Harsh Stress Research Articles

Protective effect of berberine against oxidative stress-induced apoptosis in rat bone marrow-derived mesenchymal stem cells

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to be used for the treatment of delayed union, nonunion or persistent bone defects in MSC-based cell therapy. However, implantation of BMSCs into the fracture site is confronted with apoptosis on account of harsh conditions and oxidative stress. In the present study, the anti-apoptotic effects of berberine (BBR) on BMSCs subjected to hydrogen peroxide (H2O2) are investigated, and the potential underlying mechanisms are explored. Oxidative injury was induced by exposure to H2O2, and cell viability was assessed using a cell counting kit-8 assay. The apoptosis of BMSCs was measured by Hoechst 33258 and Annexin V-fluorescein isothiocyanate/propidium iodide assay. Reactive oxygen species staining and superoxide dismutase (SOD) assay were applied to assess the anti-oxidative effect of BBR. Finally, western blot was performed to measure the expression levels of phosphorylated (p)-Akt, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. In the present study, it was identified that BBR remarkably attenuated H2O2-induced apoptotic cell death via quenching ROS production and increasing SOD activity. Further studies indicated that BBR can reduce apoptosis by upregulating the expression level of p-Akt and Bcl-2, and downregulating the expression levels of Bax and cleaved caspase-3. Taken together, the results of the present study demonstrate that pretreatment with BBR could alleviate H2O2-induced apoptosis in rat BMSCs in vitro.

Antioxidant effects of alfalfa can improve iron oxide nanoparticle damage: Invivo and invitro studies

Medicago sativa Linn. or alfalfa (Leguminosae) has been used traditionally as an effective cure for CNS, heart and metabolic disorders and digestive aids. Alfalfa is a resistant plant against stress due to small antioxidant molecules and enzymes. Our previous work demonstrated that 100 μg/ml of 50 nm size Fe2O3-NP causes harsh oxidative stress in HepG2 cells and 100 mg/kg of same nanoparticle causes extreme damage in rat's liver. Therefore it can be used as a useful model for invivo and invitro studies of oxidative stress. This study assessed the effects of two concentration of alfalfa on the mentioned invivo and invitro damage. Our results showed alfalfa reduced reactive oxygen species (ROS) production and enhanced reduced glutathione (GSH) that cause reduction of DNA fragmentation and prevent apoptosis pathway so improve viability of the cells. Results also showed alfalfa decreased hepatic enzymes penetrating and lipid peroxidation in rat's liver. Note that Fe2O3-NP potentially has widespread biological application but its usage is limited due to bio incompatibility. A suitable antioxidant compound that reduce nanoparticle side effects can be used as an effective adjuvant with iron oxide nanoparticle (and may be other nanomaterials) in biological applications.

Acclimation Changes of Flavonoids in Needles of Conifers during Heat and Drought Stress 2015

The long-term harsh climate conditions in 2015 distorted already from June up to November in all study trees of Tsuga and Taxus the intracellular organization of the needles. Intimately involved in these repressive processes were the flavanols, a small subgroup of the flavonoids. They were not only deposited in vacuoles of conifer needles but also in the nuclei and chromosomes. Among the many flavonoids the small group of catechin derivatives and polymers named flavanols can exclusively be stained blue with DMACA (dimethylaminocinnamaldehyde). From mid-July onward, the vacuolar flavanols of the epidermal cell layers were gradually diminished as evidenced by decreasing blue staining of nuclei and vacuoles. Subsequently, in August also the large spongy mesophyll cells showed the flavanols decreasing progressively. Apparently, the antioxidant flavanols operate as oxygen radical scavengers. (ROS) were used up during the harsh environmental stress conditions. Both, Tsuga and Taxus reacted in this way. However, it is quite surprising that in all study trees the palisade cells did not contain such vacuolar flavanols. Only these cells were in June the first to show a loss of chlorophyll from chloroplasts as well as an efflux of flavanols from the nuclei. Conversely, from September onward another group of phenols, the yellow-staining flavanols were newly formed in the palisade cells and later on also in the mesophyll cells. Obviously, they were assembled finally to stabilize finally the fragile cell sites. Summing up, the present study shows by cytological studies that the climatic conditions in 2015 produced the worst disturbance of subcellular structures observed since 2000 when our studies on nuclear phenols in needles of conifers were initiated.

A Short Review on the Development of Salt Tolerant Cultivars in Rice

Rice is staple food for half of the world. With a population of almost 9.6 billion by the year 2050, there is a dire need of developing techniques to improve the crop plants, not only in terms of better yield but also to withstand harsh environmental conditions and stresses like drought, temperature, flood and salinity. Salinity is second to drought stress and hence it is very important to develop crops tolerant to salinity stress. This review discusses the mechanisms of salt tolerance and the recent developments in understanding the complex tolerance phenomena. One way to address the salinity issue is to develop tolerant rice varieties using conventional and modern breeding techniques for which screening the rice germplasm for the varieties with desired traits is critical. Conventional methods to develop tolerant rice varieties are discussed along with modern biotechnology techniques are also discussed. Quantitative Trait Loci (QTL) and Marker Assisted Selection (MAS) are promising techniques. In addition to these modern techniques, some recent developments in the fields of transgenic plants, haploid breeding and Somaclonal variations have also been discussed. The limited knowledge about molecular and genetic mechanisms to tolerate abiotic stresses, however is a barrier to efficiently develop tolerant cultivars. A combination of conventional and modern biotechnology techniques could possibly open up the new ways.

A Short Review On The Development Of Salt Tolerant Cultivars In Rice

Rice is staple food for half of the world. With a population of almost 9.6 billion by the year 2050, there is a dire need of developing techniques to improve the crop plants, not only in terms of better yield but also to withstand harsh environmental conditions and stresses like drought, temperature, flood and salinity. Salinity is second to drought stress and hence it is very important to develop crops tolerant to salinity stress. This review discusses the mechanisms of salt tolerance and the recent developments in understanding the complex tolerance phenomena. One way to address the salinity issue is to develop tolerant rice varieties using conventional and modern breeding techniques for which screening the rice germplasm for the varieties with desired traits is critical. Conventional methods to develop tolerant rice varieties are discussed along with modern biotechnology techniques are also discussed. Quantitative Trait Loci (QTL) and Marker Assisted Selection (MAS) are promising techniques. In addition to these modern techniques, some recent developments in the fields of transgenic plants, haploid breeding and Somaclonal variations have also been discussed. The limited knowledge about molecular and genetic mechanisms to tolerate abiotic stresses, however is a barrier to efficiently develop tolerant cultivars. A combination of conventional and modern biotechnology techniques could possibly open up the new ways.

Response of long-term acid stress to biofilm formation of meat-related Salmonella Enteritidis

Salmonella commonly preferred to survive in the pattern of biofilm rather than planktonic cells in food processing environment, where various stress was widely encountered. In the present study, the response of biofilm formation of four-isolate cocktail of Salmonella Enteritidis on stainless steel surface to long-term acid stress was determined within a pH range of 5.0–7.2. The results showed that a short-term weak acid stress (pH 6.0 and 5.5) could enhance the attachment of S. Enteritidis, whereas short-term harsh stress significantly reduced cells attachment; Long-term weak and harsh stress obviously inhibited the biofilm formation of S. Enteritidis as compared with control group (pH 7.2), and the inhibition was significant depend on pH values, however, no difference was observed in planktonic cells numbers. Many small cell clusters rather than large cells aggregates were observed by fluorescence microscopy in harsh stress group, however, a classical process of biofilm formation and the complex three-dimensional structure formed by dense aggregates were found in control group. Consistent finding was also revealed by the observation of ATR-FTIR, which suggested that the harsh acid stress decreased the amount of various components formed in biofilm matrix, in particular of polysaccharides and proteins. Our finding suggested that long-term harsh acid stress could exert a great impact on biofilm formation of S. Enteritidis, and the obtained information was benefit for developing novel disinfection procedures in food processing industry.

Determinants of emigration and their impact on survival during dispersal in fox and jackal populations.

Animals disperse in response to poor resource conditions as a strategy of escaping harsh competition and stress, but may also disperse under good resource conditions, as these provide better chances of surviving dispersal and gaining fitness benefits such as avoiding kin competition and inbreeding. Individual traits should mediate the effect of resources, yielding a complex condition-dependent dispersal response. We investigated how experimental food reductions in a food-rich environment around poultry-growing villages interact with individual-traits (age, gender, body-mass) in two sympatric canids, red foxes and golden jackals, to jointly affect emigration propensity and survival during dispersal. Sub-adult foxes emigrated more frequently from the food-rich habitat than from the pristine, food-limited habitat, while adult foxes showed the opposite trend. During dispersal, adults exhibited lower survival while sub-adults did not experience additional mortality costs. Although fox mortality rates increased in response to food reduction, dispersal remained unchanged, while jackals showed strong dispersal response in two of the three repetitions. Jackal survival under food reduction was lowest for the dispersing individuals. While resources are an important dispersal determinant, different age classes and species experience the same resource environment differently and consequently have different motivations, yielding different dispersal responses and consequences.

The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli.

Flexible adaptation to environmental stress is vital for bacteria. An energy-efficient post-transcriptional stress response mechanism in Escherichia coli is governed by the toxin MazF. After stress-induced activation the endoribonuclease MazF processes a distinct subset of transcripts as well as the 16S ribosomal RNA in the context of mature ribosomes. As these ‘stress-ribosomes’ are specific for the MazF-processed mRNAs, the translational program is changed. To identify this ‘MazF-regulon’ we employed Poly-seq (polysome fractionation coupled with RNA-seq analysis) and analyzed alterations introduced into the transcriptome and translatome after mazF overexpression. Unexpectedly, our results reveal that the corresponding protein products are involved in all cellular processes and do not particularly contribute to the general stress response. Moreover, our findings suggest that translational reprogramming serves as a fast-track reaction to harsh stress and highlight the so far underestimated significance of selective translation as a global regulatory mechanism in gene expression. Considering the reported implication of toxin-antitoxin (TA) systems in persistence, our results indicate that MazF acts as a prime effector during harsh stress that potentially introduces translational heterogeneity within a bacterial population thereby stimulating persister cell formation.

Topological analysis of carbon flux during multi-stress adaptation in Halomonas sp. AAD12

Background: Osmolytes with their effective stabilizing properties are accumulated as protectants not only against salinity but also against denaturing harsh environmental stresses such as freezing, drying, high temperatures, oxygen radicals and radiation. The present work seeks to understand how Halomonas sp. AAD12 cells redirect carbon flux specifically to replenish reactions for biomass and osmolyte synthesis under changing salinity and temperature. To accomplish this goal, a combined FBA-PCA approach has been utilized. Results: Experimental data were collected to supply model constraints for FBA and for the verification of the model predictions, which were satisfactory. With restrictions on the various combinations of selected anaplerotic paths (reactions catalyzed by phosphoenolpyruvate carboxylase, pyruvate carboxylase or glyoxylate shunt), two major phenotypes were found. Moreover, under high salt concentrations, when the glucose uptake rate was over 1.1 mmoL DCW - 1 hr - 1 , an overflow metabolism that led to the synthesis of ethanol caused a slight change in both phenotypes. Conclusions: The operation of the glyoxylate shunt as the major anaplerotic pathway and the degradation of 6-phosphogluconate through the Entner-Doudoroff Pathway were the major factors in causing a distinction between the observed phenotypes.

Autophagic activity in neuronal cell death.

As post-mitotic cells with great energy demands, neurons depend upon the homeostatic and waste-recycling functions provided by autophagy. In addition, autophagy also promotes survival during periods of harsh stress and targets aggregate-prone proteins associated with neurodegeneration for degradation. Despite this, autophagy has also been controversially described as a mechanism of programmed cell death. Instances of autophagic cell death are typically associated with elevated numbers of cytoplasmic autophagosomes, which have been assumed to lead to excessive degradation of cellular components. Due to the high activity and reliance on autophagy in neurons, these cells may be particularly susceptible to autophagic death. In this review, we summarize and assess current evidence in support of autophagic cell death in neurons, as well as how the dysregulation of autophagy commonly seen in neurodegeneration can contribute to neuron loss. From here, we discuss potential treatment strategies relevant to such cell-death pathways.

Speech and language in a genotyped cohort of individuals with Kabuki syndrome.

Speech and language deficits are commonly associated with Kabuki syndrome. Yet little is known regarding the specific symptomatology of these disorders, preventing use of targeted treatment programs. Here we detail speech and language in 16 individuals with Kabuki syndrome (thirteen with KMT2D mutations, one with a KDM6A mutation, and two mutation-negative cases), aged 4-21 years. The most striking speech deficit was dysarthria, characterised by imprecise consonants, harsh vocal quality, hypernasality, reduced rate and stress, and distorted pitch. Oromotor functioning was also impaired. Delayed, rather than disordered, articulation and phonology was common. Both receptive and expressive language abilities were reduced in the majority and deficits were noted across all language sub-domains (i.e., semantics, syntax, morphology, and pragmatics) with no clear differentiation or specific language profile. Individuals with Kabuki syndrome present with a heterogenous pattern of oromotor, speech, and language deficits. This variability fits with the multisystem nature of the disorder, which may encompass neurological, orofacial structural, hearing, and cognitive deficits, any or all of which may contribute to speech or language impairment. Our results suggest that all individuals with Kabuki syndrome have some level of communication deficit, warranting speech pathology involvement in all cases.

Transcriptome analysis of cyst formation in Rhodospirillum centenum reveals large global changes in expression during cyst development.

BackgroundRhodospirillum centenum is a photosynthetic member of the Gram-negative Azospirillum clade members of which exhibit a complex developmental life-cycle featuring morphologically distinct cell types. Under periods of nutrient deprivation, replicative vegetative cells differentiate into metabolically dormant cysts that survive harsh environmental stresses such as desiccation. Encystment involves a multi-stage developmental process that includes the rounding of cells, production of large intracellular storage granules of poly-hydroxybutyrate (PHB) and the excretion of a protective exopolysaccharide coating that envelops dormant cysts.ResultsTo study the process of cyst development, we performed RNA-seq studies on cells that were induced to undergo cyst development. To assay for temporal changes in gene expression, RNA was extracted at 4, 24, 48, 72, 96 hours during development and subjected to deep sequence analysis. These results show that 812 genes exhibit log2 ≥ 1.5-fold changes in expression over a 96 hour cyst induction period demonstrating large global changes in gene expression during cyst development.ConclusionsNotable changes in expression occurred in numerous genes involved in cell wall and lipid biosynthesis, metabolic enzymes, and numerous regulatory genes such as histidine kinases and transcription factors. Many genes involved in protein synthesis and DNA replication were also significantly reduced during late stages of cyst development. Genes previously identified by genetic screens as being critical for cyst development also exhibited changes of expression during cyst induction. This study provides the first transcriptome profile of global changes in gene expression that occur during development of cysts in a Gram-negative species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1250-9) contains supplementary material, which is available to authorized users.

Harsh parenting, parasympathetic activity, and development of delinquency and substance use.

Stress response systems are thought to play an important role in the development of psychopathology. In addition, family stress may have a significant influence on the development of stress response systems. One potential avenue of change is through alterations to thresholds for the activation of stress responses: Decreased threshold for responding may mark increased stress sensitivity. Our first aim was to evaluate the interaction between thresholds for parasympathetic nervous system (PNS) responding, operationalized as resting respiratory sinus arrhythmia (RSA), and harsh parenting in the prediction of development of delinquency and adolescent substance use (resting RSA as a biomarker of risk). The second aim was to evaluate if resting RSA changes over time as a function of harsh parenting and stress reactivity indexed by RSA withdrawal (altered threshold for stress responding). Our third aim was to evaluate the moderating role of sex in these relations. We used longitudinal data from 251 children ages 8-16 years. Mother-reports of child delinquency and RSA were acquired at all ages. Adolescents self-reported substance use at age 16 years. Family stress was assessed with child-reported harsh parenting. Controlling for marital conflict and change over time in harsh parenting, lower resting RSA predicted increases in delinquency and increased likelihood of drug use in contexts of harsh parenting, especially for boys. Harsh parenting was associated with declining resting RSA for children who exhibited greater RSA withdrawal to stress. Findings support resting PNS activity as a moderator of developmental risk that can be altered over time.

The immunogenicity of antibody aggregates in a novel transgenic mouse model.

Protein aggregates have been discussed as a potential risk factor related to immunogenicity. Here we developed a novel human IgG transgenic (tg) mouse system expressing a mini-repertoire of human IgG1 antibodies (Abs) for the assessment of immunogenic properties of human mAb preparations. Transgenic mice were generated using germline versions of the human Ig heavy chain γ1 (IgH-γ1), and the human Ig light chain (IgL) κ and λ genes. Only the soluble form of human IgH-γ1 was used to avoid expression of the membrane Ig-H chain and concomitant allelic exclusion of endogenous murine Ig genes. IgG1 aggregates were generated by different stress conditions such as process-related, low pH and exposure to artificial light. The expression of human Ig proteins induced immunological tolerance to a broad range of human IgG1 molecules in the tg mice. Immunization with IgG1 aggregates demonstrated that soluble oligomers induced by significant light-exposure and carrying neo-epitopes induced a strong immune response in tg mice. In contrast, Ab aggregates alone and monomers with neo-epitopes were not immunogenic. This mouse model is able to recognize immunogenic modifications of human IgG1. While the degree of stress-induced aggregation varies for different mAbs, our findings using a particular mAb (mAb1) demonstrate that non-covalently modified aggregates do not break tolerance, contrary to widely held opinion. The immunogenic potential of soluble aggregates of human IgG strongly depends on the presence of neo-epitopes resulting from harsh stress conditions, i.e. extensive exposure to artificial light.

Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

ABSTRACTRibosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress.

Robustness Estimation of Wireless MEMS Vibration Test under Harsh Environment

Robustness estimation is important issue to ensure stability, reliability, and precision of Wireless MEMS vibration test under harsh environment stress ing . Although the robustness of vibration test is limited mainly by the embedded electronics and sensors, how to obtain precise and robust data by using energy effective and resources constrained wireless sensor nodes is still a problem. Paper uses the multivariate uncertainty statistics method to estimate robustness of online test data under harsh environment, and uses Fisher information distance to estimat e transmitting robustness in its complication communication process. E xperiments and simulation are designed t o analyze the robustness and precise of wireless MEMS nodes in numerical value, results show estimation methods and model are effective.

Application of PCDA/SPH/CHO/Lysine vesicles to detect pathogenic bacteria in chicken

During the course of infection, Salmonella must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments, as lysine decarboxylation to cadaverine. The idea of Salmonella defenses responses could be employed in systems as polydiacetylene (PDA) to detect this pathogen so important to public health system. Beside that PDA is an important substance because of the unique optical property; that undergoes a colorimetric transitions by various external stimuli. Therefore 10,12-pentacosadyinoic acid (PCDA)/Sphingomyelin(SPH)/Cholesterol(CHO)/Lysine system was tested to determine the colorimetric response induced by Salmonella choleraesuis. PCDA/SPH/CHO/Lysine vesicles showed a colour change even in low S. choleraesuis concentration present in laboratory conditions and in chicken meat. Thus, this work showed a PCDA/SPH/CHO/Lysine vesicle application to simplify routine analyses in food industry, as chicken meat industry.

Chilling acclimation provides immunity to stress by altering regulatory networks and inducing genes with protective functions in cassava.

BackgroundStress acclimation is an effective mechanism that plants acquired for adaption to dynamic environment. Even though generally considered to be sensitive to low temperature, Cassava, a major tropical crop, can be tolerant to much lower temperature after chilling acclimation. Improvement to chilling resistance could be beneficial to breeding. However, the underlying mechanism and the effects of chilling acclimation on chilling tolerance remain largely unexplored.ResultsIn order to understand the mechanism of chilling acclimation, we profiled and analyzed the transcriptome and microRNAome of Cassava, using high-throughput deep sequencing, across the normal condition, a moderate chilling stress (14°C), a harsh stress (4°C) after chilling acclimation (14°C), and a chilling shock from 24°C to 4°C. The results revealed that moderate stress and chilling shock triggered comparable degrees of transcriptional perturbation, and more importantly, about two thirds of differentially expressed genes reversed their expression from up-regulation to down-regulation or vice versa in response to hash stress after experiencing moderate stress. In addition, microRNAs played important roles in the process of this massive genetic circuitry rewiring. Furthermore, function analysis revealed that chilling acclimation helped the plant develop immunity to further harsh stress by exclusively inducing genes with function for nutrient reservation therefore providing protection, whereas chilling shock induced genes with function for viral reproduction therefore causing damage.ConclusionsOur study revealed, for the first time, the molecular basis of chilling acclimation, and showed potential regulation role of microRNA in chilling response and acclimation in Euphorbia.

C-Ski inhibits autophagy of vascular smooth muscle cells induced by oxLDL and PDGF.

Autophagy is increasingly being recognized as a critical determinant of vascular smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski inhibits VSMC proliferation stimulated by transforming growth factor β (TGF-β), but it is not clear whether c-Ski has the similar protective role against other vascular injury factors and whether regulation of autophagy is involved in its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs were treated with 40 µg/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml platelet-derived growth factor (PDGF), both of which were autophagy inducers and closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy. This action of c-Ski resulted in inhibiting the cell proliferation, the decrease of contractile phenotype marker α-SMA expression while the increase of synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF. Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL or PDGF on A10 cell growth and phenotype transition. And further investigation found that inhibition of AKT phosphorylation to downregulate proliferating cell nuclear antigen (PCNA) expression, was involved in the regulation of autophagy and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs. Collectively, c-Ski may play an important role in inhibiting autophagy to protect VSMCs against some harsh stress including oxLDL and PDGF.

Review on Joint Shear Strength of Nano-Silver Paste and Its Long-Term High Temperature Reliability

Soldering has been the main die attach technology for several decades. Recently, in order to meet the high temperature electronic requirements (high temperature-operating SiC and GaN devices) as well as the health recommendations (replacing the toxic lead present in common solder alloys with lead-free alternatives), several new attach technologies have been developed. Among others, the sintering of nano-silver particles seems to be one of the most interesting choices, and has been extensively investigated during recent years. The emergence of this technology is mainly due to the desired high electrical and high thermal conductivities of the sintered joint, its low elastic modulus offering a good thermo-mechanical reliability, its low process temperature, and its high operating temperature. In this paper, a review of parameters affecting the initial shear strength of the sintered silver joint will be summarized as well as the high temperature long-term reliability issues. The sintering cycle (bonding pressure, bonding temperature, sintering dwell time, heating rate, and the sintering atmosphere), the joint size, and the attached materials properties (nature, roughness), are found to closely affect the initially measured shear strength of the joint. The long-term reliability of the joint has been shown to suffer initially from three phenomena: the silver electro-migration, the decrease of shear strength under harsh thermo-mechanical stresses, and the swelling of the sintered layer. While the latter phenomenon is observed during the storage at temperatures above 350°C, the electro-migration and thermo-mechanical stresses can influence the package reliability at temperatures as low as 250°C. However, some suggested precautions during the module fabrication can lead to the minimizing of the effects of these phenomena and the achievem a more reliable joint.