Riding the waves from epidemic to endemic: Viral mutations, immunological change and policy responses.

Nonpharmaceutical interventions (NPI) are an important tool for countering pandemics such as COVID-19. Some are cheap; others disrupt economic, educational, and social activity. The latter force governments to balance the health benefits of reduced infection and death against broader lockdown-induced societal costs. A literature has developed modeling how to optimally adjust lockdown intensity as an epidemic evolves. This paper extends that literature by augmenting the classic SIR model with additional states and flows capturing decay over time in vaccine-conferred immunity, the possibility that mutations create variants that erode immunity, and that protection against infection erodes faster than protecting against severe illness. As in past models, we find that small changes in parameter values can tip the optimal response between very different solutions, but the extensions considered here create new types of solutions. In some instances, it can be optimal to incur perpetual epidemic waves even if the uncontrolled infection prevalence would settle down to a stable intermediate level.

The hammer and the jab: Are COVID-19 lockdowns and vaccinations complements or substitutes?

The COVID-19 pandemic has devastated lives and economies around the world. Initially a primary response was locking down parts of the economy to reduce social interactions and, hence, the virus' spread. After vaccines have been developed and produced in sufficient quantity, they can largely replace broad lock downs. This paper explores how lockdown policies should be varied during the year or so gap between when a vaccine is approved and when all who wish have been vaccinated. Are vaccines and lockdowns substitutes during that crucial time, in the sense that lockdowns should be reduced as vaccination rates rise? Or might they be complementary with the prospect of imminent vaccination increasing the value of stricter lockdowns, since hospitalization and death averted then may be permanently prevented, not just delayed? We investigate this question with a simple dynamic optimization model that captures both epidemiological and economic considerations. In this model, increasing the rate of vaccine deployment may increase or reduce the optimal total lockdown intensity and duration, depending on the values of other model parameters. That vaccines and lockdowns can act as either substitutes or complements even in a relatively simple model casts doubt on whether in more complicated models or the real world one should expect them to always be just one or the other. Within our model, for parameter values reflecting conditions in developed countries, the typical finding is to ease lockdown intensity gradually after substantial shares of the population have been vaccinated, but other strategies can be optimal for other parameter values. Reserving vaccines for those who have not yet been infected barely outperforms simpler strategies that ignore prior infection status. For certain parameter combinations, there are instances in which two quite different policies can perform equally well, and sometimes very small increases in vaccine capacity can tip the optimal solution to one that involves much longer and more intense lockdowns.

Deletion of the N-terminal domain of the yeast vacuolar (Na+ ,K+ )/H+ antiporter Vnx1p improves salt tolerance in yeast and transgenic Arabidopsis.

Cation/proton antiporters play a major role in the control of cytosolic ion concentrations in prokaryotes and eukaryotes organisms. In yeast, we previously demonstrated that Vnx1p is a vacuolar monovalent cation/H+ exchanger showing Na+ /H+ and K+ /H+ antiporter activity. We have also shown that disruption of VNX1 results in an almost complete abolishment of vacuolar Na+ /H+ exchange, but yeast cells overexpressing the complete protein do not show improved salinity tolerance. In this study, we have identified an autoinhibitory N-terminal domain and have engineered a constitutively activated version of Vnx1p, by removing this domain. Contrary to the wild type protein, the activated protein has a pronounced effect on yeast salt tolerance and vacuolar pH. Expression of this truncated VNX1 gene also improves Arabidopsis salt tolerance and increases Na+ and K+ accumulation of salt grown plants thus suggesting a biotechnological potential of activated Vnx1p to improve salt tolerance of crop plants.

Recogida, transporte y procesamiento general de las muestras en el laboratorio de Microbiología / Collection, transport and general processing of clinical specimens in Microbiology laboratory

La interpretación y el rigor de los resultados microbiológicos siguen dependiendo en gran medida de la calidad de las muestras y el procesamiento de las mismas dentro del Servicio de Microbiología. Conocer el tipo de muestra, el momento adecuado y la manera de obtención, su conservación y transporte determinará la rentabilidad de la misma en el proceso infeccioso. En este sentido, la disponibilidad de nuevas técnicas dentro del laboratorio y el manejo, cada vez menos excepcional, de muestras con sospecha de infección por patógenos no habituales nos obligan a revisar y actualizar todos los pasos implicados en el procesamiento de las muestras. Hoy día, la automatización del laboratorio y la amplia variedad de técnicas rápidas utilizadas han hecho que el diagnóstico microbiológico tenga la rapidez y precisión necesaria para realizar un diagnóstico de calidad y clínicamente relevante; sin olvidar que, en todos los casos, la información clínica es necesaria y de vital importancia para que el microbiólogo pueda aplicar las técnicas diagnósticas disponibles de la manera más eficiente

The interpretation and the accuracy of the microbiological results still depend to a great extent on the quality of the samples and their processing within the Microbiology laboratory. The type of specimen, the appropriate time to obtain the sample, the way of sampling, the storage and transport are critical points in the diagnostic process. The availability of new laboratory techniques for unusual pathogens, makes necessary the review and update of all the steps involved in the processing of the samples. Nowadays, the laboratory automation and the availability of rapid techniques allow the precision and turn-around time necessary to help the clinicians in the decision making. In order to be efficient, it is very important to obtain clinical information to use the best diagnostic tools

Collection, transport and general processing of clinical specimens in Microbiology laboratory. / Recogida, transporte y procesamiento general de las muestras en el laboratorio de Microbiología.

The interpretation and the accuracy of the microbiological results still depend to a great extent on the quality of the samples and their processing within the Microbiology laboratory. The type of specimen, the appropriate time to obtain the sample, the way of sampling, the storage and transport are critical points in the diagnostic process. The availability of new laboratory techniques for unusual pathogens, makes necessary the review and update of all the steps involved in the processing of the samples. Nowadays, the laboratory automation and the availability of rapid techniques allow the precision and turn-around time necessary to help the clinicians in the decision making. In order to be efficient, it is very important to obtain clinical information to use the best diagnostic tools.

Correlation between ribonucleoside-diphosphate reductase and three replication proteins in Escherichia coli.

BACKGROUND: There has long been evidence supporting the idea that RNR and the dNTP-synthesizing complex must be closely linked to the replication complex or replisome. We contributed to this body of evidence in proposing the hypothesis of the replication hyperstructure. A recently published work called this postulate into question, reporting that NrdB is evenly distributed throughout the cytoplasm. Consequently we were interested in the localization of RNR protein and its relationship with other replication proteins. RESULTS: We tagged NrdB protein with 3xFLAG epitope and detected its subcellular location by immunofluorescence microscopy. We found that this protein is located in nucleoid-associated clusters, that the number of foci correlates with the number of replication forks at any cell age, and that after the replication process ends the number of cells containing NrdB foci decreases.We show that the number of NrdB foci is very similar to the number of SeqA, DnaB, and DnaX foci, both in the whole culture and in different cell cycle periods. In addition, interfoci distances between NrdB and three replication proteins are similar to the distances between two replication protein foci. CONCLUSIONS: NrdB is present in nucleoid-associated clusters during the replication period. These clusters disappear after replication ends. The number of these clusters is closely related to the number of replication forks and the number of three replication protein clusters in any cell cycle period. Therefore we conclude that NrdB protein, and most likely RNR protein, is closely linked to the replication proteins or replisome at the replication fork. These results clearly support the replication hyperstructure model.