The loss of Normandy and the invention of Terre Normannorum, 1204

The conquest of Normandy by Philip Augustus of France effectively ended the ‘Anglo-Norman’ realm created in 1066, forcing cross-Channel landholders to choose between their English and their Norman estates. The best source for the resulting tenurial upheaval in England is the Rotulus de valore terrarum Normannorum, a list of seized properties and their former holders, and this article seeks to expand our understanding of the impact of the loss of Normandy through a detailed analysis of this document. First, it demonstrates that the compilation of the roll can be divided into two distinct stages, the first containing valuations taken before royal justices in June 1204 and enrolled before the end of July, and the second consisting of returns to orders for the valuation of particular properties issued during the summer and autumn, as part of the process by which these estates were committed to new holders. Second, study of the roll and other documentary sources permits a better understanding of the order for the seizure of the lands of those who had remained in Normandy, the text of which does not survive. This establishes that this royal order was issued in late May 1204 and, further, that it enjoined the temporary seizure rather than the permanent confiscation of these lands. Moreover, the seizure was not retrospective and covers a specific window of time in 1204. On the one hand, this means that the roll is far from a comprehensive record of terre Normannorum. On the other hand, it is possible to correlate the identities of those Anglo-Norman landholders whose English estates were seized with the military progress of the French king through the duchy in May and June and thus shed new light on the campaign of 1204. Third, the article considers the initial management of the seized estates and highlights the fact that, when making arrangements for the these lands, John was primarily concerned to maintain his freedom of manoeuvre, since he was not prepared to accept that Normandy had been lost for good.

Loss of language in early development of autism and specific language impairment

Background:  Several authors have highlighted areas of overlap in symptoms and impairment among children with autism spectrum disorder (ASD) and children with specific language impairment (SLI). By contrast, loss of language and broadly defined regression have been reported as relatively specific to autism. We compare the incidence of language loss and language progression of children with autism and SLI. Methods:  We used two complementary studies: the Special Needs and Autism Project (SNAP) and the Manchester Language Study (MLS) involving children with SLI. This yielded a combined sample of 368 children (305 males and 63 females) assessed in late childhood for autism, history of language loss, epilepsy, language abilities and nonverbal IQ. Results:  language loss occurred in just 1% of children with SLI but in 15% of children classified as having autism or autism spectrum disorder. Loss was more common among children with autism rather than milder ASD and is much less frequently reported when language development is delayed. For children who lost language skills before their first phrases, the phrased speech milestone was postponed but long-term language skills were not significantly lower than children with autism but without loss. For the few who experienced language loss after acquiring phrased speech, subsequent cognitive performance is more uncertain. Conclusions:  Language loss is highly specific to ASD. The underlying developmental abnormality may be more prevalent than raw data might suggest, its possible presence being hidden for children whose language development is delayed.

Cyclic loss of open solar flux since 1868: the link to heliospheric current sheet tilt and implications for the Maunder Minimum

Open solar flux (OSF) variations can be described by the imbalance between source and loss terms. We use spacecraft and geomagnetic observations of OSF from 1868 to present and assume the OSF source, S, varies with the observed sunspot number, R. Computing the required fractional OSF loss, χ, reveals a clear solar cycle variation, in approximate phase with R. While peak R varies significantly from cycle to cycle, χ is surprisingly constant in both amplitude and waveform. Comparisons of χ with measures of heliospheric current sheet (HCS) orientation reveal a strong correlation. The cyclic nature of χ is exploited to reconstruct OSF back to the start of sunspot records in 1610. This agrees well with the available spacecraft, geomagnetic, and cosmogenic isotope observations. Assuming S is proportional to R yields near-zero OSF throughout the Maunder Minimum. However, χ becomes negative during periods of low R, particularly the most recent solar minimum, meaning OSF production is underestimated. This is related to continued coronal mass ejection (CME) activity, and therefore OSF production, throughout solar minimum, despite R falling to zero. Correcting S for this produces a better match to the recent solar minimum OSF observations. It also results in a cycling, nonzero OSF during the Maunder Minimum, in agreement with cosmogenic isotope observations. These results suggest that during the Maunder Minimum, HCS tilt cycled as over recent solar cycles, and the CME rate was roughly constant at the levels measured during the most recent two solar minima.

Accelerated loss of alpine glaciers in the Kodar Mountains, south-eastern Siberia

The recession of mountain glaciers around the world has been linked to anthropogenic climate change and small glaciers (e.g. < 2 km2) are thought to be particularly vulnerable, with reports of their disappearance from several regions. However, the response of small glaciers to climate change can be modulated by non-climatic factors such as topography and debris cover and there remain a number of regions where their recent change has evaded scrutiny. This paper presents results of the first multi-year remote sensing survey of glaciers in the Kodar Mountains, the only glaciers in SE Siberia, which we compare to previous glacier inventories from this continental setting that reported total glacier areas of 18.8 km2 in ca. 1963 (12.6 km2 of exposed ice) and 15.5 km2 in 1974 (12 km2 of exposed ice). Mapping their debris-covered termini is difficult but delineation of debris-free ice on Landsat imagery reveals 34 glaciers with a total area of 11.72 ± 0.72 km2 in 1995, followed by a reduction to 9.53 ± 0.29 km2 in 2001 and 7.01 ± 0.23 km2 in 2010. This represents a ~ 44% decrease in exposed glacier ice between ca. 1963 and 2010, but with 40% lost since 1995 and with individual glaciers losing as much as 93% of their exposed ice. Thus, although continental glaciers are generally thought to be less sensitive than their maritime counterparts, a recent acceleration in shrinkage of exposed ice has taken place and we note its coincidence with a strong summer warming trend in the region initiated at the start of the 1980s. Whilst smaller and shorter glaciers have, proportionally, tended to shrink more rapidly, we find no statistically significant relationship between shrinkage and elevation characteristics, aspect or solar radiation. This is probably due to the small sample size, limited elevation range, and topographic setting of the glaciers in deep valleys-heads. Furthermore, many of the glaciers possess debris-covered termini and it is likely that the ablation of buried ice is lagging the shrinkage of exposed ice, such that a growth in the proportion of debris cover is occurring, as observed elsewhere. If recent trends continue, we hypothesise that glaciers could evolve into a type of rock glacier within the next few decades, introducing additional complexity in their response and delaying their potential demise.

Repressor element 1 silencing transcription factor couples loss of pluripotency with neural induction and neural differentiation

Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory program and reciprocal activation of the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie maintenance of pluripotency are partially characterized whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (repressor element 1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors and more recently, and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Furthermore, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes, and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation.

Use of mutants to dissect the role of ethylene signalling in organ senescence and the regulation of yield in Arabidopsis thaliana

The role of ethylene in regulating organ senescence in Arabidopsis has been investigated by studying the development of mutants that have an attenu- ated capacity to perceive the gas. The onset of leaf senescence and floral organ abscission was delayed in the ethylene-insensitive mutant etr1. The photosynthetic life span of rosette leaves was similarly extended in the gain- of-function mutant ers2, and this mutant also exhibited a delay in the timing of pod dehiscence primarily as a con- sequence of an extension in the final stages of senescence. A detailed analysis of yield revealed that whilst thousand grain weight was increased, by as much as 20 %, in etr1, ein4, and the loss-of-function mutant etr2, only the latter showed a significant increase in total weight of seeds produced per plant. The other studied mutants exhibited a reduction in total seed yield of almost 40 %. These observations are discussed in the context of the possible role of ethylene in regulating organ senescence and their significance in the breeding of crop plants with enhanced phenotypic characteristics.

Loss of Dictyostelium HSPC300 causes a scar-like phenotype and loss of SCAR protein.

HSPC300 is essential for most SCAR complex functions. The phenotype of HSPC300 knockouts is most similar to mutants in scar, not the other members of the SCAR complex, suggesting that HSPC300 acts most directly on SCAR itself.

Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null mouse

Background: Obese adults are prone to develop metabolic and cardiovascular diseases. Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and cardiovascular diseases. Fundamental advancements to better understand the pathophysiology of obesity are critical in the development of anti-obesity therapies not only for this but also future generations. Skeletal muscle plays a major role in fat metabolism and much work has focused in promoting this activity in order to control the development of obesity. Research has evaluated myostatin inhibition as a strategy to prevent the development of obesity and concluded in some cases that it offers a protective mechanism against a high-fat diet. Results: We hypothesised that myostatin inhibition should protect not only the mother but also its developing foetus from the detrimental effects of a high-fat diet. Unexpectedly, we found muscle development was attenuated in the foetus of myostatin null mice raised on a high-fat diet. We therefore re-examined the effect of the high-fat diet on adults and found myostatin null mice were more susceptible to diet-induced obesity through a mechanism involving impairment of inter-organ fat utilization. Conclusions: Loss of myostatin alters fatty acid uptake and oxidation in skeletal muscle and liver. We show that abnormally high metabolic activity of fat in myostatin null mice is decreased by a high-fat diet resulting in excessive adipose deposition and lipotoxicity. Collectively, our genetic loss-of-function studies offer an explanation of the lean phenotype displayed by a host of animals lacking myostatin signalling. Keywords: Muscle, Obesity, High-fat diet, Metabolism, Myostatin

Loss of Methylation at H19 DMD Is Associated with Biallelic Expression and Reduced Development in Cattle Derived by Somatic Cell Nuclear Transfer

Although cloning of mammals has been achieved successfully, the percentage of live offspring is very low because of reduced fetal size and fewer implantation sites. Recent studies have attributed such pathological conditions to abnormal reprogramming of the donor cell used for cloning. The inability of the oocyte to fully restore the differentiated status of a somatic cell to its pluripotent and undifferentiated state is normally evidenced by aberrant DNA methylation patterns established throughout the genome during development to blastocyst. These aberrant methylation patterns are associated with abnormal expression of imprinted genes, which among other genes are essential for normal embryo development and gestation. We hypothesized that embryo loss and low implantation rates in cattle derived by somatic cell nuclear transfer (SCNT) are caused by abnormal epigenetic reprogramming of imprinted genes. To verify our hypothesis, we analyzed the parental expression and the differentially methylated domain (DMD) methylation status of the H19 gene. Using a parental-specific analysis, we confirmed for the first time that H19 biallelic expression is tightly associated with a severe demethylation of the paternal H19 DMD in SCNT embryos, suggesting that these epigenetic anomalies to the H19 locus could be directly responsible for the reduced size and low implantation rates of cloned embryos in cattle.

Deficiency of the Cytoskeletal Protein SPECC1L Leads to Oblique Facial Clefting

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L. are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Speed 1 1 is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.