Changes in tissue geometry during developmental processes are associated with collective migration of cells. Recent experimental and numerical results suggest that these changes could leverage on the coexistence of nematic and hexatic orientational order at different length scales. How this multiscale organization is affected by the material properties of the cells and their substrate is presently unknown. In this study, we address these questions in monolayers of Madin-Darby canine kidney cells having various cell densities and molecular repertoires. At small length scales, confluent monolayers are characterized by a prominent hexatic order, independent of the presence of E-cadherin, monolayer density, and underlying substrate stiffness. However, all three properties affect the meso-scale tissue organization. The length scale at which hexatic order transits to nematic order, the “hexanematic” crossover scale, strongly depends on cell-cell adhesions and correlates with monolayer density. Our study demonstrates how epithelial organization is affected by mechanical properties, and provides a robust description of tissue organization during developmental processes.

Numerous studies observed a link between the herpes smplex virus-1 (HSV-1) and Alzheimer's disease. However, the exact viral and cellular dynamics that lead from an HSV-1 infection to Alzheimer's disease are unknown. In this paper, we use the microcompetition model to formulate these dynamics by connecting seemingly unconnected observations reported in the literature. We concentrate on four pathologies characteristic of Alzheimer's disease. First, we explain how an increase in the copy number of HSV-1 during latency can decrease the expression of BECN1/Beclin1, the degradative trafficking protein, which, in turn, can cause a dysregulation of autophagy and Alzheimer's disease. Second, we show how an increase in the copy number of the latent HSV-1 can decrease the expression of many genes important for mitochondrial genome metabolism, respiratory chain, and homeostasis, which can lead to oxidative stress and neuronal damage, resulting in Alzheimer's disease. Third, we describe how an increase in this copy number can reduce the concentration of the NMDA receptor subunits NR1 and NR2b (Grin1 and Grin2b genes), and brain derived neurotrophic factor (BDNF), which can cause an impaired synaptic plasticity, Aβ accumulation and eventually Alzheimer's disease. Finally, we show how an increase in the copy number of HSV-1 in neural stem/progenitor cells in the hippocampus during the latent phase can lead to an abnormal quantity and quality of neurogenesis, and the clinical presentation of Alzheimer's disease. Since the current understanding of the dynamics and homeostasis of the HSV-1 reservoir during latency is limited, the proposed model represents only a first step towards a complete understanding of the relationship between the copy number of HSV-1 during latency and Alzheimer's disease.

Abstract Background: Deep sternal wound infection (DSWI) is a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. Here we first present a case of a patient successfully treated for antibiotic-loaded bone cement(ALBC) combined with vacuum sealing drainage(VSD) of DSWI.Case presentation: This case report presented a patient who underwent open heart surgery, and suffered postoperatively from a DSWI associated with enterococcus cloacae. Focus debridement combined with ALBC filling and VSD was conducted in stage I. Appropriate antibiotics were started according to sensitivity to be continued for two weeks until the inflammatory markers decreased to normal. One month after the surgery, patient’s wound was almost healed and was discharged from hospital with a drainage tube. Two months after the stage I surgery procedure, the major step was removing the previous ALBC, and extensive debridement in stage II. The patient fully recovered without further surgical treatment.Conclusions: The results of this case suggest that ALBC combined with VSD may be a viable and safe option for deep sternal wound reconstruction.

The cause of most Parkinson's disease cases is unknown. However, it is well documented that mitochondrial dysfunction and misfolded α synuclein aggregation are important cellular abnormalities associated with the disease. In this paper, we use the microcompetition model to show how latent viruses, which infect the central and peripheral nervous systems, can cause the observed mitochondrial dysfunction and excess α synuclein aggregation, and eventually, Parkinson's disease.

Many studies showed that the p300/CBP coactivator is limiting. Here we review three studies that showed how transcription complexes formed on viral cis-regulator elements compete with cellular transcription complexes by sequestrating the p300/CBP coactivator. According to the microcompetition model, this sequestering can cause disease. We use the microcompetition model to explain how a specific type of sequestering, caused by a latent virus that has an active cis-regulatory element in its promoter/enhancer that binds the transcription complex p300/CBP ·GABP can cause diseases such as cancer, atherosclerosis, diabetes, and certain autoimmune diseases.

The coronavirus (SARS-CoV-2), which causes COVID-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV). The recent COVID-19 outbreak created an urgent need for treatment. To expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. Gene-Eden-VIR and Novirin are natural, broad-spectrum, antiviral treatments proven to be safe and effective in several clinical studies. In this article, we present evidence indicating that the 5 Gene-Eden-VIR/Novirin ingredients have anti-betacoronavirus, and specifically, anti-SARS-CoV effects. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on individuals at risk and those infected with the virus.

Many studies showed the existence of a positive association between cytomegalovirus (CMV) seropositivity and all-cause mortality. In this paper, we use the microcompetition model to explain how the latent CMV sequesters the limiting GABP∙p300/CBP transcription complex, which causes abnormal cellular gene expression, a chronic disease and mortality. Since most people harbour the latent CMV, we urge further research on this topic.

The Editor of this journal has published this Expression of Concern to alert readers that, following publication of the article [1], it came to light that there were undeclared competing interests that have a direct impact on the article and the strength of its findings. In addition, post publication peer review has indicated that the conclusions may not be supported by the results due to methodological flaws in the study. Pending further investigation of these concerns, further editorial action may be taken. The authors have not responded to any correspondence about this Expression of Concern.

Most breast cancer cases show a decrease in the concentration of the breast cancer type 1 susceptibility protein (BRCA1). However, only a small portion of these cases have a mutated BRCA1 gene. Although many attempts have been made to identify the reason for the decrease in BRCA1 concentration in sporadic, non-heritable breast cancer cases, the cause is still unknown. In this review, we use the Microcompetition Model to explain how certain latent viruses, which are frequently detected in breast cancer tumors, can decrease the expression of the BRCA1 gene and cause the development of breast tumors.