Characteristics of the Clostridium difficile cell envelope and its importance in therapeutics

Clostridium difficile infection (CDI) is a challenging threat to human health. Infections occur after disruption of the normal microbiota, most commonly through the use of antibiotics. Current treatment for CDI largely relies on the broad-spectrum antibiotics vancomycin and metronidazole that further disrupt the microbiota resulting in frequent recurrence, highlighting the need for C. difficile-specific antimicrobials. The cell surface of C. difficile represents a promising target for the development of new drugs. C. difficile possesses a highly deacetylated peptidoglycan cell wall containing unique secondary cell wall polymers. Bound to the cell wall is an essential S-layer, formed of SlpA and decorated with an additional 28 related proteins. In addition to the S-layer, many other cell surface proteins have been identified, including several with roles in host colonization. This review aims to summarize our current understanding of these different C. difficile cell surface components and their viability as therapeutic targets

Particle Acceleration at Relativistic Shocks

I review the current status of Fermi acceleration theory at relativistic shocks. I first discuss the relativistic shock jump conditions, then describe the non-relativistic Fermi mechanism and the differences introduced by relativistic flows. I present numerical calculations of the accelerated particle spectrum, and examine the maximum energy attainable by this process. I briefly consider the minimum energy for Fermi acceleration, and a possible electron pre-acceleration mechanism.Comment: 17 pages, 4 figures. To appear in "Relativistic Flows in Astrophysics", A.W. Guthmann, M. Georganopoulos, A. Marcowith and K. Manolokou, eds., Lecture Notes in Pysics, Springer Verla

A cortex-specific PBP contributes to cephalosporin resistance in Clostridium difficile

Sporulation is a complex cell differentiation programme shared by many members of the Firmicutes, the end result of which is a highly resistant, metabolically inert spore that can survive harsh environmental insults. Clostridium difficile spores are essential for transmission of disease and are also required for recurrent infection. However, the molecular basis of sporulation is poorly understood, despite parallels with the well-studied Bacillus subtilis system. The spore envelope consists of multiple protective layers, one which is a specialised layer of peptidoglycan, called the cortex, that is essential for the resistant properties of the spore. We have identified and characterised a penicillin binding protein (PBP) that is required for cortex synthesis in C. difficile. Surprisingly this PBP was also found to contribute to cephalosporin resistance, indicating an additional role in the synthesis of vegetative cell wall. This is the first description of a cortex-specific PBP in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen

Babo1, formerly Vop1 and Cop1/2, is no eyespot photoreceptor but a basal-body protein illuminating cell division in Volvox carteri.

von der Heyde EL, Hallmann A. Babo1, formerly Vop1 and Cop1/2, is no eyespot photoreceptor but a basal-body protein illuminating cell division in Volvox carteri. The Plant journal : for cell and molecular biology. 2020;102(2):276-298.In photosynthetic organisms many processes are light-dependent and sensing of light requires light-sensitive proteins. The supposed eyespot-photoreceptor protein Babo1 (formerly Vop1) has previously been classified as an opsin due to the capacity for binding retinal. Here, we analyze Babo1 and provide evidence that it is no opsin. Due to the localization at the basal bodies, the former Vop1 and Cop1/2 proteins were renamed V.c. Babo1 and C.r. Babo1. We reveal a large family of more than sixty Babo1-related proteins from a wide range of species. The detailed subcellular localization of fluorescence-tagged Babo1 shows that it accumulates at the basal apparatus. More precisely, it is located predominantly at the basal bodies and to a lesser extent at the four strands of rootlet microtubules. We trace Babo1 during basal body separation and cell division. Dynamic structural rearrangements of Babo1 particularly occur right before the first cell division. In four-celled embryos Babo1 was exclusively found at the oldest basal bodies of the embryo and on the corresponding d-roots. The unequal distribution of Babo1 in four-celled embryos could be an integral part of a geometrical system in early embryogenesis, which establishes the anterior-posterior polarity and influences the spatial arrangement of all embryonic structures and characteristics. Due to its retinal-binding capacity, Babo1 could also be responsible for the unequal distribution of retinoids, knowing that such concentration gradients of retinoids can be essential for the correct patterning during embryogenesis of more complex organisms. Thus, our findings push the Babo1 research in another direction. © 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd

The position of graptolites within Lower Palaeozoic planktic ecosystems.

An integrated approach has been used to assess the palaeoecology of graptolites both as a discrete group and also as a part of the biota present within Ordovician and Silurian planktic realms. Study of the functional morphology of graptolites and comparisons with recent ecological analogues demonstrates that graptolites most probably filled a variety of niches as primary consumers, with modes of life related to the colony morphotype. Graptolite coloniality was extremely ordered, lacking any close morphological analogues in Recent faunas. To obtain maximum functional efficiency, graptolites would have needed varying degrees of coordinated automobility. A change in lifestyle related to ontogenetic changes was prevalent within many graptolite groups. Differing lifestyle was reflected by differing reproductive strategies, with synrhabdosomes most likely being a method for rapid asexual reproduction. Direct evidence in the form of graptolithophage 'coprolitic' bodies, as well as indirect evidence in the form of probable defensive adaptations, indicate that graptolites comprised a food item for a variety of predators. Graptolites were also hosts to a variety of parasitic organisms and provided an important nutrient source for scavenging organisms

A systematic review and qualitative synthesis of weight management interventions for people with spinal cord injury

People with spinal cord injury (SCI) are at greater risk of developing obesity and related co-morbidities than those without SCI. The objectives of this systematic review were to examine the effectiveness of weight management interventions for people with SCI and to synthesize the experiences of people involved with SCI weight management (e.g., SCI healthcare professionals and caregivers). Five databases were searched (up to July 31, 2023) and 5,491 potentially eligible articles were identified. Following screening, 22 articles were included, comprising 562 adults. There was considerable heterogeneity in study design and weight loss interventions included behavioral nutritional and exercise education sessions, recalling food diaries, exercise interventions, and pharmaceuticals. The mean percentage change of the pooled body mass data equated to −4.0 ± 2.3%, with a range from −0.5 to −7.6%. In addition, 38% of the individuals with SCI who completed a weight loss intervention (N = 262) had a ≥5% reduction in body weight. Collectively, although on average the included interventions led to moderate weight loss, the finding that just over a third of individuals achieved clinically meaningful 5% weight loss suggests that available interventions for this population may need to be improved

Drum vortons in high density QCD

Recently it was shown that high density QCD supports of number of topological defects. In particular, there are U(1)_Y strings that arise due to K^0 condensation that occurs when the strange quark mass is relatively large. The unique feature of these strings is that they possess a nonzero K^+ condensate that is trapped on the core. In the following we will show that these strings (with nontrivial core structure) can form closed loops with conserved charge and currents trapped on the string worldsheet. The presence of conserved charges allows these topological defects, called vortons, to carry angular momentum, which makes them classically stable objects. We also give arguments demonstrating that vortons carry angular momentum very efficiently (in terms of energy per unit angular momentum) such that they might be the important degrees of freedom in the cores of neutron stars.Comment: 11 pages, accepted for publication in Physical Review

Modeling the Emission Processes in Blazars

Blazars are the most violent steady/recurrent sources of high-energy gamma-ray emission in the known Universe. They are prominent emitters of electromagnetic radiation throughout the entire electromagnetic spectrum. The observable radiation most likely originates in a relativistic jet oriented at a small angle with respect to the line of sight. This review starts out with a general overview of the phenomenology of blazars, including results from a recent multiwavelength observing campaign on 3C279. Subsequently, issues of modeling broadband spectra will be discussed. Spectral information alone is not sufficient to distinguish between competing models and to constrain essential parameters, in particular related to the primary particle acceleration and radiation mechanisms in the jet. Short-term spectral variability information may help to break such model degeneracies, which will require snap-shot spectral information on intraday time scales, which may soon be achievable for many blazars even in the gamma-ray regime with the upcoming GLAST mission and current advances in Atmospheric Cherenkov Telescope technology. In addition to pure leptonic and hadronic models of gamma-ray emission from blazars, leptonic/hadronic hybrid models are reviewed, and the recently developed hadronic synchrotron mirror model for TeV gamma-ray flares which are not accompanied by simultaneous X-ray flares (``orphan TeV flares'') is revisited.Comment: Invited Review at "The Multimessenger Approach to Gamma-Ray Sources", Barcelona, Spain, July 2006; submitted to Astrophysics and Space Science. 10 pages, including 6 eps figures. Uses Springer's ApSS macro