Significant increase in natural disturbance impacts on European forests since 1950

Over the last decades, the natural disturbance is increasingly putting pressure on European forests. Shifts in disturbance regimes may compromise forest functioning and the continuous provisioning of ecosystem services to society, including their climate change mitigation potential. Although forests are central to many European policies, we lack the long-term empirical data needed for thoroughly understanding disturbance dynamics, modeling them, and developing adaptive management strategies. Here, we present a unique database of >170,000 records of ground-based natural disturbance observations in European forests from 1950 to 2019. Reported data confirm a significant increase in forest disturbance in 34 European countries, causing on an average of 43.8 million m³ of disturbed timber volume per year over the 70-year study period. This value is likely a conservative estimate due to under-reporting, especially of small-scale disturbances. We used machine learning techniques for assessing the magnitude of unreported disturbances, which are estimated to be between 8.6 and 18.3 million m³/year. In the last 20 years, disturbances on average accounted for 16% of the mean annual harvest in Europe. Wind was the most important disturbance agent over the study period (46% of total damage), followed by fire (24%) and bark beetles (17%). Bark beetle disturbance doubled its share of the total damage in the last 20 years. Forest disturbances can profoundly impact ecosystem services (e.g., climate change mitigation), affect regional forest resource provisioning and consequently disrupt long-term management planning objectives and timber markets. We conclude that adaptation to changing disturbance regimes must be placed at the core of the European forest management and policy debate. Furthermore, a coherent and homogeneous monitoring system of natural disturbances is urgently needed in Europe, to better observe and respond to the ongoing changes in forest disturbance regimes.     

Mutations in BICD2, which Encodes a Golgin and Important Motor Adaptor,Cause Congenital Autosomal-Dominant Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA. Affected individuals displayed congenital slowly progressive muscle weakness mainly of the lower limbs and congenital contractures. In a large Dutch family, linkage analysis identified a 9q22.3 locus in which exome sequencing uncovered c.320C>T (p.Ser107Leu) in BICD2. Sequencing of 23 additional families affected by dominant SMA led to the identification of pathogenic variants in one family from Canada (c.2108C>T [p.Thr703Met]) and one from the Netherlands (c.563A>C [p.Asn188Thr]). BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport. Transient transfection of HeLa cells with all three mutant BICD2 cDNAs caused massive Golgi fragmentation. This observation was even more prominent in primary fibroblasts from an individual harboring c.2108C>T (p.Thr703Met) (affecting the C-terminal coiled-coil domain) and slightly less evident in individuals with c.563A>C (p.Asn188Thr) (affecting the N-terminal coiled-coil domain). Furthermore, BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi. Previous studies have shown that Drosophila mutant BicD causes reduced larvae locomotion by impaired clathrin-mediated synaptic endocytosis in neuromuscular junctions. These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA.     

Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure

Human Papillomaviruses (HPVs) are the etiological agents of cervical cancer, and HPV‐16 is the most prevalent type. Several HPVs require heparan sulfate proteoglycans (HSPGs) for cell binding. Here, we analyse the phenomenon that preincubation of HPV‐16 with increasing concentrations of heparin results in partial restoration rather than more efficient inhibition of infection. While corroborating that the HSPGs are cell‐binding receptors for HPV‐16, heparin‐preincubated virus bound to the extracellular matrix (ECM) via laminin‐332. Furthermore, the interaction of virions with heparin, a representative of the highly sulfated S‐domains of heparan sulfate (HS) chains of HSPGs, allowed HPV‐16 infection in the absence of cell surface HSPGs. Therefore, we concluded that specific glycan moieties but not specific HSPG protein backbones are required for infection. The increased binding of an epitope‐specific antibody to the viral capsid after heparin binding suggested that initial conformational changes in the HPV‐16 virion occur during infection by interaction with‘heparin‐like’ domains of cellular HSPGs. We propose that HS sequences with specific sulfation patterns are required to facilitate HPV‐16 infection.     

A Ran-binding protein facilitates nuclear import of human papillomavirus type 16

Human papillomaviruses (HPVs) utilize an atypical mode of nuclear import during cell entry. Residing in the Golgi apparatus until mitosis onset, a subviral complex composed of the minor capsid protein L2 and viral DNA (L2/vDNA) is imported into the nucleus after nuclear envelope breakdown by associating with mitotic chromatin. In this complex, L2 plays a crucial role in the interactions with cellular factors that enable delivery and ultimately tethering of the viral genome to mitotic chromatin. To date, the cellular proteins facilitating these steps remain unknown. Here, we addressed which cellular proteins may be required for this process. Using label-free mass spectrometry, biochemical assays, microscopy, and functional virological assays, we discovered that L2 engages a hitherto unknown protein complex of Ran-binding protein 10 (RanBP10), karyopherin alpha2 (KPNA2), and dynein light chain DYNLT3 to facilitate transport towards mitotic chromatin. Thus, our study not only identifies novel cellular interactors and mechanism that facilitate a poorly understood step in HPV entry, but also a novel cellular transport complex.     

Come in and take your coat off – how host cells provide endocytosis for virus entry

Viruses are intracellular parasites that rely upon the host cell machinery for their life cycle. Newly generated virus particles have to transmit their genomic information to uninfected cells/organisms. Viral entry is the process to gain access to viral replication sites within uninfected cells, a multistep course of events that starts with binding to target cells. Since viruses are simple in structure and composition and lack any locomotive capacity, viruses depend on hundreds of host cell proteins during entry. Most animal viruses take advantage of endocytosis to enter cells. Cell biological, morphological and biochemical studies, live cell imaging and systematic approaches have identified various new endocytic mechanisms besides clathrin‐mediated endocytosis, macropinocytosis and caveolar/lipid raft‐mediated endocytosis. Hence, studying virus entry has become ever more complex. This review provides a cell biological overview of the existing endocytic mechanisms and strategies used or potentially used by viruses to enter cells.     

Human Papillomavirus Types 16, 18, and 31 Share Similar Endocytic Requirements for Entry

Human papillomavirus type 18 (HPV18), one of the HPVs with malignant potential, enters cells by an unknown endocytic mechanism. The key cellular requirements for HPV18 endocytosis were tested in comparison to those for HPV16 and -31 endocytoses. HPV18 (like HPV16 and -31) entry was independent of clathrin, caveolin, dynamin, and lipid rafts but required actin polymerization and tetraspanin CD151, and the viruses were routed to the same LAMP-1-positive compartment. Hence, the viruses shared similar cellular requirements for endocytic entry.     

Reconstruction and attribution of the carbon sink of European forests between 1950 and 2000

European forests are an important carbon sink; however, the relative contributions to this sink of climate, atmospheric CO₂ concentration ([CO₂]), nitrogen deposition and forest management are under debate. We attributed the European carbon sink in forests using ORCHIDEE‐FM, a process‐based vegetation model that differs from earlier versions of ORCHIDEE by its explicit representation of stand growth and idealized forest management. The model was applied on a grid across Europe to simulate changes in the net ecosystem productivity (NEP) of forests with and without changes in climate, [CO₂] and age structure, the three drivers represented in ORCHIDEE‐FM. The model simulates carbon stocks and volume increment that are comparable – root mean square error of 2 m³ ha^?1 yr^?1 and 1.7 kg C m^?2 respectively – with inventory‐derived estimates at country level for 20 European countries. Our simulations estimate a mean European forest NEP of 175 ± 52 g C m^?2 yr^?1 in the 1990s. The model simulation that is most consistent with inventory records provides an upwards trend of forest NEP of 1 ± 0.5 g C m^?2 yr^?2 between 1950 and 2000 across the EU 25. Furthermore, the method used for reconstructing past age structure was found to dominate its contribution to temporal trends in NEP. The potentially large fertilizing effect of nitrogen deposition cannot be told apart, as the model does not explicitly simulate the nitrogen cycle. Among the three drivers that were considered in this study, the fertilizing effect of increasing [CO₂] explains about 61% of the simulated trend, against 26% to changes in climate and 13% only to changes in forest age structure. The major role of [CO₂] at the continental scale is due to its homogeneous impact on net primary productivity (NPP). At the local scale, however, changes in climate and forest age structure often dominate trends in NEP by affecting NPP and heterotrophic respiration.     

Identification of a novel SCA locus ( SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21

We present a linkage study in a four-generation autosomal dominant cerebellar ataxia (ADCA) family of Dutch ancestry. The family shows a clinically and genetically distinct form of ADCA. This neurodegenerative disorder manifests in the family as a relatively mild ataxia syndrome with some additional characteristic symptoms. We have identified a SCA19 locus, approved by the Human Genome Nomenclature Committee that can be assigned to the chromosome region 1p21-q21. Our mutation analysis failed to identify any mutations in the known spinocerebellar ataxia ( SCA) genes and linkage analysis excluded the remaining SCA loci. We therefore performed a genome-wide scan with 350 microsatellite markers to identify the location of the disease-causing gene in this family. Multi-point analysis was performed and exclusion maps were generated. Linkage and haplotype analysis revealed linkage to an interval located on chromosome 1. The estimated minimal prevalence of ADCA in the Netherlands is about 3:100,000. To date, sixteen different SCA loci have been identified in ADCA ( SCA1-8 and SCA10-17). However, mutation analysis has been commercially available only for the SCA1, 2, 3, 6 and 7 genes. So far, a molecular analysis in these SCA genes cannot be made in about one-third of the ADCA families. Thus, the identification of this new, additional SCA19 locus will contribute to expanding the DNA diagnostic possibilities.