Direct Response Research Articles

Direct and indirect shoot regeneration from leaf explants of Centratherum punctatum Cass., A wild ornamental plant

Centratherum punctatum Cass. is an important wild ornamental medicinal plant belonging to Asteraceae family. It has anti-inflammatory, anti-cancerous, anti-hypersensitive, anti-bacterial and anti-fungal properties and is commonly used in hair care preparations. In this study we describe a protocol for high frequency direct and indirect shoot regeneration from leaf explants. In vitro derived leaves were cultured on MS medium supplemented with different concentrations of TDZ, ZN or BAP (0.1–2.0 mg/L) alone or in combination with NAA (0.1–0.7 mg/L) for shoot regeneration and varying concentrations of 2, 4-D or NAA (0.2–2.0 mg/L) for callus induction. Optimum direct shoot regeneration response was obtained from in vitro derived leaves in MS medium supplemented with 0.5 mg/L TDZ (61.4 ± 3.90% response; 27.4 ± 1.99 shoots per explant; mean shoot length of 4.8 ± 0.81 cm). Out of the 7, 14, 21 and 28-day-old leaves, 14-day-old leaves resulted in maximum shoot induction indicating the influence of explant age. Lamina with petiole exhibited a significant increase in shoot regeneration compared to that without petiole. Pretreating the explants with 1.0 mg/L TDZ for 24 h prior to culture produced the highest response of 92 ± 1.84% with a mean number of 38.7 ± 1.24 shoots per explant. 2, 4-D was found favourable for callus induction than NAA for callus induction from leaf explants of C. punctatum. The 21-day-old leaf showed the optimum callus induction. The optimum shoot regeneration from callus was obtained in 1.5 mg/L TDZ (84.2 ± 4.09% response with 58.2 ± 2.46 shoots per explant). Well-developed shoots with 3.0–4.0 cm length were rooted on half strength MS medium containing 0.5 mg/L IBA. The rooted shoots were transplanted to soil and acclimatized with 96.8 ± 3.26% success. Analysis of clonal fidelity of the micropropagated plants through SCoT marker analysis revealed the genetic similarity of mother plant and in vitro derived plants.

Adjuvant polypeptide vaccines for high-risk uveal melanoma.

e21509 Background: Due to biologic differences, uveal melanoma patients are often excluded from clinical trials for cutaneous melanoma; however, many antigens are shared between the two melanoma subtypes. Thus, our vaccine trials at the University of Virginia (UVA) have allowed enrollment of high-risk uveal melanoma patients, who have substantial risk of relapse without FDA-approved adjuvant therapy available. For the present study, we hypothesized that the vaccines would be well-tolerated and immunogenic in this population. We examined the clinical, immunogenicity and safety outcomes of subjects with uveal melanoma enrolled in our adjuvant vaccine clinical studies. Methods: Patients were identified through participation in an adjuvant vaccine study at UVA between 2012-2022. Ten patients received the 6-Melanoma-Helper Peptide (6-MHP) vaccine through Mel-65 and Mel-66 clinical trials (NCT03617328 and NCT04364230) and one patient received the 12-peptide MELITAC vaccine through the Mel-58 clinical trial (NCT01585350). Clinical outcomes included relapse-free (RFS) and overall survival (OS) and trial toxicity reporting. Immunogenicity was assessed by ex vivo interferon-gamma ELISpot assay of peripheral T cells. OS and RFS were reported by Kaplan-Meier survival analysis and compared by log rank test between groups. Results: Of the 11 identified patients, nine were male (82%) and two were female (18%), with a median age of 64 years. All patients were high risk by molecular testing, the majority by Castle Bioscience DecisionDx-UM. Five were PRAME positive, five PRAME negative, and one not reported. In the cohort, three patients had uveal melanoma recurrence and one subject died from metastatic disease during the evaluation period. The 5-year RFS and OS were 71% (95% CI 43-100) and 80% (95% CI 52-100), respectively. Two patients experienced dose-limiting, grade 3 toxicities to the vaccine, requiring early trial discontinuation, including one grade 3 injection-site reaction and one grade 3 uveitis. Nine patients experienced grade 1-2 toxicities, mostly injection-site reactions and constitutional symptoms. Of nine patients with available immunogenicity data, five (55%) had direct antigen-mediated immune response to vaccine. Two patients’ responses are pending. Patients with immunogenic response had a non-significant trend toward better RFS and OS (both p = 0.22). The 3-year RFS and OS were 100% for subjects with T cell response and the RFS and OS were 50% (95% CI 13-100) for patients without T cell response. Two of the relapsed patients did not have an immune response to vaccine, and response data were not available for the third. Conclusions: Melanoma polypeptide vaccines are immunogenic and safe in patients with uveal melanoma. Our early data suggests the possibility of early benefit with direct antigen response, though longer follow up and further study will be needed to investigate these findings.

Physiological biomarkers of silent brain damage leading to cognitive impairment and Dementia – direct and accessible clinical evidence

AbstractBackgroundCognitive assessment is the best clinical tool to detect cognitive impairments, yet it is evident only at late stages of disease progression. In contrast, silent brain network changes occur at early stages of the disease and it is estimated that a large proportion of dementias may be prevented or at‐least delayed if detected during early pathophysiology stages. Neuroimaging studies have shown that silent brain network findings, including white matter hyperintensities, lacunar infarctions and temporal atrophy are evident before objective cognitive impairment is detected and even more in ‘at risk’ population with risk factors for dementia. We aimed to evaluate direct physiological biomarkers that provide accessible clinical evidence of silent brain network damage that precede clinical cognitive findings and provide early clinical biomarkers that can facilitate early interventions.MethodBrain network performance was evaluated in 168 subjects ‘at risk’ for developing dementia (Table 1). Direct electrophysiological imaging (“Delphi”) was used to measure magnetically induced brain network electrophysiological response. MRI scans included T1, T2, FLAIR, Diffusion Weighted Imaging (DWI) and (SWI). They were analysed according to Fazekas scale for white matter Hyperintensities (WMH), lacunar Infarctions and medial temporal lobe atrophy (MTA). Objective cognitive evaluations were performed by a neuropsychologist interview and a computerized cognitive battery (NeurotraxTM).ResultDirect electrophysiological imaging (“Delphi”) was able to distinguish between severities of different MRI detected silent brain network damage findings. Magnetically induced direct electrophysiological response wave form adherence (WFA) significantly decreased with increase in WMH (Fig.1A; p<0.0001) and increase in MTA levels (Fig.1B; p<0.0001). Furthermore, WFA significantly decreased in subjects with lacunar infarctions (Fig.1C; p<0.0001).ConclusionSilent brain network deficits preceding dementia and cognitive decline are widely under detected due to lack of accessible tools. Data presented in this study demonstrates “Delphi” technology’s ability to detect silent brain network damage findings and severity levels that are identified in MRI scans. “Delphi” is a clinically accessible, direct, and objective technology that can facilitate early detection, prevention, delayed progression and management of mild cognitive impairment and dementia.

Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb.

Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages. We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug. Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only. We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.

Dynamic biophysical responses of neuronal cell nuclei and cytoskeletal structure following high impulse loading.

Cells are continuously exposed to dynamic environmental cues that influence their behavior. Mechanical cues can influence cellular and genomic architecture, gene expression, and intranuclear mechanics, providing evidence of mechanosensing by the nucleus, and a mechanoreciprocity between the nucleus and environment. Force disruption at the tissue level through aging, disease, or trauma, propagates to the nucleus and can have lasting consequences on proper functioning of the cell and nucleus. While the influence of mechanical cues leading to axonal damage has been well studied in neuronal cells, the mechanics of the nucleus following high impulse loading is still largely unexplored. Using an in vitro model of traumatic neural injury, we show a dynamic nuclear behavioral response to impulse stretch (up to 170% strain per second) through quantitative measures of nuclear movement, including tracking of rotation and internal motion. Differences in nuclear movement were observed between low and high strain magnitudes. Increased exposure to impulse stretch exaggerated the decrease in internal motion, assessed by particle tracking microrheology, and intranuclear displacements, assessed through high-resolution deformable image registration. An increase in F-actin puncta surrounding nuclei exposed to impulse stretch additionally demonstrated a corresponding disruption of the cytoskeletal network. Our results show direct biophysical nuclear responsiveness in neuronal cells through force propagation from the substrate to the nucleus. Understanding how mechanical forces perturb the morphological and behavioral response can lead to a greater understanding of how mechanical strain drives changes within the cell and nucleus, and may inform fundamental nuclear behavior after traumatic axonal injury. STATEMENT OF SIGNIFICANCE: The nucleus of the cell has been implicated as a mechano-sensitive organelle, courting molecular sensors and transmitting physical cues in order to maintain cellular and tissue homeostasis. Disruption of this network due to disease or high velocity forces (e.g., trauma) can not only result in orchestrated biochemical cascades, but also biophysical perturbations. Using an in vitro model of traumatic neural injury, we aimed to provide insight into the neuronal nuclear mechanics and biophysical responses at a continuum of strain magnitudes and after repetitive loads. Our image-based methods demonstrate mechanically-induced changes in cellular and nuclear behavior after high intensity loading and have the potential to further define mechanical thresholds of neuronal cell injury.

Estimating and minimizing movement artifacts in surface electromyogram

While recording surface electromyography [sEMG], it is possible to record the electrical activities coming from the muscles and transients in the half-cell potential at the electrode-electrolyte interface due to micromovements of the electrode-skin interface. Separating the two sources of electrical activity usually fails due to the overlapping frequency characteristics of the signals. This paper aims to develop a method that detects movement artifacts and suggests a minimization technique. Towards that aim, we first estimated the frequency characteristics of movement artifacts under various static and dynamic experimental conditions. We found that the extent of the movement artifact depended on the nature of the movement and varied from person to person. Our study's highest movement artifact frequency for the stand position was 10Hz, tiptoe 22, walk 32, run 23, jump from box 41, and jump up and down 40Hz. Secondly, using a 40Hz highpass filter, we cut out most of the frequencies belonging to the movement artifacts. Finally, we checked whether the latencies and amplitudes of reflex and direct muscle responses were still observed in the highpass-filtered sEMG. We showed that the 40Hz highpass filter did not significantly alter reflex and direct muscle variables. Therefore, we recommend that researchers who use sEMG under similar conditions employ the recommended level of highpass filtering to reduce movement artifacts from their records. However, suppose different movement conditions are used. In that case, it is best to estimate the frequency characteristics of the movement artifact before applying any highpass filtering to minimize movement artifacts and their harmonics from sEMG.

Confederate Conscription and the Struggle for Southern Soldiers by John M. Sacher

Reviewed by: Confederate Conscription and the Struggle for Southern Soldiers by John M. Sacher Kenneth W. Noe (bio) Confederate Conscription and the Struggle for Southern Soldiers. By John M. Sacher. (Baton Rouge: Louisiana State University Press, 2021. Pp. 296. Cloth, $45.00.) Alas the poor conscript, we hardly know him. Forced into Civil War armies against his will, sometimes at bayonet point, he suffered and sometimes died for a cause that was never fully his. Succeeding generations shut their eyes to him in their urgency to depict every soldier-ancestor as a heroic volunteer worthy of veneration. In the avalanche of scholarly books about the Civil War soldier experience that ensued in the 1980s, historians ignore him too. Despite conventional estimates that perhaps 4 percent of Federal soldiers and 10 percent of Confederate soldiers or more were draftees, scholars hasten past the conscript’s embarrassing shade in favor of those eager boys of 1861. Often illiterate or nearly so, the conscript, to be sure, did himself no favors by leaving many fewer traditional sources for later students. Small surprise that Albert Burton Moore’s standard examination of conscription appeared almost a century ago.1 Like Moore’s venerable volume, John M. Sacher’s new study is more concerned with the policy of conscription and its top-down implementation than the draftees themselves. Unlike the older book, Sacher’s firmly rejects the familiar argument that conscription undermined the Confederacy from within. Embracing an “externalist” interpretation of Confederate defeat, the author contends that most white Confederates understood that they were outnumbered, grasped the need to field as many soldiers as possible, and supported the draft when volunteering failed to meet expectations. The first conscription laws of 1862 passed with little debate or opposition in Congress or in public. Only a few die-hard states’ rights proponents, hardly more than unpatriotic ideologues according to the author, attacked conscription’s constitutionality then and later. Where [End Page 261] most Confederate loyalists came to differ with the law, Sacher argues, was in the devilish details of conscription, in terms both of a community’s individual cases and of questions about which additional professions and trades deserved exemptions in order to feed and serve both soldiers and civilians. While such debates reflected real class and ideological fault lines in the Confederacy, as well as competing ties of loyalty to locality and the nation-state, Sacher insists that, as a rule, they did not indicate significant general opposition to conscription itself or to the government that mandated it. Soldiers resented the extension of their enlistments, disliked the rules of substitution, and damned the men at home who gained exemptions denied to volunteers already under arms, yet they too supported the overall concept and largely fought on. Richmond’s willingness to debate and amend the rules and practice of conscription several times won further support. Conscription constantly evolved, according to Sacher, reacting to civilian and military needs. Both Jefferson Davis and Congress demonstrated responsiveness to a supportive public that largely wanted the draft tweaked for fairness but not eliminated, as the 1863 congressional election results seem to indicate. Congress notably passed, and then later in the war tightened, the notorious “Twenty Negro Law,” first in direct response to complaints from the folks at home who feared starvation and violence in the aftermath of the Emancipation Proclamation, then again later when citizens came to fear the evils allegedly wrought by stay-at-home speculators. Sacher adds that no more than 10 percent of planters ever took advantage of the law. Rich men fought the so-called rich man’s war. In a similar manner, Congress widened age limits for the draft as a direct reaction to the expressed needs of proconscription generals, such as Robert E. Lee and Joseph E. Johnston, after Antietam, Gettysburg, and Vicksburg. The lull before the Federal onslaught in 1864 brought similar calls for more men, resulting in the elimination of substitution and in the drafting of men who had hired substitutes. Lee’s need for more men at Petersburg likewise led directly to congressional debate over drafting the enslaved. Sacher admits that Bureau of Conscription officers still had their hands full when it came...

An action-reaction cycle in the Sino-Indian rivalry?

ABSTRACT The Sino-Indian rivalry traces its origins to the founding of each state in the late 1940s. Over the past decade Indian concerns over Chinese activities in South Asia have significantly increased. While New Delhi has sought to counter Beijing in South Asia, a key question is to what extent has China responded to India in the same region? Do we find evidence of a tit-for-tat rivalry escalation process in South Asia where both China and India are actively trying to counter each other? The central argument in this article is that China is not actively engaging in a direct form of rivalry reciprocity with India. While certain activities by Beijing in the region are designed to enhance Chinese influence and power, there is less evidence that these are a direct response to India. This is in contrast to New Delhi’s behavior in the region where we do find evidence of Indian leaders directly responding to China. This articles’ main contribution is to demonstrate that maintenance in asymmetrical positional rivalries does not require clearly identifiable points of escalation, or follow a linear path of a tit-for-tat action-reaction cycle.

Convergent Dynamics In Physiological Response As A Window-Based Robust Control System

The process adapted here delivers physiological readings and maps out the major components that make up the physiological system. The contribution of this component can also be determined on each of the parameters. The skin conductance response (SCR) has a major effect on the synchronous readings of the physiological metrics used. The paper investigates this default by developing a prototypical representation of integrated physiological readings with real-time analytics using a convergent dynamic control model as the inference engine. The major components that make up the physiological system and errors, are characterised by either their noisiness or systematic disturbance. The noisy error is based on the obvious pattern in each time interval and it is measured based on the mean root square error(MRSE). The SCR has a major effect on the synchronous readings of the physiological metrics used. The results obtained from test runs indicate that the Tonic phase of the physiological response signal is the skin conductance level (SCL) that represents the base level of the signal. The Phasic level is the component of the skin conductance response that reflects the direct response to the external stimulus, and this is set between 1-4secs after the stimulus onset at the baseline phase. There also exists the non-specific SCR known as the anomalies that appear post-stimuli; this represents the number of conductance responses that appear within and among subsequent physiological response readings. The originality of work is its ability to visualise multi-modal response signals in a single frame and detect optimal responses significant to a particular event-related protocol

Experimental investigation of the direct and subharmonic responses of a new design of centrifugal pendulum vibration absorber

Centrifugal pendulum vibration absorbers (CPVAs) are often used by the automotive industry to reduce vibrations of the drivetrain. These passive devices consist of several masses oscillating along a given path relative to a rotor. Recent CPVA systems make use of rocking pendulums, meaning that the pendulums rotate about their centre of mass during their motion along their path. In this work, measurements on a new CPVA architecture made of ball-type rocking pendulums are performed in classical and subharmonic operations. To the authors’ knowledge, they lead to the first comparisons between experimental and analytical results regarding the nonlinear detuning of the rotor’s antiresonance and the saturation of the rotor’s response. It is also the first time this saturation phenomenon is observed experimentally. The CPVA investigated is shown to have a high filtering efficiency but its pendulums are subjected to slipping, which limits the operating range of the system. Experimental and analytical investigations of the slipping are carried-out to estimate the limit of adherence of the system.

Risk assessment of ionizing radiation and radiological thresholds to compound an environmental baseline for the unconventional gas industry.

The exploration of unconventional hydrocarbons may be very effective in promoting economic development and confronting energy crisis around the world. However, the environmental risks associated with this practice might be an impediment if not adequately dimensioned. In this context, naturally occurring radioactive materials and ionizing radiation are sensitive aspects in the unconventional gas industry that may compromise the environmental sustainability of gas production and they should be properly monitored. This paper provides a radioecological assessment of the São Francisco Basin (Brazil) as part of an environmental baseline evaluation regarding the Brazilian potential for exploring its unconventional gas reserves. Eleven and thirteen samples of surface waters and groundwater were analyzed for gross alpha and beta using a gas flow proportional counter. A radiological background range was proposed using the ± 2 Median Absolute Deviation method. Using geoprocessing tools, the annual equivalent doses and lifetime cancer risk indexes were spatialized. Gross alpha and beta background thresholds in surface water ranged from 0.04-0.40Bq L-1 to 0.17-0.46Bq L-, respectively. Groundwater radiological background varies from 0.006-0.81Bq L-1 to 0.06-0.72Bq L-1 for gross alpha and beta, respectively. All environmental indexes are relatively higher in the south of the basin, probably a direct response to the local volcanic formations. Traçadal fault and local gas seepages might also influence the gross alpha and beta distribution. All samples have radiological indexes below the environmental thresholds, and should remain at acceptable levels with the development of the unconventional gas industry in Brazil.

Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice.

The intake of dietary phosphate far exceeds recommended levels; however, the long-term health consequences remain relatively unknown. Here, the chronic physiological response to sustained elevated and reduced dietary phosphate consumption was investigated in mice. Although serum phosphate levels were brought into homeostatic balance, the prolonged intake of a high-phosphate diet dramatically and negatively impacted bone volume; generated a sustained increase in the phosphate responsive circulating factors FGF23, PTH, osteopontin and osteocalcin; and produced a chronic low-grade inflammatory state in the BM, marked by increased numbers of T cells expressing IL-17a, RANKL, and TNF-α. In contrast, a low-phosphate diet preserved trabecular bone while increasing cortical bone volume over time, and it reduced inflammatory T cell populations. Cell-based studies identified a direct response of T cells to elevated extracellular phosphate. Neutralizing antibodies against proosteoclastic cytokines RANKL, TNF-α, and IL-17a blunted the high-phosphate diet-induced bone loss identifying bone resorption as a regulatory mechanism. Collectively, this study illuminates that habitual consumption of a high-phosphate diet in mice induces chronic inflammation in bone, even in the absence of elevated serum phosphate. Furthermore, the study supports the concept that a reduced phosphate diet may be a simple yet effective strategy to reduce inflammation and improve bone health during aging.

Reproduction of bacterial chemotaxis by a non-living self-propelled object

Taxic behavior as a response to an external stimulus is a fundamental function of living organisms. Some bacteria successfully implement chemotaxis without directly controlling the direction of movement. They periodically alternate between run and tumble, i.e., straight movement and change in direction, respectively. They tune their running period depending on the concentration gradient of attractants around them. Consequently, they respond to a gentle concentration gradient stochastically, which is called “bacterial chemotaxis.” In this study, such a stochastic response was reproduced by a non-living self-propelled object. We used a phenanthroline disk floating on an aqueous solution of Fe^{2+}. The disk spontaneously alternated between rapid motion and rest, similar to the run-and-tumble motion of bacteria. The movement direction of the disk was isotropic independent of the concentration gradient. However, the existing probability of the self-propelled object was higher at the low-concentration region, where the run length was longer. To explain the mechanism underlying this phenomenon, we proposed a simple mathematical model that considers random walkers whose run length depends on the local concentration and direction of movement against the gradient. Our model adopts deterministic functions to reproduce the both effects, which is instead of stochastic tuning the period of operation used in the previous reports. This allows us to analyze the proposed model mathematically, which indicated that our model reproduces both positive and negative chemotaxis depending on the competition between the local concentration effect and it’s gradient effect. Owing to the newly introduced directional bias, the experimental observations were reproduced numerically and analytically. The results indicate that the directional bias response to the concentration gradient is an essential parameter for determining bacterial chemotaxis. This rule might be universal for the stochastic response of self-propelled particles in living and non-living systems.

Single cell transcriptomics of bone marrow derived macrophages reveals Ccl5 as a biomarker of direct IFNAR-independent responses to DNA sensing.

The type I interferon (IFN) response is an innate immune program that mediates anti-viral, anti-cancer, auto-immune, auto-inflammatory, and sterile injury responses. Bone marrow derived macrophages (BMDMs) are commonly used to model macrophage type I IFN responses, but the use of bulk measurement techniques obscures underlying cellular heterogeneity. This is particularly important for the IFN response to immune stimulatory double-stranded DNA (dsDNA) because it elicits overlapping direct and indirect responses, the latter of which depend on type I IFN cytokines signaling via the IFN alpha receptor (IFNAR) to upregulate expression of interferon stimulated genes (ISGs). Single cell transcriptomics has emerged as a powerful tool for revealing functional variability within cell populations. Here, we use single cell RNA-Seq to examine BMDM heterogeneity at steady state and after immune-stimulatory DNA stimulation, with or without IFNAR-dependent amplification. We find that many macrophages express ISGs after DNA stimulation. We also find that a subset of macrophages express ISGs even if IFNAR is inhibited, suggesting that they are direct responders. Analysis of this subset reveals Ccl5 to be an IFNAR-independent marker gene of direct DNA sensing cells. Our studies provide a method for studying direct responders to IFN-inducing stimuli and demonstrate the importance of characterizing BMDM models of innate immune responses with single cell resolution.

The use of polarized light in the zonal orientation of the sandhopper Talitrus saltator (Montagu)

It is well known that the celestial polarization is used as a compass cue by many species of insects and crustaceans. Although it has been shown that the sandhopper Talitrus saltator perceives polarized light and possesses an arrangement of the rhabdomeres that could allow e-vector interpretation and utilization, T. saltator does not use the e-vector of the skylight polarization as a compass cue when making excursions along the sea–land axis of sandy shores. We performed tests in confined conditions to clarify if skylight polarization is somehow involved in the zonal recovery of T. saltator. We observed the directional responses of sandhoppers in a transparent bowl under an artificial sky (an opaline Plexiglas dome). The bowl was covered by a blue gelatin filter with a grey filter (control condition) and a linear polarizing filter (experimental conditions) positioned under the blue one in such a way as to occupy half of the upper surface of the Plexiglas bowl so as to create a linear polarization gradient. Our experiments confirm that T. saltator perceives polarized light and highlight that this visual capability determines the perception, or perhaps the increase, of the radiance and/or spectral gradient and their use as compass cues in the zonal orientation. Moreover, our findings confirm that the radiance gradient is used as a chronometric compass orienting reference in the absence of other celestial orienting cues.

The influence of polyguanidin on the direction of biochemical processes in wheat (Triti- cum L.) plants.

Modern crop production requires a balance of high and sustainable productivity with maximum safety for the environment, consumers and agricultural workers. The well-known chemical compound polyguanidine, which was previously used as a disinfectant, surfactant and complexing agent, has recently become widely used as a plant growth and development stimulant. Despite the increasing use of polyguanidine preparations as a growth stimulant, there is no data in the literature on its mechanism of action on plants. There are many studies that try to determine whether the effect of biostimulants on plant productivity is a direct or indirect response, for example, through the soil or microbiome. In many cases, biostimulants are considered in terms of their effects on various plant regulatory and functional systems (signaling, metabolic, uptake and transport mechanisms, etc.). But, in general, these modes of action are very diverse and may include activation of nitrogen metabolism or release of phosphorus from soils, general stimulation of soil microbial activity, or stimulation of root growth and increased plant nutrition. The effect of polyguanidin on the physiological parameters of wheat plants was studied under vegetation and laboratory conditions. Seeds of winter wheat variety Bogdana were used for the study. For the determination of flavonoids, a spectrophotometric method based on the measurement of their absorption with aluminum chloride complex was used. It was proved that the treatment of wheat in the tillering and earing phases with polyguanidin had the greatest effect on the protein content in winter wheat grain, which ensured the formation of this indicator at the level of 11.0–13.4% compared to the control. The treatment of wheat seeds with a preparation based on polyguanidine increased the amount of chlorophyll a by almost two times, while the content of chlorophyll b and carotene increased somewhat less. Thus, the use of polyguanidine contributes to the efficient functioning of the photosynthetic apparatus of plants, which will increase their productivity. Since the energy basis of photosynthesis is the absorption of solar radiation by photosynthetic pigments, which are used to form organic matter, there is a direct link between chlorophyll content and plant productivity. Therefore, we decided to check the content of the main photosynthetic pigments in plants after treatment with polyguanidine. At the first stage of our research, plants at the early stages of ontogenesis were analyzed. Thus, we have shown that the treatment of wheat seeds with a polyguanidine-based preparation increases the amount of chlorophyll a almost twice. Evaluation of flavonoid content in wheat plants showed a decrease in their amount after treatment with polyguanidin. That is, after the treatment, the plants, on the contrary, reduced their adaptive potential, because at the biochemical stage it was believed that there were no unfavorable factors in the environment. The analysis of the free proline content showed an increase in its concentration after treatment with the test substance almost doubled both after the first and after the second treatment. Also, it should be noted that reducing the concentration of the drug to 0.15 liters per 200 liters of the working solution increases the level of proline after the first treatment. The increase in proline, in this case, can lead to an increase in stress resistance, which is provided by metabolic and physiological changes. Consequently, its accumulation and conversion into other amino acids due to changes in the activity of proline oxidase contributes to an increase in the protein content in the grain.

Ingrained city rhythms: flexible activity timing but more persistent circadian pace in urban birds.

Urbanization dramatically increases the amount of light at night, which may disrupt avian circadian organization. We measured activity patterns of great tits breeding in the city and forest, and subsequently measured two clock properties of these birds under controlled conditions: tau (endogenous circadian clock speed) and after-effects (history dependency of the clock relative to previous conditions). City and forest birds showed a high repeatability of activity onset (0.60 and 0.41, respectively), with no difference between habitats after controlling for date effects. Activity duration and offset showed more variance, without a difference between birds from the two habitats. Tau did not differ between city and forest birds, however, city birds showed stronger after-effects, taking more days to revert to their endogenous circadian period. Finally, onset of activity was correlated with clocks speed in both habitats. Our results suggest that potential differences in activity timing of city birds is not caused by different clock speeds, but by a direct response to light. Persistence in after-effects suggests a reduced sensitivity of the clock to light at night. Urbanization may select for clock properties that increase the inertia of the endogenous circadian system to improve accuracy of activity rhythms when exposed to noisier lighting cues.

The Effect of Good Corporate Governance, Profitability, and Corporate Social Responsibility on Market Reaction and Company Value in the Registered Mining Industry on the Indonesian Stock Exchange

Purpose: The objective of this analysis was to analyze the direct impact of good corporate governance, profitability and corporate social duty on market response and company value. Theoretical framework: The data analysis process used in this research is a descriptive, namely, analysis that aims to determine the extent to which the variables of moral corporate governance, profitability, and corporate social responsibility influence market reactions and firm value in mining companies listed on the Indonesia Stock Exchange which are based on empirical and theoretical facts. Design/methodology/approach: This research uses secondary data from 27 mining companies listed on the Indonesian Stock Exchange between 2017 and 2019. The data analysis methods used in this study are quantitative and qualitative descriptive research methods, as well as relational research methods. The analysis used to test the hypothesis using SEM (Structural Equation Model Analysis). Findings: The consequences of this report show that good corporate governance (1) does not directly affect market reactions with a positive correlation. (2) profitability does not directly affect market response with a negative correlation; (3) corporate social responsibility does not directly influence the market response in a positive direction; (4) good corporate governance does not directly affect company value, with a positive relationship; Research, Practical & Social implications: Since there are no evaluation standards or standard form for determining the rate of diffusion of corporate social responsibility, the assessment of the spread of corporate social responsibility remains subjective, so there will be differences in each researcher. The announcement of the dissemination of corporate social responsibility is made by the company, together with the announcement of the Annual Report, so there are other aspects made by investors in investment decisions. Originality/value: corporate social responsibility does not directly disturb the company's values with a positive relationship; market response does not directly affect company value with negative correlation; good corporate governance does not directly affect company value through a negative correlation market response; profitability does not directly affect company value through market feedback with a positive correlation.

Activation, Amplification, and Ablation as Dynamic Mechanisms of Dendritic Cell Maturation.

T cell responses to cognate antigens crucially depend on the specific functionality of dendritic cells (DCs) activated in a process referred to as maturation. Maturation was initially described as alterations of the functional status of DCs in direct response to multiple extrinsic innate signals derived from foreign organisms. More recent studies, conducted mainly in mice, revealed an intricate network of intrinsic signals dependent on cytokines and various immunomodulatory pathways facilitating communication between individual DCs and other cells for the orchestration of specific maturation outcomes. These signals selectively amplify the initial activation of DCs mediated by innate factors and dynamically shape DC functionalities by ablating DCs with specific functions. Here, we discuss the effects of the initial activation of DCs that crucially includes the production of cytokine intermediaries to collectively achieve amplification of the maturation process and further precise sculpting of the functional landscapes among DCs. By emphasizing the interconnectedness of the intracellular and intercellular mechanisms, we reveal activation, amplification, and ablation as the mechanistically integrated components of the DC maturation process.

Asymmetric evidence of foreign direct investment response to stock returns in Nigeria

This study examines the response of foreign direct investment (FDI) to asymmetric changes in stock returns in Nigeria. We employed disaggregated monthly data for Nigeria (1985M01–2017M12) to test the magnitude of stock returns’ elasticity of FDI using a nonlinear ARDL modelling framework. By controlling for exchange rate and output size, evidence of asymmetric response of FDI to stock market returns in Nigeria could not be denied. Hence, sustainable development in Nigeria requires a long-run balance between FDI and Stock market through a stable exchange rate management system and efficiency of the capital market is necessary for increased FDI.