Functional Lifespan Research Articles

Acute Metastatic Spinal Cord Compression: Urgent Surgery versus Radiotherapy and Treatment Result Prediction versus Actual Results.

Background Context: The role of radiotherapy versus surgery in treating acute metastatic spinal cord compression (AMSCC) has changed over the years. Purpose: Our study evaluates neurological and functional outcomes following urgent surgery and radiotherapy (USFR) versus urgent radiotherapy alone in treating AMSCC. Study Design/Setting: A retrospective cohort of 54 patients with AMSCC with variable neurological deficits. Overall, 32 patients were treated with USFR, and 22 received urgent radiotherapy alone. Outcome Measures: Neurological status regarding the Asia and Frankel scores, continence and ambulation, and Kranofsky’s functional score and patient life span comprised the outcome measures. Methods: This was a retrospective EMR study. Results: USFR and radiotherapy cohorts were similar in age, gender, tumor origin, and the number of spinal metastases. The most common cause of AMSCC was carcinoma of the breast (24.1%), followed by carcinoma of the lung (16.7%) and multiple myeloma (13%). Neurological status at AMSCC presentation was similar between cohorts regarding Asia and Frankel scores, continence and ambulation, and Kranofsky’s functional score. Following USFR, 59.3% of the patients had a motor strength improvement, 31.3% regained sphincter function, and 34.4% regained ambulation, while 90% of the patients treated by radiotherapy did not show any improvement. One patient under radiotherapy lost sphincter function. The treatment received did not affect the patient’s survival. A subanalysis of patients with a short life expectancy, by Tomita and Tokuhashi scores, showed missed prediction in 29.4% of cases. Conclusion: The study supports the beneficial effect of UFSR compared to urgent radiotherapy alone in treating AMSCC in all subgroups. Early surgery improved function, motor strength, sphincter control, and ambulation without affecting life span. Prognostic scores failed to predict life span in almost one-third of the patients, requiring further investigation.

Development of a new environmental scoring methodology for building products, a French case study

The building sector consumes about one-third of total final energy and contributes to 38% of greenhouse gas (GHG) emissions around the world. Thus, the EU has established a set of directives that includes the EPBD and the EED to achieve carbon neutrality by 2050. Hence, France adopted more challenging legislation by introducing the new environmental regulation RE2020. Among other measures, the RE2020 allocates a carbon budget to new housings starting from 2022. As a consequence, it promotes the use of materials and products that have a lower environmental impact. In this low carbon material competition, one of the challenges is related to the comparability of environmental product declarations (EPDs) and the lack of harmonization in terms of functional units and lifespan. Also, EPDs have multiple impact categories that make the decision-making process complex. In this context, the objective of this research is to develop a new environmental scoring methodology for building products based on their life cycle assessment. The methodology has been applied to two product families: windows and insulation as case studies thanks to the French EPD database called INIES.

Factors affecting true and functional productive lifespan in Italian Holstein-Friesian cows

The identification of factors affecting longevity in dairy cows is of great importance to improve their length of productive life. Cows can be replaced for poor milk production (i.e. true productive lifespan, TPL) or other reasons than production (functional productive lifespan, FPL). The objective of the present study was to investigate the influence of milk yield, fat and protein contents, insemination status (INS), somatic cell count (SCC) and β-hydroxybutyrate (BHB) concentration in milk on TPL and FPL. Data included 70,748 Italian Holstein-Friesian cows that calved for the first time between 2014 and 2018. Proportional hazards models assuming a piecewise Weibull distribution of the baseline hazard function, with or without adjustment for milk production, were used to compute relative risks of culling associated with FPL and TPL, respectively. Our study revealed that milk yield, protein and fat contents, INS, SCC and concentration of BHB in milk exhibited significant relationships with TPL and FPL. In particular, the huge difference in risk ratios between high- and low-producing cows confirms the central role of milk production in culling decision-making. In addition, farmers appear more prone to cull cows with several events of high SCC and BHB concentration in milk. HIGHLIGHTS Milk yield, fat and protein contents, insemination status, somatic cell count and ketosis affect productive lifespan in Italian Holstein cows. These factors, therefore, contribute significantly to culling decisions. The identified risk factors of culling can be exploited to improve the current management practices in Italian Holstein Friesian herds and cows’ longevity.

Occurrence, concentration, and distribution of 38 organic micropollutants in the filter material of 12 stormwater bioretention facilities

The increased use of bioretention facilities as a low impact development measure for treating stormwater runoff underscores the need to further understand their long-term function. Eventually, bioretention filter media must be (partly) replaced and disposed of at the end of its functional lifespan. While there are several studies of metal accumulation and distributions in bioretention media, less is known about organic pollutant pathways and accumulation in these filters. The present study considers the occurrence and accumulation of 16 polycyclic aromatic hydrocarbons, 7 polychlorinated biphenyls, 13 phthalates, and two alkylphenols throughout 12 older bioretention facilities (7–13 years old) used for stormwater treatment in Michigan and Ohio, USA. These pollutant groups appear to behave similarly, with greater instances of detection and higher concentrations in the upper media layers which decrease with increased depth from the surface. The patterns of detection and concentration in the filter material may be explained by characteristics of the pollutants, such as molecular structures and solubility that affect the removal of the organic pollutants by the filter material. There is also a large variation in concentration magnitudes between the bioretention sites, most likely due to differences in pollutant sources, contributing catchment size and/or land uses.

Assessment of conservations actions for the critically endangered spotted handfish (Brachionichthyidae), following curation of data collected by multiple investigators into a long-term time-series

Multi-decadal datasets for endangered species that track both populations and performance of management interventions are rare. One such dataset is for the critically endangered Spotted handfish, a species which has been used as a conservation model for the most endangered of the marine bony fish families the Brachionichthyidae. We assessed a 23-year, multi-site, time-series of population density surveys for the spotted handfish as well as a conservation intervention, the planting of ∼ 14,000 artificial spawning habitats (ASH). Data ownership spanned multiple Principal Investigators (PIs) and key data and covariates, such as monitoring and interventions, were often documented within personal files and difficult to access grey literature. We consolidated and curated these data, identifying gaps in the time-series and their causes and isolating confounding factors before we assessed population trends and the effectiveness of ASH planting. Both funding gaps and the 2020 Covid-19 lockdown produced breaks in the time-series. Breeding season observations mostly occurred in the early part of the dataset and there was also a change in method that needed to be considered when interpretating the time-series. There was an overall decline in fish observed between 1997 and 2019 but, at least since 2014, there has been stabilisation of the population. Local populations of spotted handfish can either be highly dynamic or relatively stable but population increases were linked to the long-running, conservation intervention of planting ASH. As local populations can be dynamic, the functional life span of the ASH is limited and threats to the species - chronic, stochastic and climate - are ongoing, spotted handfish may be a ‘conservation reliant’ species that require annual site-specific monitoring, insitu interventions and existu captive husbandry.

Methoxyfenozide has minimal effects on replacement queens but may negatively affect sperm storage

Honey bees are incidentally exposed to pesticides such as the insect growth regulator methoxyfenozide (MEOF) during crop pollination, exposures that extend into the hive via contaminated stored food. We examined the sublethal effects of MEOF-contaminated pollen and queen cell wax on replacement queen development. MEOF-exposed colonies were largely able to produce replacement queens of similar physiological and reproductive quality as unexposed colonies. Newly established queens did not differ in their body mass, ovariole development, or protein and fatty acid contents in their ovaries and fat bodies. MEOF and control queens had similar glandular contents of queen mandibular pheromone (QMP) and queen retinue pheromone (QRP) compounds. However, MEOF queens stored less sperm in their spermathecae than control queens. Given that queen productivity is ultimately limited by sperm availability, MEOF contamination might shorten the functional lifespan of exposed queens.

Design and Fabrication of Rehabilitation Instrument for Upper and Lower Limb

Abstract: In today’s world, most of the people have a busy and hectic schedule. They hardly get time to look after their physical health which then affects them in their elderly age or in some cases at a young age. To take care of such physical problems rehabilitation is necessary. Rehabilitation improves and returns functional capacity and quality lifespan of people with physical injuries or disorders. Rehabilitation is not only used for treatment of physical diseases but also in sports industry. It helps in fast recovery of athletes and increases their performance on the field. Our project proposes a design of a rehabilitation instrument for upper and lower limbs. The upper limb rehabilitation instrument is designed for our shoulders and arm. It is designed to provide natural shoulder and arm movements in all directions possible. The lower limb rehabilitation instrument focuses mostly on knee and ankle joints and the EMS (Electro –Muscle Stimulator) is used to send external electric signals to the inactive muscles (muscles which have lost contact with the brain). The external electric signals sent are similar to the signals sent by brain to muscles. These signals help in contraction and expansion of muscles and thus, help in movement of that part of the body. The Rehabilitation instrument we are developing would be user-friendly, compact and budget friendly. Index Terms: Rehabilitation, Upper limb, Lower limb, Shoulder flexion, Shoulder extension, elbow inward rotation, elbow outward rotation, Paralysis, Physiotherapy.

KIL1 terminates fertility in maize by controlling silk senescence.

Plant flowers have a functional life span during which pollination and fertilization occur to ensure seed and fruit development. Once flower senescence is initiated, the potential to set seed or fruit is irrevocably lost. In maize, silk strands are the elongated floral stigmas that emerge from the husk-enveloped inflorescence to intercept airborne pollen. Here we show that KIRA1-LIKE1 (KIL1), an ortholog of the Arabidopsis NAC (NAM (NO APICAL MERISTEM), ATAF1/2 (Arabidopsis thaliana Activation Factor1 and 2) and CUC (CUP-SHAPED COTYLEDON 2)) transcription factor KIRA1, promotes senescence and programmed cell death (PCD) in the silk strand base, ending the window of accessibility for fertilization of the ovary. Loss of KIL1 function extends silk receptivity and thus strongly increases kernel yield following late pollination. This phenotype offers new opportunities for possibly improving yield stability in cereal crops. Moreover, despite diverging flower morphologies and the substantial evolutionary distance between Arabidopsis and maize, our data indicate remarkably similar principles in terminating floral receptivity by PCD, whose modulation offers the potential to be widely used in agriculture.

The emerging oral pathogen, Filifactor alocis, extends the functional lifespan of human neutrophils.

Periodontitis is a chronic inflammatory infectious disease that affects the integrity of tooth‐supporting tissues and has adverse systemic consequences. Advances in sequencing technologies have uncovered organisms that are exclusively found in high numbers in periodontal lesions, such as the gram‐positive anaerobic rod, Filifactor alocis. F. alocis can manipulate neutrophil effector functions, which allows the organism to survive within these granulocytes. Several neutrophil functions have been tested in the context of F. alocis challenge, but the effect of the organism on neutrophil apoptosis is still unknown. RNA sequencing of human neutrophils challenged with F. alocis showed that apoptosis pathways were differentially regulated. Compared to media‐cultured controls, F. alocis‐challenged neutrophils maintain their nuclear morphology, do not stain for Annexin V or 7‐AAD, and have decreased DNA fragmentation. Inhibition of apoptosis by F. alocis involved reduced caspase‐3, −8, and − 9 activation and upregulation of important anti‐apoptotic proteins. Prolonged lifespan was dependent on contact through TLR2/6, and F. alocis‐challenged neutrophils retained their functional capacity to induce inflammation for longer timepoints. This is the first in‐depth characterization of neutrophil apoptotic programs in response to an oral pathogen and provides key information on how bacteria manipulate immune cell mechanisms to maintain a dysregulated inflammatory response.

Functional Encapsulating Structure for Wireless and Immediate Monitoring of the Fluid Penetration

AbstractWith the fast‐paced development of biomedical electronics, monitoring physiological processes have become ubiquitous throughout the field of implantable devices. Nevertheless, inherent challenges remain extant when long‐term applications are concerned. For the stable and reliable function of these devices, hermetic and biocompatible encapsulation is of paramount importance; however, extrinsic defects and intrinsic swelling properties of the encapsulating layer present the key limitation to ideal barrier performance. Thus, the ability to monitor biofluid penetration and predict the device's functional lifespan is necessary for safe and stable operation within the body. This paper presents the functional encapsulation structure that quantitatively measures the diffusion of fluids into the encapsulation layer. The hydrolysis of Magnesium (Mg) electrodes underneath the encapsulating material shows the capability to wirelessly monitor the water penetration rate and the presence of defects, such as pinholes and cracks, in the encapsulating material. The experiments conducted throughout this paper analyze the Mg thickness and geometry of the antenna to optimize the device's susceptivity to water penetration when submerged in aqueous environments. The facile fabrication process and the compatibility with prevailing implantable electronics further substantiate the device's usability in diverse applications where chronic implants are necessary for monitoring disease or administering required treatments.

Pollination-associated shortening of the functional flower lifespan in an alpine species of Alstroemeria and the water content of flowers

Pollination-associated shortening of the functional flower lifespan in an alpine species of Alstroemeria and the water content of flowers

Seasonal patterns of increases in stem girth, vessel development, and hydraulic function in deciduous tree species.

The onset of spring growth and vessel formation were examined within three deciduous woody plant species, Acer rubrum, Populus balsamifera ssp. trichocarpa and Quercus rubra. We were broadly interested in the lag between the onset of girth expansion and the formation of mature and hydraulically conductive vessels within the new xylem. Dendrometers were installed on 20 trees (6-7 per species), and expansion of both bole and distal stems was monitored throughout the growing season in a common garden. For each species, four to six distal stems were harvested every other week for anatomical examination of vessel formation. Additionally, for Populus and Quercus, hydraulic conductivity measurements and active xylem staining were completed on all stem samples. For all three species, the timing of girth expansion was similar. Expansion of distal branches occurred 12-37 d earlier than that of the bole. Vessel formation initiated several weeks prior to leaf-out, but no new earlywood vessels were mature at the time of bud break for Acer and Populus and only a few were present in Quercus. Initial stem girth expansion occurred 2 to >6 weeks before the maturation of the first current-year vessels, and there was an additional delay of up to 4 weeks before mature vessels became hydraulically functional. Hydraulic conductivity was strongly correlated with the number and diameter of stained vessels. Bud break and leaf expansion relied predominantly on water supplied by vessels formed during prior seasons. Early-season activity is likely affected by the function of older xylem vessels and the environmental factors that influence their structure and function. Understanding the functional lifespan of vessels and the varying contributions of new and older vessels to conductivity are critical to understanding of the phenology and vascular function of long-lived woody plants in response to changing climates.

Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors.

Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. Available diagnostic assessments for FLT3-ITD are incapable of combining cost-effective detection platforms with high analytical performances. To circumvent this, we developed an efficient DNA biosensor for the recognition of AML caused by FLT3-ITD mutation utilizing electrochemical impedance characterization. The system was designed by adhering gold-sputtered zinc oxide (ZnO) nanorods onto interdigitated electrode (IDE) sensor chips. The sensing surface was biointerfaced with capture probes designed to hybridize with unmutated FLT3 sequences instead of the mutated FLT3-ITD gene, establishing a reverse manner of target detection. The developed biosensor demonstrated specific detection of mutated FLT3 genes, with high levels of sensitivity in response to analyte concentrations as low as 1 nM. The sensor also exhibited a stable functional life span of more than five weeks with good reproducibility and high discriminatory properties against FLT3 gene targets. Hence, the developed sensor is a promising tool for rapid and low-cost diagnostic applications relevant to the clinical prognosis of AML stemming from FLT3-ITD mutations.

Understanding consumers’ perspectives of electronic waste in an emerging economy: a case study of New Delhi, India

Obsolete electronics or E-waste has observed significant escalation in the recent years. Young adults, in particular, are one of the largest consumers of electronic equipments in the contemporary world, although research on their perceptions, awareness and disposal behavior of E-waste has been far and few in between. Considering the growth trajectory of E-waste in the emerging economies, a study has been carried out in the capital city of India, New Delhi with 1039 respondents in the age group of 18–22. Contemplating its aggressive generation, obsolete mobile phone was considered as a representative of E-waste. Both purchase and disposal behaviors of mobile phones were evaluated through the lens of theoretical frameworks such as conspicuous consumption and throwaway society. The concepts of planned and premature obsolescence were also explored. A structured questionnaire survey was carried out through a respondent driven snowball sampling method. We observed that the functional need is the foremost consideration while deciding to purchase a new mobile phone within our study sample. Over 49% of our respondents change their mobile phones between 1 and 3 years. This corresponds to the fact that mobile phones are discarded very much within their actual functional lifespan. Overall, it could be concluded that the major attributes of conspicuous consumption and a throwaway society are still not dominant in our study sample. The experiences of India’s E-waste have the potential to provide important insights for policy formulation and sustainable management particularly in other emerging economies and developing countries.

Translational Research of Hemoglobin Vesicles as a Transfusion Alternative.

Clinical situations arise in which blood for transfusion becomes scarce or unavailable. Considerable demand for a transfusion alternative persists because of various difficulties posed by blood donation and transfusion systems. Hemoglobin-vesicles (Hb- V) are artificial oxygen carriers being developed for use as a transfusion alternative. Just as biomembranes of red blood cells (RBCs) do, phospholipid vesicles (liposomes) for Hb encapsulation can protect the human body from the toxic effects of molecular Hb. The main HbV component, Hb, is obtained from discarded human donated blood. Therefore, HbV can be categorized as a biologic agent targeting oxygen for peripheral tissues. The purification procedure strictly eliminates the possibility of viral contamination. It also removes all concomitant unstable enzymes present in RBC for utmost safety from infection. The deoxygenated HbVs, which are storable for over the years at ambient temperature, can function as an alternative to blood transfusion for resuscitation from hemorrhagic shock and O2 therapeutics. Moreover, a recent study clarified beneficial effects for anti- oxidation and anti-inflammation by carbon monoxide (CO)-bound HbVs. Autoxidation of HbV (HbO2 → metHb + O2 -.) is unavoidable after intravenous administration. Co-injection of methylene blue can extract the intraerythrocytic glycolytic electron energy effectively and reduce metHb. Other phenothiazine dyes can also function as electron mediators to improve the functional life span of HbV. This review paper summarizes recent progress of the research and development of HbV, aimed at clinical applications.

Alpine dwarf shrubs show high proportions of nonfunctional xylem: Visualization and quantification of species-specific patterns.

Xylem conductive capacity is a key determinant of plant hydraulic function and intimately linked to photosynthesis and productivity, but can be impeded by temporary or permanent conduit dysfunctions. Here we show that persistent xylem dysfunctions in unstressed plants are frequent in Alpine dwarf shrubs and occur in various but species-specific cross-sectional patterns. Combined synchrotron micro-computed tomography (micro-CT) imaging, xylem staining, and flow measurements in saturated samples of six widespread Ericaceae species evidence a high proportion (19%-50%) of hydraulically nonfunctional xylem areas in the absence of drought stress, with regular distribution of dysfunctions between or within growth rings. Dysfunctions were only partly reversible and reduced the specific hydraulic conductivity to 1.38 to 3.57 ×10-4 m2 s-1 MPa-1 . Decommission of inner growth rings was clearly related to stem age and a higher vulnerability to cavitation of older rings, while the high proportion of nonfunctional conduits in each annual ring needs further investigations. The lower the xylem fraction contributing to the transport function, the higher was the hydraulic efficiency of conducting xylem areas. Improved understanding of the functional lifespan of xylem elements and the prevalence and nature of dysfunctions is critical to correctly assess structure-function relationships and whole-plant hydraulic strategies.

Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

ALSTaR Cells - Novel Stem-cell-based Therapy for Amyotrophic Lateral Sclerosis: A Research Protocol

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that results in the loss of motor neurons leading to limb paralysis and eventual death. Stem cell transplantation can be used to replenish the atrophied motor neurons and slow the progression of the disease, while the use of biomaterials, genetic engineering, and nanoparticles can reduce the hostility of the microenvironment. Thus, we propose a novel combinatorial therapeutic approach termed Amyotrophic Lateral Sclerosis Therapeutic and Regenerative (ALSTaR) cell treatment. Methods: This unified strategy will employ miRNA-124 and chitosan polyplex biomaterial to subsequently enhance engraftment of neural progenitor cells (NPCs), which will be engineered to overexpress an autophagy-regulatory gene, TFEB, and secrete an autophagy-inducing drug, trehalose. We will bioengineer an organoid model of the ventral column of the spinal cord which will be used for extensive in vitro characterization of ALSTaR cells through single-slice electrophysiology and immunocytochemistry, followed by in vivo work. Using the SOD1G93A mutant mouse model, weekly behavioural assessments of motor recovery will be conducted until the humane endpoint; thereafter extensive immunohistochemical and protein quantification analyses will be performed to determine treatment efficacy. Results: ALSTaR cell treatment should result in motor functional recovery and lifespan elongation through several cellular and molecular mechanisms, including decreased neuroinflammation, upregulation of autophagy, degradation of protein aggregates, enhancement of transplanted cell integration, and regeneration of axons. Discussion: In vitro characterization of ALSTaR cells in bioengineered spinal cord organoids will reveal stable electrophysiological recordings of motor neurons, higher levels of neuronal differentiation markers, and lower levels of inflammation markers in the ALSTaR group compared to the control group or the groups treated with just the biomaterial or just the NPCs, suggesting neuronal recovery. Behavioural assessments in the ALS mouse model will reveal increased motor coordination, neuromuscular strength, and motor activity in the ALSTaR group compared to other groups, suggesting motor functional recovery. In vivo characteriz ation of ALSTaR cells in the ALS mouse model will suggest enhanced stem cell integration and recovery of cellular and molecular processes. Conclusion: With currently no effective treatment for ALS, this novel combinatorial treatment strategy could improve the health-related quality of life of patients suffering from this debilitating disease.

DMD – ANIMAL MODELS: EP.95 Downregulation of the genetic modifier PITPNA as means of therapy in Duchenne muscular dystrophy

We identified PITPNA as a new genetic modifier of Duchenne Muscular Dystrophy (DMD) in two exceptional mildly affected Golden Retriever Muscular Dystrophy (GRMD) dogs. Downregulation of PITPNA allowed dystrophin-deficient dogs to retain functional muscle and normal lifespan and may represent an unexplored territory for therapy. This was confirmed in our dystrophin-deficient zebrafish in which pitpna downregulation by morpholino antisense nucleotide resulted in improved muscle structure and function. In the present study, we explored different strategies that both aimed to downregulate PTPNA and prevent the muscle pathology. In dystrophin-deficient zebrafish, we developed a straightforward phenotypic drug screening assay that would be inconceivable in mouse model systems. We identified that phosphodiesterase 10A (PDE10A) inhibitors improved muscle integrity and reduced pitpna expression. The PDE10A pathway was confirmed with the use of pde10a morpholino and we combined different functional assays that showed improvement in locomotion, muscle, and vascular function as well as long-term survival in dmd zebrafish. In dystrophin-deficient mice, we are currently evaluating the potential benefit of Pitpna downregulation on muscle pathology based on two different strategies: (i) the use of PDE10A inhibitors and (ii) the use of Pitpna shRNA-AAV. Despite recent advances in dystrophin replacement strategies, there is still precedence to pursue pharmacological therapies targeting genetic modifiers that can complement dystrophin-based therapies and are independent of patients’ genetic mutations. In different animal models of DMD, downregulation of the genetic modifier PITPNA presents several reasons for there to be further studied of it as a potential DMD therapeutic via two strategies that may benefit patients.

The ins and outs of Bacillus proteases: activities, functions and commercial significance

ABSTRACTBecause the majority of bacterial species divide by binary fission, and do not have distinguishable somatic and germline cells, they could be considered to be immortal. However, bacteria ‘age’ due to damage to vital cell components such as DNA and proteins. DNA damage can often be repaired using efficient DNA repair mechanisms. However, many proteins have a functional ‘shelf life’; some are short lived, while others are relatively stable. Specific degradation processes are built into the life span of proteins whose activities are required to fulfil a specific function during a prescribed period of time (e.g. cell cycle, differentiation process, stress response). In addition, proteins that are irreparably damaged or that have come to the end of their functional life span need to be removed by quality control proteases. Other proteases are involved in performing a variety of specific functions that can be broadly divided into three categories: processing, regulation and feeding. This review presents a systematic account of the proteases of Bacillus subtilis and their activities. It reviews the proteases found in, or associated with, the cytoplasm, the cell membrane, the cell wall and the external milieu. Where known, the impacts of the deletion of particular proteases are discussed, particularly in relation to industrial applications.