A cervical ligamentum flavum cyst in an 82-year-old woman presenting with spinal cord compression: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>We report on a very rare case of a cervical ligamentum flavum cyst, which presented with progressive myelopathy and radiculopathy. The cyst was radically extirpated and our patient showed significant recovery. A review of the relevant literature yielded seven cases.</p> <p>Case presentation</p> <p>An 82-year-old Greek woman presented with progressive bilateral weakness of her upper extremities and causalgia, cervical pain, episodes of upper extremity numbness and significant walking difficulties. Her neurological examination showed diffusely decreased motor strength in both her upper and lower extremities. Magnetic resonance imaging of her cervical spine demonstrated a large, well-demarcated cystic lesion on the dorsal aspect of her spinal cord at the C3 to C4 level, significantly compressing the spinal cord at this level, in close proximity to the yellow ligament and the C3 left lamina. The largest diameter of this lesion was 1.4 cm, and there was no lesion enhancement after the intravenous administration of a paramagnetic contrast. The lesion was surgically removed after a bilateral C3 laminectomy. The thick cystic wall was yellow and fibro-elastic in consistency, while its content was gelatinous and yellow-brownish. A postoperative cervical-spine magnetic resonance image was obtained before her discharge, demonstrating decompression of her spinal cord and dural expansion. Her six-month follow-up evaluation revealed complete resolution of her walking difficulties, improvement in the muscle strength of her arms (4+/5 in all the affected muscle groups), no causalgia and a significant decrease in her preoperative upper extremity numbness.</p> <p>Conclusion</p> <p>Cervical ligamentum flavum cysts are rare benign lesions, which should be included in the list of differential diagnosis of spinal cystic lesions. They can be differentiated from other intracanalicular lesions by their hypointense appearance on T₁-weighted and hyperintense appearance on T₂-weighted magnetic resonance images, with contrast enhancement of the cystic wall. Surgical extirpation of the cyst is required for symptom alleviation and decompression of the spinal cord. The outcome of these cysts is excellent with no risk of recurrence.</p

Smy2p Participates in COPII Vesicle Formation Through the Interaction with Sec23p/Sec24p Subcomplex

The coat protein complex II (COPII) is essential for vesicle formation from the endoplasmic reticulum (ER) and is composed of two heterodimeric subcomplexes, Sec23p/Sec24p and Sec13p/Sec31p, and the small guanosine triphosphatase Sar1p. In an effort to identify novel factors that may participate in COPII vesicle formation, we isolated SMY2, a yeast gene encoding a protein of unknown function, as a multicopy suppressor of the temperature-sensitive sec24-20 mutant. We found that even a low-copy expression of SMY2 was sufficient for the suppression of the sec24-20 phenotypes, and the chromosomal deletion of SMY2 led to a severe growth defect in the sec24-20 background. In addition, SMY2 exhibited genetic interactions with several other genes involved in the ER-to-Golgi transport. Subcellular fractionation analysis showed that Smy2p was a peripheral membrane protein fractionating together with COPII components. However, Smy2p was not loaded onto COPII vesicles generated in vitro. Interestingly, coimmunoprecipitation between Smy2p and the Sec23p/Sec24p subcomplex was specifically observed in sec23-1 and sec24-20 backgrounds, suggesting that this interaction was a prerequisite for the suppression of the sec24-20 phenotypes by overexpression of SMY2. We propose that Smy2p is located on the surface of the ER and facilitates COPII vesicle formation through the interaction with Sec23p/Sec24p subcomplex

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5.Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02.info:eu-repo/semantics/publishedVersio

Status, trends and future dynamics of biodiversity and ecosystems underpinning nature's contributions to people

Biodiversity at the species and ecosystem levels is currently under multiple threats almost everywhere in the Asia-Pacific region, and in many areas the situation is now critical (well established). Of the various ecosystems, lowland evergreen forests, alpine ecosystems, limestone karsts, inland wetlands, and estuarine and coastal habitats are most threatened (well established). Genetic diversity within species, both wild and domestic, is also decreasing in many cases as a result of decreasing ranges (established but incomplete). In several countries there has been a small increase in the forest cover which is mostly attributed to monoculture forestry plantations and enabling policies of the governments. Forest fires associated with rapid loss of forest cover is leading to enormous environmental and socio-economic loss (well established) {3.2.1; 3.2.2; 3.2.3; 3.2.4; 3.2.5; 3.3.1}. There has been a steady decline in the populations of large vertebrates due to poaching and illegal trade in wildlife parts and products in the Asia-Pacific region (well established). As a result, most of these species now survive only in the best-managed protected areas (well established). Widespread loss of large vertebrates has had a measureable impact on several forest functions and services, including seed dispersal (established but incomplete). Australia has the highest rate of mammal extinction (>10 per cent) of any continent globally. Bird extinctions on individual Pacific islands range from 15.4 per cent to 87.5 per cent for those with good fossil records, and these extinctions have resulted in the loss of many ecological functions previously performed by birds (well established). Besides wildlife, there is a massive regional trade in timber, traditional medicines and other products (well established). Without adequate protection, remediation and proper policies, the current decline in biodiversity and nature's contributions to people on land, in freshwaters, and in the sea will threaten the quality of life of future generations in the Asia-Pacific region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.7; 3.2.2.1; 3.3.1} With the current rate of human population growth, expansion of urban industrial environments, transformation of agriculture in favour of high yielding varieties, transforming forests to uniform plantations of oil palm, rubber or timber trees, the biodiversity and nature's contributions to people in the Asia-Pacific region are likely to be adversely affected in the coming decades (well established). It is predicted that most of the biodiversity in the next few decades may be confined to protected areas or in places where the local communities have taken the lead in local level conservation in lieu of economic incentives and equitable compensation by the stake-holders. Unprecedented increase in human population of the Asia-Pacific region has stressed the fragile ecosystems to their limits; while arable cropping has been extended to sites which were not entirely suitable for it, resulting in soil degradation and erosion (well established) {3.2.1.1; 3.2.1.2; 3.2.1.5; 3.2.2.2; 3.2.2.4; 3.3; 3.3.1; 3.3.6; 3.4}. Freshwater ecosystems in the Asia-Pacific region support more than 28 per cent of aquatic and semi-aquatic species but nearly 37 per cent of these species are threatened due to anthropogenic and climatic drivers (well established). Cumulative impacts of global warming and damming of rivers in some of the river basins will have significant negative impacts on fish production and environmental flows (well established). Likewise, degradation of wetlands has had severe negative impacts on migratory waterfowl, fish production and local livelihoods (well established). However, there are scientific data gaps on the current status of biodiversity and nature's contributions to people in most of the river basins, inland wetlands and peatlands of the region {3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.2.4}. Coastal and marine habitats are likewise threatened due to commercial aquaculture, overfishing, and pollution affecting biodiversity and nature's contributions to people (well established). Detailed analyses of fisheries production in the region have shown severe decline in recent decades. It is projected that if unsustainable fishing practices continue, there could be no exploitable stocks of fish by as early as 2048. This could lead to trophic cascades and collapse of marine ecosystems (established but incomplete). Loss of seagrass beds which forms main diet of several threatened species such as dugong is a major concern (well established). There is a need to conduct systematic and region-wide assessment of fisheries stocks and coastal habitat in the region to aid conservation, management and restoration. {3.1.3.1; 3.2.3.3; 3.2.3.6; 3.2.4.6; 3.4}. Mangrove ecosystems in the Asia-Pacific region are most diverse in the world. They support a rich biodiversity and provide a range of provisioning, regulating and supporting services, which are crucial for the livelihood of local communities (well established). Both mangrove and intertidal habitats form a buffer from siltation for offshore coral reefs protection hence affecting productivity of reefs including seagrass. However, up to 75 per cent of the mangroves have been degraded or converted in recent decades (well established). The conversion of mangroves to aquaculture, rice, oil palm, and other land-use changes is leading to the loss of the buffer between sea and land which can reduce the impact of natural disasters such as cyclones and tsunamis. It is projected that rise in sea level due to global warming would pose the biggest threat to mangroves, thereby affecting nature's contributions to people especially in Bangladesh, Philippines, New Zealand, Viet Nam and China (well established) {3.2.3.1; 3.2.3.2; 3.3.4}. There has been a steady increase in the number, abundance and impacts of invasive alien species in the Asia-Pacific region, negatively affecting native biodiversity, ecosystem functioning and socio-cultural environments (well established). The total annual loss caused by invasive alien species has been estimated at US$35.5 billion in SE Asia and US$9B in Australia. Costs to agriculture due to invasive alien species are likewise immense in the region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.5; 3.2.1.6; 3.2.1.7; 3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.3.6; 3.3.5}. There has been a nearly 30 per cent decline in biocultural diversity in the Asia-Pacific region since the 1970s (well established). Decline of linguistic diversity has been catastrophic in the indigenous Australian and Trans-New Guinean families, as a result of a shifting away from small indigenous languages towards larger, national or regional languages (well established). Linguistic and biological diversity often coincide in the Asia-Pacific region and parallel strategies need to be developed for their conservation. National conservation priorities should take into consideration the bioculturally rich areas that are facing great threats {3.2.5; 3.2.5.2; 3.2.5.4; 3.4}. Protected Area coverage in the Asia-Pacific region has increased substantially since last three decades. Despite this progress, however, at least 75 per cent of Key Biodiversity Areas remain unprotected, suggesting that the region is not on track to conserve areas of particular importance for biodiversity, as called for under Aichi Target 11 (well established). Oceania has the highest overall Protected Area coverage in the region. North-East Asia has the highest proportion of Key Biodiversity Areas covered by Protected Areas, but only 1 per cent of its marine area is protected (well established) {3.2.5.6; 3.2.6; 3.2.6.1}. The Asia-Pacific region has high levels of endemism, and some 25 per cent of the region’s endemic species are facing high extinction risks as per the IUCN Red List. Endemic species in some subregions face an extinction risk as high as 46 per cent of endemic species threatened in South Asia (well established). South-East Asia has the greatest number of threatened species and the fastest increases in extinction risk (Red List Index) in the Asia-Pacific region. North Asian endemic species extinction risk is also higher than the regional average; the high percentage of Data Deficient species (36 per cent) indicates that more research and conservation action are needed for endemic species in this subregion (well established) {3.2.1; 3.2.2; 3.2.6.2; 3.3.4}. Some aspects of biodiversity have recently started to recover in several countries in the Asia-Pacific region (established but incomplete). This recovery has resulted from various changes, including population concentration in cities, increased agricultural production per unit area, increasing conservation awareness among citizens, and the enabling policies of the governments. Future trends of biodiversity in the Asia-Pacific region will largely depend on whether other countries will follow this recovering trajectory by stabilizing land/sea use change, manage their natural resources sustainably, and cooperating with each other in meeting the Aichi Targets and the Sustainable Development Goals {3.2.1.5; 3.2.3.5; 3.3.1; 3.3.3; 3.3.6}. Given that the scientific information on the status and trends of biodiversity and nature's contributions to people is not available uniformly across all ecosystems and habitats in the region, the national governments are encouraged to initiate systematic documentation and monitoring of health of ecosystems and ecosystem flows (established but incomplete). Saving terrestrial fauna especially big mammals and other fauna that require large roaming areas such as Orangutans, proboscis monkey, hornbills, tigers, Sumatran rhinoceros, gaurs and Asian elephants can be done by connecting large tracts of forests with wildlife corridors or through rehabilitation projects; the same goes for coastal and marine, freshwater and other ecosystems in the region {3.2.1.1; 3.2.2.4; 3.3.4; 3.4}

Genome-wide profiling of humoral immunity and pathogen genes under selection identifies immune evasion tactics of Chlamydia trachomatis during ocular infection

The frequency and duration of Chlamydia trachomatis (Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection

Identifying lineage effects when controlling for population structure improves power in bacterial association studies

Bacteria pose unique challenges for genome-wide association studies because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome1,2. Although methods developed for human studies can correct for strain structure3,4, this risks considerable loss-of-power because genetic differences between strains often contribute substantial phenotypic variability5. Here, we propose a new method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped. We demonstrate its ability to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3,144 isolates from four taxonomically diverse clonal and recombining bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Strong selection, recombination and penetrance confer high power to recover known antimicrobial resistance mechanisms and reveal a candidate association between the outer membrane porin nmpC and cefazolin resistance in E. coli. Hence, our method pinpoints locus-specific effects where possible and boosts power by detecting lineage-level differences when fine-mapping is intractable

Conservation of intron and intein insertion sites: implications for life histories of parasitic genetic elements

<p>Abstract</p> <p>Background</p> <p>Inteins and introns are genetic elements that are removed from proteins and RNA after translation or transcription, respectively. Previous studies have suggested that these genetic elements are found in conserved parts of the host protein. To our knowledge this type of analysis has not been done for group II introns residing within a gene. Here we provide quantitative statistical support from an analyses of proteins that host inteins, group I introns, group II introns and spliceosomal introns across all three domains of life.</p> <p>Results</p> <p>To determine whether or not inteins, group I, group II, and spliceosomal introns are found preferentially in conserved regions of their respective host protein, conservation profiles were generated and intein and intron positions were mapped to the profiles. Fisher's combined probability test was used to determine the significance of the distribution of insertion sites across the conservation profile for each protein. For a subset of studied proteins, the conservation profile and insertion positions were mapped to protein structures to determine if the insertion sites correlate to regions of functional activity. All inteins and most group I introns were found to be preferentially located within conserved regions; in contrast, a bacterial intein-like protein, group II and spliceosomal introns did not show a preference for conserved sites.</p> <p>Conclusions</p> <p>These findings demonstrate that inteins and group I introns are found preferentially in conserved regions of their respective host proteins. Homing endonucleases are often located within inteins and group I introns and these may facilitate mobility to conserved regions. Insertion at these conserved positions decreases the chance of elimination, and slows deletion of the elements, since removal of the elements has to be precise as not to disrupt the function of the protein. Furthermore, functional constrains on the targeted site make it more difficult for hosts to evolve immunity to the homing endonuclease. Therefore, these elements will better survive and propagate as molecular parasites in conserved sites. In contrast, spliceosomal introns and group II introns do not show significant preference for conserved sites and appear to have adopted a different strategy to evade loss.</p

A Deficiency of Ceramide Biosynthesis Causes Cerebellar Purkinje Cell Neurodegeneration and Lipofuscin Accumulation

Sphingolipids, lipids with a common sphingoid base (also termed long chain base) backbone, play essential cellular structural and signaling functions. Alterations of sphingolipid levels have been implicated in many diseases, including neurodegenerative disorders. However, it remains largely unclear whether sphingolipid changes in these diseases are pathological events or homeostatic responses. Furthermore, how changes in sphingolipid homeostasis shape the progression of aging and neurodegeneration remains to be clarified. We identified two mouse strains, flincher (fln) and toppler (to), with spontaneous recessive mutations that cause cerebellar ataxia and Purkinje cell degeneration. Positional cloning demonstrated that these mutations reside in the Lass1 gene. Lass1 encodes (dihydro)ceramide synthase 1 (CerS1), which is highly expressed in neurons. Both fln and to mutations caused complete loss of CerS1 catalytic activity, which resulted in a reduction in sphingolipid biosynthesis in the brain and dramatic changes in steady-state levels of sphingolipids and sphingoid bases. In addition to Purkinje cell death, deficiency of CerS1 function also induced accumulation of lipofuscin with ubiquitylated proteins in many brain regions. Our results demonstrate clearly that ceramide biosynthesis deficiency can cause neurodegeneration and suggest a novel mechanism of lipofuscin formation, a common phenomenon that occurs during normal aging and in some neurodegenerative diseases