Uncertainty in identifying local extinctions: the distribution of missing data and its effects on biodiversity measures

Identifying local extinctions is integral to estimating species richness and geographic range changes and informing extinction risk assessments. However, the species occurrence records underpinning these estimates are frequently compromised by a lack of recorded species absences making it impossible to distinguish between local extinction and lack of survey effort—for a rigorously compiled database of European and Asian Galliformes, approximately 40% of half-degree cells contain records from before but not after 1980. We investigate the distribution of these cells, finding differences between the Palaearctic (forests, low mean human influence index (HII), outside protected areas (PAs)) and Indo-Malaya (grassland, high mean HII, outside PAs). Such cells also occur more in less peaceful countries. We show that different interpretations of these cells can lead to large over/under-estimations of species richness and extent of occurrences, potentially misleading prioritization and extinction risk assessment schemes. To avoid mistakes, local extinctions inferred from sightings records need to account for the history of survey effort in a locality.     

On the PAM matrix model of protein evolution

The internal consistency of the PAM matrix model of protein evolution is here investigated. The 1 PAM matrix has been constructed from amino acid replacements observed in closely related sequences. Such replacements are of two types, those that do not require an intermediate amino acid replacement and those that do. The second type of replacement must generally be produced by a repetition of the first. This allows data on the first type to be used in predicting data on the second type so that some elements of the 1 PAM matrix may be used to predict others. A discrepancy of more than two orders of magnitude is found between the predictions and the data when this is carried out. This is partly accounted for by an error in constructing the matrix. However, it also seems necessary that the basic model be modified. Several possibilities are considered. One of these is to incorporate a site-dependent spectrum of mutabilities associated with each amino acid.      

Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.     

Natural population die-offs: causes and consequences for terrestrial mammals

Extreme changes in the environment can generate high mortalities in wildlife populations. When these mortalities are attributable to extreme natural events, they are referred to as natural population die-offs. Despite growing reports of such die-offs, a consensus on how to define them has not emerged. Furthermore, although anthropogenically caused extreme events are predicted to occur at a higher frequency and intensity compared with natural events, an integrative synthesis assessing their significance for wildlife population viability is lacking. These issues hamper the ability to identify populations most at risk. Here, we propose a functional definition of natural population die-offs, an assessment of extrinsic and intrinsic processes shaping these die-offs, and a framework for assessing the vulnerability of terrestrial mammals to natural and anthropogenically caused extreme events.