No abstract

Spinocerebellar ataxia 1 (SCA1) is a devastating neurodegenerative disease associated with cerebellar degeneration and motor deficits. However, many patients also exhibit neuropsychiatric impairments such as depression and apathy; nevertheless, the existence of a causal link between the psychiatric symptoms and SCA1 neuropathology remains controversial. This study aimed to explore behavioral deficits in a knock-in mouse SCA1 (SCA1 154Q/2Q) model and to identify the underlying neuropathology. We found that the SCA1 mice exhibit previously undescribed behavioral impairments such as increased anxiety-and depressive-like behavior and reduced prepulse inhibition and cognitive flexibility. Surprisingly, non-motor deficits characterize the early SCA1 stage in mice better than does ataxia. Moreover, the SCA1 mice exhibit significant hippocampal atrophy with decreased plasticity-related markers and markedly impaired neurogenesis. Interestingly, the hippocampal atrophy commences earlier than the cerebellar degeneration and directly reflects the individual severity of some of the behavioral deficits. Finally, mitochondrial respirometry suggests profound mitochondrial dysfunction in the hippocampus, but not in the cerebellum of the young SCA1 mice. These findings imply the essential role of hippocampal impairments, associated with profound mitochondrial dysfunction, in SCA1 behavioral deficits. Moreover, they underline the view of SCA1 as a complex neurodegenerative disease and suggest new avenues in the search for novel SCA1 therapies. Spinocerebellar ataxia type 1 (SCA1) is a lethal dominantly-inherited neurodegenerative disease, caused by CAG repeat expansion (> 40 CAG repeats) in the ataxin-1 encoding gene (ATXN1) 1. This mutation results in ataxin-1 protein toxicity and aggregation which leads, in particular, to cerebellar and brainstem degeneration 2 , although ATXN1 is widely expressed throughout the brain 1. SCA1 symptoms usually appear in early middle-age and include motor incoordination and gait deficits followed by muscular and swallowing problems in the later stages of the disease 3. However, in a similar way to other types of spinocerebellar ataxias (SCAs), over 50% of patients also demonstrate neuropsychiatric issues 4-7 including cognitive impairments, anxiety, apathy and depression 7-9. Interestingly, in contrast to progressive ataxia, the psychiatric impairments tend to remain relatively stable over time 8. Although they are often overlooked, they profoundly impact the quality of life and health outcomes of patients with SCA1 and related diseases 9. However, the question of whether these psychiatric impairments are causally linked to SCA1 neuropathology, or if they represent an emotional response to SCA1 diagnosis and subsequent physical disability, remains controversial 9 .

No abstract

Background: Survival studies in intestinal cancers have generally shown favorable devel-opment, but few studies have been able to pinpoint the timing of the changes in survival over an extended period. Here, we compared the relative survival rates for colon, rectal and small intestinal cancers from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). Design: Relative 1-, 5- and 5/1-year conditional survival data were obtained from the NORDCAN database for the years 1971–2020. Results: The 50-year survival patterns were country-specific. For colon and rectal can-cers, the slopes of survival curves bended upwards for DK, were almost linear for NO and bended downwards for FI and SE; 5-year survival was the highest in DK. Survival in small intestinal cancer was initially below colon and rectal cancers but in FI and NO it caught up toward the end of the follow-up. Conclusions: Relative survival in intestinal cancers has developed well in the Nordic countries, and DK is an example of a country which in 20 years was able to achieve excellent survival rates in colon and rectal cancers. In the other countries, the increase in survival curves for colon and rectal cancer has slowed down, which may be a challenge posed by metastatic cancers.

Headwaters and small streams are crucial components of riverine systems, harbouring many highly specialized and unique invertebrate species. Unfortunately, the overwhelming majority of the Central European lowland headwaters are channelized, eutrophicated and/or polluted, and many related species have become critically endangered. Artificial streams established to drain some post-mining sites supplement a network of headwaters and generally do not suffer from agricultural pollution. Nevertheless, the biodiversity and conservation potential of the streams at post-mining sites has never been evaluated. We studied the biodiversity of dragonflies and damselflies (Odonata) at 53 sections (30 m) of an extraordinarily dense system of drainage ditches at a large lignite spoil heap in the Czech Republic. We recorded 22 dragonfly species, of which eight are threatened according to the national Red List. Moreover, four of them are closely associated with the endangered environment of small streams. Overall diversity was generally low at very tiny and/or narrowed streams and was also strongly reduced by high water velocity, high bankside inclination and dominance of expansive common reeds. Sufficient cover of rather shallow sediment layers strongly supports the studied diversity indicators. We thus conclude that post-mining streams in drainage ditches could have a strong potential to offer secondary habitats for threatened headwater biodiversity. However, intermittent reed suppression and the establishment of gently sloping banks and a structured stream bottom are necessary measures for maximizing post-mining stream conservation.