Adaptation of the emerging pathogenic yeast Candida auris to high caspofungin concentrations correlates with cell wall changes

Candida auris has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. C. auris exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all C. auris isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two FKS genes in C. auris that encode the echinocandins target, namely β-1,3-glucan synthase. FKS1 contained the consensus hot-spot (HS) 1 and HS2 sequences. FKS2 only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in C. glabrata. PG has been characterized in other species, mainly C. albicans, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In C. auris CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as BCK2, HOG1 and MKC1 (SLT2). Our work highlights some of the processes induced in C. auris to adapt to echinocandins.This work was funded by grant SAF2017-86192-R from the Ministerio de Ciencia e Innovación, OZ was also sponsored by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/CIII/0004/0003), co-financed by European Development Regional Fund ERDF “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020 and by Red Española de Investigación en Patología Infecciosa (REIPI RD16/CIII/0004/0003).S

Measurement of Organic Chemical Refractive Indexes Using an Optical Time-Domain Reflectometer

In this investigation, we propose and experimentally demonstrate a method for measuring the refractive index (RI) of liquid organic chemicals. The scheme is based on a single-mode fiber (SMF) sensor and an optical time-domain reflectometer (OTDR). Here, due to the different reflectance (R) between the SMF and organic liquid chemicals, the reflected power level of the backscattering light (BSL) measured by the OTDR would be different. Therefore, we can measure the RI of chemical under test via the measured BSL level. The proposed RI sensor is simple and easy to manipulate, with stable detected signals, and has the potential to be a valuable tool for use in biological and chemical applications

An Intrinsic Fiber-Optic Single Loop Micro-Displacement Sensor

A micro-displacement sensor consisting of a fiber-loop made with a tapered fiber is reported. The sensor operation is based on the interaction between the fundamental cladding mode propagating through the taper waist and higher order cladding modes excited when the taper is deformed to form a loop. As a result, a transmission spectrum with several notches is observed, where the notch wavelength resonances shift as a function of the loop diameter. The loop diameter is varied by the spatial displacement of one end of the fiber-loop attached to a linear translation stage. In a displacement range of 3.125 mm the maximum wavelength shift is 360.93 nm, with 0.116 nm/μm sensitivity. By using a 1,280 nm broadband low-power LED source and a single Ge-photodetector in a power transmission sensor setup, a sensitivity in the order of 2.7 nW/μm is obtained in ∼1 mm range. The proposed sensor is easy to implement and has a plenty of room to improve its performance

Plan estratégico para la empresa DynaTEC: período 2023-2027

DynaTEC aprovechará las condiciones favorables del mercado capitalizando los esfuerzos a partir de sus ventajas competitivas (Gestión del Recurso Humano, I+D+i (Investigación, desarrollo e innovación) y Propiedad Intelectual), con miras a desarrollar una estrategia competitiva de diferenciación, que busca mejorar los componentes tecnológicos del equipo para aprovechar al máximo las capacidades internas del procesador y así obtener fluidez de operatividad, alargar la duración de la batería, en uso y vida útil, y evitar el recalentamiento del equipo. Finalmente, al realizar una estimación de la proyección del flujo económico de la compañía, en el periodo 2023-2027, con miras a un crecimiento promedio de ventas de 5.7 % y un promedio de participación de mercado de 3.29 %, se aprecia que el ROE (Return of equity, rentabilidad sobre patrimonio) del último periodo cierra en 23 %; el valor agregado neto (VAN) sería de 4 248 020 USD (miles) y la tasa interna de retorno (TIR) sería 74.27 % (mayor a 9.25 % - CAPM, exigido por el inversionista). Todo ello indica que seguir el planteamiento estratégico generaría valor a la compañía, lo cual revela que el escenario planteado sería viable.DynaTEC will take advantage of the favorable market conditions by capitalizing the efforts from their competitive advantages (human resources management, research, development innovation, and Copyright), aiming at developing a competitive differentiation strategy, to improve the technological components of the devices to take the greatest advantage of the internal capacities of the processor and to obtain a good operational flow, enhance the battery life in use and useful life, and to prevent the overheating of the device. Finally, when realizing an estimate of the economical flow projections for the company in the 2023-2027 period, expecting an average growth of 5.7% in sales and an average market share of 3.29%, it is clear that the ROE (return of equity) of the last period closes at 23%; the net value added (VAN) would be around 4 248 020 USD (in thousands) and the internal return rate (TIR) would be 74.27 % (over 9.25 % - CAPM, demanded by the investor). All this indicates that following the strategic plan would generate value to the company, which reveals the uggested scenario would viable

A user-centred approach to design Transport Interchange Hubs (TIH): A discussion illustrated by a case study in the Russian Arctic

This paper proposes a user-centred approach to design Transport In-terchange Hubs (TIH). It is based on a literature review of existing information related to TIHs outside the domain of transport engineering, so the focus is on the building and the usage of it by its main customers: the travellers. A literature review is used to extract high level information on travellers’ needs, technical and functional requirements of TIHs, constraints and design parameters. A prod-uct development approach is used to classify and combine this data so a proper set of design specifications to better address users’ needs is proposed. The method is illustrated through an example in the Russian Arctic, an area with un-der-developed transport facilities for travellers which would benefit from high-level design specifications to address complex needs, requirements and parame-ters involved in designing for extreme climate conditions. A proof of concept, using Axiomatic Design, to develop design specifications and manage constraints is applied and discussed considering major needs involved in building in the Rus-sian Arctic including how different types of simulation tools, essential to assess performance of complex buildings, can be integrated in the early stages of the design workflow. Robust specifications, despite being part of parametric design methods, are underexplored in the architecture design domain, meaning this work can contribute to further research in how to define common design targets and objectives for different stakeholders as well as to manage the collaborative work of consultants involved in designing complex buildings

Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder

Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations.This research was funded by INSTITUTO DE SALUD CARLOS III, institutional project Spain UDP and grant PT20CIII/00009.S

Exploring the training and scope of practice of GPs in England, Germany and Spain

OBJECTIVE: To explore general practitioner (GP) training, continuing professional development, scope of practice, ethical issues and challenges in the working environment in three European countries. METHOD: Qualitative study of 35 GPs from England, Germany and Spain working in urban primary care practices. Participants were recruited using convenience and snowball sampling techniques. Semi-structured interviews were recorded, transcribed and analysed by four independent researchers adopting a thematic approach. RESULTS: Entrance to and length of GP training differ between the three countries, while continuing professional development is required in all three, although with different characteristics. Key variations in the scope of practice include whether there is a gatekeeping role, whether GPs work in multidisciplinary teams or singlehandedly, the existence of appraisal processes, and the balance between administrative and clinical tasks. However, similar challenges, including the need to adapt to an ageing population, end-of-life care, ethical dilemmas, the impact of austerity measures, limited time for patients and gaps in coordination between primary and secondary care are experienced by GPs in all three countries. CONCLUSION: Primary health care variations have strong historical roots, derived from the different national experiences and the range of clinical services delivered by GPs. There is a need for an accessible source of information for GPs themselves and those responsible for safety and quality standards of the healthcare workforce. This paper maps out the current situation before Brexit is being implemented in the UK which could see many of the current EU arrangements and legislation to assure professional mobility between the UK and the rest of Europe dismantled