 tail self-association and underwent rapid endocytosis in cardiac muscle cells. Our observations illustrate a new mechanism desmosomal cadherins use to control their surface levels, a key factor in determining their adhesion and signaling roles.     

Should laboratory mice be anaesthetized for tail biopsy?

Tail biopsies are routinely taken to genotype genetically modified mice. However, the effect of this procedure on the wellbeing of the animals has rarely been investigated. Thus, it has not yet been clearly demonstrated to what extent the mice suffer from tail biopsy (TB) and for how long. The aim of our study was to assess the impact of a single TB on the physiological and behavioural parameters of adult mice and to investigate whether or not anaesthesia can be beneficial. Body weight (BW) curves, daily food/water consumption and telemetric measurements of heart rate, body core temperature, and locomotor activity were recorded for three days following TB, both with and without anaesthesia with methoxyflurane (MOF) or diethylether (ether). Additionally, the impact of anaesthesia alone was characterized. TB without anaesthesia induced an increase in heart rate and locomotor activity for 1 h. Body core temperature was elevated for 2 h. In contrast, heart rate was increased for up to 4 h after anaesthesia. Body core temperature remained altered for up to 20 h after exposure to ether and for 44 h after exposure to MOF. BW was slightly reduced after MOF. Cases of death occurred exclusively under ether at a rate of 7%. Our results indicate a short-lived impact of a TB, whereas anaesthesia with either MOF or ether induced remarkable alterations in the parameters analysed. In conclusion, these types of anaesthesia did not improve mouse wellbeing following tail biopsy.     

Huntington’s disease—the sting in the tail

Huntington's disease (HD) is a progressive neurodegenerative condition caused by the abnormal expansion of a polyglutamine tract in the N‐terminus of the huntingtin protein. Over the last 20 years, HD pathogenesis has been explained by the generation of N‐terminal fragments containing the polyglutamine stretch. A new study from Frederic Saudou's group now investigates the function of the C‐terminal fragments generated upon cleavage and shows that these products may also contribute to cellular toxicity in HD (El‐Daher et al, 2015 ).     

Myosin structure: does the tail wag the dog?

Previous crystal structures of the myosin head have shown two different conformations, postulated to be the beginning and the end of the actomyosin power stroke. A new crystal structure reveals a dramatically different conformation; but how does this conformation fit into the force-generating cycle of actomyosin interactions?     

Cytoplasmic tail adaptors of alzheimer’s amyloid-β protein precursor

Alzheimer’s disease is characterized pathologically by senile plaques in the brain. The major component of senile plaques is amyloid-β (Aβ), which is cleaved from Alzheimer’s Aβ protein precursor (AβPP). Recently, information regarding the cytoplasmic tail of AβPP has started to emerge, opening up various insights into the physiological roles of AβPP and its pathological role in Alzheimer’s disease. The cytoplasmic domain of AβPP shares the evolutionarily conserved GYENPTY motif, which binds to a number of adaptor proteins containing the phosphotyrosine interaction domain (PID). Among the PID-containing proteins, this article focuses on four groups of adaptor proteins of AβPP: Fe65, X11, mDab1, and c-Jun N-terminal kinase-interacting protein 1b/islet-brain 1. These two authors contributed equally to this study.     

p53 ubiquitination by Mdm2: A never ending tail?

p53 function is of critical importance in suppressing human cancer formation, highlighted by the fact that the majority of human tumors harbor compromised p53 activity. In normal cells, p53 is held at low levels in a latent form and cellular stress results in the rapid stabilization of p53. Mdm2 mediates ubiquitin-dependent degradation of p53 which plays a key role in maintaining cellular p53 levels. Ubiquitination was, until recently, considered a straightforward system involved in p53 degradation, but recent work has demonstrated how ubiquitination can alter p53 activity, not stability. In this review we summarize current understanding on p53 ubiquitination by Mdm2 with a particular focus on how the balance between protein levels and other post-translational modifications will direct the p53 response.     

A note on the fine structure of the Ochromonas danica “tail”

Summary The fine structure of the Ochromonas danica tail is detailed. The microtubules, microtubule anchoring structures, posterior swelling, surface vesicles, and in some instances cup shape of the tail end are described and used to explain the behavior of the organism when attached to surfaces.Aided by a grant GB 20825 from the National Science Foundation.     

Cell death: Are new proteins synthesized during hormone-induced tadpole tail regression?

The possibility that tadpole tail regression might be initiated by thyroid hormone-induced synthesis of new proteins was investigated. Changes in the newly-synthesized proteins of cultured Xenopus laevis tadpole tails treated with 1.5 × 10^?7 M tri-iodothyronine (T₃) were studied, using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate for protein separation. After initial studies of unfractionated tail proteins, fractionated mixtures of [³H]methionine and [³⁵S]methionine labelled proteins derived from control and hormone-treated tails respectively were examined for hormone-induced changes. Using a new procedure developed to allow effective analysis of small differences in distribution of two isotopes within gel slices, it was shown that no significant changes in synthesis of fractionated tail proteins are induced by the hormone during the first 3–4 days in culture. The average detection limit was approx. 0.02% of total tail protein synthesis. Although no changes in the synthesis of the tissue structural or enzymic proteins are induced by the hormone this study still leaves open the possibility of changes in the synthesis of regulatory proteins. Based on the known method of activation of the tadpole tail collagenase (which is shown here directly for the first time to be involved in T₃-induced tail regression), it is suggested that many of the initial hormone-induced changes might result from T₃-induced activation of proteolytic “cascades”.     

The intracellular region of Notch ligands: does the tail make the difference?

   

The cytoplasmic tail of Notch ligands drives endocytosis, mediates association with proteins implicated in the organization of cell-cell junctions and, through regulated intra-membrane proteolysis, is released from the membrane as a signaling fragment. We survey these findings and discuss the role of Notch ligands intracellular region in bidirectional signaling and possibly in signal modulation in mammals.     

Old breeds,new solutions? Effects of two different traditional sire breeds on skin lesions,tail lesions,tail losses,performance and behaviour of rearing pigs

Some studies indicated a relationship between modern, fast-growing, lean-meat-producing hybrid pigs and the occurrence of tail-biting, one of the major issues of conventional pig husbandry. Therefore, this study investigated the effects of different local, traditional sire breeds on the behaviour and performance of rearing pigs. Between December 2019 and November 2020, a total of 1 561 piglets were weaned from hybrid sows (Bundes Hybrid Zucht Programm (BHZP) Landrace × BHZP Large White) that were paired with either Swabian-Hall (SH), Bentheim Black Pied (BB) or BHZP-Piétrain (Pi) boars. Tails of the piglets were left intact (43.5%) or docked (56.5%), and male piglets were castrated. Piglets were conventionally reared on fully slatted plastic flooring in mixed-sex groups. Starting one day after weaning, skin lesions were scored once per pig, and tail lesions and losses were scored weekly until the end of rearing. The average daily gain was documented for the suckling and rearing period. The activity behaviour of eight focal pens was analysed using video recordings. Differences between modern and traditional breeds were found in this study for so-called aggressive and non-aggressive biting pronounced by skin and tail lesions and tail losses. Significantly fewer BB pigs had severe skin lesions on the front body than SH or Pi pigs (P < 0.05). Additionally, piglets that were classified as light (<5.6 kg) at weaning showed skin lesion scores of 0 more often than piglets that were classified with a medium (≥5.6–≤8.3 kg) or heavy (>8.3 kg) weaning weight (P < 0.05). In the first half of the rearing period, significantly more BB pigs were assessed as having no tail lesions and tail losses than SH and Pi pigs (P < 0.01). However, these differences disappeared in the second half of rearing. Either docked or undocked Pi pigs had significantly higher average daily gains than SH and BB pigs (P < 0.05). The activity of the focal pens was not influenced by the sire breed or tail lesion class, which might be due to the limited sample size of eight pens. To conclude, the use of the traditional sire breed BB has the potential to reduce injurious behaviour in the offspring. However, adjustments to the housing and feeding should be taken to further reduce the incidence of tail lesions and losses and to enhance performance.     

The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation

The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS) domain (residues 26-135) as well as an amphipathic α-helix (residues 13-23) and an initial unstructured segment (residues 2-9). Deletion of residues 2-25, only the unstructured segment (residues 2-9) or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.     

Congenital absence of a tail in a Reeves‘ muntjac (Muntiacus reevesi)

Two abnormalities of the tail have been observed in Reeves muntjac. A male was born acaudate and an adult doe had a tail less than a third of the normal length. The range and mean of lengths of body and tail are given for animals over 2 years old.     

Is partial tail loss the key to a complete understanding of caudal autotomy?

Autotomy, the self‐amputation of limbs or appendages, is a dramatic anti‐predator tactic that has repeatedly evolved in a range of invertebrate and vertebrate groups. In lizards, caudal autotomy enables the individual to break away from the predator's grasp, with the post‐autotomy thrashing of the tail distracting the attacker while the lizard makes its escape. This drastic defensive strategy should be selectively advantageous when the benefit (i.e. survival) exceeds the subsequent costs associated with tail loss. Here, we highlight how the position of autotomy along the length of the tail may influence the costs and benefits of the tactic, and thus the adaptive advantage of the strategy. We argue that most studies of caudal autotomy in lizards have focused on complete tail loss and failed to consider variation in the amount of tail shed, and, therefore, our understanding of this anti‐predator behaviour is more limited than previously thought. We suggest that future research should investigate how partial tail loss influences the likelihood of surviving encounters with a predator, and both the severity and duration of costs associated with caudal autotomy. Investigation of partial autotomy may also enhance our understanding of this defensive strategy in other vertebrate and invertebrate groups.     

Morphology of the “spindle-shaped body” in the developing tail of human spermatids

Summary At the beginning of the late cap phase of the normal differentiation of human spermatids, a unique structure, the spindle shaped body, occupies part of the future middlepiece. This spindle-shaped body was followed throughout its development, and its functional relationship to the formation of the fibrous sheath is discussed. The spindle-shaped body disappears when the fibrous sheath is completed and the annulus moves down, giving rise to the middle-piece.Supported by Grants from the Deutsche Forschungsgemeinschaft.