Miracle-dz/UniFAR-FTUs huggingface dataset:
Acoustic and magnetic communication in plants

Over the last two decades, important insights into our understanding of plant ecology and the communicative nature of plants have not only confirmed the existence of a wide range of communication means used by plants, but most excitingly have indicated that more modalities remain to be discovered. In fact, we have recently found that seeds and seedlings of the chili plant, Capsicum annuum, are able to sense neighbors and identify relatives using alternative mechanisms beyond previously studied channels of plant communication. In this addendum, we offer a hypothetical mechanistic explanation as to how plants may do this by quantum-assisted magnetic and/or acoustic sensing and signaling. If proven correct, this hypothesis prompts for a re-interpretation of our current understanding of plasticity in germination and growth of plants and more generally, calls for developing a new perspective of these biological phenomena.
Functional divergence in the Arabidopsis LOB-domain gene family

The Arabidopsis LOB-domain (LBD) gene family is composed by 43 members divided in two classes based on amino acid conservation within the LOB-domain. The LOB domain is known to be responsible for DNA binding and protein-protein interactions. There is very little functional information available for most genes in the LBD family and many lbd single mutants do not exhibit conspicuous phenotypes. One plausible explanation for the limited loss-of-function phenotypes observed in this family is that LBD genes exhibit significant functional redundancy. Here we discuss an example of one phylogenetic subgroup of the LBD family, in which genes that are closely related based on phylogeny exhibit distinctly different expression patterns and do not have overlapping functions. We discuss the challenges of using phylogenetic analyses to predict redundancy in gene families.
Redox control of copper homeostasis in cyanobacteria

Copper is essential for all living organisms but is toxic when present in excess. Therefore organisms have developed homeostatic mechanism to tightly regulate its cellular concentration. In a recent study we have shown that CopRS two-component system is essential for copper resistance in the cyanobacterium Synechocystis sp PCC 6803. This two-component regulates expression of a heavy-metal RND type copper efflux system (encoded by copBAC) as well as its own expression (in the copMRS operon) in response to an excess of copper in the media. We have also observed that both operons are induced under condition that reduces the photosynthetic electron flow and this induction depends on the presence of the copper-protein, plastocyanin. These findings, together with CopS localization to the thylakoid membrane and its periplasmic domain being able to bind copper directly, suggest that CopS could be involved in copper detection in both the periplasm and the thylakoid lumen.
Proteasome-dependent proteolysis has a critical role in fine-tuning the feedback inhibition of cytokinin signaling

The ubiquitin/26S proteasome-dependent proteolysis of response regulators is a critical element of many plant hormone signaling pathways. We have recently shown that cytokinin signaling requires the AXR1 component of the related to ubiquitin (RUB) protein modification pathway to promote the proteasome-dependent degradation of the cytokinin response inhibitor ARR5. Here, we show that ARR5 also accumulates in the 26S proteasome mutant rpn12a-1, and leads to a marked resistance to cytokinins. Collectively, these results suggest that proteasome-dependent proteolysis of feedback inhibitors such as ARR5 is essential for the maintenance of optimal responsivity and plasticity in cytokinin signaling.
Integration of boolean models on hormonal interactions and prospects of cytokinin-auxin crosstalk in plant immunity

Crosstalk between auxin and cytokinin in plant growth and development has already been established. However, their dynamics in plant immunity is still not well understood and requires systems biological approaches for analysis. Omics based public databases are exploited for the reconstruction, integration and analysis of Boolean models for hormonal interactions in plants. We established a meta-network by combining the plant immune regulatory network and the pathogen virulence specific network and used it as substrate for dynamic simulations on hormonal aspects of plant immunity. Our integrated analysis of this meta-network reveals antagonistic crosstalk between auxin and cytokinin in the Pst DC3000 and Arabidopsis interaction. Moreover, we discuss here the importance of Boolean models in unfolding inferences relevant to plant pathogen interactions.
Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons

Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2–based ratiometric Ca2+-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca2+ imaging protocols revealed that HiK+ (30 mM)-induced intracellular free Ca2+ ([Ca2+]i) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca2+]i. This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca2+, providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.
Bacterial-like PPP protein phosphatases

Reversible phosphorylation is a widespread modification affecting the great majority of eukaryotic cellular proteins, and whose effects influence nearly every cellular function. Protein phosphatases are increasingly recognized as exquisitely regulated contributors to these changes. The PPP (phosphoprotein phosphatase) family comprises enzymes, which catalyze dephosphorylation at serine and threonine residues. Nearly a decade ago, “bacterial-like” enzymes were recognized with similarity to proteins from various bacterial sources: SLPs (Shewanella-like phosphatases), RLPHs (Rhizobiales-like phosphatases), and ALPHs (ApaH-like phosphatases). A recent article from our laboratory appearing in Plant Physiology characterizes their extensive organismal distribution, abundance in plant species, predicted subcellular localization, motif organization, and sequence evolution. One salient observation is the distinct evolutionary trajectory followed by SLP genes and proteins in photosynthetic eukaryotes vs. animal and plant pathogens derived from photosynthetic ancestors. We present here a closer look at sequence data that emphasizes the distinctiveness of pathogen SLP proteins and that suggests that they might represent novel drug targets. A second observation in our original report was the high degree of similarity between the bacterial-like PPPs of eukaryotes and closely related proteins of the “eukaryotic-like” phyla Myxococcales and Planctomycetes. We here reflect on the possible implications of these observations and their importance for future research.
Association between chemokine receptor 5 delta32 polymorphism and susceptibility to cancer: a meta-analysis

Abstract Objective: To explore whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to cancer. Methods: A meta-analysis was conducted on the association between the CCR5-Δ32 polymorphism and cancer using (i) allele contrast and (ii) the dominant model. Results: Thirteen articles, including 16 comparative studies on a total of 3087 patients and 3735 controls, were included in the meta-analysis. These studies encompassed breast cancer (n = 3), bladder cancer (n = 3), cervical cancer (n = 2), pancreatic cancer (n = 2), prostate cancer (n = 2), head and neck cancer (n = 2), lymphoma (n = 1), gallbladder cancer (n = 1), skin cancer (n = 1) and mixed cancer (n = 1). The meta-analysis revealed an association between cancer and the CCR5-Δ32 allele (OR = 1.368, 95% CI = 1.064–1.758, p = 0.014), and stratification by ethnicity showed an association between the CCR5-Δ32 allele and cancer in Indians (OR = 2.480, 95% CI = 1.247–4.932, p = 0.010). The meta-analysis also revealed an association between breast cancer and the CCR5-Δ32 allele (OR = 1.689, 95% CI = 1.012–2.821, p = 0.045). However, allele contrast and the dominant model failed to reveal an association between the CCR5-Δ32 polymorphism and bladder cancer, cervical cancer, pancreatic cancer, prostate cancer, and head and neck cancer. Conclusions: This meta-analysis demonstrates that the CCR5-Δ32 polymorphism is associated with susceptibility to cancer in Indians and is associated with breast cancer.
SLCO Transport Genes in Prostate Cancer—Response

We thank Figg and colleagues for their interest in our manuscript ([1][1]) and their comments about the potential role of organic anion–transporting polypeptide (OATP) transport proteins in prostate cancer outcomes. Consistent with findings reported by Hamada and colleagues ([2][2]), Sharifi and
Anti‐Tumour Necrosis Factor‐α Therapy in Heart Failure: Future Directions

The elevated level of tumour necrosis factor-a (TNF-a) in patients with heart failure has triggered interest in investigating the role of TNF-a in the pathogenesis of heart failure. Both clinical and experimental evidence has suggested that high levels of TNF-a occur in heart failure and lead to progression of left ventricular dysfunction. In addition, it has been documented that inhibition of TNF-a reverses its deleterious effects in heart failure. A number of clinical trials have been initiated to investigate the effect of anti-TNF-a therapy in patients with heart failure. The discouraging results of recent clinical trials of anti-TNF-a therapy in patients with heart failure have raised a number of questions about the role of TNF-a in heart failure. The present review critically analyzes the reasons of failure of anti-TNF-a therapy in heart failure. Moreover the potential approaches for the development of new anti-TNF-a therapy has been discussed which may open new vista of the management of heart failure.
Green light signaling and adaptive response

To a plant, the sun’s light is not exclusively energy for photosynthesis, it also provides a package of data about time and prevailing conditions. The plant’s surroundings may dampen or filter solar energies, altering spectral profiles of their light environment. Plants use this information to adjust form and physiology, tailoring gene expression to best match ambient conditions. Extensive literature exists on how blue, red and far-red light contribute to plant adaptive responses. A growing body of work identifies discrete effects of green light (500–565 nm) that also shape plant biology. Green light responses are known to be either mediated through, or independent of, the cryptochrome blue light receptors. Responses to green light share a general tendency to oppose blue- or red-light-induced responses, including stem growth rate inhibition, anthocyanin accumulation or chloroplast gene expression. Recent evidence demonstrates a role for green light in sensing a shaded environment, independent from far-red shade responses.
Small RNAs in streptococci

The group of streptococci includes species responsible for severe diseases in humans. To adapt to their environment and infect their hosts, streptococci depend on precise regulation of gene expression. The last decade has witnessed increasing findings of small RNAs (sRNAs) having regulatory functions in bacteria. More recently, genome-wide screens revealed that streptococcal genomes also encode multiple sRNAs. Some sRNAs including the class of CRISPR RNAs (crRNAs) play critical roles in streptococcal adaptation and virulence. Analysis of sRNA mechanisms uncovered three sRNAs that target in trans mRNA (FasX), sRNA (tracrRNA) and DNA (crRNA). Overall, the current understanding of sRNA-mediated regulation in streptococci remains very limited. Given the complexity of regulatory networks and the number of recently predicted sRNAs, future research should reveal new functions and mechanisms for the streptococcal sRNAs. Here, we provide a comprehensive summary of the information available on the topic.
New insights into siRNA amplification and RNAi

In the nematode Caenorhabditis elegans (C. elegans), gene inactivation by RNA interference can achieve remarkable potency due to the amplification of initial silencing triggers by RNA-dependent RNA polymerases (RdRPs). RdRPs catalyze the biogenesis of an abundant species of secondary small interfering RNAs (siRNAs) using the target mRNA as template. The interaction between primary siRNAs derived from the exogenous double-stranded RNA (dsRNA) trigger and the target mRNA is required for the recruitment of RdRPs. Other genetic requirements for RdRP activities have not been characterized. Recent studies have identified the RDE-10/RDE-11 complex which interacts with the primary siRNA bound target mRNA and acts upstream of the RdRPs. rde-10 and rde-11 mutants show an RNAi defective phenotype because the biogenesis of secondary siRNAs is completely abolished. In addition, the RDE-10/RDE-11 complex plays a similar role in the endogenous RNAi pathway for the biogenesis of a subset of siRNAs targeting recently acquired, duplicated genes.
Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA

p53 mRNA has been shown to be translated into two isoforms, full-length p53 (FL-p53) and a truncated isoform ΔN-p53, which modulates the functions of FL-p53 and also has independent functions. Previously, we have shown that translation of p53 and ΔN-p53 can be initiated at Internal Ribosome Entry Sites (IRES). These two IRESs were shown to regulate the translation of p53 and ΔN-p53 in a distinct cell-cycle phase-dependent manner. Earlier observations from our laboratory also suggest that the structural integrity of the p53 RNA is critical for IRES function and is compromised by mutations that affect the structure as well as RNA protein interactions. In the current study, using RNA affinity approach we have identified Annexin A2 and PTB associated Splicing Factor (PSF/SFPQ) as novel ITAFs for p53 IRESs. We have showed that the purified Annexin A2 and PSF proteins specifically bind to p53 IRES elements. Interestingly, in the presence of calcium ions Annexin A2 showed increased binding with p53 IRES. Immunopulldown experiments suggest that these two proteins associate with p53 mRNA ex vivo as well. Partial knockdown of Annexin A2 and PSF showed decrease in p53 IRES activity and reduced levels of both the p53 isoforms. More importantly the interplay between Annexin A2, PSF and PTB proteins for binding to p53mRNA appears to play a crucial role in IRES function. Taken together, our observations suggest pivotal role of two new trans-acting factors in regulating the p53-IRES function, which in turn influences the synthesis of p53 isoforms.
Timely and efficient planning of treatments through intelligent scheduling

When people experience health problems, this often leads to a period of concern and stress. Both for patients’ physical and mental well-being, it is essential that healthcare processes are organized in the best possible way. This thesis aims to support hospitals in realizing excellent quality of patient service, whilst utilizing resources efficiently. By developing methodologies based on techniques from operations research, also known as mathematical decision theory, the research presented provides decision support for the planning and scheduling of healthcare processes. Three specific challenges are addressed. First, online appointment scheduling, providing patients with prompt responses to their appointment requests. Second, as an alternative, enabling patients to walk in for certain types of diagnostics or treatment without an appointment. And third, integral capacity planning in the inpatient care chain: aligning resource capacities of inpatient wards with the operating room schedule and emergency patient arrivals, and staffing nurses accordingly. All studies in this thesis exemplify how healthcare operations research enables simultaneous improvements in both quality of care and logistical efficiency.
The Morphological Characteristics, Growth, and Etiology of the Hyperdivergent Phenotype

Due to the skeletal complexity of the problem, hyperdivergent retrognathic patients are among the most difficult for orthodontists to treat. It is imperative to treat these patients for both esthetic and functional reasons. Hyperdivergent growth patterns are generally established early and most do not improve over time. The etiology appears to be environmental, due to postural adjustments related with compromised airways and weak masticatory musculature. If a lowered mandible posture is maintained in growing subjects, the dentition, dentoalveolar complex, and the mandible should be expected to compensate. Dentoalveolar heights should be expected to be excessive (i.e., supraeruption of the teeth), the ramus is shorter, the gonial angle is larger, the mandibular symphysis is taller and thinner, the mandibular plane is steeper, the mandible is retrognathic, and anterior lower face height is increased. Moreover, the jaws, especially the upper, are narrow. The most important factor underlying these developmental adaptations is true mandibular rotation. Rotation is important because it is the major determinant of the anteroposterior (AP) chin position. The detrimental skeletal changes that characterize hyperdivergent patients are ultimately due to backward or less than average true forward rotation. Theoretically, a therapeutic treatment that mimics normal growth (i.e., one that builds in true forward rotation) is desirable because it might be expected to correct not only the anteroposterior (AP) and vertical position of the chin, but also many of the other morphological maladaptations associated with the hyperdivergent retrognathic phenotype.
RNA pentaloop structures as effective targets of regulators belonging to the RsmA/CsrA protein family

In the Gac/Rsm signal transduction pathway of Pseudomonas fluorescens CHA0, the dimeric RNA-binding proteins RsmA and RsmE, which belong to the vast bacterial RsmA/CsrA family, effectively repress translation of target mRNAs containing a typical recognition sequence near the translation start site. Three small RNAs (RsmX, RsmY, RsmZ) with clustered recognition sequences can sequester RsmA and RsmE and thereby relieve translational repression. According to a previously established structural model, the RsmE protein makes optimal contacts with an RNA sequence 5′-A/UCANGGANGU/A-3′, in which the central ribonucleotides form a hexaloop. Here, we questioned the relevance of the hexaloop structure in target RNAs. We found that two predicted pentaloop structures, AGGGA (in pltA mRNA encoding a pyoluteorin biosynthetic enzyme) and AAGGA (in mutated pltA mRNA), allowed effective interaction with the RsmE protein in vivo. By contrast, ACGGA and AUGGA were poor targets. Isothermal titration calorimetry measurements confirmed the strong binding of RsmE to the AGGGA pentaloop structure in an RNA oligomer. Modeling studies highlighted the crucial role of the second ribonucleotide in the loop structure. In conclusion, a refined structural model of RsmE-RNA interaction accommodates certain pentaloop RNAs among the preferred hexaloop RNAs.
Autoimmune Thyroiditis: A New Comorbidity of the Most Prevalent Endocrine Disease, Its Prevention and Prediction

Hashimoto’s thyroiditis as most prevalent autoimmune endocrine disorder of nowadays is detailed, with data on its natural history, etiology, pathogenesis and comorbidity. A review of authors’ original papers is given, establishing the clinical pathophysiological hypothesis, initially coined in 2002, about regular transition of adolescent hypothalamic syndrome (obesity with rose striae) with age into early metabolic syndrome, complicated by autoimmune thyroiditis. Some evidences are obtained, that witness for marfanoid phenotype and chronic disequilibrium between local, autacoid-mediated and systemic, hormone-mediated regulation, typical for inherited connective tissue disorders, may promote this transition. Pathogenetic role of hyperprolactinemia and cytokine misbalance in transition of physiologic anti-thyroid autoimmunity into autoallergic disease is evaluated. Prevention, early recognition and prediction of autoimmune thyroiditis course, as well as preventive treatment of its complications are reviewed. (7 figs, bibl.: 94 refs).
The use of hyperthermia to overcome tumour hypoxia in the treatment of advanced breast cancer

Abstract Purpose: The purpose of this review was to explore the literature on the use of hyperthermia (HT) in advanced breast cancer. Methods: A literature search was conducted to obtain information from recent trials of HT and/or chemotherapy (CH) and radiotherapy (RT) for patients with locally recurrent breast carcinoma. Issues concerned with patient compliance and side effects have also been reviewed and future recommendations for research made. Results: Results of recent trials have demonstrated promising outcomes for HT and RT in combination, particularly for recurrent disease to improve local control (LC). There is no evidence, however, to support a positive effect on overall survival. Conclusions: Despite positive results HT has not been widely embraced, due to financial and logistical limitations. Future recommendations include larger, randomised, controlled studies and the development of temperature mapping to avoid potentially limiting HT blisters.