Vestibular and Attractor Network Basis of the Head Direction Cell Signal in Subcortical Circuits

Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal\u27s directional orientation and location in space. Within this navigation system are head direction (HD) cells, which fire persistently when an animal\u27s head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animal\u27s sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. The purpose of the present review is to summarize some of the recent studies arguing that the origin of the HD signal resides subcortically, specifically within the reciprocal connections of the dorsal tegmental and lateral mammillary nuclei. Furthermore, we review recent work identifying “bursting” cellular activity in the HD cell circuit after lesions of the vestibular system, and relate these observations to the long held view that attractor network mechanisms underlie HD signal generation. Finally, we summarize anatomical and physiological work suggesting that this attractor network architecture may reside within the tegmento-mammillary circuit

Variation in Protein Quality of Forage Legumes During Spring Growth

The utilisation of forage legumes in combination with reduced N inputs as fertilisers is an alternative for the production of high quality forage. Although white clover (WC) is widely used in grassland and has a high content of crude protein (CP), a combination of this high CP content with a high proportion of rapidly-available proteins and fast degradation rate in the rumen may reduce the efficiency of N use by ruminants in comparison with other forage legumes. The objective of the present study was to investigate the variation in content of CP fractions A, B and C in different forage legume during the spring growth in comparison with WC

Head Direction Cells and Episodic Spatial Information in Rats without a Hippocampus

To successfully navigate through the environment animals rely on information concerning their directional heading and location. Many cells within the postsubiculum and anterior thalamus discharge as a function of the animal’s head direction (HD), while many cells in the hippocampus discharge in relation to the animal’s location. We placed lesions in the hippocampus and recorded from HD cells in the postsubiculum and anterior thalamus. Lesions of the hippocampus did not disrupt the HD cell signal in either brain area, indicating that the HD cell signal must be generated by structures external to the hippocampus. In addition, each cell’s preferred firing direction remained stable across days when the lesioned animal was placed into a novel environment. This stability appeared to weaken after several weeks of nonexposure to the new enclosure for two out of five animals, and subsequently recorded cells from these two animals established a new angular relationship between the familiar and novel environments. Our results suggest that extra-hippocampal structures are capable of creating and maintaining a novel representation of the animal’s environmental context. This representation shares features in common with mnemonic processes involving episodic memory that until now were assumed to require an intact hippocampus

A Sward Based Method to Estimate Herbage Selection of Grazing Dairy Cows

Diet selection of grazing animals is influenced by sward composition and vertical sward structure. Grazing studies were established in northern Germany (Kiel, Schleswig - Holstein state) to determine if selective grazing behaviour in a mixed sward can be measured by a sward based method. The hypothesis that active selection of different functional groups of forages can be documented by using the selection index (Figure 1, Hodgson, 1990) and regressive approaches vs time was tested

Systemic amyloidosis in England: an epidemiological study.

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population

Very Low Nitrogen Leaching in Grazed Ley-Arable-Systems in Northwest Europe

High input dairy farms that are located on sandy soils in northwest Europe are predisposed to substantial nitrate leaching during a surplus of winter precipitation. Leys within integrated crop-livestock systems play an important role in soil fertility, soil C sequestration and soil N mineralization potentials. Therefore, leys are a feasible option that can be utilized to reduce local N losses to the environment, especially following maize grown for silage. We hypothesize that grass-clover leys ensure low nitrate leaching losses even when grazed intensively. The extent to which NO3-leaching occurred across seven different pasture management systems in terms of their sward composition, cutting, grazing, fertilization and combinations thereof was investigated in integrated animal-crop grazing systems over three winter periods (2017/2018, 2018/2019 and 2019/2020). The observed grazed systems were comprised of cut-used- and grazed grass-clover swards (0, 1 and 2 years after establishment following cereals), a catch crop grazed late in the year as well as a cut-used permanent grassland for comparison. Overall, all treatments resulted in nitrate leaching losses that did not exceed the WHO-threshold (25 mg nitrate/L). The highest level of NO3-leaching was observed in the catch crop system and the lowest in cut-used permanent grassland, with NO3-N losses of 19.6 ± 5.3 and 2.1 ± 0.3 kg NO3-N ha−1 year−1. Annual herbage yields were in the range of 0.9 to 12.4 t DM ha−1 and nitrogen yields varied between 181 ± 51 and 228 ± 66 kg N ha−1 during the study period. The highest herbage-N-yields were observed from the 1- and 2-year-old grass-clover leys. The highest N-field-balance was observed for the grazed leys and the lowest for the cut-used permanent grassland. However, no correlation was found between the highly positive field-N-balance and the amount of NO3-leached

When and how should peritoneal endometriosis be operated on in order to improve fertility rates and symptoms? The experience and outcomes of nearly 100 cases

Purpose: To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. Methods: Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed. Results: Laparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed. Conclusion: According to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates

The T210M Substitution in the HLA-a*02:01 gp100 Epitope Strongly Affects Overall Proteasomal Cleavage Site Usage and Antigen Processing

MHC class I-restricted epitopes, which carry a tumor-specific mutation resulting in improved MHC binding affinity, are preferred T cell receptor targets in innovative adoptive T cell therapies. However, T cell therapy requires efficient generation of the selected epitope. How such mutations may affect proteasome-mediated antigen processing has so far not been studied. Therefore, we analyzed by in vitro experiments the effect on antigen processing and recognition of a T210M exchange, which previously had been introduced into the melanoma gp100209–217tumor epitope to improve the HLA-A*02:01 binding and its immunogenicity. A quantitative analysis of the main steps of antigen processing shows that the T210M exchange affects proteasomal cleavage site usage within the mutgp100201–230 polypeptide, leading to the generation of an unique set of cleavage products. The T210M substitution qualitatively affects the proteasome-catalyzed generation of spliced and non-spliced peptides predicted to bind HLA-A or -B complexes. The T210M substitution also induces an enhanced production of the mutgp100209–217 epitope and its N-terminally extended peptides. The T210M exchange revealed no effect on ERAP1-mediated N-terminal trimming of the precursor peptides. However, mutant N-terminally extended peptides exhibited significantly increased HLA-A*02:01 binding affinity and elicited CD8+ T cell stimulation in vitro similar to the wtgp100209–217 epitope. Thus, our experiments demonstrate that amino acid exchanges within an epitope can result in the generation of an altered peptide pool with new antigenic peptides and in a wider CD8+ T cell response also towards N-terminally extended versions of the minimal epitope