The dog was the first domesticated animal. Its derivation from grey wolves Canis lupus is important to the study of mammalian domestication, and wolf domestication is an active area of investigation. ...Recent popular books have promoted a hypothesis that wolves domesticated themselves as opposed to the earliest hypothesis that featured pup collection, adoption, and artificial selection. Continuing research has produced a greater understanding of wolf ecology and behaviour, including new insights into the wolf’s interaction with humans. Several characteristics make the wolf conducive to domestication: its sociality, catholic diet, excellent individual and cultural memory, inbreeding tolerance, varied personalities, and adaptable lifestyle. The wolf’s fear of humans is the main impediment and that alone is a factor strongly disfavouring the self‐selection hypothesis. However, collecting young pups from dens and raising them would foster their socialising with humans as pack members. Neither hypothesis explains how wolves undergoing domestication were separated reproductively from their wild relatives, an important condition for domestication. We combine information from the literature with information from our own research on wild wolves, archaeology, and canid morphology. We explain how pup collection and deliberate or incidental selection and encouragement to breed with similarly raised wolves could keep incipient dogs separated reproductively from wild relatives. The key is humans regularly feeding the wolves and keeping only those able to live harmoniously with humans. Well‐fed, human‐dependent wolves would remain near their food supply and in the company of humans, thus increasing their bonds to humans and vice versa. Outbreeding with wild wolves would thus be avoided. Generation after generation of these human‐fed, raised, and selected wolves would become increasingly dependent on humans and shaped by them. The pup‐adoption hypothesis presented here is more in keeping with basic wolf ecology and behaviour than the self‐domestication hypothesis.
Dogs were domesticated from wolves 15000–25000 years ago, and two theories prevail about how the domestication process originated: 1) wolves domesticated themselves by frequenting human camps and feeding on discarded food, and 2) wolf pups were collected from dens and raised by humans selecting those most tractable and suitable for living with humans. This review is the first to assess these theories in relation to the characteristics of wolf ecology and behaviour that make the wolf suitable for domestication. The second hypothesis of pup adoption followed by selection seems better supported.
The Bonn-Oberkassel dog remains (Upper Pleistocene and 14223 +- 58 years old) have been reported more than 100 years ago. Recent re-examination revealed the tooth of another older and smaller dog, ...making this domestic dog burial not only the oldest known, but also the only one with remains of two dogs. This observation brings the total known Magdalenian dogs to nine.
Domestication of dogs during the final Palaeolithic has important implications for understanding pre-Holocene hunter-gatherers. Most proposed hunter-gatherer motivations for domesticating dogs have been utilitarian. However, remains of the Bonn-Oberkassel dogs may offer another view.
The Bonn-Oberkassel dog was a late juvenile when it was buried at approximately age 27–28 weeks, with two adult humans and grave goods. Oral cavity lesions indicate a gravely ill dog that likely suffered a morbillivirus (canine distemper) infection. A dental line of suggestive enamel hypoplasia appears at the 19-week developmental stage. Two additional enamel hypoplasia lines, on the canine only, document further disease episodes at weeks 21 and 23. Pathological changes also include severe periodontal disease that may have been facilitated by immunodeficiency.
Since canine distemper has a three-week disease course with very high mortality, the dog must have been perniciously ill during the three disease bouts and between ages 19 and 23 weeks. Survival without intensive human assistance would have been unlikely. Before and during this period, the dog cannot have held any utilitarian use to humans.
We suggest that at least some Late Pleistocene humans regarded dogs not just materialistically, but may have developed emotional and caring bonds for their dogs, as reflected by the survival of this dog, quite possibly through human care.
•The dog was 7 months old when it died and was buried with 2 humans.•The dog had been perniciously ill when 19 weeks old caused by distemper.•Grave goods included a molar from another, second dog.
Lake systems are under heavy pressure impacting on their biodiversity and associated ecosystem services. This is especially acute in West Africa and developing countries which lack resources and ...technical capacities for waste disposal, water purification, as well as sufficient scientific capacities for biomonitoring and integrated management. The preservation, monitoring and improvement of lake quality in these countries are, however, of paramount importance. Throughout the developed world, an array of indicators and multimetric indices have been incorporated into lake biomonitoring and assessment. Here, we assess the numerous procedures, metrics and indices using macroinvertebrates as indicators for lake quality and assess applicability in West African lakes and in developing countries more generally. We propose a framework for macroinvertebrate-based monitoring adapted to these countries, including recommendations for developing new indices and adapting tolerance scores of taxa to local conditions. This work underlines the importance of macroinvertebrates for biomonitoring of lake health in West African lakes and developing countries more generally.
Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer's disease (AD). The long-term safety and effect ...of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed.
In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once daily (later reduced to 5 and 25 mg) for 6 months. Participants entered ALZ2004, a 12-month treatment extension with placebo or atabecestat 10 or 25 mg, followed by an open-label phase. Safety, changes in CSF biomarker levels, brain volume, and effects on cognitive performance were assessed.
Of 114 participants randomized in ALZ2002, 99 (87%) completed, 90 entered the ALZ2004 double-blind phase, and 77 progressed to the open-label phase. CSF Aβ fragments and sAPPβ were reduced dose-proportionately. Decreases in whole brain and hippocampal volumes were greater in participants with mild cognitive impairment (MCI) due to AD than in preclinical AD, but were not affected by treatment. In ALZ2004, change from baseline in RBANS trended toward worse scores for atabecestat versus placebo. Elevated liver enzyme adverse events reported in 12 participants on atabecestat resulted in dosage modification and increased frequency of safety monitoring. Treatment discontinuation normalized ALT or AST in all except one with pretreatment elevation, which remained mildly elevated. No case met ALT/AST > 3× ULN and total bilirubin > 2× ULN (Hy's law).
Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.
ALZ2002: ClinicalTrials.gov, NCT02260674, registered October 9, 2014; ALZ2004: ClinicalTrials.gov, NCT02406027, registered April 1, 2015.
In a recent article in this journal, Galeta et al., (2020) discussed eight Pleistocene “protodogs” and seven Pleistocene wolves. Those “protodogs” had been diagnosed in earlier publications, based on ...skull morphology. We re‐examined the Galeta et al. paper to offer comments on their observed outcomes, and the conclusion of presumed domestication. Of seven metrics that the authors used, five differed statistically between their two groups. However, from more elaborate studies, some of those same metrics had been rejected previously as not valid species‐distinguishing traits. In this respect, we do accept cranium size and wider palate as species‐distinguishing metrics. The physical size of their specimens was much larger than other archaeological specimens that have been accepted as dogs. Additionally, their sample size was small, compared to the number of available specimens, as shown from previous publications by the same group. Thus, we considered statistical differences that were found between groups in their study, and assessed whether the outcomes could have resulted from natural morphological variation. We examined a group of 73 dire wolves ((Aenocyon Canis dirus; Perri et al., 2021), using the same methods as used by Galeta et al., (2020). We could segregate two distinct morphological groups in our study, one having outcomes that were identical to the “protodogs” in Galeta et al. (2020). For the specimens of extinct dire wolves to segregate in the same way as the subjects from Galeta et al. indicates that natural variation probably was the driver of their observed outcomes, domestication being an unlikely assumption.
Rheumatic heart disease (RHD) is one of the most common causes of cardiovascular complications in developing countries. It is a heart valve disease that typically affects children. Impaired heart ...valves stop functioning properly, resulting in a turbulent blood flow within the heart known as a murmur. This murmur can be detected by cardiac auscultation. However, the specificity and sensitivity of manual auscultation were reported to be low. The other alternative is echocardiography, which is costly and requires a highly qualified physician. Given the disease's current high prevalence rate (the latest reported rate in the study area (Ethiopia) was 5.65%), there is a pressing need for early detection of the disease through mass screening programs. This paper proposes an automated RHD screening approach using machine learning that can be used by non-medically trained persons outside of a clinical setting. Heart sound data was collected from 124 persons with RHD (PwRHD) and 46 healthy controls (HC) in Ethiopia with an additional 81 HC records from an open-access dataset. Thirty-one distinct features were extracted to correctly represent RHD. A support vector machine (SVM) classifier was evaluated using two nested cross-validation approaches to quantitatively assess the generalization of the system to previously unseen subjects. For regular nested 10-fold cross-validation, an f1-score of 96.0 ± 0.9%, recall 95.8 ± 1.5%, precision 96.2 ± 0.6% and a specificity of 96.0 ± 0.6% were achieved. In the imbalanced nested cross-validation at a prevalence rate of 5%, it achieved an f1-score of 72.2 ± 0.8%, recall 92.3 ± 0.4%, precision 59.2 ± 3.6%, and a specificity of 94.8 ± 0.6%. In screening tasks where the prevalence of the disease is small, recall is more important than precision. The findings are encouraging, and the proposed screening tool can be inexpensive, easy to deploy, and has an excellent detection rate. As a result, it has the potential for mass screening and early detection of RHD in developing countries.
Prassack et al. (2020) analyzed dental microwear in a sample of canids from the Gravettian site of Předmostí that had been identified as either Paleolithic dogs or Pleistocene wolves (n = 10 in each ...group), accepting that the morphological differences between the groups validly distinguished the (self-domesticating) protodogs from wolves. The authors then concluded that differences in one m2 microwear pattern separated those groups and indicated enhanced anthropogenic based durophagy in the putative protodogs. The study also inferred protodog diets from another isotope study.
We disagree with this report for several reasons. First morphological criteria (skull and mandible) accepted here to distinguish the groups have been challenged based on robust research and can be explained by variability within wolves. Thus, we reject that one of the groups represents protodogs. We also question why only ten specimens were examined in each group, while about 130 were available in the original study, and why no specimen-selection criteria were reported. The study accepts the self-domestication hypothesis, which we reject based on solid knowledge of wolf behavior and inferences about what prey remains would be available, and where, in a hunter-gatherer setting. In summary, we can neither accept the existence of protodogs, nor the proposed difference in m2 microwear as being related to anthropogenic durophagy.
•We challenge the existence of protodogs.•And that microwear change in m2 was caused by anthropogenic durophagy.•We criticize many of the reported so-called difference to distinguish between wolves and dogs.
Purpose
The accumulation of misfolded tau is a common feature of several neurodegenerative disorders, with Alzheimer’s disease (AD) being the most common. Earlier we identified JNJ-64326067, a novel ...isoquinoline derivative with high affinity and selectivity for tau aggregates from human AD brain. We report the dosimetry of
18
F JNJ-64326067 and results of a proof-of-concept study comparing subjects with probable Alzheimer’s disease to age-matched healthy controls.
Methods
18
F JNJ-64326067 PET scans were acquired for 90 min and then from 120 to 180 min in 5 participants with
18
F-florbetapir PET amyloid positive probable AD (73 ± 9 years) and 5
18
F-florbetapir PET amyloid negative healthy controls (71 ± 7 years). Whole-body
18
F JNJ-64326067 PET CT scans were acquired in six healthy subjects for 5.5 h in 3 scanning sessions. Brain PET scans were visually reviewed. Regional quantification included kinetic analysis of distribution volume ration (DVR) estimated by Logan graphical analysis over the entire scan and static analysis of SUVr in late frames. Both methods used ventral cerebellar cortex as a reference region.
Results
One of the healthy controls had focal areas of PET signal in occipital and parietal cortex underlying the site of a gunshot injury as an adolescent; the other four healthy subjects had no tau brain signal. Four of the 5 AD participants had visually apparent retention of
18
F JNJ-64326067 in relevant cortical regions. One of the AD subjects was visually negative. Cortical signal in visually positive subjects approached steady state by 120 min. Temporal and frontal cortical SUVr/DVR values in visually positive AD subjects ranged from 1.21 to 3.09/1.2 to 2.18 and from 0.92 to 1.28/0.91 to 1.16 in healthy controls. Whole-body effective dose was estimated to be 0.0257 mSv/MBq for females and 0.0254 mSv/MBq for males.
Conclusions
18
F JNJ-64326067 could be useful for detection and quantitation of tau aggregates.
•Mollusc community ecology analysis using SOM and machine learning models.•SOM in conjunction with IndVal, LDA and RF models are effective tools.•Mollusc assemblages are structured by physicochemical ...variables related to the river–estuary continuum.•Progressively downstream ward habitats faced to increasing anthropogenic stress.•Our approach can likely be applied for a variety of freshwater systems.
The poor understanding of changes in mollusc ecology along rivers, especially in West Africa, hampers the implementation of management measures. We used a self–organizing map, indicator species analysis, linear discriminant analysis and a random forest model to distinguish mollusc assemblages, to determine the ecological preferences of individual mollusc species and to associate major physicochemical variables with mollusc assemblages and occurrences in the Sô River Basin, Benin. We identified four mollusc assemblages along an upstream–downstream gradient. Dissolved oxygen (DO), biochemical oxygen demand (BOD), salinity, calcium (Ca), total nitrogen (TN), copper (Cu), lead (Pb), nickel (Ni), cadmium (Cd) and mercury (Hg) were the major physicochemical variables responsible for structuring these mollusc assemblages. However, the physicochemical factors responsible for shaping the distribution of individual species varied per species. Upstream sites (assemblage I) showed high DO and low BOD and mineral compounds (i.e., TN, salinity, and Ca), which are primarily responsible for structuring the occurrences of bivalves (Afropisidium pirothi, Etheria elliptica, Sphaerium hartmanni) and the gastropod Lanistes varicus. Sites along the middle reach (assemblage II) were characterised by a high degree of organic pollution but low heavy metal pollution; we detected no specific mollusc indicator species. Downstream sites (assemblage III) displayed high mineral and heavy metal concentrations and a fauna without specific indicator species. Finally, downstream sites associated with brackish water (assemblage IV) displayed important levels of organic and heavy metal pollution. These sites are dominated by diverse gastropods (i.e., Bulinus spp., Gabbiella africana, Indoplanorbis exustus, Pachymelania fusca, Radix natalensis, Stenophysa marmorata and Tympanotonos fuscatus). Our results highlight that mollusc communities in the Sô River Basin are structured by key physicochemical variables related to the river–estuary continuum. Habitats that are progressively more downstream are confronted with increasing anthropogenic stress. Conservation and management plans should focus on downstream habitats.